Acyl enamine

The preparation of enamines by reduction of aromatic heterocyclic bases and their quaternary salts or of lactams is not the most useful approach (97). The lithium aluminum hydride reduction of N-acyl enamines has been used with both fruitful and unsuccessful results. A series of 3-N-acetyl -d -cholestenes (104) has been prepared by desulfurization of the appropriate thiazolidine (105) (98,99). Lithium aluminum hydride reduction of the... 

The intermediacy of ketenes in some enamine acylation reactions using acid chlorides was described above (386,387). Direct addition of ketene to enamines was studied simultaneously by several groups (414-420). The initially formed aminocyclobutanone products could be isolated in some instances, depending on the substitution of the initial enamine. Opening to give either the acylated enamine or the alternative vinylogous amide was found to occur spontaneously or on heating, particularly in adducts derived from enamines with an olefinic proton. 

The reactions of vinylogous amides and vinylogous urethanes with excess ketene were found to give a-pyrones (421), which could also be obtained from further reactions of acylated enamines with ketene (383,421). 

In the acylation of enamines, the weakly basic acylated enamine does not absorb the acid formed. Consequently, one must employ 2 equivalents of the enamine or use a second tertiary amine to absorb the acid liberated. In the procedure, triethylamine is employed to absorb the hydrochloric acid. 

Ketene itself reacts with enamines and if in excess produces pyran-2-ones which are substituted in the 4-, 5- and 6-positions (65JOC2642). It seems likely that the acylated enamine undergoes a 1,4-addition with ketene to give an intermediate 4-amino-3,4-dihydropyranone, which eliminates the secondary amine on further reaction with ketene. 

Strategies that lead to the formation of isoxazoles during cleavage from an insoluble support include the oxidative cleavage of /V-(4-alkoxybenzyl)isoxazolidincs with DDQ to yield isoxazolines (Entry 14, Table 15.16), the nucleophilic cleavage of 2-acyl enamines with hydroxylamine (Entry 15, Table 15.16), and the acidolysis of 2-cyano-phenols etherified with an oxime resin (Entry 17, Table 15.16). The required oxime ethers for the latter synthesis were prepared by reaction of the corresponding 2-fluorobenzonitriles with Kaiser oxime resin [203],... 

Bach, T. (1996) N-acyl enamines in the Paterno-Buchi reaction stereoselective preparation of 1,2-amino alcohols by C-C bond formation. Angewandte Chemie, International Edition in English, 35 (8), 884-886. 

Several efforts were also made by the same group to achieve chiral auxiliary control in 7V-acyl enamines 155, but only moderate diastereoselec-tivities for the 3-amido oxetanes 156 were reported (Sch. 54) [152]. The photocycloaddition of an axial chiral 7V-acyl enamine 157 with benzalde-hyde resulted in oxetane (158) formation with moderate diastereomeric excess [153],... 

The enamine (37) has also been benzoylated.73 The acylated enamines (64), which are easily oxidized by air or manganese dioxide to iso-carbostyrils (67), are protonated at oxygen to give ions of the type (68),8 in agreement with other experience.98... 

A-Alkylimides, and the sodium (but not lithium) anions of A-unsubstituted imides (84), behave similarly, and the cyclisations of 84 and 86 provide a stereoselective (with regard to the enamine double bond) route to cyclic acyl enamines 85 and 87 - again, effectively an N —> C acyl transfer.49... 

You will not be surprised to find that the immediate product tautomerizes to an acyl-enamine further stabilized by an internal hydrogen bond. Mild acidic work-up releases the diketone product. The overall procedure may sound complicated—Me2NNH2 then base then acyl chloride then acidic methanol—but it is performed in a single flask and the products, the 1,3-diketones, are formed in excellent yield—in this case 83% overall. 

Enamides R2C=CHNRCOR (N-acylated enamines) are thermally stable compounds under neutral or basic conditions. However, they show sensitivity to aqueous acid, hydrolysing to form aldehydes or ketones and amides. The photocyclization of enamides has been used to form a wide variety of natural products because it gave higher yields than the conventional thermal syntheses620-623. 

