A domino reaction for generating β-aryl aldehydes from alkynes by substrate recognition catalysis

Abstract

The development of universal catalyst systems that enable efficient, selective, and straightforward chemical transformations is of immense scientific importance. Here we develop a domino process comprising three consecutive reaction steps based on the strategy of supramolecular substrate recognition. This approach provides valuable β-aryl aldehydes from readily accessible α-alkynoic acids and arenes under mild reaction conditions, employing a supramolecular Rh catalyst containing an acylguanidine-bearing phosphine ligand. Furthermore, the synthesis of a key intermediate of Avitriptan using this protocol is accomplished. The first step of the reaction sequence is proved to be the regioselective hydroformylation of α-alkynoic acids. Remarkably, molecular recognition of the ligand and the substrate via hydrogen bonding plays a key role in this step. Control experiments indicate that the reaction further proceeds via 1,4-addition of an arene nucleophile to the unsaturated aldehyde intermediate and subsequent decarboxylation.

Transition Metal Catalysis Controlled by Hydrogen Bonding in the Second Coordination Sphere

“…The yield for the alcohol can be 99% when 230 is used or when a mixture of ligands is used. Finally, the supramolecular approach was used for the Rh catalyzed hydroformylation of α-alkynoic acids followed by Michael addition and decarboxylation, using an electron-poor phosphorus ligand equipped with the acyl guanidine moiety ( 252 ) (see Scheme e) . This domino reaction is triggered by the Rh catalyzed hydroformylation of α-alkynoic acids, requiring the hydrogen bonding interaction between the ligand and the substrate.…”

“…Finally, the supramolecular approach was used for the Rh catalyzed hydroformylation of α-alkynoic acids followed by Michael addition and decarboxylation, using an electron-poor phosphorus ligand equipped with the acyl guanidine moiety (252) (see Scheme 48e). 387 This domino reaction is triggered by the Rh catalyzed hydroformylation of α-alkynoic acids, requiring the hydrogen bonding interaction between the ligand and the substrate. Consecutive Michael addition of arenes as nucleophiles lead to an intermediate which after decarboxylation of the carboxyl function leads to the β-aryl aldehyde products.…”

Selective Rhodium-Catalyzed Hydroformylation of Terminal Arylalkynes and Conjugated Enynes to (Poly)enals Enabled by a π-Acceptor Biphosphoramidite Ligand

“…However, only a handful of successful examples of alkyne hydroformylation are available in the literature. The work of our predecessors, such as Buchwald, Hidai, Alper, Beller, Breit, Zhang, You, Jia, Girard, Dydio, Morandi, and Zhou, has led to great progress in the hydroformylation of internal alkynes. Regrettably, all of these benign catalytic systems do not seem to work well for terminal alkynes.…”

A Tandem Hydroformylation‐Organocatalyzed Friedel‐Crafts Reaction for the Synthesis of Diindolylmethanes

“…Initial test reactions started from commercially available nonanal and indole (1 a). The reaction after 20 h at 80 °C in toluene-d8, employing standard hydroformylation conditions from our group, [28][29][30][31][32][33][34] yielded the desired diindolylmethane (3 a) in 1 %, while the thiourea-catalyzed reaction yielded 68 % (see SI for further information). This demonstrates the capability of the thiourea organocatalyst to activate the aldehyde carbonyl group.…”