1.1- Enediamines arylation

Reaction of l-azirine-3-methylaciylates (155) with imidazoles and pyrazoles under mild conditions results in the formation of 2-aza-1,3-dienes (156), which are useful as dienes in hetero Diels-Alder reactions with electron-deficient dienophiles <99JOC49>. When the related methyl 2-aryl-2ff-azirine-3-carboxylate (157) was used as fee substrate, reaction with an amine induced a ting opening by addition of the amino group onto fee C=N bond followed by cleavage to provide enediamine 158 <99JCS(P1)1305>. 

As mentioned in Section I, one of the remarkable features of 1,1-enediamines is the enhanced enaminic reactivity of the / -carbon atom. 1,1-Enediamines can serve as nucleophiles in substitution of and addition reactions to a wide variety of electron-deficient reagents. In this section we discuss mainly the alkylation, arylation and acylation reactions of 1,1-enediamines, emphasizing their synthetic utilities, especially those of secondary enediamines. 

No arylation was observed when 1,1-enediamines 8 reacted with 2,4-dinitrohalo-benzenes 147 under neutral conditions. However, the a-anion of 8, prepared with sodium hydride in DMF, can displace a halide ion from 147 to afford C-arylated products 148. Excellent yield was obtained with 2,4-dinitrofluorobenzene (equation 56)131. It has been demonstrated that the reaction proceeds via the radical nucleophilic substitution (SRN1) mechanism. 

Rajappa and coworkers20 used isothiocyanates as a probe to examine the enaminic reactivity of nitro-substituted enamines and enediamines. The results were usually consistent with predictions based on the chemical shift of the vinyl proton and on extended Huckel calculations. However, cyclic enediamine 7 was found to be unreactive toward aryl and alkyl isothiocyanates (see Section II.A). Very recently, the same reaction has been re-examined21 and it has been found that cyclic enediamine 7 indeed reacts easily with aryl isothiocyanate to give the addition products 176 in 54-65% yield (equation 68). 

The reaction of benzoyl-substituted 1,1-enediamines 8 with aryl isothiocyanates gives excellent yields of /Tcarbon adducts 177 (equation 69). 

In contrast to benzenesulfonyl azide, the reaction between 8 and aryl azides gives only a small amount of 226. Instead, highly substituted triazoles 228 are formed as the major products176,177. When 4-nitrophenyl azide is used, the reaction furnishes 228 exclusively. It has been believed that the reaction involves two competitive pathways and benzoyl-substituted 1,1-enediamines 8 act mainly as nucleophiles rather than as 1,3-dipolarophiles toward aryl azides. Consequently, they add to the azide group and, following intramolecular cyclocondensation, give products 228. Only in the case of unfavorable electronic factors does 1,3-cycloaddition reaction to give 226 take place (Scheme 13)177. 

Denmark utilized the BINAP/Pd-catalyst to doubly arylate 1,2-diphenylethyl-enediamine with 2-iodonaphthalene, Eq. (100) [102]. The reaction below proceeded in 70% yield, and no epimerization due to /1-hydride elimination/rein-sertion was observed. The resulting diamine was used to prepare a chiral HMPA derivative. 

THF models transfer their C-2 fragment in between 1,4- or 1,5-binucleophilic sites to generate five- or six-membered rings. The acid-catalyzed reactions of 2-aryloxazolidines and oxazinanes with o-aminobenzamide, o-aminothiophenol, and o-phenylenediamine give 2-aryl-4( 1 //)-quinazolinones 69, 2-arylthiazoles, and a mixture of 2-arylbenzimidazole and l-benzyl-2-arylbenzimidazole 68, respectively. Whereas benzothiazole and benzimidazole could be formed by air oxidation of their initially formed dihydro derivatives, l-benzyl-2-phenylbenzimidazole, as formulated below, could arise from initially formed diimine, its cyclization, and subsequent 1,3-hydride shift (88JCR(S)322, 89IJC(B)802). It is the sole product when o-phenyl-enediamine and the model are used in 1 2 stoichiometry. 

Another important product from 2-toluidine is a mixture of arylated p-phenyl-enediamines, which is widely used as an antioxidant material in rubber processing it is manufactured by the reaction of hydroquinone, aniline and 2-toluidine and consists of N,N -ditolyl- and N,N -diphenyl-p-phenylenediamine (DTPD, DPPD) and N-o-tolyl-N -phenyl-p-phenylenediamine (Goodyear). 

Synthesis of benzoxazines through aziridine ring opening followed by intramolecular C—N bond formation was reported by Sekar and co-workers. " In this approach, a domino ring opening of A -Ts aziridines 332 with o-iodo-phenols 333 followed by copper-catalyzed intramolecular C(aryl)-N(amide) bond formation in the presence of ethyl-enediamine ligand has been established to afford the resultant product 334 in excellent yield (Scheme 40.73). The trans selectivity was confirmed by H NMR spectroscopy and single crystal X-ray analysis. 

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