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Regio‐ and Enantioselective Synthesis of Trifluoromethyl‐Substituted Homoallylic α‐Tertiary NH 2 ‐Amines by Reactions Facilitated by a Threonine‐Based Boron‐Containing Catalyst
Author(s) -
Fager Diana C.,
Morrison Ryan J.,
Hoveyda Amir H.
Publication year - 2020
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.202001184
Subject(s) - chemistry , enantioselective synthesis , regioselectivity , selectivity , catalysis , trifluoromethyl , organic chemistry , alkene , tertiary amine , metathesis , enantiomer , medicinal chemistry , alkyl , polymer , polymerization
A method for catalytic regio‐ and enantioselective synthesis of trifluoromethyl‐substituted and aryl‐, heteroaryl‐, alkenyl‐, and alkynyl‐substituted homoallylic α‐tertiary NH 2 ‐amines is introduced. Easy‐to‐synthesize and robust N ‐silyl ketimines are converted to NH‐ketimines in situ, which then react with a Z‐allyl boronate. Transformations are promoted by a readily accessible l ‐threonine‐derived aminophenol‐based boryl catalyst, affording the desired products in up to 91 % yield, >98:2 α:γ selectivity, >98:2 Z : E selectivity, and >99:1 enantiomeric ratio. A commercially available aminophenol may be used, and allyl boronates, which may contain an alkyl‐, a chloro‐, or a bromo‐substituted Z ‐alkene, can either be purchased or prepared by catalytic stereoretentive cross‐metathesis. What is more, Z ‐trisubstituted allyl boronates may be used. Various chemo‐, regio‐, and diastereoselective transformations of the α‐tertiary homoallylic NH 2 ‐amine products highlight the utility of the approach; this includes diastereo‐ and regioselective epoxide formation/trichloroacetic acid cleavage to generate differentiated diol derivatives.