Imino-, intramolecular

The high reactivity of the exocyclic 4-NH- group is again illustrated by the reaction of 2-imino-3-phenyl-4-amino-5-(ethoxycarbonyl)-4-thiazoline with EtOjCCH SCN, which yields 134 (296), and by the intramolecular preparation of the dihydrothiazolo[4,5-h]pyridine derivative 136 (297) (Scheme 89). 

Even in tricyclic bis-imidazole 57, for which the potential imino-tautomer 57b would be stabilized by the intramolecular N-H -N bond, the only observable form is the amino tautomer 57a (Scheme 30) [73KGS807 76AHC(S1), p. 431]. 

According to an X-ray crystallographic study, 2-(A-phenylamino)thia-zole forms in the crystal dimers of the imino tautomers, which are linked together by the intramolecular NH—N bonds [77AX(B)106]. 

Phenylcyclopent[c]azcpine (33a) and 6,7-fused cyclopentazepines 33b-d are formed in moderate yields in a one-pot, two-stage process involving initial condensation of triphenyl-[(l-phenylvinyl)imino]phosphoranes 32 with 6-(dimethylamino)fulvene-2-carbaldehyde (30), followed by an intramolecular aza-Wittig reaction of the iminophosphorane with the pendant aldehyde function.5 The method fails with the unsubstituted vinylphosphorane 32 (R1 = R2 = H). 

An intramolecular aza-Wittig reaction of the imino-A5-phosphancs 4, prepared by the action of triphenylphosphane on the corresponding azido compounds, affords l//-l,2,4-benzo-triazepines 5.346 The reactions were carried out by heating compounds 4 in acetonitrile or 2-hydroxyethyl methyl ether for the time indicated. No further details were reported. 

The diastereoselectivity of the intramolecular cyclization of acyclic imino-substituted enones, although predominantly trans, also strongly depends upon the conditions for cyclization, i.e., heat, pressure or Lewis acid138 387. 

In contrast LP-DE gives disappointing results for intramolecular imino Diels-Alder reactions, even in the presence of CSA. This is due to the fact that weak acids become strong acids in highly polar media such as 5.0m LP-DE and the protonation of diene, with concomitant diene isomerization, competes with cycloaddition [42]. This observation was supported by using trifluoroacetic acid (TEA). The imine 33 (Scheme 6.21) in LP-DE at room temperature in the presence of TEA gave a 1 1 mixture of cycloadduct 34 and the isomerized diene 35 within the unreacted imine 33. No Diels-Alder cycloadduct 36 was detected. 

Scheme 7 Intramolecular arene coordination in bis(imino)pyridine iron complex 10...

Oppolzer, W., Francotte, E., Battig, K. (1981) Total Synthesis of ( )-Lysergic Acid by an Intramolecular Imino-Diels-Alder Reaction. Helvetica ChimicaActa, 64, 478 81. 

An intramolecular imino-ene reaction was used as the key step in the synthesis of the non-natural perhydrohis-trionicotoxin.90 The spirocycle 147 was obtained as a single diastereomer upon exposure of 145 to TiGl2(01Pr)2 (Scheme 31). The transition structure 146 was proposed to explain the high diastereoselectivity of this reaction. 

A stereospecific intramolecular imino-ene reaction was used by Weinreb and co-workers92 to provide the enantio-selective total syntheses of (-)-montanine, (-)-coccinine, and (-)-pancracine. Refluxing the imine resulting from the condensation of 151 and 152 in mesitylene produces the amine 153 (Scheme 33) as a single stereoisomer in 63% yield after removal of the silyl group from the alkyne. The high stereoselectivity is thought to arise from a concerted ene process. 

Fig. 9.2 Part of a quantitative- /NN HNN-COSY spectrum of a 1.5 mM uniformly 13C/15N-labeled intramolecular DNA triplex. This triplex consists of five Hoogsteen-Watson-Crick T A-T and three Hoogsteen C+ G-C base triplets. The spectral region corresponds to the 10 imino resonances of the Hoogsteen-Watson-Crick T A-T triplets. The data matrix consisted of 250 (q) X1024 (i2) data points (where n refers to complex points) with acquisition times of 45 ms (tn) and 85 ms...

In contrast to the above benzonitriles, 2-methylbenzonitrile (11.88) did undergo cyano hydrolysis, but by a very indirect route involving cytochrome P450 catalyzed hydroxylation of the 2-Me group to form 2-(hydroxyme-thyl)benzonitrile (11.89), followed by intramolecular nucleophilic addition. The cyclization reaction yielded an unstable imino ether derivative (11.90), which hydrolyzes to phthalide (11.91). The conversion of 2-(hydroxyme-thyl)benzonitrile to phthalide followed first-order kinetics with a f1/2 value of 2.8 h at pH 7.4 and 37° [124],... 

Intramolecular formation of an imino group is possible in compounds that contain properly positioned carbonyl and amino groups (primary or secondary). The equilibrium between the open-chain parent and the cyclic Schiff base product will be pH-dependent, as explained in Sect. 11.6.1. 

The diastereofacial selective imine-ene reactions with a-imino esters prepared from (—)-8-phenylmenthyl glyoxylate have provided an efficient entry to the asymmetric synthesis of a-amino acids, and a Lewis acid-mediated intramolecular imine-ene reaction has been used for the key spirocyclization step in a recent synthesis of (—)-perhydrohistrionicotoxin. Asymmetric azo-ene reactions have been effected using the chiral azo-enophile, di-(—)-(lR,2S)-2-phenyl-l-cyclohexyldiazenedicarboxylate. ... 

The formation of tluorinated Q -hydroxy-jS-imino esters (180) by treatment of fluorinated imino ethers (179) with lithium 2,2,6,6-tetramethylpiperidide has been reported. A possible explanation for this interesting intramolecular rearrangement is proposed in Scheme 64. Acyclic imides derived from primary benzylic amines and amino acid esters have been found to undergo a novel nitrogen to carbon acyl migration via a base-generated carbanion to yield the corresponding a-amino... 

In another approach, 2-(alkylamino)alcohol is employed as starting material for aziridine syntheses with the aid of dihalogenophosphoranes (70BCJ1185). Intramolecular transformation of 3-azidopropyloxirane 73 results in a simultaneous formation of a condensed aziridino[l,2-a]pyrrol-idine system (Scheme 39). The azide group is first transformed into imino-phosphorane 74, the nucleophilic N atom cleaves the oxirane to form betaine 75 [as in the Mitsunobu reaction (81S1)], and the phosphorus is shifted from N to O and then eliminated as phosphane oxide under simultaneous cyclization to bicyclic 76 (89JA7500). 

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