Design and Development of New Catalytic Carbon-Carbon Bond Forming Reactions: I. N-Heterocyclic Carbene Based Catalytic Platform for Hauser-Kraus Annulations II. Copper-Catalyzed Selective Allylic Alkylation of Allylic Systems Using Grignard Reagents

The construction of carbon-carbon bonds has always been at the forefront of synthetic organic chemistry for generating products of greater utilities. Owing to their extraordinary applications in the synthesis of a wide range of therapeutic small molecules and natural products, the design and the development of new and practical synthetic methodologies will always be desirable. Our studies on the development of new catalytic methods to synthesize polycyclic aromatic compounds via a benzannulated reaction and the formation of valuable allylic products from selective allylic alkylation reactions are described. First, the development of N-Heterocyclic carbene catalyzed benzannulation will be discussed based on a venerable reaction called the Hauser-Kraus annulation, developed in 1978 by F. M. Hauser and G. A. Kraus. This reaction has enormous utilization in the synthesis of complex natural products with dihydroxynaphthalene and anthraquinone core structures. However, this method suffers from several drawbacks in a complex molecular setting. We design and develop the first catalytic platform of this traditional reaction based on NHC-mediated umpolung chemistry. The method provides a milder protocol for the synthesis of polycyclic aromatic compounds and also eliminates the drawbacks of the traditional Hauser-Kraus annulation. Secondly, the development of a series of general but highly selective methods for the synthesis of functionalized olefin products from simple unsaturated systems will be described. Unsaturated hydrocarbons are usually low-cost and highly abundant chemical species, making them attractive target substrates for their transformation into synthetically valuable products. However, they pose various challenges during their conversion into a selective product as they possess electronically and sterically similar carbon-hydrogen bonds and often require a highly selective reaction to differentiate between them. The catalytic methods described herein exploit the power of transition-metal catalysis to control the selective formation of allylic alkylation products through a new carbon-carbon bond formation using Grignard reagents. More specifically, two new copper-catalyzed methods will be discussed: (i) a regioselective method for the alkylation of unbiased internal allylic carbonates (ii) a branch selective method for the alkylation of terminal alkenes.