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A Theoretical Investigation of Enantioselectivity: Michael Reaction of Secondary Enamines with Enones
Author(s) -
Sevin Alain,
Masure Daniel,
GiessnerPrettre Claude,
Pfau Michel
Publication year - 1990
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19900730303
Subject(s) - chemistry , conformational isomerism , mndo , steric effects , ab initio , degenerate energy levels , computational chemistry , lone pair , sequence (biology) , enantioselective synthesis , ab initio quantum chemistry methods , stereochemistry , crystallography , molecule , organic chemistry , quantum mechanics , catalysis , biochemistry , physics
A theoretical study of the enantioselective Michael ‐type addition of chiral secondary enamines to enones has been achieved. In a first step, the structures of various free enamines have been investigated at the ab initio and MNDO levels. The results clearly show that upon substitution of the prototype vinylamine, the N‐center is pyramidalized. The study of enamines with chiral N‐substituents such as ( S )‐Ph(Me)CH or ( S )‐cyclohexyl(Me)CH reveals a very complex pattern, where up to 8 local energy minimums are characterized whose examination shows that no prediction can be. done regarding the final enantioselectivity of their reaction with enones. These sets of conformers can be regarded as nearly energetically degenerate, at least for the three or four ones of lowest energy. The study of the compact complexes formed between the latter optimal conformers and acrylaldehyde shows that: ( i ) syn complexation with respect to the N lone pair is the only one which remains possible for steric reason, ( ii ) small geometrical rearrangements take place as the complexation proceeds, ( iii ) no clear‐cut correspondence exists between the relative sequence of the low‐energy conformers of the free enamines and the sequence of the low‐energy complexes, ( iv ) the examination of the relative gradients of the complexation energies provides an index for predicting the relative facilities of the enantiometric pathways, in good agreement with the experimental facts. Our study emphasizes the great complexity of systems of realistic size and brings about critical conclusions regarding classical ad hoc models.