Copper-Catalyzed Diastereo-, Enantio-, and (Z)-Selective Aminoallylation of Ketones through Reductive Couplings of Azatrienes for the Synthesis of Allylic 1,2-Amino Tertiary Alcohols

Abstract

We introduce a method for the (Z)-selective aminoallylation of a range of ketones to prepare allylic 1,2-amino tertiary alcohols with excellent diastereo-and enantioselectivity. Copper-catalyzed reductive couplings of 2-azatrienes with aryl/alkyl and dialkyl ketones proceed with Ph-BPE as the supporting ligand, generating anti-amino alcohols with >98% (Z)-selectivity under mild conditions. The utility of the products is highlighted through several transformations, including those that leverage the (Z)-allylic amine moiety for diastereoselective reactions of the alkene. Calculations illustrate Curtin−Hammett control in the product formation over other possible isomers and the origin of (Z)-selectivity.

Stereoconvergent and Enantioselective Synthesis of Z-Homoallylic Alcohols via Nickel-Catalyzed Reductive Coupling of Z/E-1,3-Dienes with Aldehydes

“…Z -Homoallylic alcohols, characterized by their Z -olefin structure and homoallylic stereocenter, such as the Z -hex-4-en-2-ol motif, are prevalent in natural products and have pharmaceutical importance (Figure A) . Traditionally, synthesizing these alcohols involves multistep processes that separately construct stereochemical elements like olefin geometry and homoallylic stereocenter configuration (Figure B). − Achieving high stereocontrol over both aspects in a single-step synthesis has been elusive. − Recent advancements include catalytic Z -selective and enantioselective aldehyde allylation protocols, as reported by Malkov and Chen, utilizing chiral phosphoric acid catalysis (Figure B). However, these methods are restricted to using allylic boronates under cryogenic conditions and are limited to products with methyl, n -propyl, and vinyl-substituted Z -olefins.…”