Enantioselective Reaction Catalyzed by Chiral Cationic Silicon Lewis Acids

硅作为刘易斯酸催化剂用于不对称合成的可能性一直吸引着有机化学家的想象力。研究了手性硅刘易斯酸（R-BINOL）催化的不对称Diels-Alder反应。在含有未取代R-BINOL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，以高产率得到了对映体过量的endo Diels-Alder加成物（-78 ℃反应6 h，产率87%，endo/exo=98/2，（2S）-Diels-Alder加成物=69% ee/endo）。对映选择性强烈地依赖于BINOL配体3，3 '-位上取代基的大小和硅原子上取代基的大小。因此，当使用具有（R）-3，3 ′-二溴-联萘的硅催化剂时，对映选择性被逆转，并且获得具有相反绝对构型（2 R）的内加成物（61%ee，内/外=98/2）。此外，对映体选择性随温度升高而增加， 关于我们 这是BINOL配体3，3 ′-位上芳基取代基的空间体积。在含（R）-3，3 '-双（4-（2-萘基）苯基）联萘的硅刘易斯酸催化下，3-酰基-1，3-恶唑烷-2-酮与环戊二烯反应，得到相应的Diels-Alder加成物，其ee（2 R）为91%。硅原子上取代基的大小对反应的对映选择性也有很大的影响。例如，当在硅上具有苯基和（R）-3，3 '-双（2-甲氧基苯基）-3，3-二（2-甲氧基苯基）-3，4-二（2-以4-（2-萘基）苯基）联萘为催化剂，在优化的反应条件下，带有（R）-BINOL配体的手性硅基三酰亚胺（Si-NTf 2）也能有效地催化烯酰基-1，3-恶唑烷-2-酮与环己丁烯和直链1，3-二烯反应，得到相应的Diels-Alder加成物，产率高，对映选择性高达98%ee。低至2.5mol%的催化剂负载量足以完成反应。Si ~（29）-NMR研究表明，在反应的过渡态中存在与亲双烯体配位形成的五配位硅物种。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