Ligand Rearrangement Leads to Tetrahydrothiophene-Functionalized N,S-Heterocyclic Carbene Palladium(II) Complexes

Abstract

Tetrahydrothiophene-functionalized N,S-heterocyclic carbene palladium(II) complexes are synthesized through an unexpected rearrangement that proceeds with palladium(II) trifluoroacetate and not with palladium(II) acetate, palladium(II) bromide, or palladium(II) chloride. A series of these complexes were isolated and characterized by X-ray crystallography. The mechanism of formation of these [3.2.1]-palladabicycles was explored, and the catalytic capabilities of these complexes were demonstrated in representative C–C coupling reactions.

Graphical Abstract

INTRODUCTION

The past few decades have witnessed a surge of interest in carbenes as spectator ligands in transition metal catalysis.¹ An increasingly vast collection of ligands, including N-heterocylic carbenes (NHCs),² cyclic (alkyl)- and (aryl)-(amino)carbenes (CAACs),³ and abnormal NHCs (aNHCs)⁴ have been developed, which collectively grant access to diverse steric and electronic properties useful in catalyst development (Scheme 1, Panel A). While much of the research on NHC–metal complexes has focused on those in which the metal is coordinated to the C atom between two nitrogen atoms in an imidazole-based framework,^{1d, 2i} interest in similar carbenes,⁵ such as those where one N atom is replaced with an O (oxazole), P (phosphazole), or S (thiazole) has led to the naming system N,X-heterocyclic carbenes (X = O, P, S, etc.) or NXHC (Scheme 1b).⁶ NXHC–metal complexes have been extensively explored,⁷ with a number of studies focused specifically on NSHC–metal complexes.⁶

Scheme 1.

Examples of Relevant Carbenes^a

Polydentate ligands containing either multiple tethered NHCs or an NHC and an additional pendant functional group, such as an aminophosphine⁸, an ester⁹, or others¹⁰ have also been synthetically explored. Notably, a number of palladium complexes bearing sulfur-containing NHCs have been characterized (Scheme 1c)¹¹ and shown to catalyze various reactions, such as Suzuki couplings,¹² Mizoroki–Heck reactions,¹³ asymmetric allylic alkylations,¹⁴ hydroaminations,¹⁵ direct arylations^{15b, 16}, Sonogashira couplings,¹⁷ and nitrile-amide interconversions.¹⁷ In catalysis, metal-bound thioethers are hemilabile ligands that, when incorporated in a polydentate ligand framework that contains one or multiple NHCs, exhibit reversible binding to the metal center; this property can be useful in ligand design, for example in stabilizing resting states while still allowing dissociation to open a coordination cite for association of reactants.^{11d, 15b, 18}

RESULTS AND DISCUSSION

During the course of a previous study,¹⁹ a mixture of 2-(but-3-en-1-ylthio)benzo[d]thiazole (1a) and palladium(II) trifluoroacetate (Pd(TFA)₂) was stirred at 45 °C in 1,2-dichloroethane (1,2-DCE) for 12 h in attempt to isolate a palladium species bound to both the benzothiazole directing group and pendent alkene. After filtration and vapor diffusion of diethyl ether into the filtrate, a large number of yellow crystals formed. X-ray analysis revealed these crystals to be composed of an unexpected dimeric Pd₂(NSHC)₂(TFA)₄ complex containing the C,S-bidentate bridging NSHC ligand 3-(tetrahydrothiophen-3-yl)benzo[d]thiazol-3-ium-2-ide (Figure 1). This product, (±)-2a, was isolated in 82% yield and its structure was further confirmed by ¹H-NMR, ¹³C-NMR, and high-resolution mass spectrometry (HRMS). As of yet, a palladium complex with this type of bidentate ligand based on an NSHC with pendent thioether has not been reported to the best of our knowledge. Notably, when using other palladium sources, PdBr₂, PdCl₂, and Pd(OAc)₂, this product was not observed, suggesting that trifluoroacetate (TFA) ligands are uniquely suited for the formation of the NSHC-complex (Table 1). This may be attributed to the highly electrophilic nature of the Pd center in Pd(TFA)₂, which may promote key steps in the rearrangement process (vide infra).

Figure 1.

Molecular structure of (±)-2a showing 50% probability ellipsoids; hydrogen atoms and (CO)CF₃ groups from trifluoroacetate ligands are omitted for clarity. Selected bond lengths [Å] and bond angles [deg]: Pd1–Pd1’ 3.2086(5), Pd1–S1 2.2581(10), N1–C1 1.482(5), N1–C5 1.332(5), N1–C11 1.407(5), S2–C5 1.711(4), S2–C10 1.736(4), S1–Pd1–C5 94.21(11), C5–Pd1–O3 90.14(13), O3–Pd1–O1 83.25(11), O1–Pd1–S1 92.48(8), C5–Pd1–Pd1’ 91.49(10).

Table 1.

Synthesis of Bidentate NSHC Pd(TFA)₂ Complex^a

^aIsolated yields calculated as percentage of total possible product.

^bNone isolated.

