Synthesis and derivatization of substituted (R)- and (S)-C-allylglycines

Article abstract of DOI:10.1002/adsc.200404102

Various (R)- and (S)-C-allylglycine derivatives were synthesized by means of an auxiliary controlled diastereoselective aza-Claisen rearrangement. Starting from (S)-configured auxiliaries derived from optically active proline, an aza-Claisen rearrangement enabled us to synthesize α(R)-configured γ,δ-unsaturated amides. Since (R)-allylglycine derivatives could be directly generated by reacting N-allylproline derivatives and various protected glycine fluorides, the corresponding (S)-enantiomers were built-up via an initial α-chloroacetyl chloride rearrangement and a subsequent chloride azide substitution with complete inversion of the configuration. High diastereoselectivities were obtained (>15:1). The auxiliary could be efficiently removed by organolithium reactions of the amides furnishing α-amino ketones. Another allyllithium addition allowed us to introduce a second allyl chain with high diastereoselectivity. Final ring closures by means of metatheses using Grubbs' (1) catalyst gave raise to the formation of enantiopure phenanthridines and cyclohexenes displaying defined substitution patterns ready for alkaloid total syntheses.