Highly Stereoselective and Flexible Synthesis of 6-Alkoxy-5,6-dihydro-4H-1,2-oxazines by Conjugate Addition of Organolithium Compounds to 6H-1,2-Oxazines Followed by Trapping with Electrophiles

Abstract

Conjugate additions of reactive organolithium compounds such as phenyllithium, n-butyllithium, tert-butyllithium, and 2-propenyllithium to 6H-1,2-oxazines 1, 24, and 25 followed by trapping of the intermediates with electrophiles gave a variety of highly substituted 6-alkoxy-5,6-dihydro-4H-1,2-oxazines 2-15 and 27-30 generally in very good yields. Most interestingly, this reaction sequence proceeds with high stereocontrol producing in large excess or exclusively the trans,trans-diastereomers. Using benzaldehyde as the electrophile, only compound 8, which is one of eight possible diastereomers, was formed. Methyllithium or lithiated methoxyallene as the nucleophilic component provide expected addition products 17 and 19, but formation of bis-1,2-oxazines 18 and 20 seems to be inevitable with these less reactive organolithium compounds.

Key Words

asymmetric synthesis - conjugate addition - organolithium compounds - 1,2-oxazines - alkylation

References

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Buchholz, M.; Hiller, F.; Reissig, H.-U. Eur. J. Org. Chem., in press.