^cObserved only by ¹H-NMR as part of a complex mixture of unassignable compounds.

^dNone observed upon crystallization.

This complex was of interest both from a structural and mechanistic perspective. First, the formation of a bridged [3.2.1]-palladabicycle containing a five-membered tetrahydrothiophene ring is a unique structure combining both an NSHC and a pendant bridging cyclic thioether. Second, the significant rearrangement of the starting material, which involves the breaking of a C(benzothiazole)–S(thioether) bond and the formation of C–S and C–N bonds, requires an unusual mechanism. Furthermore, due to the previously demonstrated synthetic utility of this benzothiazole thioether directing group,¹⁹ greater understanding of this mechanism could lead to further applications in reaction development.

Finding this complex and its formation interesting, we sought to synthesize and characterize several similar compounds to understand the generality and limitations of this process. (S)-2-(Pent-4-en-2-ylthio)benzo[d]thiazole ((S)-1b), which was added in 2 equiv relative to Pd(TFA)₂, successfully provided product 2b (70% yield) (Scheme 2A), isolated as a mixture of diastereomers (d.r. = 1.4:1, as determined by ¹H-NMR of the bulk solid) (Figure 2). ¹H-NMR spectrum of this mixture shows that only two major species are present in solution, suggesting that this series of palladium complexes, while Pd–Pd dimers in the solid state, are monomeric in solution, since three diastereomeric species would be expected in the case of dimers. Furthermore, the Pd–Pd bonds of all the dimers in crystal form are above 3.2 Å, suggesting semi-coordination that would not persist in the presence of solvent (see Table S56 in the Supporting Information). From this sample of 2b, selective crystallization of the major (S,S;S,S)-diastereomer allowed for further characterization by X-ray crystallography.²⁰ These findings suggest that the stereochemistry at the carbon–sulfur bond of the thioether in the starting material is maintained during the rearrangement, with the diastereoselectivity established in the bond-forming step between C1 (the carbon γ to the sulfur of the thioether in the starting material) and N1 with the major diastereomer favored due to attenuated steric interactions between the methyl group and palladium.

Scheme 2. Scope of NSHC Products^a.

^aIsolated yields calculated as percentage of total possible dimer. ^bProduct from (S)-2-(pent-4-en-2-ylthio)benzo[d]thiazole. ^cDiastereomeric ratio. ^dDiastereomeric ratio of 3.3:1 was seen for racemic product due likely to solubility differences during crystallization. ^eReaction conditions: Pd(TFA)₂ (1 equiv), benzo[d]thiazole-thioether (2 equiv.), 1,2-DCE, 45 °C, 12 h, air.

Figure 2.

The two diastereomers formed in a 1.36:1 ratio, respectively, from the reaction of (S)-1b when analyzing the bulk solid by ¹H-NMR. ^aMajor and minor diastereomers observed, respectively, and identified by ¹H-NMR and NOESY.

Next, (E)-2-(hex-3-en-1-ylthio)benzo[d]thiazole ((E)-1c), which was added in 2 equiv relative to Pd(TFA)₂, successfully provided complex (±)-2c (74% yield) (Scheme 2A). Analysis of the bulk solid by ¹H-NMR showed that this reaction yielded a single diastereomer, and X-ray analysis of a single crystal confirmed this to be the Pd(TFA)₂ complex with the bidentate trans-3-(2-ethyltetrahydrothiophen-3-yl)-benzo[d]thiazole-3-ium-2-ide ligand. Notably, (Z)-2-(hex-3-en-1-ylthio)benzo[d]thiazole ((Z)-1c) does not provide any product for reasons that are not immediately obvious (Scheme 3). Additionally, (E)-5-chloro-2-(hex-3-en-1-ylthio)benzo[d]thiazole (1d) was also subjected to the same conditions, and complex (±)-2d was isolated (72% yield) (Scheme 2A). No analogous complexes were observed when attempting to use S-substituted benzo[d]thiazole bearing internal or terminal alkynyl, longer or shorter tethers to the alkene, or 1,1-disubstituted terminal alkenes (Scheme 2B).

Scheme 3. Thermodynamic Product from Internal E Alkene^a.

^aIsolated yields calculated as percentage of total possible dimer. ^bReaction conditions: Pd(TFA)₂ (1 equiv), (E)-2-(hex-3-en-1-ylthio)benzo[d]thiazole (2 equiv.), 1,2-DCE, 45 °C, 12 h, air. ^cReaction conditions: Pd(TFA)₂ (1 equiv), (Z)-2-(hex-3-en-1-ylthio)benzo[d]thiazole (2 equiv.), 1,2-DCE, 45 °C, 12 h, air. ^dNo reaction.

