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

• 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
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15550087/
• 关键词: Diazo Carbonyl Compound; Carbonyl Ylide; Cycloaddition Reaction; Lewis Acid; Asymmetric Synthesis; Rare Earth Metal; Enantioselectivity; Diastereoselecivity

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

本文报道了2，6-二[（4S）-（-）-异丙基-2-恶唑啉-2-基]吡啶（（S，S）-Pybox-iPr）与Sc（OTf）_3形成的手性配合物（10mol%），在邻甲氧羰基-α-重氮苯乙酮与苄氧乙醛生成的羰基叶立德的不对称环加成反应中获得了很高的对映选择性。在相同条件下，与丙酮酸苄酯的反应虽然具有较高的外消旋选择性，但对映体选择性不高。从添加剂的调查，三氟乙酸（TFA，10摩尔%）被发现是一个有效的添加剂的高水平的不对称诱导。因此，在（S，S）-Pybox-i-Pr，Sc（OTf）_3和TFA制备的催化剂（10mol%）存在下，于-40 ℃下加入重氮底物反应1h，得到了高非对映选择性（exo：endo=93：7）和高对映选择性（94 ...更多信息 % ee（exo））。含TFA的Sc（III）-（S，S）-Pybox-i-Pr-催化体系也适用于与几种α-酮酯的反应，大多具有高的非对映选择性（exo：endo=68：12-93：7）和高的对映选择性另一方面，在上述羰基叶立德与作为烯属亲电偶极体的3-丙烯酰基-2-恶唑烷酮的反应中，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中制备的手性配合物在具有高外消旋选择性（82：18）。在与3-巴豆酰基-2-恶唑烷酮的反应中，Tm（OTf）_3和S，S）-Pybox-Ph的组合作为手性刘易斯酸是非常有效的，以高的非对映体（endo：exo=95：5）和对映体选择性方式（98%ee）得到环加合物。这种稀土金属-Pybox催化的方法也可以作为羰基叶立德的前体应用于花药染料底物。Yb（OTf）_3与2，6-二[（4S，5S）-（-）-二苯基-2-恶唑啉-2-基]吡啶（2，6-bis[（4S，5S）-（-）-diphenyl-2-oxazolinyl-2-yl]pyridine）形成的手性配合物（10mol%）催化N-重氮乙酰基吡咯烷酮与3-丙烯酰基-2-恶唑烷酮的环加成反应，主要环加成产物的ee值为71（主要：次要= 84：还开发了作为新型手性刘易斯酸的联萘二亚胺-Ni（II）催化剂，并将其应用于环戊二烯的不对称Diels-Alder反应，硅氧基呋喃的Michael加成反应，和硝酮的外选择性环加成反应，具有高水平的对映异构性。少

项目成果

Chiral 2,2′-Binaphthyldiimine–Nickel(II) Complexes as Lewis Acid Catalysts for Enantioselective Diels–Alder Reactions

• DOI: 10.1246/bcsj.77.561
• 发表时间: 2004-03
• 期刊: Bulletin of the Chemical Society of Japan
• 影响因子: 4
• 作者: H. Suga;A. Kakehi,;Masashi Mitsuda

Highly exo-selective and enantioselective cycloaddition reactions of nitrones catalyzed by a chiral binaphthyldiimine-Ni(II) complex.

• DOI: 10.1021/ol050397h
• 发表时间: 2005-03
• 期刊: Organic letters
• 影响因子: 5.2
• 作者: H. Suga;T. Nakajima;K. Itoh;A. Kakehi,

Stereoselectivity in 1,3-Dipolar Cycloaddition Reactions of 2-Benzopyrylium-4-olate with Acrylic Acid Derivatives Catalyzed by Rare Earth Metal Triflates

• DOI: 10.1055/s-2003-40190
• 发表时间: 2003-07
• 期刊: Synthesis
• 作者: Kei-ichi Inoue;H. Suga;S. Inoue;Hiroki Sato;A. Kakehi,

Chiral 2,6-bis(oxazolinyl)pyridine-rare earth metal complexes as catalysts for highly enantioselective 1,3-dipolar cycloaddition reactions of 2-benzopyrylium-4-olates.

• DOI: 10.1021/jo049007f
• 发表时间: 2005-01
• 期刊: The Journal of organic chemistry
• 作者: H. Suga;Kei-ichi Inoue;S. Inoue;A. Kakehi,;M. Shiro

Hiroyuki Suga et al.: "Chiral 2,2'-Binaphthyldiimine-nickel(II) Complexes as Lewis Acid Catalysts for Enantioselective Diels-Alder Reactions"Bull.Chem.Soc.Jpn.. 77・3. 561-568 (2004)

Hiroyuki Suga等人：“手性2,2-联萘亚胺-镍(II)配合物作为路易斯酸催化剂用于对映选择性狄尔斯-阿尔德反应”Bull.Chem.Soc.Jpn.. 77・3 (2004)。