Stereochemistry and kinetics of the reactions of bicyclo[3,2,1]octan-2- and -3-one with sodium borohydride, methylmagnesium iodide, and diazomethane

Abstract

Bicyclo[3,2,1]octan-2-(1) and -3-one (2) and norbornan-2-one (3) undergo reduction by sodium borohydride in isopropyl alcohol with second-order kinetics, the product distribution remaining unchanged during the course of the reaction. Relative rates for these reactions at room temperature are ca. 50:10:1 for (1), (3), and (2) respectively. Dissection of the rate coefficients on the basis of product distribution shows that trans-attack (with respect to the ethano bridge of the cyclohexanone skeleton) is ca. four-fold faster than cis-attack for (1), while the reverse order (by ca. 1·5-fold) is true for (2). The kinetically controlled product ratios parallel the thermodynamic values, and are very similar in the case of the norborneols. Addition of methylmagnesium iodide is only ca. five-fold faster for (1) than for (2) in diethyl ether at 0°. Dissection of rates on the basis of product distribution shows that cis-attack, which is only slightly faster than trans-attack for (1), is completely inhibited for (2). Crude experiments indicate that (1) reacts ca. 80 times faster than (2) with diazomethane in diethyl ether–methanol (1:2) at room temperature. All these observations are rationalized.