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.
Jiang
Hao
H
Center for Catalysis, Department of Chemistry, Aarhus University, DK-8000 Aarhus C, Denmark.
Falcicchio
Aurelia
A
Jensen
Kim L
KL
Paixão
Márcio W
MW
Bertelsen
Søren
S
Jørgensen
Karl Anker
KA
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