Enantioselective Reaction Catalyzed by Chiral Cationic Silicon Lewis Acids

长期以来，硅作为不对称合成的路易斯酸催化剂的可能性一直吸引着有机化学家的想象力。我们研究了含(R)-(+)-联萘酚的手性硅Lewis酸(R-BINOL)催化的不对称Diels-Alder反应。在含有未取代R-联苯醚的手性硅催化剂存在下，3-酰基-1，3-恶唑烷-2-酮与环戊二烯顺利地反应生成了高产率的Endo Diels-Alder加合物，对映体过量适中(在-78℃下反应6h，产率87%，endo/exo=98/2，(2S)-diels-alder加合物=69%ee/endo)。对映体选择性强烈依赖于BINOL配体3，3‘-位上的取代基和硅原子上的取代基的大小。因此，当使用含(R)-3，3‘-二溴联苯酚的硅催化剂时，对映体选择性发生了逆转，得到了绝对构型相反的内加合物(2R)(61%ee，endo/exo=98/2)。此外，随着…浓度的增加，对映体选择性增加比BINOL配体的3，3‘-位上的芳基取代基的空间体积更大。3-酰基-1，3-恶唑烷-2-酮与环戊二烯在含(R)-3，3‘-双(4-(2-萘基)苯基)联萘酚的硅路易斯酸催化剂上反应，得到相应的Diels-Alder加合物，ee(2R)为91%。硅原子上取代基的大小对对映体选择性也有很大影响。例如，当硅上带有苯基的硅催化剂和(R)-3，3‘-双(4-(2-萘基)苯基)联苯酚配体作为催化剂时，产物的对映体过量大大提高到99%ee。在优化的反应条件下，含(R)-BINOL配体的手性硅三酰亚胺(Si-NTf2)也有效地催化了烷基-1，3-恶唑烷-2-酮与环六丁二烯和直链1，3-二烯的对映选择性Diels-Alder反应，产率高达98%ee。催化剂负载量低至2.5mol%即可完成反应。Si29-核磁共振研究表明，在反应的过渡态中，与亲二烯基团配位形成的五配位硅物种参与了反应。较少

The possibility that silicon might serve as a useful Lewis acid catalyst for asymmetric synthesis has long captured the imagination of organic chemist. We have studied asymmetric Diels-Alder reactions catalyzed by a chiral silicon Lewis acid having (R)-(+)-binaphthol (R-BINOL). In the presence of chiral silicon catalyst having unsabstituted R-BINOL, 3-acyl-1,3-oxazolidin-2-one smoothly reacted with cyclopentadiene to afford the endo Diels-Alder adduct in high yield with moderate enantiomeric excess (at-78℃ for 6h, 87% yield, endo/exo=98/2, (2S)-Diels-Alder adduct=69% ee/endo). Enantioselectivity was found to depend strongly on the size of both the substituents on 3,3'-position of the BINOL ligands and the substituents on the silicon atom. Thus, when the silicon catalyst having (R)-3,3'-dibromo-binaphthol was used, enantioselectivity was reversed and endo adduct with opposite absolute configuration (2R) was obtained (61% ee, endo/exo=98/2). Furthermore, enantioselectivities increased wi … More th the steric bulk of the aryl substituents on 3,3'-position of the BINOL ligands. When the reaction of 3-acyl-1,3-oxazolidin-2-one with cyclopentadiene was conducted by using silicon Lewis acid catalyst bearing (R)-3,3'-bis(4-(2-naphthyl)phenyl)binaphthol, the corresponding Diels-Alder adduct was obtained with 91% ee (2R). The size of substituents on the silicon atom also exerts a strong influence to the enantioselectivity. For example, enantiomeric excess of the product was greatly improved to 99% ee when silicon catalyst having phenyl group on the silicon and (R)-3,3'-bis(4-(2-naphthyl)phenyl)binaphthol ligand was used as the catalyst.Under the optimized reaction conditions, chiral silyltriflimides (Si-NTf2) bearing (R)-BINOL ligands also effectively catalyzed the enantioselective Diels-Alder reaction of alkenoyl-1,3-oxazolidin-2-ones with cyclohexabutadiene and linear 1,3-dienes to give corresponding Diels-Alder adducts in high yields with high enantioselctivity (up to 98% ee). Catalyst loadings as low as 2.5mol% were enough to complete the reaction. Si29-NMR studies revealed that five-coordinate silicon species formed by the coordination with dienophiles are involved in transition state of the reaction. Less