Organic Chemistry Portal
Organic Chemistry Highlights

Monday, March 20, 2006
Douglass Taber
University of Delaware

Enantioselective Construction of Quaternary Centers

Keiji Maruoka of Kyoto University has developed highly selective catalysts for the alkylation of protected glycine anions. He has now shown (J. Am. Chem. Soc. 2005, 127, 5073. DOI: 10.1021/ja0459328) that in addition, the alkylated amino esters such as 1 themselves can be alkylated with high enantiocontrol, to give the α-quaternary amino acid esters such as 3.

Using quinine-derived catalysts, Li Deng of Brandeis University has achieved (J. Am. Chem. Soc. 2005, 127, 8948. DOI: 10.1021/ja0511063) remarkable enantiomeric excesses with Michael additions to establish quaternary centers. The α-R group on the cyanoacetate 4 can be alkyl or aryl. With aryl, the phenyl sulfones work well as acceptors. With alkyl, the more active acceptor 5 gives higher ee's. Note that the cyano group of 6 can be selectively hydrated to the primary amide and inverted, delivering the α-quaternary amino acid ester.

Karl Anker Jørgensen of Aarhus University has developed (Angew. Chem. Int. Ed. 2005, 44, 2896. DOI: 10.1002/anie.200500144) quinine-based catalysts that effect enantioselective addition of an α-aryl cyanoacetate 7 to a glyoxylate imine 8, setting not just one, but two stereogenic centers.

Gregory C. Fu of MIT has devised (J. Am. Chem. Soc. 2005, 127, 5604. DOI: 10.1021/ja043832w) a ferrocene-based catalyst that effects enantioselective acylation of a ketene silyl acetal such as 10. Both cyclic and acyclic silyl acetals are acetylated with high ee.

Amir Hoveyda of Boston College has reported three enantioselective dialkylzinc-based approaches to quaternary centers, using as a catalyst Cu bound to an oligopeptide designed for the particular purpose. Although tetrasubsituted acceptors such as 12 can be sluggish, he has found (J. Am. Chem. Soc. 2005, 127, 14988. DOI: 10.1021/ja0553811) that with the appropriately designed ligand, addition proceeds smoothly, and with high ee.

Professor Hoveyda has shown (J. Am. Chem. Soc. 2005, 127, 4584. DOI: 10.1021/ja050800f) that conjugate addition to β, β-disubstituted nitroalkenes can also proceed with high ee. The product nitro alkanes can easily be carried on to amines, nitriles, or carboxylic acids.

Professor Hoveyda has also reported (Org. Lett. 2005, 7, 1255. DOI: 10.1021/ol047331r) an improved procedure for the SN2´ displacement of an allylic leaving group to generate a chiral quaternary center. The ee's are a little higher with the t-butyl ester than with the ethyl ester.

D. F. Taber, Org. Chem. Highlights 2006, March 20.