On the Mechanism of an Asymmetric ,-Unsaturated C

详细信息    查看全文

• 作者：David M. Tellers ; J. Christopher McWilliams ; Guy Humphrey ; Michel Journet ; Lisa DiMichele ; Joseph Hinksmon ; Arlene E. McKeown ; Thorsten Rosner ; Yongkui Sun ; Richard D. Tillyer
• 刊名：Journal of the American Chemical Society
• 出版年：2006
• 出版时间：December 27, 2006
• 年：2006
• 卷：128
• 期：51
• 页码：17063 - 17073
• 全文大小：223K
• 年卷期：v.128,no.51(December 27, 2006)
• ISSN：1520-5126

文摘

Ruthenium complexes employing axially chiral ligands were found to be effective asymmetrichydrogenation catalysts for the reduction of mages/gifchars/alpha.gif" BORDER=0>,mages/gifchars/beta2.gif" BORDER=0 ALIGN="middle">-unsaturated ene acid 1-E to give 2, a prostaglandin D₂(PGD₂) receptor antagonist. With [(S-BINAP)Ru(p-cymene)Cl₂]₂ (3, S-BINAP = (S)-(+)-2,2'-bis(diphenylphospino)-1,1'-binapthyl), it was discovered that low hydrogen pressures (<30 psi) were essential toachieve high enantioselectivities (92% ee). A detailed mechanistic study was undertaken to elucidate thispressure dependence. It was determined that compound 1-E is in a ruthenium-catalyzed equilibrium withendocylic isomer 1-Endo and in photochemical equilibrium with Z isomer 1-Z. Each isomer could behydrogenated to give 2, albeit with different rates and enantioselectivities. Hydrogenation of 1-Endo with3 was found to give 2 in high enantiomeric excess, regardless of pressure and at a rate substantially fasterthan that of hydrogenation of 1-E and 1-Z. In contrast, isomers 1-E and 1-Z exhibited pressure-dependentenantioselectivities, with higher enantiomeric excesses obtained at lower pressures. A rationale for thispressure dependence is described. Deuterium labeling studies with 1-Endo and tiglic acid were used toelucidate the mechanism of hydride insertion and product release from ruthenium. Under neutral conditions,protonolysis was the major pathway for metal-carbon cleavage, while under basic conditions, hydrogenolysisof the metal-carbon bond was predominant.