Azomethine ylides catalytic reactions

The amino acid derived chiral oxazolidinone 188 is a very commonly used auxiliary in Diels-Alder and aldol reactions. However, its use in diastereoselective 1,3-dipolar cycloadditions is less widespread. It has, however, been used with nitrile oxides, nitrones, and azomethine ylides. In reactions of 188 (R = Bn, R =Me, R = Me) with nitrile oxides, up to 92% de have been obtained when the reaction was performed in the presence of 1 equiv of MgBr2 (303). In the absence of a metal salt, much lower selectivities were obtained. The same observation was made for reactions of 188 (R = Bn, R = H, R = Me) with cyclic nitrones in an early study by Murahashi et al. (277). In the presence of Znl2, endo/exo selectivity of 89 11 and up to 92% de was observed, whereas in the absence of additives, low selectivities resulted. In more recent studies, it has been shown for 188 (R =/-Pr, R = H, R =Me) that, in the presence of catalytic amounts of Mgl2-phenanthroline (10%) (16) or Yb(OTf)3(20%) (304), the reaction with acyclic nitrones proceeded with high yields and stereoselectivity. Once again, the presence of the metal salt was crucial for the reaction no reaction was observed in their absence. Various derivatives of 188 were used in reactions with an unsubstituted azomethine ylide (305). This reaction proceeded in the absence of metal salts with up to 60% de. The presence of metal salts led to decomposition of the azomethine ylide. 

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. 

Chiral bicyclic lactams have been successfully utilized by Meyers as chiral dipolarophiles in highly diastereoselective azomethine ylide cycloadditions (73). Treatment of the ylide precursor 218 with the unsaturated, non-racemic dipolar-ophile 219 in the presence of a catalytic amount of TFA led to the formation of tricyclic adducts 220 and 221 in excellent yields (85-100%). The diastereofacial preference for the reaction was dependent on the nature of R with a methyl group... 

There has been great interest in recent years in methods for the generation of azomethine ylides and in exploitation of these reactive species in tandem/cascade processes for the rapid assembly of polyaza, polycyclic, multifunctional systems. a-Diazo ketones have featured greatly in such studies, treatment with a catalytic amount of rhodium(II) acetate generating transient rhodium carbenoids. A very common feature of many investigations of this type is the occurrence of quite unexpected reactions. For example, treatment of the diazo ketone 1 with a catalytic amount of... 

An intramolecular [3 + 2] dipolar cycloaddition reaction has also been exploited in the design of a concise, stereospecific synthesis of ( )-a-lycorane (57) (119). Thus, cyclization of the azomethine ylide 145, which was produced in situ by the reaction of 144 with IV-benzylglycine, in refluxing toluene furnished the cw-hydroindole 146 as the exclusive product (Scheme 14). The transformation of 146 to racemic a-lycorane (57) was then achieved by N-debenzylation via catalytic, transfer hydrogenation and subsequent Pictet-Spengler cyclization. 

The tandem reaction of carbenoids with simple imines to form azomethine ylides which then undergo 1,3-dipolar cycloaddition with various dipolarophiles was first reported in 1972.81 Treatment of phenyldiazomethane with copper bronze in the presence of excess N-benzylidenemethylamine resulted in the isolation of imidazoline 170. Formation of this product was rationalized by carbenoid addition onto the imine nitrogen to give azomethine ylide 169 which then underwent a 1,3-dipolar cycloaddition with another molecule of imine to produce the observed product. Bartnik and Mloston subsequently extended this observation by using other dipolarophiles.82 For example, catalytic decomposition of phenyldiazomethane and A-benzylidenemethylamine in the presence of dimethyl maleate or benzaldehyde gave pyrrolidine 171... 

In the area of [3 + 2]-cycloadditions (1,3-dipolar cycloadditions), chiral silver catalysts have been utilized extensively for the enantioselective formation of five-membered rings from prochiral substrates. For example, Zhang and co-workers360 have reported the highly enantioselective Ag(i)-catalyzed [3 + 2]-cycloaddition of azomethine ylides to electron-deficient alkenes. Thus, reaction of ct-imino esters 442 with dimethyl maleate in the presence of catalytic amounts of silver(i) acetate and the chiral bisferrocenyl amide phosphine 443 provided the chiral pyrrolidines 444 with high stereoselectivities and chemical yields (Scheme 131). Only the endo-products were isolated in all cases. 

