Unlocking the Alkynyl Bromide Radical Anion With Alternating Current for Inverse Sonogashira C─H Coupling

Junya Wang; Xiaozhou Wang; Pui Ying Choy; Chi‐Wai Cheung; Li‐Wen Xu; Hung Kay Lee; Gui‐Juan Cheng; Fuk Yee Kwong

doi:10.1002/advs.76881

. 2026 Sep 16;13(59):e76881. doi: 10.1002/advs.76881

Unlocking the Alkynyl Bromide Radical Anion With Alternating Current for Inverse Sonogashira C─H Coupling

Junya Wang ^1,^#, Xiaozhou Wang ^1,^2,^#, Pui Ying Choy ¹, Chi‐Wai Cheung ¹, Li‐Wen Xu ³, Hung Kay Lee ¹, Gui‐Juan Cheng ^2,^✉, Fuk Yee Kwong ^1,^✉

PMCID: PMC13583124 PMID: 42750140

ABSTRACT

Carbon–bromine bond cleavage is a fundamental step in many chemical transformations. Over the past two decades, the reductive cleavage of C_(Ar)─Br bonds (via a stepwise pathway) and C_(alkyl)─Br bonds (via a concerted pathway) has been extensively studied. In contrast, the cleavage of the C_(alkynyl)─Br bond remains unreported. We hypothesized that this bond may follow a distinct dissociation pathway, diverging from the established mechanisms. Indeed, the possible generation of reactive alkynyl bromide radical anion intermediates could significantly enrich the synthetic toolbox. However, chemical additives are less attractive than an electrochemical approach. Herein, we report an alternating current (AC)‐promoted, Pd‐catalyzed ortho‐aryl C─H alkynylation employing unprecedented alkynyl bromide radical anion species. This “inverse” Sonogashira synthetic scheme accommodates a broad substrate scope, delivering alkynylated stilbene derivatives with excellent arene site selectivity. Mechanistic investigations, EPR spectroscopy, and DFT calculations suggest the involvement of a Pd(II)/Pd(III) pathway assisted by transient alkynyl bromide radical anion intermediates. This work opens a new method for bromoalkyne activation, demonstrates the capability of electrochemistry to enable efficient electrophilic alkynylation, and expands the synthetic toolkit for constructing complex stilbene‐based frameworks.

Keywords: catalysis, C─H bond functionalization, electrochemistry, inverse Sonogashira, radical coupling

An alternating current (AC)‐promoted, Pd‐catalyzed ortho‐aryl C─H alkynylation of 2,3‐diaryl acrylaldehydes is described. This synthetic scheme accommodates a broad substrate scope, delivering alkynylated stilbene derivatives with excellent arene site selectivity. Mechanistic investigations, including control experiments, EPR spectroscopy and DFT calculations, suggest the involvement of a Pd(II)/Pd(III) pathway assisted by transient alkynyl bromide radical anion intermediates.

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1. Introduction

Alkynes represent one of the most versatile classes of building blocks in organic chemistry owing to their readily modifiable carbon–carbon triple bond and exceptional inherent reactivity. These distinctive features enable a wide range of chemical transformations, rendering alkynes invaluable in the synthesis of pharmaceuticals, organic materials, and complex natural products [1, 2, 3, 4]. Consequently, the development of robust methods for installing alkyne moieties onto organic frameworks is often highly desirable in synthetic methodology. In this context, the “inverse” Sonogashira coupling [5, 6] has emerged as a complementary approach to the classical nucleophilic Sonogashira coupling (Scheme 1A) [7, 8, 9, 10, 11]. This protocol essentially flips the conventional reactivity paradigm by using haloalkynes as the electrophilic component [12, 13]. Recent investigations suggested that the directing group‐assisted activation of an inert C─H bond in the “inverse Sonogashira coupling” generally proceeds via a Pd(II)/(IV) cycle or a migratory insertion pathway [14, 15]. However, these transformations often require demanding reaction conditions, such as elevated temperatures or stoichiometric Ag(I) additives, to facilitate halide abstraction and catalyst oxidation. To circumvent these drawbacks, the development of an efficient and sustainable electrochemical protocol is highly desirable.

SCHEME 1 — Background and prior work done of inverse Sonogashira coupling.

Recent advances have shown that merging transition metal‐catalyzed C─H functionalization with electrochemical oxidation represents a promising paradigm in catalysis [16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31]. This synergistic approach provides precise control over metal oxidation states at the anode and facilitates efficient catalyst regeneration at the cathode. Within this framework, the cathode serves as a sustainable electron source for the one‐electron reductive cleavage of organohalides to generate carbon‐centered radicals and halide anions for subsequent transformations [32, 33, 34]. Carbon‐centered radicals [35, 36], particularly alkyl [37, 38, 39], alkenyl [40], allenyl [41, 42], and aryl radicals [43, 44, 45, 46, 47], have been extensively studied, whereas alkynyl radicals have remained relatively elusive in the scientific literature [48]. Generally, the reductive cleavage follows one of two pathways (Scheme 1B): a stepwise sequence, where electron transfer leads to a transient radical anion intermediate prior to C─X bond dissociation (path a: often observed with aryl halides); or a concerted process, in which electron transfer and bond breaking occur in a single elementary step (path b: mostly for aliphatic halides) [49, 50, 51, 52]. Furthermore, a refined model of the concerted pathway, known as “sticky” dissociative electron transfer (DET), has been proposed to account for ion‐dipole interactions between the two fragments, which can significantly influence the dynamics of electron transfer preceding the cleavage (path c) [32, 33, 34, 53, 54, 55]. Notably, both the alkynyl radical and the alkynyl bromine radical anion are expected to be favorable for the transformation to the Pd(II) complex due to their lower reaction energy barriers than bromoalkyne itself. Despite these insights, investigations into the reductive cleavage and radical/radical anion behavior of alkynyl halides remain unexplored, and successful examples of pallada‐electrochemical C─H alkynylation remain scarce [56, 57, 58], representing a significant knowledge gap in the field. Motivated by the untapped potential of radical/radical anions of alkynyl halides and our prior work in alkyne chemistry [59, 60, 61, 62, 63, 64], we herein report a synergistic pallada‐electrochemical system for site‐selective, direct C─H alkynylation of acrylaldehydes. This methodology utilizes an electrochemical cell in which the cathode drives the one‐electron reduction cleavage of bromoalkyne, while the anode facilitates the efficient oxidation of [Pd] catalyst (Scheme 1C).

2. Results and Discussion

We initiated our investigation by employing (E)‐2‐(naphthalen‐1‐yl)‐3‐phenylacrylaldehyde (1a) and (bromoethynyl)triisopropylsilane (2a) as model substrates to probe the effective pallada‐electrochemical conditions (Table 1). Since alternating current (AC) can significantly enhance reaction efficiency [65, 66, 67], the prototype reaction was conducted in an undivided cell fitted with two Pt electrodes under a controlled square‐waveform AC (voltage range: 1.9–2.3 V; 0.6 mA; 1/80 Hz) (entry 1). Under these conditions, the desired product was afforded in 68% yield. It is worth noting that this alkynylation exhibited exclusive regioselectivity at the β‐position of the naphthalene ring, while the C(sp²)─H bonds located at the 3‐phenyl and alkenyl groups remained untouched. Better performance was observed for AC mode compared to direct current (DC), highlighting the ability of AC to suppress the cathodic precipitation of metal catalyst complexes (entry 1 vs. 2) [57, 68, 69]. When DC or AC at either higher or lower frequencies was applied, lower yields of 3aa were obtained (entry 1 vs. entries 3–4). Various transient directing groups [70, 71, 72, 73, 74, 75, 76] were tested, and D, L‐tert‐leucine gave the best product yields (entry 1 vs. entries 8–9). Varying other reaction parameters, such as Pd catalyst, solvent, electrolyte, base, and temperatures led to diminished yields (entry 1 vs. entries 6–16). Control experiments revealed the essential roles of Pd(TFA)₂, D, L‐tert‐leucine and pyridone [77, 78, 79], as the absence of any one component completely suppressed the product formation (entries 7, 10 and 17). Notably, when iodoalkyne was used instead of bromoalkyne, only trace product was detected (entry 18).

TABLE 1.

Optimization of reaction conditions ^a .


Entry	Variation From Standard Conditions	Yield [%] ^b
1	none	72 (68) ^c
2	DC instead of AC	44
3	1/40 Hz instead of 1/80 Hz	38
4	1/120 Hz instead of 1/80 Hz	65
5	no electric current	26 (23) ^c
6	Pd(OAc)₂ instead of Pd(TFA)₂	57
7	no Pd(TFA)₂	n.r. ^d
8	D, L‐Valine instead of D, L‐tert‐leucine	47
9	L‐tert‐leucine instead of D, L‐tert‐leucine	70
10	no D, L‐tert‐leucine	n.r.
11^e	HFIP instead of AcOH	<10
12^f	TFE instead of AcOH	<10
13	N(n‐Bu)₄OAc instead N(n‐Bu)₄BF₄	33
14	KOAc instead of KOt‐Bu	55
15	KH₂PO₄ instead of KOt‐Bu	38
16	r.t. instead of 60°C; 0.3 mA instead of 0.6 mA	30
17^g	no pyridone 4	60
18	iodoalkyne instead bromoalkyne	trace

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^{^a}

Reaction conditions: 2,3‐Diaryl acrylaldehyde 1a (0.2 mmol), (bromoethynyl)triisopropylsilane (2a) (0.4 mmol), Pd(TFA)₂ (10 mol%), D, L‐tert‐leucine (40 mol%), N(n‐Bu)₄BF₄ (0.04 M), pyridone 4 (1.2 equiv.), and AcOH (5 mL) were stirred in an undivided cell with two Pt electrodes at 60°C under air atmosphere for 32 h under constant current mode. D = Duty ratio

^{^b}

Calibrated GC yields were reported using tetradecane as the internal standard

^{^c}

Isolated yields

^{^d}

n.r. = no reaction

^{^e}

HFIP = 1,1,1,3,3,3‐hexafluoro‐2‐propanol

^{^f}

TFE = 2,2,2‐trifluoroethanol

^{^g}

pyridone 4 = 5‐chloro‐3‐nitropyridin‐2(1H)‐one.

With the optimized conditions in hand, we next investigated the substrate scope (Scheme 2). Diaryl acrylaldehydes having ortho‐substituted aryl groups underwent the alkynylation smoothly to furnish the desired products in good yields (i.e., methyl – 3ba; ethyl – 3ca; isopropyl – 3 da; methoxy – 3ea; chloro – 3fa; phenyl – 3 ha). A gram‐scale synthesis of 3ba (1.13 g) was attempted with higher current (2.0 mA). Substrate 1 featuring α‐substituted polyaromatic groups, e.g., 2‐naphthyl and pyrenyl units, were applicable for the selective alkynylation at the vicinal C─H bond, affording alkynylated 3la and 3ma, respectively. Ester‐containing stilbene was a feasible substrate to afford the desired product 3ka. Moreover, substrates bearing heteroaromatic motifs such as benzofuran and benzothiophene were well‐tolerated, delivering alkynylated products 3ia, 3ja, 3na and 3oa in good yields. The structure of product 3ja was confirmed by X‐ray crystallographic analysis (CCDC 2463153, see SI for details). Furthermore, di‐alkynylation was successfully accomplished using non‐ortho‐substituted stilbene as the substrate (products 3ra, 3sa, and 3ta). Acrylaldehydes with substituents at the β‐aromatic ring were also found compatible, leading to the corresponding alkynylated analogues (i.e., methyl – 3 ua; methoxy – 3va; fluoro – 3wa; chloro – 3xa; trifluoromethyl – 3ya) with high selectivity. It is noteworthy that the chloro group remained intact under the stated reaction conditions, in which it is highly beneficial for further transformation through established cross‐coupling strategies [80, 81, 82]. Alkyl‐substituted stilbene substrates afforded the corresponding product 3za with low yield. When the triisopropylsilyl (TIPS) group of 2a was replaced by (tert‐butyl)dimethylsilyl (TBS) or triethylsilyl (TES) substituent, the corresponding silylethynyl‐functionalized products 3ab and 3ac were also well afforded.

To elucidate the mechanism, a series of control experiments were carried out. Replacing bromoalkynes 2a with iodoalkynes 5 resulted in only a trace amount of desired alkynylated product, whereas homocoupled diyne 6 was obtained in 72% yield (Scheme 3A). In contrast, bromoalkynes afforded less than 3% diyne. This suggests that the generation of free alkynyl radicals from bromoalkyne 2a is much less favorable due to a higher kinetic barrier. A radical‐trapping experiment with TEMPO completely inhibited the alkynylation (Scheme 3B), implicating the involvement of a radical‐like intermediate, which was proposed to be the alkynyl bromide radical anion 2a’. Furthermore, complex and undecipherable signals were observed in an electron paramagnetic resonance (EPR) spin‐trapping experiment with 5,5‐dimethyl‐1‐pyrroline‐N‐oxide (DMPO) (Scheme 3C‐i), while radical signal peaks derived from the proposed alkynyl bromide anion 2a’ were detected (Scheme 3C‐ii), compellingly indicating the one‐electron reduction of bromoalkyne 2a under AC conditions. Density functional theory (DFT) calculations further revealed that one‐electron reduction of the bromoalkyne 2a leads to barrierless dissociation of the C(sp)─Br bond to form a loosely associated radical anion [C(sp)···Br]•⁻ [53, 54, 55]. Additionally, the optimized structure indicates that the alkynyl bromide anion 2a’ is bent, with a C(sp)–C(sp)···Br angle of 135.7° compared to the linear structure of 2a (179.9°), accompanied by an elongation of the C(sp)···Br bond from 1.80 to 2.46 Å. While these structural distortions enhance the reactivity toward reductive cleavage of the C(sp)–Br bond, subsequent dissociation of this radical anion intermediate to release the free alkynyl radical is thermodynamically disfavoured due to the high energy and extremely short lifetime of the corresponding alkynyl radicals [48, 83, 84, 85, 86, 87], consequently accounting for the absence of homocoupling products. Complementary cyclic voltammetry (CV) analysis was performed to characterize the electrochemical behavior of the system (Scheme 3D). A reduction peak at −1.4 V (vs. aqueous Ag/AgCl) was assigned to the reduction of bromoalkyne to its radical anion, while an oxidation peak at +1.1 V (vs. aqueous Ag/AgCl) corresponds to the oxidation of low‐valent palladium species to the active Pd(II) intermediate [88]. This suggests the regeneration of the active Pd(II) species after each catalytic cycle. Finally, a H/D scrambling experiment was conducted using acetic acid‐d (CH₃CO₂D) as the solvent, and no H/D scrambling was observed (Scheme 3E‡).

SCHEME 3 — Control experiments, cyclic voltammetry (CV) analysis and electron paramagnetic resonance (EPR) studies. All standard conditions are the same as in Scheme 2.

As depicted in Scheme 4 for Pd(II)/Pd(IV) pathway (Pathway A), INT‐2 reacts with bromoalkyne 2a to form Pd(IV) intermediate INT‐A5 via a transition state TS‐A_II/IV in the absence of current. Reductive elimination via transition state TS‐A_RE furnishes INT‐A6, which is a direct precursor to alkynylated product 3aa upon hydrolysis. However, this pathway involves high‐energy transition states (ΔG ^‡ _TS‐AII/IV = 30.5 kcal/mol; ΔG ^‡ _TS‐ARE = 34.6 kcal/mol), suggesting the Pd(II) center in INT‐2 lacks sufficient electron density to facilitate oxidative addition. Thus, the Pd(II)/Pd(IV) route appears to be energetically unfavorable. For Pd(II)/Pd(III) pathway (Scheme 4, Pathway B), an electrochemical reduction of bromoalkyne generates alkynyl bromide radical anion 2a’, which interacts with Pd(II)‐palladacycle INT‐2 to form INT‐B3. The alkynyl bromide radical anion undergoes single‐electron oxidative addition via a transition state TS‐B_II/III to afford the Pd(III) species INT‐B4, which subsequently undertakes reductive elimination to produce Pd(I) intermediate INT‐B6, a precursor to alkynylated product 3aa. Then, the Pd(I) species is reoxidized to Pd(II) via an anodic oxidation. This reaction pathway is both kinetically and thermodynamically favorable, featuring low activation barriers for mutual oxidative addition and reductive elimination steps (Δ G ^‡ = 0.8 kcal/mol; ΔG ^‡ = 10.6 kcal/mol).

In addition to substrate scope exploration and mechanistic studies, the synthetic utility of this electrochemical alkynylation was investigated (Scheme 5). The alkynylated diaryl acrylaldehydes were readily derivatized through either reduction or oxidation to afford the resulting compounds 8–10 in excellent yields. The structures of products 8 and 10 were also unambiguously confirmed by X‐ray crystallographic analysis (CCDC 2463058 and 2463060, see SI for details). These structurally diverse alkynyl stilbenes are versatile scaffolds for further development of a bioactive compound library in the drug discovery process.

SCHEME 5 — Further transformation of alkynylated diaryl acryladehdyes.

