Organic Chemistry Portal
Organic Chemistry Highlights

Monday, May 31, 2010
Douglass F. Taber
University of Delaware

Best Synthetic Methods: C-C Bond Construction

Nobuaki Kambe of Osaka University found (Tetrahedron Lett. 2009, 50, 5644. DOI: 10.1016/j.tetlet.2009.07.094) that with a Ni catalyst, Grignard reagents coupled preferentially with primary alkyl iodides, even in the presence of the usually reactive ketone. Maurice Santelli of the Université d'Aix-Marseille devised (Tetrahedron Lett. 2009, 50, 5238. DOI: 10.1016/j.tetlet.2009.07.033) a protocol for the conversion of a ketal 4 to the doubly homologated product 6.

Brian T. Gregg of AMRI established (Tetrahedron Lett. 2009, 50, 3978, DOI: 10.1016/j.tetlet.2009.04.081; Tetrahedron Lett. 2009, 50, 7070, DOI: 10.1016/j.tetlet.2009.09.178) a procedure for the homologation of a nitrile 7 to the amine 9. Replacement of the NaBH4 with a second Grignard reagent led to the α-quaternary amine (not shown). Toshiaki Murai of Gifu University independently (J. Org. Chem. 2009, 74, 5703. DOI: 10.1021/jo900915n) developed a protocol for coupling two Grignard reagents with the linchpin reagent 11 to give the amine 12. Laurel L. Schafer of the University of British Columbia demonstrated (Angew. Chem. Int. Ed. 2009, 48, 8361. DOI: 10.1002/anie.200903656) Ta-catalyzed intramolecular addition of a methyl amine 14 to the terminal alkene 13 to give 15. Jason S. Kingsbury of Boston College extended (Org. Lett. 2009, 11, 3202. DOI: 10.1021/ol9010932) the Roskamp protocol to unstable diazo alkanes such as 17, to give 18.

Katsukiyo Miura of Saitama University found (Org. Lett. 2009, 11, 5066. DOI: 10.1021/ol902060r) that Pt catalyzed the branched addition of a terminal alkenyl silane 19 to an aldehyde 16 to give the branched adduct 20. Silanes such as 19 are readily prepared directly from the corresponding terminal alkene. Kálmán J. Szabó of Stockholm University observed (J. Org. Chem. 2009, 74, 5695. DOI: 10.1021/jo9008673) that the allyl boronate derived from the allylic alcohol 21 could add to the aldehyde 23 to give, depending on the solvent, either the branched product 24 or the linear product 25. The Wittig reaction is a major producer of byproduct waste in chemical synthesis. Yong Tang of the Shanghai Institute of Organic Chemistry found (J. Org. Chem. 2007, 72, 6628. DOI: 10.1021/jo0709899) that Ph3As could serve catalytically in the condensation of 26 with an aldehyde. Christopher J. O'Brien of the University of Texas at Arlington and Gregory A. Chass of the University of Wales described (Angew. Chem. Int. Ed. 2009, 48, 6836. DOI: 10.1002/anie.200902525) a related procedure using a cyclic phosphine. Masaharu Nakamura of Kyoto University found (Org. Lett. 2009, 11, 4496. DOI: 10.1021/ol901555r) that the mixed organozinc 29 selectively transferred the alkenyl group even to a cyclic secondary bromide.

Two versatile methods for the specific construction of trisubstituted alkenes were recently reported. Yoshiaki Nakao and Tamejiro Hiyama of Kyoto University devised (J. Am. Chem. Soc. 2009, 131, 10964, DOI: 10.1021/ja901374v; for a related study see Chem. Commun. 2009, 3931, DOI: 10.1039/b907290j) a Ni catalyst for the addition of allyl cyanide 32 to a terminal alkyne, to give the alkene 33 with high regioselectivity and geometric control. Ei-ichi Negishi of Purdue University effected (Org. Lett. 2009, 11, 4092. DOI: 10.1021/ol901566e) addition of BBr3 to a termnal alkyne to give specifically the bromo borane 35.

Pd catalysis for the coupling of a terminal alkyne to an aryl halide was first reported by Richard F. Heck (J. Organomet. Chem. 1975, 93, 259. DOI: 10.1016/S0022-328X(00)94049-X). Jeffrey S. Moore of the University of lllinois reported (J. Org. Chem. 2009, 74, 8897. DOI: 10.1021/jo902015w) an improved catalyst that mediated the coupling at room temperature. Yasumasa Hamada of Chiba University uncovered (Adv. Synth. Catal. 2009, 351, 1773. DOI: 10.1002/adsc.200900151) a remarkable protocol for the conversion of a racemic allenyl acetate 39 to the enantiomerically enriched product 41.

D. F. Taber, Org. Chem. Highlights 2010, May 31.