DFT Studies on Cu-Catalyzed Cross-Coupling of Diazo Compounds

Jul 18, 2014 - Chengpeng Wang , Fei Ye , Chenggui Wu , Yan Zhang , and Jianbo Wang. The Journal of Organic Chemistry 2015 80 (17), 8748-8757...
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DFT Studies on Cu-Catalyzed Cross-Coupling of Diazo Compounds with Trimethylsilylethyne and tert-Butylethyne: Formation of Alkynes for Trimethylsilylethyne while Allenes for tert-Butylethyne Ting Wang, Meiyan Wang,* Sheng Fang, and Jing-yao Liu* Institute of Theoretical Chemistry, State Key Laboratory of Theoretical and Computational Chemistry, Jilin University, Changchun 130023, People’s Republic of China S Supporting Information *

ABSTRACT: The detailed reaction mechanism for the Cu(I)catalyzed cross-coupling of (diazomethyl)benzene with trimethylsilylethyne and tert-butylethyne was studied with the aid of density functional theory calculations. For both reactions, two catalytic cycles were considered. In one catalytic cycle, the active species reacts first with trimethylsilylethyne or tert-butylethyne, whereas, in the other one, the active species reacts first with (diazomethyl)benzene. In both catalytic cycles, the copper acetylide formation, copper carbene migratory insertion, and protonation steps are involved. The calculation results show that the protonation step is crucial for the product selectivity. In addition, the reaction of diazoethane with tert-butylethyne and the reaction of (diazomethyl)benzene with phenylacetylene were also considered theoretically.

1. INTRODUCTION Transition-metal-catalyzed cross-coupling reactions have been considered to be indispensable to the processes of carbon− carbon and carbon−heteroatom bond formations in modern organic synthetic chemistry.1 Pd-catalyzed cross-coupling reactions of aryl or vinyl halides with terminal alkynes, which are commonly termed as Sonogashira reactions,2−4 offer a powerful method to incorporate an alkynyl moiety into organic molecules to form new carbon−carbon bonds.5−9 Sonogashira crosscoupling reactions have been widely applied in the synthesis of organic materials, conjugate macrocyclic molecules, and natural products.10,11 In the past decade, the diazo compounds have been widely used as partners in Pd-catalyzed cross-coupling reactions to react with other reagents. These cross-coupling reactions are proposed through palladium carbene intermediates.12 While the combination of carbene formation and cross-coupling in one catalytic cycle is not restricted to Pd-catalyzed reactions, Cu-,13−17 Rh-,18 and Ni-catalyzed19 cross-coupling reactions using diazo compounds as reactants have also been explored. Because of the lower cost of copper catalysts, Cu-catalyzed reactions have obvious advantages in some cases for large-scale applications and for synthesis of pharmaceuticals. Recently, the cross-coupling of N-tosylhydrazones with trialkylsilylethyne and tert-butylethyne (eqs 1 and 2) have been reported by Wang and co-workers.20,21 The cross-coupling reactions were catalyzed by CuI in the presence of base LiOtBu in dioxane as solvent. © 2014 American Chemical Society

Interestingly, the substituents in terminal alkynes are important for the formation of products in the cross-coupling of N-tosylhydrazones with terminal alkynes. It is found that, under the identical reaction conditions, the reaction of the trimethylsilyl-substituted terminal alkyne gives the alkyne product, while the reaction of the tert-butyl-substituted terminal alkyne gives the allene product. Although the authors proposed a plausible reaction mechanism for the reactions of N-tosylhydrazones with trialkylsilyl-substituted terminal alkynes, the details of the reaction mechanism are ambiguous. In this paper, our goal is to elucidate the detailed reaction mechanism involved in the title reactions and gain some deep insights into how the substituents of terminal alkynes affect the product selectivity.

