Through the years, we have utilized electrochemistry as a method to explore radical cation intermediates and the oxidative cyclization reactions they trigger. On the mechanistic side of things, we have uncovered a set of empirical rules that govern radical cation reactivity and allow for the design of new reactions. On the synthetic side of things, we have used the ensuing reactions to make heterocycles, fused-, spirocyclic-, and bridged molecules, and highly hindered tetrasubstituted carbons.

Recently, we have found that these initial mechanistic models have to be adjusted to account for not only the initial cyclization reaction, but also the intermediates generated downstream of that step. In particular, the oxidation of a second electron from the molecule (k₂ in Scheme 1) frequently plays a key role in the synthetic success of a transformation.

While this observation was clear for cases for slower trapping reactions that might have a reversible first step, it was assumed that our very best trapping reactions that were known to be kinetically fast had no such issues. This assumption has also proven problematic.

Photoelectron transfer reactions that are ideally suited for conducting one-electron oxidation based processes are ideal tools for probing cyclizations that require the loss of a second electron (Scheme 2). Note that all three substrates shown underwent a two electron oxidative cyclization nicely at an anode to give the cyclic products shown. The substrate with the alcohol trapping group also worked well providing a redox neutral complementary product to the electrolysis reaction. The substrate with the sulfonamide trapping group led to no reaction. This was not a surprise since the cyclization with the sulfonamide trapping group is slower than the alcohol trapping reaction. The reaction is dominated by a back electron transfer from the dithioketene acetal derived radical cation to the catalyst. The reaction with the enol ether trapping group led to polymer that showed evidence for consumption of both olefins in the starting material. This was a surprise since the cyclization is known to be very fast (much faster than the alcohol trapping of the radical cation). The reaction clearly required the loss of a second electron to form the desired cyclized product. This was a conclusion that could only be reached by comparing the photochemical and electrochemical reactions.

In the talk to be presented, the historical context and future synthetic ramifications of this and other mechanistic studies that define the nature of the reactive intermediate needed for the initial cyclization will be discussed.