Esters from nitrogen heterocycles

Protonated nitrogen heterocycles can be carbalkoxylated" by treatment with esters of a-keto acids and Fenton s reagent. Pyridine is carbalkoxylated at C-2 and C-4, for example. The attack is by "COOR radicals generated from the esters ... 

In Table IV some physical data and spectral characteristics of 6,7-secoberbines are listed. Only methyl corydalate (55) is optically active. Formula 55 presents the spatial structure of this compound, deduced by Nonaka et al. (65) and confirmed by Cushman et al. by both correlation with (+)-mesotetrahydrocorysamine (72) (<5S) and total synthesis (69). It is difficult to find common characteristic features in both the mass and H-NMR spectra of these alkaloids because they differ significantly from each other in their structures. On one hand, corydalic acid methyl ester (55) incorporates a saturated nitrogen heterocycle, while the three aromatic bases (56-58) differ in the character of the side chain nitrogen. For example, in mass fragmentation, ions of the following structures may be ascribed to the most intensive bands in the spectrum of 55 ... 

At that time, as now, the enantiomers of many chiral amines were obtained as natural products or by synthesis from naturally occurring amines, a-amino acids and alkaloids, while others were only prepared by introduction of an amino group by appropriate reactions into substances from the chiral pool carbohydrates, hydroxy acids, terpenes and alkaloids. In this connection, a recent review10 outlines the preparation of chiral aziridines from enantiomerically pure starting materials from natural or synthetic sources and the use of these aziridines in stereoselective transformations. Another report11 gives the use of the enantiomers of the a-amino acid esters for the asymmetric synthesis of nitrogen heterocyclic compounds. 

The IR, NMR, and mass spectra of daphmacrine (18) suggest that it has a nitrogen heterocyclic skeleton similar to that of daphniphylline (1) but differs in the oxygen-containing moiety. The IR spectrum of this alkaloid showed two carbonyl bands at 1770 and 1730 cm-1 resulting from a five-membered lactone and an ester group, respectively. The NMR spectrum showed the presence of two tertiary methyl... 

In addition to epoxides, three-membered nitrogen heterocycles, aziridines, can be obtained by means of catalytic asymmetric aziridinations (Eq. 30). To this aim, chiral ruthenium(salen) complexes 67 [56] and 68 [57] were useful (Fig. 1). The former phosphine complexes 67 gave the aziridine from two cy-cloalkenes with 19-83% ee [56]. On the other hand, terminal alkenes selectively underwent aziridination in the presence of the latter carbonyl complex 68 with 87-95% ee [57]. In these examples, N-tosyliminophenyliodinane or N-tosyl azide were used as nitrene sources. Quite recently, catalytic intramolecular ami-dation of saturated C-H bonds was achieved by the use of a ruthenium(por-phyrin) complex (Eq. 31) [58]. In the presence of the ruthenium catalyst and 2 equiv iodosobenzene diacetate, sulfamate esters 69 were converted into cyclic sulfamidates 70 in moderate-to-good yields. 

Chiral 2//-azirines have been prepared by dehydrochlorination of 7V-chloroaziridines, Swem oxidation of aziridines and elimination from A -sulfinylaziridines. These reactions require the use of high enantiopure aziridine esters as starting materials <03T2345>. Chiral enriched ethyl 3-methyl-2//-azirine-2-carboxylate was found to act as an efficient alkylating agent for the preparation of a variety of five-membered aromatic nitrogen heterocycles <03TL6277>. 

The N-acyliminium ion cyclization method for the synthesis of nitrogen heterocycles, developed by Speckamp and his collaborators, has also been applied to the synthesis of the vindorosine intermediate 529 (315). In this synthesis, the imine 531, derived from 3-(o-aminophenyl)-N-benzylsuccini-mide, was cyclized by base and acetylated to give 532, which was partially reduced to give the substrate 533 for N-acyliminium cyclization. Treatment of 533 with acid then gave the tetracyclic enol ester 534, which was converted into the target tetracyclic amino ketone 529a by obvious methods (Scheme 61) 315). 

A method of esterification introduced by Meyer807 is to dissolve the carboxylic acid in an excess of concentrated sulfuric acid (if necessary with warming) and to treat the solution cautiously with a small excess of the requisite alcohol when the reaction, which is often violent, ceases—if the mixture does not become warm, it must be heated—the solution is poured on solid sodium carbonate and worked up. This method has been used for esterification of sterically hindered acids and for carboxy derivatives of nitrogenous heterocycles, also for preparation of acetonedicarboxylic esters from citric acid and alcohols.808... 

Nitrogen heterocycles Various cyano-substituted pyridines have been described. They were prepared from 10 and ethyl cyanoacetic ester, and from 10 and acetylenic esters or ketones ". Aromatic aldehydes (e.g. 2-furyl, 4-pyridyl, and 2-thienyl aldehydes) have been condensed with 10 and aromatic ketones to yield 2-amino-3-pyridinecarbonitriles. Benzylidenemalononitrile (43) reacted with 10 in aniline to yield dicyanopyridine 44. ... 

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