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γ‐, Diastereo‐, and Enantioselective Addition of MEMO‐Substituted Allylboron Compounds to Aldimines Catalyzed by Organoboron–Ammonium Complexes
Author(s) -
Morrison Ryan J.,
Hoveyda Amir H.
Publication year - 2018
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.201805811
Subject(s) - enantioselective synthesis , diastereomer , aldimine , steric effects , chemistry , catalysis , reagent , aryl , enantiomer , alkyl , yield (engineering) , organic chemistry , medicinal chemistry , combinatorial chemistry , materials science , metallurgy
The first catalytic, broadly applicable, efficient, γ‐, diastereo‐, and enantioselective method for addition of O‐substituted allyl‐B(pin) compounds to phosphinoylimines (MEM=methoxyethoxymethyl, pin=pinacolato) is presented. The identity of the most effective catalyst and the optimal protecting group for the organoboron reagent were determined by consideration of the steric and electronic requirements at different stages of the catalytic cycle, namely, the generation of the chiral allylboronate, the subsequent 1,3‐borotropic shift, and the addition step. Aryl‐, heteroaryl‐, alkenyl‐ and alkyl‐substituted vicinal phosphinoylamido MEM‐ethers were thus accessed in 57–92 % yield, 89:11 to >98:2 γ:α selectivity, 76:24–97:3 diastereomeric ratio, and 90:10–99:1 enantiomeric ratio. The method is scalable, and the phosphinoyl and MEM groups may be removed selectively or simultaneously. Utility is highlighted by enantioselective synthesis of an NK‐1 receptor antagonist.