Asymmetric Carboamination of Alkenylboronates
Lead Research Organisation:
University of Bristol
Department Name: Chemistry
Abstract
This proposed Fellowship brings together an Experienced Researcher from China, with expertise in asymmetric catalysis, methodology, and organic synthesis, with an internationally recognized Host Laboratory in the UK under the expert supervision of Prof. Varinder K. Aggarwal FRS. His research interests focus on total synthesis, asymmetric synthesis, photoredox-driven processes, and the development of new reactivity in organic chemistry, in particular, boron chemistry.
The successful realization of this highly interdisciplinary project will:
Enhance European excellence in organic synthesis and catalysis, which are fundamentally important branches of chemistry.
Enable the ER to acquire new skills in the field of organoboron chemistry, asymmetric copper catalysis, and to develop new drug candidates in collaboration with a partner pharmaceutical company, which will expand his scientific knowledge and network.
Amino boronic esters are bioisosteres of amino acids, which can act as protease inhibitors. Indeed several have even progressed to the market with others in clinical development highlighting their growing importance. In this proposal, we aim to access such entities by introducing new methodologies that merge a copper-catalyzed asymmetric functional-group transfer process with the stereospecific 1,2-metallate nitrogen or carbon rearrangement of alkenylboronates. This novel method employs catalytic, chiral copper-oxazoline complexes in combination with 3-iodane reagents, to provide rapid access to highly electrophilic, chiral Cu(III) species, enabling a subsequent 1,2-metallate nitrogen or carbon rearrangement of alkenylboronates while achieving bond carboamination. This ambitious approach will allow for the facile synthesis of enantiomerically enriched and medicinally relevant aminoalkylboron reagents, which will be employed to access new potential drug candidates in collaboration with AstraZeneca.
The successful realization of this highly interdisciplinary project will:
Enhance European excellence in organic synthesis and catalysis, which are fundamentally important branches of chemistry.
Enable the ER to acquire new skills in the field of organoboron chemistry, asymmetric copper catalysis, and to develop new drug candidates in collaboration with a partner pharmaceutical company, which will expand his scientific knowledge and network.
Amino boronic esters are bioisosteres of amino acids, which can act as protease inhibitors. Indeed several have even progressed to the market with others in clinical development highlighting their growing importance. In this proposal, we aim to access such entities by introducing new methodologies that merge a copper-catalyzed asymmetric functional-group transfer process with the stereospecific 1,2-metallate nitrogen or carbon rearrangement of alkenylboronates. This novel method employs catalytic, chiral copper-oxazoline complexes in combination with 3-iodane reagents, to provide rapid access to highly electrophilic, chiral Cu(III) species, enabling a subsequent 1,2-metallate nitrogen or carbon rearrangement of alkenylboronates while achieving bond carboamination. This ambitious approach will allow for the facile synthesis of enantiomerically enriched and medicinally relevant aminoalkylboron reagents, which will be employed to access new potential drug candidates in collaboration with AstraZeneca.
