Enantioselective chemoenzymatic synthesis of cis- and trans-2,5-disubstituted morpholines.

Bas Ritzen, Steven Hoekman, Elena Durán Verdasco, Floris L van Delft, Floris P J T Rutjes

Radboud University Nijmegen, Institute for Molecules and Materials, Heyendaalseweg 135, NL-6525 AJ Nijmegen, The Netherlands.

The Journal of organic chemistry 2010 May 21

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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.

Citation

Bas Ritzen, Steven Hoekman, Elena Durán Verdasco, Floris L van Delft, Floris P J T Rutjes. Enantioselective chemoenzymatic synthesis of cis- and trans-2,5-disubstituted morpholines. The Journal of organic chemistry. 2010 May 21;75(10):3461-4