Mechanistic Elucidation of Gold(I)-Catalyzed Oxidation of a

Article Cite This: Organometallics XXXX, XXX, XXX−XXX

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Mechanistic Elucidation of Gold(I)-Catalyzed Oxidation of a Propargylic Alcohol by a N‑Oxide in the Presence of an Imine Using DFT Calculations Fatemeh Zarkoob† and Alireza Ariafard*,†,‡ †

Department of Chemistry, Islamic Azad University, Central Tehran Branch, Poonak, Tehran, Iran School of Natural Sciences (Chemistry), University of Tasmania, Private Bag 75, Hobart, Tasmania 7001, Australia

‡

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S Supporting Information *

ABSTRACT: Density functional theory (DFT) calculations were utilized to investigate the mechanism of the oxidation of an indolyl propargylic alcohol by a N-oxide in the presence of an imine and a gold(I) catalyst. The catalytic reaction is proposed to start from regioselective oxidation of the gold(I)-activated alkyne dictated by a hydrogen bond interaction between the OH group of the propargylic alcohol and the N-oxide. This oxidation was expected to give an α-carbonyl gold carbene complex. In contrast to this expectation, our calculations showed that the corresponding carbene is not a local minimum and the complex undergoes a very fast 1,2 aryl shift to form an alkene complex. Subsequently, an imine is added to the ensuing alkene complex to give an iminium cation from which a cycloaddition process occurs and an indolium is formed. Finally, an N-oxide deprotonates the indolium complex and affords an intermediate which is significantly reactive toward water elimination. Our calculations indicate that the 1,2-aryl shift in α-carbonyl gold carbene complexes is decelerated if the aryl is substituted by an electron-withdrawing group. At the end, we investigated the stability of different gold carbene complexes and found that the identity of the carbene is the determinant of how these carbenes are trapped.

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INTRODUCTION Quinoline/pyridine N-oxides (Z+−O−) are well-established to oxidize alkynes with the aid of gold(I) catalysts and produce functionalized organic products in the presence of internal/ external nucleophiles.1 Such a catalytic reaction is believed to commence with the nucleophilic attack of an N-oxide on a gold(I)-activated alkyne, followed by elimination of quinoline/ pyridine (Z) to give an α-carbonyl gold carbenoid/carbene complex (Scheme 1).2 Due to the high electrophilicity of the resultant carbene species, they are subject to internal/external nucleophilic attacks. For example, gold-catalyzed oxidation of internal alkynes by N-oxides gives carbenes, which can be trapped by three different routes to yield different intermediates/products as outlined in Scheme 1.3−5 In this context, Liu et al. synthesized dihydro-γ-carbolines (II) through reaction between indolyl propargylic alcohols (I) and imines in the presence of quinoline N-oxides:6

Scheme 1. Gold-Assisted Oxidation of an Alkyne by a NOxide (Z+−O−) Followed by Trapping of the Ensuing αCarbonyl Gold Carbene Complex via Three Different Pathways

species is then immediately trapped by the external imine nucleophile to give iminium complex IV. Subsequently, the nucleophilic addition of the indole moiety to the iminium carbon affords V from which a water is eliminated and intermediate VI is generated. Interestingly, the authors

They proposed that the oxidants regioselectively oxidize the propargylic alcohols at the position substituted by the R′ group and thus produces carbene complex III (Scheme 2). This elusive © XXXX American Chemical Society

Received: November 4, 2018

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DOI: 10.1021/acs.organomet.8b00808 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics Scheme 2. Mechanism Proposed by Liu et al. for the Reaction Given in Equation 1 (Mechanism A)

Scheme 3. Alternative Mechanism Proposed by Liu et al. for the Reaction Given in Equation 1 (Mechanism B)

Scheme 4. Stability Comparison between Different Gold Adductsa

a

The Gibbs free energies are given in kcal/mol.

