S -Ethyl Lactate

Solubility sol water, alcohols, ethers, THE, and common organic solvents. 

Related Reagents. (/ ,/ )-[Ethylene-l,2-bis(i -4,5,6,7-tetra-hydro-l-indenyl)]titanium (/ )- ,l -Bi-2,2 -naphtholate ( )-1, l -Ethylenebis(4,5,6,7-tetrahydro-l-indenyl)zirconium Dichloride. 

Takeo Taguchi Yuji Hanzawa Tokyo College of Pharmacy, Japan 

Use as a Chiral Pool Reagent. ( i-Ethyl lactate has been extensively used as a chiral pool reagent, often via transformation into a diverse array of simple, enantiomerically pure analogs. Principal among these are a variety of 0-protected (5)-2-hydroxypropanals (eq 1). 

These have been prepared by various combinations of straightforward steps including ester to amide conversion, alcohol protection, direct reduction of the ester or amide to the aldehyde group, and reduction of the ester to the alcohol followed by reoxidation to the aldehyde. The sensitivity of the (5)-propanals to epimeriza-tion has been of paramount concern. One of the best procedures which avoids racemization and has been run on a preparative scale is noted (eq 2).  

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A. (S)-Ethyl 2-(t-Butyldimethylsilyloxy)propanoate (1). A 2-L, two-necked, round-bottomed flask equipped with a mechanical stirrer and inert gas inlet (Note 1) is charged with (S)-ethyl lactate (118 g, 1.0 mol), 500 mL of dimethylformamide (DMF), and imidazole (102 g, 1.5 mol) (Note 2). The solution is cooled in a ice bath and te/ t-butyldimethy 1 si 1 y 1 chloride (TBDMSC1) (150 g, 1.0 mol) is added in three 50-g portions, at intervals of 30 min between each addition. After the addition of the third portion, a white precipitate forms. The ice bath allowed to melt gradually overnight. After 18 hr, the reaction mixture is diluted with 300 mL of water and 500 mL of hexanes. The aqueous phase is separated and extracted with 300 mL of hexanes, and the combined hexane extracts are washed with three 50-mL portions of saturated brine, dried over MgS04, filtered, and concentrated by rotary evaporation to afford 240 g (103%) of the TBDMS ether as a colorless liquid. The product is distilled under vacuum (bp 70-78°C, 0.5 mm bath temperature 95-105°C) (Note 3) to afford 222 g (96%) of ester 1 as a colorless liquid (Notes 4, 5). 

S)-Ethyl lactate, [other chemicals employed in this procedure were obtained from Aldrich Chemical Company, Inc. Anhydrous tetrahydrofuran was prepared by distillation under argon from sodium benzophenone ketyl. 

The sequence detailed here provides 3-(S)-((tert-butyldiphenylsilyl)oxy)-2-butanone in high purity and on a preparative scale from inexpensive (S)-ethyl lactate. This optically active ketone should be a useful intermediate for the preparation of a variety of enantiomerically pure materials. It has been used in our laboratory for an asymmetric synthesis of (+)-muscarine3 and in the preparation of various other optically active tetrahydrofurans.4 Mitsunobu inversion of (S)-ethyl lactate followed by protection to provide 2-(R)-((tert-butyldiphenylsilyl)oxy)propanoate5 affords, by this method, ready access to the enantiomer of the title compound. 

S)-(-)-Ethyl lactate Lactic acid, ethyl ester, L- (8) Propanoic acid, 2-hydroxy-, ethyl ester, (S)- (9) (687-47-8)... 

A multistep stereospecific synthesis of ethylmethylpropylsulfonium 2,4,6-trinitrobenzenesulfonate 116 from (->(S)-ethyl lactate was recently elaborated by Kjaer and his co-workers (160) and is shown in Scheme 6. 

Theoretical calculations proved that the reaction intermediate leading to R-ethyl lactate on cinchonidine-modified Pt(lll) is energetically more stable than the intermediate leading to the S-ethyl lactate [147], However, the catalytic system is complex and the formation and breaking of intermediates are transient, so it is certainly difficult to obtain direct information spectroscopically. It is therefore advisable to use simplified model systems and investigate each possible pairwise interaction among reactants, products, catalyst, chiral modifier, and solvent separately [147, 148]. In order to constitute these model systems, it is important to get initial inputs from specific catalytic phenomena. 

