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The possible mechanisms and origin of the enantioselectivity of the reaction between 2H-azirine and an aldehyde catalyzed by an N-heterocyclic carbene (NHC) were theoretically studied and predicted at the M06-2X/6-31G(d,p)/IEF-PCM MTBE //M06-2X-GD3/6-311++G(2df, 2pd)/IEF-PCM MTBE level. The most favorable reaction pathway consists of four steps, i.e., complexation of the NHC and the aldehyde, stepwise [1,2]-proton transfer, C-C bond formation coupled with another proton transfer, and recycling of the NHC. The computational results indicate that the stereoselectivity-determining step is also the rate-determining step, which is the third step (i.e., intermolecular addition). The calculated 99 % ee is very close to the experimentally observed value of 96 % ee, demonstrating that the calculations are reliable. Two important roles of the NHC were identified by global reaction index (GRI) analysis and natural population analysis (NPA), that is, realizing the umpolung reactivity of the aldehyde and facilitating the deprotonation of aldehyde. Moreover, the efficiency of different NHC catalysts can be mainly predicted by computing the nucleophilic index of the corresponding Breslow intermediates. Furthermore, distortion/interaction and noncovalent interaction (NCI) analyses revealed that the π⋅⋅⋅π interactions between the NHC and substrates were the key factor in the reaction enantioselectivity., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The base-controlled mechanisms for N-heterocyclic carbene (NHC)-catalyzed divergent [3+3] and [3+2] annulation reactions were examined by using the DFT method. The reaction initiates with the complexation of NHC and enal to give the Breslow intermediate, which diverges afterward. Then, the azomethine imine can either react with the Breslow intermediate to give the six-membered ring product or the β-carbon protonation occurs for forming the enolate intermediate controlled by different bases. The formed enolate intermediate reacts with azomethine imine to afford the five-membered ring product. The calculated results show that only the base K 2 CO 3 can facilitate the structural transformation between homoenolate and enolate to switch the chemoselectivity; therefore, the [3+3] annulation happens preferentially in the presence of base DBU while the other situation occurs with K 2 CO 3 as base. The NCI analysis results reveal that the stereoselectivity is predominately determined by the π⋅⋅⋅π, C-H⋅⋅⋅O, and C-H⋅⋅⋅N interactions. The obtained mechanistic insights should provide valuable clues for the rational design of these kinds of divergent reactions., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

One of the most challenging questions in the Lewis base organocatalyst field is how to predict the most electrophilic carbon for the complexation of N-heterocyclic carbene (NHC) and reactant. This study provides a valuable case for this issue. Multiple mechanisms (A, B, C, D, and E) for the intramolecular cyclization of aldimine catalyzed by NHC were investigated by using density functional theory (DFT). The computed results reveal that the NHC energetically prefers attacking the iminyl carbon (AIC mode, which is associated with mechanisms A and C) rather than attacking the olefin carbon (AOC mode, which is associated with mechanisms B and D) or attacking the carbonyl carbon (ACC mode, which is associated with mechanism E) of aldimine. The calculated results based on the different reaction models indicate that mechanism A (AIC mode), which is associated with the formation of the aza-Breslow intermediate, is the most favorable pathway. For mechanism A, there are five steps: (1) nucleophilic addition of NHC to the iminyl carbon of aldimine; (2) [1,2]-proton transfer to form an aza-Breslow intermediate; (3) intramolecular cyclization; (4) the other [1,2]-proton transfer; and (5) regeneration of NHC. The analyses of reactivity indexes have been applied to explain the chemoselectivity, and the general principles regarding the possible mechanisms would be useful for the rational design of NHC-catalyzed chemoselective reactions., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Organocatalysis has emerged as an effective strategy for chemical synthesis. Within this area, phosphine-catalyzed coupling reactions have attracted considerable attention because of their versatility and wide range of applications in the construction of new C-C bonds. Recently, various experimental studies on the phosphine-catalyzed coupling reaction of allenes have been reported, and mechanistic and computational studies have also progressed considerably. As a nucleophile, phosphine can react with an allene to form a zwitterionic phosphoniopropenide intermediate. After stepwise cycloaddition and proton transfer, the phosphine catalyst can be regenerated by C-P bond cleavage. Alternatively, the zwitterionic phosphoniopropenide intermediate could also be protonated by a Brønsted acid to generate a phosphonium intermediate, which can be used to construct new C-C bonds by electrophilic addition. In this review, we have summarized details of mechanistic studies of phosphine-catalyzed allene coupling reactions that follow these two reaction modes. In addition to detailing the reaction pathway, the regioselectivity and diastereoselectivity of the phosphine-catalyzed allene coupling reaction are also discussed in this review., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)