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.
Authors
- Xuling Pan
- You Huang (ORCID: https://orcid.org/0000-0002-9430-4034)
- Weiguo Xiao
- Li‐Jun Xiao (ORCID: https://orcid.org/0000-0002-3998-3628)
- Qi‐Lin Zhou (ORCID: https://orcid.org/0000-0002-4700-3765)
Institutions
- Nankai University (CN)
- Zero to Three (US)
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