New Enantioselective Entry to Cycloheptane Amino Acid Polyols

A diversity-oriented protocol has been developed for the assembly of densely hydroxylated cycloheptane amino acids via succession of a vinylogous Mukaiyama aldol reaction (VMAR), a Morita−Baylis−Hillman reaction (MBHR), and an intramolecular pinacol coupling reaction (IPCR). The plan utilizes d- or l-configured glyceraldehyde derivatives as “chiral” surrogates of glyoxal and <i>N</i>-[(<i>tert</i>-butoxycarbonyl)-2-(<i>tert</i>-butyldimethylsilyl)oxy]pyrrole as the synthetic equivalent of the α,γ-dianion of γ-aminobutanoic acid. The parallel, asymmetric syntheses of four cycloheptane representatives proceed with high diastereocontrol and virtually complete enantioselectivity in ten steps and overall yields of 15−37%.