A-acylimines

A/ Acylimines and N-acyliminium species are the most thoroughly studied and widely used class of imino dienophiles. The first reports of Diels- 

A transient N-acyliminium intermediate is presumably involved in this process. The structures of these species have been investigated by H NMR, and protonated N-acylaldimines appear to have the E configuration.  

In addition to generating M-acylimines from biscarbamates, other methods can be used. For example, Lewis acid-catalyzed elimination of methanol from a-alkoxycarbamates [Eq. (3)] 

Cycloadditions with acyclic N-acylimiiles show reasonably good kinetic stereochemical control. In an important series of papers, Krow et have thoroughly investigated the stereochemistry of the Diels-Al-der reaction of 1,3-cyclohexadiene with a large numbef of C-substituted N-acyliminium dienophiles (20) [Eq. (4)]. 

These imines were generated in situ from the precursors shown in Eqs. (2) and (3) using BF3 as catalyst, and the ratios of exo and endo adducts were determined for a variety of substituents (R). The results of this work are summarized in Table 2-III. In general, exo adducts 21 are usually favored 

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These results may be rationalized by assuming a chelation model 4. The nucleophile preferentially attacks the Re-face of the A -acylimine double bond, because the S/ -face is shielded by the phenyl group of the auxiliary9. 

The selectivity decreases with increasing amide size. This may be due to steric hindrance which prevents the chiral ligand from approaching the reaction site or may reflect a change in the reaction mechanism going from an SN1 reaction (A-acylimine 2 as intermediate) to an SN2 displacement of benzotriazole11. 

Another example of the addition of terminal alkynes to C=N in water is the coupling of alkynes with in-situ-generated A-acylimines (Eq. 4.32) and A-acyliminium ions (Eq. 4.33). In 2002, Li et al. developed a coupling reaction of alkynes with A-acylimines and A-acyliminium ions mediated by Cu(I) in water to generate propargyl amide derivatives.57 Either an activated imine derivative or imininum derivative was proposed as the intermediate, respectively. 

Heating 4-alkyl-2-substituted-5(477)-oxazolones 287 (Rj = Me, Ph) effects elimination of CO to generate A -acylimines 288 that rearrange to the more stable enamides 289 if an acidic a-hydrogen is present (Scheme 7.94). Representative examples of enamides prepared in this manner are shown in Table 7.25 (Fig. 7.27). 

However, in the presence of a quaternary a-carbon this rearrangement is precluded and the A -acyhmines 288 may be isolated. Finally, pyrolysis of 4,4-dialkyl-5(4f/)-oxazolones affords mixtures of A -acylimines and enamides. The composition of the mixture depends on the pyrolysis temperature. ... 

In a special case, the spirocyclic oxazoline 640 was found to be unstable and undergoes rearrangement to the thietane A -acylimine 641 (Scheme 8.202). ° A zwitterionic intermediate 642 was proposed to account for the formation of 641. A biradical 643 is also a possible intermediate for this rearrangement. 

Pd-catalyzed amidocarbonylation conditions. Then, it was found that A -acylphenylalanine was indeed formed in 78% yield (including 21% as its methyl ester). Accordingly, enamide 19 is likely to be an intermediate of this reaction. When an aryl aldehyde is used, the corresponding enamide cannot be formed and an A -acylimine or an Wacyliminium ion 18 should be the intermediate instead. These intermediates can readily form the key intermediate alkyl-Pd complex 20 as well (Scheme 3). ... 

The A-acylimine-enamide tautomerism of methyl 2-acetamidoacrylate has been studied641 by means of ab initio calculations. A 13C NMR investigation has been undertaken to study the tautomerism between the hydrazone imine and diazenylen-amine forms of 3-(arylhydrazono)methyl-2-oxo-l,2-dihydroquinoxalines,642 and the effects of temperature and side-chain on the imine-enamine tautomerism in quinoxalinone and pyridopyrazinone systems have been studied.643 A detailed... 

The 2-aroylaziridines (303), on thermolysis, provide aroylazomethine ylides which undergo [3 + 2] cycloadditions with various dipolarophiles. Whereas imines are normally inert to dipole synthons, Lown and Landberg reported that the polarized A -sulfonyl-a-acylimines afford initially the 1-sulfonyl-4,5-diacylimidazolines (304) which undergo cyclodehydration (Paal-Knorr reaction) to the furo[3,4-fi ]imidazolines (305) (Scheme 57). A further variant with other substituted A-sulfonylimines (R1 = 4-ClC6H4S02) and sequential amination affords the l,5-dihydropyrrolo[3,4-. 

Af-Trimethylsilyl enamines undergo TV-acylation on treatment with acid chlorides (replacement of the trimethylsilyl group) to give the amide and starting ketone on hydrolysis. However, in the presence of potassium fluoride and a catalytic amount of crown ether, C-acylation occurs to give the a-acylimine in high yield196 (Scheme 85). 

A wide range of hetero 2-aza-1,3-butadienes have been shown to participate as 4rr components of Diels-Alder reactions (Figure 4). Perhaps the most widely recognized class of hetero 2-aza-1,3-butadienes is the A -acylimines (l-oxa-3-aza-l,3-butadiene) ° and comprehensive reviews of their 4tt participation in LUMOdiene-controlled Diels-Alder reactions are available. The recent disclosure of the 4ir participation of A -acylimines in intramolecular [4 + 2] cycloaddition reactions (equation 11), and the use of optically active A -acylimines in productive LUMOdiene-controlled [4 + 2] cycloaddition reactions, illustrate applications of the systems that have not been explored fully (equation 12). ... 

