[37595-74-7]  · C8H5F6NO4S2  · N-Phenyltrifluoromethanesulfonimide  · (MW 357.28)

(mild triflating agent2 for amine protection;3,4 vinyl triflate formation from thermodynamic2 and kinetic enolates5 generated by deprotonation, conjugate reduction,6,7 or conjugate addition;7 formation of aryl triflates2)

Alternate Names: N-phenyltriflimide; Hendrickson-McMurray reagent.6

Physical Data: mp 101-103 °C (Aldrich), 93-94 °C.2

Form Supplied in: white solid; widely available.

Preparative Methods: prepared in 92% yield from the reaction of aniline with 2 equiv each of Trifluoromethanesulfonic Anhydride and Triethylamine in CH2Cl2 at -78 °C.2

Handling, Storage, and Precautions: nonhygroscopic and extremely stable.

Utility and Selectivity with Amines and Alcohols.

The trifluoromethanesulfonyl group provides for effective protection of primary and secondary amines4 and the monoalkylation of secondary trifluoromethanesulfonamides.3 These substrates are typically formed by the reaction of the amine with Trifluoromethanesulfonic Anhydride (triflic anhydride, Tf2O). As a less reactive triflating reagent, N-phenyltrifluoromethanesulfonimide2 (Tf2NPh) is more convenient to use and provides higher selectivity than that encountered with triflic anydride. Triflates of secondary aliphatic amines are easily isolated from the byproduct phenyltriflamide by carbonate extraction3 and Tf2NPh does not react with aromatic secondary amines under similar or more vigorous conditions.3 This selectivity is also observed in selective triflation of primary over secondary alcohols, allowing selective dehydration in a series of dipeptides (eq 1).9

Formation of Enol Trifluoromethanesulfonates (Enol Triflates).

Kinetic or thermodynamic enolate formation, through reaction of unsymmetrical ketones with properly selected strong bases, followed by treatment with Tf2NPh provides regioselective formation of vinyl triflates7,8,10,11 in good to excellent yields (eq 2). Minor discrepancies to these generalities have been documented, but appear to be substrate (eq 3)12,13 or base dependent (eq 4).13 This sequence surpasses the triflic anhydride/base protocol (which provides predominantly thermodynamic products) both in regiocontrol and material yield and has led to preparation of enol triflates where triflic anhydride fails (eq 5).7,14-16 Enol triflates of symmetrical and unidirectionally enolizable ketones13,14,17-20 are produced in typically higher yield by trapping with Tf2NPh compared with Tf2O7,16 or (trifluoromethylsulfonyl)imidazole14,17 and enolates of five- to seven-membered lactones have been isolated as their trifluoromethanesulfonyl ketene acetals (eq 6).21

Regiospecific Generation of Enol Triflates.

A variety of enolate generation methods followed by exposure to Tf2NPh provides regiospecific vinyl triflates. Regiospecific enolates generated from conjugate reduction of enones with Lithium7,22 in liquid Ammonia, from pure silyl enol ethers with Methyllithium,6 and by conjugate addition of dialkylcuprate reagents to enones6,23 are all successfully trapped by Tf2NPh. N-Phenyltriflimide efficiently captures regiospecific enolates generated from conjugate reduction of cyclopentenones6 and cyclohexenones6,24 with Lithium Tri-s-butylborohydride (eqs 7 and 8), with the exception of sterically encumbered substrates.6 N-Phenyltriflimide has become a widely utilized reagent for the conversion of phenols to aryl triflates. Optimal yields2 and chemoselectivity2,25 allow aryl triflate formation in the presence of amines, alcohols, or carboxylates2 and on relatively sensitive substrates.25

Utility of Enol and Aryl Triflates.

Enol triflates have been utilized for the generation of vinyl cations and carbenes,26 and the transient 1,2,3-cyclohexatriene.27 Enol triflates and trifluoromethanesulfonyl ketene acetals21 undergo coupling with diorganocuprate reagents to give alkenes and substituted enol ethers, respectively. Palladium-catalyzed coupling and carbonylation reactions of enol and aryl triflates with organostannanes, alkenes, and alkynes abound in the literature.14

Other Applications.

A selected number of primary and secondary saturated triflones are available from the reaction of the respective alkyllithium or dialkylcuprate reagent with N-phenyltriflimide.28

1. FF 1986, 12, 395; 1988, 13, 248.
2. Hendrickson, J. B.; Bergeron, R. TL 1973, 4607.
3. Hendrickson, J. B.; Bergeron, R.; Sternbach, D. D. T 1975, 31, 2517.
4. Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis; Wiley: New York, 1991.
5. Scott, W. J.; Crisp, G. T.; Stille, J. K. JACS 1984, 106, 4630.
6. Crisp, G. T.; Scott, W. J. S 1985, 335.
7. McMurry, J. E.; Scott, W. J. TL 1983, 24, 979.
8. Corey, E. J.; Wu, L. I. JACS 1993, 115, 9327.
9. Torrini, I.; Zecchini, G. P.; Paradisi, M. P. SC 1989, 19, 695.
10. Crisp, G. T.; Scott, W. J.; Stille, J. K. JACS 1984, 106, 7500.
11. Mascareñas, J. L.; Sarandeses, L. A.; Castedo, L.; Mouriño, A. T 1991, 47, 3485.
12. Cheney, D. L.; Paquette, L. A. JOC 1989, 54, 3334.
13. Piers, E.; Friesen, R. W. CJC 1992, 70, 1204.
14. Scott, W. J.; McMurry, J. E. ACR 1988, 21, 47.
15. Paquette, L. A.; Moriarty, K. J.; McKinney, J. A.; Rogers, R. D. OM 1989, 8, 1707.
16. Nakatani, K.; Arai, K.; Hirayama, N.; Matsuda, F.; Terashima, S. T 1992, 48, 633.
17. Subramanian, L. R.; Bentz, H.; Hanack, M. S 1973, 293.
18. Thompson, S. K.; Heathcock, C. H. JOC 1990, 55, 3004.
19. Queneau, Y.; Krol, W. J.; Bornmann, W. G.; Danishefsky, S. J. JOC 1992, 57, 4043.
20. Freskos, J. N.; Ripin, D. H.; Reilly, M. L. TL 1993, 34, 255.
21. Tsushima, K.; Araki, K.; Murai, A. CL 1989, 1313.
22. Holt, D. A.; Levy, M. A.; Oh, H.-J.; Erb, J. M.; Heaslip, J. I.; Brandt, M.; Lan-Hargest, H.-Y.; Metcalf, B. W. JMC 1990, 33, 943.
23. Wulff, W. D.; Peterson, G. A.; Bauta, W. E.; Chan, K.-S.; Faron, K. L.; Gilbertson, S. R.; Kaesler, R. W.; Yang, D. C.; Murray, C. K. JOC 1986, 51, 277.
24. Scott, W. J.; Peña, M. R.; Swärd, K.; Stoessel, S. J.; Stille, J. K. JOC 1985, 50, 2302.
25. Petrakis, K. S.; Nagabhushan, T. L. JACS 1987, 109, 2831.
26. (a) Stang, P. J. ACR 1978, 11, 107. (b) Stang, P. J.; Hanack, M.; Subramanian, L. R. S 1982, 85.
27. Shakespeare, W. C.; Johnson, R. P. JACS 1990, 112, 8578.
28. Hendrickson, J. B.; Bair, K. W. JOC 1977, 42, 3875.

Wayne E. Zeller

Illinois State University, Normal, IL, USA

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