Access to a Catalytically Generated Umpolung Reagent through the Use of Cu-Catalyzed Reductive Coupling of Ketones and Allenes for the Synthesis of Chiral Vicinal Aminoalcohol Synthons

Abstract

We report the development of a stereoselective method for the allylation of ketones utilizing N-substituted allyl equivalents generated from a chiral allenamide. By employing N-heterocyclic carbenes as ligands for the Cu catalyst, good branched selectivity can be obtained with high diastereocontrol. This methodology allows access to a catalytically generated, polarity-reversed (umpolung) allyl nucleophile to enable the preparation of chiral 1,2-aminoalcohol synthons containing a dissonant functional group relationship.

Metal-Catalyzed Intermolecular Hydrofunctionalization of Allenes: Easy Access to Allylic Structures via the Selective Formation of C–N, C–C, and C–O Bonds

“…In 2019, the team of Sieber also reported the enantioselective copper-catalyzed allylation of ketones using allenamides. , As for the copper-catalyzed functionalization of imines, an inversion of the selectivity is possible, here thanks to the modification of the ligand (Scheme ). Indeed, using a phosphoramidite ligand allowed the formation of linear products (γ-hydroxyaldehyde equivalent) whereas the use of an NHC-type ligand gave branched products (1,2-amino alcohol synthon).…”

A Diastereodivergent and Enantioselective Approach to syn- and anti-Diamines: Development of 2-Azatrienes for Cu-Catalyzed Reductive Couplings with Imines That Furnish Allylic Amines

“…A recent elegant report from the Krische group utilizes their hydrogen autotransfer technology to couple an allenimide with a primary alcohol-derived aldehyde to afford 1,2-amino alcohols where the amino group is allylic (Scheme ). − Allylic amines are important structural features in numerous bioactive molecules and natural products . Furthermore, the unsaturation may serve as a functional group handle for downstream transformations .…”

A Diastereodivergent and Enantioselective Approach to syn- and anti-Diamines: Development of 2-Azatrienes for Cu-Catalyzed Reductive Couplings with Imines that Furnish Allylic Amines

“…A recent elegant report was disclosed by the Krische group, utilizing their hydrogen auto-transfer technology to couple an allenimide with a primary alcohol-derived aldehyde to afford 1,2-amino alcohols where the amino group is allylic (Scheme 1). [4][5][6][7] Allylic amines are important structural features in numerous bioactive molecules and natural products. [8] Furthermore, the unsaturation may serve as a functional group handle for downstream transformations.…”