Scheme 5. Relative Gibbs Free Energy (kcal/mol) of Key Stationary Points for Addition of Z+−O− to 3

anticipated that VI is reactive toward 1,2 acyl migration and not gold elimination and so produces gold carbene complex VII. Finally, a 1,2 hydrogen shift process occurs, and product II is formed. However, we have to point out that as proposed by Liu et al.6 there is an alternative pathway for formation of II (Scheme 3, mechanism B) in which intermediate III rather than trapping by an external nucleophile undergoes intramolecular aryl migration to give alkene−gold complex VIII. This intermediate then produces alkyl complex IX via regioselective addition of imine to the carbon substituted by the OH group. Thereafter, the nucleophilic addition of the indole moiety to the iminium carbon in IX affords X, an intermediate which finally generates II preceded by water elimination.

In this contribution, we employed density functional theory (DFT) calculations to investigate both mechanisms in details with the aim of identifying which of these mechanisms may operate. Another purpose of this work is to provide a better understanding as to how the electrophilicity of the gold carbene complexes controls competition between internal (H- and Rmigration) and external nucleophiles in trapping these elusive species.

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RESULTS AND DISCUSSION Regioselective Addition of Z+−O− to the Gold(I)Activated Alkyne. The first aim of this study is to understand why quinoline N-oxides are regioselectively added to a propargylic alcohol activated by Au(I). An analysis of factors B


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Organometallics

imine →11 (ΔG = −8.2 kcal/mol, Scheme 6) as compared to 3 + Z+−O− → 10 (ΔG = 0.3 kcal/mol, Scheme 5). The higher nucleophilicity of Z+−O− might be rationalized by the fact that the HOMO of Z+−O− (−5.47 eV) is by 1.29 eV higher in energy than that of the imine (−6.76 eV). Origin of Unfavorability of Mechanism A. Once 10 is formed, the alkyne oxidation is complete by liberation of the quinoline (Z) via transition structure TS6 (Scheme 7). This

that control the regioselectivity is needed due to the fact that the oxidation of internal alkynes by N-oxides does not usually occur in a regioselective fashion.1a,5c To commence, we considered in our calculations 1 as a model propargylic alcohol, Z+−O− as the oxidant, MeCHNMe as the external imine nucleophile, and PMe3Au+ as a model for the cationic Au(I) complex (Scheme 4). The gold(I) complex is bonded to the imine more strongly than other substrates from which we infer that adduct 2 is likely the resting state of the catalyst.7 As discussed above, the reaction is surmised to commence with nucleophilic addition of Z+−O− to π-complex 3. For this addition to proceed, 3 is initially hydrogen bonded to Z+−O− through its alcohol functional group to give outersphere complex 9 (Scheme 5). From this complex, there are two variants for nucleophilic addition of the N-oxide to the activated alkyne, occurring either by transition structure TS1 or by TS2. The calculations show that TS1 is about 1.9 kcal/mol lower in energy than TS2. This result indicates that in agreement with the experimental findings the alkyne prefers to be oxidized at its C1 atom. Inspection of the O2···H bond distance for 9, TS1, and TS2 reveals that the hydrogen bond is weakened upon moving from 9 to the transition structures; the O2···H bond distance in 9 (1.657 Å) is shorter than those in TS1 (1.790 Å) and TS2 (1.918 Å). However, we have to note that the weakening is less significant in TS1 than in TS2, a feature which leads to the former lying lower in energy than the latter. The O2−H−O1 bond angle in TS2 is calculated to be 128.9°, implying that the attack on C2 forces the hydrogen bond to considerably deviate from the optimal condition (180° for an ideal hydrogen bond), rendering the O2···H bond in TS2 weaker than in TS1. It follows from these results that the strength of the O2···H hydrogen bond plays a major role in the regioselective oxidation of these systems. To further shed light on the importance of the O2···H hydrogen bonding, we calculated TS3 and TS4 in which the relevant interaction is turned off (Scheme 5). The energies of these two transition structures are calculated to be comparable and are both higher in energy than TS1 and TS2. Thus, in the lack of the hydrogen bond, the N-oxide is predicted to add to the alkyne in a nonregioselective manner. In addition, the hydrogen bond helps accelerate the nucleophilic addition of the N-oxide by stabilizing the corresponding transition structure (TS1). Can 3 Be Trapped by an Imine? As discussed above, the imine is bonded more strongly to the gold center than the Noxide which suggests that the former is likely a stronger Lewis acid than the latter. This raises the question about whether the imine also serves as a better nucleophile than the N-oxide. To address this assumption, transition structure TS5 was calculated (Scheme 6). This transition structure is computed to be higher in energy than TS1 by 4.2 kcal/mol, implying that although the imine is a stronger Lewis base, it is a weaker nucleophile than the N-oxide (Z+−O−). The stronger Lewis basicity of the imine is also supported by the greater exergonicity of the reaction 3 +

