Synthesis of natural fragrant molecules cis-3-methyl-4-decanolide and aerangis lactone.: General enantioselective routes to β,γ-cis-disubstituted γ-lactones and γ,δ-cis-disubstituted δ-lactones

General enantioselective routes to 3,4-cis-dialkyl substituted gamma-lactones and 4,5-cis-dialkyl substituted delta-lactones using TiCl4-mediated Evans asymmetric aldolization as the key step are reported. The syntheses are exemplified with two natural fragrant molecules, cis-3-methyl-4-decanolide (1) and aerangis lactone (2). The (R,R) steroegenic centers were established using (S)-phenylalanine-derived 2-oxazolidinone or thiazolidinethione as chiral auxiliary, whereas the (S,S) ones were constructed with auxiliary prepared from (R)-phenylglycine. NaBH4/CaCl2/THF in the presence of a small amount of EtOH was introduced as a new effective method for reductive cleavage of chiral oxazolidinone auxiliaries. Previously unknown, tricky concentration effects were observed during the monotosylation of diol 7 and BOM protection of Evans aldol 23.