Phosphine-mediated reactions play an important role in contemporary organic synthesis. Dehydrative processes such as the Wittig and Mitsunobu reactions are foundational reactions in organic chemistry, driven by formation of a stabile phosphine oxide. The presence of super-stoichiometric amounts of phosphines limit the atom economy of these transformations and purification of desired products is often not trivial. O’Brien and co-workers pioneered a catalytic solution to this problem by recycling a phosphorus heterocycle with chemoselective reduction of the phosphine oxide.[1] Recently, we[2] and others[3] have used this catalytic strategy to study and expand the usage of recyclable phosphine reagents. Usually, a cyclic phosphorus catalyst is employed as reduction of cyclic phosphine oxides by silanes is facile. Mechanistic details of phosphine oxide reductions have not been determined experimentally, although ring-strain has been hypothesized as an important factor. Yet, triphenylphosphine can also be recycled by silanes with heating.[4] Herein we report the detailed kinetic and mechanistic characterization of these phosphine oxide reductions using 31P NMR with a suite of 4- and 5-membered phosphorus heterocycles that vary in ring-strain and electronic properties. We were able to parse a multi-step mechanism of reduction of cyclic phosphine oxides by silanes including a phosphine-independent step (Figure 1A) and determine the elementary rate constants for each step as well as the activation energies by measuring the temperature dependence of the rate constants. This identified favorable properties which enable broader synthetic utility in catalytic versions of organic reactions such as the Mitsunobu reaction (Figure 1B). [1] O’Brien, C. J.; et. al. Angew. Chem. Int. Ed. 2009, 48, 6836 [2] Buonomo, J. A.; Aldrich, C. C. Angew. Chem. Int. Ed. 2015, 54, DOI: 10.1002/anie.201506263 [3] A) van Kalkeren, H. A.; et. al. Chem. Eur. J. 2011, 17, 11290; B) Zhao, W.; et. al.. J. Am. Chem. Soc., 2015, 137, 616 [4] A) O’Brien, C. J.; et. al. Chem. Eur. J. 2013, 19, 5854 B) Lenstra, D. C.; et. al. Chem. Commun. 2014, 50, 5763

Applications of recyclable phosphorous reagents: Mechanistic insights drive improvements towards greener methodologies

251st National Meeting (2016)

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