2. COMPUTATIONAL DETAILS Molecular geometries of the model complexes were optimized without constraints via DFT calculations using the B3LYP functional.22−25 The Wachters−Hay basis set26,27 6-311G(d) was used for Cu. This basis set has been shown to be appropriate for studies of many copper-catalyzed reactions.28−31 The 6-311G(d,p) basis set was used for all other main group atoms. Frequency calculations were carried out at the same level of theory to identify whether the computed stationary points as Received: November 7, 2013 Published: July 18, 2014 3941

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Scheme 1. Possible Reaction Mechanism

Figure 1. Energy profile calculated for the reactions of [tBuO−Cu−OtBu]− 1 with H−CC−SiMe3 and then with Ph(H)CN2 to form the allenylcopper intermediate 5. The calculated relative free energies are given in kcal/mol. minima (zero imaginary frequencies) or transition states (one imaginary frequency) and to provide the thermal correction to free energies at 298.15 K. Intrinsic reaction coordinate (IRC)32,33 calculations were performed for all transition states to confirm that the structures indeed connect two relevant minima. To take the solvent effect into account, single-point energy calculations were performed for all the structures at the ωB97X-D34 level using the 6-311G(d) basis set for Cu, and the 6-311+G(d,p) basis set for all other atoms with the continuum solvent model SMD35 in dioxane, which was used as solvent in the experiments.20,21 In this paper, solvation- and entropycorrected relative free energies are used to analyze the reaction mechanism. All calculations were performed with the Gaussian 09 software package.36

3. RESULTS AND DISCUSSION The possible reaction mechanism is presented in Scheme 1, in which the catalytic cycle I was proposed by Wang and coworkers13,20 and the catalytic cycle II was proposed by us. In catalytic cycle I, the Cu(I) species reacts first with terminal alkyne in the presence of base to form a copper acetylide A, followed by the reaction of A with diazo substrate B, which is generated in situ from the N-tosylhydrazone in the presence of base, generating the copper carbene species C. From intermediate C, migratory insertion into the Cu−carbene bond gives intermediate D. Subsequently, the protonation occurs, affording 3942

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Figure 2. Energy profiles calculated for the generation of alkyne product. (a) Oxidation addition of HOtBu and reductive elimination of alkyne product. (b) Protonation of intermediate 4 by HOtBu with the involvement of ortho carbon of the phenyl ring. (c) Protonation of the allenylcopper intermediate 5 by HOtBu and H−CC−SiMe3, respectively. The calculated relative free energies are given in kcal/mol.

the alkyne product or allene product. The initial step in catalytic cycle II is different from that in catalytic cycle I. In catalytic cycle II, the Cu(I) species reacts first with the diazo substrate B, giving the copper carbene species E. Then, intermediate E reacts with the terminal alkyne, forming C, which is involved in catalytic cycle I. In the following sections, both catalytic cycles I and II will be studied for the cross-coupling of N-tosylhydrazone with trimethylsilylethyne and tert-butylethyne, respectively. To understand the detailed mechanism of the crosscoupling reactions of N-tosylhydrazones with trialkylsilylethyne and tert-butylethyne (eqs 1 and 2), the following model reactions (eqs 3 and 4) were employed in our theoretical calculations.

The anionic complex [tBuO−Cu−OtBu]− was considered as the active species, which could be generated from the precatalyst CuI in the presence of an excess of the base LiOtBu.37,38 In the 3943

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Figure 3. Energy profile calculated for the protonation of intermediate 4 by HOtBu and H−CC−SiMe3, respectively, generating the allene product. The calculated relative free energies are given in kcal/mol.

