Asymmetric centers nitrogen atoms

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. 

Atoms Other than carbon can be asymmetric centers. Any atom that has four different groups or atoms attached to it is an asymmetric center. For example, the following pairs of compounds, with nitrogen and phosphorus asymmetric centers, are enantiomers. 

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. 

Pyramidal nitrogen is favorable for slow inversion. In this case, two methyl groups in the SilV Bu fragment are nonequivalent, whereas two SiMej groups are, on the contrary, equivalent. However, any two identical substituents at the nitrogen atom become nonequivalent in the presence of the asymmetric center G attached to the C,C double bond. 

Coordination of ammonia or a substituted ammonia to a metal ion alters markedly the N — H dissociation rate (see See. 6.4.2). Since also proton dissoeiation of complexed ammines is base-catalyzed, then exchange can be made quite slow in an aeid medium. Thus, in a eoordinated system of the type 12, containing an asymmetric nitrogen atom (and this is the only potential souree of optical activity), there is every chance for a successful resolution in acid conditions, since inversion is expected only after deprotonation. It was not until 1966 that this was suc-eessfully performed, however, using the complex ion 12. A number of Co(III), Pt(II) and Pt(IV) complexes containing sarcosine or secondary amines have been resolved and their raeemizations studied.Asymmetrie nitrogen centers appear eonfined to d and d ... 

Nitrogen, Phosphorus and Sulfur Atoms as Asymmetric Centers 232... 

In this series of compounds, the chiral center is located at the nitrogen atom whereas most chiral catalysts used for asymmetric induction have a chiral center removed from the nitrogen atom and, moreover, contain a hydroxy group / to the nitrogen atom, which may lead to the decomposition... 

Marks et al. [77, 294]. The formation of heterocyclic nitrogen compounds is of relevance in natural products, particularly in alkaloid synthesis, when the formation of the C-N bond occurs with asymmetric induction. The cyclization is not restricted to primary amines and produces 2-methylheterocycles (5-, 6-, 7-membered) with >99% regioselectivity and a new asymmetric center adjacent to the heterocyclic nitrogen atom (Scheme 17). 

When a group containing a homochiral center derived from camphor, (S)-phenylethylamine or phenylalanine is bonded to the nitrogen atom of a 4-alkenylamine, a good asymmetric induction can be realized in the cyclization mediated by electrophiles. 

The spatial relationships that exist for the human body also exist at the molecular level because the molecules of nature exist as three-dimensional symmetrical and asymmetrical figures. One of the most common asymmetric molecules is a tetravalent carbon atom with four different ligands attached to it. The spatial arrangement of the atoms in this molecule is shown in Fig. 2, The carbon atom depicted in Fig. 2 is the asymmetric center of the molecule, and the molecule is a chiral stereoisomer. If the molecule and its mirror image are nonsuperimposable, the relationship between the two molecules is enantiomeric, and the two stereoisomers are enantiomers. Carbon is not the only atom that can act as an asymmetric center. Phosphorus, sulfur, and nitrogen are among some of the other atoms that can form chiral molecules. 

Molecules that do not possess an asymmetric center may still have nonsuperimposable mirror images and exist as enantiomers. These molecules contain a chiral plane or chiral axis and are dissymmetric with respect to either that plane or axis. The structures of the enantiomers of the sedative-hypnotic methaqualone are presented in Fig. 4. In this molecule there is a chiral axis between the nitrogen atom (N-1) and phenyl ring (C-1). The dissymmetry of the two forms of the molecule is a result of hindered rotation around this axis, which is due to steric interactions between methyl groups (M-1 and M-2). Other axially dissymmetric molecules include allene, biaryls, alkylidenecyclohexanes, and spiranes. Planar dissymmetric molecules are exemplified by molecules such as tra s-cycloalkenes. 

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. 

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