A Catalyst Designed for the Enantioselective Construction of Methyl‐ and Alkyl‐Substituted Tertiary Stereocenters |
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Authors: | Dr Aurélie Claraz Dr Gokarneswar Sahoo Dénes Berta Dr Ádám Madarász Dr Imre Pápai Prof Dr Petri M Pihko |
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Institution: | 1. Department of Chemistry, Nanoscience Center, University of Jyv?skyl?, P. O. B. 35, 40014 JYU (Finland) http://tinyurl.com/pihkogroup;2. Institute of Organic Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences, 1525 Budapest (Hungary) |
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Abstract: | 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. |
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Keywords: | asymmetric catalysis density functional calculations diastereoselectivity natural products organocatalysis |
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