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A Catalyst Designed for the Enantioselective Construction of Methyl‐ and Alkyl‐Substituted Tertiary Stereocenters
Author(s) -
Claraz Aurélie,
Sahoo Gokarneswar,
Berta Dénes,
Madarász Ádám,
Pápai Imre,
Pihko Petri M.
Publication year - 2016
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201509302
Subject(s) - stereocenter , enantioselective synthesis , substituent , nucleophile , iminium , silylation , catalysis , chemistry , ketene , acrolein , combinatorial chemistry , alkyl , michael reaction , organic chemistry
Tertiary methyl‐substituted stereocenters are present in numerous biologically active natural products. Reported herein is a catalytic enantioselective method for accessing these chiral building blocks using the Mukaiyama–Michael reaction between silyl ketene thioacetals and acrolein. To enable remote enantioface control on the nucleophile, a new iminium catalyst, optimized by three‐parameter tuning and by identifying substituent effects on enantioselectivity, was designed. The catalytic process allows rapid access to chiral thioesters, amides, aldehydes, and ketones bearing an α‐methyl stereocenter with excellent enantioselectivities, and allowed rapid access to the C4–C13 segment of (−)‐bistramide A. DFT calculations rationalized the observed sense and level of enantioselectivity.