Mechanisms and stereoselectivities of the DABCO-catalyzed Rauhut–Currier reaction of α,β-unsaturated ketones and aryl acrylates: a computational investigation

A chemoselective cross Rauhut-Currier-type reaction has been developed involving a tri-substituted alkene (trifluoromethyl-containing acrylonitrile derivative) with a di- or tri-substituted alkene to yield tetra-substituted double bonds in RC-type products. This approach can support the synthesis of trifluoromethylated tetra-substituted olefins and synthetically important, structurally complex 3-allylic-type oxindole skeletons. The asymmetric version of this RC-type reaction can be realized by combining a Brønsted acid and Lewis base for bifunctional H-bonding-tertiary amine catalysis. Subsequent transformation of multi-functionalized RC-type product leads to pharmacologically interesting cyclohexane-based spiro-pyrazolones bearing six contiguous chiral centers and two highly congested, vicinal quaternary carbon centers.

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Chemoselective Intramolecular Rauhut‐Currier Reaction on a Labile Framework of Enone and Acrylamide: Tricyclohexylphosphine as a Stable and Economical Catalyst

Verma,

Bairwa,

Bharadwaj

2024

Eur J Org Chem

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Intramolecular Rauhut‐Currier (IRC) reaction is an atom‐economical way of making carbocyclic and heterocyclic rings. However, its sensitivity towards electronic and steric parameters limits the reaction and stems the need for further development. Acrylamides have been one such left out of their sensitivity. Herein we report an IRC reaction, using acrylamide as a source of initial enolate. The cyclization has been achieved on a labile and challenging framework, prone to decomposition. Different control experiments have addressed the instability of the precursor. Protocol was further extendable to annulation for benzo analogs. We also report tricyclohexylphosphine (PCy3) as a stable, commercial, and easy‐to‐use nucleophilic catalyst in the field of IRC reactions as compared to earlier well‐established trimethyl and tributyl phosphines. Me3P and Bu3P although useful, are sensitive, prone to oxidation, and need careful handling. The protocol leads to the synthesis of piperidone and dihydroquinolone frameworks. A quick study to test the feasibility of catalyzing the Morita‐Baylis‐Hillman (MBH) reaction by PCy3 was also done successfully, although in moderate yields.

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Mechanisms and stereoselectivities of the DABCO-catalyzed Rauhut–Currier reaction of α,β-unsaturated ketones and aryl acrylates: a computational investigation

Cited by 6 publications

References 47 publications

Addition Reactions

Addition Reactions

Chemo‐ and Stereoselective Cross Rauhut–Currier‐Type Reaction of Tri‐substituted Alkenes Containing Trifluoromethyl Groups

Chemoselective Intramolecular Rauhut‐Currier Reaction on a Labile Framework of Enone and Acrylamide: Tricyclohexylphosphine as a Stable and Economical Catalyst

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