Chiral amines ephedrine

Conjugate addition of chiral amines to allenic and acetylenic sulfones has been reported73. The reaction 112 with (—)-ephedrine gives only one of the two possible diastereomeric oxazolines in high yield (equation 89). 

The most successful modifier is cinchonidine and its enantiomer cinchonine, but some work in expanding the repertoire of substrate/modifier/catalyst combinations has been reported (S)-(-)-l-(l-naphthyl)ethylamine or (//)-1 -(I -naphth T)eth Tamine for Pt/alumina [108,231], derivatives of cinchona alkaloid such as 10,11-dihydrocinchonidine [36,71], 2-phenyl-9-deoxy-10, 11-dihydrocinchonidine [55], and O-methyl-cinchonidine for Pt/alumina [133], ephedrine for Pd/alumina [107], (-)-dihydroapovincaminic acid ethyl ester (-)-DHVIN for Pd/TiOz [122], (-)-dihydrovinpocetine for Pt/alumina [42], chiral amines such as 1 -(1 -naphtln I)-2-(I -pyrro 1 idiny 1) ethanol, l-(9-anthracenyl)-2-(l-pyrrolidinyl)ethanol, l-(9-triptycenyl)-2-(l-pyrrol idi nyl)cthanol, (Z )-2-(l-pyrrolidinyl)-l-(l-naphthyl)ethanol for Pt/alumina [37,116], D- and L-histidine and methyl esters of d- and L-tryptophan for Pt/alumina [35], morphine alkaloids [113],... 

Analogous to the use of chiral enoates (see previous section), a, -unsaturated carboxylic amides, prepared from chiral amines, may be utilized in asymmetric 1,4-additions. When Grignard reagents are added to unsaturated amides (21), derived from (-)-ephedrine (20),25 highly optically active fi-sub-stituted alkanoic acids (22 R and R = alkyl or phenyl) are obtained in a variety of cases, after hydrolysis of the initially formed adducts (Scheme 7). This method was used for the synthesis of the antibiotic (-) malyngolide and its stereoisomers.26 Recrystallization of the intermediate (saturated) amide was necess-... 

A chiral reagent 2 of the same type has been prepared from (—)-ephedrine and used to obtain chiral amines in 20-45% ee.4... 

Production of enantiomerically pure a-arylpropanoic acids, also known as profens, is of critical importance to the pharmaceutical industry because they constitute a major class of antiinflammatory agents. One of the most practical approaches to preparing optically pure a-arylpropanoic acids is by resolution with chiral amines. Notable examples include brucine, quinidine, cinchonidine, morphine, ephedrine, and a-(l-naphthyl)ethylamine. For instance, (.Sj-a-methylbenzylaminc and... 

D-(-)-Pantoyl lactone 1s a key intermediate for the synthesis of pantothenic acid which is a member of the vitamin B-complex and is an important constituent of Coenzyme A. Although D-(-)-pantoyl lactone has been obtained by classical optical resolution using quinine, ephedrine, and other chiral amines, catalytic asymmetric synthesis appears to be more effective... 

In a more recent study, the enamide photocyclization with very similar photosubstrates was examined in the presence of chiral amino alcohols and chiral amines as asymmetric inductors [47]. The achieved enantioselectivities are in the same range as the ones reported by Ninomiya and Naito, but in this approach the asymmetric induction was more effective for the cis products. In cyclopentane at — 40°C, 0.1 equivalents of the most effective inductor, (— )-ephedrine (entity, gave the cis cyclization products with up to 37% ee and the trans products with only 2% ee. The role of the chiral inductor as a Br0nsted acid was supported by flash photolysis experiments. The presence of the chiral amino alcohol led to an increase in the rate of disappearance of a transient that was assigned to the primary cyclization intermediate of type 29, i.e., the chiral inductor accelerates the protonation/deprotonation sequence that reestablishes the aromatic ring. 