3. Conclusion

In conclusion, while the nucleophilic Sonogashira cross‐coupling is a well‐established synthetic tool for constructing C(sp)‐C(sp²) bonds, the development of “inverse Sonogashira coupling” as a valuable synthetic complement remains in great demand. Herein, we have developed a pallada‐electrocatalytic system for the ortho‐aryl C─H alkynylation of 2,3‐diaryl acrylaldehydes. Under modulated AC‐promoted conditions, the reaction proceeds via a transient, unstable alkynyl bromide radical anion intermediate, which demonstrates favorable efficacy in electrophilic alkynylation for delivering alkynylated stilbene frameworks in good‐to‐excellent yields. Notably, this method achieves exclusive C─H site‐selectivity at the aldehyde‐bearing geminal arene. Mechanistic studies, including control experiments, EPR spectroscopy, and DFT calculations, support an intriguing Pd(II)/Pd(III) catalytic cycle involving a key alkynyl bromide radical anion species. We anticipate that this new catalyst system will serve as a highly useful tool for tackling other versatile arene alkynylation in relevance.

4. Experimental Section/Methods

4.1. General Procedures for Electrochemical Pd‐Catalyzed Alkynylation Reaction

The electrocatalysis reaction was carried out in an undivided cell, with a platinum anode (30 mm × 5 mm × 0.1 mm) and a platinum cathode (30 mm × 5 mm × 0.1 mm). Stilbene 1 (1.0 equiv.), alkynyl bromide 2 (2.0‐4.0 equiv.), Pd(TFA)₂ (10 mol%), D, L‐tert‐Leucine (40 mol%), N(n‐Bu)₄BF₄ (0.04 M), KOt‐Bu (1.2 equiv.) and 5‐chloro‐3‐nitropyridin‐2(1H)‐one (4) (1.2 equiv.) were placed in a 7 mL cell and dissolved in acetic acid (5 mL). Electrocatalysis was performed at 60°C with a constant current of 0.6 mA under an air atmosphere for 32 h. The reaction was then allowed to cool to room temperature. Ethyl acetate (EtOAc) was added, and the electrodes were washed with EtOAc (3 × 1 mL). The organic layer was collected and filtered through a Celite pad and concentrated in vacuo. The mixture was then purified by flash column chromatography with ethyl acetate and hexane as the elution solvent to give the desired product 3.

4.2. General Procedures for Gram‐Scale Synthesis of Compound 3ba

The electrocatalysis reaction was carried out in an undivided cell, with a platinum anode (15 mm × 15 mm × 0.1 mm) and a platinum cathode (15 mm × 15 mm × 0.1 mm). Stilbene 1b (5.0 mmol, 1.0 equiv.), alkynyl bromide 2a (10.0 mmol, 2.0 equiv.), Pd(TFA)₂ (0.5 mmol, 10 mol%), D, L‐tert‐Leucine (2.0 mmol, 40 mol%), N(n‐Bu)₄BF₄ (0.8 mmol, 0.04 M), KOt‐Bu (6.0 mmol, 1.2 equiv.) and 5‐chloro‐3‐nitropyridin‐2(1H)‐one (4) (6.0 mmol, 1.2 equiv.) were placed in a cell and dissolved in acetic acid (20 mL). Electrocatalysis was performed at 60°C with a constant current of 2.0 mA under an air atmosphere for 7 days. The reaction was then allowed to cool to room temperature. Ethyl acetate was added, and the electrodes were washed with EtOAc (3 × 1 mL). The organic layer was collected and filtered through a Celite pad and concentrated in vacuo. The mixture was then purified by flash column chromatography with ethyl acetate and hexane as the elution solvent to give the desired product 3ba in 56% (1.13 g).

4.3. General Procedures for Synthesis of Product 8

Compound 3ba (2 mmol, 1.0 equiv.) was dissolved in ethanol (EtOH) (2 mL) and dichloromethane (DCM) (2 mL), and then NaBH₄ (2.0 equiv.) were added at 0 °C. The reaction mixture was stirred at room temperature for 3 h. After the completion of the reaction (monitored by TLC), saturated NH₄Cl was added, and the crude products were extracted with EtOAc. The organic layers were combined, dried over Na₂SO₄, filtered, and the solvent was then evaporated under vacuum. The mixture was purified by flash column chromatography with silica gel (200–300 mesh), using ethyl acetate and hexane (1:10, v/v, R _f = 0.12) as the elution solvent to give the desired product 8 in 96% yield (0.78 g, white solid).

4.4. General Procedures for Synthesis of Product 9

Compound 3ba (2 mmol, 1.0 equiv.) was dissolved in t‐BuOH (1 M), and then a solution of NaH₂PO₄ (10 mmol, 5.0 equiv.) and NaClO₂ (7.4 mmol, 3.7 equiv.) in water (10 mL) were added followed by 2‐methyl‐2‐ butene (18 mmol, 9.0 equiv.). The reaction mixture was stirred at 40 °C for 4 h. After the completion of the reaction (monitored by TLC), saturated NH₄Cl was added, and the crude products were extracted with EtOAc. The organic layers were combined, dried over Na₂SO₄, filtered, and the solvent was then evaporated under vacuum to obtain crude acid. The mixture was purified by flash column chromatography with silica gel (200‐300 mesh), using methanol, ethyl acetate, and hexane (1:5:15, v/v, R _f = 0.12) as the elution solvent to give the desired product 9 in 95% yield (0.79 g, colorless oil).

4.5. General Procedures for Synthesis of Product 10

Compound 3ha (0.5 mmol, 1.0 equiv.) was dissolved in dry THF (5 mL), and cooled to 0 °C. TBAF (2.0 M in THF) (1.0 mmol, 2 equiv.) was added to the mixture dropwise. The reaction mixture was stirred at 0 °C for 30 min. After the completion of the reaction (monitored by TLC), the crude products were extracted with EtOAc and brine. The organic layers were combined, dried over Na₂SO₄, filtered, and the solvent was then evaporated under vacuum. The mixture was purified by flash column chromatography with silica gel (200‐300 mesh), using ethyl acetate and hexane (1:10, v/v, R _f = 0.55) as the elution solvent to give the desired product 10 in 90% yield (0.145 g).

4.5.1. (E)‐3‐Phenyl‐2‐(2‐((triisopropylsilyl)ethynyl)naphthalen‐1‐yl)acrylaldehyde (Scheme 2, Product 3aa)

This compound was prepared according to General Procedures using stilbene 1a (0.2 mmol, 1.0 equiv.) and alkynyl bromide 2a (0.4 mmol, 2.0 equiv.) as substrates, and the reaction was performed under constant current 0.6 mA (1/80 Hz. D = 50%). The crude product was purified by column chromatography (EtOAc/Hexane = 1:10, R _f = 0.42) to afford a sticky yellow oil in 68% yield (59.6 mg). ¹H NMR (500 MHz, CDCl₃) δ 9.12 (s, 1H), 7.87 (dd, J = 8.0, 3 Hz, 2H), 7.78 (s, 1H), 7.65 (d, J = 8.5 Hz, 1H), 7.61 (d, J = 8.5 Hz, 1H), 7.48 (t, J = 7.5 Hz, 1H), 7.39 (t, J = 7.5 Hz, 1H), 7.23 (t, J = 7.5 Hz, 1H), 7.14 (t, J = 7.5 Hz, 1H), 7.10 (t, J = 8.0 Hz, 1H), 1.01 (s, 21H). ¹³C NMR (125 MHz, CDCl₃) δ 193.4, 151.6, 139.3, 135.7, 134.0, 133.2, 131.1, 130.7, 129.3, 128.7, 128.6, 128.6, 127.3, 126.9, 125.3, 121.1, 105.7, 95.4, 18.7, 11.3. HRMS (HESI‐II): m/z [M+Na]⁺ calcd for C₃₀H₃₄NaOSi: 461.2271; found 461.2270.

4.5.2. (E)‐2‐(2‐Methyl‐6‐((triisopropylsilyl)ethynyl)phenyl)‐3‐phenylacrylaldehyde (Scheme 2, Product 3ba)

This compound was prepared according to General Procedures using stilbene 1b (0.25 mmol, 1.0 equiv.) and alkynyl bromide 2a (0.5 mmol, 2.0 equiv.) as substrates, and the reaction was performed under constant current 0.8 mA (1/80 Hz. D = 50%). The crude product was purified by column chromatography (EtOAc/Hexane = 1:10, R _f = 0.45) to afford a sticky colorless oil in 62% yield (62.4 mg). ¹H NMR (500 MHz, CDCl₃) δ 9.76 (s, 1H), 7.51 (s, 1H), 7.45 (d, J = 7.5 Hz, 1H), 7.30‐7.21 (m, 6H), 7.13 (d, J = 8.0 Hz, 1H), 2.04 (s, 3H), 0.95 (s, 21H). ¹³C NMR (125 MHz, CDCl₃) δ 193.4, 150.6, 140.6, 136.7, 136.6, 134.4, 130.8, 130.6, 130.5, 130.4, 128.8, 128.3, 123.5, 105.4, 93.8, 19.9, 18.7, 11.3. HRMS (HESI‐II): m/z [M+Na]⁺ calcd for C₂₇H₃₄NaOSi: 425.2271; found 425.2264.

4.5.3. (E)‐2‐(2‐Ethyl‐6‐((triisopropylsilyl)ethynyl)phenyl)‐3‐phenylacrylaldehyde (Scheme 2, Product 3ca)

This compound was prepared according to General Procedures using stilbene 1c (0.25 mmol, 1.0 equiv.) and alkynyl bromide 2a (0.5 mmol, 2.0 equiv.) as substrates, and the reaction was performed under constant current 0.8 mA(1/80 Hz. D = 50%). The crude product was purified by column chromatography (EtOAc/Hexane = 1:10, R _f = 0.46) to afford a white solid in 66% yield (68.7 mg). ¹H NMR (500 MHz, CDCl₃) δ 9.78 (s, 1H), 7.53 (s, 1H), 7.47 (d, J = 7.3 Hz, 1H), 7.34‐7.28 (m, 3H), 7.22 (t, J = 7.8 Hz, 2H), 7.14 (d, J = 7.6 Hz, 2H), 2.26‐2.29 (m, 2H), 1.00 (t, J = 7.5 Hz, 3H), 0.96 (s, 21H). ¹³C NMR (125 MHz, CDCl₃) δ 193.7, 150.8, 142.5, 142.4, 136.1, 134.4, 130.9, 130.7, 130.6, 128.9, 128.8, 128.5, 123.5, 105.5, 93.7, 26.6, 18.6, 14.8, 11.3. HRMS (HESI‐II): m/z [M+Na]⁺ calcd for C₂₈H₃₆NaOSi: 439.2428; found 439.2424. Melting point 74.3‐75.2°C.

4.5.4. (E)‐2‐(2‐Isopropyl‐6‐((triisopropylsilyl)ethynyl)phenyl)‐3‐phenylacrylaldehyde (Scheme 2, Product 3da)

This compound was prepared according to General Procedures using stilbene 1d (0.25 mmol, 1.0 equiv.) and alkynyl bromide 2a (0.5 mmol, 2.0 equiv.) as substrates, and the reaction was performed under constant current 0.8 mA(1/80 Hz. D = 50%). The crude product was purified by column chromatography (EtOAc/Hexane = 1:10, R _f = 0.55) to afford a sticky colorless oil in 67% yield (72.0 mg). ¹H NMR (500 MHz, CDCl₃) δ 9.79 (s, 1H), 7.53 (s, 1H), 7.46 (t, J = 4.1 Hz, 1H), 7.36 (d, J = 4.1 Hz, 1H), 7.28 (t, J = 7.2 Hz, 1H), 7.21 (t, J = 7.6 Hz, 2H), 7.12 (d, J = 7.9 Hz, 2H), 2.70 (septet, J = 6.5 Hz, 1H), 1.12 (d, J = 6.5 Hz, 3H), 0.95 (s, 21H), 0.90 (d, J = 6.8 Hz, 3H). ¹³C NMR (125 MHz, CDCl₃) δ 193.7, 150.9, 147.3, 140.5, 135.3, 134.4, 130.9, 130.7, 130.6, 128.7, 128.7, 126.2, 123.3, 105.6, 93.5, 31.2, 24.1, 23.7, 18.6, 11.3. HRMS (HESI‐II): m/z [M+Na]⁺ calcd for C₂₉H₃₈NaOSi: 453.2584; found 453.2578.

4.5.5. (E)‐2‐(2‐Methoxy‐6‐((triisopropylsilyl)ethynyl)phenyl)‐3‐phenylacrylaldehyde (Scheme 2, Product 3ea)

This compound was prepared according to General Procedures using stilbene 1e (0.25 mmol, 1.0 equiv.) and alkynyl bromide 2a (0.5 mmol, 2.0 equiv.) as substrates, and the reaction was performed under constant current 0.8 mA(1/80 Hz. D = 50%). The crude product was purified by column chromatography (EtOAc/Hexane = 1:10, R _f = 0.28) to afford a sticky colorless oil in 65% yield (63.0 mg). ¹H NMR (500 MHz, CDCl₃) δ 9.73 (s, 1H), 7.52 (s, 1H), 7.33 (t, J = 8.0 Hz, 1H), 7.30‐ 7.26 (m, 1H), 7.24‐7.19 (m, 5H), 7.96 (dd, J = 8.0, 0.6 Hz, 1H), 3.69 (s, 3H), 0.94(s, 21H). ¹³C NMR (125 MHz, CDCl₃) δ 193.3, 157.1, 150.7, 137.8, 134.6, 130.4, 130.3, 129.5, 128.6, 126.1, 125.6, 124.7, 111.6, 104.7, 94.2, 56.1, 18.6, 11.3. HRMS (HESI‐II): m/z [M+Na]⁺ calcd for C₂₇H₃₄NaO₂Si: 411.2220; found 411.2214.

4.5.6. (E)‐2‐(2‐Chloro‐6‐((triisopropylsilyl)ethynyl)phenyl)‐3‐phenylacrylaldehyde (Scheme 2, Product 3fa)

This compound was prepared according to General Procedures using stilbene 1f (0.25 mmol, 1.0 equiv.) and alkynyl bromide 2a (0.5 mmol, 2.0 equiv.) as substrates, and the reaction was performed under constant current 0.8 mA(1/80 Hz. D = 50%). The crude product was purified by column chromatography (EtOAc/Hexane = 1:10, R _f = 0.40) to afford a sticky colorless oil in 55% yield (58.0 mg). ¹H NMR (500 MHz, CDCl₃) δ 9.74 (s, 1H), 7.57 (s, 1H), 7.50 (dd, J = 7.5, 1.0 Hz, 1H), 7.45 (dd, J = 8.0, 1.0 Hz, 1H), 7.33‐7.29 (m, 2H), 7.26‐7.23 (m, 2H), 7.17–7.15 (m, 2H), 0.95 (s, 21H). ¹³C NMR (125 MHz, CDCl₃) δ 192.2, 151.3, 138.6, 136.1, 134.0, 133.9, 131.6, 130.8, 130.4, 129.8, 129.4, 128.9, 125.6, 103.9, 95.6, 18.6, 11.2. HRMS (HESI‐II): m/z [M+Na]⁺ calcd for C₂₆H₃₁ClNaOSi: 445.1725; found 445.1723.

4.5.7. (E)‐2‐(2‐Fluoro‐6‐((triisopropylsilyl)ethynyl)phenyl)‐3‐phenylacrylaldehyde (Scheme 2, Product 3ga)

This compound was prepared according to General Procedures using stilbene 1 g (0.25 mmol, 1.0 equiv.) and alkynyl bromide 2a (0.5 mmol, 2.0 equiv.) as substrates, and the reaction was performed under constant current 0.8 mA (1/80 Hz. D = 50%). The crude product was purified by column chromatography (EtOAc/Hexane = 1:10, R _f = 0.40) to afford a sticky colorless oil in 31% yield (31.4 mg). ¹H NMR (500 MHz, CDCl₃) δ 9.75 (s, 1H), 7.60 (s, 1H), 7.40 (dd, J = 7.8, 1.1 Hz, 1H), 7.37–7.31 (m, 2H), 7.27‐7.21 (m, 4H), 7.12 (td, J = 8.6, 1.1 Hz, 1H), 0.95 (s, 21H). ¹³C NMR (125 MHz, CDCl₃) δ 192.4, 159.7 (d, J_F = 245.4 Hz), 152.0, 135.1, 134.0, 130.8, 130.4, 130.0 (d, J_F = 8.9 Hz), 129.0 (d, J_F = 2.9 Hz), 128.8, 125.7 (d, J_F = 4.7 Hz), 124.7 (d, J_F = 18.3 Hz), 116.3 (d, J_F = 22.3 Hz), 103.6 (d, J_F = 4.1 Hz), 95.7, 18.6, 11.2. ¹⁹F NMR (470 MHz, CDCl₃) δ ‐112.5(m). HRMS (HESI‐II): m/z [M+Na]⁺ calcd for C₂₆H₃₁FNaOSi: 429.2020; found 429.2015.

