Target-directed organocatalysis: a direct asymmetric catalytic approach to chiral propargylic and allylic fluorides.
A simple, direct one-pot organocatalytic approach to the formation of optically active propargylic fluorides is presented. The approach is based on organocatalytic alpha-fluorination of aldehydes and trapping and homologation of the intermediate providing optically active propargylic fluorides in good yields and enantioselectivities up to 99% ee. The procedure takes place by addition of NFSI, in the presence of 2-[bis(3,5-bis-trifluoromethylphenyl)trimethylsilyloxymethyl]pyrrolidine (as low as 0.25 mol %) as the catalyst, to aldehydes in combination with dimethyl 2-oxopropylphosphonate and 4-acetamidobenzenesulfonyl azide. The scope of the reaction is demonstrated by the formation of a number of optically active propargylic fluorides. It is also shown that optically active fluoro-containing triazoles can be obtained in one-pot procedures from aldehydes using click-chemistry. Furthermore, important coupling and multicomponent reactions of the optically active propargylic fluorides can be performed without affecting the enantiomeric excess. The direct one-pot formation of optically active allylic fluorides from aldehydes is also demonstrated. Finally, the mechanisms for both the formation of the propargylic and allylic fluorides are outlined.
Center for Catalysis, Department of Chemistry, Aarhus University, DK-8000 Aarhus C, Denmark.
Hao
H
Jiang
Aurelia
A
Falcicchio
Kim L
KL
Jensen
Márcio W
MW
Paixão
Søren
S
Bertelsen
Karl Anker
KA
Jørgensen
D000447:Aldehydes / Q000737:chemistry*; D000480:Alkynes / Q000138:chemical synthesis; D000498:Allyl Compounds / Q000138:chemical synthesis*; D002384:Catalysis; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis*; D011759:Pyrrolidines / Q000737:chemistry; D013237:Stereoisomerism; D013449:Sulfonamides / Q000737:chemistry
D000447:Aldehydes; D000480:Alkynes; D000498:Allyl Compounds; D006845:Hydrocarbons, Fluorinated; D011759:Pyrrolidines; D013449:Sulfonamides; C517788:fluorodi(phenylsulfonyl)amine