Ketones brucine

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. 

If 2-camphanyloxyacrylonitrile (15 R = C8H 02C00) is taken for cycloaddition, diastereoisomeric cycloadducts can be separated, and the basic system, 7-oxabicyclo-[2.2.1]hept-5-en-2-one 17, can be obtained in optically pure form [36]. Another way of obtaining enantiomeric ketones is based on crystallization of a brucine complex obtained from the corresponding cyanohydrines (see Sec. III). Ketone 17 can be converted [e.g., by cis-hydroxylation (—>18), protection of the diol system, and Baeyer-Villiger oxidation] to lactone 19, the opening of which leads to furanuronic acid 20. A new development in this field is based in cycloaddition between furan and 2-chloro- or 2-bromoacrolein in the presence of 5 mol% chiral oxazaborolidine 21 as catalyst [37],... 

D-(-)-Pantolactone was obtained from the complex in the following manner. The 65.4 grams of complex obtained above were treated with 65 ml of chloroform and 5.35 grams of sodium hydroxide contained in 35 ml of water for one hour at room temperature. The aqueous layer was extracted 6 times with 20 ml portions of chloroform in order to remove the brucine. The sodium pantoate contained in the aqueous layer was relactonized by treatment with 11 ml of concentrated hydrochloric acid. Extraction of the crude D-(-)-pantolactone yielded 15.29 grams. This material was then recrystallized from 7 ml of methyl isobutyl ketone and 7 ml hexane thereby yielding 9.77 grams of D-(-)-pantolactone (37% of theory). The aD25 was -44.8°. 

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... 

Resolution of crystalline rac-29 (by means of brucine) gives 29, which, after conversion to 30, affords 15 Scheme 9) by Dieckmann condensation. The bicyclic hydroxy ketone 15 reacts with crotylmagnesium bromide to furnish 31a -I- 31b. On successive treatment with osmium tetroxide and lead tetraacetate the diastereoisomeric aldehydes arise which can be dehydrated to afford 16 -I- 32. The latter compound, obtainable by chromatography, on Wittig reaction leads to 33 which, on catalytic hydrogenation, gives 18 Scheme 9). Oxidation converts 18 to 19, and by successive Wittig reaction, followed by selective ozonolysis, unsaturated aldehyde 20 finally is formed. 

Acid (S)-12 was separated as its brucine salt [20,21] and subsequently converted into ketone (S)-ll. Hydroxyketones (K)-IO [22] and (S)-ll [23] were obtained by separation of the mixture of diastereoisomeric imines obtained from rac-10 or rac-ll and (-)-(S)-phenylethylamine. 

The ketone moiety of a cyclic keto-ester need not be in conjugation with the carboxyl moiety. This allows other methods for introduction of the amine group. Conversion of R-7.127 (resolved from the racemic material with brucine) to its oxime (7.128) was accomplished by treatment with hydroxylamine and pyridine.20... 

The reaction of H"CH0 with Al-acyl protected dialkyl aminomalonates and a-amino-ketones stops at the hydroxymethylation step. This behavior could be exploited for the synthesis of (R,S)-, (R)- and (5)-[3-"C]serine, (/f,5)-[3- C]cysteine and e.p. [1-"C]-chloramphenicol, as illustrated in Figure 5.38. In the [3-"C]serine preparations, saponification and decarboxylation converted the hydroxy["C]methyl derivatives 121 (R = acetyl orp-nitrobenzoyl), generated from H"CH0 and diethyl iV-acylaminomalonate, to racemic Af-acyl[3-"C]serine (122). Optical resolution of 122 with quinine and brucine followed by acid-catalyzed cleavage of the A -acyl groups afforded the enantiomerically pure... 

---