Enantioselective Copper-Catalyzed Carboetherification of Unactivated Alkenes

• Published in: Angewandte Chemie International Edition 2014-06, Vol.53 (25), p.6383-6387
• Main Authors: Bovino, Michael T., Liwosz, Timothy W., Kendel, Nicole E., Miller, Yan, Tyminska, Nina, Zurek, Eva, Chemler, Sherry R.
• Format: Article
• Language: English
• Subjects: Alcohols; Alkenes; Alkenes - chemistry; asymmetric catalysis; Asymmetry; Bioactive compounds; Biocompatibility; Bonding; Catalysis; Chemical synthesis; Copper; Copper - chemistry; Crystallography, X-Ray; Cyclization; Enantiomers; enantioselectivity; Ethers - chemistry; heterocycles; Joining; Mathematical analysis; Molecular Structure; Stereochemistry; Stereoisomerism; Synthesis; Tetrahydrofuran
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201402462

Chiral saturated oxygen heterocycles are important components of bioactive compounds. Cyclization of alcohols onto pendant alkenes is a direct route to their synthesis, but few catalytic enantioselective methods enabling cyclization onto unactivated alkenes exist. Herein reported is a highly efficient copper‐catalyzed cyclization of γ‐unsaturated pentenols which terminates in CC bond formation, a net alkene carboetherification. Both intra‐ and intermolecular CC bond formations are demonstrated, thus yielding functionalized chiral tetrahydrofurans as well as fused‐ring and bridged‐ring oxabicyclic products. Transition‐state calculations support a cis‐oxycupration stereochemistry‐determining step. A general scheme: A highly enantioselective copper‐catalyzed carboetherification of 4‐pentenols has been developed. Both intramolecular (formal CH functionalization) and intermolecular (net alkyl Heck‐type coupling; see scheme) CC bond formation can occur, thus forming a range of chiral functionalized tetrahydrofurans. DFT transition‐state calculations provide a rationale for the observed asymmetric induction.