6533b850fe1ef96bd12a851d
RESEARCH PRODUCT
A Catalyst Designed for the Enantioselective Construction of Methyl- and Alkyl-Substituted Tertiary Stereocenters
Petri M. PihkoDénes BertaGokarneswar SahooAurélie ClarazImre PápaiÁDám Madarászsubject
natural productsSubstituentKetene010402 general chemistry01 natural sciencesCatalysisStereocenterchemistry.chemical_compoundNucleophileOrganic chemistryorganocatalysista116Alkylchemistry.chemical_classification010405 organic chemistryChemistryEnantioselective synthesisIminiumasymmetric catalysisGeneral MedicineGeneral Chemistrydiastereoselectivity0104 chemical sciences3. Good healthOrganocatalysisdensity functional calculationsdescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2015-11-25 | Angewandte Chemie International Edition |