Amine chirality

Recently Turner and coworkers have sought to extend the deracemization method beyond a-amino acids to encompass chiral amines. Chiral amines are increasingly important building blocks for pharmaceutical compounds that are either in clinical development or currently licensed for use as drugs (Figure 5.7). At the outset of this work, it was known that type II monoamine oxidases were able to catalyze the oxidation of simple amines to imines in an analogous fashion to amino acid oxidases. However, monoamine oxidases generally possess narrow substrate specificity and moreover have been only documented to catalyze the oxidation of simple, nonchiral... 

Now let us turn to an examination of the A-[Co(en)2(Ala-(S)-AlaOMe)]3+ products. When 0.03 M (S)-AlaOMe was used RP-HPLC gave 50% A-RS and 50% ASS after 8 s, building to 76% A-RS and 24% ASS at the conclusion of the reaction (500 s). With 0.06 M (S)-AlaOMe the result was 32% A-RS and 68% ASS (4 s) building to 58% A-R-S and 42% ASS (24 s) with 0.06 M (R)-AlaOMe the comparison were 34% A-R-S (4 s) building to 55% (24 s), i.e., nearly the same distributions. These results require the A-R ester to react with (S)- or CR)-AlaOMe to give the A-R-S (or A-R-R) product at a considerably faster rate (via k4) than does the A-S ester to give ASS (or A-S-R). Also, either differences between the rate constants for epimerization and aminolysis cancel the effect of chirality of the amine base or the rate constants themselves are little affected by the amine chirality. Subsequent analysis on other systems found the latter explanation to hold. 

ImH+ imidazolium cation amine (chiral auxiliary reagent derived... 

Keywords Asymmetric hydrosilylation, optically active alcohols, amines, Chiral Titanocene Catalysts, Acyclic Imines, Cyclic Imines, Chiral Rhodium Catalysts, aromatic ketones... 

Prochiral imines to chiral amines Chiral enamine reductions Ir/Perfluoroalkyl modified-phosphinodihydrooxazoles/B(ArF)4 (it,R)-Et-DuPHOS-Rh+X X = B(f)4 or CF3S03]... 

Enantioselective synthesis of primary amines Chiral -substituted primary amines (3) can be prepared in 95% ee from SAMP hydrazones (2) of primary aldehydes (equation I). 

Amin- (chirale) Vl/lb, 248 Amin-cyan-dihydro- XIII/3b, 501 Amino-diaryl- XIII/3b, 71 Aryl-benzyl-chlor- XIII/3a, 398 Aryl-bis-[2,4,6-trimethyl-phenyl]-XIII/3a, 167 Aryl-dijod- XIII/3a, 465 Azido-diorgano- XIII/3b, 114 Bis-[alkylamino]-phenyl- XIII/3b,... 

A closely related method does not require conversion of enantiomers to diastereomers, but relies on the fact that (in principle, at least) enantiomers have different NMR spectra in a chiral solvent, or when mixed with a chiral molecule (in which case transient diastereomeric species may form). In such cases, the peaks may be separated enough to permit the proportions of enantiomers to be determined from their intensities.Another variation, which gives better results in many cases, is to use an achiral solvent but with the addition of a chiral lanthanide shift reagent such as fn5[3-trifluoroacetyl-(i-camphorato]europium(III). ° Lanthanide shift reagents have the property of spreading NMR peaks of compounds with which they can form coordination compounds, for example, alcohols, carbonyl compounds, and amines. Chiral lanthanide shift reagents shift the peaks of the two enantiomers of many such compounds to different extents. 

Deoxygenations. with PhjP-DEAD and Formation of o-hydroxybenzaldoxin accomplished at room Amines. Chiral reaction employing nucleophile. The a-a means of an intramole acids. Thus, subject] conditions leads to... 

Amines. Chiral a-amino acids are obtained from cyanohydrins via a Mitsunobu reaction employing A-f-butoxycarbonyl-A-(2-trimethylsilyl)ethylsulfonamide as the nucleophile. The a-aminonitrile derivatives thus generated are hydrolyzed with acid. By means of an intramolecular displacement (3-hydroxy acids are transformed into (3-amino acids. Thus, subjecting the derived 0-benzylhydroxamides to Mitsunobu reaction conditions leads to (3-lactams which are readily processed (LiOH H, Pd/C). 

