P(O)H to P-OH Tautomerism: A Theoretical and Experimental Study Benjamin G. Janesko,* Henry C. Fisher, Mark J. Bridle, and Jean-Luc Montchamp* Department of Chemistry, Texas Christian University, Box 298860, Fort Worth, Texas 76129, United States * S Supporting Information ABSTRACT: Phosphinylidene compounds R 1 R 2 P(O)H are important func- tionalities in organophosphorus chemistry and display prototropic tautomerism. Quantifying the tautomerization rate is paramount to understanding these compounds’ tautomerization behavior, which may impact their reactivities in various reactions. We report a combined theoretical and experimental study of the initial tautomerization rate of a range of phosphinylidene compounds. Initial tautomerization rates are found to decrease in the order H 3 PO 2 > Ph 2 P(O)H > (PhO) 2 P(O)H > PhP(O) (OAlk)H > AlkP(O)(OAlk)H ≈ (AlkO) 2 P(O)H, where “Alk” denotes an alkyl substituent. The combination of computational investigations with experimental validation establishes a quantitative measure for the reactivity of various phosphorus compounds, as well as an accurate predictive tool. ■ INTRODUCTION Organophosphorus compounds are critically important in the synthesis of pharmaceuticals, herbicides, pesticides, and phosphine ligands. Methods for formation of phosphorus- carbon bonds continue to receive a great deal of attention. 1 Phosphinylidene 2 (hydrophosphoryl) compounds 1 are an important family of organophosphorus compounds, which includes phosphinates (hypophosphites) 2, H-phosphonates 3, H-phosphinates 4, and secondary phosphine oxides 5 (Figure 1). Tautomerization is an important class of chemical reactions involving the interconversion of constitutional isomers (tau- tomers). A common subclass is prototropy, in which a hydrogen atom moves from one atom to another. Perhaps the best-known example is the keto-enol tautomerism taught in sophomore organic classes. The phosphinylidene moiety also displays prototropic tautomerism (eq 1). Phosphinylidenes’ prototropic tautomerism appears to be critical to their reactivity. 3 The so-called P(V) form 1a/1b is almost invariably the most stable species. 3a,b (Note that strong electron acceptors such as R 1 =R 2 = CF 3 can make 1c more stable, 4 that the issue of the best representation between the classic P(V) form 1a and the phosphonium form 1b has been previously studied, 5 and that the resonance form 1b must be more heavily represented on the basis of electronegativities.) In contrast, the less stable P(III) form 1c is the reactive species in most reactions involving phosphinylidenes. For example, dimethyl H-phosphonate’s reaction with chloroacetone is proposed to proceed through base-catalyzed tautomerization. 6 Catalyzed imine hydrophosphonylation is proposed to involve the catalyst’s stabilization of the P(III) phosphite. 7 One of us proposed that base-promoted alkylation of alkyl phosphinates and H-phosphinates involved base-catalyzed tautomerization or stabilization of deprotonated P(III). 8,9 Several reactions involve trapping the P(III) form by coordination to transition-metal complexes 10 or Lewis acids, 11 or through silylation. Reference 12 reviews additional evidence for the reactivity of 1c. Substituent effects on tautomerism are particularly critical for phosphinylidene reactivity. While the equilibrium in eq 1 generally lies far toward the P(V) form, small electronic differences due to substituents R 1 and R 2 dramatically affect the overall rates of reactions involving phosphinylidenes. For example, the “special” reactivity of aryl H-phosphinates 4 (R 1 = aryl, R 2 = OAlk) in addition to alkenes has been attributed to stabilization of the P(III) lone pair in 1c through the aryl’s electron-withdrawing effect. 13-15 However, it is at present unclear whether these substituent effects arise from thermody- namic stabilization of the reactive species 1c, from kinetic acceleration of the rate of 1c formation, or from other effects. Thus, a fundamental understanding of substituent effects on eq 1 is critical to the practical development of new synthetic organophosphorus chemistry. Received: July 13, 2015 Published: September 15, 2015 Figure 1. Important types of phosphinylidene compounds. Article pubs.acs.org/joc © 2015 American Chemical Society 10025 DOI: 10.1021/acs.joc.5b01618 J. Org. Chem. 2015, 80, 10025-10032