Enantioselective Trimethylsilylcyanation of Aldehydes --- The Development of New Camphor-based Chiral Schiff Base-Titanium Alkoxide Complexes

• Main Authors: Shiou-Ming Shiu, 許修銘
• Other Authors: Ta-Jung Lu
• Format: Others
• Language: en_US
• Published: 1999
• Online Access: http://ndltd.ncl.edu.tw/handle/98618233585345129415

碩士 === 國立中興大學 === 化學系 === 87 === We will report the development of an effective, and highly enantioselective, camphor-based chiral catalyst for the formation of cyanohydrin from aldehyde in this thesis. Camphorquinone, prepared from (1R)-(+)-camphor and SeO2, was reacted with 1.5 equiv of NH2OH·HCl at room temperature to afford the C-3 mono-oxime in 93% yield after purification by recrystallization from diethyl ether and column chromatography. The C-2 carbonyl group and the C-3 oxime were reduced with excess LAH in diethyl ether to give b-amino alcohol 5 in 78% yield after recrystallization from petroleum ether. Compound 5 was then treated with 1 equiv of salicylaldehyde in benzene to furnish the chiral Schiff base 6 in 84% yield after recrystallization from diethyl ether. Alternatively, the C-3 carbonyl group of camphorquinone was protected selectively with ethylene glycol followed by NaBH4 reduction of the C-2 carbonyl group. Acidic work up provided the 3-oxo-epiborneol (12) in 38% yield over two steps from camphorquinone. Reaction of a-hydroxy ketone 12 with o-aminophenol in refluxing ethanol for 72 h generated the corresponding imine 16 in 62% after recrystallization from dichloromethane. The chiral catalysts were formed by mixing 6 or 16 with Ti(OPr-i)4 at 0 °C in dichloromethane which were then employed in the asymmetric formation of cyanohydrins of nine different aldehydes at -40 °C. With Schiff base 6, the S- cyanohydrin was obtained as the major product in quantitative yield (>99 %) except cinnamaldehyde (75%) with 63 ~ 88 % enantiomeric excess. On the contrary, benzaldehyde gave low yield (36%) of the cyanohydrin in favor of the R-product with poor facial selectivity (11% ee) when chiral ligand 16 was utilized. Moreover, the addition of molecular sieves, salicylic acid, or methyl salicylate failed to improve the reaction yield and the facial selectivity. Furthermore, the use of phase transfer catalyst (BTEAC, TBAB, Aliquat 336), potassium cyanide and chiral ligand 6 on benzaldehyde produced the cyanohydrin in only 4-11% yield and 0-43% ee. In conclusion, a highly efficient chiral catalyst for the formation of cyanohydrin in excellent yield and good enantioselectivity from the corresponding aldehydes was prepared from Schiff base 6 and Ti(OPr-i)4. Chiral ligand 6 was synthesized from camphor in four steps in 60% overall yield. Thus, a new, enantioselective and practical method for the synthesis of cyanohydrins has been established.