Catalytic, asymmetric alpha-fluorination of acid chlorides: dual metal-ketene enolate activation.
In this Communication, we disclose a catalytic, highly enantioselective (up to >99% ee) alpha-fluorination of acid chlorides to produce a variety of optically active carboxylic acid derivatives from readily accessible and commercially available starting materials. The reaction depends on dually activated ketene enolates generated from two discrete catalysts--a chiral nucleophile and an achiral transition metal complex working in tandem. The active, putative alpha-fluorobis(sulfonimide) intermediates readily transacylate in situ under mild conditions upon addition of a wide variety of nucleophiles, including complex natural products. As a consequence, the power of this method is witnessed by the broad range of alpha-fluorinated products that can be accessed efficiently depending on the work up conditions.
Paull
Daniel H
DH
Johns Hopkins University, Department of Chemistry, 3400 North Charles Street, Baltimore, Maryland 21218, USA.
Scerba
Michael T
MT
Alden-Danforth
Ethan
E
Widger
Leland R
LR
Lectka
Thomas
T
D000143:Acids / Q000737:chemistry*; D002264:Carboxylic Acids / Q000737:chemistry; D002384:Catalysis; D002625:Chemistry, Organic / Q000379:methods*; D002712:Chlorides / Q000737:chemistry*; D005030:Ethylenes / Q000737:chemistry*; D005461:Fluorine / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry*; D008670:Metals / Q000737:chemistry*; D008956:Models, Chemical; D013449:Sulfonamides / Q000737:chemistry
D000143:Acids; D002264:Carboxylic Acids; D002712:Chlorides; D005030:Ethylenes; D007659:Ketones; D008670:Metals; D013449:Sulfonamides; D005461:Fluorine; C008223:ketene