Coordination Assisted Distal C-H Alkylation of Fused Heterocycles.

Distal C-H bond functionalization of heterocycles remained extremely challenging with covalently attached directing groups (DG). Lack of proper site for DG attachment and inherent catalyst poisoning by heterocycles demand alternate routes for site selective functionalization of their distal C-H bonds. Utilizing non-productive coordinating property to hold the heterocycle into the cavity of a template system in a host-guest manner, we report distal C-H alkylation (C-5 of quinoline and thiazole, C-7 of benzothiazole and benzoxazole) of heterocycles. Upon complexation with heterocyclic substrate, nitrile DG in template directs the metal catalyst towards close vicinity of the specific distal C-H bond of the heterocycles. Our hypothesized pathway has been supported by various X-ray crystallographically characterized intermediates.

Palladium-Catalyzed Template Directed C-5 Selective Olefination of Thiazoles.

An efficient method has been developed to afford highly C-5 selective olefination of thiazole derivatives utilizing a bifunctional template in an intermolecular fashion. Coordinative interaction between the substrates and the metal chelated template backbone plays a crucial role in high C-5 selectivity. Excellent selectivity for the C-5 position was observed while mono substituted (2- or 4-) or even more challenging unsubstituted thiazoles were employed.

Regiocontrolled Remote C-H Olefination of Small Heterocycles.

Achieving site-selective C-H functionalization of arene is a fundamental challenge, as it is mainly controlled by the electronic nature of the molecules. A chelation-assisted C-H functionalization strategy overcomes the selectivity issues by utilizing distance and geometry of covalently attached directing groups (DGs). This strategy requires stoichiometric DG installation/removal and a suitable functional group on which to tether the DG. Such strategies are ineffective for small heterocycles unless suitable functional groups are added. Moreover, heterocycles are not the judicious choice as substrates owing to the possibilities of catalyst deactivation. Inspired by recent developments, this work demonstrates the utilization of a chelating template backbone bearing covalently attached directing groups, which enables site-selective remote C-H functionalization of heterocycles. The observed selectivity is the outcome of non-covalent interactions between the heterocycles and bifunctional template backbone.

Iridium catalyzed acceptor/acceptor carbene insertion into N-H bonds in water.

The chemistry of A and D/A carbenes (D and A are donor and acceptor groups, respectively) is known to a great extent in the literature. Nevertheless the chemistry of the A/A class of carbenes is less explored, although the A/A class of carbenes is more important in natural product synthesis. The known catalysts for A/A carbene chemistry are also less in number and are found to be efficient only in typical organic solvents. These limitations prompted us to search for new catalysts and environmentally benign reaction conditions for the A/A class of carbenes. The present study reveals that [(COD)IrCl]2 is found to be an efficient catalyst for the A/A class of carbenes, and Pd2(dba)3 for the D/A class of carbenes, for insertion into N-H bonds in water under mild reaction conditions. A reactivity comparison study with different classes of carbenes revealed that silver based catalysts are the right choice for the D/D class of carbenes for insertion into N-H bonds in water. A large number of α-amino malonates and amino esters, which are important for the synthesis of heterocycles and several natural products, have been synthesized by following the current methodology, and characterized using standard analytical and spectroscopic techniques.

A Green Approach to the Synthesis of α-Amino Phosphonate in Water Medium: Carbene Insertion into the N-H Bond by Cu(I) Catalyst.

Synthesis of amino phosphonates is more important owing to their significant applications in the biological systems. There are few methods already known in the literature to make these molecules; however, known methods have their own disadvantages. In this regard, synthesis of different kinds of amino phosphonates have been achieved via phosphonate substituted carbene insertion into the N-H bond of aniline catalyzed by readily available copper salt under mild reaction conditions in water. In order to find an efficient catalyst for carbene insertion reaction in neat water, a large number of transition metal catalysts were screened, and we found that the [Cu(CH3CN)4]ClO4 was the best catalyst under employed reaction conditions. Using this environmentally benign methodology (copper catalyzed reaction in water), a large number of biologically important amino phosphonates have been synthesized, isolated (37 examples), and characterized using standard analytical and spectroscopic techniques.

Synthesis of Aminobenzoic Acid Derivatives via Chemoselective Carbene Insertion into the -NH Bond Catalyzed by Cu(I) Complex.

Phosphine ligand stabilized air-stable Cu(I) complexes have been successfully used to functionalize the aromatic aminobenzoic acids in a chemoselective manner without implementing protection and deprotection strategy under mild reaction conditions. This chemoselective carbene insertion into -NH bond over -COOH and -OH bonds leads to the wide range of carboxy and hydroxy functionalized α-amino esters (27 examples). All of the isolated new products have been fully characterized using standard analytical methods.

Chemoselective Carbene insertion into the N-H Bond over O-H Bond Using a Well-Defined Single Site (P-P)Cu(I) Catalyst.

Phosphine-coordinated air-stable Cu(I) catalyst (1) has been synthesized and characterized. Catalyst 1 is found to be active toward highly chemoselective carbene insertion into the N-H bond over the O-H bond and also over the formation of olefins when numerous aminophenols were treated with a variety of α-aryl diazoesters under normal experimental conditions.