Keteniminium salts

A review of the mechanism of thermal 2 + 2-cycloadditions of activated alkenes to allenes and ketenes has been published. " Stereoselective intramolecular 2 + 2-cycloadditions of alkene-keteniminium salts (19) derived from L-glutamic salts yield... 

Reaction of an alkene with keteniminium salts resulted in [2 + 2]-cycloaddition reactions (see Section 1.3.5.3). Hydrolysis of the intermediate cyclobutanone iminium salts 3 gave the cy-clobutanone 4.- 12 316 The cyclobutanone iminium salts are usually not isolated since they hydrolyze on aqueous workup. 

Intramolecular [2+2 cycloadditions ofketeniminium triflates. Two laboratories1,2 report that unsaturated keteniminium salts, generated from an unsaturated amide with 1 equiv. each of triflic anhydride and collidine, undergo intramolecular [2 + 2]cycloadditions. 

Keteniminium salts are more electrophilic than ketenes and are thus able to react with less nucleophilic olefins. Ketoketeniminium salts can be conveniently prepared from the corresponding a-chloroenamines and Lewis acids.3 However, the method cannot be applied well to the preparation of the less stable aldoketeniminium salts. 

This transformation is in general not easily achieved and therefore, the first versions of this reaction involved the much more electrophilic keteniminium salts [81-83], usually generated from carboxamides (Scheme 21). 

Asymmetric synthesis of cyclobutanonesf The co-unsaturated keteniminium salts (a) formed from amides (2) derived from chiral R,R-1 undergo intramolecular... 

A computational study of thermal [2+2] cycloaddition reactions between imines and keteniminium salts toward azetidine derivatives has been reported (Scheme 73) <1999JOC1831>. 

Cycloaddition Reactions. Chiral acrylamides derived from pyrrolidines (2) or (3) undergo stereoselective [4 + 2] cycloaddition reactions with a variety of cyclic dienes. Similarly, nitroso compounds derivatized with pyrrolidine (2) and generated in situ give cycloadducts with a high degree of stereoselectivity (eq 6). Intramolecular [2 + 2] cycloadditions involving pyrrolidine-derived keteniminium salts have been shown to produce chiral cyclobutanones. ... 

Stereoselective Diels-Alder reactions have been performed variously, using chirally modified sulfines as dienophiles, chiral ynamines, SMP enamines, SMP acrylamides, and the in situ preparation of SMP A-acylnitroso dienophiles. The [2 + 2] cycloaddition reactions of chiral keteniminium salts obtained from SMP amides with alkenes have been studied. ... 

AZETIDINIMINIUM SALTS FROM KETENIMINIUM SALTS AND IMINES... 

P-Disubstituted a-chloroenamines are readily converted into the corresponding keteniminium salts (33) in the presence of a Lewis acid (equation 68). Silver tetrafluoroborate, zinc, tin and aluminum chlorides have been successfully used. 3-Disubstituted keteniminium salts have been isolated and characterized. " Unlike the corresponding ketenes, they do not dimerize or polymerize. However, they readily undergo [2 + 2] cycloaddition reactions with unsaturated substrates. ... 

While cycloadditions of imines with ketenes or their precursors often produce cis P-lactams, the corresponding reactions of keteniminium salts are trans stereoselective (equations 70 and 71). 0 222 It is not clear whether the trans stereoselectivity is kinetic or results from an equilibration of 2-azetidiniminium salts under the basic conditions used in both cycloaddition and hydrolysis steps. 

For a review see L. Ghosez and J. Marchand-Brynaert, a-Halo Enamines and Keteniminium Salts in H. Bohme and H. G. Viehe, Eds., Iminium Salts in Organic Chemistry, Part 1 Vol, 9 m the series Advances in Organic Chemistry, E. C. Taylor, Ed., John Wiley Sons, Wiley-Interscience, New York, 1976, p. 421. 

Snider, B. B. Intramolecular cycloaddition reactions of ketenes and keteniminium salts with alkenes. Chem. Rev. 1988, 88, 793-811. 

The thermal [2 + 2J cycloaddition of cumulenes with alkenes, imines, and carbonyl compounds is one of the most useful routes to four-membered ring compounds. Ketenes and keteniminium salts add to alkenes to give cyclobutanones (Houben-Weyl Vol. IV/4 pp 174 205) 41 al-lenes add to alkenes to give methylenecyclobutanes (Houben-Weyl Vol. IV/4 pp 151-173), ketenes add to carbonyl compounds to give //-lactones (Houben-Weyl Vol. VI/2 pp 520-527), ketenes add to imines to give /1-lactams, and isocyanates add to alkenes to give //-lactams (Houben-Weyl Vol. V/lb p 1098). 

Intermolecular Cycloadditions of Keteniminium Salts with Alkenes... 

Keteniminium salts arc an attractive alternative to ketenes for cycloaddition with alkenes to give cyclobutanones31-32. Keteniminium salts do not dimerize and are more electrophilic than ketenes. They can be easily prepared by treatment of a dialkyl amide with 2,4,6-trimethylpyri-dine (collidine) and triflic anhydride in an inert solvent or from an a-haloenamine and a Lewis acid. The cycloadditions of keteniminium salts with alkenes are stepwise, not concerted, so that products from syn addition to the alkene are not always obtained stereoselectively. Of greater concern is the fact that the major product from alkenes which can form a tertiary carbocation is the Kriedel-Crafts product. The cycloaddition procedure is therefore limited to mono- and 1,2-disubstituted alkenes. 

Keteniminium salts offer greater opportunity for asymmetric induction than ketenes, since there are tw o substituents on the nitrogen of keteniminium salts which are not present on the oxygen of ketenes. Introduction of chiral substituents onto the nitrogen provides an efficient method for controlling the stereochemistry of the cycloaddition32. Initial studies were carried out with keteniminium salts derived from proline. 

Keteniminium salt la gives cycloadduct 2a with 55% ee. Dimethylketeniminium salt lb gives cyclobutanone 3b, which has the opposite configuration to 2a, with >97% ee33. 

Acetyl-2-(methoxymethyl)-pyrrolidine is converted into 2-(methoxymethyl)-1-vinylidenepyrrolidinium triflate by treatment with 1 equiv of triflic anhydride (added over a period of 6 h) in CH2C12 at reflux in the presence of 1.2 equiv of collidine. The keteniminium salt 1 a is trapped in situ by 5 equiv of cyclopentene to give 2 and 3, after hydrolysis in water overnight yield 30% d.r. (2/3) 77 23. The enantiomeric excess (55%) and absolute configuration are determined by comparison with an authentic sample. 

High diastereoselectivity is also obtained with keteniminium salts 7, obtained from (—)-ephedrine. and 8. obtained from (— )-2-methylpyrrolidine, indicating that the methoxy group is not important. 

Examination of models for the transition state 9 indicates that the cyclopentene approaches from the less hindered face of the keteniminium salt and that an oletlnic carbon attacks the y/i-hybridized keteniminium carbon to give intermediate 10, which closes to iminium salt 11, giving cyclobutanone 3 b on hydrolysis. 

Keteniminium salt lb reacts with ( )-2-butene to give the /ran.Mctramethylcyclobutaniminium salt exclusively with d.r. (trans eis) >97 333a. Hydrolysis occurs with partial isomerization at the carbon a to the carbonyl group giving a transjeis mixture of 2,2,3,4-tetramethylcyclobu-... 

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