The dibromoalkene S-40 can be prepared from S-ethyl lactate by introduction of the MEM (methoxyethoxymethyl) protecting group, reduction to the O-protected lactaldehyde and Corey-Fuchs carbonyl olefination (Scheme 19). The l -enantiomer of 40 is available analogously from f -isobutyl lactate and serves as the reagent in the enantiomeric series. The lithium carbenoid S-41 is generated from S-40 by treatment with n-butyllithium in diethyl ether and reacted with aliphatic and aromatic aldehydes in tetrahydrofuran. High diastereoselectivities are reached, as shown in Scheme 19 . ... 

Parker has outlined an elegant, enantioselective synthesis of L-vancosamine derivatives commencing from noncarbohydrate precursors (Scheme 17.38) [116]. This approach features a diastereoselective allenylstannane addition and W(CO)5-catalyzed cycloisomerization to construct the pyranose core. Oxidative cyclization of the C4-carba-mate 128 is performed with 10 mol% Rh2(OAc)4 and proceeds stereospecifically to give the crystalline oxazolidinone 129 (86%). All told, synthesis of this useful L-vancosa-mine glycal equivalent covers seven steps from (S)-(-)-ethyl lactate 127 and is accomplished in 44% overall yield. 

The results collected in Table 5 suggest that hydrocarbon residues, especially aromatic groups, in the solvent are strongly responsible for the interaction with cis-(1+4). The position of the largest hydrocarbon residue apparently determines whether P- or M-[6]-helicene will be formed in excess. Replacement of the methyl group in (S)-ethyl lactate (b) by a phenyl group giving (S)-ethyl mandelate (d), increases the optical yield fivefold. 

Introduction of a benzoyl residue in the polar hydroxy function of (S)-ethyl lactate gives, however, [6]-helicene in which the antipodal, laevorotatory enantiomer predominates. 

Figure 9. Cavities of the inclusion compounds, (a) 2 (,S )-ethyl lactate (1 1), (b)...

S)-Sulcatol cannot be made by this route, because the L-sugar is unavailable (even D-deoxyri-bose is quite expensive), so an alternative synthesis was needed that could be adapted to give either isomer. The solution is to go back to another hydroxy-acid, ethyl lactate, which is more widely available as its (5)-enantiomer, but which can be converted simply to either enantiomer of a key epoxide intermediate. From (S)-ethyl lactate, protection of the alcohol, reduction of the ester, and tosylation allows ring closure to one enantiomer of the epoxide tosylation of the secondary hydroxyl group followed by reduction and ring closure gives the other enantiomer. 

Solvent-controlled diastereoselectivities have also been observed in Diels-Alder cycloaddition reactions of cyclopentadiene with bis-(—)-menthyl fumarate [707] and with the acrylate of (S)-ethyl lactate, CH2=CH-C0-0CH(CH3)-C02Et [708]. In the latter reaction, giving four diastereomeric cycloadducts, diastereoselectivities of up to 85 15 have been obtained in n-hexane [708], The diastereoselectivities decrease with increasing solvent polarity, while the endojexo selectivity increases. This is in agreement with the pattern found for simple achiral acrylates [124] cf. Eq. (5-43) in Section 5.3.3. We shall conclude this section with reference to the E)I Z) isomerization of R ... 

Related Reagents. 10-Dicyclohexylsulfonamidoisobotneol (S)-Ethyl Lactate 3-Hydroxyisobomeol a-Methyltoluene-2,a-sultam. 

Related Reagents. (S)-Ethyl Lactate Ethyl Mandelate 3-Hydroxyisobomeol. 

A variety of alcohols, for example, 2-octanol (182,183), (-)-2-butanol (184), (+)-3-methyl-2-butanol (185), (-)-menthol (186), (S)-ethyl lactate (187), (R)-l-phenylethanol (188), etc., have been used. Several different sets... 

Ethyl Pyruvate (R)-Ethyl Lactate (S)-Ethyl Lactate... 

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