Enantioselective chemoenzymatic synthesis of cis- and trans-2,5-disubstituted morpholines.
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.
Ritzen
Bas
B
Radboud University Nijmegen, Institute for Molecules and Materials, Heyendaalseweg 135, NL-6525 AJ Nijmegen, The Netherlands.
Hoekman
Steven
S
Verdasco
Elena Durán
ED
van Delft
Floris L
FL
Rutjes
Floris P J T
FP
D000446:Aldehyde-Lyases / Q000737:chemistry* / Q000378:metabolism; D003500:Cyclization; D015394:Molecular Structure; D009025:Morpholines / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D009025:Morpholines; D000446:Aldehyde-Lyases; C087495:acetone-cyanohydrin lyase