4.5.8. (E)‐3‐Phenyl‐2‐(3‐((triisopropylsilyl)ethynyl)‐[1,1'‐biphenyl]‐2‐yl)acrylaldehyde (Scheme 2, Product 3ha)

This compound was prepared according to General Procedures using stilbene 1 h (0.25 mmol, 1.0 equiv.) and alkynyl bromide 2a (0.5 mmol, 2.0 equiv.) as substrates, and the reaction was performed under constant current 0.8 mA (1/80 Hz. D = 50%). The crude product was purified by column chromatography (EtOAc/Hexane = 1:10, R _f = 0.62) to afford a sticky colorless oil in 60% yield (69.7 mg). ¹H NMR (500 MHz, CDCl₃) δ 9.53 (s, 1H), 7.63 (dd, J = 7.8, 1.3 Hz, 1H), 7.42 (t, J = 7.8 Hz, 1H), 7.32‐7.28 (m, 2H), 7.27 (s, 1H), 7.23‐7.20 (m, 2H), 7.19‐7.17 (m, 1H), 7.16‐7.12 (m, 2H), 7.07 (d, J = 7.4 Hz, 2H), 6.97 (d, J = 6.9 Hz, 2H), 0.97 (s, 21H). ¹³C NMR (125 MHz, CDCl₃) δ 193.4, 151.0, 142.4, 140.8, 140.7, 135.6, 134.5, 132.4, 130.5, 130.4, 130.3, 128.6, 128.5, 128.4, 127.8, 127.2, 124.1, 105.3, 94.4, 18.7, 11.3. HRMS (HESI‐II): m/z [M+Na]⁺ calcd for C₃₂H₃₆NaOSi: 487.2428; found 487.2425.

4.5.9. (E)‐3‐Phenyl‐2‐(3‐((triisopropylsilyl)ethynyl)dibenzo[b,d]furan‐4‐yl)acrylaldehyde (Scheme 2, Product 3ia)

This compound was prepared according to General Procedures using stilbene 1i (0.2 mmol, 1.0 equiv.) and alkynyl bromide 2a (0.4 mmol, 2.0 equiv.) as substrates, and the reaction was performed under constant current 0.6 mA (1/80 Hz. D = 50%). The crude product was purified by column chromatography (EtOAc/Hexane = 1:10, R _f = 0.38) to afford a sticky yellow oil in 70% yield (67.0 mg). ¹H NMR (500 MHz, CDCl₃) δ 9.88 (s, 1H), 7.94 (t, J = 8.0 Hz, 2H), 7.74 (s, 1H), 7.60 (d, J = 8.0 Hz, 1H), 7.45‐7.41 (m, 2H), 7.36‐7.32 (m, 1H), 7.26‐7.24 (m, 1H), 7.21‐7.19 (m, 2H), 7.18‐7.15 (m, 2H), 0.98 (s, 21H). ¹³C NMR (125 MHz, CDCl₃) δ 192.6, 156.9, 153.6, 152.0, 135.6, 134.1, 130.8, 130.6, 128.8, 128.0, 127.8, 124.9, 124.0, 123.2, 122.2, 121.5, 121.0, 120.6, 112.1, 104.9, 95.2, 18.7, 11.3. HRMS (HESI‐II): m/z [M+Na]⁺ calcd for C₃₂H₃₄NaO₂Si: 501.2220; found 501.2216.

4.5.10. (E)‐3‐Phenyl‐2‐(3‐((triisopropylsilyl)ethynyl)dibenzo[b,d]thiophen‐4‐yl)acrylaldehyde (Scheme 2, Product 3ja)

This compound was prepared according to General Procedures using stilbene 1i (0.2 mmol, 1.0 equiv.) and alkynyl bromide 2a (0.4 mmol, 2.0 equiv.) as substrates, and the reaction was performed under constant current 0.6 mA (1/80 Hz. D = 50%). The crude product was purified by column chromatography (EtOAc/Hexane = 1:10, R _f = 0.40) to afford a yellow solid in 78% yield (77.1 mg). ¹H NMR (500 MHz, CDCl₃) δ 9.86 (s, 1H), 8.15 (t, J = 7.5 Hz, 2H), 7.74‐7.70 (m, 3H), 7.46 (t, J = 7.5 Hz, 1H), 7.42 (t, J = 7.4 Hz, 1H), 7.27‐7.24 (m, 1H), 7.21‐7.15 (m, 4H), 1.00 (s, 21H). ¹³C NMR (125 MHz, CDCl₃) δ 192.2, 151.2, 140.3, 139.7, 139.0, 135.8, 135.7, 133.8, 132.2, 130.9, 130.5, 129.4, 128.8, 127.2, 124.7, 123.0, 122.1, 121.9, 121.3, 105.0, 95.5, 18.7, 11.3. HRMS (HESI‐II): m/z [M+Na]⁺ calcd for C₃₂H₃₄NaOSSi: 517.1992; found 517.1986. Melting point 114.8‐116.2°C

4.5.11. Methyl (E)‐3‐(3‐oxo‐1‐phenylprop‐1‐en‐2‐yl)‐4‐((triisopropylsilyl)ethynyl)benzoate (Scheme 2, Product 3ka)

This compound was prepared according to General Procedures using stibene 1k (0.20 mmol, 1.0 equiv.) and alkynyl bromide 2a (0.4 mmol, 2.0 equiv.) as substrates, and the reaction was performed under constant current 0.6 mA (1/80 Hz. D = 50%). The crude product was purified by column chromatography (EtOAc/Hexane = 1:10, R _f = 0.18) to afford a sticky colorless oil in 30% yield (33.5 mg). ¹H NMR (500 MHz, CDCl₃) δ 9.76 (s, 1H), 8.04 (dd, J = 8.5 Hz, 2H), 7.81(d, J = 8.5 Hz, 1H), 7.67(d, J = 8.5 Hz, 1H), 7.51 (s, 1H), 7.29 (t, J = 8.5 Hz, 1H), 7.22 (t, J = 8.3 Hz, 2H), 7.14 (d, J = 8.1 Hz, 2H), 3.88 (s, 3H), 0.96 (s, 21H). ¹³C NMR (100 MHz, CDCl₃) δ 192.9, 166.3, 150.9, 140.3, 137.4, 133.8, 133.3, 130.7, 130.6, 130.2, 129.3, 128.8, 128.2, 104.1, 98.2, 52.4, 18.6, 11.2. HRMS (HESI‐II): m/z [M+H]⁺ calcd for C₂₈H₃₅O₃Si: 447.2350; found 447.2352.

4.5.12. (E)‐3‐Phenyl‐2‐(3‐((triisopropylsilyl)ethynyl)naphthalen‐2‐yl)acrylaldehyde (Scheme 2, Product 3la)

This compound was prepared according to General Procedures using stilbene 1l (0.2 mmol, 1.0 equiv.) and alkynyl bromide 2a (0.4 mmol, 2.0 equiv.) as substrates, and the reaction was performed under constant current 0.6 mA (1/80 Hz. D = 50%). The crude product was purified by column chromatography (EtOAc/Hexane = 1:10, R _f = 0.44) to afford a sticky colorless oil in 52% yield (45.6 mg). ¹H NMR (500 MHz, CDCl₃) δ 9.86 (s, 1H), 8.19 (s, 1H), 7.82 (d, J = 8.0 Hz, 1H), 7.82 (d, J = 7.9 Hz, 1H),7.64 (s, 1H), 7.58 (s, 1H), 7.57‐7.50 (m, 2H), 7.30‐7.27 (m, 1H), 7.23‐7.19 (m, 4H), 1.03 (s, 21H). ¹³C NMR (125 MHz, CDCl₃) δ 193.6, 150.6, 141.0, 134.2, 133.6, 133.5, 133.1, 132.8, 130.9, 130.5, 128.7, 128.1, 127.7, 127.1, 127.0, 121.1, 105.2, 94.2, 18.7, 11.3. HRMS (HESI‐II): m/z [M+Na]⁺ calcd for C₃₀H₃₄NaOSi: 461.2271; found 461.2265.

4.5.13. (E)‐3‐Phenyl‐2‐(2‐((triisopropylsilyl)ethynyl)pyren‐1‐yl)acrylaldehyde (Scheme 2, Product 3ma)

This compound was prepared according to General Procedures using stilbene 1m (0.2 mmol, 1.0 equiv.) and alkynyl bromide 2a (0.4 mmol, 2.0 equiv.) as substrates, and the reaction was performed under constant current 0.6 mA (1/80 Hz. D = 50%). The crude product was purified by column chromatography (EtOAc/Hexane = 1:10, R _f = 0.45) to afford a sticky colorless oil in 50% yield (51.3 mg). ¹H NMR (500 MHz, CDCl₃) δ 10.01 (s, 1H), 8.42 (s, 1H), 8.20 (d, J = 7.6 Hz, 1H), 8.15‐8.11 (m, 2H), 8.06 (d, J = 9.0 Hz, 1H), 8.02‐7.97 (m, 2H), 7.88 (s, 1H), 7.81 (d, J = 9.0 Hz, 1H), 7.19‐7.16 (m, 1H), 7.06‐7.04 (m, 4H), 1.03 (s, 21H). ¹³C NMR (125 MHz, CDCl₃) δ 193.7, 151.9, 139.7, 134.2, 131.8, 131.5, 131.3, 131.2, 130.7, 130.7, 129.2, 128.9, 128.8, 128.5, 127.1, 126.7, 125.8, 125.7, 124.7, 124.7, 124.5, 121.1, 105.8, 94.9, 18.8, 11.4. HRMS (HESI‐II): m/z [M+Na]⁺ calcd for C₃₆H₃₆NaOSi: 535.2428; found 535.2422.

4.5.14. (E)‐3‐Phenyl‐2‐(2‐((triisopropylsilyl)ethynyl)benzo[b]thiophen‐3‐yl)acrylaldehyde (Scheme 2, Product 3na)

This compound was prepared according to General Procedures using stilbene 1n (0.2 mmol, 1.0 equiv.) and alkynyl bromide 2a (0.4 mmol, 2.0 equiv.) as substrates. The crude product was purified by column chromatography (EtOAc/Hexane = 1:10, R _f = 0.42) to afford a sticky yellow oil in 57% yield (63.3 mg). ¹H NMR (500 MHz, CDCl₃) δ 9.85 (s, 1H), 7.80 (d, J = 8.1 Hz, 1H), 7.74 (s, 1H), 7.38 (t, J = 7.5 Hz, 1H), 7.32 (d, J = 7.6 Hz, 1H), 7.28‐7.25 (m, 2H), 7.22‐7.19 (m, 4H), 0.98 (s, 21H). ¹³C NMR (125 MHz, CDCl₃) δ 192.6, 152.2, 139.7, 137.3, 134.7, 134.7, 133.9, 130.9, 130.7, 128.8, 126.1, 125.0, 123.3, 122.4, 122.3, 101.6, 98.5, 18.6, 11.2. HRMS (HESI‐II): m/z [M+H]⁺ calcd for C₂₈H₃₃OSSi: 444.2016; found 444.2009. m/z [M+Na]⁺ calcd for C₂₈H₃₂NaOSSi: 467.1835; found 467.1829.

4.5.15. (E)‐3‐Phenyl‐2‐(2‐((triisopropylsilyl)ethynyl)benzo[b]furan‐3‐yl)acrylaldehyde (Scheme 2, Product 3oa)

This compound was prepared according to General Procedures using stilbene 1o (0.2 mmol, 1.0 equiv.) and alkynyl bromide 2a (0.4 mmol, 2.0 equiv.) as substrates, and the reaction was performed under constant current 0.6 mA (1/80 Hz. D = 50%). The crude product was purified by column chromatography (EtOAc/Hexane = 1:10, R _f = 0.48) to afford a sticky colorless oil in 42% yield (45.0 mg). ¹H NMR (500 MHz, CDCl₃) δ 9.83 (s, 1H), 7.69 (s, 1H), 7.49 (d, J = 8.4 Hz, 1H), 7.37‐7.33 (m, 3H), 7.30 (t, J = 7.4 Hz, 1H), 7.23 (t, J = 7.5 Hz, 2H), 7.18‐7.13 (m, 2H), 1.00 (s, 21H). ¹³C NMR (125 MHz, CDCl₃) δ 192.4, 154.7, 151.7, 137.1, 134.0, 131.2, 130.9, 130.8, 128.8, 126.8, 126.3, 123.6, 121.1, 119.0, 111.7, 102.7, 95.3, 18.6, 11.2. HRMS (HESI‐II): m/z [M+H]⁺ calcd for C₂₈H₃₃O₂Si: 429.2244; found 429.2237. [M+Na]⁺ calcd for C₂₈H₃₂NaO₂Si: 451.2064; found 451.2055.

4.5.16. (E)‐2‐(2,6‐Bis((triisopropylsilyl)ethynyl)phenyl)‐3‐phenylacrylaldehyde (Scheme 2, Product 3ra)

This compound was prepared according to General Procedures using stilbene 1r (0.2 mmol, 1.0 equiv.) and alkynyl bromide 2a (0.8 mmol, 4.0 equiv.) as substrates, and the reaction was performed under constant current 0.6 mA (1/80 Hz. D = 50%). The crude product was purified by column chromatography (EtOAc/Hexane = 1:10, R _f = 0.42) to afford a white solid in 52% yield (59.1 mg). ¹H NMR (500 MHz, CDCl₃) δ 9.72 (s, 1H), 7.54 (d, J = 8.0 Hz, 2H), 7.51 (s, 1H), 7.31 (t, J = 7.5 Hz, 1H), 7.27 (d, J = 7.5 Hz, 1H), 7.21 (t, J = 7.5 Hz, 2H), 7.16 (t, J = 8.0 Hz, 2H), 0.95 (s, 42H). ¹³C NMR (125 MHz, CDCl₃) δ 192.6, 150.6, 140.2, 134.3, 132.9, 130.5, 130.5, 128.7, 128.2, 124.1, 104.4, 94.9, 18.6, 11.3. HRMS (HESI‐II): m/z [M+Na]⁺ calcd for C₃₇H₅₂NaOSi₂: 591.3449; found 591.3441. Melting point 76.5‐77.9°C

4.5.17. (E)‐2‐(4‐Methoxy‐2,6‐bis((triisopropylsilyl)ethynyl)phenyl)‐3‐phenylacrylaldehyde (Scheme 2, Product 3sa)

This compound was prepared according to General Procedures using stilbene 1s (0.2 mmol, 1.0 equiv.) and alkynyl bromide 2a (0.8 mmol, 4.0 equiv.) as substrates, and the reaction was performed under constant current 0.6 mA (1/80 Hz. D = 50%). The crude product was purified by column chromatography (EtOAc/Hexane = 1:10, R _f = 0.32) to afford a sticky colorless oil in 56% yield (67.0 mg). ¹H NMR (500 MHz, CDCl₃) δ 9.71 (s, 1H), 7.49 (s, 1H), 7.30‐7.27 (m, 1H), 7.23 (d, J = 7.5 Hz, 2H), 7.18 (d, J = 7.0 Hz, 2H), 7.08 (s, 2H), 3.85 (s, 3H), 0.95 (s, 42H). ¹³C NMR (125 MHz, CDCl₃) δ 193.00, 158.9, 150.9, 140.0, 134.4, 132.6, 130.5, 130.4, 128.6, 124.9, 118.7, 104.4, 94.6, 55.7, 18.6, 11.3. HRMS (HESI‐II): m/z [M+Na]⁺ calcd for C₂₇H₃₄NaO₂Si: 621.3555; found 621.3547.

