title: Enantioselective chemoenzymatic synthesis of cis- and trans-2,5-disubstituted morpholines.
abstract: A versatile synthesis of enantiomerically pure cis- and trans-2,5-disubstituted morpholines is described. Hydroxynitrile lyase-mediated cyanide addition onto aldehydes provided cyanohydrins in virtually quantitative yield and excellent enantioselectivity. Subsequent formation of diastereomerically pure amino esters via a three-step, one-pot reduction-transimination-reduction sequence followed by reduction and simultaneous protection provided cyclization precursors. Finally, cyclization and SmI(2)-mediated reductive detosylation completed the synthesis of cis- and trans-2,5-disubstituted morpholines in good yields and excellent diastereoselectivities.
authors.affiliation: Radboud University Nijmegen, Institute for Molecules and Materials, Heyendaalseweg 135, NL-6525 AJ Nijmegen, The Netherlands.
authors.forename: Bas
authors.initials: B
authors.lastname: Ritzen
authors.forename: Steven
authors.initials: S
authors.lastname: Hoekman
authors.forename: Elena Durán
authors.initials: ED
authors.lastname: Verdasco
authors.forename: Floris L
authors.initials: FL
authors.lastname: van Delft
authors.forename: Floris P J T
authors.initials: FP
authors.lastname: Rutjes
mesh_terms: D000446:Aldehyde-Lyases / Q000737:chemistry* / Q000378:metabolism; D003500:Cyclization; D015394:Molecular Structure; D009025:Morpholines / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D009025:Morpholines; D000446:Aldehyde-Lyases; C087495:acetone-cyanohydrin lyase