Stereoselective approaches to amides from chiral alcohols

thumbnail image: New Route to Chiral Amides

A Direct and Stereoretentive Synthesis of Amides from Cyclic Alcohols
D. Mondal, L. Bellucci, S. D. Lepore,
Eur. J. Org. Chem. 2011.
DOI: 10.1002/ejoc.201101165

Salvatore Lepore and colleagues, Florida Atlantic University, USA, report a one-pot amidation reaction for cyclic alcohols that gives complete retention of configuration. They use a chlorosulfite leaving group formed in situ by reaction of the alcohol and thionyl chloride. The leaving group is chelated by a TiIV nitrile complex that is also generated in situ by reaction of TiF4 and alkyl or aryl nitrile.

One-pot, stereoretentive amidation of alcohols

The Ti nitrile complex is thought to chelate the chlorosulfite in the transition state to create a carbocation that is rapidly captured by the nitrile nucleophile through a front-side attack mechanism. This is the first experimental verification of secondary hyperconjomers, a theory of non-planar carbocations developed by Sorensen and Schleyer.

Most stereoselective approaches to amides from chiral alcohols require multistep procedures.




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