Stereoselective Connection of a C₂- and a Linear C_n-Unit to a Cyclopropane by a Formal Twofold Nucleophilic Substitution

Bicyclo[4.1.0]heptan-7-one O,N-acetals such as 7-methoxy-7-morpholinobicyclo[4.1.0]heptane can be easily converted into 7-substituted 7-(2-oxoalkyl)bicyclo[4.1.0]heptanes via a formal twofold nucleophilic substitution. In the first reaction step, the methoxy group of the O,N-acetal is replaced by the 2,2-dimethyl-4,6-dioxo-1, 3-dioxan-5-yl group by reaction with Meldrum's acid; in the second step, the morpholino group is replaced by a 2-oxoalkyl group by reaction with a 2-alkanone or an enamine. The resultant 2,2-dimethyl-4,6-dioxo-5-[7-(2-oxoalkyl)bicyclo [4.1.0]hept-7-yl]-1,3-dioxanes can be selectively reduced to the corresponding 2-hydroxyalkyl derivatives which readily undergo lactone formation with degradation of the Meldrum's acid moiety, or they can be thermally degradated in the presence of morpholine to give 7-(2-oxoalkyl)bicyclo[4.1.0]heptane-7-acetic acid morpholides. Thus, starting from the O,N-acetal, a C₂-unit and a linear or cyclic C_n-unit can be stereospecifically introduced into position 7 of the bicyclo[4.1.0]heptane system.