Scheme 7. Sequence Showing Conversion of 10−13a

a


transition structure (TS6) is slightly below TS1 (about 0.3 kcal/ mol). According to previous proposals,1,2 the oxidation is expected to yield α-carbonyl gold carbene 12. However, the IRC calculations for TS6 show that such an intermediate is not a local minimum, and attempts to optimize it led to formation of 13. In fact, the 1,2-aryl shift in carbene complex 12 is so fast that it makes this species too elusive to be trapped by an external nucleophile. As such, mechanism A (Scheme 2) in which the carbene complex 12 is required to be trapped by an imine is ruled out, thereby supporting the likely operation of mechanism B (Scheme 3). One possibility for formation of a structure analogous to IV (Scheme 2) is that 10 is involved in attack of the imine to C2 while Z is being released (Scheme 7). Attempts to locate such a transition structure led to TS′6 in which the imine resides beyond a productive distance (4.477 Å). This transition structure is calculated to be 4.2 kcal/mol higher in energy than TS6.8 The IRC calculation indicates that TS′6 is connected to 13 and not a structure analogous to IV.9 Trapping of 13 by an External Nucleophile Followed by Cycloaddition. There are two possibilities for the imine to nucleophilically attack intermediate 13 (either via attack to C3 or to C2, Figure 1). The imine addition to C3 take place via transition structure TS7a with a low barrier of 10.6 kcal/mol. The ensuing iminium intermediate (14) triggers the C−C coupling process through transition structure TS7b, forming 15 which lies 13.4 kcal/mol above 13. The overall activation barrier for this process is calculated to be as much as 16.6 kcal/mol, indicating that the C−C coupling commenced by the imine addition to C3 is energetically accessible. In contrast, the addition of the imine to the C2 atom is extremely energy demanding with an activation barrier of 34.3 kcal/mol. The smaller electrophilicity of the C2 atom to receive the nucleophile is reflected in relative stability of iminium intermediate 16 which is calculated to be 17.7 kcal/mol less stable than that of its regioisomer 14. This excellent regioselectivity for the imine addition to 13 is most likely

Scheme 6. Relative Gibbs Free Energy (kcal/mol) of Key Stationary Points for Addition of the Imine to 3

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Organometallics

Figure 1. Gibbs energy profile comparing regioselective addition of the imine to 13. The Gibbs free energies are given in kcal/mol.