An attempt to prepare an oxazabicyclobutane by peroxidation of an azirine yielded only an A-acylimine, but that product may have been derived from the heterobicycle. 

Many of these reactions occur with formation of A -acyliminium ions 2 as intermediates (equation 1), which give the enamides after elimination of the electrofuge from -carbon atom, or the A-acylimines by removal of R group from nitrogen atom. In that way, the iV-acyliminium ions 2 appear not only as the intermediates in acid-catalyzed conversions of enamides but also as direct precursors of the latter, In other words, the chemistry of enamides and their A-acylimine tautomers is closely connected with A -acyliminium chemistry, a topic which has been reviewed comprehensively ... 

Cyclic derivatives having the A -acylenamines or A -acylimines structure can be prepared starting from the cyano esters as well as from the enol forms of -ketonitriles. 

Without deviating from the theme of this review, the 3-azapyrylium (1,3-oxazi-nylium , l,3-oxazin-l-ium ) salts formed by the reactions described above deserve particular attention. Their conversions to both jS-A -acyl amino vinyl ketones 49 and 200 and to polyunsaturated A -acylimines 50-52 have been shown above (equations 18 and 63). Their properties and methods of their synthesis were investigated in detail by Schmidt and coworkers ° and summarized in a number of revie 19.123 3-azapyrylium salts are easily converted in reactions with amino... 

Intramolecular hetero-Diels-Alder cycloaddition of A-acylimines 173 and 178, prepared in situ from an isomeric mixture of methylol acetates (172) by heating (81JA7573 84JA3240) or from chloroformate (177) and A-trimethylsilylimines (176) derived from aldehydes 175 (91TL4371), respectively, diastereoselectively afforded only one type of the cycloaddition products 174 and 179, containing trans-fa ed bicycles. 

Although extension of this process to include the [3 + 2] addition to a,/ -unsaturated aldehydes has been unsuccessful, reaction with saturated ketones or with A-acylimines presents a novel and often stereocontrolled entry into oxygen and nitrogen heterocycles7. The use of a (tert-butyldimethylsilyl)allene is necessary to prevent a competing hydrolysis pathway. In the case of dihydrofuran syntheses, the stereochemical tendency is for the formation of m-substituted products. 

In addition to heterolysis of compounds of type (2), N-acyliminium intermediates (1) are also obtained by protonation of A/-acylimines (27) and by protonation of enamides or enecarbamates (28). The former method is mainly of theoretical interest,49 because N-acylimines (27) are rather unstable compounds. The latter technique is occasionally applied,30 although compounds (28) are usually synthesized through elimination of HX from (2).51 Other preparatively very useful methods for the in situ generation of the N-acyliminium ion are the acid-mediated coupling of an aldehyde (or ketone) with a primary (or secondary) amide or a nitrile, and the thermal reaction between an acid chloride and an imine/... 

Yet another extension of this type of procedure utilizes cyclobutadienes (198 R = Me, or Bu ) as the alkene component. These react with A-acylimines to form azaoxabicyclo[4.2.0]octadienes (199) and azabicyclo[2.2.0]hexenes (200). When exposed to acid the latter products rearrange into the former (Scheme 54) <85TL3315>. 

Stereochemistry the Boron Trifluoride-Catidyzed Cydoaddition of MonO C-Snbstituted A-Acylimines with 1,3-Cydohexadiene... 

The intramolecular 47t participation of an AAacylimine in a Diels-Alder reaction73 and the use of A/-acylimines bearing chiral auxiliaries in inverse electron demand Diels-Alder reactions with an observable high degree of asymmetric induction74 illustrate additional capabilities for the applica-... 

The number of papers published on A-imines is relatively small. Efficient methods of preparation were not discovered until recently, and only since 1965 has the study of the A-imines been pursued to any extent. Nevertheless, Ar-imines have been known hitherto only as derivatives of pyridines, quinolines, isoquinolines, benzocinnolines, p-triazoles, s-tria-zoles, and thiazoles. Ar-Imines can be classified not only by the heterocyclic nucleus but also according to the substituent at the exocyclic imino group. Unsubstituted A-imines (4), A-arylimines (5), A-acylimines (6), A-carbamoylimines and A-thiocarbamoylimines (7), A-sulfonylimincs (8), A-nitroimines (9), and A-cyanoimines (10) have all been synthesized. 

Some paths are available for the synthesis of cyanocyclopropyl systems from cyanoalkenes. An interesting example of this is the photoisomerization of 2-aminopropenenitrile to yield the aziridine 201. Products of fragmentation such as HCN and acetonitrile are also obtained The A-acylimine 202 is converted on irradiation into the bicyclic products 203 and 204. The route to products involves bond formation by attack of the carbonyl oxygen atom on the styryl moiety. This affords the biradical intermediate 205, where radical stabilization by the cyano group is important. Cyclization within this yields the two bicyclic compounds. The same reaction path is followed on irradiation of202 in the crystalline phase. Here, however, this path is minor (30%) and the major path affords a (2 + 2)-cycloadduct. ... 

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