barrier less than 5 kcal/mol calculated and reported recently by Wang and co-workers.50 In Figure 1, the copper moiety in intermediate 4 migrates from the phenyl-substituted carbon to the trimethylsilyl-substituted carbon via transition state TS(4‑5), transforming into the allenylcopper intermediate 5. For the process 4 → TS(4‑5) → 5, the energy barrier is only 10.3 kcal/mol and intermediate 5 is lower than intermediate 4 by 5.0 kcal/mol, showing that intermediate 4 tends to transform into intermediate 5. Moreover, intermediate 5 can easily go back to 4 due to the relatively small reverse energy barrier of 15.3 kcal/mol. In other words, intermediates 4 and 5 are in equilibrium since the forward and reverse energy barriers are small. Furthermore, there is another reaction pathway from 2 to generate allenylcopper intermediate 5. Intermediate 2 combines with Ph(H)CN2 via a five-membered transition state TS(2‑3′) with an energy barrier of 26.8 kcal/mol, forming a five-membered ring intermediate 3′. From intermediate 3′, the copper moiety migrates toward the trimethylsilyl-substituted carbon and releases a N2 molecule to generate the intermediate 5. Although TS(2‑3) is only 0.9 kcal/mol lower than TS(2‑3′), the former is 2.1 kcal/mol higher than the latter when using another DFT method M0649 instead of ωB97X-D to perform the single-point energy calculation in dioxane. Therefore, the pathway 2 → TS(2‑3) → 3 → TS(3‑4) → 4 → TS(4‑5) → 5 is favored over 2 → TS(2‑3′) → 3′ → TS(3′‑5) → 5. Figure 2 gives an illustration of the energy profiles for the reaction processes generating the alkyne product. As shown in Figure 2a, oxidative addition of HOtBu to Cu(I) intermediate 4 proceeds via transition state TS(4‑6) with a high energy barrier of 47.8 kcal/mol to produce a square-planar Cu(III) intermediate 6, from which reductive elimination takes place via TS(6‑1), giving the alkyne product and regenerating the active species 1. Transition state TS(6‑1) is 1.2 kcal/mol lower than intermediate 6 in free energy, indicating that oxidative addition and reductive elimination may proceed in a one-step process to directly give the alkyne product and regenerate the active species 1. Intermediate 6 is 39.0 kcal/mol higher than intermediate 4, showing that the Cu(III) species 6 is thermodynamically highly unstable, consistent with the instability of Cu(III) species found in previous studies.37,51 Since it is the benzyl that bonded to Cu in intermediate 4, the copper moiety would migrate to the ortho carbon of the phenyl ring (Figure 2b). The copper moiety in 4 migrates from the benzyl carbon to the ortho carbon of the phenyl ring via an η 3-benzyl transition state TS(4‑7), forming intermediate 7, from which coordination of HO tBu generates intermediate 8.

model reactions, (diazomethyl)benzene Ph(H)CN2 was the model for diazo substrate Ar(H)CN2, which could be generated in situ in experiments.20 The trimethylsilylethyne H−C C−SiMe3 and tert-butylethyne H−CC−tBu were used the same as the reactants in experiments.20 Cross-Coupling Reaction of (Diazomethyl)benzene with Trimethylsilylethyne. Catalytic Cycle I. According to the catalytic cycle I shown in Scheme 1, the calculated energy profiles for the cross-coupling of (diazomethyl)benzene Ph(H)CN2 with trimethylsilylethyne H−CC−SiMe3 are illustrated in Figures 1−3. In Figure 1, the reaction of active species [tBuO−Cu−OtBu]− 1 with H−CC−SiMe3 proceeds through a concerted metalation−deprotonation (CMD) process38−40 via the four-membered transition state TS(1‑2) with an energy barrier of 17.7 kcal/mol to release a HOtBu molecule and give the copper acetylide 2. Then, intermediate 2 reacts with (diazomethyl)benzene Ph(H)CN2 via transition state TS(2‑3) to generate the copper carbene intermediate 3 and release a N2 molecule. This result resembles the Cu−carbene bond formation steps in the previous theoretical calculation of the alkylation of N-iminopyridinium ylides with diazo compounds by Wang and co-workers,41 as well as the DFT study of cyclopropanation reaction by Salvatella and co-workers.42 The same reaction step is also found in the previous studies of Pd-catalyzed cross-coupling reactions of diazo compounds reported by Wang and coworkers,43−45 where the reaction of diazo compounds releases a N2 molecule, forming a palladium carbene intermediate. The calculated Cu−carbene bond length in intermediate 3 is 1.8294 Å, close to the values observed in the X-ray structures (in a range of 1.822−1.834 Å) of the Cu−carbene bond in previous studies.46−48 Migratory insertion of the alkynyl group into the Cu−carbene bond of intermediate 3 occurs through transition state TS(3‑4), generating intermediate 4. Although transition state TS(3‑4) is 1.1 kcal/mol lower than intermediate 3 in solvation-corrected free energy, TS(3‑4) is 0.1 kcal/mol higher than intermediate 3 in electronic energy at the B3LYP level in the gas phase. Moreover, intermediate 3 and transition state TS(3‑4) were optimized in solution at the B3LYP level, and both can be located with TS(3‑4) higher than 3 by 1.3 kcal/mol in free energy. In addition, TS(3‑4) and 3 have also been located by another DFT method M06-l49 in the gas phase, and TS(3‑4) is 0.9 kcal/mol higher than 3 in electronic energy. Therefore, the migratory insertion process has a small energy barrier, similar to the palladium carbene migratory insertion process with an energy 3944