Scheme 8. Relative Gibbs Free Energy (kcal/mol) of Key Stationary Points for Addition of Z+−O− to 13a

a


these results that Z+−O− not only oxidizes the activated alkynes but also mediates the proton transfer processes. However, it should be noted that this oxidant is a weaker base than the imine (as discussed above), a claim which is further supported by the lower exergonicity for transformation 15 + Z+−O− → 16 (ΔG = −3.9 kcal/mol) as compared to 15 + 2 → 16 (ΔG = −4.7 kcal/ mol). The reactivity of Z+−O− being higher than the imine for removal of a proton might again be explained by higher lying HOMO for Z+−O− (vide supra). Passing through transition structure TS8, intermediate 17 is formed. This intermediate is predicted to be in equilibrium with its more stable isomer 18 in which Z+−OH is stabilized by a hydrogen bonding interaction with the alcohol’s OH group (Scheme 9). 18 is susceptible to lose a water with a Gibbs free energy of 7.5 kcal/mol to form the final product (prod). Proposed Mechanism Derived from DFT Calculations. A detailed catalytic cycle derived from DFT calculations for gold-catalyzed formation of a γ-carboline by reaction between an α-(2-indolyl) propargylic alcohol and an imine in the presence of a quinoline N-oxide (Z+−O−) as the oxidant and the deprotonating agent is summarized in Scheme 10. In this catalytic reaction, the catalyst resting state is predicted to be complex 2 due to the fact that gold(I) complex is coordinated to the imine more strongly than other substrates. According to the calculations, the reaction is surmised to commence by nucleophilic attack of Z+−O− on gold(I)-activated alkyne 3

dictated by π-donating characteristic of the alcohol functional group which polarize the C3−C2 double bond mainly toward C2, rendering C3 more susceptible to nucleophilic attack. This supposition finds support from unsymmetrical coordination of the alkene in 13; the Au−C3 bond is computed to be 0.326 Å longer than the Au−C2 bond. The higher electron deficiency of C3 than that of C2 is also corroborated by the NBO charge population analysis; the charge carried by C2 and C3 in 13 are computed as +0.309 and −0.441, respectively. We also explored the possibility that Z+−O− instead of imine serves as a nucleophile and conducts the C−C coupling process (Scheme 8). On the basis of the calculations, Z+−O− is much less reactive than the imine toward the C−C coupling reaction (cycloaddition). This is most likely due to the fact that the cycloaddition between indolyl and quinoline leads to dearomatization of the latter causing it to be very energy consuming. Formation of Final Product from 15. Once intermediate 15 is formed, it can be deprotonated by an appropriate base. There are a few potential bases in this catalytic reaction which are able to promote the deprotonation. Among the bases, Z+− O− is found to be the most reactive (Figure 2). Starting from 15, Z+−O− abstracts the proton with a Gibbs free energy barrier of 2.5 kcal/mol, while the same process occurs with higher activation barriers when the other bases are employed (5.3, 7.5, and 9.5 kcal/mol for the imine (2), (H2O)3,10 and a free quinoline, respectively, Figure 2). It can be concluded from D