In order to gain insight into the rearrangement mechanism, we revisited the results in Table 1 to more rigorously characterize the coordination mode of the substrates in non-rearranged complexes containing other counterions. Notably, complex 3a, trans-PdBr₂(1a)₂ contains two molecules of starting material coordinated through nitrogen (Figure 3). The analogous product, 3b, was also observed with PdCl₂ (see Table 1 and Figure S11 in the Supporting Information). Under the same conditions, treating Pd(TFA)₂ with 2-((2-methylbutyl)thio)benzo[d]thiazole (1e), which contains no alkene, provides the corresponding structure, 4 (Scheme 4). Of note, no evidence of palladium C5(benzothiazole)–S1(thioether) insertion was observed, which suggests that C5(benzothiazole)–S1(thioether) oxidative addition occurs after cyclization onto the alkene. Next, we tested whether other transition metals can trigger this cyclization. To this end, 1a was treated with numerous commercially available salts, including those derived from nickel, copper, platinum, iron, ruthenium, and silver. From these experiments, we obtained a novel silver complex from the treatment of 2 equiv 1a with silver(I) trifluoromethanesulfonate (AgOTf), which provided complex 5 (Figure 4). In the solid-state structure, Ag(I) is simultaneously bound to the thioether, the nitrogen of the benzothiazole group in a bimetallic dimer form, and the corresponding alkene, establishing that late transition metals can indeed coordinate to the alkene moiety in the presence of a benzothiazole group. Lastly, consistent with a recent literature report,²¹ we found that the treatment of 1a with an iodine source leads the substrate to undergo iodocyclization through nitrogen to give compound 6 (Figure 4).

Figure 3.

Molecular structure of 3a showing 50% probability ellipsoids; hydrogen atoms not on alkene are omitted for clarity. Selected bond lengths [Å] and bond angles [deg]: Pd1–N1 2.017(4), N1–C5 1.311(7), N1–C11 1.405(7), S2–C5 1.738(6), S2–C10 1.741(6), N1–Pd1–Br1 88.81(13), N1–Pd1–Br2 90.61(13), N1’–Pd1–Br1 88.90(13), N1’–Pd1–Br2 91.86(13).

Scheme 4. Pd(TFA)₂ Coordination to Benzo[d]thiazole^a.

^aIsolated yield.

Figure 4.

Isolated compounds with relevance to the proposed mechanisms.

Based on these initial results, several possible mechanisms of formation can be envisioned. Herein we describe two plausible pathways. In both proposals, we suggest that the Pd(TFA)₂ first coordinates to the starting material through the benzothiazole nitrogen and the alkene, as was previously computationally determined for the same starting material in an oxidative-Heck reaction with Pd(OAc)₂.¹⁹ While in principle this coordination could alternatively proceed through the thioether, as is seen in complex 5, or through a manner akin to complexes 3a, 3b, and 4 in which the Pd coordinates only to the benzo[d]thiazole nitrogen and not the alkene, the time course data suggests that an N1-bound-Pd(II) species coordinated to the alkene is the major species in solution (vide infra). After substrate coordination, the first mechanistic proposal involves a cyclization via anti-aminopalladation, with the benzothiazole nitrogen acting as the nucleophile, similar to the known cyclization induced by iodine. This cyclization step most likely requires a highly electrophilic Pd, which explains the unique reactivity observed with Pd(TFA)₂ over Pd(OAc)₂, PdBr₂, and PdCl₂. This could then be followed by intramolecular oxidative addition into the now weakened C5(benzothiazole)–S1(thioether) bond.²² Following this, a C2(sp³)–S1 S_N2-type reductive elimination would need to occur in a stereoinvertive fashion, as has been observed previously in C(sp³)–heteroatom reductive elimination from Pd(IV) centers.²³ This inversion would provide the observed final product upon S1-coordination and complex dimerization (Scheme 5A). Alternatively, a cyclization could occur first through a syn-aminopalladation that, when followed by oxidative addition into the C5(benzothiazole)–S1(thioether) bond and stereoretentive C2(sp³)–S1 reductive elimination, would lead to the observed product upon thioether coordination and dimerization (Scheme 5B).

Scheme 5.

Plausible Mechanisms of Formation

To further probe the viability of the proposed mechanisms, we monitored reaction progress over time with two model substrates, 1a and 1c at 45 °C under air in CDCl₃ by setting up a series of parallel trials and halting them at predetermined time points; we then assayed the solution (CDCl₃) and precipitate (DMSO-d₆). In both reaction sets, a new downfield peak was observed at 9.31 ppm in CDCl₃ upon mixing of 1a or 1c with Pd(TFA)₂. Based on shift, integration, and data from analogous compounds 3a, 3b, and 4, this peak was assigned to the N-bound-Pd(II) species. This species was short-lived for the reaction with terminal alkene 1a (Figure 5) and persistent in the reaction with the internal alkene 1c suggesting that the initial cyclization is much faster for the terminal alkene. In the time-course experiment with 1c, a downfield shift by 0.10 ppm of the alkene protons is observed, and the new ¹H resonances integrate in a 1:1:1 ratio with the aryl proton peak at 9.31 ppm, suggesting formation of a stable intermediate with palladium coordinated to the alkene, such as is seen with silver in complex 5, and to the benzothiazole nitrogen (and not the thioether). Furthermore, at 1–3 h, novels peaks at 5.88 and 6.51 ppm for the reaction with 1a in CDCl₃ and DMSO-d₆, respectively, are observed, consistent with the proposed cyclized intermediates. Similarly, the corresponding cyclic alkyl proton at 1’ in 6 (Figure 4) is significantly downfield at 5.58–5.51 ppm in DMSO-d₆.²¹ Similar compounds, such as 2,3-dihydro[1,3]thiazolo[2,3-b][1,3]benzothiazol-4-ium bromide,²⁴ also show downfield cyclic alkyl protons around 5 ppm in DMSO-d₆.