4.5.18. (E)‐2‐(3‐Methoxy‐2,6‐bis((triisopropylsilyl)ethynyl)phenyl)‐3‐phenylacrylaldehyde (Scheme 2, Product 3ta)

This compound was prepared according to General Procedures using stilbene 1t (0.2 mmol, 1.0 equiv.) and alkynyl bromide 2a (0.8 mmol, 4.0 equiv.) as substrates, and the reaction was performed under constant current 0.6 mA (1/80 Hz. D = 50%). The crude product was purified by column chromatography (EtOAc/Hexane = 1:10, R _f = 0.30) to afford a white solid in 46% yield (55.1 mg). ¹H NMR (500 MHz, CDCl₃) δ 9.70 (s, 1H), 7.51‐7.49 (m, 2H), 7.28‐7.26 (m, 1H), 7.23‐7.18 (m, 4H), 3.90 (s, 3H), 0.97 (s, 21H), 0.94 (s, 21H). ¹³C NMR (125 MHz, CDCl₃) δ 192.5, 161.1, 150.4, 142.2, 140.1, 134.3, 134.0, 130.6, 130.4, 128.6, 116.0, 113.5, 110.6, 104.5, 100.3, 99.6, 92.5, 56.2, 18.7, 11.4, 11.3. HRMS (HESI‐II): m/z [M+Na]⁺ calcd for C₂₇H₃₄NaO₂Si: 621.3555; found 621.3547. Melting point 79.1‐80.5°C

4.5.19. (E)‐3‐(p‐Tolyl)‐2‐(2‐((triisopropylsilyl)ethynyl)naphthalen‐1‐yl)acrylaldehyde (Scheme 2, Product 3ua)

This compound was prepared according to General Procedures using stilbene 1u (0.2 mmol, 1.0 equiv.) and alkynyl bromide 2a (0.4 mmol, 2.0 equiv.) as substrates, and the reaction was performed under constant current 0.6 mA (1/80 Hz. D = 50%). The crude product was purified by column chromatography (EtOAc/Hexane = 1:10, R _f = 0.44) to afford a sticky yellow oil in 58% yield (52.5 mg). ¹H NMR (500 MHz, CDCl₃) δ 9.88 (s, 1H), 7.86 (d, J = 8.5 Hz, 1H), 7.86 (d, J = 8.5 Hz, 1H), 7.73 (s, 1H), 7.64 (d, J = 8.5 Hz, 1H), 7.60 (d, J = 8.5 Hz, 1H), 7.48‐7.45 (m,1H), 7.40‐7.38 (m, 1H), 6.96‐6.91(m, 4H), 2.23 (s, 3H), 0.99 (s, 21H). ¹³C NMR (125 MHz, CDCl₃) δ 193.4, 151.8, 141.3, 138.4, 136.0, 133.2, 131.4, 131.1, 130.8, 129.5, 129.3, 128.5, 128.5, 127.3, 126.9, 125.4, 121.1, 105.8, 95.3, 21.6, 18.7, 11.3. HRMS (HESI‐II): m/z [M+Na]⁺ calcd for C₃₁H₃₆NaOSi: 475.2428; found 475.2423.

4.5.20. (E)‐3‐(4‐Methoxyphenyl)‐2‐(2‐((triisopropylsilyl)ethynyl)naphthalen‐1‐yl)acrylaldehyde (Scheme 2, Product 3va)

This compound was prepared according to General Procedures using stilbene 1v (0.2 mmol, 1.0 equiv.) and alkynyl bromide 2a (0.4 mmol, 2.0 equiv.) as substrates, and the reaction was performed under constant current 0.6 mA (1/80 Hz. D = 50%). The crude product was purified by column chromatography (EtOAc/Hexane = 1:10, R _f = 0.40) to afford a sticky yellow oil in 48% yield (45.0 mg). ¹H NMR (500 MHz, CDCl₃) δ 9.85 (s, 1H), 7.86 (t, J = 8.1 Hz, 1H), 7.85 (d, J = 8.1 Hz, 1H), 7.70 (s, 1H), 7.64 (d, J = 8.5 Hz, 1H), 7.61 (d, J = 8.4 Hz, 1H), 7.49‐7.45 (m, 1H), 7.40‐7.37 (m, 1H), 7.02‐7.00 (m, 2H), 6.65‐6.52 (m, 2H), 3.71 (s, 1H), 7.02 (d, J = 7.8 Hz, 2H), 6.46 (d, J = 15.9 Hz, 1H), 3.73 (s, 3H), 0.99 (s, 21H). ¹³C NMR (125 MHz, CDCl₃) δ 193.3, 161.6, 151.5, 137.0, 136.1, 133.3, 132.7, 131.2, 129.3, 128.5, 128.5, 127.3, 127.0, 126.9, 125.4, 121.1, 114.3, 105.8, 95.1, 55.4, 18.7, 11.3. HRMS (HESI‐II): m/z [M+Na]⁺ calcd for C₃₁H₃₆NaO₂Si: 491.2377; found 491.2372.

4.5.21. (E)‐3‐(4‐Fluorophenyl)‐2‐(2‐((triisopropylsilyl)ethynyl)naphthalen‐1‐yl)acrylaldehyde (Scheme 2, Product 3wa)

This compound was prepared according to General Procedures using stilbene 1w (0.2 mmol, 1.0 equiv.) and alkynyl bromide 2a (0.4 mmol, 2.0 equiv.) as substrates, and the reaction was performed under constant current 0.6 mA (1/80 Hz. D = 50%). The crude product was purified by column chromatography (EtOAc/Hexane = 1:10, R _f = 0.33) to afford a sticky colorless oil in 55% yield (50.2 mg). ¹H NMR (500 MHz, CDCl₃) δ 9.87 (s, 1H), 7.87 (d, J = 8.1 Hz, 1H), 7.86 (d, J = 8.5 Hz, 1H), 7.72 (s, 1H), 7.64 (d, J = 8.5 Hz, 1H), 7.57 (d, J = 8.4 Hz, 1H), 7.50‐7.47(m, 1H), 7.41‐7.38 (m, 1H), 7.08‐7.05 (m, 2H), 6.83‐6.80 (m, 2H), 0.99 (s, 21H). ¹³C NMR (125 MHz, CDCl₃) δ 193.2, 163.9 (d, J_F = 252 Hz), 149.9, 138.9 (d, J_F = 2.0 Hz), 135.3, 133.3, 132.7 (d, J_F = 8.8 Hz), 131.0, 130.4 (d, J_F = 3.0 Hz), 129.3, 128.7, 128.4, 127.4, 127.1, 125.1, 121.2, 116.0 (d, J_F = 21.7 Hz), 105.6, 95.6, 18.7, 11.3. ¹⁹F NMR (470 MHz, CDCl₃) δ ‐108.4. HRMS (HESI‐II): m/z [M+Na]⁺ calcd for C₃₀H₃₃FNaOSi: 479.21769; found 479.21755. Melting point 136.1‐137.3°C.

4.5.22. (E)‐3‐(4‐Chlorophenyl)‐2‐(2‐((triisopropylsilyl)ethynyl)naphthalen‐1‐yl)acrylaldehyde (Scheme 2, Product 3xa)

This compound was prepared according to General Procedures using stilbene 1x (0.2 mmol, 1.0 equiv.) and alkynyl bromide 2a (0.4 mmol, 2.0 equiv.) as substrates, and the reaction was performed under constant current 0.6 mA (1/80 Hz. D = 50%). The crude product was purified by column chromatography (EtOAc/Hexane = 1:10, R _f = 0.38) to afford a sticky colorless oil in 80% yield (75.5 mg). ¹H NMR (500 MHz, CDCl₃) δ 9.88 (s, 1H), 7.87 (d, J = 8.1 Hz, 1H), 7.86 (d, J = 8.5 Hz, 1H), 7.71 (s, 1H), 7.63 (d, J = 8.5 Hz, 1H), 7.56 (d, J = 8.4 Hz, 1H), 7.50‐7.47(m, 1H), 7.41‐7.38 (m, 1H), 7.10‐7.08 (m, 2H), 7.01‐6.98 (m, 2H), 1.00 (s, 21H). ¹³C NMR (125 MHz, CDCl₃) δ 193.0, 149.6, 139.7, 136.7, 135.2, 133.2, 132.6, 131.7, 130.9, 129.3, 129.1, 128.8, 128.7, 127.5, 127.1, 125.1, 121.1, 105.5, 95.8, 18.7, 11.3. HRMS (HESI‐II): m/z [M+Na]⁺ calcd for C₃₀H₃₃ClNaOSi: 495.1881; found 495.1876. Melting point 116.1‐117.5°C

4.5.23. (E)‐3‐(3‐(Trifluoromethyl)phenyl‐2‐(2‐((triisopropylsilyl)ethynyl)naphthalen‐1‐yl)acrylaldehyde (Scheme 2, Product 3ya)

This compound was prepared according to General Procedures using stibene 1y (0.2 mmol, 1.0 equiv.) and alkynyl bromide 2a (0.5 mmol, 2.0 equiv.) as substrates, and the reaction was performed under constant current 0.6 mA (1/80 Hz. D = 50%). The crude product was purified by column chromatography (EtOAc/Hexane = 1:10, R _f = 0.30) to afford a sticky colorless oil in 42% yield (47.0 mg). ¹H NMR (500 MHz, CDCl₃) δ 9.92 (s, 1H), 7.88 (d, J = 8.5 Hz, 2H), 7.78 (s, 1H), 7.63 (d, J = 8.5 Hz, 1H), 7.56 (d, J = 8.3 Hz, 1H), 7.51‐7.45 (m, 2H), 7.44 (s, 1H), 7.42‐7.39 (m, 1H), 7.18 (t, J = 7.8 Hz, 1H), 7.12 (d, J = 8.1 Hz, 1H), 0.98 (s, 21H). ¹³C NMR (125 MHz, CDCl₃) δ 192.9, 148.9, 140.9, 133.2, 132.7, 131.2 (d, J_F = 32.5 Hz), 131.0, 129.3, 129.2, 129.0, 128.7, 127.7 (d, J_F = 3.8 Hz), 127.5, 127.1, 126.9 (d, J_F = 3.6 Hz), 125.0, 123.4 (d, J_F = 270.8 Hz), 121.1, 105.4, 96.0, 18.6, 11.3. ¹⁹F NMR (470 MHz, CDCl₃) δ ‐63.3. HRMS (HESI‐II): m/z [M+H]⁺ calcd for C₃₁H₃₃F₃OSi: 507.2326; found 507.2336.

4.5.24. (E)‐4‐Methyl‐2‐(2‐((triisopropylsilyl)ethynyl)naphthalen‐1‐yl)pent‐2‐enal (Scheme 2, Product 3za)

This compound was prepared according to General Procedures using stibene 1z (0.20 mmol, 1.0 equiv.) and alkynyl bromide 2a (0.4 mmol, 2.0 equiv.) as substrates, and the reaction was performed under constant current 0.6 mA (1/80 Hz. D = 50%). The crude product was purified by column chromatography (EtOAc/Hexane = 1:10, R _f = 0.62) to afford a light‐yellow oil in 15% yield (11.7 mg). ¹H NMR (400 MHz, CDCl₃) δ 10.32 (s, 1H), 7.82 (dd, J = 7.4, 1.6 Hz, 1H), 7.76 (d, J = 8.5 Hz, 1H), 7.58(d, J = 8.5 Hz, 1H), 7.54 (dd, J = 7.5, 1.4 Hz, 1H), 7.44 (quintd, J = 7.4, 2.0 Hz, 2H), 2.47 (s, 3H), 1.69 (s, 3H), 1.10 (s, 21H). ¹³C NMR (100 MHz, CDCl₃) δ 189.6, 158.7, 138.1, 136.2, 133.2, 131.9, 129.1, 128.5, 127.9, 126.9, 126.6, 125.4, 121.4, 106.4, 94.2, 29.9, 24.7, 18.8, 11.4. HRMS (HESI‐II): m/z [M+H]⁺ calcd for C₂₆H₃₅OSi: 391.2452; found 391.2452; m/z [M+Na]⁺ calcd for C₂₆H₃₄NaOSi: 413.2271; found 413.2271.

4.5.25. (E)‐2‐(2‐((tert‐Butyldimethylsilyl)ethynyl)naphthalen‐1‐yl)‐3‐phenylacrylaldehyde (Scheme 2, Product 3ab)

This compound was prepared according to General Procedures using stilbene 1a (0.2 mmol, 1.0 equiv.) and TBS‐protected alkynyl bromide 2b (0.4 mmol, 2.0 equiv.) as substrates, and the reaction was performed under constant current 0.6 mA (1/80 Hz. D = 50%). The crude product was purified by column chromatography (EtOAc/Hexane = 1:10, R _f = 0.56) to afford a sticky colorless oil in 67% yield (53.0 mg). ¹H NMR (500 MHz, CDCl₃) δ 9.89 (s, 1H), 7.86 (d, J = 8.0 Hz, 1H), 7.85 (d, J = 8.1 Hz, 1H), 7.77 (s, 1H), 7.62 (d, J = 8.5 Hz, 1H), 7.59 (d, J = 8.5 Hz, 1H), 7.49‐7.46(m, 1H), 7.40‐7.37 (m, 1H), 7.23 (t, J = 7.3 Hz, 1H), 7.12 (t, J = 7.5 Hz, 2H), 7.07 (d, J = 7.9 Hz, 2H), 0.58 (s, 9H), 0.06 (s, 3H), 0.03(s, 3H). ¹³C NMR (125 MHz, CDCl₃) δ 193.3, 151.5, 139.2, 135.9, 134.1, 133.3, 131.1, 130.7, 130.6, 129.0, 128.8, 128.6, 128.6, 127.3, 127.0, 125.3, 120.8, 104.6, 97.4, 26.1, 16.8, ‐4.6. HRMS (HESI‐II): m/z [M+Na]⁺ calcd for C₂₇H₂₈NaOSi: 419.1802; found 419.1795.

4.5.26. (E)‐3‐Phenyl‐2‐(2‐((triethylsilyl)ethynyl)naphthalen‐1‐yl)acrylaldehyde (Scheme 2, Product 3ac)

This compound was prepared according to General Procedures using stilbene 1a (0.2 mmol, 1.0 equiv.) and TES‐procted alkynyl bromide 2c (0.4 mmol, 2.0 equiv.) as substrates, and the reaction was performed under constant current 0.6 mA (1/80 Hz. D = 50%). The crude product was purified by column chromatography (EtOAc/Hexane = 1:10, R _f = 0.55) to afford a sticky colorless oil in 62% yield (49.1 mg). ¹H NMR (500 MHz, CDCl₃) δ 9.89 (s, 1H), 7.87‐7.84 (m, 2H), 7.77 (s, 1H), 7.62 (d, J = 8.5 Hz, 1H), 7.59 (d, J = 8.5 Hz, 1H), 7.49‐7.46(m, 1H), 7.40‐7.37 (m, 1H), 7.23 (t, J = 7.3 Hz, 1H), 7.12 (t, J = 7.5 Hz, 1H), 7.07 (d, J = 7.9 Hz, 1H), 0.90 (t, J = 8.0 Hz, 9H), 0.53 (q, J = 8.0 Hz, 6H). ¹³C NMR (125 MHz, CDCl₃) δ 193.3, 151.4, 139.2, 136.0, 134.1, 133.3, 131.1, 130.6, 130.6, 129.0, 128.8, 128.6, 128.6, 127.3, 127.0, 125.4, 120.9, 105.2, 96.6, 7.6, 4.5. HRMS (HESI‐II): m/z [M+Na]⁺ calcd for C₂₇H₂₈NaOSi: 419.1802; found 419.1797.

4.5.27. (E)‐2‐(2‐Methyl‐6‐((triisopropylsilyl)ethynyl)phenyl)‐3‐phenylprop‐2‐en‐1‐ol (Scheme 5, Compound 8)

This compound was prepared according to General Procedures using compound 3ba (2.0 mmol, 1.0 equiv.) as substrate. The crude product was purified by column chromatography (EtOAc/Hexane = 1:10, R _f = 0.12) to afford a white solid in 96% yield (0.77 g). ¹H NMR (500 MHz, CDCl₃) δ 7.43 (d, J = 7.1 Hz, 1H), 7.20‐7.15 (m, 2H), 7.11‐7.10 (m, 3H), 6.95 (d, J = 3.3, 2H), 6.94 (s, 1H), 6.79 (s, 1H), 4.47 (s, 2H), 2.11 (s, 3H), 4.47 (s, 2H), 1.04 (s, 21H). ¹³C NMR (125 MHz, CDCl₃) δ 140.9, 139.5, 136.7, 136.4, 130.8, 130.7, 128.4, 128.2, 127.8, 127.4, 127.1, 123.4, 106.3, 93.5, 68.2, 19.8, 18.7, 18.7, 11.4. HRMS (HESI‐II): m/z [M+Na]⁺ calcd for C₂₇H₃₆NaOSi: 427.2428; found 427.2420. Melting point: 102.3‐104.5 °C

4.5.28. (E)‐2‐(2‐Methyl‐6‐((triisopropylsilyl)ethynyl)phenyl)‐3‐phenylacrylic acid (Scheme 5, Compound 9)

This compound was prepared according to General Procedures using compound 3ba (2.0 mmol, 1.0 equiv.) as substrate. The crude product was purified by column chromatography (MeOH/EtOAc/Hexane = 1:5:10, R _f = 0.12) to afford a colorless oil in 95% yield (0.79 g). ¹H NMR (500 MHz, CDCl₃) δ 7.43 (d, J = 8.0 Hz, 1H), 7.26‐7.16 (m, 5H), 7.05 (d, J = 8.0 Hz, 2H), 2.10 (s, 3H), 0.98 (s, 21H). ¹³C NMR (125 MHz, CDCl₃) δ 172.3, 143.2, 138.1, 136.9, 134.7, 130.5, 130.4, 130.3, 129.8, 129.7, 128.6, 128.0, 124.0, 105.4, 94.2, 19.9, 18.7, 11.3. HRMS (HESI‐II): m/z [M‐H]⁻ calcd for C₂₇H₃₄O₂Si: 417.2255; found 417.2256.

