Brucine ketone resolution

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 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 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. 

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... 

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