Copper-catalyzed intramolecular alkene carboetherification: synthesis of fused-ring and bridged-ring tetrahydrofurans.
Fused-ring and bridged-ring tetrahydrofuran scaffolds are found in a number of natural products and biologically active compounds. A new copper-catalyzed intramolecular carboetherification of alkenes for the synthesis of bicyclic tetrahydrofurans is reported herein. The reaction involves Cu-catalyzed intramolecular addition of alcohols to unactivated alkenes and subsequent aryl C-H functionalization provides the C-C bond. Mechanistic studies indicate a primary carbon radical intermediate is involved and radical addition to the aryl ring is the likely C-C bond-forming mechanism. Preliminary catalytic enantioselective reactions are promising (up to 75% ee) and provide evidence that copper is involved in the alkene addition step, likely through a cis-oxycupration mechanism. Catalytic enantioselective alkene carboetherification reactions are rare and future development of this new method into a highly enantioselective process is promising. During the course of the mechanistic studies a protocol for alkene hydroetherification was also developed.
Department of Chemistry, The State University of New York at Buffalo, Buffalo, New York 14260, USA.
Yan
Y
Miller
Lei
L
Miao
Azade S
AS
Hosseini
Sherry R
SR
Chemler
D000475:Alkenes / Q000138:chemical synthesis / Q000737:chemistry*; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D004987:Ethers / Q000138:chemical synthesis / Q000737:chemistry; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry
D000475:Alkenes; D001643:Bridged Bicyclo Compounds; D004987:Ethers; D005663:Furans; D003300:Copper