New Approaches for the Synthesis of Spirocycles and Macrocycles

Dr Will Unsworth, University of York Heriot-Watt October 2018

New approaches for the synthesis of spirocycles and macrocycles

The talk will be split into two parts. In the first part, I will discuss our efforts to develop improved methods to generate spirocyclic compounds via dearomatisation reactions.1-14 We are particularly interested in using new catalytic methods (especially using Ag(I) salts) and the concept of catalyst selective synthesis to assemble spirocycles, which are compounds of interest in view of their medicinal potential and 3D spatial properties. In the second part, I will discuss a conceptually new way to construct macrocycles via an iterative ring enlargement approach known as ‘Successive Ring Expansion’ (SuRE).12-16 Macrocycles have known efficacy in drug discovery, but the well-established synthetic difficulties associated with their preparation can serve as a barrier to progress in this area. One of the key challenges here is the effective control of intra- and intermolecular reactions, which we aim to address using SuRE. Background, methods development, substrate scope/limitations and the synthesis of compound libraries for biological evaluation will all be covered.

References
1) Org. Lett. 2013, 15, 3306; 2) Angew. Chem. Int. Ed. 2015, 54, 7640; 3) Org. Lett. 2015, 17, 4372; 4) M. J. James, P. O’Brien, R. J. K. Taylor, W. P. Unsworth, Chem. Eur. J. 2016, 22, 2856; 5) Chem. Eur. J. 2016, 22, 6496; 6) Chem. Eur. J. 2016, 22, 8777; 7) Angew. Chem. Int. Ed. 2016, 54, 9671; 8) Angew. Chem. Int. Ed. 2016, 55, 13798; 9) Org. Lett. 2016, 18, 6328; 10) Org. Lett. 2016, 18, 6256−6259; 11) Org. Biomol. Chem., 2017, 15, 233; 12) Org. Lett. 2018, 20 1439; 13) Org. Lett. 2018, 20, 3349; 14) ACS Catal. 2018, 8, 684; 15) Angew. Chem. Int. Ed. 2015, 54, 15794; 16) Chem. Eur. J. 2017, 9, 2225; 17) Chem. Eur. J. 2017, 23, 8780; 18) Chem. Eur. J. 2017, 23, 13314.; 19) Chem. Eur. J. 2018, DOI: 10.1002/chem.201803064