In this enantiodifferentiating photoreduction, the chiral amine plays two roles, as a chiral inductor and as an electron donor. Irradiation of 25 (Scheme 10) in a hexane slurry of unmodified NaY zeolite gave only the intramolecular hydrogen abstraction product 26. However, photolysis of 25 coimmobilized with ephedrine, pseudoephedrine, or norephedrine in NaY supercages afforded the reduction product 27 along with 26. It is clear that the immobilized amine plays the decisive role in the photoinduced electron-transfer reduction of 25, since 27 was not formed in unmodified or (— )-diethyl tartrate-modified zeolites. Consequently, the ee of obtained 27 was independent of the loading level of the chiral inductor. 

The addition of chiral amines to a,/(-unsaturated sulfoximines has been employed for the resolution of racemic sulfoximines 3 utilizing 0.5 equivalents of a chiral amine in chloroform 117. After completion of the reaction, the unreacted starting material is isolated by column chromatography and its optical purity determined by comparison with the reported optical rotation, or by HNMR using a chiral shift reagent. While (—)-(l/f,2.S,)-2-mcthylamino-1-phenyl-l-propanol [(l/ ,2S)-ephedrine] affords material of moderate optical purity, racemic products are isolated from addition reactions with (—)-l-phenyl-2-propanamine [(—)-am-phetamine] or ( + )-( )-l-phenylethylamine. 

Unsymmetrically substituted irondiene carbonyl complexes are chiral, and some are easily accessible in an enantiomerically pure form by resolution Complexes 1.152 (R = H, Me, rt-Bu, Y = CHO) or 1.153 (Y = CHO), bearing an aldehyde functional group, can be resolved via chiral hydrazones [526], chiral aminals [527], or derivatives of ephedrine 1.61 [528], The diastereoisomers thus formed are separated by chromatography, and the aldehydes are easily regenerated. The resolution of trimethyienemethane complexes 1.154 can be accomplished similarly [529]. Complexes bearing an ester functionality 1.152 (R = COOMe) are resolved through lactates, which are subsequently treated with KOH/MeOH [530], From these enantiomerically pure complexes, classical reactions lead to other systems such as 1.152 (R = CH2OH, Y = CHO) [531], 1.152 (R = w-Bu,... 

Progress has been made toward enantioselective and highly regioselective Michael type alkylations of 2-cyclohexen-l -one using alkylcuprates with chiral auxiliary ligands, e. g., anions of either enantiomer of N-[2-(dimethylamino)ethyl]ephedrine (E. J. Corey, 1986), of (S)-2-(methoxymethyl)pyrrolidine (from L-proline R. K. EHeter, 1987) or of chiramt (= (R,R)-N-(l-phenylethyl)-7-[(l-phenylethyl)iinino]-l,3,5-cycloheptatrien-l-amine, a chiral aminotro-ponimine G. M. Villacorta, 1988). Enantioselectivities of up to 95% have been reported. 

Formation of PAC from benzaldehyde and pyruvate catalysed by PDC and reductive amination of if-PAC to produce the chiral biopharmaceutical product ephedrine. 

Diastereomeric complexes can also be formed by ion-pairing of an enantiomer with a chiral counterion. In order to form this diastereomeric complex, it has been postulated that at least three interaction points between the ion pair are required [250]. Nearly all of these form weak complexes in aqueous mobile phases. Consequently, the chromatographic methods that have been developed have been either silica or diol columns with low-polarity mobile phases. Enantiomeric amines, such as the beta-blockers, have been optically resolved when (-l-)-lO-camphorsulfonic acid was used as the chiral counterion [251]. Enantiomers of norephedrine, ephedrine, pseudoephedrine, and phenyramidol have all been resolved from their respective enantiomers with n-dibutyltartrate [252]. Enantiomers of naproxen, a chiral carboxylic acid, are resolved from each other by either using quinidine or quinine in the mobile phase [253]. In these studies, silica... 

Various molecules were considered for studying the influence of the five-mem-bered ring conformations, and of the bulkiness of the ring substituents on the dia-stereomeric excess of the aminated products. Optically active (+)-ephedrine 89a and (—)-pseudo-ephedrine 89b were chosen as the chiral amino alcohols because of their relatively low cost and in view of the excellent results obtained in the similar asymmetric synthesis of a-amino carboxylic acids [13]. 

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