The elucidation of single electron transfer (SET) mechanisms in the reactions of nucleophiles with carbonyl compounds

Abstract

The chemistry of the radical anion generated from 1,I-dimethyl-5,7-di-tbutylspiro[ 2,5]octa-4,7-dien-6-one (20) was studied electrochemically using cyclic and linear sweep voltammetry (CV, LSV). The reduction potential of20 was estimated to be -2.5 V VS. 0.1 M Ag+/Ag, similar to the reduction potentials observed for aryl ketones and enones. LSV results for the reduction of 20 are consistent with the occurrence of substrate reduction followed by a subsequent chemical step (an EC mechanism). The broadness of the reduction wave and variation of peak potential with sweep rate suggest that the rate limiting step is heterogeneous electron transfer. Ring opening of the radical anion generated from 20 results in a 9: 1 ratio of the 3° and 1 ° distonic radical anions. The rate constant for ring opening has been estimated to be k ≥ 107 s-1 with a calculated (AMI) enthalpy of ring opening of ~ > -15 kcallmol. The facile nature of radical anion ring opening can be ascribed to the relief of cyclopropyl ring strain in conjunction with the establishment of aromaticity. On this basis, the regiochemistry of the ring opening of the radical anion derived from 20 suggests that polar and SET pathways can be differentiated based upon the regiospecificity of cyclopropyl ring opening. In reactions between 20 and nucleophiles known to react via SET with carbonyl compounds, 20 successfully produced products characteristic of SET pathways. However, subsequent studies of the reaction between 20 and thiophenoxide, a nucleophile purported to undergo SET, produced no evidence for a SET pathway. It was discovered that ring opened products may also be formed by competing polar pathways involving a carbocationic intermediate, especially in protic solvents. In dipolar aprotic solvents, ring opening occurs primarily via an Sn2 process, with nucleophilic attack occurring preferentially at the least hindered carbon. The strengths and weaknesses of 20 as a SET probe are discussed