Stereoselective Pd-Catalyzed Synthesis of Quaternary α-D-C-Mannosyl-(S)-amino Acids

In this paper, we report the stereoselective synthesis of alpha-D-C-mannosyl-(S)-amino acids exploiting, as a key step, an allylic alkylation of glycal-derived pi-allyl Pd(II) intermediates, prepared by oxidative addition of Pd(0) species to 2,3-unsaturated pyranosides (pseudoglycals). The reaction of 4,6-di-O-acetyl alpha-pseudoglucal carbonate 10a with racemic alanine-, valine-, and phenylalanine-derived azlactones gave the corresponding (4S)-4-alpha-D-C-mannosyl-2-phenyloxazol-5(4H)-ones as the major diastereoisomers in high yields. The final alpha-D-C-mannosyl-(S)-amino acids were obtained in a few steps comprising highly diastereoselective dihydroxylation of the glucal derivative double bond followed by the one-pot hydrolysis of the benzamido and acetate protecting groups. Main features of this method are the conciseness of the synthetic sequence, the high diastereoselection of the allylic alkylation step, the use of racemic alpha-amino acids as starting material, and the good overall yields.