Enantioselective Reaction Catalyzed by Chiral Cationic Silicon Lewis Acids

硅作为一种有用的路易斯酸催化剂用于不对称合成的可能性长期以来一直吸引着有机化学家的想象力。本文研究了手性硅Lewis酸(R)-(+)-联萘酚（R- binol）催化的不对称Diels-Alder反应。在含未取代R-BINOL的手性硅催化剂存在下，3-酰基-1,3-羟唑烷-2- 1与环戊二烯顺利反应，生成了高收率的Diels-Alder内加合物，对映体过量适中（在78℃下反应6h，产率87%，内/外=98/2,(2S)-Diels-Alder内加合物=69% ee/endo）。对映体选择性强烈地依赖于BINOL配体的3,3'位置上的取代基和硅原子上的取代基的大小。因此，当使用含有(R)-3,3′-二溴-联萘酚的硅催化剂时，对映选择性被逆转，得到绝对构型相反的内加合物（2R） （61% ee，内do/exo=98/2）。此外，对映选择性随3,3'位芳基取代基空间体积的增加而增加。当3-酰基-1,3-恶唑烷-2- 1与环戊二烯在硅Lewis酸催化剂上反应(R)-3,3'-双（4-（2-萘基）苯基）联萘酚时，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选择性也有很大影响。例如，当硅上有苯基的硅催化剂和(R)-3,3'-双（4-（2-萘基）苯基）双萘酚配体作为催化剂时，产物的对映体过量量大大提高到99% ee。在优化后的反应条件下，手性硅三酰亚胺（Si-NTf2） (R)-BINOL配体还能有效催化烯基-1,3-恶唑烷-2- 1与环己丁二烯和线性1,3-二烯的对映选择性Diels-Alder反应，得到相应的Diels-Alder加合物，产率高，对映选择性高（可达98% ee）。催化剂负荷低至2.5mol%就足以完成反应。Si29-NMR研究表明，与二亲体配位形成的五配位硅参与了反应的过渡态。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