Malonic acid, chiral

In the following sections we discuss the methods that have been developed to study the steric course of reactions at proprochiral and proproprochiral centers on carbon and phosphorus, and some of the biochemical applications of these methods. Specifically, we consider chiral methyl groups, chiral malonic acid, chiral phosphate monoesters, and chiral inorganic phosphate. 

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... 

In the next stage the introduction of a fluorine atom onto the chiral center was examined with some 2-fluoro-2-alkyl malonic acid diesters with lipases. When the hydrolysis of 2-fluoro-2-methyl malonic aicd diester was examined with pig... 

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... 

We also studied the pyridoxal-dependent decarboxylation of an aminomalonic acid, a process providing an a-amino acid as the product. Our interest was to induce stereoselectivity in the process. Therefore, we synthesized catalysts 42 and 43, which rigidly held chirally mounted groups [42]. With the basic 42 we obtained 42% ee favoring l-phenylalanine in the decarboxylation of 2-amino-2-benzyl-malonic acid, while with non-basic 43 the ee was too low to detect. We proposed that the basic side chain delivered a proton to the decarboxylation intermediate in a stereoselective fashion. 

Fig. 5. Biosynthetic pathways for (I) 6-methylsalicylic acid and (II) the triacetic acid lactone. The structures of the intermediates have not been identified. The stereochemical course of the prochiral carbons (C-2 and C-4 in the triketide intermediate, C-3 and C-5 in 6-MSA) was investigated using R)- and (S)- [l- C,2- H]malonic acid extender substrate analogs in a coupled assay with 6-MSAS and succinyl-CoA transferase. The distinguishable hydrogens originating from the chiral malonyl CoA are labeled with H and H. Triacetic acid lactone synthesis is catalyzed by 6-MSAS in the absence NADPH...

In the synthesis of chiral 1,2-diamines, selective hydrolysis of the aminal function group of 653 was achieved with malonic acid to give the BOC-protected diamine 654. In the presence of TFA, both aminal and BOC were cleaved to give 655 (Scheme 157) <20010L3799>. 

The heterocoupling of carboxylic acids bearing chiral auxiliaries has been used to study the diastereoselectivity of the coupling of Kolbe radicals [204b]. For that purpose, 2-substituted malonic acid amides bound to seven different chiral auxiliaries were coelectrolyzed with different coacids [Eq. (200]- The yields in heterodimer ranged between 13 to 69%, and the diastereoselectivities between 20 and 86% de. 

Asymmetric alkylations can be performed in the presence of catalytic amounts of chiral phase transfer catalysts or through the intermediacy of 7t-allyl-palladium complexes bearing chiral ligands. Both methods normally require relatively acidic carbon acids (pKa 5 17) such as (3-diketones, P-keto- or cyanoesters or malonic acid derivatives. 

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. 

Malonic acid half thioesters, H02C-CH(R )-C0-SR (R =H/Me), undergo an enantioselective decarboxylative aldol reaction with aldehydes, using a chiral catalyst bearing a hydrogen-bond donor and acceptor. In situ ESI-MS evidence supports a complex between the conjugate base of the substrate and the conjugate acid of the... 

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