Comins三氟甲磺酸化试剂

N,N-二三氟甲磺酰基-5-氯-2-氨基吡啶或N,N-二三氟甲磺酰基苯胺，此类芳胺的二三氟甲磺酰胺被称为Comins三氟甲磺酸化试剂。其可以将酮类，酯，硫代酸酯转化为相应的三氟甲磺酸烯酯。由于此试剂的活性较高，反应条件温和，因此广泛应用于全合成。

【Comins DL， Tet Lett， 1992， 33， 6299】

试剂的制备

N-(2-Pyridyl)triflimide (1). A 2-L, two-necked, round-bottomed flask equipped with amechanical stirrer (Note 1) and a rubber septum is charged with 2-aminopyridine (19.859 g, 0.211 mol)(Note 2) and pyridine (35.04 g, 35.88 mL, 0.443 mol) (Note 3) in 800 mL of dichloromethane (CH2Cl2)(Note 4) under an argon atmosphere. The reaction mixture is cooled to −78°C and a solution of triflicanhydride (125 g, 74.54 mL, 0.443 mol) (Note 5) in 150 mL of CH2Cl2 is added dropwise via a cannulaover 3.5 hr with vigorous stirring. After the solution is stirred for 2 hr at −78°C, the cooling bath isremoved and stirring is continued at room temperature for 19 hr. The reaction mixture is quenched with50 mL of cold water and the layers are separated. The aqueous layer is extracted with CH2Cl2 (4 × 50mL). The combined organic extracts are washed with cold aqueous 10% sodium hydroxide (1 × 150mL), cold water (1 × 100 mL), brine (1 × 100 mL) and dried over magnesium sulfate. After filtration,the solvent is removed under vacuum to give 69 g of the crude product. After Kugelrohr distillation(Note 6), 61 g (81%) of pure N-(2-pyridyl)triflimide (bp 85–100°C/0.25 mm, mp 41–42°C) (Note 7) isobtained as a white solid.

【Joseph SP, Org Synth, 1997, 74, 77】

反应实例

【Joseph SP, Org Synth, 1997, 74, 77】

Enol triflate (5). Under N2 at 78 C, b-thio-butyrolactone 4 (0.17 mL, 2 mmol) in THF (5 mL) was treated with KHMDS (4.4 mL, solution of 0.5 M in PhMe). After 1 h stirring, 3 (780 mg, 2 mmol) in THF (2 mL) was added. After 3 h at 78 C, quenching (H2O), extraction (Et2O), evaporation and chromatography (Al2O3 neutral) gave 342 mg of 5 (73%).

【O’Neil IA, Synlett, 1995, 151】

【Nicolaou KC, J Am Chem Soc, 2009, 131, 10587】

To a solution of compound 13 (15 mg, 0.052 mmol) in dry THF (5 mL) was added KHMDS (115μL, 0.057 mmol) at -78 oC, and the mixture was stirred at the same temperature for 30 min. To thissolution was added Comins reagent (N-(5-chloro-2-pyridyl) triflimide) (23 mg, 0.057 mmol) in dryTHF (2 mL) -78 oC, and the mixture was then stirred at the same temperature for additional 3 h. Thereaction was quenched by addition of a saturated solution of NH4Cl (5 mL), and the mixture wasextracted with Et2O (3 x 10 mL). The combined extracts were dried over sodium sulfate. The solventwas removed in vacuo and the residue was purified by a flash chromatography on silica gel(hexane/ethyl acetate，10/1) to give 13a (21 mg) in 92% yield as white solid. It is worthwhile tomention that excessive KHMDS will lead to lower yielding.

【Yang Z, J Am Chem Soc, 2010, 132, 13608】

Enol triflate (–)-67: To a solution of ketone (–)-65 (1.80 g, 5.48 mmol) in THF (100 mL) at –78°C was added KHMDS (1.5 equiv, 0.5 M in PhMe, 16.4 mL, 8.22 mmol). The reaction mixture was stirred 10 min before a solution of Commins reagent (1.5 equiv, 3.22 g, 8.22 mmol) in THF(20 mL) was added dropwise. The resulting mixture was warmed to –40 °C then quenched with saturated aqueous NH4Cl solution (50iphasic mixture was extracted with Et2O (50 mLTfO(MgSO4), and concentrated under reduced pressure. The crude residue waspurified by flash column chromatography (silica, Et2O/hexanes, 1 → 4%) tofurnish enol triflate (–)-67 (2.43 g, 5.15 mmol, 94%) as a colorless oil.

【Nicolaou KC, J Am Chem Soc, 2010, 132, 7138】

编译自：Organic Syntheses Based On Name Reactions, 3RdEd, A. Hassner, Page 94.