The origin of diastereoselectivity in the Michael addition reaction: a computational study of the interaction between CH-acidic Schiff base and α,β-unsaturated ketones

Theoretical quantum chemical computations were applied in answering a question set from the experiment: why the Michael addition to chalcones is a highly diastereoselective process? Density functional theory methods were used to examine the mechanistic pathways for the Michael reaction of [(diphenylmethylene)amino]acetonitrile—CH-acidic Schiff base with α,β-unsaturated ketones (enones). Transition state structures, prereactive complexes and reaction path energetics for different channels of the reaction are determined. The theoretical predictions reveal that the difference in the stabilization of the prereactive complex explains adequately the experimental findings for diastereoselectivity of the addition to benzylideneacetophenone (chalcone), compared to the nonselective process in the case of 4,4-dimethyl-1-phenyl-1-pentene-3-one.

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