Reaction Mechanism of Phosphane‐Catalyzed [4+2] Annulations between α‐Alkylallenoates and Activated Alkenes: A Computational Study

Abstract

A DFT study has been performed to understand the [4+2] annulation reaction between α‐methylallenoate (2) and benzylidenemalononitrile (3), catalyzed by P(NMe2)3 (1). For the reaction channel to produce cyclohexene 4a as the predominated product, the catalytic cycle can be characterized by three stages: in situ generation of the 1,3‐dipole IM2 between 1 and 2 (stage I); the addition of 3 to IM2 giving six‐membered‐ring intermediate IM8 (stage II); and catalyst 1 liberation from IM8 to produce 4a (stage III). For stage II, the pathway through direct [4+2] addition, followed by [1,3]‐H transfer, enabled by the alkene carbon bearing nitrile groups, is feasible, but less favorable than the [3+2] addition pathway followed by water‐aided [1,3]‐H transfer. The pathway leading to the regioisomer of 4a (i.e., 4b) is substantially less favorable, which accounts for the exclusive regioselectivity (4a/4b = 100:0) of the reaction. The [4+2] annulations are different from the conventional [3+2] cycloadditions of allenoates and activated alkenes. For the latter, a trace of water was demonstrated to be critical, even though the reactions are carried out in so‐called “anhydrous” solvents, because water is the only available hydrogen transfer mediator. In other words, the traditional [3+2] cycloadditions would not occur if the solvent were absolutely free of water. In contrast, [4+2] annulations can take place, even though water is completely absent, because the carbon (CCN of alkene 3) bearing the nitrile groups can serve as the hydrogen transfer mediator. The substitution effects of alkenes on the addition step of alkenes to IM2 have been further investigated.

Formylation or methylation: what determines the chemoselectivity of the reaction of amine, CO2, and hydrosilane catalyzed by 1,3,2-diazaphospholene?

“…The C–N bond formation through mode A and B involves a four-membered TS featuring hydrogen transfer (see Scheme 3 ). Thus a protic molecule such as water may act as a hydrogen transfer shuttle (H-shuttle) 32 , 33 to facilitate the stage. In the present system, the possible H-shuttles could be water (trace water could not be excluded absolutely), N -methylaniline 1a , and silanol (HO[Si]OCHO and [Si](OH) 2 ), which are available when the reaction is initiated.…”

Mechanism of Phosphine‐Catalyzed Allene Coupling Reactions: Advances in Theoretical Investigations

“…As shown in Figure , Wang's group performed a theoretical investigation of the mechanism of [4+2] cycloaddition between α‐alkyl allenoate 59 and highly electron‐deficient olefin 60 through DFT calculations . In their theoretical studies, three stages of the reaction were identified including: 1) addition of phosphine catalyst 61 to α‐alkyl allenoate 60 to generate zwitterionic phosphinopropenide intermediate 64 , 2) formal [4+2] annulation of 64 with electron‐deficient olefin, 3) catalyst regeneration and product formation.…”

Theoretical study on the Rh-catalyzed C−C activation of cyclopropanol to construct diketone or monoketone

“…Such a correction has been applied in other theoretical studies. [35][36][37][38][39][40][41][42][43][44] 3. RESULTS AND DISCUSSION…”