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Organometallics

Interestingly, we found that for numerous Ar substituents (Scheme 11) the carbene complex is not a minimum and immediately undergoes a 1,2 aryl shift process to give alkene complex 13. Structure 12 is only located when the Ar group bears an electron-withdrawing substituent. This result implies that the 1,2 aryl shift is decelerated for electron-deficient aryl groups, causing very elusive carbene 12 to be a local minimum. Due to the fact that 12 with Ar = para-NO2-phenyl is located as a minimum, it gave us the opportunity to compare the reactivity of this carbene toward the three routes outlined in Scheme 1. According to the calculations (Scheme 12), TS13 is lower in energy than TS14 and TS15, suggesting that 1,2-Ar shift is the most viable route for trapping this carbene. The carbene trapping by an external nucleophile is calculated to be the least feasible as evidenced by the finding that TS15 lies above the other two transition structures. The relatively low reactivity of 12 to be trapped by an external nucleophile can be attributed to the presence of an interaction between the carbene and the carbonyl oxygen atom. This interaction, which is supported by a significant value of Wiberg bond index (WBI), reduces the tendency of this carbene for attack of an external nucleophile. The small energy difference between TS13 and TS14 in favor of the former rationalizes why Liu et al. observed trace amounts of 1,3-diketone as the byproduct caused by the 1,2-H shift.6 How Does the Identity of the Carbene Affect Its Reactivity? To address this question, we optimized different vinyl gold carbene complexes (Table 1). The vinyl gold carbene complexes are usually obtained when a transition metal mediates the ring-opening of a cyclopropene.11 Table 1 also compares the activation Gibbs energies of the three different routes shown in Scheme 1 for these vinyl gold carbenes. Several points can be inferred from this table. First, an electron-donating X substituent such as OMe enhances the activation energy of all routes. Second, the 1,2-Ar shift is more sensitive to the nature of the X substituent than the other two routes; its barrier spans a range from 4.1 to 20.2 kcal/mol. In contrast, the imine nucleophilic attack shows less sensitivity.12 Third, opposite to the case of αcarbonyl gold carbene complex (Scheme 12), the imine nucleophilic attack to the vinyl gold carbene complexes is more favorable than the other two routes. This discrepancy is most likely related to the absence of any blocking group (like carbonyl group in 12) in the vinyl gold carbene complexes. The activation energy of 1,2-Ar shift for 12 (Scheme 12) is lower than that for 20_CN (Table 1). It follows that the electron deficiency of 12 is even greater than a vinyl gold complex with an electron withdrawing substituent. This assertion finds support from the fact that 12 has a longer C1−C2 distance than does 20_CN (Scheme 13). This suggests that the ease of the aryl migration depends on the contribution of Lewis structure (A) to the bonding of the gold carbene complex (Scheme 13). In simple terms, a longer C1−C2 distance means a larger

Figure 2. Gibbs energy profile for deprotonation of 15 by different possible bases. Energies are given in kcal/mol.

via transition structure TS1. The strong hydrogen bond between the alcoholic functional group and Z+−O− in TS1 renders C1 more prone than C 2 to the nucleophilic attack. The regioselective addition of Z+−O− gives 10 which can liberate a quinoline to afford α-carbonyl gold carbene complex 12. Interestingly, the expected carbene complex is so reactive toward 1,2 aryl shift that it does not allow us to locate it as a local minimum. Indeed, the 1,2 aryl shift occurs without any activation barrier and immediately forms complex 13. The imine is then added to 13 to form iminium 14 from which a carbon−carbon coupling process is established and 15 is produced. Due to the π-donicity of the hydroxyl group, the C3 atom in 13 becomes much more electron-deficient than C2, favoring the nucleophilic attack to occur at this position. Once 15 is formed, a Z+−O− is most likely to deprotonate it to give 18. Finally, a water liberation from 18 affords the γ-carboline and regenerates the catalyst. According to our calculations, the transformation 3 + Z+−O− → 10 with an overall activation energy of 16.5 kcal/mol is the rate-determining step and the overall reaction is exergonic by about −89.9 kcal/mol. Impact of the Ar Group Identity on the Stability of 12. To evaluate whether the stability of α-carbonyl gold carbene complex 12 is affected by the nature of the Ar group, we calculated this species by employing various Ar groups.

Scheme 9. Relative Gibbs Free Energy (kcal/mol) of Key Stationary Points for Water Elimination and the Release of Final Product prod Starting from 17

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Organometallics Scheme 10. Catalytic Cycle Derived from DFT Calculations

Scheme 11. Effect of the Ar Nature on Whether 12 is a Local Minimum or Is Isomerized to 13 through an Immediate 1,2Ar Shift

