PREPARATIONS AND TRANSFORMATIONS OF BIFUNCTIONAL EXO-2-PHOSPHORUS SUBSTITUTED BICYCLO[2.2.1]HEPTANES

The secondary phosphonate ester exo-2-(dimethoxyphosphoryl)bicyclo[2.2 .1]heptane 1 was prepared by literature methods on a mole scale. This synthetic method was extended to include the stereoselective preparati on of the exo-diethyl phosphonate analog 3 in 71% yield. Derivatizatio n of these exo-phosphonates 1 and 3 required vigorous conditions, but proceeded in moderate to high yields. The configuration about carbon-2 was retained in all but one case. Isomerization about carbon-2 was ob served during the desulfurization of exo-thiophosphonic dichloride 15 with triphenylphosphine at 240 degrees C. A 3:2 ratio of exo- to endo- phosphonous dichlorides 16 resulted. When the reaction was conducted a t 100 degrees C, exo-phosphonous dichloride 16 was formed without epim erization at carbon-2 (97% exo isomer). The exo-dichloride 16 isomeriz ed to the endo-isomer upon treatment with triphenylphosphine at 240-26 0 degrees C. The intermediate phosphaalkene 17 was implicated to prece de this isomerization. Moreover, intentional isomerization of the pare nt compound 3 could be readily effected by treatment with LDA at -78 d egrees C. Attempts were also made to stereoselectively displace a benz yl group from the prochiral phosphorus center in exo-dibenzylphosphoni um salt 21. However, alkaline hydrolysis of exo-methyldibenzylphosphon ium bromide 21 under a variety of conditions gave a 1:1 mixture of xo- 2-(benzylmethylphosphoryl)bicyclo[2.2.1]heptane 22.