Ketoesterification stands as a pivotal
technique in organic
synthesis,
particularly due to its essential role in the construction of numerous
natural products and bioactive compounds. In this study, we have successfully
accomplished a visible-light-induced cyclization and diastereoselective
direct ketoesterification of cyclohexadienones, facilitating access
to cis 6,5-fused tetrahydrobenzofuranone derivatives. The utilization
of TEMPO radical quenching experiments has provided insights, suggesting
an ionic mechanism underlying this methodology. Additionally, the
regioselective addition of 2-oxo-2-phenylacetate to the least hindered
side in a cis-selective fashion makes this protocol more appealing
toward natural product development. Incorporation of a continuous
flow reaction into the batch protocol has notably bolstered the efficiency
and reaction rate. Furthermore, the demonstration of gram-scale reactions
in the flow setup and synthetic utility with NaOH underscore the scalability
and practical applicability of this approach.