Evaluation of calix[4]arene-based chiral diphosphite ligands in Rh-catalyzed asymmetric hydrogenation of simple dehydroamino acid derivatives

The calix[4]arene framework was readily modified to generate a number of chiral BINOL-based diphosphite ligands (3) capable of forming in situ Rh-complexes which catalyzed the asymmetric hydrogenation of model substrates methyl-(Z)-2-(acetamido)acrylate (1a) and methyl-(Z)-2-(acetamido)cinnamate (1b). The (S,S)-catalyst generated the (R)-product. Upper rim (R1) and 1,3-O-alkylation (R2) substitution on the calixarene strongly influenced catalyst activity and chiral induction. Optimum results were obtained when R1 was –C(CH3)3 and R2 was –CH2CH2CH3 (3b). Under optimized conditions, 3b hydrogenated 1a and 1b in 98 and 96% ee, respectively. Overall, better catalyst performance was observed for “locked” cone-conformers of 3, with higher activity evident for the less sterically hindered 1a (TOF up to 1300 h−1 at P(H2) = 5 atm).

Graphical abstractThe versatile calix[4]arene framework yielded chiral diphosphite ligands applicable for Rh-catalyzed asymmetric hydrogenation of dehydroamino acid derivatives. Optimum efficiency was obtained for: R1 = –C(CH3)3; R2 = –CH2CH2CH3; and R3 = H.Figure optionsDownload full-size imageDownload high-quality image (69 K)Download as PowerPoint slide