Organic Chemistry Portal
Organic Chemistry Highlights

Monday, January 17, 2011
Douglass F. Taber
University of Delaware

Alkene and Alkyne Metathesis: Grandisol (Goess), 8-Epihalosilane (Kouklovsky /Vincent), (+)-Chinensiolide B (Hall)

The cost of using Grubbs-type catalysts could be reduced dramatically if the turnover could be improved. Richard L. Pederson of Materia, Inc. found (Org. Lett. 2010, 12, 984. DOI: 10.1021/ol9029808) that in MTBE at 50°C, the ring-closing metathesis of 1 proceeded to completion in 8 h with just 500 ppm of H2 catalyst (2). Jianhui Wang of Tianjin University constructed (Angew. Chem. Int. Ed. 2010, 49, 4425. DOI: 10.1002/anie.200906034) a modified H2 catalyst 5 tethered to a nitrobenzospiropyran. After the cyclization of 4 to 6 was run in CH2Cl2, the mixture was irradiated with visible light, converting 5 into its ionic form, that could be extracted with glycol/methanol, leaving little Ru residue in the cyclized product. In the dark, the catalyst reverted, and could be extracted back into CH2Cl2 and reused. In a complementary approach, David W. Knight of Cardiff University found (Tetrahedron Lett. 2010, 51, 638. DOI: 10.1016/j.tetlet.2009.11.092) that the residual Ru after metathesis could be reduced to < 2 ppm simply by stirring the product with H2O2.

Cyclopropenes such as 6 are readily available in enantiomerically-pure form by the addition of diazoacetates to alkynes. Christophe Meyer and Janine Cossy of ESPCI Paris showed (Org. Lett. 2010, 12, 248. DOI: 10.1021/ol9025606) that with a Ti additive, G2 cyclized 7 to 8. Siegfried Blechert of the Technische Universität Berlin devised (Angew. Chem. Int. Ed. 2010, 49, 3972. DOI: 10.1002/anie.201000940) the chiral Ru catalyst 11, that converted the prochiral 9 to 12 in high ee.

Daesung Lee of the University of Illinois, Chicago explored (J. Am. Chem. Soc. 2010, 132, 8840. DOI: 10.1021/ja1020525) the cyclization of the diyne 13 with 14 under G2 catalysis. Depending on the terminal substituent, the cyclization could be directed selectively to 15 or to 16.

Bran C. Goess of Furman University took advantage (J. Org. Chem. 2010, 75, 226. DOI: 10.1021/jo9020375) of alkyne ring closing metathesis for the conversion of 17 to 18. Selective hydrogenation then delivered the boll weevil pheromone Grandisol (19). Cyrille Kouklovsky and Guillaume Vincent of the Université de Paris Sud extended (J. Org. Chem. 2010, 75, 4333. DOI: 10.1021/jo100768d) ring-opening/ring closing metathesis to the nitroso Diels-Alder adduct 20. Reduction led to 8-Epihalosilane (22).

Ring-closing metathesis leading to medium rings, particularly that form tri- or tetrasubstituted alkenes, can be challenging. Dennis G. Hall of the University of Alberta found (J. Am. Chem. Soc. 2010, 132, 1488. DOI: 10.1021/ja9104478) that the cyclization of 23 to 24 proceeded smoothly. Functional group conversion then completed the synthesis of (+)-Chinensiolide B (25).

D. F. Taber, Org. Chem. Highlights 2011, January 17.