Similar azomethine ylides 48 are involved as key intermediates in the racemi-zation of optically active a-amino acids in the presence of a catalytic amount of aldehyde (83JOC843). Grigg confirmed this mechanism (83TL4457) and carried out the reactions of optically pure a-amino acids with salicyl- or o-methoxybenzaldehyde and maleic anhydride or N-phenylmaleimide in acetic acid. Cycloadducts of N-unsubstituted azomethine ylides 48 with dipolaropbiles were obtained only as racemates. These results indicate that the a-amino acids first produced the corresponding imine carboxylic acids with the retention of optical activity but these then undergo a tautomeric equilibration with N-protonated azomethine ylides 48 losing their optical purity. The ylides 48 were captured by several dipolaropbiles as racemic cycloadducts. As the imines of a-amino acids usually suffer spontaneous decarboxylation (as will be discussed later in Section (II,E), the formation of... 

However, at this stage relatively little progress has been made in research on asymmetric catalytic carbene transfer to imines. In 1995, Jacobsen and Jorgensen reported independently that reaction of ethyl diazoacetate with selected imines can be catalyzed by copper salts [27,28]. In the former case [27], moderate levels of enantioselection were found to be imparted by bisoxazoline ligands associated with the copper catalyst (Scheme 11). The observation of racemic pyrrolidine byproducts in the reaction was taken to support a mechanism of catalysis involving initial formation of a copper-bound azomethine yhde intermediate (Scheme 12 ). Collapse of this intermediate to the optically active aziridine apparently competes with dissociation of the copper to a free azomethine ylide. The latter can react with fumarate formed by diazoester decomposition in a dipolar cycloaddition to afford racemic pyrrolidine. 

Catalytic [3 + 2]-cycloaddition of the carbonyl and azomethine ylides 129 with olefins gives the five-membered heterocycles 130 (Scheme 45). Longmire et al. reported that the catalytic asymmetric [3 + 2]-cycloaddition of the azomethine ylides 131 with dimethyl maleate in the presence of AgOAc and a bis-ferrocenyl amide ligand 133 gave the pyrrolidine triesters 132 in excellent yields with very high enantiomeric excesses (Scheme 46).122 As described in section 8, the [3 + 2]-cycloaddition reaction of diazo compounds with olefins proceeds similarly through the formation of carbonyl ylides. 

Similar azomethine ylides 48 are involved as key intermediates in the racemi-zation of optically active a-amino acids in the presence of a catalytic amount of aldehyde (83JOC843). Grigg confirmed this mechanism (83TL4457) and carried out the reactions of optically pure a-amino acids with salicyl- or... 

The greater part of this chapter is concerned with the Diels-Alder and hetero-Diels-Alder reaction. The asymmetric version of both of these reactions can be catalysed with metal-based Lewis acids and also organocatalysts. The catalytic asymmetric 1,3-dipolar cycloaddition of nitrones and azomethine ylides is also discussed. Again, most success in this area has been achieved using metal-based Lewis acids and the use of organocatalysts is begiiming to be explored. This chapter concludes with a brief account of recent research into the asymmetric [2+2]-cycloaddition, catalysed by enantiomerically pure Lewis acids and amine bases, and also the Pauson-Khand [2- -2- -l] cycloaddition mediated by titanium, rhodium and iridium complexes. 

Tricyclic dihydropyrrolizinesj The reaction of N-acyl-2-(l-diazoacetyl)-pyrro-lidines (1) with a catalytic amount of a rhodium(II) carboxylate, particularly rhodium(Il) octanoate and a dipolarophile (DMAD), results in a tricyclic dihydropyrrolizine 3 as the major product. The expected product (2) is formed only in traces (10%). Apparently the intermediate carbonyl ylide a rearranges to the more stable azomethine ylide b. 

Lee et al. reported on the reaction of mono- and dinitro-substituted benzenes, naphthalenes, and some other benzo-annelated heterocycles with unstabilized N-benzyl azomethine ylide, which was generated in situ from hemiaminal 169 by action of catalytic amounts of trifluoroacetic acid (Scheme 81) [134],... 

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