Designing of templates to reach the distal C-H bond:

A practical protocol to simplify natural product synthesis by site selective C–H functionalization had always been a coveted target for chemists. Most often, directing group assisted metallacycle formation has served as an efficient strategy in ensuring promising regioselectivity. In this regard wide variety of ortho- functionalization stands as an archetype. Despite significant progress, directing group- assisted selective distal C–H functionalization in arenes (at meta- and para- positions) had remained an unexplored venture mainly due to the formation of a geometrically constrained metallacyclic transition state. To address these issues, a novel class of cleavable linker with nitrile based templates that direct efficient functionalization of distal para- and meta-C–H bonds are introduced. Recently, more robust heterocycle-based directing template has been designed to deliver the various and most useful functionalizations at remote meta-position. Applicability of these template based strategies have been demonstrated by synthesizing various natural products and complex molecules through post synthetic modifications.

Aliphatic remote C-H functionalization:

The evolution of C–H activation/functionalization strategy has been potentially expediting the synthesis of target molecules through new disconnections in retrosynthetic analysis. By far the toughest challenge in this area is to regioselectively functionalize a particular sp3 C-H bond in alkanes. The minute reactivity differences of multitude of inert C‒H bonds and the fluxionality in aliphatic chains restricts the selective transformation at a core site within a complex molecule. Hence to incorporate functionality at a-sp3 carbon to a functional group relies on the traditional electrophilic addition or radical based reactions. While the same at b-carbon of carboxylic acid or g-carbon of amine can be performed by the assistance of directing group and transition metal. The feasibility of these reactions depends on the favored thermodynamics of the stable five membered metallacycle. However, striving for a distal sp3 C–H bond activation, other than these accessible positions, leads to more complex issues owing to thermodynamic constraints of larger metallacycle. Hence a paradigm for C-H activation reactions to functionalize more distal carbon centers is required that may impart the molecule with specific structural and functional features which would be acceptable as a lucrative molecule. The group is currently involved in designing of more efficient of directing groups that can address the existing shortcomings and go out of stretch to offer more efficient and reliable method for distal aliphatic C–H activation at d, e and further in a selective way alongside overcoming the constitutional and conformational barriers inherent in a linear molecule. The developed protocols will open up the gates to exploit C-H activations in industries for step-economic synthesis of drugs, natural products and agrochemicals by ornamenting different molecules regioselectively, making it a versatile tool in chemist’s pocket.

Representative Publications

 Remote para-C-H Functionalization of Arenes by a D-Shaped Biphenyl Template-Based Assembly.

 J. Am. Chem. Soc. 2015, 137, 11888-11891

  • LinkedIn Social Icon
  • orcid
  • facebook

  Created and Maintained by  Joy