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. 2010 Sep 1;132(34):12150-4.
doi: 10.1021/ja105834t.

Silver-catalyzed late-stage fluorination

Pingping Tang  1 , Takeru Furuya, Tobias Ritter
Affiliations

Silver-catalyzed late-stage fluorination

Pingping Tang et al. J Am Chem Soc. .

Abstract

Carbon-fluorine bond formation by transition metal catalysis is difficult, and only a few methods for the synthesis of aryl fluorides have been developed. All reported transition-metal-catalyzed fluorination reactions for the synthesis of functionalized arenes are based on palladium. Here we present silver catalysis for carbon-fluorine bond formation. Our report is the first example of the use of the transition metal silver to form carbon-heteroatom bonds by cross-coupling catalysis. The functional group tolerance and substrate scope presented here have not been demonstrated for any other fluorination reaction to date.

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Figures

Scheme 1
Scheme 1
Late-stage fluorination of ezetimibe and strychnine. a: i) PhNTf2, Et3N, DMAP, CH2Cl2, 23 °C, 95%; ii) LiCl, 5 mol% Pd(PPh3)4, (n-Bu3Sn)2, dioxane, 100 °C, 50%; b: Ag2O (5 mol%), NaHCO3, NaOTf, F-TEDA-PF6, acetone, 65 °C, 90%; c: Et3N, 5 mol% Pd(PPh3)4, (n-Bu3Sn)2, dioxane, 100 °C, 34%; d: BnBr, acetone; AgOTf; Ag2O (5 mol%), NaHCO3, NaOTf, F-TEDA-PF6, 65 °C; e: 1,4-cyclohexadiene, Pd/C, MeOH, 40 °C, 60% for two steps.
Scheme 2
Scheme 2
Proposed mechanism for silver-catalyzed fluorination.
Chart 1
Chart 1
Limitations of the presented fluorination reaction.a a) The fluorination was attempted from the corresponding arylstannane: 5.0 mol% Ag2O, 1.5 equiv F-TEDA-PF6, 2.0 equiv NaHCO3, 1.0 equiv NaOTf, 5.0 equiv MeOH, acetone, 65 °C, 4 h. b) 20 mol% of AgOTf, 2 equiv of NaOTf and 2 equiv of F-TEDA-PF6 were used at 90 °C.
See this image and copyright information in PMC

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