With -brucine

An interesting aspect of the benzofuran cationic polymerization was uncovered by Natta, Farina, Peraldo and Bressan who reported in 196160,61 that an asymmetric synthesis of an optically active poly(benzofuran) could be achieved by using AlCl2Et coupled with (-)j3-phenylalanine, (+)camphorsulphonic acid or with (-)brucine. The optical activity was definitely due to the asymmetric carbon atoms in the polymer chain, indicating that at least some of the polymer s macromolecules possessed a di-isotactic structure, v/ z.62 ... 

COOH racemate resolution with brucine in isoproponol... 

Enantionmerically enriched pairs of /i-stannylated benzoic acids (+)/(—)-35 and (+)/(—)-36 were obtained by resolution with brucine or strychnine (Scheme 13)20. Again, neither the configuration nor the enantiomeric enrichment could be determined. 

Binaphthyl-2,2 -dicarboxylic acid (1). (RS)-l can be resolved with brucine, which selectively forms a salt with (R)-l that is insoluble in acetone. 

Among the compounds to be discussed in this subsection we also encounter thiabenzene systems that, according to Mislow (168), are best described as cyclic sulfonium ylides. l-Pentafluorophenyl-2-methyl-2-thianaphthalene 130 the first example of an optically active thiabenzene, was prepared by Mislow and co-workers (169) by deprotonation of thiochromenium tetrafluoroborate 131 with brucine in anhydrous dimethylsulfoxide. 

Nitric Acid. — 0.2 gm. of diphenylamine should dissolve in 20 cc. of pure concentrated sulphuric acid with 2 cc. of water, and yield a colorless solution. Should a blue color develop, the sulphuric acid should be tested with brucine for the possible presence of nitric acid. 

For amounts of potassium nitrate higher than o-i% the reaction is sharp and intense. A feeble coloration with brucine or a slightly colomed ring with ferrous sulphate should be neglected, since extracts may derive traces of mtnc anhydride from the water used m their preparation, such quantities, however, never amount to o-i% of the extract... 

Diarylcarbinols (47) were easily resolved by complexation with brucine (4). For example, when a solution of 4 (1.8 g, 4.56 mmol) and... 

Toda, F., and Tanaka, K. (1981) ANew Optical Resolution Method of Tertiary Acetylenic Alcohol Utilizing Complexation with Brucine, Tetrahedron Lett., 22, 4669-4672. 

Conversion of Racemic Cyanohydrin into One Optically Acrtive Iosmer in the Presence of Brucine, Chem. Lett., 661-664. b) Tanaka, K. and Toda, F. (1987) Chiral Recognition and Optical Resolution of Cyanohydrin by Complexation with Brucine, Nippon Kagaku Kaishi, 456-459. 

Cellulose was the first sorbent for which the resolution of racemic amino acids was demonstrated [23]. From this beginning, derivatives such as microcrystalline triacetylcellulose and /3-cyclodextrin bonded to silica were developed. The most popular sorbent for the control of optical purity is a reversed-phase silica gel impregnated with a chiral selector (a proline derivative) and copper (II) ions. Separations are possible if the analytes of interest form chelate complexes with the copper ions such as D,L-Dopa and D.L-penicillamine [24], Silica gel has also been impregnated with (-) brucine for resolving enantiomeric mixtures of amino acids [25] and a number of amino alcohol adrenergic blockers were resolved with another chiral selector [26]. A worthwhile review on enantiomer separations by TLC has been published [27],... 

To complete the total synthesis of the optically active form of veatchine, the successful resolution of the synthetic racemic ketone 244 was accomplished. Compound 244 was reduced stereoselectively with sodium boro-hydride to give the alcohol 248. The latter was heated with succinic anhydride and pyridine in xylene to yield the racemic half-ester 249. Treatment of 249 with brucine afforded the diastereoisomeric brucine salts, which were separated by fractional crystallization. The separated salts were decomposed... 

Crystallization-induced asymmetric transformation has already been described by Leuchs in 1913 during the resolution of 2-(2-carboxybenzyl)-l-indanone with brucine.34 In this case spontaneous racemization occurred. More recently researchers at Sanofi observed spontaneous racemization during the resolution of 3-cyano-3-(3,4-dichlorophenyl)propionic acid (7), most likely as a result of the basic resolving agent [>-(-)-N-1 n etli y I g I near nine [d-(-)-MGA] (8) (Scheme 7.6).35 The enantiopure cyano acid, obtained in 91% overall yield, is subsequently reduced to (+)-4-amino-3-(3,4-dichlorophenyl)-l-butanol (9), a key intermediate in the phase 2 synthesis of tachykinin antagonists. 

This appeared to be supported by the findings of Ray and Palinchak [55] who resolved 9-nitro-2-benzoylfluorene with brucine. The brucine salt contained alcohol of crystallization and could probably be represented by the formula V ... 

