Diethyl -tartrate reaction with methyl

Easily prepared and removed under mild acidic conditions, the methoxymethyl ether (MOM) protecting group has been widely utilized with a variety of tartrate derivatives. Treatment of diethyl tartrate (lb) with excess chloromethyl methyl ether in the presence of 7V, -diiso-propylethylamine furnishes in 79% yield diethyl 2,3-0-bis(methoxymethyl)-L-tartrate (623). This reaction is easily performed on a scale greater than 100 g [199,200]. 

An achiral reagent cannot distinguish between these two faces. In a complex with a chiral reagent, however, the two (phantom ligand) electron pairs are in different (enantiotopic) environments. The two complexes are therefore diastereomeric and are formed and react at different rates. Two reaction systems that have been used successfully for enantioselective formation of sulfoxides are illustrated below. In the first example, the Ti(0-i-Pr)4-f-BuOOH-diethyl tartrate reagent is chiral by virtue of the presence of the chiral tartrate ester in the reactive complex. With simple aryl methyl sulfides, up to 90% enantiomeric purity of the product is obtained. 

A crystal structure of the C02 derivative of (8), K[Co(salen)( 71-C02)], haso been reported in which the Co—C bond is 1.99 A, the C—O bonds are both equivalent at 1.22 A and the O-C-O angle is 132°.125 Carboxylation of benzylic and allylic chlorides with C02 in THF-HMPA was achieved with (8) electrogenerated by controlled-potential electrolysis,126 in addition to reductive coupling of methyl pyruvate, diethyl ketomalonate and / -tolylcarbodiimide via C—C bond formation. Methyl pyruvate is transformed into diastereomeric tartrates concomitant with oxidation to the divalent Co(salen) and a free-radical mechanism is proposed involving the homolytic cleavage of the Co—C bond. However, reaction with diphenylketene (DPK) suggests an alternative pathway for the reductive coupling of C02-like compounds. 

Chiral allenylboronic esters.1 The enantioselectivity in synthesis of homo-propargylic esters by the reaction of aldehydes with chiral allenylboronic esters (11, 181) is markedly increased by use of bis-2,4-dimethyl-3-pentyl esters of d- or vAaxtaric acid rather than the diethyl ester. Yields in the reaction of various saturated aldehydes are 70-90%, and optical yields are consistently greater than 90% and even higher (97-99%) when the aldehyde is present in excess. However, yields are poor in reactions with aryl and a,p-unsaturated aldehydes. This modified procedure was used in a synthesis of (S)-(—)-ipsenol (2) from d-(—)-bis(2,4-di-methyl-3-pentyl) tartrate (1) (equation I). 

The reagent is prepared from (R,R)-( + )-diethyl tartrate by reaction with di-methylamine followed by methylation (dimethyl sulfate and 2,2-dimethoxypro-pane). 

A-f-Butoxycarbonylphenylalanine methyl ester (3.6 mmol) was dissolved in 15 ml toluene, then cooled to -78° C, and treated with the dropwise addition of 9.0 ml 1M solution of diisobutylaluminum hydride in toluene over 5 minutes. After 1 hour, the reaction was slowly quenched with 1 ml methyl alcohol, and then poured into a cooled aqueous solution of potassium sodium tartrate. The mixture was stirred 2 hours, then extracted with diethyl ether, washed with water and brine, dried over Na2S04, and concentrated to a colorless oil. The oil was purified by chromatography using silica gel with 20% EtOAc/heptane and the product isolated in 88% yield as a white solid. 

Starting from (+)-diethyl tartrate (2), bromobutenolide 18 was obtained in nine steps. Three of the four C=C double bonds were built up using a Wittig reaction (11—>12), an Ando- y Q Horner-Wadsworth-Emmons reaction (13— 15) and (3-elimination (16 18). From (-)-actinol (3) stannane 23 and sulfone 24 were synthesized in 9 and 13 steps, respectively. Their common intermediate, alkyne 22, was synthesized using methoxycarbonylation. Sharpless asymmetric epoxidation and Ci-elongation with lithio trimethylsilyldiazomethane. Stannane 23 was obtained upon hydrostannylation and TBS deprotection. Sulfone 24 was obtained after addition to methyl tetrolate, reduction, Mukaiyama redox condensation, acetylation and catalytic oxidation. 

Experiments in methyl isobutyl ketone with 1 equiv. Ti-catalyst indicated that the amount of H20, the ratio Ti/tartrate ester ligand, and the reaction temperature had a strong influence. The best relation between wanted and unwanted sulfoxide stereoisomers was obtained at 0.5 equiv. H20 and with Ti/diethyl tartrate equal to 1 2 at 40°C. 

Asymmetric induction has been employed in the synthesis of methyl a-L-daunosaminide and its D-xy/o-isomer from the non-chiral acetal 1, l-dimethoxyhex-4-ene. The first step is an acetal exchange reaction with diethyl (+)-tartrate to give the acetal (15), followed by functionalization of (15) by allylic tosylamination and hydroxylation of the double bond. ... 

Perhaps the most direct approach to 2,3-di-O-methyl tartrates is to treat the corresponding ester, such as lb, with a base like sodium hydride together with excess methyl iodide. Performed on a scale of up to one kilogram, this reaction provides in 66% yield diethyl (+ )-2,3-di-O-methyltartrate (569). Saponification of the diesters followed by anhydride formation with refluxing acetyl chloride furnishes 570, which is converted to 3,4-dimethoxy-thiopyrrolidone (571). This is the key intermediate for the synthesis of the antibiotic ani-somycin (572). The synthesis itself is not diastereoselective, and suffers from the tedious methodology required to introduce the correct acetoxy functionality present in 572 [183] (Scheme 126). 

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