Organic Syntheses Procedure

^
Top

Org. Synth. 1997, 74, 77

DOI: 10.15227/orgsyn.074.0077

PYRIDINE-DERIVED TRIFLATING REAGENTS: N-(2-PYRIDYL)-TRIFLIMIDE AND N-(5-CHLORO-2-PYRIDYL)TRIFLIMIDE

[Methanesulfonamide, 1,1,1-trifluoro-N-2-pyridinyl-N-[(trifluoromethyl)sulfonyl]-] and Methanesulfonamide, N-(5-chloro-2-pyridinyl)-1,1,1-trifluoro-N-[(trifluoromethyl)sulfonyl]-]

Submitted by Daniel L. Comins, Ali Dehghani, Christopher J. Foti, and Sajan P. Joseph¹.

Checked by Maria A. Cichy and Amos B. Smith, III.

1. Procedure

A. N-(2-Pyridyl)triflimide (1). A 2-L, two-necked, round-bottomed flask equipped with a mechanical 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 triflic anhydride (125 g, 74.54 mL, 0.443 mol) (Note 5) in 150 mL of CH₂Cl₂ is added dropwise via a cannula over 3.5 hr with vigorous stirring. After the solution is stirred for 2 hr at −78°C, the cooling bath is removed and stirring is continued at room temperature for 19 hr. The reaction mixture is quenched with 50 mL of cold water and the layers are separated. The aqueous layer is extracted with CH₂Cl₂ (4 × 50 mL). The combined organic extracts are washed with cold aqueous 10% sodium hydroxide (1 × 150 mL), 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) is obtained as a white solid.

B. N-(5-Chloro-2-pyridyl)triflimide (2). Using the same procedure as described above, 2-amino-5-chloropyridine (27.13 g, 0.211 mol) (Note 8) is converted to N-(5-chloro-2-pyridyl)triflimide (mp 47–48°C) (61.84 g, 75%, bp 88–100°C/0.15 mm) (Note 9).

2. Notes

1. A magnetic stirrer can be used with a large stirrer bar and 1.5 L of dichloromethane.

2. 2-Aminopyridine was purchased from Aldrich Chemical Company, Inc., and used without further purification.

3. Anhydrous pyridine was purchased from Aldrich Chemical Company, Inc., and kept over 3 Å molecular sieves for two days prior to use.

4. Anhydrous dichloromethane was purchased from Aldrich Chemical Company, Inc., and used without further purification.

5. Triflic anhydride was purchased from Aldrich Chemical Company, Inc., and used as such.

6. Sometimes a second distillation is needed to obtain pure compound.

7. The spectral properties of N-(2-pyridyl)triflimide are as follows: IR (nujol) cm⁻¹: 1590, 1570, 1460, 1220, 1215, 1120, 1040, 990, 940, 910, 880, 735, 710; ¹H NMR (300 MHz, CDCl₃) δ: 7.46–7.55 (m, 2 H), 7.91–7.97 (dt, 1 H, J = 8.06, 2.2), 8.63 (dd, 1 H, J = 4.4, 1.46); ¹³C NMR (75 MHz, CDCl₃) δ: 112.80, 117.10, 121.39, 125.50, 125.69, 126.79, 139.71, 145.98, 150.31.

8. 2-Amino-5-chloropyridine was purchased from Aldrich Chemical Company, Inc., and used without further purification.

9. The spectral properties of N-(5-chloro-2-pyridyl)triflimide are as follows: IR (nujol) cm⁻¹: 1570, 1460, 1230, 1215, 1125, 1010, 925, 905, 745, 730; ¹H NMR (300 MHz, CDCl₃) δ: 7.42 (d, 1 H, J = 8.8), 7.90 (dd, 1 H, J = 8.8, 2.2), 8.58 (d, 1 H, J = 2.93); ¹³C NMR (75 MHz, CDCl₃) δ: 112.77, 117.06, 121.36, 125.66, 126.18, 135.84, 139.33, 143.82, 149.31.

Handling and Disposal of Hazardous Chemicals

The procedures in this article are intended for use only by persons with prior training in experimental organic chemistry. All hazardous materials should be handled using the standard procedures for work with chemicals described in references such as "Prudent Practices in the Laboratory" (The National Academies Press, Washington, D.C., 2011 www.nap.edu). All chemical waste should be disposed of in accordance with local regulations. For general guidelines for the management of chemical waste, see Chapter 8 of Prudent Practices.

These procedures must be conducted at one's own risk. Organic Syntheses, Inc., its Editors, and its Board of Directors do not warrant or guarantee the safety of individuals using these procedures and hereby disclaim any liability for any injuries or damages claimed to have resulted from or related in any way to the procedures herein.

