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Abstract Cyclopentene rings possessing a chiral quaternary center are important structural motifs found in various natural products. In this work, we disclose expedient and efficient access to this class of synthetically valuable structuresviahighly enantioselective desymmetrization of prochiral propargylic alcohols. The efficient chirality induction in this asymmetric gold catalysis is achievedviatwo‐point bindings between a gold catalyst featuring a bifunctional phosphine ligand and the substrate homopropargylic alcohol moiety—an H‐bonding interaction between the substrate HO group and a ligand phosphine oxide moiety and the gold‐alkyne complexation. The propargylic alcohol substrates can be prepared readilyviapropargylation of enoate and ketone precursors. In addition to monocyclic cyclopentenes, spirocyclic and bicyclic ones are formed with additional neighboring chiral centers of flexible stereochemistry in addition to the quaternary center. This work represents rare gold‐catalyzed highly enantioselective cycloisomerization of 1,5‐enynes. Density functional theory (DFT) calculations support the chirality induction model and suggest that the rate acceleration enabled by the bifunctional ligand can be attributed to a facilitated protodeauration step at the end of the catalysis.
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Shaping of a Reactive Manganese Catalyst Enables Access to Polyfunctionalized Cyclohexanes via Enantioselective C( sp3 )─H Bond Oxidation of 1,3‐ meso Diethers
Abstract Chiral polyoxygenated cyclohexanes are valuable constituents of biologically relevant products. Herein, we report a protocol for the direct access to these scaffolds via site‐ and enantioselective non‐directed oxidation of cyclohexyl‐3,5‐mesodiethers using aqueous H₂O₂. Structural shaping of a highly reactive chiral Mn‐oxo species, achieved through the combination of a sterically encumbered ligand and a bulky carboxylic acid, promotes a precise fit of the substrate within the catalyst pocket, which translates into exceptional enantioselectivity (up to >99% ee). Computational studies reveal that C─H oxidation proceeds via an initial hydrogen atom transfer, followed by electron transfer, leading to the formation of a chiral cationic intermediate. The resulting desymmetrized 3‐methoxycyclohexanone products serve as valuable intermediates for the synthesis of bioactive cores, as they can undergo orthogonal chemical modifications to enable further structural diversification.
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- Award ID(s):
- 2154502
- PAR ID:
- 10649755
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Angewandte Chemie International Edition
- Volume:
- 64
- Issue:
- 30
- ISSN:
- 1433-7851
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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