Chirality nitrogen atom

Another compound in which nitrogen is connected to two oxygens is 11. In this case there is no ring at all, but it has been resolved into ( + ) and (-) enantiomers ([a] = 3°).37 This compound and several similar ones reported in the same paper are the first examples of compounds whose optical activity is solely due to an acyclic tervalent chiral nitrogen atom. However, 11 is not optically stable and racemizes at 20°C with a half-life of 1.22 hr. A similar compound (11, with OCH2Ph replaced by OEt) has a longer half-life— 37.5 hr at 20°C. 

An interesting version of this concept was published recently [18]. After reaction of the alanine ester 5 with borane, the mixture of the diastereo-mers 6 and 7 could be separated (Scheme 1). The chiral nitrogen atom directs the attack of the electrophile at the enolate. The direction of the attack can be explained by the Felkin - Anh model, because the electrophile approaches anti to the largest (benzyl) substituent. The enolate shown... 

The chirality of the phenylalanine derivative 10 is used for a direct, stereoselective a-alkylation (Scheme 2) [19]. After treatment with base and reaction with an electrophile the a-alkylated amino acid 11 is obtained in up to 88 % ee. It is not yet clear whether the deprotonated species is an enolate with a chiral nitrogen atom (12) or a chiral, a-metallated compound (13). The protecting groups on the nitrogen seem to play an important role. It is not yet possible to alkylate other phenylalanine derivatives by means of this reaction. 

A promising Pd(II)-catalyzed enantioselective C—H activation reaction has been demonstrated using monoprotected a-amino acids as chiral ligands (Equation 11.32) [70]. The coordination of a chiral nitrogen atom at the metal center is believed to be crucial for the enantiocontrol. This approach opens the door for chiral recognition in the C—H activation step. 

Canying out the process of resolution repeatedly they obtained the opticaly pure (-)-product willi an [a]546 = -1992°. On lactose Prelog and Wieland succeded in resolving racemic "Troger s base ", which contains chiral nitrogen atoms (Scheme 7). 

Forms of [CoXjftrien)] . Chiral nitrogen atoms are blue. 

Figure 4.5 Isomerization change by decoordination, inversion, and recoordination of a pyramidal chiral nitrogen atom. The 8 conformation is recovered at the end of the reaction.

Figure 10.3-40. The rating for the disconnection strategy carbon-heteroatom bonds is illustrated, Please focus on the nitrogen atom of the tertiary amino group. It is surrounded by three strategic bonds with different values. The low value of 9 for one ofthese bonds arises because this bond leads to a chiral center. Since its formation requires a stereospecific reaction the strategic weight of this bond has been devalued. In contrast to that, the value of the bond connecting the exocyclic rest has been increased to 85, which may be compared with its basic value as an amine bond.

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.)... 

Secondary amines having one oi two chiral groups attached to the nitrogen atom are prepared from boronic esters by their conversion into alkyldichlotobotanes, followed by treatment with organic azides (518). The second chiral group can be derived from an optically active azide. 

For example, only those dihydropyrimidines that contained a hydrogen-bonding donor at position 3 next to the chiral center were separated. Remarkably, dihydropyrimidines with non-substituted nitrogen atoms at positions 1 and 3 resulted in separations with longer retention times and decreased separation factors a. Increas-... 

As described previously, lipophilic monoimidazole ligands form 2 1 complexes with the Zn2 + ion (n = 2 in Scheme 2) as active catalysts except for some sterically hindered ligands (Table 3, 5, 7), and bisimidazole ligands form 1 1 complexes (n = 1 in Scheme 2, Table 5). In this chiral system, the latter 1 1 complex accords with kinetic analyses for both L-47 and L,L-49 ligands as shown in Fig. 12 and Table 11. These conclusions seem to be reasonable since monoimidazole derivatives have only one imidazole nitrogen, while the other bisimidazole and chiral ligands have more than two nitrogen atoms which can effectively coordinate to the Zn2 + ion. 

One consequence of tetrahedral geometry is that an amine with three different substituents on nitrogen is chiral, as we saw in Section 9.12. Unlike chiral carbon compounds, however, chiral amines can t usually be resolved because the two enantiomeric forms rapidly interconvert by a pyramidal inversion, much as an alkyl halide inverts in an Sfg2 reaction. Pyramidal inversion occurs by a momentary rehybridization of the nitrogen atom to planar, sp2 geometry, followed by rehybridization of the planar intermediate to tetrahedral, 5p3 geometry... 

In addition to ketone enolates, azaenolatcs with chiral auxiliary groups attached to the nitrogen atom are suitable for the introduction of an a-unsubstituted enolate of the keto-type into an aldehyde in a stereoselective manner (see Section D.1.3.5.). 

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. 

In molecules in which the nitrogen atom is at a bridgehead, pyramidal inversion is of course prevented. Such molecules, if chiral, can be resolved even without the presence of the two structural features noted above. For example, optically active 12 (Trdger s base) has been prepared. Phosphorus inverts more slowly and arsenic still more slowly." Nonbridgehead phosphorus," arsenic, and antimony compounds have also been resolved... 

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. 

---