Chiral 4-hydroxy-2-cyclopentenones. Both (R)- and (S)-4-hydroxy-2-cyclo-pentenones can be obtained from phenol. The first step is alkaline hypochlorite oxidation to the acid 1, which is resolved with brucine. Oxidative decarboxylation of 1 gives 2, which is partially dechlorinated and protected as the silyl ether (3). The last step to 4 is reduction with zinc-silver (S, 760) or zinc-copper. ... 

Resolution of Acids. The number of acids resolved with brucine is too large to attempt to list even a small portion of them in this synopsis. An excellent tabulation of all published resolutions with brucine up to 1972 is available. Only a few representative examples will be described here (eqs 1-4). In all these cases, the resolved acids were obtained in high yield and with almost absolute enantiomeric purity. The solvents most frequently used for brucine resolutions are acetone and alcohol solvents. However, water, hexane, and others have also been used as cosolvents. 

Additional types of carboxylic acids that have been successfully resolved with brucine are represented by structures (1H5). - "... 

As mentioned above, one of the limitations of using naturally occurring resolving agents is that only one enantiomer of the compound being resolved may be readily accessible by resolution. However, many examples have been described where brucine and some other alkaloid favor crystallization with opposite enantiomers of a given acid. For example, resolution of acid (6) with brucine yields the (+)-enantiomer, while cinchonidine provides material that is enriched in the (—)-enantiomerof the acid. Similarly, diacid (7) is resolved into its (—)-enantiomer by brucine and into its (+)-enantiomer by strychnine. The (+)-enantiomer of acid (8) can be obtained with brucine, while the (—)-enantiomer crystallizes with cinchonidine. Additional examples of the same phenomenon can be found in the literature. ... 

Resolution of Alcohols. Although not a well exploited use of brucine, a variety of secondary benzylic alcohols have been resolved by complexation and crystallization with brucine (eq 5). About a dozen alcohols were obtained in close to enantiomeric purity by this procedure. Also resolved by crystallization of their brucine inclusion complexes were a series of tertiary propargylic alcohols (eq 6). In this case, the enantiomer that does not crystallize with brucine can be obtained in almost complete optical purity from the mother liquors. 

A more traditional and general approach to the resolution of alcohols is the formation of the corresponding hemiphthalate or hemisuccinate esters, followed by resolution of these acidic derivatives with brucine or some other chiral base (eqs 7-9). 

Resolution of Ketones. Brucine has not been used very extensively for the resolution of neutral compounds. However, in some cases, ketones or ketone derivatives may form diastereomeric inclusion complexes with brucine, providing an opportunity for their resolution. For example, the cyanohydrin of a bicyclic ketone has been resolved by this procedure (eq 10). Following resolution of the cyanohydrin, the ketone was regenerated and determined to be of 94% ee. 

Resolution of Sulfoxides. Although it can be considered as the resolution of an unique type of carboxylic acid, some racemic sulfoxides containing carboxyhc acids have been resolved via diastereomeric crystalline complexes with brucine (eq 11). ... 

Brucine has been used to produce enantiomerically enriched compounds by selective reaction with or destruction of one of the enantiomers. The optical purity of the resulting compound is usually modest, although some exceptions have been described. For example, dibromo compound (9) was obtained [enriched in the (—)-enantiomer] by selective destruction of the (+)-enantiomer with brucine in chloroform. The resolution of ( )-2,3-dibromobutane may have also been a case of enantioselective destruction, although more recent reports suggest that it is more likely a case of enantioselective entrapment in the brucine crystals (eq 14). ... 

One synthesis of cyclopentenone [80], requiring a resolution, involved initial ring contraction of phenol when treated with alkaline hypochlorite (49). Resolution of the resulting cis acid [85] was effected with brucine. The desired enantiomer [86] formed the more soluble brucine salt and was thus obtained from the mother liquors of the initial resolution. Oxidative decarboxylation with lead tetracetate, partial dechlorination with chro-mous chloride, and alcohol protection gave chloro enone [87]. Zinc-silver couple (50) dechlorinated [87] to the desired cyclopentenone [80]. 

Furan adds to vinylene carbonate to produce an exolendo mixture of Diels-Alder adducts [165]. Double hydroxylation of the 7-oxanorbornene double bond is highly exo face selective (Scheme 13.88). The diol thus obtained is protected as an acetonide. Saponification of the carbonate liberates a mixture of diols that is oxidized into m 5 6>-l,5-anhydroallaric acid derivative 316. Treatment of 316 with AC2O generates the anhydride 317. Subsequent reaction of 317 with methanol gives racemic 318 that can be resolved by fractional crystallization with brucine or by chromatographic separation of the (7 )-l-((3-naphthyl)ethylamides. The individual isomers of 318 each react with ClCOOEt and Me3SiN3 in situ to provide enantiomerically pure d- and L-riboside derivatives [166]. 

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