Facile route to 3,5-disubstituted morpholines: enantioselective synthesis of O-protected trans-3,5-bis(hydroxymethyl)morpholines

Rajesh Dave; N André Sasaki

doi:10.1021/ol035998s

Facile route to 3,5-disubstituted morpholines: enantioselective synthesis of O-protected trans-3,5-bis(hydroxymethyl)morpholines

Org Lett. 2004 Jan 8;6(1):15-8. doi: 10.1021/ol035998s.

Authors

Rajesh Dave¹, N André Sasaki

Affiliation

¹ Institut de Chimie des Substances Naturelles, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France.

PMID: 14703339
DOI: 10.1021/ol035998s

Abstract

[reaction: see text] (3R,5R)-1 R1 & R2 = TBDPS, (3S,5R)-2 R1 = Bn,R2 = TBDPS, (3S,5S)-3 R2 & R2 = Bn. trans-3,5-Bis(benzyl/tert-butyldiphenylsilyloxymethyl)morpholines, promising candidates for the C(2)-symmetric class of chiral reagents, were prepared with excellent optical purity. A key step in the synthesis is the coupling of a serinol derivative with 2,3-O-isopropylideneglycerol triflate or its equivalent. This methodology was extended to the synthesis of chiral trans-3-(benzyloxymethyl)-5-(tert-butyldiphenylsilyloxymethyl)morpholine, a potentially useful chiral building block.