Second-generation DBFOX ligands for the synthesis of beta-substituted alpha-amino acids via enantioselective radical conjugate additions.

A set of second-generation DBFOX ligands possessing extended aryl or benzyl-type groups was synthesized. The requisite amino alcohols were either commercially available (DBFOX/Bn) or constructed via Sharpless asymmetric aminohydroxylation (DBFOX/Nap, DBFOX/ t-BuPh, DBFOX/Pip) or phase-transfer-catalyzed asymmetric alkylation (DBFOX/MeNap). Complexes of the ligands with Mg(NTf2)2 were evaluated as promoters of enantioselective radical conjugate additions to alpha,beta-unsaturated alpha-nitro amides and esters. Reactions employing the DBFOX/Nap ligand exhibited improved enantioselectivity relative to previously published additions mediated by DBFOX/Ph. However, the relatively modest increase in diastereomeric ratio suggests that our substrate-Lewis acid binding model, which was formulated based on results from DBFOX/Ph-promoted radical conjugate additions, is in need of revision.