Robinson carboxylic acid

Pyridine-4-carboxylic acid Britton-Robinson buffer, pH 6.1 -1.14... 

These formulae explain the scission products of the two alkaloids and the conversion of evodiamine into rutaecarpine, and were accepted by Asahina. A partial synthesis of rutaecarpine was effected by Asahina, Irie and Ohta, who prepared the o-nitrobenzoyl derivative of 3-)3-amino-ethylindole-2-carboxylic acid, and reduced this to the corresponding amine (partial formula I), which on warming with phosphorus oxychloride in carbon tetrachloride solution furnished rutaecarpine. This synthesis was completed in 1928 by the same authors by the preparation of 3-)S-amino-ethylindole-2-carboxylic acid by the action of alcoholic potassium hydroxide on 2-keto-2 3 4 5-tetrahydro-3-carboline. An equally simple synthesis was effected almost simultaneously by Asahina, Manske and Robinson, who condensed methyl anthranilate with 2-keto-2 3 4 5-tetrahydro-3-carboline (for notation, see p. 492) by the use of phosphorus trichloride (see partial formulae II). Ohta has also synthesised rutaecarpine by heating a mixture of 2-keto-2 3 4 5-tetrahydrocarboline with isatoic anhydride at 195° for 20 minutes. 

To set the stage for the crucial aza-Robinson annulation, a reaction in which the nucleophilic character of the newly introduced thiolactam function is expected to play an important role, it is necessary to manipulate the methyl propionate side chain in 19. To this end, alkaline hydrolysis of the methyl ester in 19, followed by treatment of the resulting carboxylic acid with isobutyl chlorofor-mate, provides a mixed anhydride. The latter substance is a reactive acylating agent that combines smoothly with diazomethane to give diazo ketone 12 (77 % overall yield from 19). 

The starting point for the 5-fluoropentanecarboxylic esters was cyclohexanone, which was oxidized to 5-hydroxypentane-carboxylic acid by a modification of Robinson and Smith s method.3 This was then converted into the bromo acid by means of hydrogen bromide and sulphuric acid.4... 

Their previous screening of catalysts for of aldol reactions and Robinson annu-lations suggested the possibility that chiral amines might also be able to catalyze the Mannich reaction [30, 31]. Thus, screening of catalysts for Mannich-type reactions between N-OMP-protected aldimines and acetone revealed that chiral diamine salt 10, L-proline 11, and 5,5-dimethylthiazolidine-4-carboxylic acid (DMTC) 12 are catalysts of Mannich-type reactions affording Mannich adducts in moderate yields with 60-88 % ee. To extend the Mannich-type reactions to aliphatic imines, the DMTC 12-catalyzed reactions are performed as one-pot three-component procedures. The o-anisidine component has to be exchanged with p-anisidine for the one-pot reactions to occur. The DMTC 12-catalyzed one-pot three-component direct asymmetric Mannich reactions provide Mannich adducts in moderate yield with 50-86 % ee. 

EttdaUne sesquiterpenes. Syntheses of eudaicne-type sesquiterpenes commonly utilize the Robinson annelation reaction to construct the bicyclic ring system. However, this annelation reaction often proceeds in low yields and with stereochemical difficulties. Huffman and Mole have recently reported a new stereoselective synthesis. 8-Methoxy-tctralin-2-carboxylic acid (1) is reduced under Birch conditions followed by acid... 

Nagra, B.S., Shaw, G., and Robinson, D.H., A novel synthesis of acyl cyanides from diethyl phosphorocyanidate and some 1-substituted imidazole carboxylic acids including a D-ribofuranoside, J. Chem. Soc., Chem. Commun., 459, 1985. 

Acetone, the component that must enolise, is present in large excess but the achievement is considerable. The reaction involves formation of the proline enamine of acetone 91 which then attacks the aldehyde through a chair-like transition state 92 held together by the acidic proton of proline s carboxylic acid. This gives the imine salt 93 hydrolysed to the product with regeneration of proline. The intermediates are like those in the Robinson annelation enamines and imines. Organic catalysis with amines relies on equilibria between these intermediates and carbonyl compounds. 

The introduction of a nonenolizable substituent on nitrogen allows the separation of 5-carboxylic acids and their derivatives. Such compounds have been prepared in a variety of ways, including the oxidation of alkyl groups (Eq. 15) or formyl groups (Eq. 16). Sheehan and Robinson carried out a similar reaction sequence (Eq. 17) using a diethylacetal. ... 

A range of tetrahydro-9f/-xanthen-9-ones arise from photo-induced C-O bond formation of 2-methoxyaryl 2-chlorocyclohex-l-enyl ketones and related compounds (14CC5254). Some examples of tetrahydro-9ff-xanthen-9-ones were obtained as diastereomeric mixtures of cis- and traws-isomers through a 4-DMAP-mediated tandem addition reaction of l-(2-hydroxyaryl)alkynones bearing an aldehyde function (Scheme 76) (140L1642). A Robinson annulation of a P-keto ester and methyl vinyl ketone mediated by tin(lV) chloride afforded a tetrahydro-9H-xanthen-9-one-l-carboxylic acid-type compound (14JOC10689). 

How could this complex bicycllc compound be synthesized efficiently Using the positioning of the nitrogen atom reiative to the ketone, Robinson believed that the entire molecule could potentially arise from a dialdehyde, methylamine, and acetone dicarboxyiic acid in a single, one-pot transformation, as color-coded below. The key reactions in the actual union would be a series of carefully orchestrated iminium ion formations and Mannich reactions to make the new C—C bonds (colored in green), followed by carboxylic acid decarboxylations to complete the target. 

The mechanism involves a Michael reaction followed by a Dieckmann reaction (intramolecular Claisen), all base promoted. Loss of the ester group begins with an add-catalyzed hydrolysis, followed by decarboxylation of the resulting carboxylic acid. Finally, a Robinson annulation with methyl vinyl ketone affords the final product. 

Recently, Barbas and Bui looked at the one-pot proline-catalysed Robinson annulation sequence to see if proline can catalyse the entire reaction sequence they found that substituted hydroxyproline derivatives 17-19 were viable catalysts for the reaction, producing the desired products in 60 to 70% ee. The corresponding smaller analog 20 gave the product in less than 10% ee. Additional work looked at analogs in which the carboxylic acid was reduced or replaced by other functional groups these compounds, which are not shown, were not viable catalysts for the entire reaction sequence. Instead, the intermediate Michael adduct or cyclized, but not dehydrated, intermediates were observed. 

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