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Monday, January 24, 2005
Douglass Taber
University of Delaware

Best Methods for C-C Bond Formation: Part Three of Three

Carbon-carbon bond formation is fundamental to all of organic chemistry. The emphasis again this week is on practical, scalable methods.

Formylation of organometallics is usually carried out with dimethylformamide (DMF). T. Ross Kelly of Boston College found (J. Org. Chem. 2004, 69, 2191. ) that although o-lithiation of 1 proceeded smoothly, formylation with DMF and with methyl formate failed. The inexpensive Fe(CO)5, however, worked smoothly.

The Wittig reaction can be controlled to give a high percentage of the cis alkene. Young Gyu Kim of Seoul National University has shown (Tetrahedron Lett. 2004, 45, 3925. ) that addition of an excess of methanol to the -78C Wittig reaction of 3 led to the complementary trans alkene 4.

Another way to construct alkenes is by the addition of carbon radicals to nitrostyrenes such as 5. Ching-Fa Yao of National Taiwan Normal University in Taipei has reported (J. Org. Chem. 2004, 69, 3961. ) an extension of this work, generating the acyl radical from the aldehyde 6, cyclizing it to generate a new radical, then trapping that radical with 5 to give 7. This article includes an overview of the several ways of adding radicals to 5.

Telescoping of reaction steps, where feasible, can significantly improve the overall efficiency of a target-directed sequence. Zoapatanol 10 features a delicate combination of organic functional groups, in particular the α,β-unsaturated ketone. In the last step of a total synthesis of 10 (Org. Lett. 2004, 6, 2149. ), Janine Cossy of ESPCI, Paris, describes the addition of prenyl lithium to the Weinreb amide 8. The intermediate 9 was stable to dissolving metal reduction, where the ketone 10 would not have been. Work up then gave zoapatanol 10. In the preceding paper (Org. Lett. 2004, 6, 2145. ), the authors describe in detail the development of this method. Note that in natural zoapatanol 10, the stereogenic center adjacent to the ketone is a 1:1 epimeric mixture.

D. F. Taber, Org. Chem. Highlights 2005, January 24.