Journal of Advanced Chemical Engineering

Metal free aryne mediated cross dehydrogenative coupling

Joint Event 19^th European Organic Chemistry Congress 10^th International Conference on Physical and Theoretical Chemistry

November 07, 2023 | Webinar

Khushal Siddiq

Queen Mary University of London, UK

Posters & Accepted Abstracts: J Adv Chem Eng

Abstract:

Arynes are neutral but extremely versatile, unstable, and reactive intermediates that have experienced a recent resurgence in interest due to the development of precursors that act under mild conditions, with the most prominent being 2-(trimethylsilyl)aryl triflates also known as Kobayashi’s aryne precursor. The distinctive reactivity of arynes enables the construction of complex polycyclic and heterocyclic aromatic frameworks in short order which has captivated the interest of organic chemists. Direct functionalization of otherwise chemically inert C(sp3)-H bonds provides a potent strategic approach for the synthesis of complex molecules by removing the need for pre- functionalization of the coupling partners. This in turn reduces the number of synthetic steps involved in the synthetic route. Over the last decade, Cross dehydrogenative coupling (CDC) has emerged as a powerful tool for the selective construction of C-C bonds, from simple and abundant C-H bonds via tandem oxidation. However, some challenges remain to be solved. For instance, an external driving force in the form of a transition metal catalyst and/or sacrificial oxidant is required to overcome the unfavorable thermodynamics associated with forming a C-C bond and the accompanying loss of hydrogen (H2). By exploiting the reactivity of transient aryne intermediates, a metal- free, redox-neutral approach to C(sp3)-C(sp3/sp2/sp) coupling via an intramolecular 1,5-hydride transfer onto an aryne intermediate has been developed. Mechanistic studies have provided support for a zwitterion intermediate which activates a pronucleophile. Subsequent recombination yields the α-C-H functionalized amines. A diverse range of pronucleophiles have been demonstrated to be amenable to this new approach to CDC reactions which utilizes aryne intermediates. Preliminary work has shown that the scope can be extended beyond C- C coupling with a number of examples of phosphites undergoing the cross dehydrogenative coupling with tetrahydroisoquinoline derivatives, furnishing α-aminophosphonates.

Biography :

Khushal Siddiq was born in Samangan Province of Afghanistan in 1999, and migrated to England, Liverpool in 2009 and then to London in 2010 to attend secondary school. He graduated from University College London (UCL) in 2021 with a master’s degree in Organic Chemistry: Drug Discovery. Then he moved to Queen Mary University of London (QMUL) in 2022 to pursue a PhD in Organic Chemistry, currently working on extending the scope of ‘Metal-Free Aryne-Mediated Cross Dehydrogenative Coupling’ supervised by Dr Christopher R. Jones at the School of Physical and Chemical Sciences (SPCS).