Methyl tartrate, reactions

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). 

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. 

Glaucidine (item 56 list, p. 173), composition unknown m.p. 209-10°, gives the characteristic colour reactions of glaueine. It is a phenolic base and on methylation gives a product of which the hydrogen tartrate closely resembles that of glaueine. ... 

The synthesis in Scheme 13.49 features use of an enantioselective allylic boronate reagent derived from diisopropyl tartrate to establish the C(4) and C(5) stereochemistry. The ring is closed by an olefin metathesis reaction. The C(2) methyl group was introduced by alkylation of the lactone enolate. The alkylation is not stereoselective, but base-catalyzed epimerization favors the desired stereoisomer by 4 1. 

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. 

Another route to a methyl-branched derivative makes use of reductive cleavage of spiro epoxides ( ). The realization of this process was tested in the monosaccharide series. Hittig olefination of was used to form the exocyclic methylene compound 48. This sugar contains an inherent allyl alcohol fragmenC the chiral C-4 alcohol function of which should be idealy suited to determine the chirality of the epoxide to be formed by the Sharpless method. With tert-butvl hydroperoxide, titanium tetraisopropoxide and (-)-tartrate (for a "like mode" process) no reaction occured. After a number of attempts, the Sharpless method was abandoned and extended back to the well-established m-chloroperoxybenzoic acid epoxida-tion. The (3 )-epoxide was obtained stereospecifically in excellent yield (83%rT and this could be readily reduced to give the D-ribo compound 50. The exclusive formation of 49 is unexpected and may be associated with a strong ster chemical induction by the chiral centers at C-1, C-4, and C-5. 

To improve the levels of selectivity in additions to chiral aldehydes, it is possible to resort to the tactic of double diastereoselection with the use of chiral allylic boranes and boronates (see section Double Diastereoselection ). Bis(isopinocampheyl) allylic boranes and the tartrate allylic boronates (see following section), in particular, are very useful in the synthesis of polypropionate natmal products by reaction with a-methyl and a-alkoxy functionalized aldehydes. 

Stoichiometric oxidation using TBHP and a 2 1 Ti tetraisopropox-ide-diisopropyl tartrate system can kinetically resolve racemic dialkyl-amino alcohols (Scheme 46) (106). The efficiency, which ranges from 0-95% ee, is largely dependent on the substrates. When methyl groups or polymethylene rings are used, the reaction proceeds to afford greater than 90% ee, whereas iV.iV-dibenzyl derivatives show little or no resolution. Use of natural (2/ ,3/ )-diisopropyl tartrate consistently gives R amino alcohols. 

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). 

Asymmetric induction in the [2 + 2] cycloaddition of enamines, e.g. 42, with methyl ( )-4-oxo-4-(2-oxo-l,3-oxazolidin-3-yl)-2-butenoate (41) has been reported (equation 7)35. The reaction is promoted by a chiral titanium reagent generated in situ from dichlorodiisopropoxytitanium and a tartrate-derived chiral 1,4-diol (43). In the presence of excess amounts of the titanium reagent, 77% ee of cycloadduct 44 was achieved together with 45. The reaction also works with only a catalytic amount of the chiral reagent. 

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. 

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