RESUMEN
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.
RESUMEN
Herein, we demonstrated a silver/K2S2O8-mediated highly regio- and diastereoselective 6/5-exo trig radical cascade cyclization of alkyne-tethered cyclohexadienones with sulfonyl hydrazides or sodium sulfinates and subsequent selenation to access 6,6-dihydrochromenone and 6,5-fused tetrahydro benzofuranone derivatives. This reaction protocol features high functional group compatibility and has a wide substrate scope providing a variety of dihydrochromenones and tetrahydro benzofuranone derivatives in good to excellent yields. The reaction proceeds via the attack of a sulfonyl radical to alkyne over the activated Michael acceptor. The TEMPO quenching experiment implies the presence of a radical intermediate. Further synthetic versatility of 6,6- and 5,6-fused derivatives is also showcased.