Enantioselective Rhodium-Catalyzed Allylic Substitution with a Nitrile Anion: Construction of Acyclic Quaternary Carbon Stereogenic Centers

Abstract

A direct and highly enantioselective rhodium-catalyzed allylic alkylation of allyl benzoate with α-substituted benzyl nitrile pronucleophiles is described. This simple protocol provides a new approach toward the synthesis of acyclic quaternary carbon stereogenic centers and provides the first example of the direct asymmetric alkylation of a nitrile anion. The synthetic utility of the nitrile products is amply demonstrated through conversion to various functional groups and the synthesis of a bioactive aryl piperazine in an expeditious four-step sequence.

Acyclic Quaternary Carbon Stereocenters via Enantioselective Transition Metal Catalysis

“…132 These conditions were applicable to α-branched aldehydes. 133 Remarkably, mechanistic studies reveal a mixture of prochiral (E)- and (Z)-enolates are generated under these conditions, yet high levels of enantioselectivity are nevertheless achieved.…”

Palladium-Catalyzed Asymmetric Allylic Alkylation Strategies for the Synthesis of Acyclic Tetrasubstituted Stereocenters

“…The Evans group demonstrated the first direct asymmetric alkylation reaction of -tertiary nitriles 219 by Rhcatalyzed AAA (Scheme 76). 70 The process improves stepeconomy in the -functionalization of nitriles by generating the reactive anion in situ, thus side-stepping the synthesis and isolation of racemic N-silylketenimines. The reaction was shown to proceed smoothly in the absence of additives; however, improved enantioselectivity was observed in the presence of a crown ether.…”

Alkylating Reagents Employed in Catellani‐Type Reactions

“…Nitrile compounds are versatile intermediates in organic synthesis that can be transformed into many other useful compounds,s uch as aldehydes, ketones,e sters, amides, and alkylamines. [39] Zhou and co-workers reported that, in the presence of as trongb ase, such as LiOtBu, a-arylation of nitrilesc ould be employed as the terminating step for the Catellani reaction (Scheme 19). [38] It shouldb en oted that the thus-obtained aaryl nitrilesare difficult to access in an alternative way.…”