Primary and Secondary Allyltitanium(IV) Reagents in Aldehyde Allylation II: Application to an Enantioselective Preparation of a C1-C7 Fragment of Spiramycin

Abstract

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.

Key words

spiramycin - synthesis - Hoppe allylation - secondary allyltitanium reagent - double stereodifferentiation

References

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10

The structure of 36 was established by comparison of its ¹H and ¹³C NMR spectra with those of compound 46. Analysis of ¹H and ¹³C NMR spectra was supported by 2D experiments.