Unprecedented Reactivity Pattern of Chromium Fischer Carbene Complexes. Direct Application to One-Pot Synthesis of 4-Aryl-3,4-dihydrocoumarins on a Multigram Scale

Abstract

[reaction: see text] Reaction of alkenyl carbene chromium(0) complexes and ketene acetals triggers the formation of 4-aryl-3,4-dihydrocoumarins. The reaction can be carried out as a simple one-pot protocol in air atmosphere. The huge interest of dihydrocoumarins has prompted us to optimize a multigram-scale process.

Selective Synthesis of 3,4-Dihydrocoumarins and Chalcones from Substituted Aryl Cinnamic Esters

“…7 Dihydrocoumarins are also widely distributed and have shown so many biological activities such as aldose reductase inhibition, 8 antiherpetic, 9 protein kinases, 10 flavoring agent to a variety of foods (soft drinks, yogurt, muffins). 11 The conventional methods for the synthesis of dihydrocoumarins were reported as follows: 1) the hydroarylation of cinnamic acids with phenols in strong acidic media 12 2) the catalytic hydrogenation of coumarins 13 3) Lewis acid promoted reaction of activated phenols with arylonitrile 14 4) reaction of Fischer carbene complexes with ketene acetals 15 5) p-TSA mediated hydroarylation of cinnamic acids with anisols or phenols 16 6) AlCl 3 -mediated C-C coupling reaction between hydroxyketene S,S-acetals and arenes 17 7) [4+2] cycloaddition reaction of o-quinone methides with silyl ketene acetals 18 8) biotransformation of coumarins by microorganisms. 19 Another type of intramolecular ring formation for coumarins was known as Pechmann condensation 20 which is the most widely employed method for coumarin synthesis.…”

Reactions of Alkenyl Fischer Carbene Complexes with Ketene Acetals: Formation of Alkynes

“…A related observation has recently been made by Barluenga and co-workers. [8] They found that the reaction of alkenyl carbene complexes of the type 42 (Scheme 6) with β,β-disubstituted ketene acetals give the dihydrocoumarins 44 in good chemical yield. This product results from two sequential reactions.…”

Enantioselective Synthesis of Dihydrocoumarins via N‐Heterocyclic Carbene‐Catalyzed Cycloaddition of Ketenes and o‐Quinone Methides

“…Beside the hydrogenation of coumarins, hydroarylation of cinnamic acids and their derivatives is an efficient method to construct dihydrocoumarins 3. Metal‐mediated or metal‐catalyzed reactions, such as reaction of chromium Fishcer carbenes with ketene acetals,4 palladium‐catalyzed cyclocarbonylation of o ‐isopropenylphenols,5 rhodium‐catalyzed reaction of 3‐(2‐hydroxyphenyl)cyclobutanones,6 were also developed. In addition, several interesting approaches have been reported recently, including the AlCl 3 ‐mediated reactions of α‐hydroxyketene S , S ‐acetals with arenes,7 isocyanide‐based four‐component reactions,8 intramolecular redox lactonization of o ‐hydroxycinnamaldehydes,9 and domino Michael addition/acyaltion of aryloxyacetaldydes 10…”