Azomethine moieties

When 2,2-dimethylpropanal is used to prepare the azomethine moiety, the corresponding azaallyl anion may be obtained when l,8-diazabicyclo[5.4.0]undec-7-ene/lithium bromide is used as base. The subsequent addition to various enones or methyl ( )-2-butenoate proceeds with anti selectivity, presumably via a chelated enolate. However, no reaction occurs when triethylamine is used as the base, whereas lithium diisopropylamide as the base leads to the formation of a cycloadduct, e.g., dimethyl 5-isopropyl-3-methyl-2,4-pyrrolidinedicarboxylate using methyl ( )-2-butenoate as the enone84 89,384. 

A similar, although less marked difference characterizes the cyclopropanation of olefins 41 and 42. In the presence of either copper or copper complexes whose chelating ligands contain an azomethine moiety derived from an a-amino acid, no stereoselectivity was observed with diene 41, whereas the cyclopropanes derived from 42 occur with cisjtrans ratios of 57 43 to 69 31, depending on the catalyst93). 

Most of the (5,5) (2N2)-fused heterocyclic systems are fully substituted aromatic systems and therefore they do not have any hydrogens attached to the ring. Very little is reported on C-unsubstituted compounds. Methine groups are generally part of a ring azomethine moiety and are either linked to a fusion atom C or N or to a nonfusion atom N or S (Table 1). 

Yadav and Kapoor <2003TL8951> reported on a microwave-assisted ring closure leading to novel thiazolo[l,3,5]-triazines, as shown in Scheme 36. This three-component one-pot procedure started from the thiazolyl Schiff base 230, to which ammonium acetate and an aldehyde was added. In the first step, the azomethine moiety of the Schiff base reacted with ammonia to give the zwitterionic first intermediate 231, which underwent deprotonation to the amine 232, and, finally, reaction of this second intermediate with the aldehyde involving the ring-closure step afforded the product 233. It is important to emphasize that the MW-assisted technique ensured high yields (76-88%)... 

Dihydro derivatives of pyridine and pyrimidine are able to add nucleophiles through their double bonds. For example, heating compound 294 in the presence of potassium hydroxide leads not only to complete hydrolysis of the azomethine moiety but, according to Meyers [326], also yields the product 295 formed by the addition of a water molecule (Scheme 3.104). 

Scheme 15).160 Similarly, the hydrazone 147 reacts at the amino (and not azomethine) moiety, to yield the amide 148, which cyclizes with dimethyl acetylenedicarboxylate to give the quinazolone 149174 (Scheme 24).

Minor pathways arise from hydrolytic or oxidative cleavage of the azomethine moiety and reduction to dihydro-CR (French et al., 1983b). No samples from human exposures have been reported. 

Methine groups are generally part of a ring azomethine moiety and are either linked to a fusion atom (C or N) or to a nonfusion atom (N or S) (Table 2). 

POLYMERIC MATERIALS BASED ON AZOMETHINE MOIETIES FOR THE PREPARATION OF ORGANIC ONE-DIMENSIONAL SUPERLATTICES... 

With relatively few exceptions, the R function contains the azomethine (—CH=N—) moiety. The most prominent exceptions contain the olefinic... 

In 1990, Baumeister et al. [127] described the crystal and molecular structure of 4-ethoxy-3 -(4-ethoxyphenyliminomethyl)-4 -(4-methoxy-benzoy-loxy)azobenzene. The molecules have a bifurcated shape. The phenyliminom-ethyl branch is bent markedly from the nearly linear three ring fragment, but is almost coplanar with the azobenzene moiety. They found that the molecular conformation is affected by an intramolecular interaction of the carboxylic and azomethine groups. The crystal packing was described in terms of a sheet structure with interdigitating rows of molecules. 

In terms of synthetic methodologies for the preparation of porphyrinic azomethine ylides, the porphyrin moiety, in the examples above, was the carbonyl component. However, there are also examples where the porphyrin is used as the a-amino acid component. 

The azo group (—N=N—) may be replaced by the analogous (—CH=N—) moiety to form an azomethine complex pigment, usually with copper as a chelating metal. The number of commercially available products in this group is also restricted. They typically afford yellow shades. Those species that provide the required lightfastness and weather resistance are used in automotive finishes and other industrial coatings. 

The aromatic moieties are possibly substituted benzene or napthaline rings. In azomethine pigments, only one form of metal complex is possible. This is in contrast to azo metal complexes, which may assume either structure 31 or 32 ... 

Triphenylthieno[3,4-c]pyrazole (414) can be presented as a hybrid of dipolar-contributing azomethine imine ylide (415) or thiocarbonyl ylide canonical forms 416. Upon reacting this ylide with electron-poor olefins, it behaved like a thiocarbonyl ylide. Thus, with maleimide, a mixture of endo (419) and exo adducts (420) were obtained (74JA4276), which resulted from addition at the thiocarbonyl moiety. The reaction of 414 with dimethyl acetylenedicarboxylate gives the desulfurized indazole 418 in addition to the adduct 417 (Scheme 41). 

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)). 

