Carboxylic optically active

These complexes can be isolated in some cases in others they are generated in situ from appropriate precursors, of which diazo compounds are among the most important. These compounds, including CH2N2 and other diazoalkanes, react with metals or metal salts (copper, palladium, and rhodium are most commonly used) to give the carbene complexes that add CRR to double bonds. Ethyl a-diazoacetate reacts with styrene in the presence of bis(ferrocenyl) bis(imine), for example, to give ethyl 2-phenylcyclopropane-l-carboxylate. Optically active complexes have... 

This substance (dA, I A) contains a free carboxyl group and is treated in warm acetone solution with an equimolecular quantity of the optically active base brucine (IB) upon cooling, the brucine salt (dA, IB) separates out first in a moderately pure condition, whilst the brucine salt (lA, IB) remains in solution ... 

The asymmetric cyclopalladation of dimethylaminomethylferrocene takes place in the presence of an optically active carboxylic acid (e.g, A -acetylvaline), giving the cyclopalladation product 478 in 78% ee, from which optically active ferrocene derivatives were prepared[434]. 

Hydrolysis of cinenn I gives an optically active carboxylic acid (+) chrysanthemic acid Ozonolysis of (+) chrysanthemic acid followed by oxidation gives acetone and an optically active dicarboxyhc acid (—) caronic acid (C7H10O4) What is the struc ture of (—) caronic acid" Are the two carboxyl groups cis or trans to each other What does this information tell you about the structure of (+) chrysanthemic acid" ... 

Chirazymes. These are commercially available enzymes e.g. lipases, esterases, that can be used for the preparation of a variety of optically active carboxylic acids, alcohols and amines. They can cause regio and stereospecific hydrolysis and do not require cofactors. Some can be used also for esterification or transesterification in neat organic solvents. The proteases, amidases and oxidases are obtained from bacteria or fungi, whereas esterases are from pig liver and thermophilic bacteria. For preparative work the enzymes are covalently bound to a carrier and do not therefore contaminate the reaction products. Chirazymes are available form Roche Molecular Biochemicals and are used without further purification. 

A series of optically active substituted l,2-dihydro-6-oxo-6//-pyr-rolo[3,2,l-j ]quinoline-5-carboxylic acids were prepared (95CPB1678). 

Compound A, C/H, was found to be optically active. On catalytic reductior over a palladium catalyst, 2 equivalents of hydrogen were absorbed, yielding compound B, CyH. On ozonolysis of A, two fragments were obtained. One fragment was identified as acetic acid. The other fragment, compound C, wa an optically active carboxylic acid, C5Hl002- Write the reactions, and drav structures for A. B and C. 

When an optically active carboxylic acid such as (jR)-2-phenylpropanoic acid is brominated under Hell-Volhard-Zelinskii conditions, is the product optically active or racemic Explain. 

The synthesis of key intermediate 12, in optically active form, commences with the resolution of racemic trans-2,3-epoxybutyric acid (27), a substance readily obtained by epoxidation of crotonic acid (26) (see Scheme 5). Treatment of racemic 27 with enantio-merically pure (S)-(-)-1 -a-napthylethylamine affords a 1 1 mixture of diastereomeric ammonium salts which can be resolved by recrystallization from absolute ethanol. Acidification of the resolved diastereomeric ammonium salts with methanesulfonic acid and extraction furnishes both epoxy acid enantiomers in eantiomerically pure form. Because the optical rotation and absolute configuration of one of the antipodes was known, the identity of enantiomerically pure epoxy acid, (+)-27, with the absolute configuration required for a synthesis of erythronolide B, could be confirmed. Sequential treatment of (+)-27 with ethyl chloroformate, excess sodium boro-hydride, and 2-methoxypropene with a trace of phosphorous oxychloride affords protected intermediate 28 in an overall yield of 76%. The action of ethyl chloroformate on carboxylic acid (+)-27 affords a mixed carbonic anhydride which is subsequently reduced by sodium borohydride to a primary alcohol. Protection of the primary hydroxyl group in the form of a mixed ketal is achieved easily with 2-methoxypropene and a catalytic amount of phosphorous oxychloride. 

