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SummaryPerfluorotriethylamine is a good alternative reaction medium forLewis acid catalyzed reactions and it can be easily recycled by

simple extractive workup.

IntroductionOne of the most important issues in scientific society is the envi-

ronmental problem. Thus far, there have been increasing

demands for substitutes for toxic and/or harmful solvents like

CH2Cl

2.1 Recently, inert and less toxic fluorous (perfluorinated)

fluids have been recognized and are attracting attention as new

alternative solvents.2 However, it is still not clear what kind of

reactions to run in these solvents and how to run them. This fact

allowed us to survey the scope and limitations of the utility of

fluorous liquids as alternative reaction media for Lewis acid cat-alyzed reactions, which are of great current interest due to their

unique reactivities and selectivities. We examined the

HosomiSakurai reaction3 as a model reaction, and the results are

summarized in Table 1.

Results and discussionAs shown in Table 1, perfluorotrialkylamines were better reac-tion media than perfluorohexane4 and perfluoro-2-butyltetra-

hydrofuran (entries 14). In addition, perfluorotriethylamine was

Table 1 Results of the HosomiSakurai allylation in vari-

ous solvents

Entry R Solvent Yield (%)a

1 n-C5H

11Perfluorohexane 67

2 Perfluoro-2-butyltetrahydro-

furan 57

3 Perfluorotributylamine 78

4 Perfluorotriethylamine 90

5 CH2Cl

292

6 Hexanes 63

7 Neat 67

8 CH2CH

2Ph Perfluorotriethylamine 98

9 c-C6H

11Quantitative

a Isolated yield.

Organic reactions without an

organic mediumUtilization of perfluorotriethylamine as a reaction medium

Hirofumi Nakano and Tomoya Kitazume*

Department of Bioengineering, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama 226-

8501, Japan. E-mail: tkitazum@bio.titech.ac.jp

Received 5th October 1998

superior to perfluorotri-n-butylamine (entry 3 vs. 4) presumably

due to higher lipid solubility derived from the shorter perfluoro-alkyl chains, and turned out to be as appropriate a solvent as

CH2Cl

2which is commonly used in this reaction (entry 4 vs. 5).

Only modest yields were obtained when the reaction was carried

out in nonpolar hexanes (entry 6) or without solvent (entry 7).

These results clearly show that some solvent effects of perfluoro-

triethylamine promoted the reaction. Some comments are worth

noting, e.g. (1) the basicity of perfluorotrialkylamine is so low

that the amine does not interact with a strong Lewis acid like

TiCl4,5 (2) however, the amines polarity might be retained to

some extent,6 which might be as important a factor in the promo-

tion of reaction as lipophilicity. Althogh the lipid solubility of

perfluorotri-n-butylamine is lower than that of perfluorohexane,

perfluoro-2-butyltetrahydrofuran (critical solution temperaturesin mixtures with n-hexane are 59 C for perfluorotributylamine,

20 C for perfluorohexane and 29 C for perfluoro-2-butyl-

tetrahydrofuran)7 and hexanes, it was found to be a better reac-

tion medium. Among fluorous amines, perfluorotriethylamine,

which exhibits relatively high lipophilicity due to its short per-

fluoroalkyl chains and suitable boiling point, could be an ideal

alternative solvent. To the best of our knowledge, this is the first

application of perfluorotriethylamine as a reaction medium.

The catalytic version of this reaction8 using acetal in place of

aldehyde also proceeded smoothly (Fig. 1). Furthermore, recy-

Fig. 1 Catalytic allylation in perfluorotriethylamine.

cling of the solvents is under investigation from both environ-

mental and economical points of view. While perfluorotriethyl-

Ph OMe

OMeTMS

Ph

OMe

+TMSOTf (10 mol %)

0 C, then rt. 1h.quant.

(C2F5)3N

Green Chemistry February 1999 21

The search for replacements for halogenated solvents is a

key area for investigation, with many of these solvents

due to be phased out or banned completely. This report

describes the use of perfluorinated amines as an alterna-tive medium for reactions involving Lewis acid catalysts.

