Imine ylides from

In addition to cydocondensation reactions of the Paal-Knorr type, cycloaddition processes play a prominent role in the construction of pyrrole rings. Thus, 1,3-dipo-lar cycloadditions of azomethine ylides with alkene dipolarophiles are very important in the preparation of pyrroles. The group of de la Hoz has studied the micro-wave-induced thermal isomerization of imines, derived from a-aminoesters, to azomethine ylides (Scheme 6.185) [346]. In the presence of equimolar amounts of /i-nitrostyrenes, three isomeric pyrrolidines (nitroproline esters) were obtained under solvent-free conditions in 81-86% yield within 10-15 min at 110-120 °C through a [3+2] cycloaddition process. Interestingly, using classical heating in an oil bath (toluene reflux, 24 h), only two of the three isomers were observed. 

Fig. 4.9. Formation and transformations of azomethine ylides from imines and electrophilic carbene complexes.

Table 4.17. Generation and rearrangement of azomethine ylides from acceptor-substituted carbene complexes and imines.

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). 

Thus far, in the alkaloid series discussed, the nitrogen atom has always been part of the core of the alkaloid strucmre, rather than acting in a dipolarophilic manner in the cycloaddition of the carbonyl ylide. Recently, Padwa et al. (117) addressed this deficiency by conducting model studies to synthesize the core of ribasine, an alkaloid containing the indanobenzazepine skeleton with a bridging ether moiety (Scheme 4.57). Padwa found that indeed it was possible to use a C = N 7i-bond as the dipolarophile. In the first generation, a substimted benzylidene imine (219) was added after formation of the putative carbonyl ylide from diazoketone 218. The result was formation of both the endo and exo adduct with the endo adduct favored in an 8 1 ratio. This indicates that the endo transition state was shghtly favored as dictated by symmetry controlled HOMO—LUMO interactions. 

Imine ylides 7 and carbonyl ylides 8 are not stable but may be generated in situ by pyrolysis of suitably substituted aziridines and oxiranes. The energy of the HOMO, and therefore the nucleophilicity of the parent 18-electron dipoles, decreases from very high to very low across the series 7-18. In the same series, the electrophilicity increases from moderate to high, being consistently higher when the central atom is oxygen. 

Furans (133) are obtained from acyltriafulvenes [(acylmethylene)cyclopropenes] (131) and azomethine-imines, -ylides or oxides (132) (75TL3919). The reaction involves the transfer of the group X from the azomethine dipole to the triafulvene and may proceed as shown in Scheme 28. I... 

Heating imines derived from 3-amino-l,4-benzodiazepin-2-ones with iV-methylmaleimide in boiling toluene provided adducts derived from the stereospecific cycloaddition of the resonance-stabilized azo-methine ylide 45, formed by a 1,2-prototropic rearrangement, in 82-89% yield (Scheme 16) <1996T13455>. The relative stereochemistry was established by analysis of H NMR NOE data and comparison with the single crystal X-ray structure of an analogous compound. 

Dai and coworkers have investigated the addition of ylides derived from allylic sulfonium salts to IV-sulfonyl imines derived from aromatic aldehydes to produce 2-vinyl aziridines [98]. The general reaction studied is shown in Eq. (69), where a sulfonium salt 285 can be converted to its ylide in situ under either phase transfer conditions, or by use of a strong amides base, and then combined with an N-sulfonyl imine to provide a 2-vinyl aziridine 286. In gene-... 

The non-classical system (182) has been synthesized, starting from 4,5-bis(chloromethyl)-l,2,5-thiadiazole, and characterized by the isolation of its dimer and adducts. The more complex but stable non-classical thiophens (183)—(185) have been prepared, starting from azomethine imine ylides, generated in situ from 1-aminopyridinium, 1-aminoquinolinium, or... 

A conceptually different approach was taken by Novikov and coworkers using difluorocarbene as a building block. 1,3-Dipolar addition of dipolarophiles to azomethine ylides derived by addition of difluorocarbene to imines produces substituted 2-fluoropyrroles. The process is illustrated below with the imine derived from benzaldehyde and aniline. Using dimethyl acetylenedicarboxylate (DMAD) as the dipolarophile produces the 2-fluoropyrrole derivative 73 (Fig. 3.32). Several substrates were studied and such issues as regiochemistry were addressed. 

Dipolar [3 + 2] cycloadditions are one of the most important reactions for the formation of five-membered rings [68]. The 1,3-dipolar cycloaddition reaction is frequently utilized to obtain highly substituted pyrrolidines starting from imines and alkenes. Imines 98, obtained from a-amino esters and nitroalkenes 99, are mixed together in an open vessel microwave reactor to undergo 1,3-dipolar cycloaddition to produce highly substituted nitroprolines esters 101 (Scheme 35) [69]. Imines derived from a-aminoesters are thermally isomerized by microwave irradiation to azomethine ylides 100,... 

Ag-catalyzed in situ generation of azomethine ylides from alkynyl A-benzylidene glycinates 35 and their reaction with electron-deficient alkynes 36 were demonstrated by Su and Porco (Scheme 16.17) [26]. This reaction is supposed to be initiated by cycloisomerization of alkynyl imines 35 to isoquinolinium species A with the assistance of AgOTf. Subsequent proton transfer would afford azomethine ylides B with regeneration of Ag(I). 1,3-Dipolar cycloaddition with alkynes 36 followed by aerobic oxidation may furnish pyrroloisoquinoline products 37. It is worth noting that various types of electron-deficient alkynes, irrespective of internal and terminal alkynes, are applicable to this reaction. 

Solladie-Cavallo has recently reported a two-step asymmetric synthesis of dis-ubstituted N-tosylaziridines from (R,R,R,Ss)-(-)-sulfonium salt 2 (derived from Eliel s oxathiane see Section 1.2.1.1) and N-tosyl imines with use of phosphazine base (EtP2) to generate the ylide (Scheme 1.42) [67], Although the diastereoselectiv-ity was highly substrate-dependent, the enantioselectivities obtained were very high (98.7-99.9%). The chiral auxiliary, although used in stoichiometric quantities, could be isolated and reused, but the practicality and scope of this procedure is limited by the use of the strong - as well as expensive and sensitive - phospha-zene base. 

Of course, the key limitation of the ylide-mediated methods discussed so far is the use of stoichiometric amounts of the chiral reagent. Building on their success with catalytic asymmetric ylide-mediated epoxidation (see Section 1.2.1.2), Aggarwal and co-workers have reported an aza version that provides a highly efficient catalytic asymmetric synthesis of trans-aziridines from imines and diazo compounds or the corresponding tosylhydrazone salts (Scheme 1.43) [68-70]. 

D. Miscellaneous.—Low yields of the spirophosphoranes (34) were obtained on heating the phosphorane (32) with the aziridines (33). Stable phosphoranes have been obtained from phenanthraquinone mono-imine (35) and trialkyl phosphites, and from 2-chlorotropone (36) and ylides. In the latter reaction cyanomethylenetriphenylphosphorane gave instead the betaine (37). 

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