Synthesis of 1,1-Disubstituted Allenylic Silyl Ethers Through Iron-Catalyzed Regioselective C(sp²)─H Functionalization of Allenes

Abstract

We report a synthesis of allenylic silyl ethers through iron-catalyzed functionalization of the C(sp²)─H bonds of monosubstituted alkylallenes. In the presence of a cyclopentadienyliron dicarbonyl based catalyst and triisopropylsilyl triflate as a silylation agent, a variety of aryl aldehydes were suitable coupling partners in this transformation, furnishing a collection of 1,1-disubstituted allenylic triisopropylsilyl ethers as products in moderate to excellent yields as a single regioisomer. Lithium bistriflimide was identified as a critical additive in this transformation. The optimized protocol was scalable, and the products were amenable to further transformation to give a number of unsaturated, polyfunctional derivatives.

Graphical Abstract

Allene derivatives have attracted considerable interest as unsaturated intermediates with distinctive reactivity patterns and stereochemical properties.^[1] As a result, they have been employed as useful building blocks for the synthesis of functional materials, bioactive molecules, and pharmaceutically relevant compounds.^[2] As an important subclass of compounds containing the allene substructure, allenylic alcohols (α-hydroxy allenes) and their derivatives have served as versatile starting materials for further transformation, including processes that form α,β-unsaturated ketones,^[3] heterocyclic ring systems,^[4] vinyloxiranes,^[5] and numerous other useful compounds. A number of natural products, including peridinin,^[6] (+)-varitriol,^[7] (+)-furanomycin,^[8] and striatisporolide A^[9] have also been synthesized using allenylic alcohols as key intermediates.

Numerous strategies for the synthesis of allenylic alcohols have been developed, including the use of general processes for allene synthesis (e.g., the Crabbé and Doering–LaFlamme reactions),^[10][11] as well as processes specific to allenylic alcohol synthesis. Wittig chemistry,^[12] the Claisen rearrangement,^[13] Cu-catalyzed S_N2' substitution,^[14] Barbier-type carbonyl addition,^[15] and 1,2-elimination reactions^[16] have all been employed for the synthesis of allenylic alcohols (Scheme 1). However, among these diverse processes, the Crabbé reaction is mostly limited to the synthesis of allenylic alcohols that are monosubstituted or 1,3-disubstituted on the allene moiety, while other methods for preparing allenylic alcohols generally require multistep procedures or utilize polyfunctional starting materials requiring lengthy syntheses and are often subject to limited substrate scope or challenges with respect to regioselectivity (Scheme 1).

Scheme 1.

Common strategies for synthesizing allenylic alcohols

In contrast, methods that allow for direct introduction of the allenylic hydroxy group to a pre-existing allene substructure are rarely reported, especially in the case of unactivated monosubstituted allenes. We felt that allenic C─H functionalization could serve as an attractive strategy to access allenylic alcohols from readily accessible simple monosubstituted alkylallenes. While numerous synthetic methods for the functionalization of allene derivatives have been developed, the selective C─H functionalization of allenic C(sp²)─H bonds remains a synthetic challenge. The adjacent double bonds render this functional group more reactive compared to isolated alkenes, leading to facile insertion by metal complexes that ultimately result in the formation of monoolefinic products.^[17] Moreover, the coexistence of allenic and allenylic C─H bonds presents an additional challenge for regioselective functionalization.^[18]

Several catalytic allenic C-H functionalization strategies do successfully retain the allene moiety (Scheme 2A). One approach, employed in Morita–Baylis–Hillman (MBH) and Heck-type processes, is to temporarily cleave one of the C─C double bonds as part of a net C─H functionalization process. However, the substrates are restricted to electron-deficient allenes for the organocatalyzed allenic MBH reactions,^[19] while the scope of Ru- and Rh-catalyzed Heck-type arylation reactions is limited to specialized silyl- and sulfonyl-substituted allenes.^[20] The alkenylation of allenes by direct C─H activation through a Pd-catalyzed concerted metalation-deprotonation pathway has also been achieved by using a well-engineered directing group on the allene.^[21] Finally, the Au-catalyzed C─H functionalization of allenoate esters using a π-activation strategy has also been reported.^[22] However, to the best of our knowledge, these approaches are not amenable to the preparation of 1,1-disubstituted allenes from electronically-neutral monosubstituted allenes.

Scheme 2.

Reported approaches to the C-H functionalization of allenes

Previously, we reported the use of cyclopentadienyliron complexes as catalysts for the coupling of monosubstituted alkylallenes with iminium electrophiles to generate 1,1-disubstituted allene products.^[23] The proposed mechanism for these processes involves formation of a cationic iron-allene π complex leading to the acidification of the allenic C─H bond proximal to the alkyl substituent. Upon deprotonation, the resultant propargyliron species can react with the electrophile with S_E2’ selectivity to form the 1,1-disubstituted contrasteric coupling product (Scheme 2B). We previously reported the use of iminium electrophiles for these processes. However, the use of aryl aldehydes as carbonyl electrophiles under conditions developed for propargylic functionalization (using BF₃•Et₂O as Lewis acid activator) was ineffective. In this article, we report that the use of a silyl triflate as Lewis acid and alkoxide trap, together with LiNTf₂ as a critical additive, allowed for the formation of 1,1-disubstituted allenylic alcohol products in their silyl-protected forms, providing convenient and scalable access to this class of allene derivatives.

We suspected that in previous attempts to develop a catalytic allene–aldehyde coupling, iron-mediated cyclization of the initially formed allenylic alkoxide led to the formation of a catalytically inactive vinyliron species.^[24] To suppress this deleterious process, we replaced BF₃•Et₂O with a silyl triflate Lewis acid to trap the incipient alkoxide as a stable silyl ether, which could subsequently be desilylated with a fluoride source to provide the allenylic alcohol. Informed by our previously developed protocols, we initiated our investigation by exploring the coupling of trideca-1,2-diene (1a) and 4-bromobenzaldehyde (2a) using [Cp*Fe(CO)₂(thf)]⁺BF₄⁻ (20 mol %) as the catalyst and 4-chloro-2,6-lutidine as the base for deprotonation of the allene. In place of BF₃•Et₂O, we employed triisopropylsilyl triflate (TIPSOTf) as the Lewis acid. Encouragingly, these initial conditions afforded 25% yield of the desired adduct 3aa (Table 1, entry 1). Further optimization of the base, silyl triflate, solvent, and reagent stoichiometry, however, did not significantly improve the yield.

Table 1.