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Figure 4. Energy profile calculated for the initial steps of catalytic cycle II. The calculated relative free energies are given in kcal/mol.

Catalytic Cycle II. According to the catalytic cycle II presented in Scheme 1, the calculated potential energy profile is presented in Figure 4. The reaction between [tBuO−Cu−OtBu]− and Ph(H)CN2 takes place via transition state TS(1‑10), generating copper carbene complex 10 and releasing a N2 molecule. The reaction of copper carbene complex 10 with H−CC−SiMe3 may occur through three possible pathways. A CMD process proceeds via four-membered transition state TS(10‑3) to release a HOtBu molecule and give intermediate 3, which is involved in cycle I, and the related energy profile has been discussed in Figure 1. The other two pathways involve the metathesis mechanism. The metathesis of copper carbene complex 10 with H−CC−SiMe3, in a fashion of Cu connecting to the trimethylsilyl-substituted carbon or the terminal carbon, via transition state TS(10‑11) or TS(10‑12) forms the metallacyclobutene intermediate 11 or 12. TS(10‑3) is lower than TS(10‑11) and TS(10‑12) by ca. 10 kcal/mol, suggesting that the pathway through transition state TS(10‑3) and intermediate 3 is preferred. In Figure 4, for the process 1 → 10 → 3, the energy barrier of TS(1‑10) is 26.4 kcal/mol relative to 1, whereas, for the process 1 → 2 → 3 shown in Figure 1, the energy barrier of TS(1‑2) is 17.7 kcal/mol relative to 1, indicating that 1 → 2 → 3, i.e., catalytic cycle I, is preferred. Above all, for the cross-coupling reaction of Ph(H)CN2 with H−CC−SiMe3, the overall energy profile is illustrated in Figure 5. The energy barriers of TS(5‑2), TS(4‑2), and TS(1‑2) (in the pathway 4 → TS(4‑1) → 1 + allene → TS(1‑2) → 2 + allene), are 24.6, 27.3, and 27.3 kcal/mol relative to 5, respectively. It is clear that the energy barrier of TS(5‑2) is 2.7 kcal/mol lower than those of TS(4‑2) and TS(1‑2), indicating that the alkyne product is preferred to be formed, in agreement with the observation in experiment.20 Moreover, when using another DFT method M0649 instead of ωB97X-D to perform the single-point energy calculation in dioxane, TS(5‑2) is 2.7 kcal/mol lower than those of TS(4‑2) and TS(1‑2), giving the pathway 4 → TS(4‑5) → 5 → TS(5‑2) → 2 + alkyne favorable. In one word, the catalytic cycle for this cross-coupling reaction is 2 → TS(2‑3) → 3 → TS(3‑4) → 4 → TS(4‑5) → 5 → TS(5‑2) → 2 + alkyne.

