1-methylephedrine

Another possibility for asymmetric reduction is the use of chiral complex hydrides derived from LiAlH. and chiral alcohols, e.g. N-methylephedrine (I. Jacquet, 1974), or 1,4-bis(dimethylamino)butanediol (D. Seebach, 1974). But stereoselectivities are mostly below 50%. At the present time attempts to form chiral alcohols from ketones are less successful than the asymmetric reduction of C = C double bonds via hydroboration or hydrogenation with Wilkinson type catalysts (G. Zweifel, 1963 H.B. Kagan, 1978 see p. 102f.). 

Nagai s ephedrine was obtained from Ma-Huang and the same alkaloid, together with its stereoisomeride pseudoephednne ( -ephedrine), was isolated by Merck from the European species, E. helvetica C. A. Meyer. From commercial Ma-Huang Smith prepared two additional bases, 1-W-methylephedrine and nnr-d- -ephedrine. Nagai and Kanao added two more, viz., d-W-methyl- -ephedrine and Z-norephedrine, and... 

Chen, Stuart and Chen isolated benzylmethylamine (B. HCl, m.p. 180-5° aurichloride, m.p. 139-140°), while Chou and Mei obtained a volatile base, ephedine, CgHig02N2 [m.p. 76° or 87° (dry) B. HCl, m.p. 90° pierate, m.p. 190°]. From the European speeies Wolfes has also isolated Z-iV-methylephedrine and Z-norephedrine, and fromE. mono tachya, Spehr obtained a base C gH gON, monoelinie prisms, m.p. 112°, whieh is said to be physiologieally inaetive, and is generally known as ephedrine, Spehr. ... 

Tab. 3.7 N-Methylephedrine reagent modification in Simmons-Smith cyclopropanation...

The combination of the enantiomerically pure 7V-methylephedrine derived silylketene acetal l-[(l/ ,2S)-2-dimethylamino-1-phenylpropoxy]-l-triniethylsilyloxy-l-propene with the chiral aldehyde (,R)-3-benzyloxy-2-methylpropanal leads, after reduction with lithium aluminum hydride, to the formation of a single 1,3-pentanediol 9 ( matched pair ). 

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. 

Enantioselective addition of CjH zZn to aldehydes.1 Addition of diethylzinc to either aromatic or aliphatic aldehydes catalyzed by 1 (6 mole %) results in (S)-secondary alcohols in generally 90-95% ee. Although several chiral amino alcohols are known to effect enantioselective addition of R2Zn to aromatic aldehydes, this one is the first catalyst to be effective for aliphatic aldehydes. The dibutylamino group of 1 is essential for the high enantioselectivity the dimethylamino analog of 1, (lS,2R)-N-methylephedrine, effects this addition in only about 60% ee. 

The third group4 used (1R,2S)-N methylephedrine as the chiral auxiliary. Thus the derived silylketene acetal (6) reacts with 1 in the presence of TiCl4 to give 7 in 45-70% yield with —90% stereoselectivity. The products are converted by TFA and LiOH to (R)-a-hydrazino acids (8), which are obtained in 5=98% ee after one crystallization. 

Chiral trms-fi-lactams. The silyl ketene acetal (1), derived from (1S,2R)-N-methylephedrine, reacts in the presence of TiCl, with benzylideneaniline (2) to give as the major products anti- and syn-3 in the ratio >10 1. Cyclization of the mixture gives the trans-p-lactam (4) in 95% ee. 

Carreira and co-workers developed a highly efficient enantioselective addition of terminal alkynes to aldehydes giving propargyl alcohols by the mediation of zinc tri-flate and N-methylephedrine [17]. This reaction serves as a convenient and powerful synthetic route to a wide variety of enantioenriched allenes via propargyl alcohols. Dieter and Yu applied this alkynylation to the asymmetric synthesis of allenes (Scheme 4.12) [18]. Reaction of phenylacetylene with isobutyraldehyde afforded the propargyl alcohol in 80% yield with 99% ee, which was mesylated to 49 in quantitative yield. Reaction of 49 with the cyanocuprate 50 afforded the desired allene 51 with 83% ee. 

V-Methylephedrine.b Homogeneous system.r Heterogeneous system.J Polystyrene-supported iV-methylephcdrinc. 33% ee with dimethylzinc.1 Supported. V-butyl-ephedrine separated from the polystyrene-backbone by a CH,0(CH )6 link. /V-benzyl-W-melhylephedrinium chloride. 

V-methylephedrine is the chiral component. Reaction temperature - 15°C,solvent ether (88). 

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... 

A chiral hydride complex, tentatively assumed to be 86, prepared by partially reacting LAH with (- )-N-methylephedrine (1 equivalent) and /V-ethylaniline (2 equivalents) was found to reduce 2-acetyl-5,8-dimethoxy-3,4-dihydronaphtha-lene (87) quantitatively to the (- )-carbinol (88) with 92% e.e. (94,95). Carbinol 88, which was obtained optically pure by recrystallization, could be converted to (/ )-(-)-2-acetyl-5,8-dimethoxy-l,2,3,4-tetrahydro-2-naphthol (89). The lat-... 

Commercial samples containing approximately 400 mg of ephedra per capsule yield roughly 5 mg of ephedrine, 1 mg of pseudoephedrine, and less than 1 mg of methylephedrine (White et al. 1997). For a dose of four capsules, yielding approximately 20 mg of ephedrine, the elimination half-life is 5.2 hours. The time to reach maxium concentration is 3.9 hours. Compared to pure ephedrine tablets, the elimination kinetics of ephedra are comparable. However, ephedra showed somewhat different absorption kinetics (e.g., lag time, area under the concentration-time curve, and maximum plasma concentration). So, ephedra tablets may vary from pure ephedrine in the onset of action, but the durations of action are grossly equivalent. 

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). " ... 

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