Optimization of reaction conditions (NMR yields)

Entry	Base	1a/2a/[Si]/base (equiv)	additive (equiv)	Yield (%)*
1	4-Cl-2,6-lutidine	2/1/2/3	N/A	25
2	4-Cl-2,6-lutidine	2/1/2/3	BF3•OEt2 (0.2)	0
3	4-Cl-2,6-lutidine	2/1/2/3	Zn(NTf2)2 (0.2)	30
4	4-Cl-2,6-lutidine	2/1/2/3	LiNTf2 (0.2)	33
5	4-Cl-2,6-lutidine	2/1/2/3	LiOTf (0.2)	14
6	4-Cl-2,6-lutidine	2/1/2/3	LiNTf2 (1.0)	43
7	4-Cl-2,6-lutidine	1/2/3/5	LiNTf2 (1.0)	78
8	4-Cl-2,6-lutidine	1/2/3/5	LiNTf2 (1.5)	83
9	4-Cl-2,6-lutidine	1/2/3/5	LiNTf2 (2.0)	61
10	4-Cl-2,6-lutidine	1/1.5/3/5	LiNTf2 (2.0)	81
11	4-Br-2,6-lutidine	1/2/3/5	LiNTf2 (1.5)	72
12	2,4,6-collidine	1/2/3/5	LiNTf2 (1.5)	26
13	3-Br-2,6-lutidine	1/2/3/5	LiNTf2 (1.5)	78
14	tetramethylpyrazine	1/2/3/6	LiNTf2 (1.5)	78

We then considered the addition of an additional Lewis acid to improve the yield. While addition of BF₃•Et₂O (20 mol %) inhibited product formation (entry 2), the addition of Zn(NTf₂)₂, a successful additive in our previously developed propargylic C─H functionalization reactions, led to a slight improvement in yield (entry 3). While LiNTf₂ also improved yield (entry 4), incorporation of LiOTf led to a decrease in yield (entry 5). The addition of a full equivalent of LiNTf₂ led to a further improvement in reaction efficiency (43% yield, entry 6). These results suggest that, in addition to playing the role of Lewis acid, these additives bearing the weakly-coordinating bistriflimide anion may serve to sequester triflate,^[25] which may otherwise coordinate to the cationic iron center and inhibit catalyst activity.

Careful optimization of the substrate and reagent stoichiometries using LiNTf₂ as a commercially available and inexpensive ($1.5/g) additive ultimately led to reaction conditions that afforded the desired product in good yield. The amount of LiNTf₂ additive used strongly impacted the yield (entries 7-9). A two-fold excess of the aldehyde relative to allene gave good results, although comparable yields could be obtained with the amount of aldehyde reduced to 1.5 equiv (entry 10). As was found for our previously developed allene functionalization reactions, 2,6-lutidine derivatives bearing electron-withdrawing substituents were found to be the most effective bases for this transformation (entries 10, 11, 13 vs. 12). In addition, the inexpensive base tetramethylpyrazine was also found to be an effective alternative, although a large excess of base was needed (entry 14).

We investigated the scope of allene functionalization reaction with the optimized reaction conditions (Scheme 3). A wide range of monosubstituted alkyl allenes with an array of functional groups was found to afford the desired allenylic silyl ethers in acceptable to good yields (17 examples, 25–86% yield). Aside from triisopropylsilyl, other common silyl triflates, including t-butyldimethylsilyl and triethylsilyl triflates, afforded product in reduced but still useful yields (3ab, 3ac). Allenes with β-branched alkyl substituents reacted to give the desired silyl ether in good yield (3b). Allenylic silyl ethers bearing an alkyl chloride (3f), an alkyl tosylate (3h), and a phthalimido group (3n), as well as ones bearing benzofuran (3l) and coumarin (3g) ring systems, could also be prepared from the corresponding functionalized allene starting materials. Finally, we found that benzylallene provided the desired product in modest yield but as a single regioisomer (3c). An exploration of the scope of the aldehyde starting material was also undertaken. While a range of starting aldehydes bearing electron withdrawing groups afforded products in moderate to good yields (3o, 3r-3t), the yields for products derived from aldehydes without electron-withdrawing groups (including benzaldehyde itself) tended to be lower (3q). In all cases, only a single regioisomer (>20:1 r.r.) was observed in the ¹H NMR spectra of the crude materials.

Scheme 3.

Substrate scope for the synthesis of allenylic silyl ethers by catalytic allenic C–H functionalization

The allenylic silyl ethers prepared could be derivatized to obtain a number of multifunctional building blocks. For instance, regioselective hydroboration-oxidation led to the formation of (E)-configured allylic alcohol 4a (10:1 E:Z ratio) in 90% yield. On the other hand, (Z)-configured allylsilane derivative 4b (1:5 E:Z ratio) was synthesized by Mo-catalyzed hydrosilylation reaction in 78% yield.^[27] Desilylation of 3aa with tetrabutylammonium fluoride gave 85% yield of the allenylic alcohol 4c. Subsequent Au-catalyzed cyclization of 4c afforded 2,5-dihydrofuran 4d in 77% yield.^[28] A brominative rearrangement of 4c to a vinyl bromide-containing aldehyde (4e) could be achieved using N-bromosuccinimide in 47% yield.^[29]

In conclusion, we have developed an iron-catalyzed C─H functionalization of monosubstituted allenes with aryl aldehydes to form 1,1-disubstituted allenes. This approach enabled a conversion of allenic C─H bonds to new C─C bonds, leading to 1,1-disubstituted allenylic silyl ethers as the products. Moreover, the developed protocol was mild and functional group tolerant and found to be scalable to up to 5 mmol scale (Scheme 5). Further mechanistic investigation and synthetic exploitation of the system are ongoing in our laboratory.

Scheme 5.

Reaction on 5 mmol scale

Anhydrous tetrahydrofuran and 1,2-dichloroethane were purchased from Acros (AcroSeal packaging) and Sigma Aldrich (Sure/Seal packaging), respectively, and were sparged with nitrogen, transferred into an argon-filled glovebox, and used without further purification. Other dried solvents were obtained by distillation and storage over 3Å or 4Å molecular sieves. All other reagents were purchased from Oakwood, Acros, Alfa Aesar, or Sigma Aldrich and used as received. Compounds were purified by flash column chromatography using SiliCycle SiliaFlash^® F60 silica gel, unless otherwise indicated.

New compounds were characterized by ¹H NMR, ¹³C NMR and HRMS. Copies of the ¹H NMR, ¹⁹F NMR and ¹³C NMR spectra can be found in the Supporting Information. ¹H, ¹⁹F, and ¹³C NMR spectra were recorded on Bruker 400 MHz, 500 or 600 MHz instruments. All ¹H NMR data are reported in δ units, parts per million (ppm), and were measured relative to the residual proton signal in the deuterated solvent at 7.16 ppm (C₆D₆), 7.26 ppm (CDCl₃) or 5.32 ppm (CD₂Cl₂). All ¹³C NMR spectra are ¹H decoupled and reported in ppm relative to the solvent signal at 128.06 ppm (C₆D₆), 77.16 ppm (CDCl₃) or 53.84 ppm (CD₂Cl₂). IR spectra were recorded on a PerkinElmer Spectrum Two FT-IR Spectrometer and are reported in terms of frequency of absorption (cm⁻¹). Thin-layer chromatography (TLC) was performed on Silicycle 250 μm (analytical) or 1000 μm (preparative) silica gel plates. Compounds were visualized by irradiation with UV light, or by staining with iodine/silica gel, potassium permanganate, or phosphomolybdic acid (PMA). Yields refer to isolated compounds, unless otherwise indicated. High resolution mass spectra were recorded on a Thermo Scientific Q-Exactive mass spectrometer. NMR yields was determined by using 2,4-dinitrotoluene as internal standard for ¹H NMR spectroscopy.