Subsequently, HOtBu provides a proton to the benzyl carbon via transition state TS(8‑9) to form intermediate 9. Then, dissociation of intermediate 9 gives alkyne product and [tBuO−Cu−OtBu]−1. In Figure 2c, HOtBu provides a proton to the phenylsubstituted carbon via transition state TS(5‑1) to release the alkyne product and regenerate [tBuO−Cu−OtBu]−1. It is notable that, for these three pathways giving alkyne product and active species 1 in Figure 2a−c, the energy barriers are all measured relative to intermediate 5, considering the equilibrium between 4 and 5. The transition states TS(4‑6) (Figure 2a), TS(8‑9) (Figure 2b), and TS(5‑1) (Figure 2c) are 52.8, 26.3, and 19.4 kcal/ mol higher than intermediate 5, respectively, suggesting that, among these three pathways giving alkyne product and active species 1, the pathway 4 → TS(4‑5) → 5 → TS(5‑1) → 1 is more favored. On the other hand, reagent H−CC−SiMe3 can also function as proton donor. H−CC−SiMe3 gives a proton to the phenyl-substituted carbon of 5 via TS(5‑2), releasing the alkyne product and directly regenerating copper acetylide 2. Comparing these two pathways (5 → TS(5‑2) → 2 + alkyne and 5 → TS(5‑1) → 1 + alkyne → TS(1‑2) → 2) in Figure 2c, TS(5‑2) is 2.8 kcal/mol lower than TS(1‑2), indicating that the reaction is inclined to pass through TS(5‑2) to give the alkyne product. Consequently, among these four pathways generating the alkyne product (Figure 2), the pathway 4 → TS(4‑5) → 5 → TS(5‑2) → 2 is preferred, using H−CC−SiMe3 as proton donor. After regenerating copper acetylide 2, the next catalytic cycle would begin with 2; i.e., 2 → ...→ 5 → TS(5‑2) → 2 + alkyne is one catalytic cycle. The energy profiles for the generation of the allene product are depicted in Figure 3. HOtBu provides a proton to the trimethylsilyl-substituted carbon of 4 via transition state TS(4‑1), releasing an allene product and regenerating the active species 1. In addition, the protonation by H−CC−SiMe3 occurs directly via TS(4‑2) to form allene product and 2. TS(4‑2) has an energy as high as TS(1‑2), showing that HOtBu and H− CC−SiMe3 are competitive to protonate intermediate 4 to give the allene product; i.e., both pathways 4 → TS(4‑1) → 1 → TS(1‑2) → 2 and 4 → TS(4‑2) → 2 are competitive to generate the allene product. 3945

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Figure 5. Overall energy profile for the cross-coupling of Ph(H)CN2 with H−CC−SiMe3. For the pathways generating alkyne and allene products, only the preferred pathways are presented. The calculated relative free energies are given in kcal/mol.

Figure 6. Energy profiles for the cross-coupling reaction of Ph(H)CN2 with H−CC−tBu. (a) The preferred pathways to generate the allene product. (b) The preferred pathways to generate the alkyne product. The calculated relative free energies are given in kcal/mol.

H−CC−tBu is similar to that of Ph(H)CN2 with H−C C−SiMe3. The energy profiles for all the possible reaction pathways are available in the Supporting Information for interested

Cross-Coupling Reaction of (Diazomethyl)benzene with tert-Butylethyne. The mechanism of the cross-coupling of (diazomethyl)benzene Ph(H)CN2 with tert-butylethyne 3946

