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N-Heterocyclic carbene-catalyzed enantioselective hetero-[10 + 2] annulation.

Qiupeng PengShi-Jun LiBei ZhangDonghui GuoYu LanJian Wang
Published in: Communications chemistry (2020)
Higher-order cycloadditions are a powerful strategy for the construction of polycycles in one step. However, an efficient and concise version for the induction of asymmetry is lacking. N-heterocyclic carbenes are widely used organocatalysts for asymmetric synthesis and could be an ideal choice for enantioselective higher-order cycloadditions. Here, we report an enantioselective [10 + 2] annulation between catalytically formed aza-benzofulvene intermediates and trifluoromethyl ketone derivatives. This protocol exhibits a wide scope, high yields, and good ee values, reflecting a robust and efficient higher-order cycloaddition. Density functional theory calculations provide an accurate prediction of the reaction enantioselectivity, and in-depth insight to the origins of stereocontrol.
Keyphrases
  • density functional theory
  • molecular dynamics
  • randomized controlled trial
  • optical coherence tomography
  • high resolution
  • solid state
  • structure activity relationship