Tosylated enamines

Synthesis of the title compound is representative of a number of syntheses of nonaromatic nitrogen heterocycles via Pd(Ill-catalyzed amination of olefins. These tosylated enamines are not readily available by standard synthetic methods, and show potential for further functionalization of the heterocycle. The saturated amine can be synthesized from the title compound by hydrogenation of the double bond followed by photolytic deprotection. ... 

A, A -BOC-protected 1,4-dihydropyrazine was prepared by dimerization of A -BOC-N-tosylated enamine (Scheme 49) <2004T8489>. 

Cyclization of aliphatic amino-olefins may be achieved by first converting the amine into the corresponding toluene-p-sulphonamide, followed by intramolecular Pd -catalysed cyclization. In this way good yields of cyclic tosylated enamines have been obtained, which in principle can be used further to introduce additional functionality. The same paper also describes the mild photolytic cleavage of the A -tosyl group. 

Tosyl azide reacts differently to give sulfonamide derivatives 134). The morpholine enamine from dibenzylketone (196) for instance reacted with tosylazide to give 197 and phenyldiazomethane (198), which was trapped with acetic acid giving benzyl acetate 134). 

The ring-opening process leading to 164 (route a) is analogous to that which has been demonstrated to follow the cycloadditions of tosyl azide to certain enamines . Similar results have been reported for the reaction of 2,3-diphenylcyclopropenone with 2-diazopropane . Other 1,3-dipolar cycloadditions with thiirene dioxides could also be affected (see below). 

Fairly complex approaches have been used to construct thiazoles substituted with an enamine group. The cyclocondensation of l-tosyl-2,2-dichloroethenyl isothiocyanate 21 with various enamines such as 22 affords enamino substituted thiazoles such as 23 in high yields <00MI109>. 

The glutamic moiety of TNP-351, a pyrrolo[2,3-d]pyrimidine glutamic acid derivative, and related compounds have been transformed into their A-co-masked ornithine analogs which show remarkable antifolate activity <00CPB1270>. The reaction of the heterocyclic enamine 77 with tosyl azide leads to the tosylimino derivative of 1,2,4-triazolo[l, 5-a]pyrimidine 79. Extrusion of nitrogen from the primary adduct 78 is followed by a 1,2-shift of a methyl group to yield 79 <00JHC195>. 

Junjappa and co-workers (9) reported the cycloaddition of sodium azide to the polarized ketene-(5,5)-acetal 33 to give the tiiazole 35 they also reported an intermolecular cycloaddition of tosyl azide 37 with the enamine 36 to give an unstable triazoline intermediate 38. Ring opening 38 followed by a Dimroth rearrangement afforded the triazole 41 (Scheme 9.9). 

The reaction of N,N- dimethylaniline with pyridine (equation 55) should also be considered in this category. Enamines usually attack acylated N- oxides at position 2 unless it is blocked, as in 2-methylquinoline 1-oxide, when attack takes place at C-4. Methyl /3-aminocrotonate attacks quinoline and isoquinoline AT-oxides at the position a to the N- oxide function in the presence of tosyl chloride (78JHC1425). However, pyridine and 2-methylpyridine 1-oxides react at the 4-position (equation 142). A low yield of by-product (242) is formed in each case, probably as a result of self-condensation of methyl /3-aminocrotonate. 4-Hydroxyquinoline 1-oxide is exceptional in that it reacts with an enamine in the presence of tosyl chloride at the /3-position (Scheme 170) (B-71MI20500). 5-Amino-3-methylisoxazole reacts with quinoline 1-oxide at the a-position, and the product can be degraded, to afford ultimately 2-methylquinoline (Scheme 171) (78CPB2759). 

Reduction of unsaturated halides 0-78 Reduction of allylic alcohols 0-82 Reductive cleavage of enamines 0-86 Coupling of vinylic halides 0-87 Coupling of unsaturated halides with organometallic reagents 0-88 Coupling of allylic halides, tosylates, or acetates... 

An unequivocal synthesis of (637), protected as its A-2 -acetyl derivative (643), was successfully accomplished as shown in Scheme 3.140 [40]. Pyruval-dehyde dimethylacetal was first converted into its enamine (108). Condensation of (108) with the O-tosyl derivative of oximinomalononitrile gave the azadiene (638), which was converted to 2-amino-3-cyano-6-dimethoxymethyl-pyrazine (639) with ammonia. This latter compound was condensed with guanidine and the product (640) hydrolyzed first with base (to remove the 4-amino group) and then with acid to give pterin-7-carboxaldehyde (641). Acetylation of (641) followed by condensation with di-t-butyl p-aminobenzoyl-glutamate (235), reduction and hydrolysis gave (643). 

Tosyl isothiocyanate adds to the dimethylamine or piperidine enamines of isobutyr-aldehyde to form isolable betaines 4, which in non-polar solvents are in equilibrium with (tosylimino)thietanes 520 (equation 3). 

The [3 + 2] cycloaddition of the azoalkene 114 to enamines results in transient azomethine imines 115, which are transformed into tricyclic A-tosyl 1-aminopyrroles 116 on heating (equation 51)72. 

The reaction of tosyl isocyanate with 2-methyl- 1-dimethylaminopropene yields the betaine 330. In contrast, the betaine formed from the less basic enamine 331, derived from TV-methylaniline, adds a further molecule of the isocyanate to afford the hex-ahydropyrimidinedione 332 (equation 134)163. 

Nitrones (268), derived from ketones, undergo a Beckmann-like rearrangement when treated with tosyl chloride in pyridine. Unlike the Beckmann rearrangement, however, the reaction is independent of the nitrone configuration, and shows a preference for vinyl migration. The consequence, for a 4-en-3-one derivative, is the formation of the unusual enamine-lactam (270). The hydroxyl-amino-O-tosylate derivative (269) is considered a likely intermediate (see also Part II, Chap. 2, p. 353). 

The cleavage of the triazolines formed by the addition of azides to oxo-enamines has already been mentioned in section II.B.3. This cleavage can be applied to the synthesis of diazo compounds unavailable otherwise. a-Diazobutyraldehyde (105) was obtained for the first time from a-ethyl- -dimethylaminoacraldehyde (104) and tosyl or picryl azide... 

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