Figure 5.

Time course of reaction between 1a and Pd(TFA)₂ to yield 2a, taken in CDCl₃ with important new peaks highlighted. Full ¹H-NMRs, precipitate analysis (DMSO-d₆), and the time course experiment with 1c are available in the supporting information.

Finally, in a series of preliminary C–C coupling experiments, we found that (±)-2a was a competent precatalyst for several reactions, including a Suzuki–Miyaura coupling, a Heck reaction, and a dehydrogenative cross coupling, when tested under air with conditions from the literature without further optimization (see Scheme S3 in the Supporting Information).

CONCLUSIONS

We have herein identified a novel rearrangement leading to tetrahydrothiophene-functionalized NSHC palladium(II) complexes. Using X-ray, NMR, and HRMS data, the identity of these [3.2.1]-palladabicyclic products were confirmed. Through the synthesis of analogous complexes as well as the monitoring of reaction progress of the formation of (±)-2a and (±)-2c, two plausible and closely related mechanisms can be proposed. Understanding this rearrangement process may bolster use of the benzo[d]thiazole directing group in catalytic alkene functionalization reactions. Additionally, (±)-2a can successfully catalyze three C–C coupling reactions, suggesting that complexes containing bidentate NSHC ligands can be developed and explored further as a new class of catalysts.

EXPERIMENTAL SECTION

General Information.

Except where otherwise stated, all materials were used as received from commercial sources without further purification. All reactants, reagents, and solvents unless otherwise mentioned were purchased from Aldrich, Alfa Aesar, Oakwood, and Combi-Blocks and used without further drying or purification. All reactions were run in an atmosphere of air. NMR spectra were recorded on an AV-600 machine. Spectra were internally referenced to SiMe₄, solvent signal, or internal standard. The following abbreviations (or combinations thereof) were used to explain multiplicities: s = singlet, d = doublet, t = triplet, q = quartet, p = pentet, m = multiplet. High-resolution mass spectra (HRMS) for new compounds were obtained with Waters I-Class LC with diode array and G2-XS time of flight (TOF) mass spectrometer or with an Agilent LC/MSD TOF mass spectrometer.

Synthesis of Complexes (±)-2a–4.

To a 1-dram (4 mL) vial equipped with a magnetic stir bar was added the corresponding benzo[d]thiazole-containing material (0.2 mmol, 2 equiv) and the palladium-containing material (PdX₂) (0.1 mmol, 1 equiv). To this mixture was added 1,2-DCE (1 mL, 0.1 M) and the vial was capped. The reaction was stirred at 500 rpm at 45 °C for 12 h. Without cooling to room temperature, the crude solution was transferred into a new 1-dram (4 mL) vial. This uncapped vial with the crude mixture was placed inside a scintillation vial (20 mL). Diethyl ether (2 mL) was added to the scintillation vial without any addition into the 1-dram vial containing the crude material in preparation for vapor diffusion. The scintillation vial was capped and allowed to sit undisturbed for 72 h. The 1-dram vial was then removed from the scintillation vial and the solvent carefully removed with a pipette leaving crystals, which were washed with additional diethyl ether (3 × 3 mL). The remaining diethyl ether was then removed in vacuo to provide the pure product.

Complex (±)-2a:

The title compound was prepared with 2-(but-3-en-1-ylthio)benzo[d]thiazole (1a) and Pd(TFA)₂ at 0.300 mmol scale. Purification afforded (±)-2a as a yellow crystal (137 mg, 41%). ¹H NMR (600 MHz, Acetone-d₆) δ 8.33 (d, J = 8.6 Hz, 1H), 8.25 (dd, J = 8.1, 1.2 Hz, 1H), 7.79 (ddd, J = 8.5, 7.2, 1.2 Hz, 1H), 7.72–7.67 (m, 1H), 6.65 (t, J = 5.6 Hz, 1H), 4.14 (tt, J = 8.4, 5.0 Hz, 1H), 3.81 (d, J = 13.9 Hz, 1H), 3.51–3.42 (m, 2H), 3.12–3.03 (m, 1H), 2.89–2.84 (m, 1H). ¹³C NMR (151 MHz, DMSO-d₆) δ 178.37, 142.99, 132.90, 127.91, 126.74, 123.18, 115.44, 66.23, 45.11, 41.96, 38.51, 34.19. HRMS calcd. for C₁₃H₁₁F₃NO₂¹⁰⁶PdS₂⁺ [M/2–TFA]⁺: 439.9218, Found: 439.9219. Single crystals suitable for X-ray diffraction were obtained directly from the procedure described above (CCDC 2057872).²⁸