Scheme 12. Gibbs Free Energy (kcal/mol) of Transition Structures TS13 (1,2-Ar shift), TS14 (1,2-H shift), TS15 (the Imine Nucleophilic Attack on 12) Relative to That of 12 where Ar Is para-NO2-phenyl

alcohol by a N-oxide in the presence of an imine. (1) Despite the expectation that an α-carbonyl gold carbene complex should be formed as the key intermediate during the course of this reaction, we found that such an intermediate is not a local minimum owing to the very fast 1,2 migration of the indolyl group. (2) The key α-carbonyl gold complex was calculated to be a minimum only when the indolyl group is replaced by an aryl with an electron-withdrawing substituent. (3) For α-carbonyl gold carbene complexes, the 1,2-aryl shift is faster than their 1,2hydride shift. In comparison, these carbene complexes are less prone to be trapped by an external nucleophile (an imine in this study), due to the stability afforded by the interaction between their carbene carbon and carbonyl oxygen. (4) In contrast to α-

contribution of (A), culminating in a smaller activation energy for 1,2-Ar shift. In addition, as discussed above, the 1,2-Ar shift is more sensitive to the electron deficiency of the carbene than the 1,2-H shift. In such a case, the very high electron deficiency of carbene 12 may provide a rationale for why the 1,2-Ar shift in this complex takes place with a lower activation energy than does the 1,2-H shift.

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CONCLUSION Several interesting points emerge from mechanistic investigation into gold(I)-catalyzed oxidation of an indolyl propargylic F


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Organometallics

obtained from the M06-D3-CPCM/BS2//B3LYP-CPCM/BS1 calculations in toluene are used for interpreting the obtained results. Wiberg bond indices were calculated by natural bond orbital analysis using NBO6 software23,24 integrated into Gaussian 09.

Table 1. Relative Gibbs Energies (kcal/mol) of Transition Structures TS16_X, TS17_X, and TS18_X for X = OMe, H, and CN where Ar Is para-NO2-phenyl

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ASSOCIATED CONTENT

S Supporting Information *

X

TS16_X

TS17_X

TS18_X

OMe H CN

20.2 8.4 4.1

13.1 3.8 2.1

6.3 −0.8 a

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.organomet.8b00808. Total potential (E), enthalpy (H), and Gibbs free energies (G) of all structures (PDF) Cartesian coordinates of all calculated species (XYZ)

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a

Due to the very fast nucleophilic attack of the imine, no transition structure was located.

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected].

Scheme 13. Hybrid Structure and Bond Distancesa

ORCID

Alireza Ariafard: 0000-0003-2383-6380 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We gratefully acknowledge the generous allocation of computing time from Australian National Computational Infrastructure and University of Tasmania. A.A. also thanks the Australian Research Council for financial support (project number DP180100904).

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(a) Resonance hybrid for a gold carbene complex described by two extreme structures (A) and (B). (b) C1−C2 bond distance in the gold carbene complexes 20_OMe, 20_H, 20_CN, and 12 (bond distances in angstroms) where Ar is para-NO2-phenyl.

