Borane assisted highly secondary selective deoxyfluorination of isoureas Nojus Cironis, Dr. Dominic Willcox, Dr. Sven Kirschner, Prof. Stephen P. Thomas, Prof. Michael J. Ingleson EaStCHEM School of Chemistry, University of Edinburgh, UK The introduction of fluorine into organic molecules is key in tuning physicochemical properties including acidity/ basicity, lipophilicity/solubility and metabolic stability. As a result fluorinated compounds have found wide applications in the pharmaceutical and agrochemical industries. 1 One of the most utilised fluorination methods is deoxyfluorination which involves replacement of an activated “oxo” group by nucleophilic fluoride. 2 A plethora of highly reactive deoxyfluorination reagents have been developed which sequentially activate the “oxo” group and provide the source of fluoride in situ . 2 A major challenge remains the selective and controlled fluorination of polyol compounds using these, and other, reagents. 3 Here we present a new method for the deoxyfluorination of alcohols, via the intermediate isourea, with a unique mode of action using fluoroboranes (F- B -9-BBN). Good yields were achieved across a series of electronically and sterically differentiated alcohols. Mechanistic studies revealed highly selective deoxyfluorination with a hidden mode of action that was unexpected at the outset of this project. Significantly, the reaction was found to offer orthogonal selectivity to all current deoxyfluorination methods and reagents towards secondary substrates. 3
References 1. E. P. Gillis, K. J. Eastman, M. D. Hill, D. J. Donnely, N. A. Meanwell, J. Med. Chem . 2015, 58 , 8315 – 8359. 2. T. Aggarwal, Sushmita; A. K. Verma, Org. Chem. Front . 2021, 8 , 6452 – 6468. 3. L. Li, C. Ni, F. Wang, J. Hu, Nat. Comm. 2016, 7 , 13320.
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