The solvent may be readily recovered and reused. SJT

Green Context

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amine shows some miscibility with organic materials, extractive

workup with ethyl acetate/water resulted in high recovery of the

reaction medium (90%). Successive reuse of the recovered sol-

vent in the same reaction without further purification yielded

amounts of product as high as in the first cycle (Fig. 2). This

Fig. 2 Recycling perfluorotriethylamine without purification.

result clearly shows that the highly hydrophobic character of the

perfluorinated material allows us to recycle directly the reaction

medium for highly moisture-sensitive reactions. This is another

merit of fluorous reaction media.

In conclusion, we have shown that perfluorotriethylamine is a

promising alternative reaction medium. Further studies to clarify

the scope and limitation of fluorous reaction media are activelyin progress in our group.

Notes and references1 For example: S. Kobayashi, T. Wakabayashi, S. Nagayama

and H. Oyamada, Tetrahedron Lett., 1997, 38, 4559; J. M.

Tanko and J. F. Blackert, Science, 1994, 263, 203; A. Ogawa

and D. Curran,J. Org. Chem., 1997, 62, 450.

2 D.-W. Zhu, Synthesis, 1993, 953; I. T. Horvth and J. Rbai,

Science, 1994, 266, 72; S. Halida and D. P. Curran, J. Am.

Chem. Soc., 1996, 118, 2531; S. G. DiMagno, P. H. Dussault

and J. A. Schultz, J. Am. Chem. Soc., 1996, 118, 5312; A.

Studer, S. Halida, R. Ferritto, S.-Y. Kim, P. Jeger, P. Wipf and

D. P. Curran, Science, 1997, 275, 823; A. Studer, P. Jeger, P.

Wipf and D. P. Curran, J. Org. Chem., 1997, 62, 2917;I. Klement, H. Ltjens and P. Knochel,Angew. Chem., Int. Ed.

Engl., 1997, 36, 1454; J. J. J. Juliette, I. T. Horvth and J. A.

Gladysz, ibid., 1997, 36, 1610; M.-A. Guillevic, A. M. Arif,

I. T. Horvth and J. A. Gladysz, ibid., 1997, 36, 1612; J.-M.

Vincent, A. Rabion, V. K. Yachandra and R. H. Fish, ibid.,

1997, 36, 2346; B. Betzemeier and P. Knochel, ibid., 1997, 36,

2623; M. Hoshino, P. Degenkolb and D. P. Curran, J. Org.

Chem., 1997, 62, 8341.

3 For reviews, see: A. Hosomi,Acc. Chem. Res., 1988, 21, 200;

I. Fleming, J. Dunogues and R. Smithers, Org. React., 1989,

37, 57.

4 99%; 85% n-isomer; bp = 57 C.

5 M. Gaensslen, U. Gross, H. Oberhammer and S. Rdiger,

Angew. Chem.,Int.Ed.Engl., 1992, 31, 1467.6 B. E. Smart, in Organofluorine Chemistry: Principles and

Commercial Applications, ed. R. E. Banks, B. E. Smart and

J. C. Tatlow, Plenum Press, New York, 1994.

7 U. Gross, G. Paske and S. Rdiger,J. Fluorine Chem., 1993,

61, 11.

8 T. Tsunoda, M. Suzuki and R. Noyori, Tetrahedron Lett.,

1980, 21, 71.

9 Typical procedure is as follows. Under a nitrogen atmosphere,

titanium tetrachloride (0.220 ml, 2 mmol) was added dropwise

to aldehyde (2 mmol) and allyltrimethylsilane (0.333 ml, 2.1

ml) in perfluorotriethylamine (4 ml) at 278 C. After comple-

tion of the addition, the dry iceacetone bath was removed and

the reaction mixture was stirred for 15 min at rt. The reactionwas quenched with 4 ml of water, and stirred for a few min-

utes. Then, 3.6 ml of fluorous solvent was recovered by three

phase extraction (organic layer: 4 ml of ethyl acetate). The

-C5H11 H

OTMS

n-C5H11

OH

+ TiCl4 (1.0 eq.)

(C2F5)3N

cycle 1: 90 %cycle 2: 92 %

organic layer was dried over anhydrous Na2SO4 and concen-

trated in vacuo. Purification of the residue by silica gel chro-

matography afforded the homoallyl alcohol.

Paper 8/08193J

22 Green Chemistry February 1999