Procedures

General procedure to make substrate scope

A reaction tube (13 mm × 100 mm, Fisherbrand, part # 14-959-35C) equipped with a magnetic stir bar was capped with a Teflon/silicone septum (Thermo/National part # C4015-66A) screw cap and flame dried under vacuum. The reaction tube was cooled under argon and transferred into an argon-filled glovebox. In the glovebox, [Cp*Fe(CO)₂(thf)]⁺[BF4]⁻ (20 mol %, 16.2 mg), aldehyde 2a (0.4 mmol, 74.0 mg,2 equiv), LiNTf₂ (0.3 mmol, 86.2 mg, 1.5 equiv), dry 1,2-dichloroethane (0.3 mL), allene 1a (0.2 mmol, 36.0 mg, 1.0 equiv), 4-chloro-2,6-lutidine (1.0 mmol, 130 μL, 5.0 equiv), and silyl triflate (0.6 mmol, TIPSOTf: 160 μL; TBDMSOTf: 140 μL; TESOTf: 136 μL, 3.0 equiv) were added in rapid succession. The reaction tube was capped and removed from the glovebox. The reaction tube was placed in an oil bath, which was preheated to 80 °C. After 24 h, the reaction mixture was cooled to room temperature. The crude mixture was concentrated under reduced pressure and purified by column chromatography.

Scale up procedure

In an argon-filled glovebox, a 25 mL round-bottom flask was charged with [Cp*Fe(CO)₂(thf)]⁺[BF₄]⁻ (20 mol %, 410 mg), aldehyde 2a (10 mmol, 1.85 g, 2 equiv), LiNTf₂ (7.5 mmol, 2.16 g, 1.5 equiv), dry 1,2-dichloroethane (5 mL), allene 1a (5 mmol, 900 mg, 1.0 equiv), 4-chloro-2,6-lutidine (25 mmol, 3.25 mL, 5.0 equiv), and triisopropylsilyl trifluoromethanesulfonate (15 mmol, 4.0 mL, 3.0 equiv). The flask was sealed with a rubber septum and electrical tape and placed in an oil bath preheated to 80 °C. After 24 h, the reaction mixture was cooled to room temperature. The crude mixture was concentrated under reduced pressure and purified by flash column chromatography on silica gel with hexanes/ethyl acetate (100:1) as the eluent to give 3aa (1.93 g, 74% yield).

((1-(4-Bromophenyl)-2-vinylidenedodecyl)oxy)triisopropylsilane (3aa)

Yield: 83.6 mg (80%, eluent: hexanes/EtOAc=100:1); colorless oil.

IR (ATR): 2923, 2854, 1956, 1590, 1484, 1463, 1247, 1010, 844 cm⁻¹.

¹H NMR (500 MHz, CDCl₃) δ 7.42 (d, J = 8.4 Hz, 2H), 7.27 (d, J = 8.4 Hz, 2H), 5.36 (s, 1H), 4.81 (dd, J = 6.2, 2.9 Hz, 2H), 2.04 – 1.81 (m, 1H), 1.66 – 1.47 (m, 1H), 1.32 – 1.15 (m, 16H), 1.14 – 0.98 (m, 21H), 0.88 (t, J = 7.0 Hz, 3H).

¹³C NMR (126 MHz, CDCl₃) δ 206.15, 143.29, 131.06, 127.76, 120.71, 107.62, 76.92, 75.93, 32.00, 29.51, 29.47, 29.39, 27.39, 24.84, 22.81, 18.14, 18.07, 14.26, 12.36

HRMS (ESI): m/z [M + H]⁺ calcd for C₂₉H₅₀OBrSi: 521.2809; found: 521.2806.

((1-(4-Bromophenyl)-2-vinylidenedodecyl)oxy)(tert-butyl)di-methylsilane (3ab)

Yield: 46.9 mg (49%, eluent: hexanes/EtOAc=100:1); colorless oil.

IR (ATR): 2925, 2854, 1955, 1591, 1485, 1463, 1252, 1010, 835 cm⁻¹.

¹H NMR (500 MHz, CDCl₃) δ 7.42 (d, J = 8.4 Hz, 2H), 7.24 (d, J = 8.4 Hz, 2H), 5.25 (s, 1H), 4.78 (dd, J = 6.2, 2.9 Hz, 2H), 1.93 – 1.81 (m, 1H), 1.65 – 1.55 (m, 1H), 1.33 – 1.18 (m, 16H), 0.92 (s, 9H), 0.88 (t, J = 7.0 Hz, 3H), 0.08 (s, 3H), 0.02 (s, 3H).

¹³C NMR (126 MHz, CDCl₃) δ 206.39, 142.84, 131.09, 127.85, 120.76, 107.16, 76.78, 75.81, 32.07, 29.74, 29.58, 29.48, 27.54, 25.99, 25.50, 22.84, 18.44, 14.27, −4.64, −5.02.

HRMS (ESI): m/z [M + H]⁺ calcd for C₂₆H₄₄OBrSi: 479.2339; found: 479.2358.

((1-(4-bromophenyl)-2-vinylidenedodecyl)oxy)triethylsilane (3ac)

Yield: 42.1 mg (44%, eluent: hexanes); colorless oil.

IR (ATR): 2924, 2854, 1956, 1591, 1484, 1457, 1010, 843 cm⁻¹.

¹H NMR (300 MHz, CDCl₃) δ 7.42 (d, J = 8.4 Hz, 2H), 7.25 (d, J = 8.4 Hz, 2H), 5.26 (s, 1H), 4.78 (t, J = 3.5 Hz, 2H), 1.96 – 1.85 (m, 1H), 1.65 – 1.54 (m, 1H), 1.35 – 1.17 (m, 16H), 0.96 – 0.85 (m, 9H), 0.68 – 0.53 (m, 6H).

¹³C NMR (75 MHz, CDCl₃) δ 206.33, 142.87, 131.06, 127.85, 120.76, 107.28, 77.36, 75.48, 32.07, 29.75, 29.58, 29.48, 27.57, 25.51, 22.84, 14.27, 6.93, 4.90.

HRMS (ESI): m/z [M + H]⁺ calcd for C₂₆H₄₄OBrSi: 479.2339; found: 479.2346.

((1-(4-Bromophenyl)-2-(cyclohexylmethyl)buta-2,3-dien-1-yl)oxy)triisopropylsilane (3b)

Yield: 72.4 mg (76%, eluent: hexanes/EtOAc=100:1); colorless oil.

IR (ATR): 2921, 2865, 1956, 1591, 1484, 1463, 1010, 843 cm⁻¹.

¹H NMR (500 MHz, CDCl₃) δ 7.51 – 7.37 (dd, J = 8.5 Hz, 2H), 7.25 (dd, J = 8.5 Hz, 2H), 5.34 (s, 1H), 4.90 – 4.61 (m, 2H), 1.80 (ddt, J = 15.3, 6.9, 3.5 Hz, 1H), 1.70 – 1.51 (m, 5H), 1.47 (ddt, J = 15.5, 6.8, 3.4 Hz, 1H), 1.37 – 1.20 (m, 1H), 1.17 – 0.97 (m, 24H), 0.83 – 0.73 (m, 1H), 0.72 – 0.62 (m, 1H).

¹³C NMR (101 MHz, CDCl₃) δ 206.39, 143.32, 131.01, 127.82, 120.70, 105.83, 76.53, 76.06, 35.78, 33.61, 33.48, 33.16, 26.71, 26.39, 26.37, 18.14, 18.09, 12.35.

HRMS (ESI): m/z [M + H]⁺ calcd for C₂₆H₄₂OBrSi: 477.2183; found: 477.2175.

((2-Benzyl-1-(4-bromophenyl)buta-2,3-dien-1-yl)oxy)triisopropyl-silane (3c)

Yield: 23.5 mg (25%, eluent: hexanes/EtOAc=20:1); colorless oil.

