Cyclic reaction networks for new synthetic methodologies.

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Cyclic reaction networks, in which opposing but non-microscopically reverse reactions operate concurrently, have been recognised by the Collins group as of potential importance in the development of novel synthetic methodologies. We are looking to develop a novel cyclic reaction network based on the principles of transition metal catalysis. Mild catalytic methods for C-H deuteration are of considerable interest, with recent potential identified in deuterated small organic molecules as active pharmaceutical agents.1 Current metal-catalysed methods often require acidic or forcing conditions; by harnessing a cyclic reaction network we will develop a novel deuteration methodology that operates under orthogonal conditions to current catalytic deuteration methodologies.2 Similarly, the importance of axial chirality has become increasingly evident, with axial chirality found in bioactive molecules and chiral ligands for asymmetric catalysis. Many methods for atroposelective synthesis of axially chiral biaryl molecules have been reported, however, one such method that has been unexplored is the deracemization of the biaryl axis.3 We believe our proposed cyclic reaction network will allow the unprecedented deracemization of configurationally stable trisubstituted biaryls through a dynamic kinetic asymmetric transformation and the transfer of chirality associated with a chiral ligand to the biaryl axis. Refences: 1) T. Pirali, M. Serafini, S. Cargnin, A. A. Genazzani J. Med. Chem. 2019, 62, 5276; 2) S. Ma, G. Villa, P. S. Thuy-Boun, A. Homs, J.-Q. Yu, Angew. Chem. Int. Ed. 2014, 53, 734; 3) . K. Cheng, S.-H. Xiang, S. Li, L. Ye, B. Tan Chem. Rev. 2021, 121, 4805