Cinchonine rearrangements

A multigram preparation of a useful chiral building block was developed, using the Beckmann rearrangement as a key synthetic step (equation 115) °. The enantiomeric addition of thiophenol to a chalcone 313, catalysed by (+)-cinchonine, provided the chiral enantiomeric carbonyl compound 314. The Beckmann rearrangement of its oxime 315 gives the anilide of (R)-(- -)-3-phenyl-3-phenylsulfanylpropanoic acid 316. Alcoholysis produced the expected enantiomerically pure ethyl ester 317. 

Cinchonine (CVI) can be transformed into dihydrocorynantheane (XV) by a series of reactions which first changes it into 9-benzoy]-2-oxyhexahydrocinchonine (CVII). The latter reacts with cyanogen bromide to give CVIII and this in turn under alkaline conditions suffers reduction and rearrangement to CIX, which on further reduction with lithium aluminum hydride followed finally by Oppenauer oxidation generates 3-epidihydrocorynantheane (CX). This can be isomerized by known means to dihydrocorynantheane (XV) (71). 

Hydroxycinchoninic acid has been prepared by the rearrangement of N-acetylisatin in alkali, -by the treatment of isatin with malonic acid in glacial acetic acid, and by heating cinchoninic acid with concentrated potassium hydroxide. ... 

The photochemical behavior of the W-oxides of the Cinchona alkaloids has been examined 49). Photolysis (> 300 nm) of the aromatic mono-iV-oxides 183 of the dihydro derivatives of quinine, quinidine, cincho-nidine, and cinchonine in alcoholic solvents gave the expected carbo-styrils 186 in yields of 70-85%. The same results were obtained with the corresponding AjiV-dioxides 184. An interesting rearrangement was observed in the case of the iV,A -dioxides of dihydrocinchonine and dihydrocinchonidine. Photolysis in benzene solution afforded, in addition to the carbostyrils, the iV -formylindole methanols 188 in 30% yield. The hydrolysis-sensitive benz[d]-l,3-oxazepines 185 were proposed as the probable intermediates. 

H 7.53%, N 9.52%, O 5.43%. A rearrangement product of cinchonine or dnehonidine obtained by boiling with acetic acid Pasteur, Compt. Rend- 37, 110 (1853)... 

---