IR (ATR): 3030, 2942, 2865, 1958, 1602, 1484, 1463, 1010, 841 cm⁻¹.

¹H NMR (500 MHz, CDCl₃) δ 7.43 (d, J = 8.4 Hz, 2H), 7.28 (d, J = 8.3 Hz, 2H), 7.23 – 7.10 (m, 3H), 7.01 (dd, J = 21.9, 10.4 Hz, 2H), 5.40 (s, 1H), 4.70 (t, J = 3.0 Hz, 2H), 3.32 (dt, J = 15.7, 3.2 Hz, 1H), 2.91 (dt, J = 15.7, 3.5 Hz, 1H), 1.20 – 0.95 (m, 21H).

¹³C NMR (126 MHz, CDCl₃) δ 206.90, 142.93, 139.27, 131.18, 129.39, 128.04, 127.93, 126.04, 120.95, 107.90, 77.51, 75.48, 32.74, 18.14, 18.09, 12.38.

HRMS (ESI): m/z [M + H]⁺ calcd for C₂₆H₃₆OBrSi: 471.1713; found: 471.1734.

((1-(4-Bromophenyl)-2-phenethylbuta-2,3-dien-1-yl)oxy)triiso-propylsilane (3d)

Yield: 46.5 mg (48%, eluent: hexanes/EtOAc=20:1); colorless oil.

IR (ATR): 3027, 2942, 2865, 1956, 1604, 1484, 1463, 1010, 837 cm⁻¹.

¹H NMR (300 MHz, CDCl₃) δ 7.40 (d, J = 8.4 Hz, 2H), 7.30 – 7.08 (m, 5H), 7.05 (d, J = 6.9 Hz, 2H), 5.40 (s, 1H), 4.92 – 4.79 (m, 2H), 2.68 – 2.47 (m, 2H), 2.35 – 2.20 (m, 1H), 1.97 – 1.81 (m, 1H), 1.17 – 0.95 (m, 21H).

¹³C NMR (75 MHz, CDCl₃) δ 206.18, 142.95, 142.28, 131.14, 128.50, 128.32, 127.71, 125.83, 120.82, 107.07, 100.14, 77.36, 75.90, 33.88, 26.70, 18.13, 18.06, 12.34.

HRMS (ESI): m/z [M + H]⁺ calcd for C₂₇H₃₈OBrSi: 485.1870; found: 485.1890.

((1-(4-Bromophenyl)-5-phenyl-2-vinylidenepentyl)oxy)triisopro-pylsilane (3e)

Yield: 70.7 mg (71%, eluent: hexanes/EtOAc=20:1); colorless oil.

IR (ATR): 3026, 2941, 2865, 1955, 1603, 1484, 1462, 1010, 840 cm⁻¹.

¹H NMR (400 MHz, CDCl₃) δ 7.42 (d, J = 8.4 Hz, 2H), 7.24 – 7.17 (m, 3H), 7.16 – 7.11 (m, 1H), 7.04 (d, J = 7.6 Hz,, 2H), 5.37 (s, 1H), 4.97 – 4.83 (m, 2H), 2.55 – 2.42 (m, 2H), 2.05 – 1.95 (m, 1H), 1.69 – 1.55 (m, 3H), 1.15 – 0.97 (m, 21H).

¹³C NMR (101 MHz, CDCl₃) δ 205.99, 143.19, 142.61, 131.12, 128.53, 128.33, 127.75, 125.72, 120.80, 107.27, 77.29, 75.87, 35.61, 29.24, 24.40, 18.13, 18.06, 12.34.

HRMS (ESI): m/z [M + H]⁺ calcd for C₂₈H₄₀OBrSi: 499.2026; found: 499.2033.

((1-(4-Bromophenyl)-6-chloro-2-vinylidenehexyl)oxy)triisopropyl-silane (3f)

Yield: 77.1 mg (82%, eluent: hexanes/EtOAc=100:1); colorless oil.

IR (ATR): 2942, 2865, 1957, 1590, 1484, 1463, 1010, 838 cm⁻¹.

¹H NMR (400 MHz, CDCl₃) δ 7.43 (dd, J = 8.4 Hz, 2H), 7.26 (dd, J = 8.5 Hz, 2H), 5.38 (s, 1H), 4.88 – 4.79 (m, 2H), 3.42 (t, J = 6.7 Hz, 2H), 2.04 – 1.94 (m, 1H), 1.72 – 1.56 (m, 3H), 1.50 – 1.36 (m, 2H), 1.17 – 0.97 (m, 21H).

¹³C NMR (101 MHz, CDCl₃) δ 205.92, 143.05, 131.15, 127.68, 120.85, 106.98, 77.42, 75.82, 45.01, 32.33, 24.67, 24.01, 18.13, 18.06, 12.33.

HRMS (ESI): m/z [M + H]⁺ calcd for C₂₇H₃₇OBrClSi: 471.1480; found: 471.1513.

7-((5-((4-Bromophenyl)((triisopropylsilyl)oxy)methyl)hepta-5,6-dien-1-yl)oxy)-2H-chromen-2-one (3g)

Yield: 58.4 mg (49%, eluent: hexanes/EtOAc=20:1); colorless oil.

IR (ATR): 2942, 2865, 1957, 1732, 1611, 1484, 1463, 1010, 831 cm⁻¹.

¹H NMR (500 MHz, CDCl₃) δ 7.62 (d, J = 9.0 Hz, 1H), 7.44 – 7.40 (d, J = 8.5 Hz, 2H), 7.34 (d, J = 9.0 Hz, 1H), 7.27 (d, J = 8.5 Hz, 2H), 6.80 – 6.71 (m, 2H), 6.23 (d, J = 9.5 Hz, 1H), 5.39 (s, 1H), 4.85 (dd, J = 6.1, 2.9 Hz, 2H), 3.89 (t, J = 6.5 Hz, 2H), 2.08 – 1.99 (m, 1H), 1.75 – 1.64 (m, 3H), 1.54 – 1.40 (m, 2H), 1.16 – 0.98 (m, 22H).

¹³C NMR (126 MHz, CDCl₃) δ 206.02, 162.52, 161.38, 156.10, 143.53, 143.12, 131.17, 128.79, 127.71, 120.87, 113.11, 113.09, 112.54, 107.11, 101.53, 75.91, 68.47, 28.64, 24.44, 23.79, 18.13, 18.07, 12.38.

HRMS (ESI): m/z [M + H]⁺ calcd for C₃₂H₄₂O₄BrSi: 597.2030; found: 597.2029.

4-((4-Bromophenyl)((triisopropylsilyl)oxy)methyl)hexa-4,5-dien-1-yl 4-methylbenzenesulfonate (3h)

Yield: 77.0 mg (65%, eluent: hexanes/EtOAc=100:1); colorless oil.

IR (ATR): 2942, 2865, 1957, 1598, 1484, 1463, 1362, 1176, 1010, 836 cm⁻¹.

¹H NMR (500 MHz, CDCl₃) δ 7.72 (d, J = 8.2 Hz, 2H), 7.41 (d, J = 8.4 Hz, 2H), 7.32 (d, J = 8.1 Hz, 2H), 7.21 (d, J = 8.3 Hz, 2H), 5.35 (s, 1H), 4.84 – 4.75 (m, 2H), 3.97 – 3.87 (m, 2H), 2.45 (s, 3H), 2.05 – 1.95 (m, 1H), 1.70 – 1.57 (m, 3H), 1.14 – 0.97 (m, 21H)

¹³C NMR (126 MHz, CDCl₃) δ 205.60, 144.68, 142.77, 133.47, 131.23, 129.89, 128.00, 127.63, 120.99, 106.32, 77.88, 75.69, 70.18, 26.90, 21.76, 20.91, 18.10, 18.04, 12.33.