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readers. In Figure 6, only the preferred reaction pathways for generating alkyne and allene products are given. The reaction of active species [tBuO−Cu−OtBu]− with H−CC−tBu, a CMD process, occurs via a four-membered transition state TS(1‑2A) to give copper acetylide 2A, which can react with Ph(H)CN2, releasing directly a N2 molecule to generate a copper carbene complex 3A. Subsequently, migratory insertion of the alkynyl group into the Cu−carbene bond in 3A gives intermediate 4A. The copper moiety of 4A migrates from the phenyl-substituted carbon to the tert-butyl-substituted carbon, forming the allenylcopper intermediate 5A (Figure 6a). Intermediates 4A and 5A are in equilibrium, for the forward and reverse energy barriers are only 10.3 and 15.4 kcal/mol, respectively. The protonation by HOtBu at the tert-butyl-substituted carbon of intermediate 4A occurs via transition state TS(4A‑1), generating the allene product and regenerating active species 1. The protonation by H−C C−tBu proceeds via transition state TS(4A‑2A) to release the allene product and regenerate copper acetylide 2A. Transition state TS(1‑2A) (in 4A → TS(4A‑1) → 1 + allene → TS(1‑2A) → 2A + allene) has the same energy as TS(4A‑2A), giving the indication of the two pathways being competitive. Figure 6b shows the two reaction pathways for the protonation by H−CC−tBu or HOtBu at the phenyl-substituted carbon of intermediate 5A, giving the alkyne product, i.e., 5A → TS(5A‑1) → 1 + alkyne → TS(1‑2A) → 2A + alkyne and 5A → TS(5A‑2A) → 2A + alkyne. As the energy difference between TS(5A‑2A) and TS(1‑2A) (in 5A → TS(5A‑1) → 1 + alkyne → TS(1‑2A) → 2A + alkyne) is only 0.1 kcal/mol, the two pathways to generate the alkyne product are also competitive. The energy barriers of these four protonation pathways (Figure 6) are all relative to 5A, taking the equilibrium between 4A and 5A into account. It is found that TS(4A‑2A) and TS(1‑2A) (in 4A → TS(4A‑1) → 1 + allene → TS(1‑2A) → 2A + allene) are ca. 3.5 kcal/ mol lower than TS(5A‑2A) and TS(1‑2A) (in 5A → TS(5A‑1) → 1 + alkyne → TS(1‑2A) → 2A + alkyne) in energy. Thus, the allene product is favored to be generated through the protonation by H− CC−tBu or HOtBu, consistent with the experimental observation21 that the allene is generated as the major product for the reaction of N-tosylhydrazone and tert-butylethyne. To understand why the preferred product changed from alkyne into allene when the substituent of reagent alkyne switched from trimethylsilyl to tert-butyl, four relevant transition states TS(4‑2), TS(5‑2), TS(4A‑2A), and TS(5A‑2A) were investigated, and the corresponding energy barriers are presented in Figure 7. The calculated gas-phase optimized geometries and solvent optimized geometries of these transition states are available in the Supporting Information. TS(4‑2) and TS(5‑2) are the key transition states in the preferred reaction pathways generating alkyne and allene products for trimethylsilyl-substituted terminal alkyne H−CC−SiMe3 (Figure 5), and TS(4A‑2A) and TS(5A‑2A) are the corresponding transition states for tert-butyl-substituted terminal alkyne H−C C−tBu (Figure 6). For the reaction of H−CC−SiMe3 (Figure 7a), TS(5‑2) lies lower than TS(4‑2) by 2.7 kcal/mol, giving the alkyne product, whereas, for the reaction of H−CC−tBu (Figure 7b), TS(4A‑2A) lies 3.5 kcal/mol lower than TS(5A‑2A), forming allene as the product. In TS(4‑2) and TS(5‑2), the length of the C(sp)−Si bond is 1.818 and 1.817 Å, close to the experimental values (1.84−1.85 Å) obtained from X-ray structures.52 The calculated bond distance of C(sp)−Si is shorter than that (in a range of 1.86−1.93 Å) of the C(sp3)−Si bond,53,54 showing that there is back-donation from the π orbital of the CC bond to the σ* antibonding orbital of the Si−CH3 bond. In Figure 7, it is noted that the energy barrier (19.2 kcal/mol) of TS(4A‑2A) is 3.1 kcal/mol lower than that (22.3 kcal/mol) of TS(4‑2), whereas

Figure 7. Geometry structures of four transition states TS(4‑2), TS(5‑2), TS(4A‑2A), and TS(5A‑2A), and the corresponding energy barriers relative to 4, 5, 4A, and 5A, respectively. The bond lengths, bond angles, and energy barriers are given in angstroms, degrees, and kcal/mol, respectively.

