Diastereodivergent and Enantioselective Organocatalytic Synthesis of Spiro-Fused Coumarins via [4+2] Cycloadditions
Raquel Hidalgo-León1, José Trujillo-Sierra1, José Miguel Sansano1
1Departamento de Química Orgánica, Centro de Innovación en Química Avanzada (ORFEO-CINQA) and Institute of Organic Synthesis, Universidad de Alicante, Ctra. Alicante-San Vicente s/n, 03080 Alicante, Spain.
Abstract:
A highly enantioselective, organocatalytic, diastereodivergent synthesis of spiro-fused coumarin derivatives via trienamine-mediated Diels-Alder reactions with cyclic 2,5-dienones is reported. Using a cinchonidine-based primary amine and either p-methylbenzoic acid or triethylamine enables reversible diastereoselectivity, providing complementary enantioenriched diastereoisomers. The influence of electron-withdrawing groups at C3 of coumarins is delineated, revealing distinct reactivity patterns. Computational studies provide insight into the mechanism and additive-controlled diastereodivergence.
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