HRMS (ESI): m/z [M + H]⁺ calcd for C₂₉H₄₂O₄BrSSi: 593.1751; found: 593.1719.

((1-(4-Bromophenyl)-5-(4-chloro-3,5-dimethylphenoxy)-2-vinyli-denepentyl)oxy)triisopropylsilane (3i)

Yield: 96.8 mg (84%, eluent: hexanes/EtOAc=20:1); colorless oil.

IR (ATR): 2942, 2865, 1957, 1589, 1484, 1465, 1168, 1010, 833 cm⁻¹.

¹H NMR (500 MHz, CDCl₃) δ 7.42 (d, J = 8.4 Hz, 2H), 7.27 (d, J = 8.4 Hz, 2H), 6.54 (s, 2H), 5.40 (s, 1H), 4.95 – 4.82 (m, 2H), 3.84 – 3.72 (m, 2H), 2.33 (s, 6H), 2.20 – 2.10 (m, 1H), 1.82 – 1.68 (m, 3H), 1.18 – 0.95 (m, 21H).

¹³C NMR (126 MHz, CDCl₃) δ 205.86, 156.98, 143.01, 137.08, 131.18, 127.71, 126.14, 120.89, 114.65, 106.99, 77.64, 75.89, 67.57, 27.17, 21.30, 21.06, 18.14, 18.07, 12.39.

HRMS (ESI): m/z [M + H]⁺ calcd for C₃₀H₄₃O₂BrClSi: 577.1899; found: 577.1904.

((1-(4-Bromophenyl)-5-(2,6-dimethylphenoxy)-2-vinylidene-pentyl)oxy)triisopropylsilane (3j)

Yield: 93.3 mg (86%, eluent: hexanes/EtOAc=20:1); colorless oil.

IR (ATR): 2942, 2865, 1955, 1591, 1484, 1463, 1202, 1010, 836 cm⁻¹.

¹H NMR (400 MHz, CDCl₃) δ 7.42 (d, J = 8.4 Hz, 2H), 7.28 (d, J = 8.4 Hz, 2H), 6.99 – 6.95 (m, 2H), 6.93 – 6.85 (m, 1H), 5.40 (s, 1H), 4.91 – 4.82 (m, 2H), 3.65 (m, 2H), 2.27 – 2.15 (m, 7H), 1.90 – 1.73 (m, 3H), 1.16 – 0.97 (m, 21H).

¹³C NMR (101 MHz, CDCl₃) δ 205.77, 156.13, 143.09, 131.17, 131.04, 128.84, 127.73, 123.69, 120.89, 107.28, 77.59, 75.85, 71.94, 28.25, 21.61, 18.13, 18.06, 16.36, 12.35.

HRMS (ESI): m/z [M + H]⁺ calcd for C₃₀H₄₄O₂BrSi: 543.2288; found: 543.2289.

((2-(2-(4-Bromophenoxy)ethyl)-1-(4-bromophenyl)buta-2,3-dien-1-yl)oxy)triisopropylsilane (3k)

Yield: 79.8 mg (69%, eluent: hexanes/EtOAc=20:1); colorless oil.

IR (ATR): 2942, 2865, 1956, 1590, 1487, 1464, 1242, 1010, 835 cm⁻¹.

¹H NMR (500 MHz, CDCl₃) δ 7.44 (d, J = 8.4 Hz, 2H), 7.34 – 7.27 (m, 4H), 6.67 – 6.60 (m, 2H), 5.44 (s, 1H), 4.91 – 4.83 (m, 2H), 3.87 (dtd, J = 23.6, 8.9, 6.2 Hz, 1H), 2.49 – 2.40 (m, 1H), 2.16 – 2.05 (m, 1H), 1.18 – 0.99 (m, 21H).

¹³C NMR (126 MHz, CDCl₃) δ 205.95, 158.09, 142.68, 132.28, 131.30, 127.70, 121.09, 116.41, 112.79, 103.60, 77.55, 75.81, 66.60, 25.00, 18.14, 18.07, 12.37.

HRMS (ESI): m/z [M + H]⁺ calcd for C₂₇H₃₇O₂Br₂Si: 579.0924; found: 579.0923.

4-((4-Bromophenyl)((triisopropylsilyl)oxy)methyl)hexa-4,5-dien-1-yl benzofuran-2-carboxylate (3l)

Yield: 76.8 mg (66%, eluent: hexanes/EtOAc=10:1); colorless oil.

IR (ATR): 2944, 2865, 1957, 1591, 1484, 1463, 1255, 1010, 833 cm⁻¹.

¹H NMR (400 MHz, CDCl₃) δ 7.66 (d, J = 9.0 Hz, 2H), 7.56 (d, J = 9.0 Hz, 2H), 7.46 – 7.34 (m, 4H), 7.33 – 7.20 (m, 3H), 5.39 (s, 1H), 4.90 – 4.84 (m, 2H), 4.35 – 4.20 (m, 2H), 2.23 – 2.10 (m, 1H), 1.88 – 1.70 (m, 3H), 1.14 – 0.97 (m, 21H).

¹³C NMR (101 MHz, CDCl₃) δ 205.78, 159.67, 155.91, 145.80, 142.92, 131.20, 127.68, 127.15, 123.88, 122.95, 120.95, 113.81, 112.52, 106.58, 77.82, 75.87, 64.99, 26.53, 21.16, 18.12, 18.05, 12.37.

HRMS (ESI): m/z [M + H]⁺ calcd for C₃₁H₄₀O₄BrSi: 583.1868; found: 583.1894.

9-(4-Bromophenyl)-11,11-diisopropyl-2,2,3,3,12-pentamethyl-8-vinylidene-4,10-dioxa-3,11-disilatridecane (3m)

Yield: 57.4 mg (52%, eluent: hexanes/EtOAc=100:1); colorless oil.

IR (ATR): 2944, 2865, 1957, 1591, 1484, 1463, 1255, 1010, 833 cm⁻¹.

¹H NMR (500 MHz, CDCl₃) δ 7.44 – 7.37 (d, J = 8.5 Hz, 2H), 7.26 (d, J = 8.5 Hz, 2H), 5.38 (s, 1H), 4.87 – 4.76 (m, 2H), 3.55 – 3.46 (m, 2H), 2.07 – 1.96 (m, 1H), 1.67 – 1.41 (m, 3H), 1.15 – 0.98 (m, 21H), 0.84 (s, 9H), −0.02 (d, 2.0 Hz, 6H).

¹³C NMR (126 MHz, CDCl₃) δ 205.92, 143.19, 131.12, 127.75, 120.80, 107.44, 77.24, 75.96, 62.99, 30.73, 26.07, 21.34, 18.44, 18.14, 18.07, 12.37, −5.19.

HRMS (ESI): m/z [M + H]⁺ calcd for C₂₈H₅₀O₂BrSi₂: 553.2527; found: 553.2524.

2-(5-((4-Bromophenyl)((triisopropylsilyl)oxy)methyl)hepta-5,6-dien-1-yl)isoindoline-1,3-dione (3n)

Yield: 84.9 mg (73%, eluent: hexanes/EtOAc=10:1); colorless oil.