the energy barrier (27.8 kcal/mol) of TS(5A‑2A) is 3.2 kcal/mol higher than that (24.6 kcal/mol) of TS(5‑2), resulting in alkyne and allene being products for trimethylsilyl-substituted and tertbutyl-substituted reagents, respectively. Comparing TS(4‑2) and TS(4A‑2A), it is found that, in TS(4A‑2A), the tert-butyl-substituted C atom of H−CC−tBu interacts with the Cu center, giving the Cu−C bond length of 2.237 Å, whereas there is no corresponding interaction in TS(4‑2). The Cu−C interaction stabilizes the alkynyl anion and makes the H−CC−tBu in TS(4A‑2A) more easy to give a proton, leading to the result that the C−H bond of H−C C−tBu in TS(4A‑2A) is longer by 0.044 Å than the C−H bond of H−CC−SiMe3 in TS(4‑2). Therefore, the energy barrier of TS(4A‑2A) is smaller than that of TS(4‑2). Comparing TS(5‑2) and TS(5A‑2A), the structures are similar and there are no corresponding Cu−C interaction in both structures. Because of the steric repulsion between tBu and OtBu in TS(5A‑2A), the O−Cu−C angle is 106.4°, larger than that (91.2°) in TS(4A‑2A), giving not enough space to allow the Cu−C interaction in TS(5A‑2A). The energy barrier of TS(5‑2) is 3.2 kcal/mol lower than that of TS(5A‑2A) 3947

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because of the back-donation from the π orbital of the CC bond to the σ* antibonding orbital of the Si−CH3 bond, for the backdonation in TS(5‑2) reduces the CC electron density and stabilizes the alkynyl anion, inducing that H−CC−SiMe3 is easier than H−CC−tBu to give a proton. In one word, the Cu−C interaction between the tert-butyl-substituted C atom of H−CC−tBu and the Cu center, as well as the back-donation from the π orbital of the CC bond to the σ* antibonding orbital of Si−CH3, switches the product from alkyne for H−CC− SiMe3 to allene for H−CC−tBu. Mechanisms Summarized for the Reactions of Ph(H)CN2 with H−CC−SiMe3 and H−CC−tBu. Scheme 2

Protonation by H−CC−SiMe3 proceeds at the phenylsubstituted carbon, releasing the alkyne product and regenerating the copper acetylide [Me3Si−CC−Cu−OtBu]−. The next catalytic cycle would begin with [Me3Si−CC−Cu−OtBu]−. The preferred catalytic cycle for the reaction of Ph(H)CN2 with H−CC−tBu is illustrated in Scheme 2b. The reaction of anionic complex [tBuO−Cu−OtBu]− with H−CC−tBu generates a copper acetylide [tBu−CC−Cu−OtBu]−, which reacts with Ph(H)CN2, generating a copper carbene complex [tBu−CC−Cu(CHPh)(OtBu)]−. Subsequent migratory insertion of the alkynyl group into the Cu−carbene bond gives complex [tBu−CC−C(HPh)−Cu−OtBu]−. The protonation by H−CC−tBu or HOtBu at the tert-butyl-substituted carbon releases the allene product and regenerates [tBu−CC−Cu− OtBu]− or [tBuO−Cu−OtBu]−. Additionally, it was found that, in experiments,20,21 the reactions affording the allene products can tolerate various functional groups on both N-tosylhydrazones and terminal alkynes; therefore, the model reactions of diazoethane Me(H)CN2 with tert-butylethyne H−CC−tBu (eq 5) and (diazomethyl)benzene Ph(H)CN2 with phenylacetylene H−CC−Ph (eq 6) are also considered theoretically. In view of the importance of protonation steps, implied by the theoretical studies on the reactions of Ph(H)CN2 with H−CC−SiMe3 and H−C C−tBu discussed above, only the protonation processes were calculated for the two reactions (eqs 5 and 6). The detailed energy profiles are given in the Supporting Information. For both reactions, the pathways to generate allenes are found to be favorable, consistent with the observation of allenes as products in experiment.21 Furthermore, the difference of the protonation in these two reactions from that in reaction of Ph(H)CN2 with H−CC−tBu (eq 4) is that it is HOtBu, not the terminal alkyne (H−CC−tBu or H−CC−Ph), that is involved in the protonation process to generate the allene product.

