Ephedrine auxiliary

Two strategies for accomplishing asymmetric hetero-IMDA reactions have been reported (Figure 44). First, Tietze has shown that (157), that includes an ephedrine auxiliary as a component of the heterodiene unit, undergoes a highly diastereoselecdve Lewis acid catalyzed cycloaddition, providing cycloadduct... 

The fluorinated diastereomers are separated by silica gel chromatography. Removal of the ephedrine auxiliary by TMSBr and TFA provides a racemization-free procedure for liberating the desired a-fluorophosphonic acids. ... 

Cleavage of Pseudoephedrine Auxiliary In contrast to the ephedrine auxiliary, which is difficult to cleave once the alkylation is performed, the pseudoephedrine moiety can be readily removed under various conditions with a limited impact on the ees [36]. 

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. 

Only few allyltitanium reagents bearing a removable chiral auxiliary at the allylic residue are known. The outstanding example is a metalated 1-alkyl-2-imidazolinone14, derived from (—)-ephedrine, representing a valuable homoenolate reagent. After deprotonation by butyllithium, metal exchange with chlorotris(diethylamino)titanium, and aldehyde or ketone addition, the homoaldol adducts are formed with 94 to 98% diastereoselectivity. 

Another chiral auxiliary for controlling the absolute stereochemistry in Mukaiyama aldol reactions of chiral silyl ketene acetals has been derived from TV-methyl ephedrine.18 This has been successfully applied to the enantioselec-tive synthesis of various natural products19 such as a-methyl-/ -hydroxy esters (ee 91-94%),18,20 a-methyl-/Miydroxy aldehydes (91% ee),21 a-hydrazino and a-amino acids (78-91% ee),22 a-methyl-d-oxoesters (72-75% ee),20b cis- and trans-l1-lactams (70-96% ee),23 and carbapenem antibiotics.24... 

Both enantiomers of 2-methylamino-l-phenylpropanol (ephedrine, 1), which are commercially available and relatively inexpensive, have been used as auxiliaries in many syntheses of chiral compounds. Ephedrine can be used for amide alkylations both directly1-3, or as derived heterocyclic compounds (see Sections 1.1.1.3.3.4.2.1. and 1.1.1.3.3.4.2.2.). Acyclic derivatives of ephedrine are discussed in this section. For example, either enantiomer of ephedrine gives A-acylephedrines 2 in good yield without epimerization if treated with an anhydride at 65 °C for 10 minutes2. 

Enantioselective reduction of acetophenone was achieved in a ruthenium-catalysed hydrogen transfer reaction using isopropanol as the hydrogen source in the presence of mono-tosylated (R, R)-diphenylethylenediamine, ephedrine or norephedrine as chiral auxiliary ligands. Under optimised conditions, ( R)-l-phenylethanol was obtained in 90% yield and 82% enantiomeric excess (ee) within 9 min. f-Butylphenylketone was reduced under similar conditions in almost quantitative yield but in moderate ee... 

Scheme 8.24 Asymmetric conjugate addition with ephedrine as chiral auxiliary.

The first asymmetric iron-catalyzed conjugate addition was reported in 1977. Benzylidene malonate 56 with an ephedrine moiety as chiral auxiliary was converted with Grignard reagents such as nBuMgBr in the presence of catalytic amounts of various metal salts. The optically active phenylpropionic acid 57 was obtained with... 

Among the preparative methods used for obtaining P-chiral phosphorus compounds, there are procedures involving the use of optically pure auxiliaries like (—)-menthol [40], (—)-ephedrin [41,42], or more recently, the kinetic resolution of 1-hydroxymethylalkylphenylphosphine oxides using Pseudomonas or Candida antarctica lipases [43], It has been found that some [(alkyl-substituted)arene] phosphinates and phosphine oxides can also be resolved efficiently by inclusion complexation with optically active 2,2 -dihydroxy-1, 1 -binaphthyl (17) [44],... 

Ramamurthy et al. have examined enantioselective and diastereoselective ODPM rearrangements of cyclohexadienone and naphthalenone derivatives within MY zeolites, where M is an alkali ion [38, 39]. For example, in Scheme 4.27, in NaY in the presence of several chiral inductors such as ephedrine, pseudoephedrine, and camphorquinone-3-oxime, an enantioselective ODPM rearrangement of 65 and 66 took place to afford 68 in 30% ee yield. In the frame of the chiral auxiliary approach, the compound 67 linked to (S)-ephedrine was irradiated within NaY to give 68 in moderate diastereoselective excess (de) (59%). Interestingly, the reaction media of KY, RbY, and CsY reverse the diastereoselectivities. The cation-dependent diastereo-meric switch has been discussed with respect to the N- or O-functional group in 67 [39]. Recently, Arumugan reported that the irradiation of naphthalenones 65 linked chiral auxiliaries (R3 = COO(—)-Ment or (S)-NHCH(Me)Ph) in Li+ or Na + Nafion resulted in chiral products ( 14% de) [40],... 

Imidazolidinones. The reaction of urea with (- )-ephedrine hydrochloride provides a chiral imidazolidinone (l),1 which can be used as a chiral auxiliary for... 

The use of aminosulfites in the synthesis of o.p. sulfoxides was described for the first time in 1973 by Wudl and Lee,98 using ephedrine as chiral auxiliary. In 1991, Benson and Snyder reported a modification of the Wudl and Lee procedure, obtaining o.p. sulfoxides in high yield by sequential displacement reactions of organometallic reagents on the 1,2,3-oxathiazolidine-S-oxide (aminosulfite 70), obtained from ephedrine and thionyl chloride.99... 

Chiral Auxiliary Used for Asymmetric Ti-ansformations (Thermodynamic Control). Racemic iV-benzyl-iV-methyl-a-amino propiophenone mixed with (2R,3R)-DPTA in acetone or dichloromethane leads with 90% yield to the corresponding salt of the (S)-amino ketone, which was reduced over Palladium on Carbon to a mixture of ephedrine (80%) and pseudo-ephedrine (20%) (eq 8). ... 

Related Reagents. Prolinol ephedrine oxazolidinones cam-phorsultams camphor-derived auxiliaries and oxazolines. 

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