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Monday, July 12, 2004
Douglass Taber
University of Delaware

Stereocontrolled Construction of Carbacycles

Intramolecular carbene insertion (e.g. 1 -> 3) has long been a useful method for ring construction. Masahisa Nakada of Waseda University in Tokyo now reports (J. Am. Chem. Soc. 2003, 125, 2860. ) that with the addition of the ligand 2 this process can be made highly enantioselective. As the starting diazo ketone 1 is easily prepared by diazo transfer to the sulfonyl ketone, this should allow facile entry to enantioenriched cyclopentanones and cyclohexanones.

An even more common method for carbacyclic ring construction is the Diels-Alder reaction. Mukund Sibi of North Dakota State University reports (J. Am. Chem. Soc. 2003, 125, 9306. ) that the flexible ligand 5 works particularly well in mediating the enantioselective addition of 4 to 5, to give 7.

Another way to approach the enantioselective construction of carbocycles is to start with a readily-available carbohydrate. Gloria Rassu of the Insituto di Chimica Biomolecolare del CNR, Sassari, and Giovanni Casiraghi of the UniversitÓ di Parma report (J. Org. Chem. 2003, 68, 5881. ) that the lactone 8 undergoes smooth aldol condensation to give the highly-substituted, and enantiomerically-pure lactone 9. The cyclization works equally well with the lactam in place of the lactone. Eight-membered rings can also be efficiently prepared using this approach.

Intramolecular alkylation, although it is enticing, has not been developed as a method for cyclohexanone construction. Joseph P.A. Harrity of the University of Sheffield reports (J. Org. Chem. 2003, 68, 4392. ) that TiCl4 smoothly transforms the enol ether 10, prepared from the corresponding alkynyl phosphonium salt, into the 2-aryl cyclohexanone 11. Alkynyl ethers such as 10 are readily prepared in enantiomerically-enriched form. Would the enantiomeric excess be maintained on cyclization?

D. F. Taber, Org. Chem. Highlights 2004, July 12.