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Monday, February 14, 2005
Douglass Taber
University of Delaware

Enantioselective Construction of Aldol Products: Part One of Two

Acyclic stereoarrays are important both in themselves and as precursors to enantiomerically-defined ring systems. Although the aldol reaction has long been a workhorse for acyclic stereoselection, there are still new things being done.

An exciting development in recent years has been the use of small organic molecules as catalysts for asymmetric transformations. Several years ago, it was reported that proline would catalyze the enantioselective addition of acetone to aldehydes. Following up on this observation, Yun-Dong Wu of the Chengdu Institute of Organic Chemistry reports (J. Am. Chem. Soc. 2003, 125, 5262. DOI: 10.1021/ja034528q) the development of the proline amide 2 as a catalyst for this reaction. The catalyst 2 gave consistently higher ee’s than did proline.

The aldol reaction can also be used to construct quaternary stereogenic centers. James L. Gleason of McGill University reports (Org. Lett. 2004, 6, 405. DOI: 10.1021/ol0364428) that reduction of the sulfide 4 with dissolving metal gives a lithium enolate. Conversion to the boron enolate followed by addition to benzaldehyde gave the product 5 in high diastereomeric excess. The authors ascribe the observed high stereocontrol to geometric control in the formation of the intermediate enolate.

“Aldol” products do not have to come from an aldol reaction. In another example of catalysis by a small organic molecule, Jeffrey Bode of UC Santa Barbara reports (J. Am. Chem. Soc. 2004, 126, 8126. DOI: 10.1021/ja047407e) that the thioazolium salt 7 effects the rearrangement of an epoxy aldehyde such as 6 to the aldol product 8. This is a net oxidation of the aldehyde, and reduction of the epoxide. As epoxy aldehydes such as 6 are readily available by Sharpless asymmetric epoxidation, this should be a general route to enantiomerically-aldol products. The rearrangement also works with an aziridine aldehyde such as 9, to give the β-amino ester 10.

D. F. Taber, Org. Chem. Highlights 2005, February 14.