Light Induced Diastereoselective\nKetoesterification\nTo Access 6,5-Fused Tetrahydrobenzofuranones in Batch and Continuous\nFlow Conditions

Ketoesterification stands as a pivotal\ntechnique in organic\nsynthesis,\nparticularly due to its essential role in the construction of numerous\nnatural products and bioactive compounds. In this study, we have successfully\naccomplished a visible-light-induced cyclization and diastereoselective\ndirect ketoesterification of cyclohexadienones, facilitating access\nto cis 6,5-fused tetrahydrobenzofuranone derivatives. The utilization\nof TEMPO radical quenching experiments has provided insights, suggesting\nan ionic mechanism underlying this methodology. Additionally, the\nregioselective addition of 2-oxo-2-phenylacetate to the least hindered\nside in a cis-selective fashion makes this protocol more appealing\ntoward natural product development. Incorporation of a continuous\nflow reaction into the batch protocol has notably bolstered the efficiency\nand reaction rate. Furthermore, the demonstration of gram-scale reactions\nin the flow setup and synthetic utility with NaOH underscore the scalability\nand practical applicability of this approach.