Rearrangement enamines from ketone

Imines derived from ketones with an a-methylene group can react via their enamine tautomers, and mixtures of triazoles are also isolated from these systems. The triazoline adducts of the enamine tautomers are aromatized by treating with acid, and in these conditions the triazoline appears to undergo a Dimroth rearrangement before elimination of the amine, because two triazoles are obtained, one of which has... 

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). 

Mamedov VA, Zhukova NA, Beschastnova TN, Syakaev VV, Krivolapov DB, Mironova EV, Zamaletdinova AI, Rizvanov IKh, Latypov ShK (2015) Rearrangement of quinoxalin-2-ones when exposed to enamines generated in situ from ketones and ammonium acetate method for the synthesis of l-(p5urolyl)benzimidazolones. J Org Chem 80(3) 1375-1386. doi 10.1021/ jo502135d... 

Finally a general approach to synthesize A -pyrrolines must be mentioned. This is tl acid-catalyzed (NH4CI or catalytic amounts of HBr) and thermally (150°C) induced tea rangement of cyclopropyl imines. These educts may be obtained from commercial cyan> acetate, cyclopropyl cyanide, or benzyl cyanide derivatives by the routes outlined below. Tl rearrangement is reminiscent of the rearrangement of 1-silyloxy-l-vinylcyclopropancs (p. 7 83) but since it is acid-catalyzed it occurs at much lower temperatures. A -Pyrrolines constitut reactive enamines and may be used in further addition reactions such as the Robinson anei lation with methyl vinyl ketone (R.V. Stevens, 1967, 1968, 1971). 

Cross-conjugated dienones are quite inert to nucleophilic reactions at C-3, and the susceptibility of these systems to dienone-phenol rearrangement precludes the use of strong acid conditions. In spite of previous statements, A " -3-ketones do not form ketals, thioketals or enamines, and therefore no convenient protecting groups are available for this chromophore. Enol ethers are not formed by the orthoformate procedure, but preparation of A -trienol ethers from A -3-ketones has been claimed. Another route to A -trien-3-ol ethers involves conjugate addition of alcohol, enol etherification and then alcohol removal from la-alkoxy compounds. 

A similar sequence of reactions takes place with the enamlnes of cyclic ketones (55-57) the initially formed unstable cyclobutene rearranges with insertion of two carbon atoms into the ring. A wide variety of cyclic ketones have been allowed to react in this way. For instance, the enamine (75) gave 76 on reaction with dimethyl acetylenedicarboxylate in refluxing toluene (55) and the heterocyclic enamine (77) obtained from dihydro-3-(2H)-... 

From the addition reaetions of acrolein- to aldehyde-derived enamines, aminotetrahydropyrans have been obtained. On heating, these products rearranged to enaminoaldehydes in examples where the initial enamine was disubstituted (320,321). The addition of acrolein to ketone derived enamines has been applied to syntheses of heterocyclic and bridged bieyclic compounds (301,321-323). 

Aliphatic c a -dibromo ketones, such as 2,4-dibromopentan-3-one (262), react with primary amines RNH2 (R = Me, Et, Pr, /-Pr or t-Bu) to give mixtures of imines 263 and lesser amounts of diimines 264. l,3-Dibromo-l-phenylpropan-2-one yields only the amide 265, the product of a Favorskii rearrangement. The nature of the products from aliphatic amines and cyclic a,a -dibromo ketones depends on ring size the cyclohexanone derivative 266 gave Favorskii amides 267 (R = Pr, /-Pr or t-Bu), while trans-2,5-dibromocyclopentanone afforded the enamines 268 (R = /-Pr or t-Bu) (equation 95)296. 

The Willgerodt Reaction allows the synthesis of amides from aryl ketones under the influence of a secondary amine and a thiating agent. The mechanism involves the formation of an enamine which undergoes thiation, and the carbonyl group migrates to the end of the chain via a cascade of thio-substituted iminium-aziridinium rearrangements. 

Similar a,a -annulations were achieved from reaction of oc,/ -unsaturated acid chlorides with cyclic ketone enamines which afforded bicyclo[3.3.1]nonane-2,9-diones41,60 65 or bicyclo[4.3.1]decanones66. In this reaction, 7V-acylation of the enamine 109 occurs as the first step giving 110, followed by a [3,3] sigmatropic rearrangement to a ketene intermediate (111). Ketene 111 subsequently cyclized via 112 to a bicyclic immonium salt (113) which after hydrolysis gave the corresponding dione 11463. If there is an axially oriented electrophilic substituent at C-4 of the enamine (for example, R = COPh) the enolate anion 115 may cyclize to an adamantane derivative 116 (equation 20). 

Reaction with enamines and related substances. Brannock el al. found that the enamines derived from acyclic aldehydes and ketones react with dimethyl acetylene-dicarboxylate to give products derived by rearrangement of cyclobutenes initially formed by 1,2-cycloaddition. Thus, N,N-dimethylisobutcnylamine (1) reacts with dimethyl acetylenedicarboxylate in refluxing ether to give dimethyl 2-dimethylamino-methylenc-3-isopropylidencsuceinate (2) in 49 % yield. 

In 1996, the same group 87) reported further work on the synthesis of indole analogues of the cephalotaxine ring system (Scheme 52). The key intermediate in this ring-expansion approach, bromoiminium ion 300, was prepared in three steps from tryptamine and the chloro diester 298 via enamine 299. On treatment with several bases, the iminium ion 300 underwent rearrangement, presumably via the intermediate alkoxide 301, to give the azepinone derivative 302, which was reduced with sodium borohydride to a mixture of isomeric alcohols 303. The alcohols 303 underwent rapid intramolecular cyclization when treated with a 95% solution of sulfuric acid to yield pentacyclic ketone 304. 

Concerted symmetry-allowed [3,3] sigmatropic rearrangements of enamines have been reported One example is the Cope rearrangement 197 (obtained easily from the methyl vinyl ketone dimer 196 by reaction with pyrrolidine on heating to 250 °C) which leads to 2-pyrrolidino-4-acetylcyclohexene 198 (equation 21). Clai-sen , aza-Claisen and aza-Cope rearrangements have also been reported. 

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