Synthetic application of rhodium carbenoid chemistry towards diversity synthesis and pharmaceutical agents
C-H activation reactions, particularly the intermolecular C-H activation reactions by means of metal-carbenoid-induced C-H insertion, are very powerful tools to the synthesis of chiral building blocks and pharmaceutical agents. In chapter 1, novel triflate-substituted phenyldiazoacetates are presented to solve the problem encountered in the synthesis of (-)-cytoxazone. These diazo compounds were used in diversity synthesis involving both rhodium(II) and palladium(II) catalysts. Two different methods to synthesize the symmetrical biaryls are also discussed. The first method is through the one-pot palladium-catalyzed coupling of aryltriflate with bis(pinacolato)diboron, while the second is through the palladium-catalyzed homocoupling of arylboronic acids. The second part of the thesis focuses on the synthesis of new tamoxifen analogs. To overcome the major side effects of the anti-cancer agent tamoxifen, a triarylcyclopropyl tamoxifen analog bearing a triflate substituent was prepared via a highly enantioselective key cyclopropanation step. Different analogs then were obtained from either Suzuki-coupling of this triflate with boronic acids or the modification of the basic side chain. The third chapter presents how Magnus' STABASE was introduced into the C-H activation chemistry. Its reaction with different methyl aryldiazoacetates afforded β-amino esters as products in high enantioselectivities. This methodology was applied to the synthesis of analogs of the antidepressant venlafaxine.