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

Abstract

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 preparation of the exo-diethyl phosphonate analog 3 in 71% yield. Derivatization of these exo-phos-phonates 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 observed during the desulfurization of exo-thiophosphonic dichloride 15 with triphenylphosphine at 240°C. A 3:2 ratio of exo- to endo-phosphonous dichlorides 16 resulted. When the reaction was conducted at 100°C, exo-phosphonous dichloride 16 was formed without epimerization at carbon-2 (97% exo isomer). The exo-dichloride 16 isomerized to the endo-isomer upon treatment with triphenylphosphine at 240–260°C. The intermediate phosphaalkene 17 was implicated to precede this isomerization. Moreover, intentional isomerization of the parent compound 3 could be readily effected by treatment with LDA at -78°C. Attempts were also made to stereoselectively displace a benzyl group from the prochiral phosphorus center in exo-dibenzylphosphonium salt 21. However, alkaline hydrolysis of exo-methyldibenzylphosphonium bromide 21 under a variety of conditions gave a 1:1 mixture of exo-2-(benzylmethylphos-phoryl)bicyclo[2.2.1]heptane 22.

Key Words:

• Bicyclo[2.2.1]heptane
• norbornyl
• phosphaalkene
• phosphonat
• epimerization
• isomerization