Further studies into the constmction of pyrrolo[l,2-a]indoles, however, revealed that the presence of a nitrile functionahty was not essential to the reaction (3). Subjecting precursor 13 to yhde formation by AgF (it should be noted that this was the only reagent to induce cycloaddition to any extent) in the presence of N-phenyhnaleimide surprisingly furnished adduct 14 in which the nitrile functionality was stiU intact. The reaction pathway was therefore assumed to proceed via initial formation of the silver bonded cation 15, which after desilyation generated the requisite silver bound azomethine yhde. Cycloaddition followed by sequential loss of silver and a hydrogen delivered the observed products. Replacement of the nitrile moiety with alternative functionalities also generated the expected products in good isolated yields (Scheme 3.4). 

The chiral dipolarophiles of Garners and Dogan, which were derived from Oppolzer s sultam, have been previously discussed in Section 3.2.1 and, in an extension to these results, the sultam moiety was used as the stereodirecting unit in enantiopure azomethine ylides (56). The ylides were generated either by thermo-lytic opening of N-substituted aziridines or by the condensation of the amine functionality with benzaldehyde followed by tautomerism. These precursors were derived from the known (+)-A-propenoylbornane-2,10-sultam. Subsequent trapping of the ylides with A-phenylmaleimide furnished the cycloaddition products shown in Schemes 3.60 and 3.61. 

The decarboxylative approach to the ylide formation generated cycloaddition products derived from cycloaddition of the ylide to the carbonyl moiety of the molecule, as opposed to the alkene as seen in previous examples. Kanemasa has reconciled this observation by consideration of the postulated transition state model of the reaction. It was assumed that the steric repulsion of the terminal olehnic substituent and the ylide would favor transition state 309 (Fig. 3.19). Additionally, nonstabilized azomethine ylides have a higher energy HOMO than stabilized ylides, and would therefore prefer the LUMO of the carbonyl than the lower lying alkene LUMO. Formation of fused hve-membered rings would also be kinetically favored over construction of six-membered ring (Scheme 3.103). 

N-Metalated azomethine ylides generated from a-(alkylideneamino) esters can exist as tautomeric forms of the chelated ester enolate (Scheme 11.8). On the basis of the reliable stereochemical and regiochemical selectivities described below, it is clear that the N-metalated tautomeric contributor of these azomethine ylides is important. Simple extension of the above irreversible lithiation method to a-(alkylideneamino) esters is not very effective, and cycloadditions of the resulting lithiated ylides to a,(3-unsaturated carbonyl compounds are not always clean reactions. When the a-(alkylideneamino) esters bear a less bulky methyl ester moiety, or when a,(3-unsaturated carbonyl compounds are sterically less hindered, these species suffer from nucleophihc attack by the organometalhcs, or the metalated cycloadducts undergo further condensation reactions (81-85). 

Azomethine ylides derived from (55,6/ )-2,3,5,6-tetrahydro-5,6-diphenyl-1,4-oxazin-2-one (53) and various aldehydes have been prepared by Williams and co-workers (87,88) (Scheme 12.19). In a recent communication they reported the application of the azomethine ylide 54 in the asymmetric total synthesis of spirotryprostatin B 56 (88). The azomethine ylide 54 is preferentially formed with ( )-geometry due to the buLkiness of the aldehyde substituent. The in situ formed azomethine ylide 54 reacted with ethyl oxindolylidene acetate to give the 1,3-dipolar cycloaddition adduct 55 in 82% yield as the sole isomer. This reaction, which sets four contiguous stereogenic centers, constmcts the entire prenylated tryprophyl moiety of spirotryprostatin B (56), in a single step. 

Chiral aziridines having the chiral moiety attached to the nitrogen atom have also been applied for diastereoselective formation of optically active pyrrolidine derivatives. In the first example, aziridines were used as precursors for azomethine ylides (90-95). Photolysis of the aziridine 57 produced the azomethine ylide 58, which was found to add smoothly to methyl acrylate (Scheme 12.20) (91,93-95). The 1,3-dipolar cycloaddition proceeded with little or no de, but this was not surprising, as the chiral center in 58 is somewhat remote from the reacting centers... 

Chiral exocyclic alkenes such as 112, also having the chiral center two bonds away from the reacting alkene moiety, have been used in highly diastereoselective reactions with azomethine ylides, and have been used as the key reaction for the asymmetric synthesis of (5)-(—)-cucurbitine (Scheme 12.37) (169). The aryl sulfone 113 was used in a 1,3-dipolar cycloaddition reaction with acyclic nitrones. In 113, the chiral center is located four bonds apart from alkene, and as a result, only moderate diastereoselectivities of 36-56% de were obtained in these reactions (170). 

Most of the conformational properties of the acyl derivatives originate in the high polarity of the C=0 bond. Comparative studies have been reported between several chemical functionalities containing the C=0 moiety, i.e., besides heterocyclic aldehydes and ketones, acyl halides, esters, amides, and urethanes, which have different electronic character. Furthermore, the behavior of the C=0 group has been compared, with regard to its conformational properties, to C=C and C=N double bonds in vinyl derivatives, oximes, and azomethines. Most of the results relative to five-membered aromatic heterocycles have been discussed previously (81RCR336 84KGS579). 

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