Exploiting a-Haloaldehydes in Complex Molecule Synthesis

Friday, 24 March – 11:00am – 12:00pm (MIH, School Seminar)

Location: Chemistry Lecture Theatre 4 and Online (Zoom)

Speaker: Prof. Robert Britton, Simon Fraser University, Canada

Host:  Prof. Rich Payne

Bio: Professor Robert Britton obtained his B. Sc. from the University of Waterloo in 1996 working with Professor Victor Snieckus. He then earned a Ph. D. in natural product isolation, structural elucidation, and total synthesis from the University of British Columbia in 2002 with Professors Edward Piers and Raymond Anderson. He spent two years at the University of Cambridge with Professor Ian Paterson as an NSERC PDF then joined the Process Research Group at Merck as a Senior Scientist in 2004. In 2005, he started an independent academic career at Simon Fraser University and was promoted to Professor in 2015. He is a Michael Smith Foundation for Health Research Career Scholar. Professor Britton has broad research interests that include natural product drug discovery, medicinal chemistry, radiotracer development and insect communication. Research in these areas have led to commercial traps for bed bugs and other crop pests, ¹⁸F-labelled amino acids and peptides for PET imaging in oncology, new tools for late-stage modification of drug leads, new processes for improving the manufacture of drugs, and new strategies for synthesizing structurally complex natural products.

Abstract: The diastereoselective addition of organometallic reagents to a-chloroaldehydes was first reported in 1959 and is historically significant as the prototypical reaction for Cornforth’s model of stereoinduction. Despite clear synthetic potential for these molecules, difficulties associated with producing enantiomerically enriched a-haloaldehydes limited their use in complex molecule synthesis through the latter half of the 20th century. Over the past 20 years, however, a variety of robust, organocatalytic processes have been reported that now provide direct access to optically enriched a-haloaldehydes and have motivated renewed interest in their use as building blocks for complex molecule synthesis. Here, our efforts to produce a-haloaldehydes and exploit these versatile building blocks in complex molecule synthesis will be discussed, including applications in the synthesis of nucleoside analogues, carbohydrate mimics and polyketides.