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Monday, August 20, 2007
Douglass F. Taber
University of Delaware

Catalytic Enantioselective Carbon-Carbon Ring Construction

A variety of effective strategies for catalytic enantioselective ring construction have recently been developed. The simplest approach is to start with a prochiral ring. Yian Shi of Colorado State University has applied (Angew. Chem. Int. Ed. 2006, 45, 1429. ) his enantioselective epoxidation protocol to arylidene cyclobutanes such as 1. The epoxide 2, formed in high ee, on pinacol rearrangement gives the cyclopentanone 3 with retention of the high ee. Alternatively, exposure of 2 to LiI gives the opposite enantiomer of 3, still in high enantiomeric excess. For the same approach with arylidene cyclopropanes to prepare cyclobutanones, see J. Org. Chem. 2006, 71, 9519. ).

A variety of enantioselective Diels-Alder catalysts work well with highly reactive dienes and dienophiles. Hisashi Yamamoto of the University of Chicago has developed (J. Am. Chem. Soc. 2006, 128, 9626. ) a chiral Bronsted acid 6 that promotes the cycloaddition of ethyl vinyl ketone 5 to less reactive dienes such as 4 with high enantioselectivity.

A variety of enantioselective Diels-Alder catalysts work well with highly reactive dienes and dienophiles. Hisashi Yamamoto of the University of Chicago has developed (J. Am. Chem. Soc. 2006, 128, 9626. ) a chiral Bronsted acid 6 that promotes the cycloaddition of ethyl vinyl ketone 5 to less reactive dienes such as 4 with high enantioselectivity.

Two elegant methods for enantioselective organic catalyst-mediated Michael addition leading to substituted cyclohexanes in high enantiomeric purity have appeared. The first, reported (Nature 2006, 441, 861. ) by Dieter Enders of RWTH Aachen, involves the condensation of an aldehyde, an α,β-unsaturated aldehyde and an aryl nitroalkene, mediated by the now-common proline-derived catalyst 9. A key question is whether alkyl nitroalkenes work as well.

A complementary approach was reported (Chem. Commun. 2006, 4928. ) by Karl Anker Jørgensen of Aarhus University. Using the proline-derived catalyst 14 that he has championed, Professor Jørgensen condensed α,β-unsaturated aldehydes such as 13 with t-butyl acetoacetates such as 15, to give, after cyclization and hydrolysis with p-TsOH, the 5-alkyl cyclohexenone 16 in high ee.

Two elegant strategies for the enantioselective construction of bicyclic systems have also appeared. Scott E. Schaus of Boston University, building on his earlier observation that the catalyst 18 directs the aldol condensation (Morita-Baylis-Hillman reaction) of cyclohexenone to aldehydes with high ee, has applied (Angew. Chem. Int. Ed. 2006, 45, 4929. ) the reaction to a series of aldehydes such as 17 bearing unsaturated silanes. Exposure of the intial adducts 19 to BF3.OEt2 leads to cyclization to the bicycle 20, in high ee.

Dan Yang of the University of Hong Kong has been developing the chiral Lewis acid-mediated radical cyclization of selenyl ketones such as 21. She has now found (Angew. Chem. Int. Ed. 2006, 45, 255. ) a Mg catalyst that directs both monocyclic and bicyclic cyclization in high ee.

Yujiro Hayashi of the Tokyo University of Science has devised (Angew. Chem. Int. Ed. 2006, 45, 6853. ) a very short approach to tricyclic products such as 26. Using yet another proline-derived catalyst, cyclopentadiene added in conjugate fashion to cinnamaldehyde 23 to give 25 as an inconsequential of double bond isomers. Homologation followed by warming then gave the tricyclic adduct 26 in high ee.

D. F. Taber, Org. Chem. Highlights 2007, August 20.
URL: http://www.organic-chemistry.org/Highlights/2007/20August.shtm