The adjacent iodine and lactone groupings in 16 constitute the structural prerequisite, or retron, for the iodolactonization transform.15 It was anticipated that the action of iodine on unsaturated carboxylic acid 17 would induce iodolactonization16 to give iodo-lactone 16. The cis C20-C21 double bond in 17 provides a convenient opportunity for molecular simplification. In the synthetic direction, a Wittig reaction17 between the nonstabilized phosphorous ylide derived from 19 and aldehyde 18 could result in the formation of cis alkene 17. Enantiomerically pure (/ )-citronellic acid (20) and (+)-/ -hydroxyisobutyric acid (11) are readily available sources of chirality that could be converted in a straightforward manner into optically active building blocks 18 and 19, respectively. 

A cursory inspection of key intermediate 8 (see Scheme 1) reveals that it possesses both vicinal and remote stereochemical relationships. To cope with the stereochemical challenge posed by this intermediate and to enhance overall efficiency, a convergent approach featuring the union of optically active intermediates 18 and 19 was adopted. Scheme 5a illustrates the synthesis of intermediate 18. Thus, oxidative cleavage of the trisubstituted olefin of (/ )-citronellic acid benzyl ester (28) with ozone, followed by oxidative workup with Jones reagent, affords a carboxylic acid which can be oxidatively decarboxylated to 29 with lead tetraacetate and copper(n) acetate. Saponification of the benzyl ester in 29 with potassium hydroxide provides an unsaturated carboxylic acid which undergoes smooth conversion to trans iodolactone 30 on treatment with iodine in acetonitrile at -15 °C (89% yield from 29).24 The diastereoselectivity of the thermodynamically controlled iodolacto-nization reaction is approximately 20 1 in favor of the more stable trans iodolactone 30. 

Optically active substituted alkylidene cyclohexanes were prepared from sulfinyl esters (obtained by carboxylation of sulfinyl anions) by thermolytic elimination of the sulfinyl group65. 

In Ugi four-component reactions (for mechanism, see Section 1.4.4.1.) all four components may potentially serve as the stereodifferentiating tool65. However, neither the isocyanide component nor the carboxylic acid have pronounced effects on the overall stereodiscrimination60 66. As a consequence, the factors influencing the stereochemical course of Ugi reactions arc similar to those in Strecker syntheses. The use of chiral aldehydes is commonly found in substrate-controlled syntheses whereas the asymmetric synthesis of new enantiomerically pure compounds via Ugi s method is restricted to the application of optically active amines as the chiral auxiliary group. 

The highest enantioselectivities in the base-catalyzed Michael additions have so far been obtained using achiral bases complexed to chiral crown ethers. The addition of methyl 2,3-dihydro-l-oxo-1//-indene-2-carboxylate (1) to 3-buten-2-one using 4 mol% of a [l,T-binaphthalcnc]-2,2 -diol derived optically active crown ether 3 in combination with potassium AY/-butoxide as the base illustrates this successful method 259 260 It is assumed that the actual Michael donor is the potassium enolate complex of 1 and crown ether 3. 

Sulfoxides were first prepared in optically active form in 1926 by the classical technique of diastereomeric salt formation followed by separation of the diastereomers by recrystallization16 17. Sulfoxides 1 and 2 were treated with d-camphorsulfonic acid and brucine, respectively, to form the diastereomeric salts. These salts were separated by crystallization after which the sulfoxides were regenerated from the diastereomers by treatment with acid or base, as appropriate. Since then numerous sulfoxides, especially those bearing carboxyl groups, have been resolved using this general technique. 

