C5‐Disubstituted Meldrum’s Acid Derivatives as Platform for the Organocatalytic Synthesis of C3‐Alkylated Dihydrocoumarins

Thomas Martzel (1) , Julien Annibaletto (1) , Vincent Levacher (1) , Jean-François Brière (1) , Sylvain Oudeyer (1)

1 COBRA - Chimie Organique et Bioorganique : Réactivité et Analyse

C5‐disubstituted Meldrum's acid precursors were shown to be a useful platform for the synthesis of an array of 3‐alkylated dihydrocoumarins with up to 93:7 er, thanks to an enantioselective domino cyclization‐decarboxylative‐protonation reaction triggered by an unprecedented benzhydryl‐derived cupreine organocatalyst. This cyclization sequence was extended to an emerging organocatalytic decarboxylative‐chlorination reaction in the presence of trichloroquinolinone and by means of a bifunctional cinchona derived Brønsted base which gave rise to the formation of dihydrocoumarins (up to 79:21 er) with a tertiary chlorinated stereocenter.

Keywords: Coumarin; organic catalysis; synthetic method; Meldrum's acid; Decarboxylative protonation

Domains: Chemical Sciences; Organic chemistry; Chemical Sciences; Catalysis

Thomas Martzel, Julien Annibaletto, Vincent Levacher, Jean-François Brière, Sylvain Oudeyer. C5‐Disubstituted Meldrum’s Acid Derivatives as Platform for the Organocatalytic Synthesis of C3‐Alkylated Dihydrocoumarins. Advanced Synthesis and Catalysis, 2019, 361 (5), pp.995-1000. ⟨10.1002/adsc.201801453⟩. ⟨hal-02197276⟩