A-methylephedrine

The ( )-trimethylsilylenolates of A-methylephedrine propanoates are useful as chiral propanoate equivalents in the titanium(IV) chloride catalyzed addition to enones. Although diastereoselec-tivities are high, this method suffers from low yields due to excessive polymerization190. 

In a synthesis of optically active allethrolone and prostaglandin intermediates, Yamada and co-workers (92) studied the reduction of certain 2-alkyl-1,3,4-cyclopentanetriones (82) with a reagent prepared by the reaction of LAH with 3 equivalents of (- )-A-methylephedrine in THF. Reduction of the cyclopen-tanetriones 82 with this reagent gave (/ )-83 in 55 to 58% e.e. (Scheme 12). Thus (/ )-83b (R2 = Ac, after acetylation) was obtained in 48% yield and 55% e.e. from 82b. The steric course and enantiomeric excess in the reduction were... 

Metal alkyl peroxides can be used for the epoxidation of electron-deficient alkenes such as enones. The use of a combination of diethylzinc, oxygen, and A-methylephedrine gave epoxides in very high yield and generally high enantio-selectivity (Figure 11.8). " ... 

Of greater synthetic interest is asymmetric induction by the use of chiral catalysis. Grigg was the first to report chiral catalysis of 1,3-dipolar cycloadditions in 1991 (101). A study of metal salts and chiral ligands revealed that 358 underwent cycloaddition with methyl acrylate to furnish adduct 359 in the presence of C0CI2 and (IR, 25)-A-methylephedrine as the chiral ligand. The pyrrolidine product was isolated in 55% yield with an ee of 84%. The use of methyl acrylate as solvent led to an improved yield of 84% with an excellent ee of 96% (Scheme 3.121). 

A cheap and efficient enantioselective aza-Henry reaction of nitromethane with a variety of A-protected arylaldimines has been reported.73 Using zinc triflate and (-)-A-methylephedrine at -20 °C, yields and ees of up to 99% have been achieved with wide tolerance of aryl substituent in terms of both electronic nature and position. The auxiliary is also easily recycled. 

An enantioselective aza-Henry reaction has been performed in the presence of zinc triflate and A-methylephedrine 47 This method features tolerance to imines that bear aryl groups of diverse electronic nature and substitution patterns. 

When irradiation of enamide 18 was carried out in the presence of a chiral metal hydride complex prepared from lithium aluminum hydride (LAH) and a chiral amino alcohol such as quinine, quinidine, A-methylephedrine,... 

Enantioselective Reduction of Ketones with Lithium Aluminum Hydride-A-Methylephedrine. Aryl alkyl ketones and... 

Figure 5 High-performance strong cation-exchange chromatography of ephedrine alkaloids and synephrine in dietary supplements. UV and fluorescence chromatograms of (A) standard solution ( 3 ng per component, except 1.6 tg of component 1), (B) Xenadrine RFA-1, (C) Xetalean, and (D) Ultra Diet Pep. Analytes 1, ( )-synephrine 2, (-)-norephedrine 3, (+)-norpseudoephedrine-HCI 4, (-)-ephedrine-HCI 5, (+)-pseudoephedrine 6, (-)-A/-methylephedrine 7, (+)-N-methylpseudoephedrine. Reproduced from R. A. Niemann M. L. Gay, J. Agric. Food Chem. 2003, 51, 5630-5638.

Ephedrine is the predominant alkaloid of ephedra plants. Other phenylalanine-derived alkaloids found in ephedra plants are (+)-pseudoephedrine, (—)-norephedrine, (-l-)-norpseudoephedrine, (l)-A-methylephedrine and phenylpropanolamines. Ephedrine is a potent central nervous system (CNS) stimulant. Because ephedra is both an a- and p-adrenergic agonist, ingestion of quantities over 50 mg lead to a rise in blood pressure, heart rate and cardiac output. 

All ephedra plants contain phenylalanine-derived alkaloids. These include (-)-ephedrine, (+)-pseudoephedrine, (-)-norephedrine, (+)-norpseudo-ephedrine (also called cathine because it is a major alkaloid of Catha edulis or khat, a plant used as a stimulant in North Africa), (-)-A-methylephedrine and (+)-A-methylpseudoephedrine, (+)-pseudoephedrine, and (+/-)-norephedrine (phenylpropanolamine). Significant enantioselective differences with regard to both pharmacokinetic and pharmacodynamic effects of these agents are possible. All of these alkaloids have important effects on the cardiovascular and respiratory systems, but not to the same degree. 

Chiral silyl ketene acetals (Il)-(20) were recently introduced for diastereoselective aldol-type additions. Camphor derivatives (11)-(16) are conformationally rigid with one diastereotopic face of the enol silane sterically shielded. - A -Methylephedrine derivatives (17)-(20) are likely to bind to TiCU through the NMe2 group with consequent dramatic conformational constraint.As a result the Lewis acid mediated additions to C=X occur in a highly stereoselective way. The chiral auxiliaries can then be removed (and recycled) by reduction, saponification or displacement with various nucleophiles to give useful synthetic intermediates. 

A -Methylephedrine-derived silyl ketene acetals react with imines in the presence of 2 mol equiv. of TiCU to give P-amino esters (equation 15) significant results are summarized in Table 7. With benzyl-ideneaniline the reaction is anti selective (entry 1), while with imino esters that chelate TiCU to give complexes such as (41), the reaction is syn selective (entries 2 and 3), in agreement with the general prin-... 

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