4.5.29. (E)‐2‐(3‐Ethynyldibenzo[b,d]furan‐4‐yl)‐3‐phenylacrylaldehyde (Scheme 5, Compound 10)

This compound was prepared according to General Procedures using compound 3ia (0.5 mmol, 1.0 equiv.) as substrate. The crude product was purified by column chromatography (EtOAc/Hexane = 1:10, R _f = 0.55) to afford a white solid in 90% yield (0.145 g). ¹H NMR (500 MHz, CDCl₃) δ 9.91 (s, 1H), 7.96 (d, J = 8.0 Hz, 2H), 7.80 (s, 1H), 7.63 (d, J = 8.0 Hz, 1H), 7.44‐7.42 (m, 2H), 7.36‐7.33 (m, 1H), 7.27‐7.24 (m, 1H), 7.26‐7.10 (m, 4H), 3.06 (s, 3H). ¹³C NMR (125 MHz, CDCl₃) δ 192.5, 156.9, 153.6, 152.2, 135.2, 134.2, 130.8, 130.4, 128.8, 128.1, 128.0, 125.4, 123.9, 123.3, 121.8, 121.1, 120.8, 112.1, 82.0, 81.1. HRMS (HESI‐II): m/z [M+Na]⁺ calcd for C₂₃H₁₄NaO₂: 345.0886; found 345.0878. Melting point 217.6‐219.2 °C.

[CCDC 2463153, CCDC 2463058, and CCDC 2463060 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.] (Supporting Information).

Author Contributions

Junya Wang: methodology, investigation, writing – original draft, data curation, formal analysis. Xiaozhou Wang: methodology, investigation, data curation. Pui Ying Choy: writing – original draft, investigation, methodology, writing – review and editing. Chi‐Wai Cheung: writing – original draft. Li‐Wen Xu: funding acquisition, project administration. Hung Kay Lee: data curation, formal analysis. Gui‐Juan Cheng: supervision, writing – review and editing, funding acquisition, project administration, conceptualization. Fuk Yee Kwong: funding acquisition, writing – review and editing, project administration, supervision, resources, conceptualization.

Conflicts of Interest

The authors declare no conflicts of interest.

Supporting information

Supporting File: advs76881‐sup‐0001‐SuppMat.pdf.

ADVS-13-e76881-s001.pdf^{(13.9MB, pdf)}

Acknowledgements

We thank the Research Grants Council of Hong Kong, General Research Fund (GRF 14310024), Collaborative Research Fund (CRF C4001‐23G), NSFC/RGC Joint Research Scheme (N_CUHK426/23), 1+1+1 CUHK‐CUHK(SZ)‐GDST Joint Collaborative Fund‐General R&D Projects (2025A0505000041), CUHK Direct Grant (2024‐25) and Innovation and Technology Commission (HKSAR, China)—State Key Laboratory of Synthetic Chemistry for financial support. We thank Junjun LIU for preparing of some starting materials.

Contributor Information

Gui‐Juan Cheng, Email: chengguijuan@cuhk.edu.cn.

Fuk Yee Kwong, Email: fykwong@cuhk.edu.hk.

Data Availability Statement

The data that support the findings of this study are available in the Supporting Information of this article. Copies of the NMR spectra are also provided. The X‐ray crystallography coordinates for structures of 3ja (CCDC 2463153), 8 (CCDC 2463058) and 10 (CCDC 2463060) have been deposited at the Cambridge Crystallographic Data Centre (CCDC).

References

1. Diederich F., Stang P. J., and Tykwinski R. R., Acetylene Chemistry: Chemistry, Biology, and Material Science (Wiley‐VCH, 2005), 10.1002/3527605487. [DOI] [Google Scholar]
2. Magano J. and Dunetz J. R., “Large‐Scale Applications of Transition Metal‐Catalyzed Couplings for the Synthesis of Pharmaceuticals,” Chemical Reviews 111, no. 3 (2011): 2177–2250, 10.1021/cr100346g. [DOI] [PubMed] [Google Scholar]
3. Wang D. and Gao S., “Sonogashira Coupling in Natural Product Synthesis,” Organic Chemistry Frontiers 1, no. 5 (2014): 556–566, 10.1039/C3QO00086A. [DOI] [Google Scholar]
4. Yan F., Zhang X., Li D., Zhu N., and Bao H., “Recent Applications of the Sonogashira Reaction in the Synthesis of Drugs and Their Derivatives: A Review,” Applied Organometallic Chemistry 39, no. 1 (2025): 7932, 10.1002/aoc.7932. [DOI] [Google Scholar]
5. Dudnik A. S. and Gevorgyan V., “Formal Inverse Sonogashira Reaction: Direct Alkynylation of Arenes and Heterocycles With Alkynyl Halides,” Angewandte Chemie International Edition 49, no. 12 (2010): 2096–2098, 10.1002/anie.200906755. [DOI] [PMC free article] [PubMed] [Google Scholar]
6. Brand J. P. and Waser J., “Electrophilic Alkynylation: The Dark Side of Acetylene Chemistry,” Chemical Society Reviews 41, no. 11 (2012): 4165–4179, 10.1039/C2CS35034C. [DOI] [PubMed] [Google Scholar]
7. Chinchilla R. and Nájera C., “The Sonogashira Reaction: A Booming Methodology in Synthetic Organic Chemistry,” Chemical Reviews 107, no. 3 (2007): 874–922, 10.1021/cr050992x. [DOI] [PubMed] [Google Scholar]
8. Chinchilla R. and Nájera C., “Recent Advances in Sonogashira Reactions,” Chemical Society Reviews 40, no. 10 (2011): 5084–5121, 10.1039/C1CS15071E. [DOI] [PubMed] [Google Scholar]
9. Choy P. Y., Gan K. B., and Kwong F. Y., “Recent Expedition in Pd‐Catalyzed Sonogashira Coupling and Related Processes †,” Chinese Journal of Chemistry 41, no. 9 (2023): 1099–1118, 10.1002/cjoc.202200703. [DOI] [Google Scholar]
10. Struwe J., Ackermann L., and Gallou F., “Recent Progress in Copper‐Free Sonogashira‐Hagihara Cross‐Couplings in Water,” Chem Catalysis 3, no. 1 (2023): 100485, 10.1016/j.checat.2022.12.002. [DOI] [Google Scholar]
11. Frankenberger S., Wendinger D., Scherer A., Sonogashira K., and Tykwinski R. R., “A Half Century of the Sonogashira Reaction,” in Organic Reactions (John Wiley & Son Inc, 2025), 1–2117, 10.1002/0471264180.or116.01. [DOI] [Google Scholar]
12. Wu W. and Jiang H., “Haloalkynes: A Powerful and Versatile Building Block in Organic Synthesis,” Accounts of Chemical Research 47, no. 8 (2014): 2483–2504, 10.1021/ar5001499. [DOI] [PubMed] [Google Scholar]
13. Chen C., Zhang Q., Li Y., et al., “Multitasking Haloalkynes in Synthetic Chemistry,” Tetrahedron Letters 147 (2024): 155229, 10.1016/j.tetlet.2024.155229. [DOI] [Google Scholar]
14. Tobisu M., Ano Y., and Chatani N., “Palladium‐Catalyzed Direct Alkynylation of C−H Bonds in Benzenes,” Organic Letters 11, no. 15 (2009): 3250–3252, 10.1021/ol901049r. [DOI] [PubMed] [Google Scholar]
15. Liao G., Yao Q.‐J., Zhang Z.‐Z., Wu Y.‐J., Huang D.‐Y., and Shi B.‐F., “Scalable, Stereocontrolled Formal Syntheses of (+)‐Isoschizandrin and (+)‐Steganone: Development and Applications of Palladium(II)‐Catalyzed Atroposelective C−H Alkynylation,” Angewandte Chemie International Edition 57, no. 14 (2018): 3661–3665, 10.1002/anie.201713106. [DOI] [PubMed] [Google Scholar]
16. Yang Q.‐L., Guo H.‐M., and Mei T.‐S., “Electrochemical Palladium‐Catalyzed C−H Functionalization,” in Handbook of CH−Functionalization, ed. Maiti D., (Wiley‐VCH, 2022), 1–32, 10.1002/9783527834242.chf0001. [DOI] [Google Scholar]
17. Ackermann A., Science of Synthesis: Electrochemistry in Organic Synthesis (Thieme, 2021). [Google Scholar]
18. Fuchigami T., Inagi S., and Atobe M., Fundamentals and Applications of Organic Electrochemistry (John Wiley & Sons, 2015), 10.1002/9781118670750. [DOI] [Google Scholar]
19. Yoshida J.‐I., Kataoka K., Horcajada R., and Nagaki A., “Modern Strategies in Electroorganic Synthesis,” Chemical Reviews 108, no. 7 (2008): 2265–2299, 10.1021/cr0680843. [DOI] [PubMed] [Google Scholar]
20. Yan M., Kawamata Y., and Baran P. S., “Synthetic Organic Electrochemical Methods Since 2000: On the Verge of a Renaissance,” Chemical Reviews 117, no. 21 (2017): 13230–13319, 10.1021/acs.chemrev.7b00397. [DOI] [PMC free article] [PubMed] [Google Scholar]
21. Möhle S., Zirbes M., Rodrigo E., Gieshoff T., Wiebe A., and Waldvogel S. R., “Modern Electrochemical Aspects for the Synthesis of Value‐Added Organic Products,” Angewandte Chemie International Edition 57 (2018): 6018–6041, 10.1002/anie.201712732. [DOI] [PMC free article] [PubMed] [Google Scholar]
22. Pollok D. and Waldvogel S. R., “Electro‐Organic Synthesis—A 21st Century Technique,” Chemical Science 11, no. 46 (2020): 12386–12400, 10.1039/D0SC01848A. [DOI] [PMC free article] [PubMed] [Google Scholar]
23. Meyer T. H., Choi I., Tian C., and Ackermann L., “Powering the Future: How Can Electrochemistry Make a Difference in Organic Synthesis?,” Chemistry 6, no. 10 (2020): 2484–2496, 10.1016/j.chempr.2020.08.025. [DOI] [Google Scholar]
24. Siu J. C., Fu N., and Lin S., “Catalyzing Electrosynthesis: A Homogeneous Electrocatalytic Approach to Reaction Discovery,” Accounts of Chemical Research 53, no. 3 (2020): 547–560, 10.1021/acs.accounts.9b00529. [DOI] [PMC free article] [PubMed] [Google Scholar]
25. Cheng X., Lei A., Mei T.‐S., Xu H.‐C., Xu K., and Zeng C., “Recent Applications of Homogeneous Catalysis in Electrochemical Organic Synthesis,” CCS Chemistry 4, no. 4 (2022): 1120–1152, 10.31635/ccschem.021.202101451. [DOI] [Google Scholar]
26. Regnier M., Vega C., Ioannou D. I., and Noël T., “Enhancing Electrochemical Reactions in Organic Synthesis: The Impact of Flow Chemistry,” Chemical Society Reviews 53, no. 21 (2024): 10741–10760, 10.1039/D4CS00539B. [DOI] [PubMed] [Google Scholar]
27. Yang Z., Shi W., Alhumade H., Yi H., and Lei A., “Electrochemical Oxidative C(sp³)–H Cross‐Coupling With Hydrogen Evolution,” Nature Synthesis 2, no. 3 (2023): 217–230, 10.1038/s44160-022-00221-2. [DOI] [Google Scholar]
28. Jiao K.‐J., Xing Y.‐K., Yang Q.‐L., Qiu H., and Mei T.‐S., “Site‐Selective C–H Functionalization via Synergistic Use of Electrochemistry and Transition Metal Catalysis,” Accounts of Chemical Research 53, no. 2 (2020): 300–310, 10.1021/acs.accounts.9b00603. [DOI] [PubMed] [Google Scholar]
29. Ma C., Fang P., and Mei T.‐S., “Recent Advances in C–H Functionalization Using Electrochemical Transition Metal Catalysis,” ACS Catalysis 8, no. 8 (2018): 7179–7189, 10.1021/acscatal.8b01697. [DOI] [Google Scholar]
30. Sauermann N., Meyer T. H., Qiu Y., and Ackermann L., “Electrocatalytic C–H Activation,” ACS Catalysis 8, no. 8 (2018): 7086–7103, 10.1021/acscatal.8b01682. [DOI] [Google Scholar]
31. Wang Y., Dana S., Long H., et al., “Electrochemical Late‐Stage Functionalization,” Chemical Reviews 123, no. 19 (2023): 11269–11335, 10.1021/acs.chemrev.3c00158. [DOI] [PMC free article] [PubMed] [Google Scholar]
32. Xiong P. and Xu H.‐C., “Chemistry With Electrochemically Generated N‐Centered Radicals,” Accounts of Chemical Research 52, no. 12 (2019): 3339–3350, 10.1021/acs.accounts.9b00472. [DOI] [PubMed] [Google Scholar]
33. Lin C. Y., Coote M. L., Gennaro A., and Matyjaszewski K., “Ab Initio Evaluation of the Thermodynamic and Electrochemical Properties of Alkyl Halides and Radicals and Their Mechanistic Implications for Atom Transfer Radical Polymerization,” Journal of the American Chemical Society 130, no. 38 (2008): 12762–12774, 10.1021/ja8038823. [DOI] [PubMed] [Google Scholar]
34. Costentin C., Robert M., and Saveant J.‐M., “Electron Transfer and Bond Breaking: Recent Advances,” Chemical Physics 324, no. 1 (2006): 40–56, 10.1016/j.chemphys.2005.09.029. [DOI] [Google Scholar]
35. Li J.‐Z., Mei L., Yu X.‐C., et al., “C‐Centered Radical‐Initiated Cyclization by Directed C(sp³)–H Oxidative Functionalization,” Organic Chemistry Frontiers 9, no. 20 (2022): 5726–5757, 10.1039/D2QO01128J. [DOI] [Google Scholar]
36. Xu T., Zhu J., Han Y., and Chi C., “Carbon‐Centered Radical Based Dynamic Covalent Chemistry for Stimuli‐Responsive Chromic Materials,” Journal of Materials Chemistry C 11, no. 24 (2023): 7957–7969, 10.1039/D3TC00117B. [DOI] [Google Scholar]
37. Fontana F., Minisci F., and Vismara E., “New General and Convenient Sources of Alkyl Radicals, Useful for Selective Syntheses,” Tetrahedron Letters 29, no. 16 (1988): 1975–1978, 10.1016/S0040-4039(00)82093-6. [DOI] [Google Scholar]
38. Crespi S. and Fagnoni M., “Generation of Alkyl Radicals: From the Tyranny of Tin to the Photon Democracy,” Chemical Reviews 120, no. 17 (2020): 9790–9833, 10.1021/acs.chemrev.0c00278. [DOI] [PMC free article] [PubMed] [Google Scholar]
39. Luo M.‐J., Ding H., Yang R., and Xiao Q., “Electrocatalytic Synthesis: An Environmentally Benign Alternative for Radical‐Mediated Aryl/Alkenyl C(sp²)–C(sp³) Cross‐Coupling Reactions,” Green Chemistry 24, no. 24 (2022): 9373–9401, 10.1039/D2GC03829C. [DOI] [Google Scholar]
40. Pagire S. K., Föll T., and Reiser O., “Shining Visible Light on Vinyl Halides: Expanding the Horizons of Photocatalysis,” Accounts of Chemical Research 53, no. 4 (2020): 782–791, 10.1021/acs.accounts.9b00615. [DOI] [PubMed] [Google Scholar]
41. Muresan M., Subramanian H., Sibi M. P., and Green J. R., “Propargyl Radicals in Organic Synthesis,” European Journal of Organic Chemistry 2021, no. 22 (2021): 3359–3375, 10.1002/ejoc.202100367. [DOI] [Google Scholar]
42. Yu Y. and Zhang J., “Allenyl Radicals in Organic Synthesis: Challenges and Recent Advances,” European Journal of Organic Chemistry 2022, no. 43 (2022): 202201017, 10.1002/ejoc.202201017. [DOI] [Google Scholar]
43. Kvasovs N. and Gevorgyan V., “Contemporary Methods for Generation of Aryl Radicals,” Chemical Society Reviews 50, no. 4 (2021): 2244–2259, 10.1039/D0CS00589D. [DOI] [PMC free article] [PubMed] [Google Scholar]
44. Grudzień K., Zlobin A., Zadworny J., Rybicka‐Jasińska K., and Sadowski B., “Modern Photo‐ and Electrochemical Approaches to Aryl Radical Generation,” Organic Chemistry Frontiers 11, no. 18 (2024): 5232–5277, 10.1039/D4QO00999A. [DOI] [Google Scholar]
45. Zeng X., “The Strategies Towards Electrochemical Generation of Aryl Radicals,” Chemistry—A European Journal 30, no. 54 (2024): 202402220, 10.1002/chem.202402220. [DOI] [PubMed] [Google Scholar]
46. Xie X.‐Q., Zhou W., Yang R., Song X.‐R., Luo M.‐J., and Xiao Q., “Electroreduction Strategy: A Sustainable Tool for the Generation of Aryl Radicals,” Organic Chemistry Frontiers 11, no. 15 (2024): 4318–4342, 10.1039/D4QO00846D. [DOI] [Google Scholar]
47. Zhao H., Cuomo V. D., Tian W., Romano C., and Procter D. J., “Light‐Assisted Functionalization of Aryl Radicals Towards Metal‐Free Cross‐Coupling,” Nature Reviews Chemistry 9, no. 1 (2025): 61–80, 10.1038/s41570-024-00664-5. [DOI] [PubMed] [Google Scholar]
48. Lakhal A., Gimbert Y., Mouriès‐Mansuy V., Ollivier C., and Fensterbank L., “Alkynyl Radicals, Myths and Realities,” JACS Au 5, no. 2 (2025): 448–465, 10.1021/jacsau.4c01040. [DOI] [PMC free article] [PubMed] [Google Scholar]
49. Saveant J.‐M., “Electron Transfer, Bond Breaking, and Bond Formation,” Accounts of Chemical Research 26, no. 9 (1993): 455–461, 10.1021/ar00033a001. [DOI] [Google Scholar]
50. Saveant J.‐M., “Dissociative Electron Transfer. New Tests of the Theory in the Electrochemical and Homogeneous Reduction of Alkyl Halides,” Journal of the American Chemical Society 114, no. 26 (1992): 10595–10602, 10.1021/ja00052a065. [DOI] [Google Scholar]
51. Costentin C., Robert M., and Savéant J.‐M., “Successive Removal of Chloride Ions From Organic Polychloride Pollutants. Mechanisms of Reductive Electrochemical Elimination in Aliphatic Gem‐Polychlorides, α,β‐Polychloroalkenes, and α,β‐Polychloroalkanes in Mildly Protic Medium,” Journal of the American Chemical Society 125, no. 35 (2003): 10729–10739, 10.1021/ja036141t. [DOI] [PubMed] [Google Scholar]
52. Costentin C., Robert M., and Savéant J.‐M., “Fragmentation of Aryl Halide π Anion Radicals. Bending of the Cleaving Bond and Activation vs Driving Force Relationships,” Journal of the American Chemical Society 126, no. 49 (2004): 16051–16057, 10.1021/ja045989u. [DOI] [PubMed] [Google Scholar]
53. Isse A. A., Scarpa L., Durante C., and Gennaro A., “Reductive Cleavage of Carbon–Chlorine Bonds at Catalytic and Non‐Catalytic Electrodes in 1‐Butyl‐3‐Methylimidazolium Tetrafluoroborate,” Physical Chemistry Chemical Physics 17, no. 46 (2015): 31228–31236, 10.1039/C5CP04142B. [DOI] [PubMed] [Google Scholar]
54. Rosokha S. V., Lukacs E., Ritzert J. T., and Wasilewski A., “Mechanism and Thermodynamics of Reductive Cleavage of Carbon–Halogen Bonds in the Polybrominated Aliphatic Electrophiles,” The Journal of Physical Chemistry A 120, no. 10 (2016): 1706–1715, 10.1021/acs.jpca.5b11410. [DOI] [PubMed] [Google Scholar]
55. Mazzucato M., Isse A. A., and Durante C., “Dissociative Electron Transfer Mechanism and Application in the Electrocatalytic Activation of Organic Halides,” Current Opinion in Electrochemistry 39 (2023): 101254, 10.1016/j.coelec.2023.101254. [DOI] [Google Scholar]
56. Zeng L., Li H., Hu J., et al., “Electrochemical Oxidative Aminocarbonylation of Terminal Alkynes,” Nature Catalysis 3, no. 5 (2020): 438–445, 10.1038/s41929-020-0443-z. [DOI] [Google Scholar]
57. Zeng L., Jiao Y., Yan W., et al., “Asymmetric‐Waveform Alternating Current‐Promoted Silver Catalysis for C–H Phosphorylation,” Nature Synthesis 2, no. 2 (2023): 172–181, 10.1038/s44160-022-00197-z. [DOI] [Google Scholar]
58. Bortolami M., Petrucci R., Rocco D., Scarano V., and Chiarotto I., “Alkynes as Building Blocks, Intermediates and Products in the Electrochemical Procedures Since 2000,” ChemElectroChem 8, no. 19 (2021): 3604–3613, 10.1002/celc.202100497. [DOI] [Google Scholar]
59. Choy P. Y., Chow W. K., So C. M., Lau C. P., and Kwong F. Y., “Palladium‐Catalyzed Sonogashira Coupling of Aryl Mesylates and Tosylates,” Chemistry—A European Journal 16, no. 33 (2010): 9982–9985, 10.1002/chem.201001269. [DOI] [PubMed] [Google Scholar]
60. Fan B.‐M., Yang Q.‐J., Hu J., et al., “Asymmetric Hydroalkynylation of Norbornadienes Promoted by Chiral Iridium Catalysts,” Angewandte Chemie International Edition 51, no. 31 (2012): 7821–7824, 10.1002/anie.201203107. [DOI] [PubMed] [Google Scholar]
61. Yang Q., Choy P. Y., Fan B., and Kwong F. Y., “Enantioselective Hydroalkynylation of Non‐Polar Carbon‐Carbon Double Bonds: Iridium‐Catalyzed Asymmetric Addition Reaction of Terminal Alkyne C─H Bonds to Substituted Norbornadienes,” Advanced Synthesis & Catalysis 357, no. 10 (2015): 2345–2350, 10.1002/adsc.201500465. [DOI] [Google Scholar]
62. Zhao Q., Fu W. C., and Kwong F. Y., “Palladium‐Catalyzed Regioselective Aromatic Extension of Internal Alkynes Through a Norbornene‐Controlled Reaction Sequence,” Angewandte Chemie International Edition 57, no. 13 (2018): 3381–3385, 10.1002/anie.201713207. [DOI] [PubMed] [Google Scholar]
63. He X., Li R., Choy P. Y., et al., “Rapid Access of Alkynyl and Alkenyl Coumarins via a Dipyridinium Methylide and Propargylamine Cascade Reaction,” Organic Letters 22, no. 18 (2020): 7348–7352, 10.1021/acs.orglett.0c02674. [DOI] [PubMed] [Google Scholar]
64. Lau Y. K., Hui C. P., Li C. L., et al., “Indole‐Based π‐Extended Monophosphine Ligands for Enhanced Palladium‐Catalyzed Sonogashira Coupling,” Journal of Heterocyclic Chemistry 63, no. 4 (2026): 727–737, 10.1002/jhet.70151. [DOI] [Google Scholar]
65. Rodrigo S., Gunasekera D., Mahajan J. P., and Luo L., “Alternating Current Electrolysis for Organic Synthesis,” Current Opinion in Electrochemistry 28 (2021): 100712, 10.1016/j.coelec.2021.100712. [DOI] [PMC free article] [PubMed] [Google Scholar]
66. Wan Q., Chen K., Dong X., Ruan X., Yi H., and Chen S., “Elucidating the Underlying Reactivities of Alternating Current Electrosynthesis by Time‐Resolved Mapping of Short‐Lived Reactive Intermediates,” Angewandte Chemie International Edition 62, no. 40 (2023): 202306460, 10.1002/anie.202306460. [DOI] [PubMed] [Google Scholar]
67. Zeng L., Yang Q., Wang J., et al., “Programmed Alternating Current Optimizationof Cu‐catalyzed C‐H Bond Transformations,” Science 385, no. 6705 (2024): 216–223, 10.1126/science.ado0875. [DOI] [PubMed] [Google Scholar]
68. Li H., Peng J., Zeng L., et al., “Augmentation of Pd‐Catalysed Oxidative C–H/C–H Carbonylation Through Alternating Current Electrosynthesis,” Green Chemistry 26, no. 22 (2024): 11177–11181, 10.1039/D4GC04569F. [DOI] [Google Scholar]
69. Bortnikov E. O. and Semenov S. N., “Coupling of Alternating Current to Transition‐Metal Catalysis: Examples of Nickel‐Catalyzed Cross‐Coupling,” The Journal of Organic Chemistry 86, no. 1 (2021): 782–793, 10.1021/acs.joc.0c02350. [DOI] [PMC free article] [PubMed] [Google Scholar]
70. Gandeepan P. and Ackermann L., “Transient Directing Groups for Transformative C–H Activation by Synergistic Metal Catalysis,” Chemistry 4, no. 2 (2018): 199–222, 10.1016/j.chempr.2017.11.002. [DOI] [Google Scholar]
71. Higham J. I. and Bull J. A., “Transient Imine Directing Groups for the C–H Functionalisation of Aldehydes, Ketones and Amines: An Update 2018–2020,” Organic & Biomolecular Chemistry 18, no. 37 (2020): 7291–7315, 10.1039/D0OB01587C. [DOI] [PubMed] [Google Scholar]
72. Jacob C., Maes B. U. W., and Evano G., “Transient Directing Groups in Metal−Organic Cooperative Catalysis,” Chemistry—A European Journal 27, no. 56 (2021): 13899–13952, 10.1002/chem.202101598. [DOI] [PubMed] [Google Scholar]
73. Goswami N., Bhattacharya T., and Maiti D., “Transient Directing Ligands for Selective Metal‐Catalysed C–H Activation,” Nature Reviews Chemistry 5, no. 9 (2021): 646–659, 10.1038/s41570-021-00311-3. [DOI] [PubMed] [Google Scholar]
74. Dhawa U., Tian C., Wdowik T., Oliveira J. C. A., Hao J., and Ackermann L., “Enantioselective Pallada‐Electrocatalyzed C−H Activation by Transient Directing Groups: Expedient Access to Helicenes,” Angewandte Chemie International Edition 59, no. 32 (2020): 13451–13457, 10.1002/anie.202003826. [DOI] [PMC free article] [PubMed] [Google Scholar]
75. Zhang F.‐L., Hong K., Li T.‐J., Park H., and Yu J.‐Q., “Functionalization of C(sp³)–H Bonds Using a Transient Directing Group,” Science 351, no. 6270 (2016): 252–256, 10.1126/science.aad7893. [DOI] [PMC free article] [PubMed] [Google Scholar]
76. Liu M., Sun J., Erbay T., et al., “Pd^II‐Catalyzed C(alkenyl)−H Activation Facilitated by a Transient Directing Group,” Angewandte Chemie International Edition 61 (2022): 202203624, 10.1002/anie.202203624. [DOI] [PMC free article] [PubMed] [Google Scholar]
77. Rawson J. M. and Winpenny R. E. P., “The Coordination Chemistry of 2‐pyridone and Its Derivatives,” Coordination Chemistry Reviews 139 (1995): 313–374, 10.1016/0010-8545(94)01117-T. [DOI] [Google Scholar]
78. Fedulin A. and von Wangelin A. J., “2‐Pyridonates: A Versatile Ligand Platform in 3d Transition Metal Coordination Chemistry and Catalysis,” Catalysis Science & Technology 14, no. 1 (2024): 26–42, 10.1039/D3CY01190A. [DOI] [Google Scholar]
79. Mandal N. and Datta A., “Harnessing the Efficacy of 2‐Pyridone Ligands for Pd‐Catalyzed (β/γ)‐C(sp³)–H Activations,” The Journal of Organic Chemistry 85, no. 20 (2020): 13228–13238, 10.1021/acs.joc.0c02210. [DOI] [PubMed] [Google Scholar]
80. de Meijere A., Bräse S., and Oestreich M., Metal‐Catalyzed Cross‐Coupling Reactions and More (Wiley‐VCH, 2013), 10.1002/9783527655588. [DOI] [Google Scholar]
81. Colacot T., New Trends in Cross‐Coupling: Theory and Applications (RSC Publishing, 2015), 10.1039/9781782620259. [DOI] [Google Scholar]
82. Tse M. H., Choy P. Y., and Kwong F. Y., “Facile Assembly of Modular‐Type Phosphines for Tackling Modern Arylation Processes,” Accounts of Chemical Research 55, no. 24 (2022): 3688–3705, 10.1021/acs.accounts.2c00587. [DOI] [PubMed] [Google Scholar]
83. Martelli G., Spagnolo P., and Tiecco M., “Homolytic Aromatic Substitution by Phenylethynyl Radicals,” Journal of the Chemical Society D: Chemical Communications (1969): 282b–283, 10.1039/C2969000282B. [DOI] [Google Scholar]
84. Martelli G., Spagnolo P., and Tiecco M., “Homolytic Aromatic Substitution by Phenylethynyl Radicals,” Journal of the Chemical Society B: Physical Organic (1970): 1413–1418, 10.1039/J29700001413. [DOI] [Google Scholar]
85. Coleman J. S., Hudson A., Root K. D. J., and Walton D. R. M., “Observation of a Free Radical During the Photolysis of Phenyliodoacetylene,” Chemical Physics Letters 11, no. 3 (1971): 300–301, 10.1016/0009-2614(71)80491-8. [DOI] [Google Scholar]
86. Boutillier P. and Zard S. Z., “Synthetic Equivalents of Alkynyl and Propargyl Radicals,” Chemical Communications 37, no. 14 (2001): 1304–1305, 10.1039/B101751I. [DOI] [Google Scholar]
87. Zhang L., Wei C., Wu J., et al., “Photoinduced Inverse Sonogashira Coupling Reaction,” Chemical Science 13, no. 25 (2022): 7475–7481, 10.1039/D2SC01933G. [DOI] [PMC free article] [PubMed] [Google Scholar]
88. Dhawa U., Wdowik T., Hou X., Yuan B., Oliveira J. C. A., and Ackermann L., “Enantioselective Palladaelectro‐Catalyzed C–H Olefinations and Allylations for N–C Axial Chirality,” Chemical Science 12, no. 42 (2021): 14182–14188, 10.1039/D1SC04687J. [DOI] [PMC free article] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Supporting File: advs76881‐sup‐0001‐SuppMat.pdf.

