Conversion of Meso to dl form and vice versa in bisphosphonates: Synthesis and structures of new Meso, dl and (Meso + dl) bisphosphonates derived from cyclic phosphites and dialkyl acetylenedicarboxylates

Abstract

The bisphosphonates [(OCH2CR2-CH2O)P(O) CHC(O)OR′]2 [R = R′ = Me (5), R′ = Me, R = Et (6), R = Et, R′ = Me (7), R = R′ = Et (8)], [CH2(6-t-Bu-4-Me- C6H4O)2P(O)CHC(O)OR]2 [R = Me (9), Et (10)] and [(OCH2CMe2-CH2O)P(S)CHC(O)OR] 2 [R = Me (11), Et (12)] have been prepared by the reaction of the corresponding cyclic phosphites with dimethyl acetylenedicarboxylate or diethyl acetylenedicarboxylate in the presence of a base [Et3N or n-BuLi]. The structures of dl-, meso-and (dl + mesa) forms [6a, 6b and 6ab] of 6 as well as the meso form of 8 are determined from X-ray crystallography. By means of combined X-ray structural and 31P NMR spectroscopic investigations, it is shown that the mesa form can be converted to the dl form and vice versa. A possible rationale invoking the intermediacy of an enolic form is proposed for this observation.