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Monday, May 25, 2009
Douglass F. Taber
University of Delaware

C-C Single Bond Construction

Several remarkable one-carbon homologations have recently appeared. André B. Charette of the Université de Montréal reported (J. Org. Chem. 2008, 73, 8097. ) the alkylation of diiodomethane with alkyl iodides such as 1, to give the diiodoalkane 2. Carlo Punta and the late Ombretta Porta of the Politecnico di Milano effected (Org. Lett. 2008, 10, 5063. ) reductive condensation of an amine 3 with an aldehyde 4 in the presence of methanol, to give the amino alcohol 5. Timothy S. Snowden of the University of Alabama showed (Org. Lett. 2008, 10, 3853. ) that NaBH4 reduced the carbinol 7, easily prepared from the aldehyde 6, to the acid 8. Ram N. Ram of the Indian Institute of Technology, Delhi found (J. Org. Chem. 2008, 73, 5633. ) that CuCl reduced 7 to the chloro ketone 9.

Kálmán J. Szabó of Stockholm University extended (Chem. Commun. 2008, 3420. ) his elegant work on in situ borinate formation, coupling, in one pot, the allylic alcohol 10 with the acetal 11 (hydrolysed in situ) to deliver the alcohol 12 as a single diastereomer. Samir Z. Zard of the Ecole Polytechnique developed (J. Am. Chem. Soc. 2008, 130, 8898. ) the 6-fluoropyridyloxy ether of 13 as an effective radical leaving group, enabling efficient coupling with 14, activated by dilauroyl peroxide, to give 15.

Shu Kobayashi of the University of Tokyo established (Chem. Commun. 2008, 6354. ) that the anion of the sulfonyl imidate 17 participated in direct Pd-mediated allylic coupling with the carbonate 16. The product sulfonyl imidate 18 is itself of medicinal interest. It is also easily converted to other functional groups, including the aldehyde 19.

Jianliang Xiao of the University of Liverpool found (J. Am. Chem. Soc. 2008, 130, 10510. ) that Pd-mediated coupling of an aldehyde 21 in the presence of pyrrolidine led to the ketone 22. The reaction is probably proceeding via Heck coupling of the aryl halide with the in situ generated enamine. Alois Fürstner of the Max Planck Institut, Mülheim observed (J. Am. Chem. Soc. 2008, 130, 8773. ) that in the presence of the simple catalyst Fe(acac)3 a Grignard reagent 24 coupled smoothly with an aryl halide 23 to give 25. Akio Baba of Osaka University established (Angew. Chem. Int. Ed. 2008, 47, 6620. ) that the GeCl2-driven Reformatsky-like addition of a halo ketone 27 to an imine 26 worked best in the presence of a catalytic Lewis acid.

The oxidative cross-coupling of ketone enolates, leading to the 1,4-diketone, has great potential as a method for rapidly assembling molecular complexity. Attempted hetero cross-coupling, however, can also lead to the homo coupled products as contaminants. Regan J. Thomson of Northwestern University has now shown (Org. Lett. 2008, 10, 5621. ) that it is possible to first prepare the hetero-coupled mixed silyl enol ethers, such as 29. Oxidation of 29 delivered 30 as predominantly a single diastereomer.

D. F. Taber, Org. Chem. Highlights 2009, May 25.