Highly Enantioselective Trapping of Carboxylic Oxonium Ylides with Imines for Direct Assembly of Enantioenriched γ-Butenolides

Abstract

Enantioenriched γ-butenolides are valuable structural cores in many pharmaceuticals and natural products, but their direct and catalytically asymmetric assembly remains rare. Here, we report an efficient, atom-economic synthetic strategy for enantioenriched γ-butenolides via a unique enantioselective reaction of cyclopropene carboxylic acids with imines under the synergistic catalysis of Rh 2 (esp) 2 / chiral Brønsted acid system. The reaction involved trapping of carboxylic oxonium ylides, generated from cyclopropene carboxylic acids, which presented as the first asymmetric trapping reactive intermediate in the process. Subsequently, enantioenriched γ-butenolide derivatives were obtained in good-to-high yields (55-94%) with excellent stereoselectivities (up to >95∶5 dr and up to 98∶2 er) under mild conditions.

Asymmetric Three-Component Propargyloxylation for Direct Assembly of Polyfunctionalized Chiral Succinate Derivatives

“…Trapping the ylide with imines produced highly functionalized chiral amino acid derivatives. [44][45][46][47][48][49][50][51][52][53][54] However, the potential of this active-intermediate trapping method has yet to be fully explored. The scope of alcohols that could efficiently enable high stereoselectivity in this context remains narrow.…”

Diastereoselective Trapping of Transient Carboxylic Oxonium Ylides with α,β‐Unsaturated 2‐Acyl Imidazoles

“…According to the control reaction and previous studies on 3-carbonylcyclopropenes [8][9][10][11] as well as the ylide trapping process, [5] a reaction mechanism is outlined in Scheme 6. Rhodium-induced ring-opening of cyclopropenes 1 generates electrophilic vinyl carbene C, followed by intramolecular attack by the tethered carboxylic group to give cyclic carboxylic oxonium ylides D. Release of the rhodium catalyst will lead to the non-metal associated ylide E and its resonance structure F, which is captured by the electron-deficient olefins 2 via Michael addition to result in the γ-alkyl γ-butenolides 3.…”

“…[10] Recently, we revealed that cyclopropene carboxylic acids could readily form cyclic carboxylic oxonium ylides, which displayed higher stability than those generated from diazo compounds and carboxylic acids (A in Scheme 1) due to stabilizing effect from conjugated C=C moiety, and thus could be trapped by electrophiles with reactive C=X (X=O, NAr) functionality (Scheme 1c, path d) via 1,2addition. [11] Herein, we reported the first conjugate addition of carboxylic oxonium ylides with electrondeficient olefins (Scheme 1c, path d), which affords direct construction of γ-butenolide derivatives, the privileged structures shared in numerous pharmaceuticals and natural products. [12] We commenced the study with the reaction of cyclopropene carboxylic acid (1 a) and α,β-unsaturated 2-acyl imidazole (2 a).…”

Asymmetric Allylation by Chiral Organocatalyst‐Promoted Formal Hetero‐Ene Reactions of Alkylgold Intermediates

“…Recently our group has reported an enantioselective Mannich-type reaction of in-situ-generated gold enolate intermediate and imine with the assistance of chiral phosphoric acid CPA (Scheme 1b). [22,23] As ac ontinuation of our research program on multicomponent reactions via trapping reactive ylide/zwitterionic intermediates, [24,25] we envisioned that novel interception transformation on the inert 4-position might be enabled through the alkylgold intermediate II, which could be generated via an aromatization driven H-shift process of vinylgold species I with the assistance of appropriate alkalic cocatalyst, instead of direct protodeauration. Herein, we report ag old/quinine-derived squaramide (QN-SQA)cooperative catalysis as an effective strategy to realize the asymmetric allylation of isatins and their ketimine derivatives via an asymmetric formal hetero-ene reaction of alkylgold intermediate II,which shows unique reactivity as an allylgold species (Scheme 1c).…”