Scheme 2. Preferred Catalytic Cycles for the Reactions of (a) Ph(H)CN2 with H−CC−SiMe3 and (b) Ph(H)CN2 with H−CC−tBu

4. CONCLUSIONS In this paper, the reaction mechanism of Cu-catalyzed crosscoupling reactions of (diazomethyl)benzene Ph(H)CN2 with trimethylsilylethyne H−CC−SiMe3 and tert-butylethyne H− CC−tBu has been investigated in detail with the aid of DFT calculations. For both reactions, catalytic cycle I was found to be preferred over catalytic cycle II, suggesting that [tBuO−Cu− OtBu]− first reacts with the alkyne reagent, not Ph(H)CN2. The reaction mechanism involves three steps: (1) copper acetylide formation, (2) copper carbene migratory insertion, and (3) protonation. It is found that the protonation processes are crucial for the selectivity of products. In cross-coupling of Ph(H)CN2 with H−CC−SiMe3, the alkyne product was favored to be generated by using H−CC−SiMe3 to provide a proton. In cross-coupling of Ph(H)CN2 with H−CC−tBu, HOtBu and H−CC−tBu are involved competitively in

summarizes the catalytic cycles for the reactions of (diazomethyl)benzene Ph(H)CN2 with trimethylsilylethyne H−CC−SiMe3 and tert-butylethyne H−CC−tBu. The preferred catalytic cycle for the reaction of Ph(H)CN2 with H−CC−SiMe3 is presented in Scheme 2a. The reaction of anionic complex [tBuO− Cu−OtBu]− with H−CC−SiMe3 generates a copper acetylide [Me3Si−CC−Cu−OtBu]−, which reacts with Ph(H)CN2, generating copper carbene complex [Me3Si−CC−Cu(CHPh)(OtBu)]−. Then, this copper carbene complex undergoes a migratory insertion through the alkynyl group, inserting into the Cu−carbene bond. Subsequently, the copper moiety in [Me3Si− CC−C(HPh)−Cu−OtBu]− migrates from the phenyl-substituted carbon toward the trimethylsilyl-substituted carbon to give an allenylcopper complex [Ph(H)CCC(SiMe3)−Cu−OtBu]−. 3948

dx.doi.org/10.1021/om4010803 | Organometallics 2014, 33, 3941−3949

Organometallics

Article

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protonation to give allene as the product. The result that the alkyne is found as the product for H−CC−SiMe3 while allene for H−CC−tBu can be explained by the Cu−C interaction between the tert-butyl-substituted C atom of H−CC−tBu and the Cu center, as well as the back-donation from the π orbital of the CC bond to the σ* antibonding orbital of Si−CH3. Furthermore, for both reactions of Me(H)CN2 with H−CC−tBu and Ph(H)CN2 with H−CC−Ph, the calculation of protonation processes indicates that the allene products would be generated using HOtBu as the proton donor.

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ASSOCIATED CONTENT

S Supporting Information *

Text giving the complete ref 36, detailed energy profiles for the reaction of Ph(H)CN2 with H−CC−tBu (eq 4), energy profiles for protonation processes of eqs 5 and 6, and a text file of all computed molecule Cartesian coordinates in .xyz format for convenient visualization. This material is available free of charge via the Internet at http://pubs.acs.org.

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AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected] (J.-y.L.). *E-mail: [email protected] (M.W.). Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was supported by the National Natural Science Foundation of China (Grants 21373098 and 21203073). The authors are grateful to the Computing Center of Jilin Province for essential support. The authors are grateful to the reviewers for their valuable comments, which have significantly improved the manuscript.

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REFERENCES

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dx.doi.org/10.1021/om4010803 | Organometallics 2014, 33, 3941−3949