Complex 2b:

The title compound was prepared with 2-(pent-4-en-2-ylthio)benzo[d]thiazole (1b) and Pd(TFA)₂. Purification afforded 2b as a yellow crystal (40 mg, 35%) with a d.r. = 1.4:1 when (S)-2-(pent-4-en-2-ylthio)benzo[d]thiazole was used and a d.r. = 1:3.3 when the racemic starting material was used. ¹H NMR (600 MHz, Acetone-d₆) δ 8.31–8.23 (m, 2H), 7.78 (dtd, J = 8.5, 7.2, 1.2 Hz, 1H), 7.69 (ddt, J = 8.2, 7.2, 1.9 Hz, 1H), 6.65 (t, J = 4.9 Hz, 0.55H), 6.57 (t, J = 6.0 Hz, 0.42H), 4.85 (h, J = 7.2 Hz, 0.59H), 3.93 (dt, J = 9.2, 6.8 Hz, 0.45H), 3.81 (d, J = 14.2 Hz, 1H), 3.66 (dd, J = 14.1, 4.3 Hz, 0.55H), 3.59 (dd, J = 14.0, 4.8 Hz, 0.39H), 3.42–3.34 (m, 0.43H), 3.13–3.06 (m, 0.44H), 2.56 (ddd, J = 14.5, 7.2, 5.7 Hz, 0.50H), 2.40–2.32 (m, 0.45H), 1.97 (d, J = 6.8 Hz, 1.34H), 1.57 (d, J = 7.1 Hz, 1.67H). ¹³C NMR (151 MHz, Acetone-d₆) δ 181.37, 144.53, 144.32, 134.62, 128.84, 128.79, 127.66, 127.64, 123.91, 123.86, 115.88, 115.77, 69.20, 66.93, 53.24, 53.13, 44.47, 44.18, 42.96, 40.41, 21.67, 21.27. HRMS calcd. for C₁₄H₁₃F₃NO₂¹⁰²PdS₂⁺ [M/2–TFA]⁺: 449.9396, Found: 449.9388. Single crystals suitable for X-ray diffraction were obtained directly from the procedure described above (CCDC 2057870).²⁸

Complex (±)-2c:

The title compound was prepared with (E)-2-(hex-3-en-1-ylthio)benzo[d]thiazole ((E)-1c) and Pd(TFA)₂. Purification afforded (±)-2c as an orange crystal (43 mg, 37%). ¹H NMR (600 MHz, Acetone-d₆) δ 8.39 (d, J = 8.6 Hz, 1H), 8.25 (dd, J = 8.1, 1.2 Hz, 1H), 7.77 (ddd, J = 8.5, 7.2, 1.2 Hz, 1H), 7.69 (t, J = 7.6 Hz, 1H), 6.35 (d, J = 6.4 Hz, 1H), 4.17–4.07 (m, 2H), 3.59 (ddd, J = 13.7, 10.7, 5.1 Hz, 1H), 3.17 (ddt, J = 14.8, 10.7, 6.0 Hz, 1H), 2.07–2.11 (m, 2H), 1.86 (ddq, J = 14.5, 9.7, 7.3 Hz, 1H), 1.21 (t, J = 7.3 Hz, 3H). ¹³C NMR (151 MHz, Acetone-d₆) δ 180.18, 143.14, 132.90, 127.40, 126.27, 122.45, 116.55, 114.60, 114.26, 70.13, 60.09, 43.94, 36.08, 32.22, 29.24, 24.09, 11.12. HRMS calcd. for C₁₅H₁₅F₃NO₂¹⁰⁶PdS₂⁺ [M/2–TFA]⁺: 467.9531, Found: 467.9530. Single crystals suitable for X-ray diffraction were obtained directly from the procedure described above in a triclinic structure (CCDC 2057864)²⁸ and regrown from CDCl₃ in a trigonal structure (CCDC 2057865).²⁸

Complex (±)-2d:

The title compound was prepared with (E)-5-chloro-2-(hex-3-en-1-ylthio)benzo[d]thiazole (1d) and Pd(TFA)₂. Purification afforded (±)-2d as an orange crystal (45 mg, 36%). ¹H NMR (600 MHz, Acetone-d₆) δ 8.57–8.49 (m, 1H), 8.27 (d, J = 8.6 Hz, 1H), 7.79–7.60 (m, 1H), 6.37 (d, J = 6.7 Hz, 1H), 4.22–4.06 (m, 2H), 3.72–3.52 (m, 1H), 3.25–3.08 (m, 1H), 2.94–2.86 (m, 1H), 2.26–2.06 (m, 1H), 1.86 (dddd, J = 17.6, 15.0, 8.4, 5.0 Hz, 1H), 1.20 (q, J = 8.1 Hz, 3H). ¹³C NMR (151 MHz, Acetone-d₆) δ 183.13, 144.60, 133.85, 132.15, 127.03, 124.14, 115.42, 115.13, 115.06, 70.98, 60.60, 44.42, 36.61, 32.65, 24.51, 11.59. HRMS calcd. for C₁₅H₁₄³⁵ClF₃NO₂¹⁰⁴PdS₂⁺ [M/2–TFA]⁺: 499.9147, Found: 499.9134. Single crystals suitable for X-ray diffraction were obtained directly from the procedure described above (CCDC 2057869).²⁸

