The double reduction of cyclic sulfonamides for the synthesis of (4S-Phenylpyrrolidin-2R-yl)methanol and 2S-methyl-4S-phenylpyrrolidine.
The synthesis of (4S-phenylpyrrolidin-2R-yl)methanol and 2S-methyl-4S-phenylpyrrolidine has been achieved via the double reduction of their cyclic sulfonamide precursors which themselves were prepared following the stereoselective intramolecular Heck reaction of a chiral pool derived 2,5-dihydropyrrole. We have recently described a process whereby cyclic aryl sulfonamides, such as 2, are reductively ring-opened to furnish amino products in which the aryl group is incorporated in the final compound. (Evans, P.; McCabe, T.; Morgan, B. S.; Reau, S. Org. Lett. 2005, 7, 43.) The precursors for this reaction were assembled using an intramolecular Heck reaction followed by reduction of the alkene. Overall, this sequence represents an efficient means to construct molecules of this type in which the aryl sulfonyl moiety acts as both an N-protecting group and as an aryl donor. Use of Benkeser's stronger reducing conditions enables molecules such as 4 to be prepared in which both the sulfonamide functional group and the aromaticity of the aryl substituent have been destroyed.
Evans
Paul
P
Centre for Synthesis and Chemical Biology, School of Chemistry and Chemical Biology, University College Dublin, Dublin 4, Ireland. paul.evans@ucd.ie
D018360:Crystallography, X-Ray; D003500:Cyclization; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D000432:Methanol / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D010084:Oxidation-Reduction; D011759:Pyrrolidines / Q000138:chemical synthesis*; D013449:Sulfonamides / Q000138:chemical synthesis*
C518863:(4S-Phenylpyrrolidin-2R-yl)methanol; C518864:2S-methyl-4S-phenylpyrrolidine; D007202:Indicators and Reagents; D011759:Pyrrolidines; D013449:Sulfonamides; D000432:Methanol