Acylimines

Moore et al. have prepared some 2-cyanoaza-p-quinones via an interesting thermal rearrangement of o-diazido-p-quinones [Eq. (6)].  

These azaquinones are very reactive imino dienophiles. Some examples of cycloadditions of this type are shown in Table 2-V (entries 9-12). 

Only a few scattered examples of Diels-Alder cycloadditions of this type of dienophile have been described to date, and not all C-acylimines appear to be reactive. The indolone shown in Eq. (7) 

They found that it reacted in Diels-Alder fashion with 2,3-dimethylbuta-diene.  

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After formation of the acylimine (12), methanol adds to the less sterically hindered a-face of the molecule with high selectivity to provide (13). A further direct incorporation of a 6a-methoxy group (41) and subsequendy a 6a-formamido group into penicillin has been achieved using ttiduoromethanesulfonamides of type (14) (42). 

TV-Amino groups are replaced by hydrogen on treatment with nitrous acid (e.g. 562 -> 563) (80AHC(27)24l) or phosphorus trichloride (l,2,4-triazole-4-acylimines are converted into triazoles (74AHC(17)213)). 

C-Acylation imidazoles in, 1, 463 ortiio-Acylation 2-alkylpyridines, 1, 436 Acylimines... 

Pyridine-2,3,6-trione, 4-chloro-5-methylamino-monohydrate structure, 2, 114 Pyridinium N-acylimines thermolysis, 2, 345... 

Halogen-free A/-acyl aldimines and N-acyl ketiimnes tautomenze readily to give enamides [J6] In contrast, perfluonnatedyV-acylimines are stable compounds These electron-deficient itnmes not only exhibit high thermal stability but also show umque properties both as electrophiles and as strongly polanzed hetero-1,3-dienes... 

Substituted isoquinoline (V-acylimines 6 undergo a photochemical rearrangement to 1-acyl-1//-1,3-benzodiazepines 7.164... 

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. 

A -(l-Phenylpropyl)amidcs 3 are enantioselectively synthesized by alkylation of acylimines 2 generated in situ from N-(amidobenzyl)benzotriazoles 1 with diethylzinc in the presence of an enantiomerically pure promoter [(— )-(l/ 2.V)-A,A-dibutylnorcphcdrine, DBNE], The best results are obtained with one equivalent of 1, one equivalent of DBNE and two or three equivalents of diethylzinc in toluene at —78 =C with slow warming to room temperature before workup11. 

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. 

Keywords asymmetric aza-Diels-Alder reactions of acylimines... 

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. 

Although disilenes do not undergo Diels-Alder reaction with 1,3-dienes,68 they react with heterodienes like benzil,67-89 acylimines,90 and 1,4-diazabutadienes91 to give [4 + 2] cycloadducts (Eqs. 26-28). 

This asymmetric alkylation of cyclic acylimines can provide optically active precursors to carbapenems.2 Thus reaction of the 4-acetoxy-2-azetidinone 5 with the chiral 3-acyl-(4S)-ethyl-l,3-thiazolidine-2-thione 6 provides the substituted aze-tidinone 7, an intermediate in a total synthesis of (- )-l-(3-methylcarbapenem. 

A (tert-butyldimethylsilyl)allene reacted with aldehydes and N-acylimine in the presence of TiCl4 to afford the five-membered heterocycles [190],... 

A new synthetic method of benzofuran was reported (equation 39). The [3,31-sigma-tropic rearrangement of Af-trifluoroacetyl enehydroxylamines 136 obtained in situ by acylation of oxime ethers 135 in the presence of trifluoroacetic anhydride lead to the synthesis of cyclic or acyclic dihydrobenzofurans 138. The effects of base and temperature on the reaction products were studied. A similar pathway to that of Fisher indolization was proposed. The acylimine formed by the [3,3]-sigmatropic rearrangement of the V-trifluoroacetyl enehydroxylamine 136 gave the dihydrobenzofuran 137 by an intramolecular cyclization or the benzofuran 138 after elimination. 

Scheme 1 Carbonylamino sulfones as acylimine/acyliminium precursors...

Good stereoselectivities have been obtained with the addition of organometallics onto homochiral cyclic acylimines (Figure 5.27), or onto sulfmylimines derived from trifluoropyruvate (Figure 5.28). " Asymmetric Strecker reaction of jS-sulfmyl... 

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. 

In neutral solvent, nitrosamides LXII readily undergo photolysis to give N-acylimines as the primary products which are susceptible to nucleophilic attack due to the conjugated C=N-C0 group (44). Photolysis of nitrosamide LXIIa in methanol gives LXVII (45%) and LXVIII (23%) obviously derived from the nucleophilic addition of methanol to and proton migration of LXVI, respectively. Photolysis of LXIIa in ether gives LXVIII (27%)... 

JV-Alkoxycarbonyl- and iV-arenesulfonyl-imines can be prepared by the reaction between pyridines and nitrenes, the latter being generated from the corresponding azides (72JOC2022, 64TL1733). Thermolysis of pyridinium iV-acylimines gives isocyanates and the parent heterocycle <79JCS(P1)446). 

Die Synthese von a,a-disubstituierten a-Amino-carbonsauren durch nukleophile Substitution von Acylimin-Derivaten hoherer a-Amino-carbonsauren ist bisher kaum un-tersucht worden. Eine solche Moglichkeit3 ist auf S. 522 beschrieben. 

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). ... 

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