Complex 3a:

The title compound was prepared with 2-(but-3-en-1-ylthio)benzo[d]thiazole (1a) and PdBr₂. Purification afforded 3a as a yellow crystal (33 mg, 46%). ¹H NMR (600 MHz, CDCl₃) δ 9.16 (d, J = 8.3 Hz, 0.75H), 9.08 (d, J = 8.2 Hz, 0.25H), 7.71 (d, J = 7.9 Hz, 1H), 7.67 (t, J = 8.0 Hz, 1H), 7.44 (t, J = 7.5 Hz, 1H), 5.99 (td, J = 16.9, 6.9 Hz, 1H), 5.40–5.11 (m, 2H), 3.50–3.38 (m, 2H), 2.86–2.70 (m, 2H). ¹³C NMR (151 MHz, CDCl₃) δ 174.35, 173.72, 150.39, 134.93, 134.86, 131.22, 131.11, 127.78, 125.72, 122.72, 122.62, 121.35, 121.26, 118.23, 118.06, 35.50, 35.45, 33.08, 32.96, 29.86. HRMS calcd. for C₂₂H₂₄⁷⁹BrN₂¹⁰⁶PdS₄⁺ [M–Br+2H]⁺: 628.9041, Found: 628.9022. Single crystals suitable for X-ray diffraction were obtained directly from the procedure described above (CCDC 2057868).²⁸

Complex 3b:

The title compound was prepared with 2-(but-3-en-1-ylthio)benzo[d]thiazole (1a) and PdCl₂. Crystals were regrown to X-ray quality by slow evaporation of CDCl₃ in an NMR tube. Purification afforded 3b as a yellow crystal (32 mg, 51%). ¹H NMR (600 MHz, CDCl₃) δ 9.26 (dt, J = 8.3, 0.9 Hz, 0.65H), 9.18 (dt, J = 8.2, 0.9 Hz, 0.35H), 7.76–7.71 (m, 1H), 7.68 (ddd, J = 8.4, 7.3, 1.2 Hz, 1H), 7.45 (dddd, J = 8.2, 7.2, 6.1, 1.1 Hz, 1H), 6.04–5.93 (m, 1H), 5.36–5.18 (m, 2H), 3.48–3.42 (m, 2H), 2.82–2.71 (m, 2H). ¹³C NMR (151 MHz, CDCl₃) δ 173.90, 173.27, 166.39, 152.87, 149.53, 135.26, 134.77, 134.33, 134.25, 130.67, 130.56, 127.32, 125.57, 125.16, 125.13, 123.73, 121.85, 121.70, 121.05, 120.77, 120.69, 120.50, 117.65, 117.48, 116.51, 34.82, 34.80, 32.90, 32.42, 32.30, 29.27. HRMS calcd. for C₂₂H₂₂³⁵ClN₂¹⁰⁶PdS₄⁺ [M–Cl]⁺: 582.9386, Found: 582.9402. Single crystals suitable for X-ray diffraction were obtained directly from the procedure described above (CCDC 2051103).²⁸

Complex 4:

The title compound was prepared with 2-((2-methylbutyl)thio)benzo[d]thiazole (1e) and Pd(TFA)₂. Purification afforded 4 as an orange crystal (23 mg, 40%). ¹H NMR (600 MHz, CDCl₃) δ 9.30 (dd, J = 11.2, 8.4 Hz, 1H), 7.70 (dq, J = 12.6, 8.8 Hz, 2H), 7.44 (t, J = 7.7 Hz, 1H), 3.37 (ddd, J = 13.1, 7.8, 5.9 Hz, 1H), 3.25–3.16 (m, 1H), 2.00 (qd, J = 13.7, 6.7 Hz, 1H), 1.68 (dtt, J = 13.0, 10.1, 6.3 Hz, 1H), 1.44 (dpd, J = 14.8, 7.4, 3.0 Hz, 1H), 1.19 (dd, J = 6.7, 4.2 Hz, 3H), 1.01 (q, J = 7.1 Hz, 3H). ¹³C NMR (151 MHz, CDCl₃) δ 176.59, 176.41, 149.81, 149.72, 130.54, 130.42, 128.08, 127.98, 125.81, 125.78, 122.02, 122.00, 121.18, 43.14, 43.04, 35.07, 35.01, 28.98, 28.94, 19.01, 11.37. HRMS calcd. for C₂₆H₃₀F₃N₂O₂¹⁰⁶PdS₄⁺ [M–TFA]⁺: 693.0177, Found: 693.0168. Single crystals suitable for X-ray diffraction were obtained directly from the procedure described above (CCDC 2057871).²⁸

Synthetic Procedure for Complex 5.

