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Monday, July 26, 2004
Douglass Taber
University of Delaware

Preparation of Enantiomerically-Pure Building Blocks

Convergent construction directed toward the preparation of enantiomerically-pure targets depends on the availability of enantomerically-pure starting materials. There are many ways that these can be prepared. One way is from carbohydrate precursors, but this approach has been limited, in that L-sugars are much more expensive than D-sugars. Tzenge-Lien Shih of Tamkang University in Taipei describes (Tetrahedron Lett. 2004, 45, 1789. ) the facile conversion of the inexpensive D-ribonolactone derivative 1 to the much more valuable L-ribonolactone derivative 3, by careful hydrolysis of the intermediate mesylate. The epoxide 2 is presumed to be an intermediate in this transformation.

While secondary alcohols are now relatively easy to prepare in enantiomerically-pure form, secondary amines have been more challenging. Larry Overman of UC Irvine reports (J. Am. Chem. Soc. 2003, 125, 12412. ) the catalytic rearrangement of primary allylic alcohols such as 4to the corresponding protected vinyl amine 5 with excellent ee. Hydrolysis of the amine 5 gives the GABA aminotransaminase inhibitor 6. Unnatural amino acids can be prepared by oxidative cleavage of the protected vinyl amines.

Another approach to secondary amines has been reported (J. Am. Chem. Soc. 2003, 125, 16178. ) by Masakatsu Shibasaki of the University of Tokyo. Addition of methoxyamine to a chalcone 7(alkyl enones work in slightly lower ee) gives the amine 8. The amine 8 can be reduced with high stereocontrol to the amino alcohol 9. K-Selectride gives the complementary diastereomer.

Professor Shibasaki has also investigated (J. Am. Chem. Soc. 2003, 125, 15837. ) Michael addition to prepare alkylated secondary centers in high enantiomeric excess. Addition of substituted acetoacetates to cyclohexenone and to cycloheptenone proceeds with high ee. With the more reactive cyclopentenone, the ee is slightly lower. 

It is apparent that "enantiomerically-pure", written over and over again, can be cumbersome. We have suggested (C&E News Aug. 1991, (19), 5; J. Org. Chem. 1992, 57, 5990.) "symchiral" as a pleasing alternative.

D. F. Taber, Org. Chem. Highlights 2004, July 26.
URL: https://www.organic-chemistry.org/Highlights/2004/26July.shtm