Light Induced Diastereoselective Ketoesterification To Access 6,5-Fused Tetrahydrobenzofuranones in Batch and
Vadla Shiva Prasad1,2, Dharavath Ravi1,2, Vadithya Ranga Rao1,2
1Department of Organic Synthesis and Process Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad-500007, Telangana, India.
Abstract:
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.
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