To a 1-dram (4 mL) vial equipped with a magnetic stir bar was added 2-(but-3-en-1-ylthio)benzo[d]thiazole (1a) (0.10 mmol, 2 equiv) and the silver triflate (AgOTf) (0.05 mmol, 1 equiv). To this mixture was added 1,2-DCE (0.5 mL, 0.1 M), and the vial was capped. The reaction was stirred at 500 rpm at 45 °C for 12 h. Without cooling to room temperature, the crude solution was transferred into a new 1-dram (4 mL) vial. This uncapped vial with the crude mixture was placed inside a scintillation vial (20 mL). Diethyl ether (2 mL) was added to the scintillation vial without any addition into the 1-dram vial containing the crude material in preparation for vapor diffusion. The scintillation vial was capped and allowed to sit undisturbed for 72 h. The 1-dram vial was then removed from the scintillation vial and the solvent carefully removed with a pipette leaving crystals, which were washed with additional diethyl ether (3 × 3 mL). The remaining diethyl ether was then removed in vacuo to provide the pure product 5 as a grey crystal (20 mg, 42%).

¹H NMR (600 MHz, Acetone-d₆) δ 8.12 (dd, J = 15.3, 8.2 Hz, 2H), 7.59 (ddd, J = 8.3, 5.0, 1.3 Hz, 1H), 7.56–7.49 (m, 1H), 6.24 (ddtd, J = 13.4, 8.4, 6.7, 1.8 Hz, 1H), 5.45–5.36 (m, 2H), 3.71 (td, J = 6.5, 1.8 Hz, 2H), 2.75 (q, J = 6.7 Hz, 2H). ¹³C NMR (151 MHz, Acetone-d₆) δ 171.79, 152.45, 135.76, 134.98, 128.28, 126.71, 122.93, 122.63, 114.01, 36.68, 33.85. HRMS calcd. for C₁₁H₁₁¹⁰⁷AgNS₂⁺ [M–OTf]⁺: 327.9384, Found: 327.9395. Single crystals suitable for X-ray diffraction were obtained directly from the procedure described above (CCDC 2057866).²⁸

Synthetic Procedure for 4-(iodomethyl)-3,4-dihydro-2H-benzo[4,5]thiazolo[2,3-b][1,3]thiazin-5-ium triiodide (6).

To a 1-dram (4 mL) vial equipped with a magnetic stir bar was added 2-(but-3-en-1-ylthio)benzo[d]thiazole (1a) (0.5 mmol, 1 equiv) and the samarium(II) iodide (SmI₂) (0.5 mmol, 0.1 M solution in THF, 1 equiv). To this mixture was added 1,2-DCE (5 mL, 0.1 M) and the vial was capped. The reaction was stirred at 500 rpm at 45 °C for 12 h. Without cooling to room temperature, the crude solution was transferred into a new 1-dram (4 mL) vial. This uncapped vial with the crude mixture was placed inside a scintillation vial (20 mL). Diethyl ether (2 mL) was added to the scintillation vial without any addition into the 1-dram vial containing the crude material. The scintillation vial was capped and allowed to sit undisturbed for 72 h. The 1-dram vial was then removed from the scintillation vial and the solvent carefully removed with a pipette leaving crystals, which were washed with additional diethyl ether (3 × 3 mL). The remaining diethyl ether was then removed in vacuo to provide the pure product. While some X-ray quality crystals were retrievable, yield of crystals appeared low (<10%). Reaction was rerun following a literature procedure.²¹

¹H NMR (600 MHz, DMSO-d₆) δ 8.32 (dt, J = 8.3, 2.0 Hz, 1H), 8.11 (dd, J = 8.6, 3.0 Hz, 1H), 7.86–7.78 (m, 1H), 7.71 (td, J = 7.7, 3.0 Hz, 1H), 5.54 (dh, J = 9.6, 3.1 Hz, 1H), 3.74–3.66 (m, 2H), 3.67–3.54 (m, 2H), 3.01 (dq, J = 15.1, 3.3 Hz, 1H), 2.46 (ddd, J = 15.5, 10.0, 4.3 Hz, 1H). ¹³C NMR (151 MHz, DMSO) δ 175.83, 140.77, 128.69, 127.66, 127.09, 123.98, 114.96, 55.10, 23.25, 23.16, 2.10. Single crystals suitable for X-ray diffraction were obtained directly from the procedure described above (CCDC 2057863).²⁸

Synthetic Procedure for [1,1’-biphenyl]-4-carbaldehyde (7):²⁵

To a 1-dram (4 mL) vial equipped with a magnetic stir bar was added 4-bromobenzaldehyde (0.3 mmol, 1 equiv), phenylboronic acid (0.36 mmol, 1.2 equiv), potassium carbonate (K₂CO₃) (1.0 mmol, 2 equiv), and (±)-2a (0.0015 mmol, 0.5 mol%). To this mixture was added a 1:1 mixture of H₂O:DMF (3 mL, 0.1 M). The vial was capped and placed on a preheated hotplate at 100 °C and stirred at 500 rpm for 12 h. The reaction was removed from the stir plate and allowed to cool. The contents of the vial were transferred to a separation vial with subsequent washing of H₂O and EtOAc. Additional H₂O (50 mL) was added to the separation vial, and the desired material was extraction with EtOAc (3 × 50 mL) and dried with Na₂SO₄. After the solvent was removed in vacuo, the crude residue was purified by SiO₂ gel column chromatography (5% EtOAc/hexanes). Purification afforded 7 as a white solid (90 mg, >95%).

