Chiral nitrogen compounds

Amines with three different substituents are potentially chiral because of the pseudotetrahedral arrangement of the three groups and the lone-pair electrons. Under normal conditions, however, these enantiomers are not separable because of the rapid inversion at the nitrogen center. As soon as the lone-pair electrons are fixed by the formation of quaternary ammonium salts, tertiary amide N-oxide, or any other fixed bonding, the inversion is prohibited, and consequently the enantiomers of chiral nitrogen compounds can be separated. 

Minder, R., Schuerch, M., Mallat, T., Baiker, A. (1995) Chiral nitrogen-compounds as new modifiers for the enantioselective hydrogenation of ethyl pyruvate, Catal. Lett. 31, 143-151. 

Although unsynunetrically substituted amines are chiral, the configuration is not stable because of rapid inversion at nitrogen. The activation energy for pyramidal inversion at phosphorus is much higher than at nitrogen, and many optically active phosphines have been prepared. The barrier to inversion is usually in the range of 30-3S kcal/mol so that enantiomerically pure phosphines are stable at room temperature but racemize by inversion at elevated tempeiatuies. Asymmetrically substituted tetracoordinate phosphorus compounds such as phosphonium salts and phosphine oxides are also chiral. Scheme 2.1 includes some examples of chiral phosphorus compounds. 

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... 

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. 

The replacement of the oxygen atom in sulfoxides by nitrogen leads to a new class of chiral sulfur compounds, namely, sulfimides, which recently have attracted considerable attention in connection with the stereochemistry of sulfoxide-sulfimide-sulfoximide conversion reactions and with the steric course of nucleophilic substitution at sulfur. The first examples of chiral sulfimides, 88 and 89, were prepared and resolved into enantiomers by Phillips (127,128) by means of the brucine and cinchonidine salts as early as 1927. In the same way, Kresze and Wustrow (129) were able to separate the enantiomers of other structurally related sulfimides. 

In recent years three other examples of asymmetric induction have been described in the literature in which the chiral sulfur reagent that induces optical activity is converted into another chiral sulfur compound. The first reaction of this type is the chlorination of 2,2-diphenylaziridine (265) by means of the optically active A -chloro-phenylmethylsulfoximide (266), affording optically active A -chloro-2, 2-diphenylaziridine (267) and the unsubstituted sulfoximide 149 (197). In this case asymmetric induction is observed on the nitrogen atom. 

Chiral protoalkaloids, such as cathinone (55), a psychotropic constituent of Catha edulis Forssk. (khat), have provided probes for studying the mechanistic properties of biogenic amine transporters, and afforded information regarding the effect of stereochemistry at the transportation level of these nitrogenous compounds. ... 

Silicon (Si) and germanium (Ge) are in the same group of the periodic table as carbon, and they form tetrahedral compounds as carbon does. When four different groups are situated around the central atom in silicon, germanium and nitrogen compounds, the molecules are chiral. Sulphoxides, where one of the four groups is a nonbonding electron pair, are also chiral. 

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. 

Electrophilic nitrogen compounds, such as arenesulfonyloxyamines, can convert alkenes to aziridines without the intervention of free nitrenes (80CC560). The ylide Ph2S+-NH adds stereospecifically to E and Z conjugated alkenes, and chiral sulfimides can transfer chirality to the aziridines formed (80T73). These reactions are often named aziridinations . 

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. 

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. 

In the second approach, a chiral nitrogen-containing compound has most often been used as the ligand to achieve enantioselectivity. Thus, oxidation of ( )-stilbene (22 equation 9) with a stoichiometric quantity of osmium tetroxide in toluene at room temperature, in the presence of dihydroquinine acetate (23), yielded r/ireo-hydrobenzoins (24) after reductive hydrolysis, with an enantiomeric excess of 83.2% in favor of the (15,25)-(-)-isomer performing the reaction at -78 C increased the eiuuitiomeric excess to 89.7%. 

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