A-chloroenamine

In the Meth-Cohn quinoline synthesis, the acetanilide becomes a nucleophile and provides the framework of the quinoline (nitrogen and the 2,3-carbons) and the 4-carbon is derived from the Vilsmeier reagent. The reaction mechanism involves the initial conversion of an acylanilide 1 into an a-iminochloride 11 by the action of POCI3. The a-chloroenamine tautomer 12 is subsequently C-formylated by the Vilsmeier reagent 13 derived from POCI3 and DMF. In examples where acetanilides 1 (r = H) are employed, a second C-formylation of 14 occurs to afford 15 subsequent cyclisation and... 

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. 

CHLOROCYCLOPROPYLIDENE METHYL ESTER (82979-45-1) 69, 148 (Chlorodimethylsilyl)methyl chloride, 69. 98 a-Chloroenamines, 66, 119... 

Obviously, the elimination goes through a-chloroenamines, which have themselves become useful synthones 70,71). Using two or more equivalents of a base, ynamines are formed in a straightforward manner (38, 39) 66,72). 

Amide should be first transformed to its hydrochloride in order to cut down the formation of a-chloro-jf(-chlorocarbonyl enamines 72,73). The method is very general but the choice of experimental conditions and of the base is critical and yields may vary strongly depending on the case (39). There is also one side-reaction which can hardly be avoided the ynamine already formed reacts with the yet unreacted amide chloride, the a-chloroenamine 70) or even with the tert-amine hydrochloride to form the very stable cyclobutene cyanines and/or allenamidinium salts. These by-products have an interest of their own and will be discussed later. Formation of these salts may strikingly lower the yield of ynamines, but because of their salt character they are not harmfull during the work-up72). 

Grignard reagents are not enough basic to abstract a vinylic hydrogen, nor do they participate in halogen metal exchange. As shown, they instead substitute the reactive chlorine atom in a-chloroenamines. More recent work has shown that 87 a, R = Me can be obtained from co-chloroacetophenone and tris-dimethylamino) arsine in 86 % yield I61). 

Activation of a carboxylic acid by reaction with a chloroenamine is reported to facilitate synthesis of ketones even with acids containing reactive functional groups [14], but detailed confirmation is lacking. 

Simple enamines cannot be deprotonated directly at the a-position due to their low acidity, but starting from a-chloroenamines 685, a-lithioenamines 686991 have been prepared by chlorine-lithium exchange using an arene-catalyzed lithiation992. The treatment of compounds 685 with an excess of lithium and a catalytic amount of 4,4 -di-tert-butylbiphenyl (DTBB) in THF at —90 °C allowed the preparation of intermediates 686, which were trapped with a variety of electrophiles (Scheme 177). For aldol reactions, the arene-catalyzed lithiation has to be performed in the presence of aldehydes (Barbier conditions) at —40 °C. These adducts were transformed into a-hydroxy ketones after acid hydrolysis with hydrochloric acid or silica gel. 

Sterically hindered enamines can be synthesized from an a-chloroenamine by treating it with t-butyllithium at — 70 °C and then adding water516 (equation 34). N-Benzoylhep-... 

Activation of allylic and propargylic alcohols. These alcohols can couple with Grignard reagents in the presence of an a-chloroenamine. For this purpose the related reagent l-chloro-2-methyl-N,N-tetramethylenepropenyIamine (2) is more effective than 1. 

The enamine-azide 1,3-dipolar cycloaddition has been found to be thermally reversible, e.g. (282) (283) (tsjhcsos). 4//-Triazoles (284), formed from sodium azide and a-chloroenamines bearing methoxycarbonyl and alkyl groups at the /3-position, give on thermolysis aromatic triazoles (285) and/or 3-amino-2//-azirines (286). On photolysis only azirines (286) are obtained (8occ94o). 

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. ... 

The nature of the anion associated with the iminium salt appears to play an important role in the diastereoselectivity of the reaction. 2 Thus while tetramethyl-a-chloroenamine (39) gives a p-lactam in high optical purity, the corresponding tetramethylketeniminium tetrafluoroborate (40) reacts with almost no diastereoselection (Scheme 41). 

Methoxyallyl cation (5a Y = OMe), derived from 2-methoxyallyl bromide (4a X = Br, Y = OMe) and silver trifluoroacetate in the presence of sodium carbonate, reacts with benzene, toluene, p-xylene or mesitylene. 2-Ethoxyallyl alcohol (4c X = OH, Y = OEt) in the presence of trifluoroacetic anhydride generates the 2-ethoxyallyl cation (5c Y = OEt). 2-Ethoxyallyl alcohol (4c) is probably more advantageous than the corresponding 2-methoxyallylic species (4a Y = OMe) because dealkylation of the intermediary oxonium ion seems to be less facile, and the ethyl enol ether is more nucleophilic than the methyl enol ether. Treatment of cyclic a-chloroenamines (4f X = Cl, Y = morpholino) and (4g X = Cl,... 

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