Graduate Student, Indian Institute Of Technology Kanpur
C-H bond funtionalization utilizing first row transition metals like cobalt catalyst.
Functionalization of unreactive C-H bonds into selective C-C or C-X bonds not only simplify the synthesis of pharmaceuticals, natural products, but also sustainable. In this regard, catalyst based on noble metals like Rh, Ir, Pd has attained its pinnacle over the past few years for a vast number of synthetic transformations through C−H bond functionalization. But, due to its meagre resources and its extortionate prices, however, we need an alternative for bringing our research to a more pragmatic or industrial level. As a result, the use of inexpensive first-row transition-metal catalysts for sustainable C−C or C-X transformations has gained considerable recent momentum. In this context, rather environmentally benign cobalt complexes bear great potential for applications in homogeneous catalysis. Cobalt possess variable oxidation state hence it is expected to have better catalytic activity and unique reactivity. To find its interesting mode of action and I explore during my thesis to study C-H bond functionalization using air stable, low cost, versatile cobalt (III) catalyst. To begin with I have chosen functional groups such as sulphonamide which are common motifs in many drugs and medicinal compounds and play a significant role in their bioactivity. We reported cobalt catalyzed C-H bond annulation of sulfonamide via C−H and N−H activation with terminal and internal alkynes.In continuation, we have also reported C–H and N–H Bond Annulation of Benzamides with Isonitriles Catalyzed by Cobalt(III) under mild conditions. Hence, we have shown atom economical sustainable insertion of isonitrile to C-H and N-H bond of benzamide using green solvent such as CPME. Moving from concept of utilizing chelation assisted directing group concept of chelation assisted directing group to traceless directing group stratergy. At times, it was difficult to remove the cheation assisted directing group after fucntionalization. Therefore, we examined reactivity of CpCo(III) where the potential for exploiting its unique reactivity is still great using weakly chelating/traceless directing groups. We have shown an unprecedented C(8)-H bond allylation of quinoline with allyl carbonate and allyl alcohol catalyzed by CpCo(III) using a quinoline-N-oxides as substrates.Further understanding of reaction mechanism and exploration of new reaction through activation of unreactive C-H bonds are currently progress in my doctoral studies.
Abstract: Chelate assisted cobalt catalyzed C–H and N–H annulation of aryl sulfonamide with terminal and internal alkynes is reported. Very high regioselectivity and excellent functional group tolerance were achieved using oxygen as a co-oxidant. The reaction is scalable under mild conditions.
Pub.: 01 Dec '15, Pinned: 30 Jun '17
Abstract: Herein, we report a Cp*Co(III)-catalyzed C-H activation approach as key step to create highly valuable isoquinolones and pyridones as building-blocks that can readily be applied in the total syntheses of a variety of aromathecin, protoberberine and tylophora alkaloids. This particular C-H activation/annulation reaction was achieved with several terminal as well as internal alkyne coupling partners delivering a broad scope with excellent functional group tolerance. The synthetic applicability of this protocol reported herein was demonstrated in the total syntheses of two Topo-I-Inhibitors and two 8-oxyprotoberberine cores that can be further elaborated into the tetrahydroprotoberberine and the protoberberine alkaloid core. Moreover these building-blocks were also transformed to six different tylophora alkaloids in expedient fashion.
Pub.: 13 Jun '17, Pinned: 30 Jun '17
Abstract: Selectivity control in hydroarylation-based C-H alkylation has been dominated by steric interactions. In contrast, we unravel a conceptually distinct strategy that exploits the programmed switch in the C-H activation mechanism by means of cobalt catalysis, setting the stage for expedient C-H alkylations with unactivated alkenes. Detailed mechanistic studies provided compelling evidence for a programmable switch in the C-H activation mechanism from a linear-selective ligand-to-ligand hydrogen transfer (LLHT) to a branched-selective base-assisted internal electrophilic-type substitution (BIES).
Pub.: 22 Jun '17, Pinned: 30 Jun '17