Nitrogen asymmetric atoms

In this chapter, metal-mediated asymmetric oxygen-, nitrogen-, and carbon-atom transfer reactions were described. The substrates were limited to olefins. Owing to limited space, examples of the reactions were collected with the priority given to enantioselectivity, except for some germinal... 

SRURC is such an interesting example of the facile formation of chiral induction from racemic mixtures in the absence of any external symmetry-breaking agent that it deserves special attention. One of the best studied examples is the crystallization of bromofluoro-l,4-benzodiazepinooxazole (Fig. 11.3), which possesses a single asymmetric carbon atom at C14 and a potentially asymmetric bridgehead nitrogen atom at N4. 

The coordination chemistry of macrocyclic ligands has been extensively studied and aspects of isomerism have been considered in numerous systems.241 Methods whereby two diastereomers of complexes of tetra- N-methylcyclam may be isolated have been discussed previously.184 This, however, is a relatively simple system and it is usually necessary to consider isomerism due to the presence of asymmetric atoms in the chelate arms, as well as that due to asymmetric donor atoms that may be rendered stable to inversion by coordination. An example of a system exhibiting this level of complexity is afforded by the nickel(II) complexes of the macrocyclic ligands generated by reduction of the readily prepared macrocycle (46). These ligands contain two asymmetric carbon atoms and four asymmetric nitrogen atoms but, because AT-inversion is rapid, it is conventional to consider that only three separable stereoisomers exist. There is an enantiomeric pair, (47a) and (47b), which constitutes the racemic isomer (R, R ), and an achiral (R, S ) diastereomer (47c), the meso isomer. 

Most chiral organic compounds have at least one asymmetric carbon atom. Some compounds are chiral because they have another asymmetric atom, such as phosphorus, sulfur, or nitrogen, serving as a chirality center. Some compounds are chiral even though they have no asymmetric atoms at all. In these types of compounds, special characteristics of the molecules shapes lend chirality to the structure. 

When the nitrogen atom is at a ring junction in bridged systems, pyramidal inversion is impossible without bond cleavage. An asymmetrically substituted nitrogen atom then becomes a stable center of chirality, a common situation in alkaloid chemistry. 

G. N. Shustov, A. B. Zolotoy, and R. G. Kostyanovskii. Asymmetrical nonbridgehead nitrogen-30 geminal systems—21. The influence of vicinal n-o interaction of the pyramidal stability of tricoordinated nitrogen atom in the X-N-Y geminal system. Tetrahedron 38, 2319-2326 (1982). 

Upon confronting the asymmetric carbon-nitrogen hydrogenation problem, we noted that, like a-enamides, A-acylhydrazones 32 possess an amide-like carbonyl oxygen that is similarly situated three atoms from the double bond to be reduced, and which could allow for chelation of the substrate to the catalytic Rh center. 

Caranine, like lycorine, forms an a- and a /3-methiodide which arise from the asymmetric quaternary nitrogen atom. At 120° Hofmann degradation of a mixture of the methiodides gave the optically inactive caranine anhydromethine. This base contains no hydroxyl group or isolated double bond. Since the nitrogen atom is known to be benzylic (lactam formation) and oxidation of the methine gave 4,5-methylene-dioxybiphenyl-2,3 -dicarboxylic acid (LXXIIIa), caranine anhydro-methine is represented by XLI. The methiodide of XLI in methyl iodide solution underwent nucleophilic attack at the benzylic position by the iodide ion to give LXXII, which was converted to its methiodide by the excess methyl iodide present in the reaction mixture. Under... 

In the absence of a kinetically stable M—N bond the asymmetry is lost due to rapid pyramidal inversion of the free amine (AG<25 kjmol ), unless the asymmetrically substituted nitrogen atom is part of a rigid organic ring system. The simplest and earliest studied coordination compound incorporating an asymmetric coordinated secondary nitrogen as the sole source of chirality is [Co(sarcosine)(NH3)4] (sarcosine = N-methylglycinate) (28). Numerous reports... 