IR (ATR): 2941, 2864, 1958, 1771, 1711, 1573, 1484, 1466, 1394, 1010, 836 cm⁻¹.

¹H NMR (400 MHz, CDCl₃) δ 7.87 – 7.79 (m, 2H), 7.73 – 7.67 (m, 2H), 7.41 (d, J = 8.4 Hz, 2H), 7.25 (d, J = 8.4 Hz, 2H), 5.36 (s, 1H), 4.85 – 4.77 (m, 2H), 3.60 (t, 7.2 Hz, 2H), 2.04 – 1.93 (m, 1H), 1.68 – 1.53 (m, 3H), 1.42 – 1.28 (m, 2H), 1.16 – 0.97 (m, 21H).

¹³C NMR (101 MHz, CDCl₃) δ 205.91, 168.48, 143.07, 133.94, 132.32, 131.11, 127.70, 123.25, 120.80, 107.06, 77.35, 75.80, 38.03, 28.34, 24.71, 24.42, 18.11, 18.05, 12.32.

HRMS (ESI): m/z [M + H]⁺ calcd for C₃₁H₄₁O₃NBrSi: 582.2034; found: 582.2037.

((1-(2,6-Dichlorophenyl)-2-vinylidenedodecyl)oxy)triisopropyl-silane (3o)

Yield: 66.3 mg (65%, eluent: hexanes/EtOAc=100:1); colorless oil.

IR (ATR): 2924, 2865, 1961, 1562, 1463, 1436, 1117, 1014, 842 cm⁻¹.

¹H NMR (400 MHz, CDCl₃) δ 7.26 (d, 8.0 Hz, 2H), 7.09 (t, J = 8.0 Hz, 1H), 6.02 (t, J = 3.8 Hz, 1H), 4.86 – 4.70 (m, 2H), 1.93 – 1.84 (m, 1H), 1.80 – 1.69 (m, 1H), 1.46 – 1.34 (m, 2H), 1.32 – 1.17 (m, 14H), 1.15 – 0.91 (m, 21H), 0.88 (m, 3H).

¹³C NMR (101 MHz, CDCl₃) δ 206.36, 137.68, 128.71, 105.99, 78.90, 77.36, 71.13, 32.08, 29.75, 29.58, 29.48, 29.40, 28.19, 27.86, 22.85, 18.14, 17.93, 14.28, 12.40.

HRMS (ESI): m/z [M + H]⁺ calcd for C₂₉H₄₉OCl₂Si: 511.2924; found: 511.2929.

((1-(4-Fluorophenyl)-2-vinylidenedodecyl)oxy)triisopropylsilane (3p)

Yield: 58.9 mg (64%, eluent: hexanes/EtOAc=100:1); colorless oil.

IR (ATR): 2924, 2865, 1957, 1603, 1506, 1463, 1222, 1062, 841 cm⁻¹.

¹H NMR (500 MHz, CDCl₃) δ 7.35 (dd, J = 8.4, 5.6 Hz, 2H), 6.99 (t, J = 8.7 Hz, 2H), 5.39 (s, 1H), 4.81 (dd, J = 6.3, 2.9 Hz, 2H), 1.99 – 1.89 (m, 1H), 1.64 – 1.54 (m, 1H), 1.33 – 1.16 (m, 16H), 1.15 – 0.98 (m, 21H), 0.88 (t, J = 7.0 Hz, 3H).

¹³C NMR (126 MHz, CDCl₃) δ 206.14, 161.98 (d, J = 244.2 Hz), 139.90 (d, J = 2.9 Hz), 127.50 (d, J = 7.9 Hz), 114.73 (d, J = 20.2 Hz), 107.90, 76.84, 75.86, 32.08, 29.74, 29.56, 29.49, 29.48, 27.45, 24.96, 22.84, 18.14, 18.08, 14.26.

¹⁹F NMR (471 MHz, CDCl3) δ −116.44.

HRMS (ESI): m/z [M + H]⁺ calcd for C₂₉H₅₀OFSi: 461.3609; found: 461.3623.

Triisopropyl((1-phenyl-2-vinylidenedodecyl)oxy)silane (3q)

Yield: 42.5 mg (48%, eluent: hexanes/EtOAc=100:1); colorless oil.

IR (ATR): 3030, 2924, 2865, 1957, 1463, 1088, 1059, 844 cm⁻¹.

¹H NMR (500 MHz, CDCl₃) δ 7.39 (d, J = 7.5 Hz, 2H), 7.30 (t, J = 7.6 Hz, 2H), 7.22 (t, J = 7.3 Hz, 1H), 5.42 (s, 1H), 4.84 – 4.77 (m, 2H), 2.02 – 1.93 (m, 1H), 1.65 – 1.57 (m, 1H), 1.33 – 1.16 (m, 16H), 1.16 – 1.01 (m, 21H), 0.88 (t, J = 7.0 Hz, 3H).

¹³C NMR (126 MHz, CDCl₃) δ 206.26, 144.18, 127.91, 126.91, 126.04, 108.05, 76.64, 76.42, 32.08, 29.74, 29.58, 29.51, 29.48, 27.49, 25.04, 22.84, 18.17, 18.11, 14.25, 12.45.

HRMS (ESI): m/z [M + H]⁺ calcd for C₂₉H₅₁OSi: 443.3704; found: 443.3706.

Methyl 4-(1-((triisopropylsilyl)oxy)-2-vinylidenedodecyl)benzoate (3r)

Yield: 71.1 mg (71%, eluent: hexanes/EtOAc=100:1); colorless oil.

IR (ATR): 2924, 2865, 1956, 1726, 1610, 1463, 1273, 1117, 1010, 845 cm⁻¹.

¹H NMR (500 MHz, CDCl₃) δ 7.98 (d, J = 8.3 Hz, 2H), 7.47 (d, J = 8.2 Hz, 2H), 5.45 (s, 1H), 4.85 – 4.78 (m, 2H), 3.90 (s, 3H), 2.00 – 1.91 (m, 1H), 1.62 – 1.51 (m, 1H), 1.34 −0.94 (m, 37H), 0.87 (t, J = 7.0 Hz, 3H).

¹³C NMR (126 MHz, CDCl₃) δ 206.39, 167.27, 149.55, 129.44, 129.00, 126.04, 107.55, 76.96, 76.34, 52.08, 32.06, 29.72, 29.53, 29.46, 27.46, 25.06, 22.82, 18.14, 18.08, 14.22, 12.43.

HRMS (ESI): m/z [M + H]⁺ calcd for C₃₁H₅₃O₃Si: 501.3758; found: 501.3783.

4-(1-((Triisopropylsilyl)oxy)-2-vinylidenedodecyl)phenyl 4-methylbenzenesulfonate (3s)

Yield: 93.1 mg (76%, eluent: hexanes/EtOAc=100:1); colorless oil.

IR (ATR): 2924, 2865, 1956, 1598, 1498, 1463, 1378, 1174, 1016, 844 cm⁻¹.

¹H NMR (500 MHz, CDCl₃) δ 7.66 (d, J = 8.3 Hz, 2H), 7.31 – 7.22 (m, 4H), 6.90 (d, J = 8.6 Hz, 2H), 5.34 (s, 1H), 4.83 – 4.73 (m, 2H), 2.42 (s, 3H), 1.93 – 1.83 (m, 1H), 1.58 – 1.47 (m, 1H), 1.28 – 1.14 (m, 16H), 1.12 – 0.95 (m, 21H), 0.86 (t, J = 7.0 Hz, 3H).

