Norephedrine, derivatives

An entry to. yyrt-2-methoxy-3-hydroxycarboxylic acids is also opened using similar methodology. Thus the norephedrine derived (4/ ,5S)-3-(2-methoxy-l-oxoethyl)-4-methyl-5-phenyl-1,3-oxazolidine-2-one 23105a, as well as the phenylalanine derived (4S)-4-benzyl-3-(2-methoxy-l-oxoethyl)-l,3-oxazolidin-2-one 25105b, can be added to aldehydes via the boron enolates to give, after oxidative workup, the adducts in a stereoselective manner (d.r. 96 4, main product/sum of all others). Subsequent methanolysis affords the methyl esters. 

Reaction of the enantiomerically pure alkoxyamines 3, prepared from L-ephedrine or norephedrine derivatives 1 with acetaldehyde, isobutyraldehyde or benzaldehyde using ethanol as the solvent, afford the corresponding oxime ethers 4 as mixtures of E/Z-stereoisomers11. 

Scheme 3.5 Norephedrine-derived amino thioacetate and thiocyanate ligands for additions of ZnEt2 to aldehydes.

Scheme 3.18 Norephedrine-derived thiophosphoramidate ligand for Ti-catalysed additions of ZnR2 to aldehydes.

The scope of this methodology was extended to the enantioselective cyclo-propylation of various aldehydes using dicyclopropylzinc in the presence of this norephedrine-derived thiophosphoramidate ligand combined with Ti(Oi-Pr)4 to achieve the corresponding cyclopropyl alkanols with enantioselectivities of up to 97% ee (Scheme 3.19). ... 

Two equiv of cyclopropylacetylene and two equiv of norephedrine derivative 46 are required to obtain good conversion and high enantiomeric excess. 

An alternative method to prepare (Mormyl esters uses different building blocks to assemble the 1,4-dicarbonyl system and is complementary in many cases.10 Base-catalyzed addition of nitromefhane to a, J-unsaturated esters, followed by a variation of the Nef reaction, provides y-dialkoxy-substituted esters. The scope of this sequence has not yet been explored. Another approach involves cuprate additions to norephedrine-derived 2-alkenyloxazolidines this process allows small-scale synthesis of several p-formyl esters in optically active form (ee up to 95%).11... 

Enantioselective reduction of ketoxime ethers with chiral boron hydrides produces chiral 0-alkylhydroxylamines with variable ee. Reduction of oxime ethers of type 94 (equation 65) with norephedrine-derived oxazoborolidine 95 proceeds with very high ee. However, an analogous reduction of acyclic aromatic oximes with chiral oxab-orazolidines produced a mixture of amine and hydroxylamine . 

In other diethylzinc studies, a neural network modelling approach has been used to predict the utility of new enantioselective catalysts,222 norephedrine-derived ligands with three stereogenic centres catalyse enantioselective addition to aldehydes and to chalcones,223 and a chiral sulfonamide ligand based on tartaric acid gives good ees in addition to both aldehydes and ketones.224... 

K. Evetraere, J.-F. Carpentier, A. Morteux, and M. Bulliard, N-Benzoyl-norephedrine derivatives as new, effident ligands for ruthenium-catalyzed asymmetric transfer hydrogenation of functionalized ketones, Tetrahedron Asymm. 1999, 10, 4083 4086. 

As shown in cycle (b) in Scheme 10.1, the iminium-oxaziridinium pair can also effect catalytic asymmetric epoxidation of alkenes. Early work in this field by Bohe et al. included investigation of the norephedrine-derived oxaziridinium salt 34 (33% ee in the catalytic epoxidation of traws-stilbene [41] ee up to 61% was achieved when 34 was employed stoichiometrically [42]), or the L-proline-derived material 35 (39% ee in the epoxidation of trans-3-phenyl-2-propenol [43]). Rapid... 

Chiral sulfoxides are useful intermediates in asymmetric synthesis. A number of methods for their preparation were developed in the last decade. An interesting displacement of dimethylphosphonylmethyl moiety, a carbon leaving group, from sulfur by Grignard reagents was used to obtain enantiomerically purep-tolyl sulfoxides.3 4 Optically pure methyl 4-bromophenyl sulfinate was subjected to a one-pot sequence yielding unsymmetrical dialkyl sulfoxides in 60-97% yield and >98% ee. A simple one-pot synthesis of chiral sulfoxides from norephedrine-derived... 

The stereochemical course of the aldol reaction can be controlled by the judicious selection of the enolization reagents. Treatment of propionate esters with <7-Hex2BOTf and triethylamine produced anti-aldol products, and that of with Bu2BOTf and diisopropylethylamine selectively gave syn-aldol products after reaction with aldehydes (Equation (180)).684 685 Complementary anti- and yy/z-selective asymmetric aldol reactions were also demonstrated in structurally related chiral norephedrine-derived propionate esters (Equation (181)).686... 

The norephedrine-derived Masamune asymmetric aldol reaction was utilized in the total synthesis of (+)-testudinariol A (12), a triterpene marine natural product that possesses a highly functionalized cyclopentanol framework with four contiguous stereocenters appended to a central 3-alkylidene tetrahydropyran6 (Scheme 2.2f). The norephedrine-derived ester 13 was enolized with dicyclo-hexylboron triflate and triethylamine in dichloromethane and then treated with 3-benzyloxypropanal to afford the aldol adduct (14) as a 97 3 mixture of anti/syn diastereomers in 72% yield. Diastereoselectivity within the anti -manifold was 90 10. Protection of alcohol as the methoxyethoxymethyl (MEM) ether followed by conversion of the ester to an aldehyde by LiAlELt reduction and subsequent Swem oxidation gave the aldehyde 16 in 64% yield over three steps. 

Based on Schlosser and coworkers results9 regarding the deprotonation of epoxides, Milne and Murphy rearranged the epoxide 7 by employing the norephedrine-derived dilithiated chiral base 9 to produce (1 / ,45 )-8 in 80% ee (Scheme 4)10,11. Also, the enantiomer of this base is readily accessible, allowing a straightforward access to both enantiomers of the product alcohol. 

Asymmetric Synthesis via Norephedrine-Derived 2-Alkenyloxazolidines. Scolastico, C. Pure. Appl. Chem. 1988, 60, 1689. 

Table 2 Enantioselective Addition of Dialkylzincs to Aldehydes using Norephedrine-Derived Chiral Catalyst (eq 7)...

The Masamune aldol condensation, in common with the Evans aldol condensation, involves a boron enolate of an ester containing a norephedrine derived chiral auxiliary however, unlike the latter, the Masamune aldol delivers a 3-hydroxy-2-methyl carbonyl moiety with the an/z-stereochemistry. Crucial to the success of this reaction is the use of dicyclohexylboron triflate to generate the boron enolate. Note in the Evans aldol condensation, dibutylboron triflate is utilized. 

Originally, Evans used the illustrated auxiliary (R = j -Pr) for one product configuration and a similar norephedrine-derived auxiliary (R = Me, plus a Ph at C-5) for the other [75]. Since that time, experience has shown [86] that a phenylalanine-derived auxiliary (R = Bn) is usually better for practical reasons, and is available as either enantiomer. 

The structurally related product L-743,726 39 was similarly prepared by addition of lithium cyclopropylacetylide to ketone 37 in the presence of a /V,/V-disubstituted norephedrine derivative. This occurred in 98% e.e. at 0°C to give adduct 38 that was subsequently cyclized to afford 39. 

---