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Diastereoselective Electrophile‐Directed Alkylations
Author(s) -
Kumar Chepuri V. Suneel,
Holyoke Caleb W.,
Fleming Fraser F.
Publication year - 2019
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.201900174
Subject(s) - electrophile , chemistry , nucleophile , alkylation , steric effects , combinatorial chemistry , stereoselectivity , stereochemistry , organic chemistry , catalysis
Electrophile‐directed alkylations in which a chiral, sp3‐hybridized electrophile, dictates the facial attack on a prochiral nucleophile, provides a powerful method of asymmetric induction. The strategy is inherently efficient because the asymmetry of an sp 3 ‐hybridized electrophile is propagated to install two contiguous chiral centers, the first through an S N 2 displacement and the second through preferential facial recognition. The two primary modes of topological matching are through steric approach control and chelation between the electrophile and nucleophile. Electrophiles capable of chelation generally induce higher diastereoselectivity for secondary and primary electrophiles. Key parameters that influence the stereoselectivity are those expected for enolate/anion alkylations: solvent, cation, complexing agents. A generalized enolate‐electrophile alkylation model is used to provide an evaluative framework for collecting related alkylations with the aim of providing insight into the origin of the electrophile‐directed diastereoselectivity as a powerful synthetic strategy.