3. Discussion

Vinyl triflates are important intermediates, since they can be used as synthetic precursors for vinyl cations and alkylidene carbenes, and as substrates for regiospecific coupling reactions.² ³^,⁴ ⁵ ⁶ ⁷ ⁸ ⁹ ¹⁰ Vinyl triflates are also valuable intermediates in a mild, two-step procedure for the deoxygenation of ketones.¹¹ ¹²^,¹³ These new triflating reagents are highly reactive and easy to prepare and handle.¹⁴ When compared with other triflating reagents, the vinyl triflate can in most cases be made at lower temperatures, and any excess reagent and by-products can be removed by washing with cold aqueous 5% sodium hydroxide solution. The utility of the pyridine-derived triflating reagents is illustrated by the examples in the Table.¹⁴ Recently reagent 2 has been used in the total syntheses of (−)-porantheridine¹⁵ and trans-decahydroquinoline alkaloid (+)-219 A.¹⁶

TABLE¹⁴
PREPARATION OF VINYL TRIFLATES FROM KETONE ENOLATES
Ketone	Base; Reagent; Condition	Product	Yield, %


	NaHMDS; 2 −78°C, 2 hr		92
	LDA; 1 −78°C, 3 hr		76
	LDA; 2 −78°C, 2 hr		77
	LDA; 2 −78°C, 3 hr		79
	LDA; 1 −78°C, 2 hr; −23°C, 4 hr; −16°C, 12 hr		76
	LDA; 2 −78°C, 2 hr		86
	LDA; 2 −78°C, 2 hr		88
	L-Selectride; 2 −23°C, 2 hr		80

References and Notes

Department of Chemistry, North Carolina State University, Raleigh, NC 27695–8204.
For reviews see: (a) Stang, P. J. Acc. Chem. Res. 1978, 11, 107;
Stang, P. J.; Hanak, M.; Subramanian, L. R. Synthesis 1982, 85.
Scott, W. J.; Pe-a, M. R.; Swärd, K.; Stoessel, S. J.; Stille, J. K. J. Org. Chem. 1985, 50, 2302;
Tamaru, Y.; Ochiai, H.; Nakamura, T.; Yoshida, Z. Tetrahedron Lett. 1986, 27, 955;
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. J. Org. Chem. 1986, 51, 277;
Cacchi, S.; Morera, E.; Ortar, G. Synthesis 1986, 320;
McCague, R. Tetrahedron Lett. 1987, 28, 701;
Arcadi, A.; Burini, A.; Cacchi, S.; Delmastro, M.; Marinelli, F.; Pietroni, B. Synlett 1990, 47, and references therein;
for recent applications in total syntheses of natural products, see: Corey, E. J.; Kigoshi, H. Tetrahedron Lett. 1991, 32, 5025; Smith, A. B., III; Sulikowski, G. A.; Sulikowski, M. M.; Fujimoto, K. J. Am. Chem. Soc. 1992, 114, 2567.
Jigajinni, V. B.; Wrightman, R. H. Tetrahedron Lett. 1982, 23, 117;
Subramanian, L. R.; Martinez, A. G.; Fernandes, A. H.; Alvarez, R. M. Synthesis 1984, 481.
The submitters successfully used this reduction procedure in their recent synthesis of (±)-pumiliotoxin C, see: Comins, D. L.; Dehghani, A. Tetrahedron Lett. 1991, 32, 5697.
Comins, D. L.; Dehghani, A. Tetrahedron Lett. 1992, 33, 6299.
Comins, D. L.; Hong, H. J. Am. Chem. Soc. 1993, 115, 8851.
Comins, D. L.; Dehghani, A. J. Org. Chem. 1995, 60, 794.

Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)

brine

Methanesulfonamide, 1,1,1-trifluoro-N-2-pyridinyl-N-[(trifluoromethyl)sulfonyl]-]

(−)-porantheridine

sodium hydroxide (1310-73-2)

pyridine (110-86-1)

dichloromethane,
CH₂Cl₂ (75-09-2)

2-aminopyridine (504-29-0)

magnesium sulfate (7487-88-9)

argon (7440-37-1)

triflic anhydride (358-23-6)

vinyl triflate

N-(2-Pyridyl)triflimide,
N-(2-PYRIDYL)-TRIFLIMIDE (145100-50-1)

N-(5-Chloro-2-pyridyl)triflimide,
Methanesulfonamide, N-(5-chloro-2-pyridinyl)-1,1,1-trifluoro-N-[(trifluoromethyl)sulfonyl]- (145100-51-2)

2-amino-5-chloropyridine (1072-98-6)

trans-decahydroquinoline

Notes

References/EndNotes

Article Compounds

Authors