The brush-type of CSP was introduced by Pirkle who was one of the pioneers of modern enantioselective liquid chromatography [55]. The most frequently used 7i-acceptor phases are derived from the amino acids phenylglycine (DNBPG) (Fig. 6.8) or leucine (DNBLeu) covalently or ionically bonded to 3-aminopropyl silica gel [56, 57]. These CSPs are commercially available for analytical or preparative separation of enantiomers. Further CSPs based on amino acid or amine chiral selectors such as valine, phenylalanine, tyrosine [58] and l,2-tr s-diaminocyclohexane (DACH-DNB phase) [59] and 1,2-traus-diphenylethylene diamine (ULMO phase) [60] were also developed (Fig. 6.8). These CSPs have been applied for the preparative separation of the enantiomers of a few racemic compounds, but the number of reported preparative applications has remained very limited over the last 10 years. 

Monodentate phosphites are another type of prominent monodentate phosphorus ligands applied in asymmetric hydrogenation of enamides for the synthesis of chiral amines. Chiral monodentate phosphites can be easily prepared from a chiral diol and an alcohol. Generally, the chiral diol was first reacted with a phosphorus trichloride to form a phosphorochloridite, followed by the reaction with an appropriate alcohol to yield a chiral monodentate phosphite [35[. The reaction of an alcohol with phos phorus trichoride to yield a phosphorodichloridite, which was then treated with a chiral diol, is also a good procedure for the synthesis of chiral monodentate phosphites [36]. 

Keywords Asymmetric hydrogenation. Asymmetric transfer hydrogenation, BINAP, Chiral alcohols, Chiral amines. Chiral phosphines. Functionalized ketones. Homogeneous catalysts. Simple ketones... 

Miscellaneous Azides. Ethyl (A-methanesulfonyl)azidoformimidate [N3C (0Et)=NS02Me] has been used to aminate chiral cyclopentanone enamines but the yields are low and the reaction could not be extended to the corresponding cyclohexanone enamines.303 Trimethylsilyl azide (TMSN3) transfers the TMS rather than the azide group to a lactam enolate.339... 

The hydrogenation of C=N double bonds is an important synthetic strategy for the synthesis of secondary amines. Chiral iridium catalysts allow the hydrogenation of prochiral imines to be carried out with high enantioselectivity in conventional liquid solvents. Such a process has already found industrial application in the preparation of (S)-metolaclor, a herbicide produced by Novartis in Switzerland [40]. Recent research at the Max Planck Institute for Coal Research has demonstrated that reactions of this type can be carried out in SCCO2 with the same level of enantioselectivity and with enhanced catalyst efficiency [12]. 

Protection and activation of amines. Chiral borane-amine complexes, such as... 

Murphy DM, Caretti I, Carter E et al (2011) Visualising diastereomeric interactions of chiral amine-chiral copper Salen adducts by EPR/ENDOR/HYSCORE spectroscopy and DFT. Inorg Chem (submitted)... 

Abstract The organocatalytic asymmetric Mannich reaction and the related aza-Morita-Baylis-Hillman have been reviewed. The activities in this field have been snbdivided based on the types of catalysts that have been ntilized, which includes catalysis by enamine-forming chiral amines, chiral Br0nsted bases, chiral Brpnsted acids, and phase-transfer catalysts. 

The most intriguing aspect, however, lies in the enantioselective formation of amides, where the center of chirality is located on the amine (chiral R ) [271]. Thus, kinetic resolution of amines may be achieved [272-274]. 

A BASF group showed that rhodium-catalyzed reaction of a-(-)-pinene gives (-l-)-3-formylpinane (Scheme 4.53) [11]. In contrast, the use of Co2(CO)g led to the formation of (-)-2-formylbornane. The Wagner-Meerwein rearrangement is mediated by the intermediarily formed HCo(CO)4 with acidic properties. Prior isomerization of a- to P-pinene can be avoided by applying a high CO partial pressure and low temperatures. Based on this protocol and a subsequent reductive amination, chiral aminomethyl-plnane was prepared in the 100 g scale. 

Kagan HB, Langlois N, Dang TP. Reduction asymetrique catalysee par des complexes de metaux de transition IV. syn-these d amines chirales au moyen d un complexe de rhodium et d isopropylidene dihydroxy-2,3 bis (diphenylphosphino)-l,4 butane (diop). J. Org. Chem. 1975 90(3) 353-365. 

The amino motif is ubiquitous in nature and can usually be found in the structure of innumerable natural and synthetic bioactive compounds. In fact, it is estimated that around 20% of drugs contain at least one amine chiral center. The DKR methodology has also been successfully applied to chiral amines, " although some years later than for alcohols. 

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