In this Action, Dr Satpathi aimed to develop tandem, one-pot processes involving imines that deliver important, functionalized amine products that are hard to make using the current state-of-the-art in synthesis. In particular, he wished to develop the copper-catalyzed enantioselective union of imines, allenes/enynes, and diborons to selectively give intermediates that can then converted using a different transition metal catalyst – in the same reaction vessel – to high-value cyclic nitrogen-containing compounds of biological significance.
Prior to the action, the Procter group had reported enantioselective copper-catalyzed three component coupling of
imines, allenes/enynes and B2pin2 that delivered functionalized homoallylic amines with universally high regio-, diastereo-, and enantiocontrol.
Dr Satpathi first utilized an efficient, enantio- and diastereoselective, copper-catalyzed coupling of imines, allenes, and diborons to give homoallylic amines. The process shows broad substrate scope and delivers complex, chiral homoallylic amines. Next, Dr Satpathi added a palladium catalyst to the reaction vessel to convert these homoallylic amine intermediates to important cyclic products from a copper/palladium-catalyzed tandem process. The main focus of the study was to prepare densely functionalized benzocyclobutenes (BCBs) for the first time – BCBs are of growing interest in materials and medicinal chemistry, although general routes for their provision remain underexplored. Crucially, by simple variation of experimental conditions or substrate modification, our strategy was expanded to deliver indoline and quinoline derivatives – via a Buchwald-Hartwig cyclization, suitable for further manipulations. Importantly, Dr Satpathi’s studies identified enantioselective conditions for the tandem catalytic protocol.
Dr Satpathi next moved on to utilize an efficient, enantio- and diastereoselective, copper-catalyzed coupling of imines, enynes, and diborons to give homopropargylic amines. The process shows broad substrate scope and delivers complex, chiral homopropargylic amines with high selectivity. Dr Satpathi then added a gold catalyst to the reaction vessel to convert these homopropargylic amine intermediates to important pyrroline products from a copper/gold-catalyzed tandem process. Furthermore, Dr Satpathi recognized that by adding a hydride reducing agent to the reaction vessel he could convert the pyrrolines to important, biologically relevant, pyrrolidines resulting from a borylative coupling/heterocyclization/reduction tandem process. Importantly, Dr Satpathi’s studies identified enantioselective conditions for the tandem catalytic protocol.
In the future, we will utilize Dr Satpathi’s new tandem catalysis tools to prepare bioactive natural product and drug targets in a sustainable fashion. We believe that the new methods will also be of high value to academic and industrial synthetic chemists involved in drug discovery and materials science.
The results obtained from Dr Satpathi’s Fellowship have resulted in one publication in the high-quality international journal, ACS Catalysis, with a further manuscript being prepared for publication. The results from Dr Satpathi’s Fellowship have been presented at several international conferences around the world by the Host and in a national meeting by the Fellow.
