Azomethines, cycloaddition

Perhydro-l,2,4,5-tetrazines 54 and 57 have become accessible via novel azomethine/azomethine cycloadditions starting from rigid N=N/N=N systems 53 and 55, respectively . 

Very recently examples of tandem Michael-azomethine ylide cyclization reactions have been presented.626 Thus, divinyl sulfone reacted with imine (124) in the presence of lithium bromide and tri-ethylamine to give (126) in 40% yield (Scheme 38). Presumably formation of Michael adduct (125), tau-tomerization to an azomethine ylide and ensuing intramolecular [3 + 2] cycloaddition afforded (126). Indeed, (125) could be independently synthesized and converted to (126) under the reaction conditions. The preference for initial Michael addition, rather than cycloaddition, was variable. When (124) and divinyl sulfone were treated with silver acetate and triethylamine in DMSO, intermolecular azomethine cycloaddition occurred giving (127) in 27% yield. 

Scheme 30 Preparation of tricyclic [1-lactam 92 using azirine-azomethine cycloaddition...

The Zhou group reported the use of silver acetate and /V,P-ferrocenyl ligand 97 in the azomethine cycloaddition with dimethyl maleate (76) as shown in Scheme 2.27... 

Aziridines can also be synthesized from their unsaturated azirine counterparts or existing aziridine rings. The first examples of enantiopure 2-substituted 2Z/-azirine 3-carboxylates 46 were prepared via dehydrochlorination of methyl 2-chloroaziridine-2-carboxylates. Bicyclic and tricyclic aziridines such as 47 were then generated via an aza-Diels-Alder reaction with the corresponding dienes <070L1707>. A related azomethine cycloaddition in the presence of an aziridine has also been reported <07JOC8506>. 

Figure 15.19 Stereoselective DOS-based approach to azomethine cycloaddition by Chen et al. [51].

Molecular mechanics calculations have recently been used to assist in explaining the stereochemical course of several intramolecular cycloaddition reactions. - In one case, calculations were carried out to determine the relative energies of four diastereomeric products which could have been produced in the intramolecular azomethine cycloaddition reaction displayed (equation 23). A single product was isolated, though in only 25% yield, llie assumption was made that the calculated difrerences in product stability were reflected by similar, but smaller, energy difrerences in the transition states. 

Scheme 31 Preparation of bicyclic P lactams 95 and 96 using azrrine azomethine cycloaddition...

As the sp nitrogen atom in many heterocycles can be alkylated and aminated, the construction of an azomethine ylide or azomethine imine dipole is readily attainable as shown in Scheme 13. These ylides are very reactive and undergo cycloaddition with a... 

Burger s criss-cross cycloaddition reaction of hexafluoracetone-azine (76S349) is also a synthetic method of the [CNN + CC] class. In turn, the azomethines thus produced, (625) and (626) (79LA133), can react with alkenes and alkynes to yield azapentalene derivatives (627) and (628), or isomerize to A -pyrazolines (629) which subsequently lose HCF3 to afford pyrazoles (630 Scheme 56) (82MI40401). 

Aziridines, e.g. (91), undergo thermal ring opening in a conrotatory manner to generate azomethine ylides. These azomethine ylides are 47r-components and can participate in [4 + 2] cycloadditions with 1-azirines acting as the 27r-component 73HCA1351). 

Diaziridine, 3-benzyl-1,3-dimethyl-inversion, 7, 7 Diaziridine, 1,2-dialkyl-reaction with iodides, 7, 217 thermal decomposition, 7, 217 Diaziridine, dibenzoyl-rearrangement, 7, 214 Diaziridine, 3,3-dimethyl-Raman spectra, 7, 202 Diaziridine, fluoro-synthesis, 7, 232 Diaziridines acylation, 7, 213 from azomethines, 7, 231 calculations, 7, 198 from chloramine, 7, 230 cycloaddition reactions, 7, 28 electron diffraction, 7, 19 199 c/s-fused NMR, 7, 201 hydrolysis, 7, 216 inversion stability, 7, 200... 

The above cycloaddition process consists of two separate [3-1-2] cycloaddition steps and represents a 1,3-2,4 addition of a multiple bond system to a hetero-1,3-diene [7S7]. The structure ot the azomethine imine intermediate has been proved unequivocally by X-ray analysis [195] Ethylene [194], acetylene [/iS2] . many alkyl- and aryl- as well sgemmal dialkyl- and diaryl-substituted alkenes [196,197, 198, 199], dienes [200], and alkynes [182, 201], certain cyclic alkenes [198, 199,... 

The azomethine imines exhibit the typical cycloaddition behavior expected of 1,3-dipolar species [fSJ] Numerous [3+2] cycloaddition reactions have been performed [201 204] Tetracyanoethylene adds to azomethine imines across the nitnle function instead of the C=C double bond This reaction is a rare example of this type of periselectivity [208] (equation 47)... 

Asymmetric dipolar cycloaddition of azomethine imines derived from diazoal-kane-pyridazine cycloadducts 98JHC1187. 

Diethylamino-4-(4-methoxyphenyl)-isothiazole 5,5-dioxide 6 is (95T(51)2455) a highly reactive partner in 1,3-dipolar cycloadditions with several dipoles. Azomethine yhdes, such as oxazolones 7 and miinchnones 8, afforded with 6 bicychc pyrrolo[3,4-d]isothiazole 5,5-dioxides 9, 10, 11 in satisfactory yield. The regioselectivity of the reaction was excellent. The thermal behavior of these new bicychc systems was investigated. When heated at their melting point or shghtly above, triarylpyrroles 12, 13 were obtained through SOj and AtiV-diethylcyanamide ehmination. 

The first report on metal-catalyzed asymmetric azomethine ylide cycloaddition reactions appeared some years before this topic was described for other 1,3-dipolar cycloaddition reactions [86]. However, since then the activity in this area has been very limited in spite of the fact that azomethine ylides are often stabilized by metal salts as shown in Scheme 6.40. 

Grigg et al. have found that chiral cobalt and manganese complexes are capable of inducing enantioselectivity in 1,3-dipolar cycloaddition reactions of azomethine... 

In a more recent publication the same group mentions that Ag(I) salts in combination with chiral phosphine ligands can catalyze the 1,3-dipolar cycloaddition involving the azomethine precursor 64b and methyl vinyl ketone (Scheme 6.43) [87]. The reaction, which presumably also required a stoichiometric amount of the catalyst, proceeds to give 65b in a good yield with 70% ee. 

Although the first metal-catalyzed asymmetric 1,3-dipolar cycloaddition reaction involved azomethine ylides, there has not been any significant activity in this area since then. The reactions that were described implied one of more equivalents of the chiral catalyst, and further development into a catalytic version has not been reported. 

Pyrrolo annulated triazine 77 was prepared (88TL4415) by the [6 + 4]-cycloaddition of azoniafulvene ion 76 with azomethine imines generated from benzylidene phenylhydrazone (Scheme 19). 

The azomethine imine 6.39 reacts readily to give various 1,3-dipolar cycloaddition products (Huisgen and Eckell, 1977 for the naming of cycloadditions see Huisgen 1968). 

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