Olefination of methyl (1S,2R,4R)-N-benzoyl-2-formyl-7-azabicyclo[2.2.1]heptane-1-carboxylate,a synthetic approach to new conformationally constrained prolines

Wittig olefinations of methyl (1S,2R,4R)-N-benzoyl-2-formyl-7-azabicyclo2.2.1]heptane-1-carboxylate with several phosphoranes and the Horner–Wittig reaction, using methyl diethylphosphonoacetate, have been tested in order to evaluate their utility in the synthesis of β-substituted conformationally constrained prolines. Subsequent elaboration of the resulting alkenes has provided proline–amino acid chimeras combinations of proline with other α-amino acids, such as l-norvaline, l-norleucine, l-α-(3-phenylpropyl)glycine or l-homoglutamic acid] with the 7-azabicyclo2.2.1]heptane skeleton in an enantiomerically pure form.