(1) (a) Zhang, L. A Non-Diazo Approach to α-Oxo Gold Carbenes via Gold-Catalyzed Alkyne Oxidation. Acc. Chem. Res. 2014, 47, 877−888. (b) Qian, D.; Zhang, J. Gold-Catalyzed Cyclopropanation Reactions using a Carbenoid Precursor Toolbox. Chem. Soc. Rev. 2015, 44, 677− 698. (c) Dorel, R.; Echavarren, A. M. Gold(I)-Catalyzed Activation of Alkynes for the Construction of Molecular Complexity. Chem. Rev. 2015, 115, 9028−9072. (d) Harris, R. J.; Widenhoefer, R. A. Gold Carbenes, Gold-Stabilized Carbocations, and Cationic Intermediates relevant to Gold-Catalyzed Enyne Cycloaddition. Chem. Soc. Rev. 2016, 45, 4533−4551. (e) Pflästerer, D.; Hashmi, A. S. K. Gold Catalysis in Total Synthesis − Recent Achievements. Chem. Soc. Rev. 2016, 45, 1331−1367. (f) Jaimes, M. C. B.; Hashmi, A. S. K. Gold-Catalyzed Oxygen-Atom Transfer to Alkynes. Mod. Gold Catal. Synth. 2012, 273−296. (2) (a) Ye, L.; He, W.; Zhang, L. Gold-Catalyzed One-Step Practical Synthesis of Oxetan-3-Ones from Readily Available Propargylic Alcohols. J. Am. Chem. Soc. 2010, 132, 8550−8551. (b) Ye, L.; Cui, L.; Zhang, G.; Zhang, L. Alkynes as Equivalents of a-Diazo Ketones in Generating a-Oxo Metal Carbenes: A Gold-Catalyzed Expedient Synthesis of Dihydrofuran-3-Ones. J. Am. Chem. Soc. 2010, 132, 3258−3259. (c) Qian, D.; Zhang, J. A Gold(I)-Catalyzed Intramolecular Oxidation-Cyclopropanation Sequence of 1,6-Enynes: A Convenient Access to [N.1.0] Bicycloalkanes. Chem. Commun. 2011, 47, 11152−11154. (d) Vasu, D.; Hung, H.-H.; Bhunia, S.; Gawade, S. A.; Das, A.; Liu, R.-S. Gold-Catalyzed Oxidative Cyclization of 1,5Enynes Using External Oxidants. Angew. Chem., Int. Ed. 2011, 50, 6911−6914. (e) Bhunia, S.; Ghorpade, S.; Huple, D. B.; Liu, R.-S. GoldCatalyzed Oxidative Cyclizations of cis-3-En-1-ynes to Form Cyclopentenone Derivatives. Angew. Chem., Int. Ed. 2012, 51, 2939−2942. (f) Qian, D.; Zhang, J. Catalytic Oxidation/C-H Functionalization of N-Arylpropiolamides by Means of Gold Carbenoids: Concise Route to 3-Acyloxindoles. Chem. Commun. 2012, 48, 7082−7084. (g) Wang, Y.; Ji, K.; Lan, S.; Zhang, L. Rapid Access to Chroman-3-Ones through Gold-Catalyzed Oxidation of Propargyl Aryl Ethers. Angew. Chem., Int. Ed. 2012, 51, 1915−1918. (h) Xu, M.; Ren, T.-T.; Li, C.-Y. Gold-

carbonyl gold carbene complexes, vinyl gold carbene complexes show distinct reactivity because they are predicted to be reliably trapped by the external imine nucleophile. This key difference might be attributed to two reasons: (a) the absence of any blocking group such as the carbonyl group mentioned in point 3 and (b) the lesser electrophilicity of a vinyl carbene with respect to an α-carbonyl carbene, leading to retardation of both 1,2hydride and -aryl shifts. (5) An N-oxide not only is capable of serving as an oxidant but also as a strong proton transferring agent (even better than water and an imine).

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REFERENCES

COMPUTATIONAL DETAILS

Gaussian 0913 was used to fully optimize all the structures reported in this paper at the B3LYP level of density functional theory (DFT)14 in toluene using the CPCM15 solvation model. The effective-core potential of Hay and Wadt with a double-ξ valence basis set (LANL2DZ)16 was chosen to describe Au. The 6-31G(d) basis set was used for other atoms.17 Polarization functions were also added for Au (ξf = 1.050).18 This basis set combination will be referred to as BS1. Frequency calculations were carried out at the same level of theory as those for the structural optimization. Transition structures were located using the Berny algorithm. Intrinsic reaction coordinate (IRC)19 calculations were used to confirm the connectivity between transition structures and minima. To further refine the energies obtained from the B3LYP/BS1 calculations, we carried out single-point energy calculations using the M06/BS2 level of theory20 in toluene with inclusion of Grimme D3 dispersion correction.21 BS2 utilizes the def2-TZVP basis set22 on all atoms. An effective core potential including scalar relativistic effects was used for gold atom. To estimate the corresponding Gibbs energies, ΔG, the corrections were calculated at the B3LYP/BS1 level and finally added to the single-point energies. The Gibbs free energies G


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Organometallics

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Mechanistic Elucidation of Gold(I)-Catalyzed Oxidation of a

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