¹³C NMR (126 MHz, CDCl₃) δ 206.19, 148.63, 145.30, 143.20, 132.60, 129.73, 128.73, 127.17, 121.88, 107.61, 76.94, 75.84, 32.05, 29.73, 29.56, 29.51, 29.46, 27.46, 25.06, 22.81, 21.81, 18.10, 18.05, 14.23, 12.36.

HRMS (ESI): m/z [M + H]⁺ calcd for C₃₆H₅₇O₄SSi: 613.3741; found: 613.3745.

Triisopropyl((1-(4-(trifluoromethyl)phenyl)-2-vinylidenedodecyl)-oxy)silane (3t)

Yield: 79.6 mg (78%, eluent: hexanes/EtOAc=100:1); colorless oil.

IR (ATR): 2925, 2866, 1957, 1619, 1464, 1323, 1127, 1066, 842 cm⁻¹.

¹H NMR (500 MHz, CDCl₃) δ 7.56 (d, J = 8.3 Hz, 2H), 7.51 (d, J = 8.3 Hz, 2H), 5.46 (s, 1H), 4.86 – 4.77 (m, 2H), 2.01 – 1.92 (m, 1H), 1.60 – 1.51 (m, 2H), 1.33 – 1.01 (m, 37H), 0.87 (t, J = 7.0 Hz, 3H).

¹³C NMR (126 MHz, CDCl₃) δ 206.28, 148.28, 129.22 (q, J = 32.1 Hz), 126.25, 124.50 (q, J = 274.7 Hz), 124.99 (q, J = 3.8 Hz), 107.47, 77.05, 76.11, 32.06, 29.73, 29.72, 29.55, 29.46, 27.38, 24.82, 22.83, 18.14, 18.06, 14.25, 12.38.

¹⁹F NMR (471 MHz, CDCl3) δ −62.26.

HRMS (ESI): m/z [M + H]⁺ calcd for C₃₀H₅₀OF₃Si: 511.3572; found: 511.3571.

(E)-3-((4-Bromophenyl)((triisopropylsilyl)oxy)methyl)tridec-2-en-1-ol (4a)

A reaction tube (13 mm × 100 mm, Fisherbrand, part # 14-959-35C) equipped with a magnetic stir bar was capped with a Teflon/silicone septum (Thermo/National part # C4015-66A) screw cap and flame dried under vacuum. 3aa (52.0 mg, 0.1 mmol) was dissolved in 0.5 mL of anhydrous THF. 9-BBN (0.4mL, 0.2 mmol, 2.0 equiv, 0.5 M in THF) was added dropwise at room temperature. The reaction mixture was stirred for 5 h. Then 1.0 mL NaOH (3 M) aqueous solution and 1.0 mL of H₂O₂ (30%) were added sequentially at 0 °C, and the reaction was stirred for another 2 h at 0 °C. The mixture was treated with water, extracted with ethyl acetate. The combined organic layers were washed with brine, dried over Na₂SO₄, and finally evaporated under reduced pressure. ¹H NMR of the crude material shows an E/Z isomer ratio of 10:1. The crude product was purified by flash column chromatography on silica gel with hexanes/ethyl acetate (10:1) as the eluent to give the pure product (E)-4a as colorless oil (48.4 mg, 90% yield).

The double-bond configuration of (E)-4a was assigned via the 2D NOESY correlation illustrated in SI.

IR (ATR): 3311, 2923, 2865, 1590, 1484, 1463, 1088, 1010, 843 cm⁻¹.

¹H NMR (500 MHz, CDCl₃) δ 7.41 (d, J = 8.4 Hz, 2H), 7.23 (d, J = 8.4 Hz, 2H), 5.91 (t, J = 6.5 Hz, 1H), 5.14 (s, 1H), 4.22 (s, 2H), 1.95 – 1.87 (m, 1H), 1.85 – 1.77 (m, 1H), 1.26 – 0.97 (m, 37H), 0.88 (t, J = 7.0 Hz, 3H).

¹³C NMR (126 MHz, CDCl₃) δ 145.37, 143.02, 131.17, 128.30, 124.53, 120.96, 78.12, 59.47, 32.05, 30.08, 30.03, 29.72, 29.65, 29.47, 29.38, 27.23, 22.84, 18.20, 18.14, 14.27, 12.40.

HRMS (ESI): m/z [M - H]⁺ calcd for C₂₉H₅₀O₂BrSi: 537.2758; found: 537.2754.

(Z)-((1-(4-Bromophenyl)-2-(2-(diphenylsilyl)ethylidene)dodecyl)-oxy)triisopropylsilane (4b)

A reaction tube (13 mm × 100 mm, Fisherbrand, part # 14-959-35C) equipped with a magnetic stir bar was capped with a Teflon/silicone septum (Thermo/National part # C4015-66A) screw cap and flame dried under vacuum. Ph₂SiH₂ (37 μL, 0.2 mmol, 2.0 equiv) was added to the suspension of 3aa (52.0 mg, 0.1 mmol) and Mo(CO)₆ (5.2 mg, 20 mol%) in 0.1 mL of anhydrous toluene under N₂. The reaction mixture was stirred at 110 °C for 36 h. Solvent was evaporated under reduced pressure, and ¹H NMR of the crude material shows a Z/E isomer ratio of 5:1. The crude product was purified by flash column chromatography on silica gel with hexanes/ethyl acetate (50:1) as the eluent to give the pure product (Z)-4b as colorless oil (54.9 mg, 78% yield).

The double-bond configuration of (Z)-4b was assigned via the 2D NOESY correlation illustrated in SI.

IR (ATR): 3069, 2923, 2864, 2125, 1589, 1484, 1463, 1429, 1107, 1062, 1010, 882 cm⁻¹.

¹H NMR (500 MHz, CDCl₃) δ 7.59 (dd, J = 7.0, 5.7 Hz, 4H), 7.47 – 7.36 (m, 6H), 7.27 (d, J = 8.4 Hz, 2H), 7.04 (d, J = 8.4 Hz, 2H), 5.78 (s, 1H), 5.28 (dd, J = 9.8, 6.7 Hz, 1H), 4.93 (t, J = 3.5 Hz, 1H), 2.43 – 2.34 (m, 1H), 2.21 – 2.14 (m, 1H), 2.03 – 1.94 (m, 1H), 1.76 – 1.69 (m, 1H), 1.31 – 1.00 (m, 37H), 0.88 (t, J = 7.0 Hz, 3H).

¹³C NMR (126 MHz, CDCl₃) δ 143.61, 141.69, 135.42, 135.38, 133.69, 130.89, 130.07, 130.03, 128.31, 128.27, 127.51, 120.15, 119.45, 71.03, 32.08, 29.77, 29.71, 29.67, 29.60, 29.50, 28.71, 22.85, 18.26, 18.17, 17.85, 14.47, 14.28, 12.53.

Satisfactory HRMS data could not be obtained for this compound.

