Biomimetic Study of Intramolecular Phosphoryl Group Transfer in Thioureas under Acid/Base and Stereoelectronic Control

Article abstract of DOI:10.1021/ja00336a036

Reaction of dicyclohexylcarbodiimide with sterically hindered thiophosphoric esters 3 leads at -80 deg C to observable (31P NMR) S-phosphorylisothioureas 5.At 20 deg C in methylene chloride the same reaction does not give 5 but its N-phosphoryl isomer 4, together with 5', 2, and the counterion 3'.The equilibrium quantity of the N-phosphoryl isomer varies with the bulk of the R group (R = Ph > 2,6-Me2C6H3 > 2,5-i-Pr2C6H3).The equilibrium can also be either approached from 4 (which is isolable) or by treating the isothiouronium salt 5' with a strong amine base (such as the proton sponge), and in each case the same observed rate constant (= k₁ + k_-1) is obtained.The equilibrium can be displaced toward 5' in the presence of acid (HBF4 or Et3NH⁺) or toward the elimination products 2 and 3' in the presence of bases (tertiary amines).In the presence of excess acid the observed rate of reaction of 4 is independent of acid concentration and type, and the rate-determining step is assigned to the intramolecular N- -> S-phosphoryl group transfer (4 -> 5), governed by k₁.In the presence of excess base the rate of reaction of 4 is independent of base type and concentration, and the step which is partly rate determining in this case is consistent with the conversion of 5 to 8 (k₂) which is correctly oriented for elimination.The implications of the observation of this mobile equilibrium governed by the presence of acid or base catalysts to the question of the involvement of O- or N-phosphoryl intermediates in the mode of action of the coenzyme biotin is briefly discussed.