C–H and Si–H functionalization using redox-active diazo compounds and decarboxylative coupling

Abstract: The work presented in this thesis is based on two basic organic chemistry concepts: carbene catalysis and radical coupling reactions. Diazo compounds in the presence of transition-metal catalysts are known to be excellent reagents for the construction of C–X bonds (X = C, Si, N, O, etc.) under mild conditions. However, their applications are limited to conventional diazo compounds (e.g. diazoacetates, diazonitriles, diazoketones, etc.), where further modifications of the products after carbene transfer are not feasible. The thesis aims at the development of new methodologies using a diazo compound with a geminal radical precursor as methylene equivalent. In Chapter 2 of this thesis, a unified C–H alkylation of indole using this redox-active diazo compound, NHPI-DA has been presented. This process includes a highly selective insertion of ruthenium-carbenes into C–H bond of indoles at the C2- and C3- positions. These products have been diversified into a variety of functionalized indoles (e.g. boryl, aryl, alkyl, alkenyl, etc.) at the C3-position. These unified alkylation conditions can be a potential alternative for late-stage functionalization of indoles. In Chapter 3 of this thesis, decarboxylative radical couplings of redox-active N-hydroxyphthalimide (NHPI) esters with electron-poor olefins have been described. This methodology utilizes self-sensitized photoreductants, dihydronicotinamides to generate alkyl radicals from redox-active carboxylates in presence of blue light. This approach, unlike the typical photo-redox chemistry, is independent of using photocatalysts or inorganic reductants. Moreover, we have demonstrated that NADH which is a native cofactor in living organisms, can efficiently couple alkyl radicals with DNA-encoded Michael acceptors. The mechanism of the reaction has been established through detailed kinetic and photophysical studies. Chapter 4 of this thesis focuses on the development of new syntheses of (borylmethyl)silanes. These compounds are unique due to the presence of orthogonal silicon and boron moiety at the same carbon atom and display significant applications for the synthesis of molecules of great synthetic value. This approach involves a ruthenium-catalyzed insertion of the NHPI-DA into Si–H bond and a subsequent decarboxylative borylation of the resulting redox-active esters. Interestingly, using this method a wide variety of silanes have been transformed into the corresponding (borylmethyl)silanes.