Primary and secondary allyltitanium(IV) reagents in aldehyde allylation II: Application to an enantioselective preparation of a C1-C7 fragment of spiramycin

Article abstract of DOI:10.1055/s-2004-834913

A synthetic approach to the eastern part of spiramycin, an important antibiotic compound, is described. Introduction of the side chain was first envisaged through a Hoppe aldehyde allylation. This reaction was carried out between an optically pure aldehyde 32 and a (±)-γ-alkoxy allyltitanium(IV) species derived from a primary γ-alkoxy allyl (diisopropyl)carbamate. Under kinetic resolution conditions, the anti-Cram compound 35 was obtained in an 80:20 mixture, with the Cram isomer 34, in 81% yield. Employing the optically pure (S)-γ-alkoxy allyl (diisopropyl)carbamate 36, the corresponding (R)-γ-alkoxy allyltitanium (R)-'Ti'-III was generated under n-BuLi·TMEDA/Ti(Oi-Pr)₄ conditions, that reacted with aldehyde 32 in double stereodifferentiation to deliver the expected Cram compound 40 in 80% yield (95% de). This latter corresponded to the C1-C7 fragment of spiramycin.