ADVS-13-e76881-s001.pdf^{(13.9MB, pdf)}

Data Availability Statement

[advs76881-bib-0001] 1. Diederich F., Stang P. J., and Tykwinski R. R., Acetylene Chemistry: Chemistry, Biology, and Material Science (Wiley‐VCH, 2005), 10.1002/3527605487. [DOI] [Google Scholar]

[advs76881-bib-0002] 2. Magano J. and Dunetz J. R., “Large‐Scale Applications of Transition Metal‐Catalyzed Couplings for the Synthesis of Pharmaceuticals,” Chemical Reviews 111, no. 3 (2011): 2177–2250, 10.1021/cr100346g. [DOI] [PubMed] [Google Scholar]

[advs76881-bib-0003] 3. Wang D. and Gao S., “Sonogashira Coupling in Natural Product Synthesis,” Organic Chemistry Frontiers 1, no. 5 (2014): 556–566, 10.1039/C3QO00086A. [DOI] [Google Scholar]

[advs76881-bib-0004] 4. Yan F., Zhang X., Li D., Zhu N., and Bao H., “Recent Applications of the Sonogashira Reaction in the Synthesis of Drugs and Their Derivatives: A Review,” Applied Organometallic Chemistry 39, no. 1 (2025): 7932, 10.1002/aoc.7932. [DOI] [Google Scholar]

[advs76881-bib-0005] 5. Dudnik A. S. and Gevorgyan V., “Formal Inverse Sonogashira Reaction: Direct Alkynylation of Arenes and Heterocycles With Alkynyl Halides,” Angewandte Chemie International Edition 49, no. 12 (2010): 2096–2098, 10.1002/anie.200906755. [DOI] [PMC free article] [PubMed] [Google Scholar]

[advs76881-bib-0006] 6. Brand J. P. and Waser J., “Electrophilic Alkynylation: The Dark Side of Acetylene Chemistry,” Chemical Society Reviews 41, no. 11 (2012): 4165–4179, 10.1039/C2CS35034C. [DOI] [PubMed] [Google Scholar]

[advs76881-bib-0007] 7. Chinchilla R. and Nájera C., “The Sonogashira Reaction: A Booming Methodology in Synthetic Organic Chemistry,” Chemical Reviews 107, no. 3 (2007): 874–922, 10.1021/cr050992x. [DOI] [PubMed] [Google Scholar]

[advs76881-bib-0008] 8. Chinchilla R. and Nájera C., “Recent Advances in Sonogashira Reactions,” Chemical Society Reviews 40, no. 10 (2011): 5084–5121, 10.1039/C1CS15071E. [DOI] [PubMed] [Google Scholar]

[advs76881-bib-0009] 9. Choy P. Y., Gan K. B., and Kwong F. Y., “Recent Expedition in Pd‐Catalyzed Sonogashira Coupling and Related Processes †,” Chinese Journal of Chemistry 41, no. 9 (2023): 1099–1118, 10.1002/cjoc.202200703. [DOI] [Google Scholar]

[advs76881-bib-0010] 10. Struwe J., Ackermann L., and Gallou F., “Recent Progress in Copper‐Free Sonogashira‐Hagihara Cross‐Couplings in Water,” Chem Catalysis 3, no. 1 (2023): 100485, 10.1016/j.checat.2022.12.002. [DOI] [Google Scholar]

[advs76881-bib-0011] 11. Frankenberger S., Wendinger D., Scherer A., Sonogashira K., and Tykwinski R. R., “A Half Century of the Sonogashira Reaction,” in Organic Reactions (John Wiley & Son Inc, 2025), 1–2117, 10.1002/0471264180.or116.01. [DOI] [Google Scholar]

