Development of Asymmetric Reactions by use of Chiral Bronsted Acid

新型高效催化剂的开发一直是合成有机化学中具有挑战性的课题。以(R)-联苯醚为起始原料，合成了一种环状磷酸衍生物。该磷酸对亚胺的亲核加成反应表现出良好的催化活性1)硅烯醇合成亚胺的Mannich反应，手性Bronsted酸催化的Mannich反应在3，3‘-双(4-硝基苯基)取代联萘酚衍生的环磷酸盐的存在下进行得很顺利。以较高的产率和良好的对映体选择性得到了β-氨基酯。联萘酚上的取代基对对映体选择性和反应活性起着至关重要的作用。O-HOC_6H_4NH_2衍生的亚胺具有最高的对映体选择性。邻羟基的存在对于手性诱导是必不可少的。2)氢膦酰化反应亚磷酸二异丙酯与亚胺的氢膦基化反应也发生了高度的对映选择性，得到了高产率的α-氨基膦酸酯。在这种情况下，在联萘环的3，3‘-位上使用含3，5-(CF_3)_2C_6H_3基团的手性磷酸是获得高对映体选择性的关键。3)环加成反应在手性B酸催化下，丹尼舍夫斯基的二烯与亚胺的氮杂Diels-Alder反应也进行得很顺利。在这种情况下，2，4，6-三异丙基苯基取代的手性催化剂效果最好。与传统的金属基手性催化剂相比，目前的Bronsted酸不含金属，在空气中稳定。目前的催化剂为手性有机催化剂增加了一个新的入口。

Development of novel efficient catalysts continue to be a challenging topics in synthetic organic chemistry. We have synthesized a cyclic phosphoric acid derivatives, starting from (R)-BINOL. The phosphoric acid exhibited excellent catalytic activity in the nucleophilic addition reaction toward imines.1) Mannich-type reaction of silyl enolate to imines.Chiral Bronsted acid catalyzed Mannich-type reaction proceeded smoothly in the presence of 10 mol% of a cyclic phosphate derived from 3,3'-bis(4-nitrophenyl)-substituted binaphthol. β-Amino esters were obtained in high to excellent yields and with excellent enantioselectivities. The substituents on binaphthol played a crucial role in enantioselectivity and reactivity. Imines derived from o-HOC_6H_4NH_2 gave the highest enantioselectivity. Presence of o-hydroxy group is essential for the chiral induction. Based on the results, we would like to propose 9-membered transition state, wherein phosphoryloxygen forms hydrogen bond with OH moiety.2) Hydrophosphonylation reactionHydrophosphonylation of diisopropyl phosphite to imine also took place highly enantioselectively to give α-amino phosphonate in high yields with good to high enantioselectivities. In this case, use of a chiral phosphate bearing 3,5-(CF_3)_2C_6H_3 group on 3,3'-position of binaphthyl ring is essential for attaining high enantio selectivity.3) Cycloaddition reactionAza Diels-Alder reaction of Danishefsky's diene with imine also proceeded smoothly by means of the chiral Bronsted acid catalyst. In this case, 2,4,6-triisopropylphenyl group substituted one gave the best results.Contrary to conventional metal-based chiral catalysts, present Bronsted acid is free from metal and is stable in air. Present catalysts adds a new entry into chiral organocatalysts.