Development of Asymmetric Reactions Catalyzed by Chiral Bronsted Acid

我们已经开发并合成了以(R)-BINOL为起始点的手性磷酸二酯，并证明了其作为手性Bronsted酸的催化活性。为了扩展手性Bronsted酸催化，我们研究了对亚胺的对映选择性亲核加成反应和环加成反应。在具有3,3'位的3,5-(CF_3)C_6H_2基团的磷酸二酯催化下，亚磷酸二异丙基与醛胺发生亲核加成反应，得到对映选择性高的a-氨基膦酸盐。富电子二烯（如Danishefsky's diene）与醛胺的Aza Diels-Alder反应顺利进行，得到具有高至优异对映选择性的含氮六元环。富电子烯烃与aza二烯的反向电按需diols - alder反应也顺利进行，通过在3,3'位上含有9-蒽基的磷酸二酯，得到对映选择性良好的四氢喹啉衍生物。我们发现，由(R)-BINOL衍生的磷酸二酯作为手性布氏酸，在亲核反应和环加成反应中表现出优异的催化活性，从而得到具有良好至优异光学纯度的含氮化合物。

We already developed and synthesized a chiral phosphoric acid diester starting from (R)-BINOL and demonstrated its catalytic activity as a chiral Bronsted acid. In order to extend the chiral Bronsted acid catalysis, we have studied the enantioselective nucleophilic addition and cycloaddition reaction toward imines.Nucleophilic addition of diisopropyl phosphite with aldimine was catalyzed by a phosphoric acid diester bearing 3,5-(CF_3)C_6H_2 groups on 3,3'-position to give a-aminophosphonate with high enantioselectivity.Aza Diels-Alder reaction of electron-rich dienes such as Danishefsky's diene with aldimine proceeded smoothly to give nitrogen-containing 6-membered rings with high to excellent enantioselectivity.The reverse electron-demand aza Diels-Alder reaction of electron-rich alkene with aza Diene also proceeded smoothly to give tetrahydroquinoline derivatives with excellent enantioselectivity by means of a phosphoric acid diester bearing 9-anthryl group on the 3,3'-positions.We have found that the phosphoric acid diesters, derived from (R)-BINOL, exhibit excellent catalytic activity as chiral Bransted acid for the nucleophilic reactions and cycloaddition reactions to give nitrogen-containing compounds with good to excellent optical purity.