¹H NMR (600 MHz, CDCl₃) δ 10.06 (s, 1H), 7.95 (d, J = 8.2 Hz, 2H), 7.75 (d, J = 8.2 Hz, 2H), 7.64 (d, J = 8.1 Hz, 2H), 7.49 (t, J = 7.8 Hz, 2H), 7.42 (t, J = 7.5 Hz, 1H). ¹³C NMR (151 MHz, CDCl₃) δ 192.00, 147.24, 139.76, 135.27, 130.35, 129.10, 128.56, 127.75, 127.44.

Synthetic Procedure for (E)-4-(4-methylstyryl)benzaldehyde (8):²⁶

To a 1-dram (4 mL) vial equipped with a magnetic stir bar was added the corresponding 4-bromobenzaldehyde (0.3 mmol, 1 equiv), 1-methyl-4-vinylbenzene (0.36 mmol, 1.2 equiv), potassium carbonate (K₂CO₃) (1.0 mmol, 2 equiv), and (±)-2a (0.0015 mmol, 0.5 mol%). To this mixture was added a 1:1 mixture of H₂O:DMF (3 mL, 0.1 M). The vial was capped and placed on a preheated hotplate at 100 °C and stirred at 500 rpm for 12 h. The reaction was removed from the stir plate and allowed to cool. The contents of the vial were transferred to a separation vial with subsequent washing of H₂O and EtOAc. Additional H₂O (50 mL) was added to the separation vial, and the desired material was extraction with EtOAc (3 × 50 mL) and dried with Na₂SO₄. After the solvent was removed in vacuo, the crude residue was purified by SiO₂ gel column chromatography (5% EtOAc/hexanes). Purification afforded 8 as a yellow solid (45 mg, 67%).

¹H NMR (600 MHz, CDCl₃) δ 9.99 (s, 1H), 7.86 (d, J = 8.0 Hz, 2H), 7.64 (d, J = 8.1 Hz, 2H), 7.45 (d, J = 7.8 Hz, 2H), 7.27–7.19 (m, 3H), 7.10 (d, J = 16.2 Hz, 1H), 2.38 (s, 3H). ¹³C NMR (151 MHz, CDCl₃) δ 191.79, 143.83, 138.77, 135.31, 133.93, 132.33, 130.40, 129.71, 126.99, 126.92, 126.47, 21.49.

Synthetic Procedure for 5-(benzo[d]oxazol-2-yl)thiophene-2-carbaldehyde (9):²⁷

To a 1-dram (4 mL) vial equipped with a magnetic stir bar was added the benzo[d]oxazole (0.1 mmol, 1 equiv), thiophene-2-carbaldehyde (0.2 mmol, 2 equiv), silver acetate (AgOAc) (0.2 mmol, 2 equiv), and (±)-2a (0.05 mmol, 5 mol%). To this mixture was added a 1:1 DMSO (1 mL, 0.1 M). The vial was capped and placed on a preheated hotplate at 110 °C and stirred at 500 rpm for 12 h. The reaction was removed from the stir plate and allowed to cool. The contents of the vial were transferred to a separation vial with subsequent washing of H₂O and EtOAc. Additional H₂O (50 mL) was added to the separation vial, and the desired material was extraction with EtOAc (3 × 50 mL) and dried with Na₂SO₄. After the solvent was removed in vacuo, the crude residue was purified by SiO₂ gel column chromatography (5% EtOAc/hexanes). Purification afforded 9 as a yellow solid (14 mg, 61%).

¹H NMR (600 MHz, CDCl₃) δ 10.00 (d, J = 2.1 Hz, 1H), 7.97 (dd, J = 3.9, 2.1 Hz, 1H), 7.82 (dd, J = 4.0, 2.1 Hz, 1H), 7.79 (dt, J = 8.5, 1.7 Hz, 1H), 7.63–7.57 (m, 1H), 7.40 (pt, J = 7.4, 1.7 Hz, 2H). ¹³C NMR (151 MHz, CDCl₃) δ 183.00, 157.81, 150.82, 146.39, 141.97, 137.78, 136.25, 130.04, 126.37, 125.41, 120.61, 110.93.

ABBREVIATIONS

NHC

N-Heterocyclic Carbene

CAAC

Cyclic (Alkyl)- and (Aryl)-(Amino)Carbenes

aNHC

abnormal N-Heterocyclic Carbene

NXHC

N,X-Heterocyclic Carbene (X = O, P, S, etc.)

Pd(TFA)₂

Palladium(II) Trifluoroacetate

1,2-DCE

1,2-Dichloroethane

HRMS

High-Resolution Mass Spectrometry

TFA

Trifluoroacetate

AgOTf

Silver(I) Trifluoromethansulfonate

AgOAc

Silver(I) Acetate