The Trifluoromethylacetophenone-N,N-dimethyltrimethylsilylamine Adduct - A New Shelf Stable Reagent for Nucleophilic Trifluoromethylation.

Abstract

The simple thermal addition product of N,N-dimethyltrimethylsilylamine with trifluoromethylacetophenone provides a shelf-stable reagent for nucleophilic trifluoromethylation of the carbonyl group.

nucleophilic trifluoromethylation - trifluoromethyl carbinols - aldehydes - ketones

References

1a Filler R. Kobayashi Y. Yagupolskii LM. Organofluorine Compounds in Medicinal Chemistry and Biomedical Applications   Elsevier; Amsterdam: 1993. 

1b Banks RE. Smart BE. Tatlow JC. Organofluorine Chemistry: Principles and Commercial Applications   Plenum Press; New York: 1994. 

1c Welch JT. Eswarakrishnan SE. Fluorine in Bioorganic Chemistry   John Wiley; New York: 1991. 

2 McClinton MA. McClinton DA. Tetrahedron  1992,  48:  6555 

3 Ruppert I. Schlich K. Volbach W. Tetrahedron Lett.  1984,  25:  2195 

4a Prakash GKS. Yudin AK. Chem. Rev.  1997,  97:  757 

4b Prakash GKS. Nucleophilic Perfluoroalkylation of Organic Compounds using Perfluorotrialkylsilanes, in Synthetic Fluorine Chemistry   Olah GA. Chambers RD. Prakash GKS. John Wiley; New York: 1992.  Chap. 10.

4c Singh RP. Shreeve JM. Tetrahedron  2000,  56:  7613 

5 Shono T. Ishifune M. Okada T. Kashimura S. J. Org. Chem.  1991,  56:  2 

6a Folléas B. Marek I. Normant J.-F. Saint-Jalmes L. Tetrahedron Lett.  1998,  39:  2973 

6b Folléas B. Marek I. Normant J.-F. Saint-Jalmes L. Tetrahedron  2000,  56:  275 

7a Russell J. Roques N. Tetrahedron  1998,  54:  13771 

7b Mispelaere C. Roques N. Tetrahedron Lett.  1999,  40:  6411 

8 Billard T. Bruns S. Langlois BR. Org. Lett.  2000,  2:  2101 

9 Abel EW. Crow JP. J. Chem. Soc. (A)  1968,  1361 

10 Boivin J. El Kaim L. Zard SZ. Tetrahedron Lett.  1992,  33:  1285 

11

Synthesis of 2: N,N-Dimethylaminotrimethylsilane (5 mL, 0.031 mol) and trifluoroacetophenone (4.34 mL, 0.031 mol) were added to a round bottom flask equipped with a reflux condenser. The neat mixture was heated in an oil bath at
110 °C for 16 h under a nitrogen atmosphere. The product was distilled between 117-118 °C/18 mmHg to give a clear oil (7.93 g, 87% yield). Calculated for C₁₃H₂₀F₃NOSi:
C, 53.59; H, 6.92; N, 4.81. Found: C, 53.45; H, 7.07; N, 4.80; IR(neat)/cm^-1: 2958, 2846, 2799, 1255, 1163, 1050. δ_H (300 MHz) 0.20 [9 H, s, Si-(CH₃)₃], 2.29 [6 H, d, J = 1, N-(CH₃)₂], 7.35 (3 H, m), 7.58 (2 H, m). δ_F (282 MHz) -71.3. δ_C (75 MHz) 1.7 [Si-(CH₃)₃], 39.9 [N-(CH₃)₂], 93.1 (q, J = 28.5,
C-CF₃), 124.2 (q, J = 292, CF₃), 127.5, 127.8, 128.5, 139.2.

12

Representative procedure: Dry, distilled THF (5 mL) was added to a round bottom flask equipped with a reflux condenser, containing pre-dried caesium fluoride (15 mg, 0.098 mmol). Benzaldehyde (100 mL, 0.98 mmol)was then added, followed by 2 (466 mL, 1.97 mmol), and the mixture was heated to reflux for 20 h. Hydrochloric acid (2 M, 1 mL) was then added and stirring was continued for 3 h. The mixture was diluted with diethyl ether, washed with water (3 × 5 mL), sat. brine (5 mL), dried with MgSO₄, and the solvent removed in vacuo. The crude product was purified by flash chromatography on silica gel using diethyl ether-hexane (1:9) to give the product as a yellow oil (139 mg, 89%) whose properties were identical with those reported in the literature.

13a Prakash GKS. Olah GA. Mloston G. Wiedemann J. Heiner T. Angew. Chem. Int. Ed.  1998,  37:  820 

13b Maggiarosa N. Tyrra W. Naumann D. Kirij NV. Yagupolskii YL. Angew. Chem. Int. Ed.  1999,  38:  2252