Acyl migration of JV-acyl enamines was first observed by Eschenmoser and coworkers, as shown in Scheme 34 for 138 - 1393e 53, and subsequently reported by Yang and Lenz in the transformation of 140 to 14154. 

In addition to the synthesis of /1-dicarbonyl compounds3,25, the acylation of enamines also gives access to a wide variety of acyclic, carbocyclic and heterocyclic systems. The course of the reaction is often critically dependent upon the type of enamine used, on the substituents present in the two reagents, and on the experimental conditions, such as temperature, solvent, presence of added tertiary amine, etc. In contrast to alkylation, A-acylation is readily reversible. Since enamines are stronger bases than the C-acylated enamines, half an equivalent of the enamine is lost by salt formation in their reaction with acid chlorides. This can be avoided by addition of a tertiary amine179, but this in... 

Among the examples of [l,3]-sigmatropic rearrangements is the photoinduced [1,33-acyl shift of A-acylenamines, which has been investigated extensively and reviewed in 197868 xhus, the irradiation of /V-acyl enamines, known as enamides, provides a facile synthesis of enaminones. 

Although A-acyl enamines and their cationoid derivatives are not the intermediates in all the above-mentioned syntheses of pyrimidines, these reactions are listed here for demonstration of the synthetic applicability of the reaction between nitriles and carbonyl compounds and their derivatives. During the course of investigation of these processes interesting theoretical results were obtained which allow one to evaluate from a new viewpoint some concepts regarding this field. 

Besides N-acylated enamines, enamides containing a functional group in the carbon skeleton are obtained in the acid-catalyzed reactions of carbonyl compounds with nitriles. Some of them were shown in equations 18, 28, 31, 33, 38, 58, 59, 63, 65, 75 and 87 and they are mainly the polyacylated enamines (e.g. /Lacylaminovinyl ketones 79, 87, 93, 200, 207 and 278). Most of them are intermediates in the synthesis of oxygen and nitrogen containing heterocycles or products of further conversions of the latter. 

In this connection the heterocyclic 3-azapyrylium system formed by acylation of both ketones and vinyl chlorides in nitrile solutions is most interesting (see Sections III.B.3 and IV). As shown above, the hydrolysis of 3-azapyrylium salts is accompanied by ring-opening to afford the double-acylated enamines, / -acylaminovinyl ketones (200,... 

Bach, T. The Patemo-Buchi reaction of N-acyl enamines and aldehydes - the development of a new synthetic method and its application to total synthesis and molecular recognition studies. SynlettZOOO, 1699-1707. 

In acidic media, the electron sink is most often the carbocation produced from protonating the acylating agent, and therefore the sink is very hard. Attack by the Z end (harder end) of the allylic source is very fast. For enols, the Z-acylated kinetic product can be isolated. Since the Z-acylated enol is itself an allylic source (but weaker), it can be forced by more vigorous conditions to equilibrate to the more stable C-acylated product. For enamines, the Z-acylated enamine is a good acylating agent any excess of enamine will attack it and equilibrate it to the more stable C-acylated product. 

A .A -Dialkyl enamines yield alkyl 2-dialkylaminocyclopropane-l-carboxylates in low yield only, or, more typically, not at all. In contrast, less nucleophilic enamines, such as 77-acyl enamines (see Houben-Weyl, Vol. El9b, p 1153), A-acyl-2,3-dihydropyrroles, 77-acyl-l,2,3,4-tetrahydropyridines and A W-bis(trimethylsilyl) enamine 15, are cyclopropanated by diazoacetic esters without problems, e.g. formation of 16. In contrast to ( )-15, the Z-isomer and related trisubstituted enamines are cyclopropanated only in low yield (5-10%). ... 

Chlorination of the acylated enamines 14 with AT-chlorosuccinimide gives conjugated chloroenamines 16 via intermediate unconjugated chloroenamines 15. Finally, nucleophile Nu attacks the intermediate imminium ion 17 from the exo face to give en /o-morpholino products 18. However, the tosylcarbamoyl moiety in 17b is deprotonated in the weakly basic reaction medium. This anionic center in the exo position repels nucleophiles attacking from the exo face, and endo-cyano product 19 is obtained exclusively. ... 

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