A domino reaction for generating \u03b2-aryl aldehydes from alkynes by substrate recognition catalysis

Weiwei Fang,Felix Bauer,Bernhard Breit,Yaxi Dong

doi:10.1038/s41467-019-12770-w

Weiwei Fang, Felix Bauer + Show 2 more

Open Access

https://doi.org/10.1038/s41467-019-12770-w

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Journal: Nature Communications	Publication Date: Oct 25, 2019
Citations: 9	License type: open-access

Affiliation: University of Freiburg

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.

Highlights

The development of universal catalyst systems that enable efficient, selective, and straightforward chemical transformations is of immense scientific importance
A nuclear magnetic resonance (NMR) study of the crude reaction mixture indicated that 3-(2,4,6-trimethoxyphenyl)butanal 1 was formed as the main product in 35% yield, similar to the conversion of TMB (36%, Table 1, entry 1)
With a phenyl ring analog of L1, ligand L6, which may allow for supramolecular substrate–ligand interactions, only poor yields and conversions were observed and it indicated the pyridyl ring of L1 is key to the catalytic activity (Table 4, entry 2)

Summary

Introduction

The development of universal catalyst systems that enable efficient, selective, and straightforward chemical transformations is of immense scientific importance. The reaction was carried out employing S1 and TMB (1:1, n/n) in 1,2-dichloroethane (DCE) at 55 °C in the presence of 1 mol% of [Rh(CO)2acac] and 5 mol% of L1 under 6 bar of CO/H2 (1:1) (Table 1, entry 1). A nuclear magnetic resonance (NMR) study of the crude reaction mixture indicated that 3-(2,4,6-trimethoxyphenyl)butanal 1 was formed as the main product in 35% yield, similar to the conversion of TMB (36%, Table 1, entry 1).

Results

Conclusion