Wieland This was the first classical demonstration that optical activity was due to an asymmetric trivalent nitrogen atom. Cyclophanes 2 in Fig. 1 consisting of two Troger base skeletons... 

Racemization of some macrocyclic Sehiff-base complexes of nickel(n) is reported to involve inversion of both asymmetric secondary nitrogen atoms activation parameters are reported. The mer- fac isomerization of [Ni(oxine)3] is facile in methanol-chloroform solvent mixtures. ... 

In the case of drugs, this element of asymmetry is a chiral carbon atom with four different substituents and less often asymmetric atoms of nitrogen, sulfur, or phosphorus. 

Chiral Center. The chiral center, which is the chiral element most commonly met, is exemplified by an asymmetric carbon with a tetrahedral arrangement of ligands about the carbon. The ligands comprise four different atoms or groups. One ligand may be a lone pair of electrons another, a phantom atom of atomic number zero. This situation is encountered in sulfoxides or with a nitrogen atom. Lactic acid is an example of a molecule with an asymmetric (chiral) carbon. (See Fig. 1.13b.)... 

It should be noted that the sense of asymmetric induction in the lithiation/ rearrangement of aziridines 274, 276, and 279 by treatment with s-butyllithium/ (-)-sparteine is opposite to that observed for the corresponding epoxides (i.e. removal of the proton occurs at the (S)-stereocenter) [102], If one accepts the proposed model to explain the selective abstraction of the proton at the (R) -stereo-center of an epoxide (Figure 5.1), then, from the large difference in steric bulk (and Lewis basicity) between an oxygen atom and a tosyl-protected nitrogen atom, it is obvious that this model cannot be applied to the analogous aziridines. 

The oxidation method can also be applied to asymmetrically substituted 1,3-diaryltriazenes. The oxygen attacks the nitrogen atom nearest to an electron-releasing... 

Chiral heterocyclic compounds containing vicinal oxygen and nitrogen atoms were achieved by an asymmetric Diels-Alder reaction [111] of chiral acylnitroso dienophiles 111. The latter were prepared in situ from alcohols 110, both antipodes of which are available from camphor, and trapped with dienes (Scheme 2.46). Both the yield (65-94 %i) and diastereoisomeric excess (91-96%) were high. 

Double asymmetric induction operates when the azomethine compound is derived from a chiral a-amino aldehyde and a chiral amine, e.g., the sulfin-imine 144 [70]. In this case, the R configuration at the sulfur of the chiral auxihary, N-tert-butanesulfinamide, matched with the S configuration of the starting a-amino aldehyde, allowing complete stereocontrol to be achieved in the preparation of the diamine derivatives 145 by the addition of trifluo-romethyl anion, which was formed from trifluoromethyltrimethylsilane in the presence of tetramethylammonium fluoride (Scheme 23). The substituents at both nitrogen atoms were easily removed by routine procedures see, for example, the preparation of the free diamine 146. On the other hand, a lower diastereoselectivity (dr 80 20) was observed in one reaction carried out on the imine derived from (it)-aldehyde and (it)-sulfinamide. 

Associated to copper(II) pre-catalysts, bis(oxazolines) also allowed the asymmetric Diels-Alder and hetero Diels-Alder transformations to be achieved in nearly quantitative yield and high diastereo- and enantioselectivities. Optically active sulfoximines, with their nitrogen-coordinating site located at close proximity to the stereogenic sulfur atom, have also proven their efficiency as copper ligands for these asymmetric cycloadditions. Other precursors for this Lewis acid-catalyzed transformation have been described (e.g., zinc salts, ruthenium derivatives, or rare earth complexes) which, when associated to bis(oxazolines), pyridine-oxazolines or pyridine-bis(oxazolines), led to efficient catalysts. 

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