Development of Asymmetric Cycloaddition Reactions of Carbonyl Ylides Using Chiral Lewis Acid Catalusts

使用手性路易斯酸催化剂开发羰基叶立德的不对称环加成反应

基本信息

批准号：
15550087
负责人：
SUGA Hiroyuki
金额：
$ 2.37万
依托单位：
Faculty of Engineering, Shinshu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

We have previously reported that the chiral complex (10 mol%), which was prepared from 2,6-bis[(4S)-(-)-isopropyl-2-oxazolin-2-yl]pyridine ((S,S)-Pybox-iPr) and Sc(OTf)_3, was quite effected for obtaining high enantioselectivity in an asymmetric cycloaddition reaction of the carbonyl ylide genenrated from o-methoxycarbonyl-α-diazoacetophenone with benzyloxyacetaldehyde. However, the reaction with benzyl pyluvate under the same conditions did not show high enantioselevtivity, although high exo-selectivity was observed. From a survey of additives, trifluoroacetic acid (TFA, 10 mol%) was found to be an efficient additive for a high level of asymmetric induction. Thus, when the reaction was carried out in the presence of the catalyst (10 mol%), which was prepared from (S,S)-Pybox-i-Pr, Sc(OTf)_3, and TFA, at -40 ℃ by adding the diazo substrate over a period of 1 h, the corresponding cydoadducts were obtained with high diastereoselectivity (exo : endo=93 : 7) and high enantioselectivity (94 … More % ee (exo)). The Sc(III)-(S,S)-Pybox-i-Pr-catalytic system including TFA was also applicable to the reactions with several α-keto esters mostly with high diastereoselectivity (exo : endo=68:12-93:7) and high enantioselectivity (80-94% ee (exo)).On the other hand, in the reaction of the above carbonyl ylide with 3-acryloyl-2-oxazolidinone as an olefinic dipolarlophile, the chiral complex, which was prepared from 2,6-bis[(4,S)-(-)-phenyl-2-oxazolin-2-yl]pyridine ((S,S)-Pybox-Ph) and Yb(OTf)_3 in THF, was superior in terms of high enantioselectivity (96% ee) of exo-cycloadduct with high exo-selectivity (82 : 18). In the case of the reaction with 3-crotonoyl-2-oxamlidinone, the combination of Tm(OTf)_3 and S,S)-Pybox-Ph was found to be extremely valid as a chiral Lewis acid to give cycloadducts in high diastereo-(endo : exo=95 : 5) and enantioselective manners (98% ee). This rare earth metal-Pybox catalyzed method could also apply to anther diem substrate as a carbonyl ylide precursor. The reaction of N-diazoacetylpyrrolidinone with 3-acryloyl-2-oxazolidinone catalyzed by the chiral complex (10 mol%), which was prepared from Yb(OTf)_3 and 2,6-bis[(4S,5S)-(-)-diphenyl-2-oxazolin-2-yl]pyridine, gave cycloadducts with 71% ee of a major cycloadduct (major : minor = 84 : 16).Binaphthyldiimine-Ni(II) catalysts as novel chiral Lewis acids were also developed and applied to asymmetric Diels-Alder reactions of cyclopentadiene, Michael addition reactions of silyloxyfurans, and exo-selective cycloaddition reactions of nitrones with high levels of enentioselevtivities. Less

我们之前报道过由2,6-双[(4S)-(-)-异丙基-2-恶唑啉-2-基]吡啶((S,S)- Pybox-iPr) 和 Sc(OTf)_3 在由生成的羰基叶立德的不对称环加成反应中获得高对映选择性非常有效邻甲氧基羰基-α-重氮苯乙酮与苄氧基乙醛的反应尽管从添加剂三氟乙酸（TFA，10 mol%）的调查中观察到高外选择性，但在相同条件下与丙酮酸苄酯的反应并未表现出高对映选择性。因此，当反应在催化剂存在下进行时，发现它是一种用于高水平不对称诱导的有效添加剂。 (10 mol%)，由(S,S)-Pybox-i-Pr、Sc(OTf)_3和TFA制备，在-40 ℃下加入重氮底物1 h，得到相应的环加合物具有高非对映选择性（exo：endo=93：7）和高对映选择性（94 … More % ee (exo)）。包含TFA的Sc(III)-(S,S)-Pybox-i-Pr-催化体系也适用于与多种α-酮酯的反应，大多具有高非对映选择性(exo : end=68:12-93:7)和高对映选择性（80-94% ee (exo)）。另一方面，在上述羰基叶立德与3-丙烯酰基-2-恶唑烷酮作为烯属偶极亲和物，是一种手性配合物，由 2,6-双[(4,S)-(-)-苯基-2-恶唑啉-2-基]吡啶 ((S ,S)-Pybox-Ph) 和 Yb(OTf)_3 在 THF 中的高对映选择性 (96% ee) 方面表现出色具有高外选择性的外环加合物 (82 : 18) 在与 3-巴豆酰基-2-oxamlidinone 的反应中，发现 Tm(OTf)_3 和 S,S)-Pybox-Ph 的组合。作为手性路易斯酸非常有效，可以以高非对映体（endo : exo=95 : 5）和对映选择性方式生成环加合物（98%这种稀土金属-Pybox催化方法也适用于作为羰基叶立德前体的花药基质，由手性络合物（10 mol%）催化的N-重氮乙酰基吡咯烷酮与3-丙烯酰基-2-恶唑烷酮的反应。由 Yb(OTf)_3 制备并且2,6-双[(4S,5S)-(-)-二苯基-2-恶唑啉-2-基]吡啶，得到环加合物，其中主要环加合物的ee为71％（主要：次要= 84：16）。联萘亚胺- Ni(II)催化剂作为新型手性路易斯酸也被开发并应用于环戊二烯的不对称Diels-Alder反应，甲硅烷基氧基呋喃的迈克尔加成反应和具有高水平对映体选择性的硝酮的外选择性环加成反应。