金鸡纳生物碱衍生手性配体的合成

文章编号:025329837(2006)0620527205

研究论文:527～531

收稿日期:2005212225.　第一作者:何　炜,女,1972年生,博士.联系人:张生勇.Tel :(029)84776945;E 2mail :syzhang @.

基金项目:国家自然科学基金(20572131)和陕西省自然科学基金(2003B20)资助项目.

金鸡纳生物碱衍生手性双胺配体的合成及其

在不对称氢转移反应中的催化作用

何　炜,　张邦乐,　刘　鹏,　孙晓莉,　张生勇

(第四军医大学药学系化学教研室,陕西西安710032)

摘要:以价廉易得的天然金鸡纳生物碱奎宁和辛可宁为原料,在温和条件下容易地合成了6种手性双胺配体.考察了它们与

过渡金属Ir 和Rh 形成的配合物在苯乙酮不对称氢转移反应中的催化活性和不对称诱导作用.结果表明,92氨基金鸡纳生物碱配体具有良好的不对称催化活性,而当配体中的氨基被取代后其对映选择性降低.将92氨基(92脱氧)表辛可宁的Ir 配合物用于其它芳香酮的不对称氢转移反应时,该配体也显示了很高的催化活性(80%～90%收率)和对映选择性(除对氯苯乙酮ee 值为72%外,其余芳香酮ee 值均为95%～97%).

关键词:金鸡纳生物碱;奎宁;辛可宁;手性双胺配体;手性催化剂;不对称氢转移反应;苯乙酮中图分类号:O643/R914 文献标识码:A

Synthesis of Chiral Diamine Ligands Derived from Cinchona

Alkaloids and Their C atalytic Perform ance for

Asymmetric T ransfer H ydrogenation

HE Wei ,ZHANG Bangle ,L IU Peng ,SUN Xiaoli ,ZHANG Shengyong

3

(Depart ment of Chemist ry ,School of Pharm acy ,The Fourth Military Medical U niversity ,Xi ’an 710032,S haanxi ,China )

Abstract :The asymmetric transfer hydrogenation using 22propanol as the hydrogen source is a practical and ver 2satile method for obtaining secondary alcohols because of the inexpensive reagents and operational simplicity.Six chiral diamine ligands were synthesized from natural Ci nchona alkaloids ,quinine and cinchonine ,under mild conditions.These were first tested by asymmetric transfer hydrogenation of acetophenone in iridium and rhodi 2um catalytic systems using 22propanol as the hydrogen source.Both the iridium and rhodium complexes of these ligands showed high activity for this reaction ,and the enantioselectivity was influenced deeply by the structure of the chiral ligands.The complexes of 92amino (92deoxy )epiquinine and 92amino (92deoxy )epicinchonine proved to be effective catalysts ,whereas their benzamides and 42chlorobenzamides provided only moderate ee.The Ir 2complex of 92amino (92deoxy )epicinchonine was also applied in the hydrogenation of seven aromatic ketone sub 2strates ,resulting in a high catalytic activity (80%～90%)and high enantioselectivity (95%～97%ee ,except 72%ee for 42chloroacetophenone ).This is the first case using Ci nchona alkaloids skeleton in the iridium cat 2alyzed asymmetric reactions.

K ey w ords :Ci nchona alkaloid ;quinine ;cinchonine ;chiral diamine ligand ;chiral catalyst ;asymmetric transfer hydrogenation ;acetophenone

氢转移反应是在催化剂的存在下,由氢原子供体作助剂的重键还原反应[1].不对称氢转移反应利

用异丙醇或甲酸作氢原子供体,在不用氢气或活性金属氢化物的情况下将潜手性酮还原为手性仲醇,

第27卷第6期

催　化　学　报

2006年6月Vol.27No.6

Chi nese Journal of Catalysis

J une 2006