A General Method for the Enantioselective Hydrogenation of β‐Keto Esters using Monodentate Binaphthophosphepine Ligands

Abstract

17 monodentate phosphepine ligands with a 4,5-dihydro-3H-dinaphtho[2,1-c;1',2'-e]phosphepine structural motif have been synthesized and tested in the asymmetric hydrogenation of various b-keto esters. By variation of the substituents of the aryl group on the phosphorus atom a fine tuning of the selectivity of the catalytic system is possible. Quantitative yield and enantioselectivities up to 95% ee have been achieved for the hydrogenation of methyl acetoacetate (7a), methyl 3-oxovalerate (7b) and ethyl 4-phenyl-3-oxo-propionate (7d) using 4-(4-methoxyphenyl)-4,5-dihydro-3H-dinaphtho-[2,1-c;1',2'-e]phosphepine (4g) as ligand. Best enantioselectivities were obtained at comparably high temperatures (100 -120 8C), which had the advantage of increased reaction rates.

Dramatic Enhancement of Enantioselectivity of Biotransformations of β-Hydroxy Nitriles Using a Simple O-Benzyl Protection/Docking Group

“…Optically active α-unsubstituted β-hydroxy carboxylic acids and their derivatives are key intermediates in the synthesis of natural products and biologically important compounds . Much effort has been devoted to their synthesis, and synthetic methods involving catalytic asymmetric hydrogenation, 14a, reduction, Mukaiyama-aldol reaction, and Reformatsky reaction have been developed. Biocatalytic reduction of β-ketoesters, kinetic resolution of secondary alcohols, and deracemization have proved useful, as well.…”