Azomethine imines cyclizations

An azomethine imine cyclization is found in Overman s construction of hexacycle 26 (Scheme 18.6) [51, 52]. The approach involved in situ formation of azamethine imine 23 with the aid of thiosemicarbazide (22), followed by dipolar cycloaddition and condensation. Product 25 was subsequently converted into 26, which served to confirm the revised structure of trans-fused palau amine (27) [52],... 

Finally, fully reduced heterocycles have been prepared either from a sequential azomethine imine cycloaddition-palladium-mediated cyclization process <2003T4451>, or from the reaction of A-( l-benzotriazolylalkyU-AyV-disubstitutcd hydrazine with methyl vinyl ether <1997JOC8210>. 

In situ generation of azomethine imines from furan-3-carbaldehyde and ]V,N -disubstituted hydrazines followed by cycloaddition to N-methylmaleimide results in a 2.8 1 mixture of pyrazolidines 94 and 95 (X = O) separatable by chromatography. Eurther Pd(0) catalyzed cyclization involving the aldehyde and hydrazine moieties leads to the formation of benzoxepines 96 and 97 (X = O) in good yield (Scheme 17 (2003X4451)). 

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. 

Azomethine imine cycloadditions provide access to pyrazolidines, pyrazolines and pyrazoles. Intramolecular cyclizations were first reported in 1970.78 The main method for generation of azomethine im-ines involves reaction of a 1,2-disubstituted hydrazine with an aldehyde or an aldehyde precursor. 

The azomethine imine (151), having the alkene attached to the terminal dipole nitrogen, was generated in situ from the corresponding hydrazine by reaction with benzaldehyde (Scheme 47).79 As is typical in these reactions, condensation at the more basic benzyl-substituted nitrogen occurred, rather than at the acyl-substituted nitrogen. Cyclization of (151) afforded the 5,5-fused pyrazolidine and no bridged product. 

Azomethine imines which contain an intervening aromatic ring between the dipole and dipolarophile are accessible from aryl aldehydes and readily undergo cyclization. Thus, imine (154), where the dipolarophile is attached at the carbon of the dipole, afforded cis- and rrans-fused tricyclic pyrazolidines in which the alkene stereochemistry was retained (Scheme 48).78 ... 

The azomethine imine (155), containing a cyclic dipolarophile, cyclized to a tetracyclic pyrazolidine in 48% yield.78 Aldehyde (156), containing a furan ring, reacted with A/-methyl-A/ -(phenylacetyl)hydra-zine to afford an azomethine imine the imine cyclized to one product, probably with the two new rings cis fused.80... 

Azomethine imines can cycloadd to an internal C—C triple bond producing new bicyclic pyrazoline systems. Thus, imine (161), prepared in situ from the corresponding aldehyde, cyclized to a tricyclic pyrazoline (Scheme 50).78 ... 

The mesoionic compounds known as sydnones serve as cyclic azomethine imines. Thus, sydnone (167), isolable after preparation from die corresponding nitrosamine, underwent cyclization as an azomethine imine at 20-35 C (Scheme 52).86 Photolysis of sydnones also results in cyclization but through nitrile imine intermediates vide infra). 

Enamines possessing /7-hydrogen atoms add hexafluoroacetone azine to form transient dipolar azomethine imines 9, as evidenced by low-temperature 19F NMR spectroscopy, which rearrange to hydrazones. If there is no hydrogen atom in the /7-position the betaines cyclize to unstable derivatives 10 of azetidine (equation 7)24. 

Thiophene containing fused 6, 7 and 8 membered ring systems 41-46 have been prepared from in situ generated azomethine imines followed by cycloaddition to N-methyl maleimide and subsequent Pd(0) catalyzed cyclizations <03T(59)4451>. 

There are only a few examples of carbene reactions that afford pyrazole derivatives. First, we mention the reaction of azobenzene with isopropylide-necarbene, which proceeds via an azomethine imine and its cyclization in indazole system 505. In the case of the unsymmetrically substituted azobenzenes, both isomeric products were obtained (77JA2597 84JA6015). Isopyrazoles are accessible via a convenient route with nucleophilic carbene... 

Selective synthesis and cycloaddition reactions of new azomethine imines 109 containing a 1,2,4-triazine ring have been reported. 4,5-Dihydro[l,2,4]triazolo[3,4-c]benzo[l,2,4]triazines 108 with aromatic aldehydes gave stable iminium salts which were deprotonated to give new mesomeric betaines 109. These underwent 1,3-dipolar cyclization reactions affording tetra- and pentacyclic heterocycles 110 <05EJO3553 05H1889>. 

Azomethane imines undergo an analogous photoinduced cyclization to give diaziridines. The dihydroisoquinoline derivative (99), for example, is converted on irradiation in cyclohexane or benzene into the diaziridine (100) the transformation is thermally reversible. In contrast, the pyrazolidinone azomethine imines (101) undergo photoreversible conversion into the diaziridines (102), providing in this way a useful reversible photochromic system. The analogous photoisomerization of a pyrene-substituted pyrazolidinone azomethinimine has... 

Similarly, heating of methyl 3-acyl-l-(diphenylmethyleneamino)-4,5-dioxo-4,5-dihydro-l//-pyrrole-2-carboxylates 96 gave the corresponding dimethyl 2,8-diacyl-3,9-dioxo-5,5,ll,ll-tetraphenyl-3,5,9,lTtetrahydrodipyrazolo[l,2- 7 l, 2 -i [l,2,4,5]tetrazine-l,7-dicarboxylates 99 in good yields. The proposed mechanism involves thermal decarbon-ylation to give the ketene intermediate 97, which cyclizes into the azomethine imine 98, followed by dimerization (Scheme 24) <2004T5319>. 

The mechanisms of the cascade cyclizations of homoallenyl aldazines and analogues to afford tetracyclic compounds have been computed and double sequential crisscross 1,3-dipolar cycloaddition through azomethine imine intermediates has been characterized both for the homoallenyl aldazine and for its ketene analogue (Scheme 23). ... 

SCHEME 7.9 Asymmetric 1,3-dipolar cycloadditions of AA -cyclized azomethine imines with aUyl alcohol by the use of only the Grignard reagent as a magnesium source. 

SCHEME 7.10 Catalytic asymmetric 1,3-dipolar cycloadditions of JV.iV -cyclized azomethine imines to allyl alcohol. 

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