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Reaction Mechanism of Phosphane‐Catalyzed [4+2] Annulations between α‐Alkylallenoates and Activated Alkenes: A Computational Study
Author(s) -
Zhao Lili,
Wen Mingwei,
Wang ZhiXiang
Publication year - 2012
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201200121
Subject(s) - chemistry , alkene , regioselectivity , annulation , nitrile , catalysis , cyclohexene , catalytic cycle , reaction mechanism , epoxide , medicinal chemistry , stereochemistry , organic chemistry
A DFT study has been performed to understand the [4+2] annulation reaction between α‐methylallenoate ( 2 ) and benzylidenemalononitrile ( 3 ), catalyzed by P(NMe 2 ) 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 (C CN 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.