Malonic acid optically active

Compounds 137 and 138 are thus synthons for carboxylic acids this is another indirect method for the a alkylation of a carboxylic acid, representing an alternative to the malonic ester synthesis (10-104) and to 10-106 and 10-109. The method can be adapted to the preparation of optically active carboxylic acids by the use of a chiral reagent. Note that, unlike 132, 137 can be alkylated even if R is alkyl. However, the C=N bond of 137 and 138 cannot be effectively reduced, so that aldehyde synthesis is not feasible here. ... 

Example Optically active acid (16) was needed (p T 107 ) for the synthesis of an ant alarm pheromone. The branch point ( in 16) is also the chiral centre so it is better to avoid disconnections there. The 1,2 C-C disconnection (16a) is ideal as it gives synthon (17), for which we use a malonate ester, and halide (18), available from optically active alcohol (19), a major by-product from fermentation. 

Malonic acid ester synthesis is a classic but still one of the most important C—C bond-forming reactions, because it is widely applicable to various types of compounds and the reaction can be performed under mild conditions without special care to remove the trace amount of water and oxygen contained in the solvent. This reaction is especially useful in the synthesis of carboxylic acids. One important class of carboxylic acids is arylpropionates because optically active ones are known to have anti-inflammatory activity and other interesting physiological... 

To obtain a better understanding of the reaction mechanism, some compounds that are considered to he intermediates were subjected to the reaction. Various reaction courses can be considered as illustrated in Fig. 21. Path A a-Methyltropic acid is oxidized to a-phenyl-a-methylmalonic acid. Then, the malonate is converted to optically active a-phenylpropionate hy arylmalonate decarboxylase. In order to confirm this assumption, incubation of the malonic acid with Rhodococcus sp. was carried out. The result obtained was the total recovery of the substrate, indicating that no decarboxylase is present in this bacterium. Path B a-Methyltropic acid is converted to racemic a-phenylpropionic acid, which is deracemized to optically active propionic acid. To examine the possibility of this route, racemic a-phenylpropionic acid was subjected to the reaction to observe... 

Bohman and Allenmark resolved a series of sulphoxide derivatives of unsaturated malonic acids of the general structure 228. The classical method of resolution via formation of diastereoisomeric salts with cinchonine and quinine has also been used by Kapovits and coworkers " to resolve sulphoxides 229, 230, 231 and 232 which are precursors of chiral sulphuranes. Miko/ajczyk and his coworkers achieved optical resolution of sulphoxide 233 by utilizing the phosphonic acid moiety for salt formation with quinine. The racemic sulphinylacetic acid 234, which has a second centre of chirality on the a-carbon atom, was resolved into pure diastereoisomers by Holmberg. Racemic 2-hydroxy- and 4-hydroxyphenyl alkyl sulphoxides were separated via the diastereoisomeric 2- or 4-(tetra-0-acetyl-D-glucopyranosyloxy)phenyl alkyl sulphoxides 235. The optically active sulphoxides were recovered from the isolated diastereoisomers 235 by deacetylation with base and cleavage of the acetal. Racemic 1,3-dithian-l-oxide 236... 

Another type of chiral Michael acceptor, the oxazepine derivatives (47), is prepared by condensation of the (-)-ephedrine-derived malonic acid derivative (46) with aldehydes (Scheme 18).51 52 Treatment of (47) with a variety of Grignard reagents in the presence of NiCh affords, after hydrolysis and decarboxylation, the 3-substituted carboxylic acids (48), in most cases with more than 90% ee. Diastereoselective Michael additions to (47) were also used for the preparation of optically active cyclopropane derivatives (49)53 and P-substituted-y-butyrolactones (50 Scheme 18).54 A total synthesis of indolmycin is based on this methodology.55... 

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... 

The optically active allylic lactone (25 equation 34), for example, reacted with sodium malonate in the presence of Pd(PPh3)4 to give stereospecifically the acid (26), which was utilized for the generation of the side chain of vitamin K." ... 

By substituting (S)-(-)-l-amino-2-(dimethylmethoxymethyl)pyrrolidine (S)-(83) for (S)-(4), Enders has developed an efficient and enantioselective Hantzsch synthesis (Scheme 4). In this synthesis, the more-hindered hydrazone formed from (83) was condensed with an acetoacetic acid ester. Deprotonation of the hydrazone so-formed (the major tautomer present was an enehydrazine) followed by addition of an arylidene malonate derivative yielded (85), which could be closed with mild acid to yield optically active... 

Dimethyl-2-phenylperhydro-l,4-oxazepine-5,7-dione W was prepared from the half ester of malonic acid and- -ephedrine and syntheses of various optically active carboxylic acids starting from this chiral oxazepine were investigated. 

Racemization also occurs on decarboxylation of optically active disub-stituted cyanoacetic acids (which can be regarded as half nitriles of malonic acids), the reaction yielding disubstituted acetonitriles ... 

In 1872 van t Hoff worked with Kekule in Bonn, but, after an enthusiastic beginning, he found Kekule unsympathetic and went to Paris in 1873, where he found the atmosphere in Wurtz s laboratory in the ficole de Medecine more congenial. He there met LeBel, and van t Hoff and LeBel in 1874 published independently the theory of optical activity in terms of the tetrahedral valency distribution of the carbon atom (see p. 755). In 1874 van t Hoff received the Utrecht doctorate for a routine dissertation on cyanacetic and malonic acids he had the good sense not to present his theoretical pamphlet on space formulae, which laid the foundations of stereochemistry and had been published a month previously. Arrhenius was less fortunate (see p. 673). 

The first discussions concerning the conditions for aeating optically active compounds in the laboratory may be traced to Pasteur and Le Bel. The first mention of the expression "asymmetric synthesis" can be found in the work of E. Fischer in 1894 concerning his stereochemical studies on sugars. He observed the formation of unequal amounts of cyanohydrins in the Kiliani reaction applied to aldehydic sugars. In 1904, Marckwald reported an asymmetric synthesis of 2-methyl-butanoic acid by decarboxylation of 2-ethyl 2-methyl-malonic acid in the presence of an alkaloid. The importance and the mechanism of this reaction were later the subject of much debate. However, this paper remains significant because Marckwald defined asymmetric synthesis, as follows "It is a reaction giving optically active products from symmetrical... 

Decarboxylation of malonic acid derivatives is a well studied process in the biosynthesis of biomolecules such as long-chain fatty acids and polyketides. A decarboxylase that exhibits enantioselectivity for substituted malonates would be useful for producing ophcally active carboxylic acids, hi fact, malonyl-CoA decarboxylase does catalyze an enantioselective decarboxylation (Figure 3.2) [5], but malonyl-CoA is an unsuitable precursor for optically active substances. Instead, we focused on the prochiral-activated compoimd arylmalonate, an intermediate of malonic ester synthesis, to develop a method for enantioselective decarboxylation. Malonates are stable at room temperature but readily decompose to arylacetate and CO2 at high temperatures. This suggests that the decarboxylation of arylmalonate may occur naturally if arylmalonate acts as a substrate for a decarboxylase. 

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