H(O)P(OPh) 2 -promoted deoxygenative halogenation of alcohols Aidan Cregan, a,b David Ryan, a Dr Gerard P. McGlacken a,b and Dr Peter A. Byrne a,b* a University College Cork, Ireland, b SSPC (Synthesis and Solid State Pharmaceutical Centre), Ireland Organic halides are ubiquitous amongst target molecules such as pharmaceuticals, natural products and agrochemicals, [1–3] however, the use of this class of compounds is more often attributed to their inherent reactivity. C(sp 3 )–halogenated compounds in particular are synthetically useful reagents as they enable molecular construction by nucleophilic substitution and can serve as precursors to organometallic reagents or carbon radicals. Traditional means of preparing organic halides from alcohols typically make use of hazardous, high- energy reagents and generate stoichiometric quantities of halogenated waste, [4] resulting in processes that are incongruent with the principles of green chemistry. We report an operationally convenient protocol for the iodination and bromination of alcohols that exploits the inherent behaviour of a commercially available diaryl H-phosphonate promoter, H(O)P(OPh) 2 . [5] Alcohol activation is achieved by a key transesterification event furnishing the reactive H-phosphonate monoester ( 1 ), thus transforming the parent alcohol into an electrophilic intermediate, under halogen-free conditions. Lithium halide salts employed at low loadings carry out the subsequent deoxygenative halogenation, circumventing the requirement for toxic molecular halogens or highly reactive, electrophilic halogenating agents. This strategy has been applied in the synthesis of a variety of primary, secondary, tertiary and benzylic organic halides, demonstrating its synthetic utility as a novel halogenation protocol. References 1. Santi, C. and co-workers, Molecules , 2022 , 27 , 1643–665. 2. Gordon, G. W. and co-workers, Environ. Chem . 2015 , 12 , 396–405. 3. Jeschke, P. Eur. J. Org. Chem . 2022 , e202101513. 4. [Larock, R.C. and co-workers, Comprehensive Organic Transformations (3 rd ed). Wiley–Blackwell, 2018 . 5. P. A. Byrne and co-workers, manuscript in preparation .
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© The Author(s), 2023
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