10.14469/HPC/4818
Alexander Boddy
0000-0001-5967-0402
Imperial College London
Imperial College London
Imperial College Research Computing Service
Alexander Boddy
0000-0001-5967-0402
Imperial College London
James A. Bull
0000-0003-3993-5818
Imperial College London
Alan Spivey
0000-0001-5114-490X
Imperial College London
Christopher Cordier
0000-0001-5702-7704
Methods that provide rapid access to new heterocyclic structures in biologically relevant chemical space provide important opportunities in drug discovery. Here, a strategy is described for the preparation of 2,2-disubstituted azetidines, pyrrolidines, piperidines and azepanes bearing ester and diverse aryl substituents. A one-pot rhodium catalyzed NâH insertion and cyclization sequence uses diazo compounds to stitch together linear 1,m-haloamines (m = 2 to 5) to rapidly assemble 4-, 5-, 6- and 7-membered saturated nitrogen heterocycles in excellent yields. Over fifty examples are demonstrated, including with diazo compounds derived from biologically active compounds. The products can be functionalized to afford alpha,alpha-disubstituted amino acids and applied to fragment synthesis.
Rapid Assembly of Saturated Nitrogen Heterocycles in One-Pot: Diazo-Heterocycle 'Stitching' by N-H Insertion and Cyclization
Imperial College London
2018
2018-11-28 17:53:10.017477
2019-10-14 13:22:02.483516
https://data.hpc.imperial.ac.uk/resolve/?ore=4818
https://data.hpc.imperial.ac.uk/resolve/?doi=4818&file=1
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https://data.hpc.imperial.ac.uk/resolve/?doi=4818&file=9
10.1002/ange.201812925
10.1002/anie.201812925
Creative Commons: Public Domain Dedication 1.0
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