Premium
Enantioselective Fluorination of β‐Ketoamides Catalyzed by Ar‐BINMOL‐derived SalanCopper Complex
Author(s) -
Zheng LongSheng,
Wei YunLong,
Jiang KeZhi,
Deng Yuan,
Zheng ZhanJiang,
Xu LiWen
Publication year - 2014
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201400603
Subject(s) - enantioselective synthesis , chemistry , electrophile , reagent , catalysis , cationic polymerization , copper , amide , organic chemistry , salt (chemistry) , combinatorial chemistry
A facile and powerful enantioselective construction of CF containing molecules was successfully developed through asymmetric fluorination of β‐ketoamides catalyzed by Ar‐BINMOL‐derived salan–Cu II system (Ar‐BINMOL=1,1′‐Binaphthalene‐2‐α‐arylmethanol‐2′‐ol, Cu = copper). The present catalytic system exhibited excellent enantioselectivity and a broad substrate scope for indanone‐derived β‐ketoamides under mild conditions (up to 99 % ee and 99 % yields). Notably, the biomimetic salan‐copper complex was demonstrated for the first time to be a highly efficient catalyst in the fluorination of β‐ketoamides. Experimental results and mechanistic studies indicated that both excess amount of copper salt and electrophilic attack of cationic fluorine to activated methylene assisted by amide group on the β‐ketoamides were key factors for high yield and excellent enantioselectivity, respectively, in this enantioselective fluorination, which was controlled by the two‐point binding between the salan–copper complex with cyclic β‐ketoamides and hydrogen‐bonding activation of the electrophilic fluorinating reagent.