The Application of Camphor - based Chiral Ligands in Asymmetric Synthesis

• Main Authors: I-Ping Wang, 王怡萍
• Other Authors: Ta-Jung Lu
• Format: Others
• Language: en_US
• Published: 2000
• Online Access: http://ndltd.ncl.edu.tw/handle/78890387906042869272

碩士 === 國立中興大學 === 化學系 === 88 === The development of effective, highly enantioselective, camphor-based chiral catalysts two for the formation of cyanohydrin from aldehyde is reported 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 94% yield after purification by recrystallization from diethyl ether followed by 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 73% 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 85% yield after recrystallization from dichloromethane. Alternatively, b-amino alcohol 5 was reacted with salicylic acid in dichloromethane in the presence of DCC and DMAP to generate the corresponding amide 9 in 93% yield after recrystallization from ethyl acetate and column chromatography. The chiral catalysts were prepared by mixing 6 or 9 with Ti(OPr-i)4 at 0 °C in dichloromethane which were then employed in the asymmetric formation of cyanohydrins of fifteen different aldehydes at -40 °C. With Schiff base 6, the S-cyanohydrins were obtained as the major products in good to excellent yields (60% ~ 98%) and enantiomeric excesses (53% ~ 87%). On the other hand, high yields (82 ~ 99%) and acceptable facial selectivities (18% ~ 83%) of the cyanohydrins in favor of the R-products were produced when chiral ligand 9 was utilized. Moreover, the chiral catalysts 6 and 9 were used to facilitate the addition reaction of diethyl zinc to aldehydes providing the secondary alcohols in favor of the R-products in good yields (54% ~ 97%) and facial selectivities ranging from 15% to 65% ee. In conclusion, two complementary, highly efficient chiral catalysts for the formation of cyanohydrin in excellent yield and good enantioselectivity from the corresponding aldehydes were prepared from Schiff base 6 and amide 9. Chiral ligand 6 and 9 were synthesized from camphor in four steps in 58% and 64% overall yield respectively. Thus, a new, enantioselective and practical method for the synthesis of cyanohydrins has been established.