Stereoselective synthesis of all four isomers of coronamic acid: A general approach to 3-methanoamino acids

A general approach to the synthesis of enantiomerically enriched 3-methanoamino acids is presented where the cyclopropyl unit was introduced by a stereoselective cyclopropanation using a D-glucose-derived chiral auxiliary. This methodology was applied to the synthesis of the four stereoisomers of coronamic acid 14, 17, 20, and 22. Starting with the readily available allylic alcohol 5, beta-D-glucopyranoses (E)-6 and (E)-7 have been selectively prepared using trichloroacetimidate 2. These olefins were cyclopropanated with very high diastereoselectivities using Et(2)Zn/CH2I2 (greater than or equal to 98% de) and Et(2)Zn/CH2ICI (greater than or equal to 97% de) in yields greater than 90%. After cleavage of the chiral auxiliary by ring contraction of the 2 O-triflyl derivative of cyclopropanes 8 and 9, cyclopropylmethanols (-)-10 and (+)-11 have been transformed to all four isomeric protected amino acids by selective protecting group manipulations, oxidation of primary alcohols, and Curtius rearrangement.