Novel Strategies for C-H Bond Functionalization of Alkynes, Arenes and Carbonyl Compounds via Copper and Scandium Catalysis

Abstract

C-H bond functionalization is a very important field of study in organic synthesis, and it is greatly explored in the synthesis of natural products and pharmaceutical agents. C-H bond functionalization of organic compounds is a powerful method for constructing new carbon-carbon (C-C) and carbon-heteroatom (C-X) bonds. C-H bond functionalization is a process in which the conversion of carbon-hydrogen bond into carbon-carbon bond or carbon-heteroatom bond is carried out irrespective of method and mechanism. Development of novel catalyst system for the functionalization of the unreactive C-H bonds is a major challenge and of great interest to synthetic organic chemists. C-H bond functionalization involves different types of intermediates based on the mechanisms of the reactions. Some of the typical intermediates are organometallic intermediates, carbenoid or ionic intermediates. The direct C-H bond functionalization reduces the number of synthetic steps and also the preactivation of starting materials is avoided thereby increasing the overall atom-efficiency. Site-selective C-H bond functionalization is a very challenging task due to the inert nature of most C-H bonds and requirement to control chemo- and regioselectivity in molecules that contain multiple C-H bonds. In this regard development of novel C-H bond functionalization protocols to access very important and useful precursors will be essential. As a part of our ongoing research programme, we developed a practical and efficient catalyst system comprising of CuI-DMAP for the homocoupling and heterocoupling of terminal alkynes under aerobic conditions by using oxidative coupling reactions. We have also developed a novel and an expedient catalyst system comprising of early transition state element-scandium for the effective C-H bond functionalization. Early transition state element (scandium) has been explored for the chemo- and regioselective C-H bond functionalization of arenes with propargyl α-aryl-α-diazoacetates. Likewise, scandium catalyst system has also been explored for the effective C-H bond functionalization of 1,3-diketones & ß- keto acids with propargyl α-aryl-α-diazoacetates. All of the above methods are highly practical, economical and environmentally friendly.