Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, M5S 3H6 Canada.
J Org Chem. 2010 Feb 5;75(3):702-15. doi: 10.1021/jo9021106.
Generally, the hetero-Diels-Alder reaction (Povarov reaction) of N-arylimine dienes are limited to reaction with activated, electron-rich alkenes. However, introduction of ring strain in the dienophile, as with moderately strained bicyclo[2.2.1]heptenes (norbornene), enables three-component Povarov reaction with in situ formed N-arylimines under Lewis acid catalyzed conditions (BF(3).OEt(2)). The reactions proceed efficiently with a diverse set of commercially available anilines and benzaldehydes, as well as a variety of substituted norbornenes. The corresponding tetrahydroquinolines are formed with high complexity in a multicomponent fashion and are obtained in good yield and high diastereoselectivity. In addition, more reactive ethyl glyoxylate derived imines were utilized to achieve faster, room temperature reactions with norbornene. In all cases, attack of the N-arylimine dienes occurred exclusively from the exo-face of the norbornene ring, but the relative stereochemistry of the substituent alpha to the tetrahydroquinoline nitrogen, as well as the regioselectivity of reaction, was shown to depend upon subtle substituent effects on the aniline precursors. In most cases, a preference for the formation of exo-exo diastereomeric adducts was observed, but for reactions of ortho- or meta-substituted anilines, the formation of exo-endo adducts was also observed. These observations may be rationalized by two competing mechanistic models, involving either a concerted asynchronous [4 + 2]-like mechanism or a stepwise mechanism.
一般来说，N-芳基亚胺二烯的杂 Diels-Alder 反应（Povarov 反应）仅限于与活化的、富电子的烯烃反应。然而，在亲二烯体中引入环张力，如中等张力的二环[2.2.1]庚烯（降冰片烯），可以在路易斯酸催化条件下（BF(3).OEt(2)）与原位形成的 N-芳基亚胺进行三组分 Povarov 反应。该反应可与多种市售苯胺和苯甲醛以及各种取代的降冰片烯高效进行，以多组分方式形成具有高复杂度的相应四氢喹啉，并以良好的收率和高非对映选择性获得。此外，利用更具反应性的乙基乙二醛衍生亚胺，可实现与降冰片烯的更快、室温反应。在所有情况下，N-芳基亚胺二烯的进攻都仅来自降冰片烯的 exo-面，但四氢喹啉氮上的取代基 alpha 的相对立体化学以及反应的区域选择性被证明取决于苯胺前体上微妙的取代基效应。在大多数情况下，观察到形成 exo-exo 非对映异构体加合物的偏好，但对于邻位或间位取代苯胺的反应，也观察到形成 exo-endo 加合物。这些观察结果可以通过两种竞争的机理模型来合理化，涉及协同异步[4 + 2]-样机理或分步机理。
