Synthesis and application of bifunctional Lewis acid: Lewis base molecules as efficient catalysts for amide bond formation

ORGN 90

Richard L Giles, r.l.giles@durham.ac.uk, Department of Chemistry, Durham University, South Road, Durham, DH1 3LE, United Kingdom, Andrew Whiting, andy.whiting@durham.ac.uk, Department of Chemistry, University of Durham, UK, Science Laboratories, South Road, Durham, DH1 3LE, United Kingdom, and Gillian E Smith, Strategic Technologies, GlaxoSmithKline, Old Powder Mills, Tonbridge, Kent, TN11 3AN.
Described here are the synthetic details en-route to, and the applications of several bifunctional molecules in catalysis. Synthetic routes to a range of benzylamine based chiral and achiral Lewis Acid – Lewis base containing molecules are detailed. N,N-diisopropylbenzylamine-2-boronic acid was found to be a highly efficient catalyst for direct amide formation from amine and carboxylic acid without a dehydrating agent. For example; the reaction of 4-phenylbutyric acid and benzylamine to produce N-benzyl-4-phenylbutyramide. Other successful coupling combinations will also be detailed as well as results for other N,N-dialkylbenzylamine-2-boronic acids including chiral examples. Also included is the synthesis of compounds based around the N,N-dimethylnaphthylamine-8-boronic acid. Results of high throughput screening of a range of bifunctional boronic acids for catalytic activity will also be detailed.