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Published on: November 9, 2019
Iterative synthesis of deoxypropionate units: the inductor effect in acyclic conformation design
Stephen Hanessian1, Navjot Chahal, Simon Giroux
1Department of Chemistry, Université de Montréal, P.O. Box 6128, Station Centre-ville Montréal, P.Q. H3C 3J7. stephen.hanessian@umontreal.ca
Abstract:
Conjugate addition of lithium dimethylcuprate to acyclic alpha,beta-unsaturated esters of varying lengths bearing terminal alkyl or phenyl groups leads to a preponderance of syn 1,3-adducts when one methyl is already present. Conversion to enoates, and iteration of cuprate additions also favors syn adducts to give contiguous deoxypropionate units in a growing chain. The effect of end-group variation (Me, i-Pr, phenyl, tert-butyl) in conjunction with the nature of the ester group (Me, tert-butyl, etc.) on the diastereoselectivity of syn and anti products was studied. The results are rationalized in terms of inductor effects related to the minimization of the 1,5-pentane interactions in energetically favored folded conformations and corroborated by homodecoupling NMR studies.
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