1-(4-Bromophenyl)-2-vinylidenedodecan-1-ol (4c)

A reaction tube (13 mm × 100 mm, Fisherbrand, part # 14-959-35C) equipped with a magnetic stir bar was capped with a Teflon/silicone septum (Thermo/National part # C4015-66A) screw cap and flame dried under vacuum. 3aa (1.92 g, 3.7 mmol) was added to a solution of tetrabutylammonium fluoride (1 M) in THF (7.4mL, 7.4 mmol). The reaction mixture was stirred at room temperature for 24 h. The mixture was treated with water, extracted with ethyl acetate. The combined organic layers were washed with brine, dried over Na₂SO₄, and finally evaporated under reduced pressure in a 50 °C oil bath. The crude residue was then purified by flash column chromatography on silica gel with hexanes/ethyl acetate (10:1) as the eluent to give the pure product 4c as colorless oil (1.08 g, 80% yield).

IR (ATR): 3365, 2923, 2852, 1954, 1592, 1485, 1466, 1070, 1010, 844 cm⁻¹.

¹H NMR (500 MHz, CDCl₃) δ 7.47 (d, J = 8.4 Hz, 2H), 7.25 (d, J = 8.4 Hz, 2H), 5.06 (s, 1H), 5.02 – 4.94 (m, 2H), 2.21 – 2.17 (m, 1H), 1.88 – 1.69 (m, 2H), 1.42 – 1.21 (m, 16H), 0.88 (t, J = 7.0 Hz, 3H).

¹³C NMR (126 MHz, CDCl₃) δ 204.29, 141.31, 131.56, 128.58, 121.73, 108.16, 80.16, 73.77, 32.05, 29.72, 29.54, 29.46, 29.38, 27.91, 27.60, 22.83, 14.26.

HRMS (ESI): m/z [M + H]⁺ calcd for C₂₀H₃₀OBr: 365.1475; found: 365.1522.

2-(4-Bromophenyl)-3-decyl-2,5-dihydrofuran (4d)

A reaction tube (13 mm × 100 mm, Fisherbrand, part # 14-959-35C) equipped with a magnetic stir bar was capped with a Teflon/silicone septum (Thermo/National part # C4015-66A) screw cap and flame dried under vacuum. AuCl₃ (1.5 mg, 5 mol %) was added to a solution of 4c (36.5 mg, 0.1 mmol) in 0.3 ml of dry dichloromethane under argon. The reaction mixture was then stirred at room temperature for 24 h. The solvent was evaporated under reduced pressure, and the crude residue was purified by rapid flash column chromatography on a short plug of silica gel with hexane/ethyl acetate (20:1) as eluent to afford the pure product 4d as a colorless oil (28.0 mg, 77%).

IR (ATR): 2922, 2853, 1746, 1591, 1486, 1466, 1071, 1014, 825 cm⁻¹.

¹H NMR (300 MHz, CDCl₃) δ 7.47 (d, J = 8.4 Hz, 2H), 7.14 (d, J = 8.4 Hz, 2H), 5.64 (dd, J = 3.3, 1.6 Hz, 1H), 5.48 (s, 1H), 4.90 – 4.79 (m, 1H), 4.76 – 4.65 (m, 1H), 1.78 (t, J = 7.3 Hz, 2H), 1.42 – 1.21 (m, 16H), 0.88 (t, J = 6.7 Hz, 3H).

¹³C NMR (75 MHz, CDCl₃) δ 143.26, 141.02, 131.72, 128.84, 121.91, 119.84, 89.31, 77.36, 75.80, 32.04, 29.72, 29.68, 29.52, 29.46, 27.43, 27.00, 22.83, 14.26.

HRMS (ESI): m/z [M + H]⁺ calcd for C₂₀H₃₀OBr: 365.1475; found: 365.1483.

2-(4-Bromophenyl)-2-(1-bromovinyl)dodecanal (4e)

A reaction tube (13 mm × 100 mm, Fisherbrand, part # 14-959-35C) equipped with a magnetic stir bar was capped with a Teflon/silicone septum (Thermo/National part # C4015-66A) screw cap and flame dried under vacuum. NBS (18.2 mg, 0.1 mmol) was added to 4c (36.5 mg, 0.1 mmol) in 1.3 mL H₂O. The reaction mixture was stirred at room temperature for 24 h. The resulting mixture was then quenched with a saturated aqueous solution of Na₂S₂O₃ (0.5 mL), extracted with ether (5 mL×3), washed with brine (5 mL), and dried over anhydrous Na₂SO₄. Filtration and evaporation under reduced pressure afforded the crude product, which was then was purified by flash column chromatography on silica gel with hexanes/ethyl acetate (20:1) as the eluent to give the pure product 4e as a colorless oil (20.8 mg, 47% yield).

IR (ATR): 2922, 2852, 1729, 1618, 1488, 1466, 1077, 1010, 898, 815 cm⁻¹.

¹H NMR (300 MHz, CDCl₃) δ 9.63 (s, 1H), 7.52 (d, J = 8.6 Hz, 2H), 7.20 (d, J = 8.6 Hz, 2H), 6.04 (d, J = 2.7 Hz, 1H), 5.97 (d, J = 2.8 Hz, 1H), 2.22 – 1.99 (m, 2H), 1.40 – 1.15 (m, 16H), 0.88 (t, J = 6.9 Hz, 3H).

¹³C NMR (75 MHz, CDCl₃) δ 195.98, 136.27, 133.45, 132.16, 130.06, 122.47, 121.85, 77.36, 65.52, 32.42, 32.04, 30.14, 29.71, 29.51, 29.45, 24.85, 22.83, 14.26.

HRMS (ESI): m/z [M + H]⁺ calcd for C₂₀H₂₉OBr₂: 443.0580; found: 443.0598.

Scheme 4.

Divergent Transformations of Products. (a) 9-BBN, THF, rt, 5 h, then H₂O₂, NaOH (3 M), 0 °C, 2 h. (b) Mo(CO)₆, Ph₂SiH₂, PhMe, 110 °C, 36 h. (c) Bu₄NF, THF, rt, 24 h. (d) AuCl₃, rt, CH₂Cl₂, 10 h. (e) NBS, H₂O, rt, 2 h.

Biographies

Yi-Ming Wang was born in Shanghai, China and grew up in Colorado, United States. He graduated with an A.B./A.M. degree in Chemistry & Physics and Mathematics from Harvard University in 2008 after conducting research in the group of Professor Andrew Myers. After obtaining his Ph.D. under the supervision of Professor Dean Toste at the University of California, Berkeley in 2013, he conducted postdoctoral research in the laboratory of Professor Stephen Buchwald at the Massachusetts Institute of Technology (USA) as a National Institutes of Health Postdoctoral Fellow. He joined the Department of Chemistry at the University of Pittsburgh in Fall 2017.

Yidong Wang was born in Zhejiang, China. He obtained his B.Sc. degree at Northeast Normal University after conducting research in the group of Professor Xihe Bi in 2012. Then he moved to East China Normal University to continue his Ph.D. study under the supervision of Professor Junliang Zhang. After obtaining his Ph.D. in 2017, he conducted postdoctoral research in Yiming Wang’s lab at the University of Pittsburgh, USA. In Fall 2022, he returned to China and joined the faculty at the School of Chemistry & Chemical Engineering at Yangzhou University.

Ruiqi Ding was born and grew up in Beijing, China. He graduated with a B.S. degree in College of Chemistry and Molecular Engineering from Peking University in 2019 after conducting research in the group of Professor Rong Zhu. He joined the Department of Chemistry at the University of Pittsburgh in Fall 2021 and now is pursuing his Ph.D. under the supervision of Professors Peng Liu and Yiming Wang.