Aminoalkyl-substituted alpha-methylene-gamma-butyrolactones from alpha-amino acids using an indium-mediated Barbier allyl addition

The indium-mediated reaction of Z-protected alpha-amino aldehydes 1-6 with 2-(bromomethyl)acrylates 8/9 in aqueous solvents has been investigated. The preference for the formation of syn-configured homoallyl alcohols 10-16 (d iastereoselectivities ranging from 2:1 to 32:1, yields 68-93%) may be expla ined by a chelate-controlled reaction. No racemization occurred during the preparation and transformation of the amino aldehydes. esterification (H2SO 4 in Et2O) led to alpha-methylene-gamma-butyrolactones 17-22 with yields ra nging from 89 to 97%. The configurations of all diastereoisomers were estab lished by five X-ray crystallographic analyses and by comparision of the NM R spectra.