Chemoselective Alkylating Esterification of Thiophosphinic Acids: An Experimental and Theoretical Study

Preparative experiments including the alkylation of diphenylthiophosphinic acid with a series of C₁-C₄ haloalkenes at 75/115°C in the presence of triethylamine in toluene suggested chemoselective formation of the corresponding S- (thiolic) ester. No O-(thionic) ester was formed. For this, we wished to clarify the confusion regarding the outcome of such alkylations described in the literature. A few analogous derivatives were also synthesized and characterized for comparison. First in the literature, crystal structures of two thiolic esters were analyzed in detail. The alkylation led to non-centrosymmetric crystal structures. Moreover, the two isostructural thiolic compounds formed chiral crystals, a rather unusual feature of achiral molecules. Weak interactions such as C-H … O bridges and dispersion dominate and tailor the structure of the crystals. As regards the mechanism, three possible pathways were investigated at the B3LYP/6-31G(d,p)/PCM[toluene] level of theory. The activation enthalpy for the rate-determining step was significantly lower for the triethylamine-catalyzed route than for the base-free variation. Moreover, in the base-catalyzed protocol, the difference of 30.8 kJ mol^-1 between the enthalpy of activation for the S and O-alkylations justified the S-selectivity. The pathway involving the anion from the thiophosphinic acid was found unfavorable and hence was excluded.