Phosphine‐Catalyzed Enantioselective [2 + 2] Annulations of <i>α</i> ‐Allyl <i>γ</i> ‐Benzyl Allenoates via a Transannular Cyclization Approach

Fused cyclobutane frameworks are valuable scaffolds in natural products and pharmaceuticals, yet catalytic asymmetric methods for their construction remain rare due to ring strain and stereocontrol challenges. Here, we report a spiro phosphine-catalyzed, stereoconvergent, and enantioselective [2 + 2] annulation of racemic α-allyl γ-benzyl allenoates via transannular cyclization, efficiently delivering bicyclo[3.2.0]heptenes in high yields and excellent enantioselectivity. Experimental studies and DFT calculations indicate a stepwise mechanism involving seven-membered zwitterion formation, dynamic kinetic resolution through reversible nucleophilic addition, and a rate- and enantioselectivity-determining deprotonation via intramolecular hydrogen transfer. This protocol offers a concise and general approach to enantioenriched fused cyclobutanes, expanding synthetic options for drug discovery.

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Publication Details

Journal
Angewandte Chemie International Edition
Published
2025-12-04
DOI
https://doi.org/10.1002/anie.202515642
Citations
1
Primary Topic
Asymmetric Hydrogenation and Catalysis
Type
article
Field-Weighted Citation Impact
0.54
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article

Phosphine‐Catalyzed Enantioselective [2 + 2] Annulations of α ‐Allyl γ ‐Benzyl Allenoates via a Transannular Cyclization Approach

Xuling Pan, You Huang, Weiguo Xiao, Li‐Jun Xiao et al.
1 citations
Angewandte Chemie International Edition
Asymmetric Hydrogenation and Catalysis
0.54
article

Phosphine‐Catalyzed Enantioselective [2 + 2] Annulations of α ‐Allyl γ ‐Benzyl Allenoates via a Transannular Cyclization Approach

Xuling Pan, You Huang, Weiguo Xiao, Li‐Jun Xiao, Qi‐Lin Zhou
article en
1 citations

Abstract

Fused cyclobutane frameworks are valuable scaffolds in natural products and pharmaceuticals, yet catalytic asymmetric methods for their construction remain rare due to ring strain and stereocontrol challenges. Here, we report a spiro phosphine-catalyzed, stereoconvergent, and enantioselective [2 + 2] annulation of racemic α-allyl γ-benzyl allenoates via transannular cyclization, efficiently delivering bicyclo[3.2.0]heptenes in high yields and excellent enantioselectivity. Experimental studies and DFT calculations indicate a stepwise mechanism involving seven-membered zwitterion formation, dynamic kinetic resolution through reversible nucleophilic addition, and a rate- and enantioselectivity-determining deprotonation via intramolecular hydrogen transfer. This protocol offers a concise and general approach to enantioenriched fused cyclobutanes, expanding synthetic options for drug discovery.

Angewandte Chemie International EditionVol. 65(3)
Nankai University (CN), Zero to Three (US)
Openalex Percentile: Top 28%
Asymmetric Hydrogenation and Catalysis
0.54
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