Organic Chemistry Portal
Organic Chemistry Highlights

Monday, June 16, 2008
Douglass F. Taber
University of Delaware

New Methods for Carbon-Carbon Bond Construction

Mohammad Navid Soltani Rad of Shiraz University of Technology has shown (Tetrahedron Lett. 2007, 48, 6779. DOI: 10.1016/j.tetlet.2007.07.091) that with tosylimidazole (TsIm) activation in the presence of NaCN, primary, secondary and tertiary alcohols are converted into the corresponding nitriles. Gregory C. Fu of MIT has devised (J. Am. Chem. Soc. 2007, 129, 9602. DOI: 10.1021/ja074008l) a Ni catalyst that mediated the coupling of sp3-hybridized halides such as 3 with sp3-hybridized organoboranes such as 4, to give 5.

Usually, carbanions with good leaving groups in the beta position do not couple efficiently, but just eliminate. Scott D. Rychnovsky of the University of California, Irvine has found (Org. Lett. 2007, 9, 4757. DOI: 10.1021/ol7020934) that initial protection of 6 as the alkoxide allowed smooth reduction of the sulfide and addition of the derived alkyl lithium to the amide 7 to give 8. Doubly-activated Michael acceptors such as 11 are often too unstable to isolate. J. S. Yadav of the Indian Institute of Chemical Technology, Hyderabad has shown (Tetrahedron Lett. 2007, 48, 7546. DOI: 10.1016/j.tetlet.2007.07.198) that Baylis-Hillman adducts such as 9 can be oxidized in situ, with concomitant Sakurai addition to give 12. Rather than use the usual Li or Na or K enolate, Don M. Coltart of Duke University has found (Org. Lett. 2007, 9, 4139. DOI: 10.1021/ol701599v) that ketones such as 13 will condense with amides such as 14 to give the diketone 15 on exposure to MgBr2.OEt2 and i-Pr2NEt.

Simultaneously, Gérard Cahiez of the Université de Cergy (Org. Lett. 2007, 9, 3253. DOI: 10.1021/ol7016092) and Janine Cossy of ESPCI Paris (Angew. Chem. Int. Ed. 2007, 46, 6521. DOI: 10.1002/anie.200702206) reported that Fe salts will catalyze the coupling of sp2-hybridized Grignard reagents such as 17 with alkyl halides. John Montgomery of the University of Michigan has described (J. Am. Chem. Soc. 2007, 129, 9568. DOI: 10.1021/ja072992f) the Ni-mediated regio- and enantioselective addition of an alkynes 20 to an aldehyde 19 to give the allylic alcohol 21. In a third example of sp2- sp3 coupling, Troels Skrydstrup of the University of Aarhus has established (J. Org. Chem. 2007, 72, 6464. DOI: 10.1021/jo070912k) that Negishi coupling with alkenyl phosponates such as 23 proceeded efficiently. José M. Concellón of the Universidad de Oviedo has developed (J. Org. Chem. 2007, 72, 7974. DOI: 10.1021/jo701417z) a linchpin approach to enone construction, reductive condensation of a dihalo amide 27 with an aldehyde 26 to give the amide 28, then addition of an alkyl lithium 29 to 28 to give 30.

Two useful new methods for alkyne construction have been put forward. Professor Yadav has developed (Tetrahedron Lett. 2007, 48, 5335. DOI: 10.1016/j.tetlet.2007.05.021) an elegant homologation of lactones such as 31 to alkynes, and Marc A. J. Johnson of the University of Michigan has reduced to practice (J. Am. Chem. Soc. 2007, 129, 3800. DOI: 10.1021/ja0693439) the long-sought metathetical coupling of two nitriles such as 34 to form the alkyne 35.

D. F. Taber, Org. Chem. Highlights 2008, June 16.