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

我们以前曾报道过2，6-bis[(4S)-(-)-isopropyl-2-oxazolin-2-yl]pyridine((S，S)-PYBOX-IPR)与Sc(OTf)_3形成的手性络合物(10mol%)在邻甲氧基甲酰基-α-重氮苯乙酮与苯甲氧基乙醛的不对称环加成反应中具有很高的对映选择性。然而，在相同条件下与丙酮酸苄酯的反应没有表现出很高的对映选择性，尽管观察到了较高的外选择性。通过对添加剂的考察，发现三氟乙酸(TFA，10mol%)是一种有效的添加剂，可用于高水平的不对称诱导。因此，当在由(S，S)-PYBOX-i-Pr，Sc(OTf)_3和TFA制备的催化剂(10mol%)的存在下，通过添加重氮底物，在-40℃，1h的时间内进行反应时，得到了相应的环加成物，具有高的非对映选择性(exo：endo=93：7)和高的对映选择性(94…更多%ee(Exo))。Sc(III)-(S，S)-Pybox-i-Pr催化体系也适用于几种α-酮酸酯的反应，它们大多具有高的非对映选择性(exo：endo=68：12-93：7)和高的对映体选择性(80-94%ee(Exo))。另一方面，在上述羰基叶立德与3-丙烯酰基-2-恶唑烷酮的反应中，以2，6-双[(4，S)-苯基-2-恶唑啉-2-基]吡啶(S，在四氢呋喃中，Yb(OTf)_3具有较高的对映选择性(96%ee)和较高的外选择性(82：18)。在与3-巴豆酰基-2-恶唑烷酮的反应中，发现Tm(OTf)_3与S(S)-Ph的结合是一种非常有效的手性Lewis酸，以高非对映(endo：exo=95：5)和对映体选择性(98%ee)的方式生成环加成产物。这种稀土金属-PYBOX催化的方法也可以应用到花药底物中，作为羰基叶立德的前体。以Yb(OTf)_3与2，6-bis[(4S，5S)-(-)-diphenyl-2-oxazolin-2-yl]pyridine，反应制得的手性络合物(10mol%)催化N-重氮乙酰基吡咯烷酮与3-丙烯酰基-2-恶唑烷酮的反应，得到主环加合物的ee为71%的环加成产物(主：次=84：16)。联萘二亚胺-镍(II)作为新型手性路易斯酸也被开发出来，并用于环戊二烯的不对称Diels-Alder反应、硅氧基呋喃的Michael加成反应以及具有较高全活性的硝酮的外选择环加成反应。较少

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