[advs76881-bib-0012] 12. Wu W. and Jiang H., “Haloalkynes: A Powerful and Versatile Building Block in Organic Synthesis,” Accounts of Chemical Research 47, no. 8 (2014): 2483–2504, 10.1021/ar5001499. [DOI] [PubMed] [Google Scholar]

[advs76881-bib-0013] 13. Chen C., Zhang Q., Li Y., et al., “Multitasking Haloalkynes in Synthetic Chemistry,” Tetrahedron Letters 147 (2024): 155229, 10.1016/j.tetlet.2024.155229. [DOI] [Google Scholar]

[advs76881-bib-0014] 14. Tobisu M., Ano Y., and Chatani N., “Palladium‐Catalyzed Direct Alkynylation of C−H Bonds in Benzenes,” Organic Letters 11, no. 15 (2009): 3250–3252, 10.1021/ol901049r. [DOI] [PubMed] [Google Scholar]

[advs76881-bib-0015] 15. Liao G., Yao Q.‐J., Zhang Z.‐Z., Wu Y.‐J., Huang D.‐Y., and Shi B.‐F., “Scalable, Stereocontrolled Formal Syntheses of (+)‐Isoschizandrin and (+)‐Steganone: Development and Applications of Palladium(II)‐Catalyzed Atroposelective C−H Alkynylation,” Angewandte Chemie International Edition 57, no. 14 (2018): 3661–3665, 10.1002/anie.201713106. [DOI] [PubMed] [Google Scholar]

[advs76881-bib-0016] 16. Yang Q.‐L., Guo H.‐M., and Mei T.‐S., “Electrochemical Palladium‐Catalyzed C−H Functionalization,” in Handbook of CH−Functionalization, ed. Maiti D., (Wiley‐VCH, 2022), 1–32, 10.1002/9783527834242.chf0001. [DOI] [Google Scholar]

[advs76881-bib-0017] 17. Ackermann A., Science of Synthesis: Electrochemistry in Organic Synthesis (Thieme, 2021). [Google Scholar]

[advs76881-bib-0018] 18. Fuchigami T., Inagi S., and Atobe M., Fundamentals and Applications of Organic Electrochemistry (John Wiley & Sons, 2015), 10.1002/9781118670750. [DOI] [Google Scholar]

[advs76881-bib-0019] 19. Yoshida J.‐I., Kataoka K., Horcajada R., and Nagaki A., “Modern Strategies in Electroorganic Synthesis,” Chemical Reviews 108, no. 7 (2008): 2265–2299, 10.1021/cr0680843. [DOI] [PubMed] [Google Scholar]

[advs76881-bib-0020] 20. Yan M., Kawamata Y., and Baran P. S., “Synthetic Organic Electrochemical Methods Since 2000: On the Verge of a Renaissance,” Chemical Reviews 117, no. 21 (2017): 13230–13319, 10.1021/acs.chemrev.7b00397. [DOI] [PMC free article] [PubMed] [Google Scholar]

[advs76881-bib-0021] 21. Möhle S., Zirbes M., Rodrigo E., Gieshoff T., Wiebe A., and Waldvogel S. R., “Modern Electrochemical Aspects for the Synthesis of Value‐Added Organic Products,” Angewandte Chemie International Edition 57 (2018): 6018–6041, 10.1002/anie.201712732. [DOI] [PMC free article] [PubMed] [Google Scholar]

[advs76881-bib-0022] 22. Pollok D. and Waldvogel S. R., “Electro‐Organic Synthesis—A 21st Century Technique,” Chemical Science 11, no. 46 (2020): 12386–12400, 10.1039/D0SC01848A. [DOI] [PMC free article] [PubMed] [Google Scholar]

[advs76881-bib-0023] 23. Meyer T. H., Choi I., Tian C., and Ackermann L., “Powering the Future: How Can Electrochemistry Make a Difference in Organic Synthesis?,” Chemistry 6, no. 10 (2020): 2484–2496, 10.1016/j.chempr.2020.08.025. [DOI] [Google Scholar]

[advs76881-bib-0024] 24. Siu J. C., Fu N., and Lin S., “Catalyzing Electrosynthesis: A Homogeneous Electrocatalytic Approach to Reaction Discovery,” Accounts of Chemical Research 53, no. 3 (2020): 547–560, 10.1021/acs.accounts.9b00529. [DOI] [PMC free article] [PubMed] [Google Scholar]

[advs76881-bib-0025] 25. Cheng X., Lei A., Mei T.‐S., Xu H.‐C., Xu K., and Zeng C., “Recent Applications of Homogeneous Catalysis in Electrochemical Organic Synthesis,” CCS Chemistry 4, no. 4 (2022): 1120–1152, 10.31635/ccschem.021.202101451. [DOI] [Google Scholar]

[advs76881-bib-0026] 26. Regnier M., Vega C., Ioannou D. I., and Noël T., “Enhancing Electrochemical Reactions in Organic Synthesis: The Impact of Flow Chemistry,” Chemical Society Reviews 53, no. 21 (2024): 10741–10760, 10.1039/D4CS00539B. [DOI] [PubMed] [Google Scholar]

[advs76881-bib-0027] 27. Yang Z., Shi W., Alhumade H., Yi H., and Lei A., “Electrochemical Oxidative C(sp³)–H Cross‐Coupling With Hydrogen Evolution,” Nature Synthesis 2, no. 3 (2023): 217–230, 10.1038/s44160-022-00221-2. [DOI] [Google Scholar]

[advs76881-bib-0028] 28. Jiao K.‐J., Xing Y.‐K., Yang Q.‐L., Qiu H., and Mei T.‐S., “Site‐Selective C–H Functionalization via Synergistic Use of Electrochemistry and Transition Metal Catalysis,” Accounts of Chemical Research 53, no. 2 (2020): 300–310, 10.1021/acs.accounts.9b00603. [DOI] [PubMed] [Google Scholar]

[advs76881-bib-0029] 29. Ma C., Fang P., and Mei T.‐S., “Recent Advances in C–H Functionalization Using Electrochemical Transition Metal Catalysis,” ACS Catalysis 8, no. 8 (2018): 7179–7189, 10.1021/acscatal.8b01697. [DOI] [Google Scholar]

[advs76881-bib-0030] 30. Sauermann N., Meyer T. H., Qiu Y., and Ackermann L., “Electrocatalytic C–H Activation,” ACS Catalysis 8, no. 8 (2018): 7086–7103, 10.1021/acscatal.8b01682. [DOI] [Google Scholar]

[advs76881-bib-0031] 31. Wang Y., Dana S., Long H., et al., “Electrochemical Late‐Stage Functionalization,” Chemical Reviews 123, no. 19 (2023): 11269–11335, 10.1021/acs.chemrev.3c00158. [DOI] [PMC free article] [PubMed] [Google Scholar]

[advs76881-bib-0032] 32. Xiong P. and Xu H.‐C., “Chemistry With Electrochemically Generated N‐Centered Radicals,” Accounts of Chemical Research 52, no. 12 (2019): 3339–3350, 10.1021/acs.accounts.9b00472. [DOI] [PubMed] [Google Scholar]

[advs76881-bib-0033] 33. Lin C. Y., Coote M. L., Gennaro A., and Matyjaszewski K., “Ab Initio Evaluation of the Thermodynamic and Electrochemical Properties of Alkyl Halides and Radicals and Their Mechanistic Implications for Atom Transfer Radical Polymerization,” Journal of the American Chemical Society 130, no. 38 (2008): 12762–12774, 10.1021/ja8038823. [DOI] [PubMed] [Google Scholar]

[advs76881-bib-0034] 34. Costentin C., Robert M., and Saveant J.‐M., “Electron Transfer and Bond Breaking: Recent Advances,” Chemical Physics 324, no. 1 (2006): 40–56, 10.1016/j.chemphys.2005.09.029. [DOI] [Google Scholar]

[advs76881-bib-0035] 35. Li J.‐Z., Mei L., Yu X.‐C., et al., “C‐Centered Radical‐Initiated Cyclization by Directed C(sp³)–H Oxidative Functionalization,” Organic Chemistry Frontiers 9, no. 20 (2022): 5726–5757, 10.1039/D2QO01128J. [DOI] [Google Scholar]

[advs76881-bib-0036] 36. Xu T., Zhu J., Han Y., and Chi C., “Carbon‐Centered Radical Based Dynamic Covalent Chemistry for Stimuli‐Responsive Chromic Materials,” Journal of Materials Chemistry C 11, no. 24 (2023): 7957–7969, 10.1039/D3TC00117B. [DOI] [Google Scholar]

[advs76881-bib-0037] 37. Fontana F., Minisci F., and Vismara E., “New General and Convenient Sources of Alkyl Radicals, Useful for Selective Syntheses,” Tetrahedron Letters 29, no. 16 (1988): 1975–1978, 10.1016/S0040-4039(00)82093-6. [DOI] [Google Scholar]

[advs76881-bib-0038] 38. Crespi S. and Fagnoni M., “Generation of Alkyl Radicals: From the Tyranny of Tin to the Photon Democracy,” Chemical Reviews 120, no. 17 (2020): 9790–9833, 10.1021/acs.chemrev.0c00278. [DOI] [PMC free article] [PubMed] [Google Scholar]

[advs76881-bib-0039] 39. Luo M.‐J., Ding H., Yang R., and Xiao Q., “Electrocatalytic Synthesis: An Environmentally Benign Alternative for Radical‐Mediated Aryl/Alkenyl C(sp²)–C(sp³) Cross‐Coupling Reactions,” Green Chemistry 24, no. 24 (2022): 9373–9401, 10.1039/D2GC03829C. [DOI] [Google Scholar]

[advs76881-bib-0040] 40. Pagire S. K., Föll T., and Reiser O., “Shining Visible Light on Vinyl Halides: Expanding the Horizons of Photocatalysis,” Accounts of Chemical Research 53, no. 4 (2020): 782–791, 10.1021/acs.accounts.9b00615. [DOI] [PubMed] [Google Scholar]

[advs76881-bib-0041] 41. Muresan M., Subramanian H., Sibi M. P., and Green J. R., “Propargyl Radicals in Organic Synthesis,” European Journal of Organic Chemistry 2021, no. 22 (2021): 3359–3375, 10.1002/ejoc.202100367. [DOI] [Google Scholar]

[advs76881-bib-0042] 42. Yu Y. and Zhang J., “Allenyl Radicals in Organic Synthesis: Challenges and Recent Advances,” European Journal of Organic Chemistry 2022, no. 43 (2022): 202201017, 10.1002/ejoc.202201017. [DOI] [Google Scholar]

[advs76881-bib-0043] 43. Kvasovs N. and Gevorgyan V., “Contemporary Methods for Generation of Aryl Radicals,” Chemical Society Reviews 50, no. 4 (2021): 2244–2259, 10.1039/D0CS00589D. [DOI] [PMC free article] [PubMed] [Google Scholar]

[advs76881-bib-0044] 44. Grudzień K., Zlobin A., Zadworny J., Rybicka‐Jasińska K., and Sadowski B., “Modern Photo‐ and Electrochemical Approaches to Aryl Radical Generation,” Organic Chemistry Frontiers 11, no. 18 (2024): 5232–5277, 10.1039/D4QO00999A. [DOI] [Google Scholar]

[advs76881-bib-0045] 45. Zeng X., “The Strategies Towards Electrochemical Generation of Aryl Radicals,” Chemistry—A European Journal 30, no. 54 (2024): 202402220, 10.1002/chem.202402220. [DOI] [PubMed] [Google Scholar]

[advs76881-bib-0046] 46. Xie X.‐Q., Zhou W., Yang R., Song X.‐R., Luo M.‐J., and Xiao Q., “Electroreduction Strategy: A Sustainable Tool for the Generation of Aryl Radicals,” Organic Chemistry Frontiers 11, no. 15 (2024): 4318–4342, 10.1039/D4QO00846D. [DOI] [Google Scholar]

[advs76881-bib-0047] 47. Zhao H., Cuomo V. D., Tian W., Romano C., and Procter D. J., “Light‐Assisted Functionalization of Aryl Radicals Towards Metal‐Free Cross‐Coupling,” Nature Reviews Chemistry 9, no. 1 (2025): 61–80, 10.1038/s41570-024-00664-5. [DOI] [PubMed] [Google Scholar]

[advs76881-bib-0048] 48. Lakhal A., Gimbert Y., Mouriès‐Mansuy V., Ollivier C., and Fensterbank L., “Alkynyl Radicals, Myths and Realities,” JACS Au 5, no. 2 (2025): 448–465, 10.1021/jacsau.4c01040. [DOI] [PMC free article] [PubMed] [Google Scholar]

[advs76881-bib-0049] 49. Saveant J.‐M., “Electron Transfer, Bond Breaking, and Bond Formation,” Accounts of Chemical Research 26, no. 9 (1993): 455–461, 10.1021/ar00033a001. [DOI] [Google Scholar]

[advs76881-bib-0050] 50. Saveant J.‐M., “Dissociative Electron Transfer. New Tests of the Theory in the Electrochemical and Homogeneous Reduction of Alkyl Halides,” Journal of the American Chemical Society 114, no. 26 (1992): 10595–10602, 10.1021/ja00052a065. [DOI] [Google Scholar]

[advs76881-bib-0051] 51. Costentin C., Robert M., and Savéant J.‐M., “Successive Removal of Chloride Ions From Organic Polychloride Pollutants. Mechanisms of Reductive Electrochemical Elimination in Aliphatic Gem‐Polychlorides, α,β‐Polychloroalkenes, and α,β‐Polychloroalkanes in Mildly Protic Medium,” Journal of the American Chemical Society 125, no. 35 (2003): 10729–10739, 10.1021/ja036141t. [DOI] [PubMed] [Google Scholar]

[advs76881-bib-0052] 52. Costentin C., Robert M., and Savéant J.‐M., “Fragmentation of Aryl Halide π Anion Radicals. Bending of the Cleaving Bond and Activation vs Driving Force Relationships,” Journal of the American Chemical Society 126, no. 49 (2004): 16051–16057, 10.1021/ja045989u. [DOI] [PubMed] [Google Scholar]

[advs76881-bib-0053] 53. Isse A. A., Scarpa L., Durante C., and Gennaro A., “Reductive Cleavage of Carbon–Chlorine Bonds at Catalytic and Non‐Catalytic Electrodes in 1‐Butyl‐3‐Methylimidazolium Tetrafluoroborate,” Physical Chemistry Chemical Physics 17, no. 46 (2015): 31228–31236, 10.1039/C5CP04142B. [DOI] [PubMed] [Google Scholar]

[advs76881-bib-0054] 54. Rosokha S. V., Lukacs E., Ritzert J. T., and Wasilewski A., “Mechanism and Thermodynamics of Reductive Cleavage of Carbon–Halogen Bonds in the Polybrominated Aliphatic Electrophiles,” The Journal of Physical Chemistry A 120, no. 10 (2016): 1706–1715, 10.1021/acs.jpca.5b11410. [DOI] [PubMed] [Google Scholar]

[advs76881-bib-0055] 55. Mazzucato M., Isse A. A., and Durante C., “Dissociative Electron Transfer Mechanism and Application in the Electrocatalytic Activation of Organic Halides,” Current Opinion in Electrochemistry 39 (2023): 101254, 10.1016/j.coelec.2023.101254. [DOI] [Google Scholar]

[advs76881-bib-0056] 56. Zeng L., Li H., Hu J., et al., “Electrochemical Oxidative Aminocarbonylation of Terminal Alkynes,” Nature Catalysis 3, no. 5 (2020): 438–445, 10.1038/s41929-020-0443-z. [DOI] [Google Scholar]

[advs76881-bib-0057] 57. Zeng L., Jiao Y., Yan W., et al., “Asymmetric‐Waveform Alternating Current‐Promoted Silver Catalysis for C–H Phosphorylation,” Nature Synthesis 2, no. 2 (2023): 172–181, 10.1038/s44160-022-00197-z. [DOI] [Google Scholar]

[advs76881-bib-0058] 58. Bortolami M., Petrucci R., Rocco D., Scarano V., and Chiarotto I., “Alkynes as Building Blocks, Intermediates and Products in the Electrochemical Procedures Since 2000,” ChemElectroChem 8, no. 19 (2021): 3604–3613, 10.1002/celc.202100497. [DOI] [Google Scholar]

[advs76881-bib-0059] 59. Choy P. Y., Chow W. K., So C. M., Lau C. P., and Kwong F. Y., “Palladium‐Catalyzed Sonogashira Coupling of Aryl Mesylates and Tosylates,” Chemistry—A European Journal 16, no. 33 (2010): 9982–9985, 10.1002/chem.201001269. [DOI] [PubMed] [Google Scholar]

