[545-06-2]  · C2Cl3N  · Trichloroacetonitrile  · (MW 144.38)

(makes trichloroacetimidates from alcohols; trichloroacetimidates are used to introduce nitrogen into molecules via rearrangements1c and cyclizations; trichloroacetimidates are useful alkylating agents1d,e)

Physical Data: mp -42 °C; bp 83-84 °C; d 1.440 g cm-3.

Solubility: sol most organic solvents.

Form Supplied in: neat colorless liquid.

Analysis of Reagent Purity: 1H NMR, 13C NMR.

Handling, Storage, and Precautions: toxic lachrymator; use only in a fume hood. Reagent can be absorbed through the skin. Always wear gloves when handling this reagent.

Preparation of Trichloroacetimidates.

The imidates derived from the addition of alcohols to trichloroacetonitrile have become important and versatile intermediates in synthetic chemistry.1 Consequently the principal synthetic use of trichloroacetonitrile has been in the formation of these useful trichloroacetimidate intermediates. The imidates are most often prepared by simple addition of a sodium or potassium alkoxide to the electron-deficient trichloroacetonitrile (eq 1).1c,d,2 In certain cases, slight modifications of the above procedure are utilized.2d,3 The product imidates are isolable and, despite their propensity to rearrange,2b,e,4 can in some instances be purified by distillation2a,d,e or chromatography. Typically the addition reaction is sufficiently clean to use the imidates without further purification.2f

Rearrangement of Trichloroacetimidates.

The thermal rearrangement of imidates has been known for many years.2b,4 In 1974, Overman2c described a useful conversion of allylic alcohols to allylic amines utilizing a [3,3]-sigmatropic rearrangement of allylic trichloroacetimidates (eq 2).1c,2e In addition to simple thermolysis it was found that the rearrangement could be catalyzed at room temperature with either HgII or PdII salts.1c,5 As with many sigmatropic rearrangements, the reaction is stereoselective and produces double bonds of defined stereochemistry while efficiently transferring chirality.1c,5,6

A comparison of reaction conditions5b,c,d has shown that palladium catalysis is particularly effective in achieving complete chiral transfer (eq 3).5b Propargylic imidates also rearrange when heated in refluxing xylene.1c,7 The initially formed allene undergoes a series of tautomerizations so that amino 1,3-dienes are the ultimate products (eq 4).1c These dienes have found use in the Diels-Alder reaction.1c

Electrophilic Cyclization of Trichloroacetimidates.

Trichloroacetimidates derived from allylic8a,c-f and homoallylic8b,c alcohols undergo electrocyclic ring closure when treated with a source of I+ (eq 5).8c Cyclization can also be triggered via the Lewis acid-mediated opening of epoxides.9 In at least one case the imidate proved more reactive than related reactions using carbamates.9c These are useful methods for the stereoselective introduction of nitrogen into cyclic and acyclic systems.

Alkylation using Trichloroacetimidates.

Under mildly acidic conditions, alkyl trichloroacetimidates act as reasonable alkylating agents2f,10 toward heteroatom nucleophiles, most notably alcohols (eq 6). Alkyl groups which have been transferred include benzyl,2f,10a,b,d allyl,2f propargyl,10e and t-butyl.10c This methodology has been used to protect alcohols. The use of glycosyl trichloroacetimidates has found widespread use in the synthesis of oligosaccharides and glycoconjugates (eq 7).1d,e,11 This is a particularly powerful method for controlling stereochemistry at the anomeric position.

1. (a) Sandler, S. R.; Karo, W. Organic Functional Group Preparations; Academic: New York, 1972; Vol. 3, Chapter 8. (b) Patai, S. The Chemistry of Amidines and Imidates; Wiley: New York, 1975. (c) Overman, L. E. ACR 1980, 13, 218. (d) Schmidt, R. R. AG(E) 1986, 25, 212. (e) Schmidt, R. R. PAC 1989, 61, 1257.
2. (a) Cramer, F.; Pawelzik, K.; Baldauf, H. J. CB 1958, 91, 1049. (b) Cramer, F.; Hennrich, N. CB 1961, 94, 976. (c) Overman, L. E. JACS 1974, 96, 597. (d) Overman, L. E. JACS 1976, 98, 2901. (e) Clizbe, L. A.; Overman, L. E. OS 1978, 58, 4. (f) Wessel, H.-P.; Iverson, T.; Bundle, D. R. JCS(P1) 1985, 2247.
3. (a) Hauser, F. M.; Ellenberger, S. R.; Glusker, J. P.; Smart, C. J.; Carrell, H. L. JOC 1986, 51, 50. (b) Oehler, E.; Kotzinger, S. S 1993, 497.
4. (a) Mumm, O.; Möller, F. CB 1937, 70, 2214. (b) McCarty, C. G.; Garner, L. A. In The Chemistry of Amidines; Patai, S., Ed.; Wiley: New York, 1975; Chapter 4.
5. (a) Overman, L. E. AG(E) 1984, 23, 579. (b) Metz, P.; Mues, C.; Schoop, A. T 1992, 48, 1071. (c) Mehmandoust, M.; Petit, Y.; Larcheveque, M. TL 1992, 33, 4313. (d) Doherty, A. M.; Kornberg, B. E.; Reily, M. D. JOC 1993, 58, 795.
6. (a) Yamamoto, Y.; Shimoda, H.; Oda, J.; Inouye, Y. BCJ 1976, 49, 3247. (b) Isobe, M.; Fukuda, Y.; Nishikawa, T.; Chabert, P.; Kawai, T.; Goto, T. TL 1990, 31, 3327.
7. Overman, L. E.; Clizbe, L. A. JACS 1976, 98, 2352.
8. (a) Cardillo, G.; Orena, M.; Porzi, G.; Sandri, S. JCS(C) 1982, 1308. (b) Cardillo, G.; Orena, M.; Porzi, G.; Sandri, S. JCS(C) 1982, 1308. (c) Fraser-Reid, B.; Pauls, H. W. JOC 1983, 48, 1392. (d) Bongini, A.; Cardillo, G.; Orena, M.; Sandri, S.; Tomasini, C. JOC 1986, 51, 4905. (e) Cardillo, G.; Orena, M.; Sandri, S.; Tomasini, C. T 1986, 42, 917. (f) Sammes, P. G.; Thetford, D. JCS(P1) 1988, 111.
9. (a) Jacobsen, S. ACS 1988, B42, 605. (b) Schuerrle, K.; Beier, B.; Piepersberg, W. JCS(P1) 1991, 2407. (c) Hart, T. W.; Vacher, B. TL 1992, 33, 3009.
10. (a) Amouroux, R.; Gerin, B.; Chastrette, M. T 1985, 41, 5321. (b) Widmer, U. S 1987, 568 (c) Armstrong, A.; Brackenridge, I.; Jackson, R. F. W.; Kirk, J. M. TL 1988, 29, 2483. (d) Audia, J. E.; Boisvert, L.; Patten, A. D.; Villalobos, A.; Danishefsky, S. J. JOC 1989, 54, 3738, (e) Wei, S. Y.; Tomooka, K.; Nakai, T. T 1993, 49, 1025. (f) Bourgeois, M. J.; Montaudon, E.; Maillard, B. T 1993, 49, 2477.
11. (a) Nicolaou, K. C.; Daines, R. A.; Ogawa, Y.; Chakraborty, T. K. JACS 1988, 110, 4696. (b) Barrett, A. G. M.; Pilipauskas, D. JOC 1991, 56, 2787.

Patrick G. McDougal

Reed College, Portland, OR, USA

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