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Monday, December 26, 2005
Douglass Taber
University of Delaware

Asymmetric Transformation of Prochiral Carbocyclic Rings

The push toward enantiomerically-pure carbocyclic intermediates has led to the development of new methods for the enantiodifferentiation of inexpensive prochiral cyclic starting materials. For instance, Robert H. Morris of the University of Toronto recently reported (Org. Lett. 2005, 7, 1757. ) that a family of enantiomerically-pure Ru complexes originally developed for asymmetric transfer hydrogenation also mediate the enantioselective addition of malonate to cyclohexenone.

Asymmetric conjugate addition has also been effected with organometallic reagents. Much of the work to date has been with dialkyl zincs, with some reports of Grignard reagents. Alexandre Alexakis of the University of Geneva and Simon Woodward of the University of Nottingham have now described (Chem Commun. 2005, 2843. ) the use of trialkyl aluminum reagents, with chiral Cu catalysis. Some organoaluminum reagents, such as Me3Al, are commercially available and easy to handle. Organoaluminum reagents can also be prepared from the alkyne or the alkene.

Enantioselective conjugate addition is not limited to 5- and 6-membered rings. Ben L. Feringa and Adriaan J. Minnaard of the University of Groningen describe (Chem Commun. 2005, 1387. ) the use of the cross-conjugated dienone 5. The initial addition proceeds with high ee, to give 6. By choice of the proper absolute configuration of the catalyst, the enone 6 was then carried on selectively to either 7 or 8.

Enantioselective conjugate addition to construct a cyclic quaternary center has been a particular challenge. Alexandre Alexakis has also shown (Angew. Chem. Int. Ed. 2005, 44, 1376. ), as illustrated by the conversion of 9 to 13, that Cu*-catalyzed organoaluminum reagents work effectively in this context.

Defined quaternary centers can also be constructed α to ketones, by enantioselective alkylation. Eric N. Jacobsen of Harvard University has found (J. Am. Chem. Soc. 2005, 127, 62. ) that tin enolates work particularly well with his Cr salen catalyst. A variety of activated alkylation agents give high ee from the alkylation. It works well for 5-, 6- and 7-membered rings.

Karl Anker Jorgensen of Aarhus University, Denmark has found (J. Am. Chem. Soc. 2005, 127, 3670. ) that face-selective addition can also be carried out on an activated aromatic ring. In this work, the chirality is delivered by a quinine-derived organocatalyst.

D. F. Taber, Org. Chem. Highlights 2005, December 26.