[advs76881-bib-0060] 60. Fan B.‐M., Yang Q.‐J., Hu J., et al., “Asymmetric Hydroalkynylation of Norbornadienes Promoted by Chiral Iridium Catalysts,” Angewandte Chemie International Edition 51, no. 31 (2012): 7821–7824, 10.1002/anie.201203107. [DOI] [PubMed] [Google Scholar]

[advs76881-bib-0061] 61. Yang Q., Choy P. Y., Fan B., and Kwong F. Y., “Enantioselective Hydroalkynylation of Non‐Polar Carbon‐Carbon Double Bonds: Iridium‐Catalyzed Asymmetric Addition Reaction of Terminal Alkyne C─H Bonds to Substituted Norbornadienes,” Advanced Synthesis & Catalysis 357, no. 10 (2015): 2345–2350, 10.1002/adsc.201500465. [DOI] [Google Scholar]

[advs76881-bib-0062] 62. Zhao Q., Fu W. C., and Kwong F. Y., “Palladium‐Catalyzed Regioselective Aromatic Extension of Internal Alkynes Through a Norbornene‐Controlled Reaction Sequence,” Angewandte Chemie International Edition 57, no. 13 (2018): 3381–3385, 10.1002/anie.201713207. [DOI] [PubMed] [Google Scholar]

[advs76881-bib-0063] 63. He X., Li R., Choy P. Y., et al., “Rapid Access of Alkynyl and Alkenyl Coumarins via a Dipyridinium Methylide and Propargylamine Cascade Reaction,” Organic Letters 22, no. 18 (2020): 7348–7352, 10.1021/acs.orglett.0c02674. [DOI] [PubMed] [Google Scholar]

[advs76881-bib-0064] 64. Lau Y. K., Hui C. P., Li C. L., et al., “Indole‐Based π‐Extended Monophosphine Ligands for Enhanced Palladium‐Catalyzed Sonogashira Coupling,” Journal of Heterocyclic Chemistry 63, no. 4 (2026): 727–737, 10.1002/jhet.70151. [DOI] [Google Scholar]

[advs76881-bib-0065] 65. Rodrigo S., Gunasekera D., Mahajan J. P., and Luo L., “Alternating Current Electrolysis for Organic Synthesis,” Current Opinion in Electrochemistry 28 (2021): 100712, 10.1016/j.coelec.2021.100712. [DOI] [PMC free article] [PubMed] [Google Scholar]

[advs76881-bib-0066] 66. Wan Q., Chen K., Dong X., Ruan X., Yi H., and Chen S., “Elucidating the Underlying Reactivities of Alternating Current Electrosynthesis by Time‐Resolved Mapping of Short‐Lived Reactive Intermediates,” Angewandte Chemie International Edition 62, no. 40 (2023): 202306460, 10.1002/anie.202306460. [DOI] [PubMed] [Google Scholar]

[advs76881-bib-0067] 67. Zeng L., Yang Q., Wang J., et al., “Programmed Alternating Current Optimizationof Cu‐catalyzed C‐H Bond Transformations,” Science 385, no. 6705 (2024): 216–223, 10.1126/science.ado0875. [DOI] [PubMed] [Google Scholar]

[advs76881-bib-0068] 68. Li H., Peng J., Zeng L., et al., “Augmentation of Pd‐Catalysed Oxidative C–H/C–H Carbonylation Through Alternating Current Electrosynthesis,” Green Chemistry 26, no. 22 (2024): 11177–11181, 10.1039/D4GC04569F. [DOI] [Google Scholar]

[advs76881-bib-0069] 69. Bortnikov E. O. and Semenov S. N., “Coupling of Alternating Current to Transition‐Metal Catalysis: Examples of Nickel‐Catalyzed Cross‐Coupling,” The Journal of Organic Chemistry 86, no. 1 (2021): 782–793, 10.1021/acs.joc.0c02350. [DOI] [PMC free article] [PubMed] [Google Scholar]

[advs76881-bib-0070] 70. Gandeepan P. and Ackermann L., “Transient Directing Groups for Transformative C–H Activation by Synergistic Metal Catalysis,” Chemistry 4, no. 2 (2018): 199–222, 10.1016/j.chempr.2017.11.002. [DOI] [Google Scholar]

[advs76881-bib-0071] 71. Higham J. I. and Bull J. A., “Transient Imine Directing Groups for the C–H Functionalisation of Aldehydes, Ketones and Amines: An Update 2018–2020,” Organic & Biomolecular Chemistry 18, no. 37 (2020): 7291–7315, 10.1039/D0OB01587C. [DOI] [PubMed] [Google Scholar]

[advs76881-bib-0072] 72. Jacob C., Maes B. U. W., and Evano G., “Transient Directing Groups in Metal−Organic Cooperative Catalysis,” Chemistry—A European Journal 27, no. 56 (2021): 13899–13952, 10.1002/chem.202101598. [DOI] [PubMed] [Google Scholar]

[advs76881-bib-0073] 73. Goswami N., Bhattacharya T., and Maiti D., “Transient Directing Ligands for Selective Metal‐Catalysed C–H Activation,” Nature Reviews Chemistry 5, no. 9 (2021): 646–659, 10.1038/s41570-021-00311-3. [DOI] [PubMed] [Google Scholar]

[advs76881-bib-0074] 74. Dhawa U., Tian C., Wdowik T., Oliveira J. C. A., Hao J., and Ackermann L., “Enantioselective Pallada‐Electrocatalyzed C−H Activation by Transient Directing Groups: Expedient Access to Helicenes,” Angewandte Chemie International Edition 59, no. 32 (2020): 13451–13457, 10.1002/anie.202003826. [DOI] [PMC free article] [PubMed] [Google Scholar]

[advs76881-bib-0075] 75. Zhang F.‐L., Hong K., Li T.‐J., Park H., and Yu J.‐Q., “Functionalization of C(sp³)–H Bonds Using a Transient Directing Group,” Science 351, no. 6270 (2016): 252–256, 10.1126/science.aad7893. [DOI] [PMC free article] [PubMed] [Google Scholar]

[advs76881-bib-0076] 76. Liu M., Sun J., Erbay T., et al., “Pd^II‐Catalyzed C(alkenyl)−H Activation Facilitated by a Transient Directing Group,” Angewandte Chemie International Edition 61 (2022): 202203624, 10.1002/anie.202203624. [DOI] [PMC free article] [PubMed] [Google Scholar]

[advs76881-bib-0077] 77. Rawson J. M. and Winpenny R. E. P., “The Coordination Chemistry of 2‐pyridone and Its Derivatives,” Coordination Chemistry Reviews 139 (1995): 313–374, 10.1016/0010-8545(94)01117-T. [DOI] [Google Scholar]

[advs76881-bib-0078] 78. Fedulin A. and von Wangelin A. J., “2‐Pyridonates: A Versatile Ligand Platform in 3d Transition Metal Coordination Chemistry and Catalysis,” Catalysis Science & Technology 14, no. 1 (2024): 26–42, 10.1039/D3CY01190A. [DOI] [Google Scholar]

[advs76881-bib-0079] 79. Mandal N. and Datta A., “Harnessing the Efficacy of 2‐Pyridone Ligands for Pd‐Catalyzed (β/γ)‐C(sp³)–H Activations,” The Journal of Organic Chemistry 85, no. 20 (2020): 13228–13238, 10.1021/acs.joc.0c02210. [DOI] [PubMed] [Google Scholar]

[advs76881-bib-0080] 80. de Meijere A., Bräse S., and Oestreich M., Metal‐Catalyzed Cross‐Coupling Reactions and More (Wiley‐VCH, 2013), 10.1002/9783527655588. [DOI] [Google Scholar]

[advs76881-bib-0081] 81. Colacot T., New Trends in Cross‐Coupling: Theory and Applications (RSC Publishing, 2015), 10.1039/9781782620259. [DOI] [Google Scholar]

[advs76881-bib-0082] 82. Tse M. H., Choy P. Y., and Kwong F. Y., “Facile Assembly of Modular‐Type Phosphines for Tackling Modern Arylation Processes,” Accounts of Chemical Research 55, no. 24 (2022): 3688–3705, 10.1021/acs.accounts.2c00587. [DOI] [PubMed] [Google Scholar]

[advs76881-bib-0083] 83. Martelli G., Spagnolo P., and Tiecco M., “Homolytic Aromatic Substitution by Phenylethynyl Radicals,” Journal of the Chemical Society D: Chemical Communications (1969): 282b–283, 10.1039/C2969000282B. [DOI] [Google Scholar]

[advs76881-bib-0084] 84. Martelli G., Spagnolo P., and Tiecco M., “Homolytic Aromatic Substitution by Phenylethynyl Radicals,” Journal of the Chemical Society B: Physical Organic (1970): 1413–1418, 10.1039/J29700001413. [DOI] [Google Scholar]

[advs76881-bib-0085] 85. Coleman J. S., Hudson A., Root K. D. J., and Walton D. R. M., “Observation of a Free Radical During the Photolysis of Phenyliodoacetylene,” Chemical Physics Letters 11, no. 3 (1971): 300–301, 10.1016/0009-2614(71)80491-8. [DOI] [Google Scholar]

[advs76881-bib-0086] 86. Boutillier P. and Zard S. Z., “Synthetic Equivalents of Alkynyl and Propargyl Radicals,” Chemical Communications 37, no. 14 (2001): 1304–1305, 10.1039/B101751I. [DOI] [Google Scholar]

[advs76881-bib-0087] 87. Zhang L., Wei C., Wu J., et al., “Photoinduced Inverse Sonogashira Coupling Reaction,” Chemical Science 13, no. 25 (2022): 7475–7481, 10.1039/D2SC01933G. [DOI] [PMC free article] [PubMed] [Google Scholar]

[advs76881-bib-0088] 88. Dhawa U., Wdowik T., Hou X., Yuan B., Oliveira J. C. A., and Ackermann L., “Enantioselective Palladaelectro‐Catalyzed C–H Olefinations and Allylations for N–C Axial Chirality,” Chemical Science 12, no. 42 (2021): 14182–14188, 10.1039/D1SC04687J. [DOI] [PMC free article] [PubMed] [Google Scholar]

PERMALINK

Unlocking the Alkynyl Bromide Radical Anion With Alternating Current for Inverse Sonogashira C─H Coupling

Junya Wang

Xiaozhou Wang

Pui Ying Choy

Chi‐Wai Cheung

Li‐Wen Xu

Hung Kay Lee

Gui‐Juan Cheng

Fuk Yee Kwong

ABSTRACT

1. Introduction

SCHEME 1.

2. Results and Discussion

TABLE 1.

SCHEME 2.

SCHEME 3.

SCHEME 4.

SCHEME 5.

3. Conclusion

4. Experimental Section/Methods

4.1. General Procedures for Electrochemical Pd‐Catalyzed Alkynylation Reaction

4.2. General Procedures for Gram‐Scale Synthesis of Compound 3ba

4.3. General Procedures for Synthesis of Product 8

4.4. General Procedures for Synthesis of Product 9

4.5. General Procedures for Synthesis of Product 10

4.5.1. (E)‐3‐Phenyl‐2‐(2‐((triisopropylsilyl)ethynyl)naphthalen‐1‐yl)acrylaldehyde (Scheme 2, Product 3aa)

4.5.2. (E)‐2‐(2‐Methyl‐6‐((triisopropylsilyl)ethynyl)phenyl)‐3‐phenylacrylaldehyde (Scheme 2, Product 3ba)

4.5.3. (E)‐2‐(2‐Ethyl‐6‐((triisopropylsilyl)ethynyl)phenyl)‐3‐phenylacrylaldehyde (Scheme 2, Product 3ca)

4.5.4. (E)‐2‐(2‐Isopropyl‐6‐((triisopropylsilyl)ethynyl)phenyl)‐3‐phenylacrylaldehyde (Scheme 2, Product 3da)

4.5.5. (E)‐2‐(2‐Methoxy‐6‐((triisopropylsilyl)ethynyl)phenyl)‐3‐phenylacrylaldehyde (Scheme 2, Product 3ea)

4.5.6. (E)‐2‐(2‐Chloro‐6‐((triisopropylsilyl)ethynyl)phenyl)‐3‐phenylacrylaldehyde (Scheme 2, Product 3fa)

4.5.7. (E)‐2‐(2‐Fluoro‐6‐((triisopropylsilyl)ethynyl)phenyl)‐3‐phenylacrylaldehyde (Scheme 2, Product 3ga)

4.5.8. (E)‐3‐Phenyl‐2‐(3‐((triisopropylsilyl)ethynyl)‐[1,1'‐biphenyl]‐2‐yl)acrylaldehyde (Scheme 2, Product 3ha)

4.5.9. (E)‐3‐Phenyl‐2‐(3‐((triisopropylsilyl)ethynyl)dibenzo[b,d]furan‐4‐yl)acrylaldehyde (Scheme 2, Product 3ia)

4.5.10. (E)‐3‐Phenyl‐2‐(3‐((triisopropylsilyl)ethynyl)dibenzo[b,d]thiophen‐4‐yl)acrylaldehyde (Scheme 2, Product 3ja)

4.5.11. Methyl (E)‐3‐(3‐oxo‐1‐phenylprop‐1‐en‐2‐yl)‐4‐((triisopropylsilyl)ethynyl)benzoate (Scheme 2, Product 3ka)

4.5.12. (E)‐3‐Phenyl‐2‐(3‐((triisopropylsilyl)ethynyl)naphthalen‐2‐yl)acrylaldehyde (Scheme 2, Product 3la)

4.5.13. (E)‐3‐Phenyl‐2‐(2‐((triisopropylsilyl)ethynyl)pyren‐1‐yl)acrylaldehyde (Scheme 2, Product 3ma)

4.5.14. (E)‐3‐Phenyl‐2‐(2‐((triisopropylsilyl)ethynyl)benzo[b]thiophen‐3‐yl)acrylaldehyde (Scheme 2, Product 3na)

4.5.15. (E)‐3‐Phenyl‐2‐(2‐((triisopropylsilyl)ethynyl)benzo[b]furan‐3‐yl)acrylaldehyde (Scheme 2, Product 3oa)

4.5.16. (E)‐2‐(2,6‐Bis((triisopropylsilyl)ethynyl)phenyl)‐3‐phenylacrylaldehyde (Scheme 2, Product 3ra)

4.5.17. (E)‐2‐(4‐Methoxy‐2,6‐bis((triisopropylsilyl)ethynyl)phenyl)‐3‐phenylacrylaldehyde (Scheme 2, Product 3sa)

4.5.18. (E)‐2‐(3‐Methoxy‐2,6‐bis((triisopropylsilyl)ethynyl)phenyl)‐3‐phenylacrylaldehyde (Scheme 2, Product 3ta)

4.5.19. (E)‐3‐(p‐Tolyl)‐2‐(2‐((triisopropylsilyl)ethynyl)naphthalen‐1‐yl)acrylaldehyde (Scheme 2, Product 3ua)

4.5.20. (E)‐3‐(4‐Methoxyphenyl)‐2‐(2‐((triisopropylsilyl)ethynyl)naphthalen‐1‐yl)acrylaldehyde (Scheme 2, Product 3va)

4.5.21. (E)‐3‐(4‐Fluorophenyl)‐2‐(2‐((triisopropylsilyl)ethynyl)naphthalen‐1‐yl)acrylaldehyde (Scheme 2, Product 3wa)

4.5.22. (E)‐3‐(4‐Chlorophenyl)‐2‐(2‐((triisopropylsilyl)ethynyl)naphthalen‐1‐yl)acrylaldehyde (Scheme 2, Product 3xa)

4.5.23. (E)‐3‐(3‐(Trifluoromethyl)phenyl‐2‐(2‐((triisopropylsilyl)ethynyl)naphthalen‐1‐yl)acrylaldehyde (Scheme 2, Product 3ya)

4.5.24. (E)‐4‐Methyl‐2‐(2‐((triisopropylsilyl)ethynyl)naphthalen‐1‐yl)pent‐2‐enal (Scheme 2, Product 3za)

4.5.25. (E)‐2‐(2‐((tert‐Butyldimethylsilyl)ethynyl)naphthalen‐1‐yl)‐3‐phenylacrylaldehyde (Scheme 2, Product 3ab)

4.5.26. (E)‐3‐Phenyl‐2‐(2‐((triethylsilyl)ethynyl)naphthalen‐1‐yl)acrylaldehyde (Scheme 2, Product 3ac)

4.5.27. (E)‐2‐(2‐Methyl‐6‐((triisopropylsilyl)ethynyl)phenyl)‐3‐phenylprop‐2‐en‐1‐ol (Scheme 5, Compound 8)

4.5.28. (E)‐2‐(2‐Methyl‐6‐((triisopropylsilyl)ethynyl)phenyl)‐3‐phenylacrylic acid (Scheme 5, Compound 9)

4.5.29. (E)‐2‐(3‐Ethynyldibenzo[b,d]furan‐4‐yl)‐3‐phenylacrylaldehyde (Scheme 5, Compound 10)

Author Contributions

Conflicts of Interest

Supporting information

Acknowledgements

Contributor Information

Data Availability Statement

References

Associated Data

Supplementary Materials

Data Availability Statement

ACTIONS

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