The preparation of enantiomerically enriched a-ketosulphoxides 272 was also based on a kinetic resolution involving the reaction of the carbanion 273 derived from racemic aryl methyl sulphoxides with a deficiency of optically active carboxylic esters 274334, (equation 151). The degree of stereoselectivity in this reaction is strongly dependent on the nature of both the group R and the chiral residue R in 274. Thus, the a-ketosulphoxide formed in the reaction with menthyl esters had an optical yield of 1.3% for R = Et. In the... 

The study of optical isomers has shown a similar development. First it was shown that the reduction potentials of several meso and racemic isomers were different (Elving et al., 1965 Feokstistov, 1968 Zavada et al., 1963) and later, studies have been made of the ratio of dljmeso compound isolated from electrolyses which form products capable of showing optical activity. Thus the conformation of the products from the pinacolization of ketones, the reduction of double bonds, the reduction of onium ions and the oxidation of carboxylic acids have been reported by several workers (reviewed by Feokstistov, 1968). Unfortunately, in many of these studies the electrolysis conditions were not controlled and it is therefore too early to draw definite conclusions about the stereochemistry of electrode processes and the possibilities for asymmetric syntheses. 

Carboxylates, which are chiral in the a-position totally lose their optical activity in mixed Kolbe electrolyses [93, 94]. This racemization supports either a free radical or its fast dynamic desorption-adsorption at the electrode. A clearer distinction can be made by looking at the diastereoselectivity of the coupling reaction. Adsorbed radicals should be stabilized and thus react via a more product like transition state... 

Hydroxy-L-prolin is converted into a 2-methoxypyrrolidine. This can be used as a valuable chiral building block to prepare optically active 2-substituted pyrrolidines (2-allyl, 2-cyano, 2-phosphono) with different nucleophiles and employing TiQ as Lewis acid (Eq. 21) [286]. Using these latent A -acylimmonium cations (Eq. 22) [287] (Table 9, No. 31), 2-(pyrimidin-l-yl)-2-amino acids [288], and 5-fluorouracil derivatives [289] have been prepared. For the synthesis of p-lactams a 4-acetoxyazetidinone, prepared by non-Kolbe electrolysis of the corresponding 4-carboxy derivative (Eq. 23) [290], proved to be a valuable intermediate. 0-Benzoylated a-hydroxyacetic acids are decarboxylated in methanol to mixed acylals [291]. By reaction of the intermediate cation, with the carboxylic acid used as precursor, esters are obtained in acetonitrile (Eq. 24) [292] and surprisingly also in methanol as solvent (Table 9, No. 32). Hydroxy compounds are formed by decarboxylation in water or in dimethyl sulfoxide (Table 9, Nos. 34, 35). 

Optical Activity Caused by Restricted Rotation of Other Types. Substituted paracyclophanes may be optically active and 25, for example, has been resolved. In this case, chirality results because the benzene ring cannot rotate in such a way that the carboxyl group goes through the alicyclic ring. Many chiral layered cyclophanes (e.g., 26) have been prepared. ... 

Most resolution is done on carboxylic acids and often, when a molecule does not contain a carboxyl group, it is converted to a carboxylic acid before resolution is attempted. However, the principle of conversion to diastereomers is not confined to carboxylic acids, and other groupsmay serve as handles to be coupled to an optically active reagent. Racemic bases can be converted to diastereomeric salts with active acids. Alcohols can be converted to diastereomeric esters, aldehydes to diastereomeric hydrazones, and so on. Even hydrocarbons can be converted to diastereomeric inclusion... 

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. ... 

Salts of aliphatic or aromatic carboxylic acids can be converted to the corresponding nitriles by heating with BrCN or CICN. Despite appearances, this is not a substitution reaction. When R COO was used, the label appeared in the nitrile, not in the C02, and optical activity in R was retained. The acyl isocyanate... 

In the special case of the prochiral carboxylic acids (36), dehydrohalogenation with an optically active lithium amide gave an optically active product with enantiomeric excesses as high as 82%. 

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