N formyl imines

Catalytic Asymmetric Nucleophilic Addition to Achiral Imines 21 Table 1.8 Copper catalyzed diethylzinc addition to N formyl imines. 

Sano et al. have reported the synthesis of the 2-benzazepines 266. The steps involved reaction of the aromatic aldehydes 260 with the amine 261 to give the imines 262, followed by reduction to the amines 263, N-formylation to 264, and oxidation to the corresponding sulfoxides 265 (Scheme 34). The seven-membered ring was then formed by a modified Pummerer reaction on 265, which was then used to complete the seven-membered ring in yields ranging from 45% to 78% (e.g., 266 R1 = R2 = H, R3 = OMe, R4 = H 78%) <2001H(54)967>. 

Imidazoles have also been prepared by thermal or catalyzed cyclization of N-formyl-j8-imines using phosphorous pentachloride or phosphorous oxochloride and are reviewed (1). 

Catalytic hydroamination of imsaturated carbon-carbon bonds has a strong potential for the access to a large variety of amines, enamines or imines [90]. The first addition of a N-H bond to alkynes catalyzed by a ruthenium catalyst was described in 1995 by Watanabe et al. [91], and involved a ruthenium-catalyzed addition of the N-H bond of N-formyl anilines to terminal alkyne (Scheme 8.29). 

Calafatimine (189) is a nonphenolic N(2 ) imine alkaloid that has only been isolated from Berberis buxifolia (Berberidaceae). Curacautine (259) and talcamine (271) are two secobisbenzylisoquinoline alkaloids that have been isolated from the same plant and that contain ring B in a higher oxidation state are. The ring C constituent in the former is a formyl group, while in the latter it is a carboxymethyl. 

Reaction of 2-(A -alkyl-A -benzylamino)- and 2-[A -(rraM-crotyl)-A -ben-zylamino]-3-formyl-4/7-pyrido[l,2-n]pyrimidin-4-ones (260, R = H, Me) with tosylamine gave compounds 268 via compounds 266 and 267 (96T13097). The results of kinetic studies and MP3 calculations on the 3-formyl derivatives 252, 260 and the imines 262, 263 suggested a concerted nature for azepine-ring formation. 

Condensation of 4-formyl-3-imidazoline (75) with tert-butyH1 ydroxy 1 amine in aqueous-alcoholic solvent gives conjugated nitrone-imine (76) (224), whereas the reaction of N-tert- butylhydroxylamine both with a-monobromomethyl nitrone (77), and a,a-dibromomethylnitrone (78) generated dinitrone (79) (Scheme 2.27) (225). 

The classical method for preparing isoxazole involves the condensation of 1,3-dicarbonyl compounds with hydroxylamine, a reagent that contains the preformed N—O bond. The regiochemistry of the reactions can usually be rationalized by assuming that the first step involves imine bond formation at the more reactive carbonyl group. Thus, reaction of formyl ketone (44-1) with hydroxylamine gives... 

N- Methoxycarbonyl-2-pyrroline undergoes Vilsmeier formylation and Friedel-Crafts acylation in the 3-position (82TL1201). In an attempt to prepare a chloropyrroline by chlorination of 2-pyrrolidone, the product (234) was obtained in 62% yield (81JOC4076). At pH 7, two molecules of 2,3-dihydropyrrole add together to give (235), thus exemplifying the dual characteristics of 2,3-dihydropyrroles as imines and enamines. The ability of pyrrolines to react with nucleophiles is central to their biosynthetic role. For example, addition of acetoacetic acid (possibly as its coenzyme A ester) to pyrroline is a key step in the biosynthesis of the alkaloid hygrine (236). 

Scheme 61, yielded thiazole 200 as the major product, along with minor amounts of carbinol 201 [152]. On the other hand, treatment of the imine formed from 199 and p-methoxyphenylamine with catalytic tetrabutylammonium cyanide, produced suc-cinimide derivative 202. In both cases, the process is initiated by nucleophilic attack to the carbaldehyde C=0 (or azomethine s C=N) group, which is followed up by an anionic rearrangement. A variation of the above process using as catalysts /V-heterocyclic carbenes (NHC) derived from base treatment of azolium, imidazo-lium, or triazolium salts, has also been developed to access gem-disubstituted succinimides [153, 154]. Unfortunately, an attempt of kinetic resolution of racemic 4-formyl (3-lactams by using chiral NHC resulted in moderate selectivities only [154]. 

Protonation of 9-formyltetrahydropyrido[l,2-a]pyrimidinones takes place at the formyl oxygen, and the protonated enol-imine tautomers on the N(l) atom became the predominant tautomer forms [86JCS)P2)1911]. Similar phenomena were observed for the 9-formyltetrahydro-2// pyrido[l,2-a]pyrimidin-2-ones and their homologs [85JCS)P2)1873 88MI7]. 

Horvath et reported that the tricyclic formyl derivatives 390 n = 0-2) exhibit triple tautomerism between forms 451 and 453. The imine-enamine-enol tautomerism depends greatly on the ring size ( ). A significant solvent dependence was observed only for the pyirolo[2,l-i ]-quinazolinones 390 n = 0), which in ethanolic solution exist predominantly in the imino form (451), and in chloroform in the enol form (453). H-NMR spectroscopy showed that in chloroform the proportion of the imine tautomer 451 was about 5%. The fast equilibrium between the en-amine and enol forms 452 and 453 was shifted considerably toward the enamine tautomer 452 in the case of the pyrido[2,l-fi]quinazolinones 390 ( = 1). The azepino[2,1 -6]quinazoline ( = 2, R = 2-NO2) is a 2 3 mixture of the imine and the enamine tautomers 451 and 452. 

Sulfinamide 46, developed by the same group, represents the most recent addition to this family. Here, the original formyl group of the proline derived catalyst 16 was replaced by the t BuSO moiety, which resulted in high enantio selectivities (<97% ee at 0 °C with 10mol% catalyst loading Table 4.10) [Ilf]. The striking feature of this catalyst is its efficiency with imines derived from nonaro matic amines, namely, benzyl, allyl, propyl, isobutyl, and p methoxybenzyl amine (Table 4.10), which renders 46 superior to 43 and dwarfs other catalysts (e.g., 16,19, and 45). Needless to say, this new feature broadens the synthetic arsenal beyond the N aryl substrates and opens new synthetic avenues. In comparison, the valine derived catalyst 47 proved to be less efficient with imines derived from aromatic... 

Vilsmeier acylation of pyrroles, formylation with dimethylformamide/phosphoryl chloride in particnlar, is a generally applicable process. The actual electrophilic species is an Al,Al-diaIkyl-chloromethyleneiminium cation (the chloride is available commercially as a solid). " Here again, the presence of a large pyrrole-A-substituent perturbs the intrinsic a-selectivity, formylation of A-tritylpyrrole favonring the P-position by 2.8 1 and trifluoroacetylation of this pyrrole giving only the 3-ketone " the nse of bulky iV-silyl substituents allows P-acylation with the possibility of subsequent removal of the N-snbstituent." The final intermediate in a Vilsmeier reaction is an iminium salt requiring hydrolysis to prodnce the isolated product aldehyde. When a secondary lactam is used, hydrolysis does not take place and a cyclic imine is obtained." ... 

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