Departamento de Química Orgánica I, Universidad del País Vasco UPV/EHU, Manuel Lardizabal 3, 20018, San Sebastián, Spain.
Department of Chemistry, KTH Royal Institute of, Technology, Teknikringen 30, 100 44, Stockholm, Sweden.
Chemistry. 2019 Sep 20;25(53):12431-12438. doi: 10.1002/chem.201902817. Epub 2019 Sep 3.
A bifunctional amine/squaramide catalyst promoted direct aldol addition of an hydantoin surrogate to pyridine 2-carbaldehyde N-oxides to afford adducts bearing two vicinal tertiary/quaternary carbons in high diastereo- and enantioselectivity (d.r. up to >20:1; ee up to 98 %) is reported. Acid hydrolysis of adducts followed by reduction of the N-oxide group yields enantiopure carbinol-tethered quaternary hydantoin-azaarene conjugates with densely functionalized skeletons. DFT studies of the potential energy surface (B3LYP/6-31+G(d)+CPCM (dichloromethane)) of the reaction correlate the activity of different catalysts and support an intramolecular hydrogen-bond-assisted activation of the squaramide moiety in the transition state of the catalytic reaction.
一种双功能的胺/脒基酰胺催化剂促进了海因代用物与吡啶 2-醛 N-氧化物的直接羟醛加成反应，以高非对映选择性和对映选择性（高达>20:1 的 dr 值；高达 98%的 ee 值）得到了带有两个相邻的三级/季碳原子的加合物。加合物的酸水解，然后还原 N-氧化物基团，得到了具有密集功能化骨架的手性醇键合的季铵海因-氮杂芳烃共轭物。反应的势能面（B3LYP/6-31+G(d)+CPCM（二氯甲烷））的密度泛函理论研究关联了不同催化剂的活性，并支持在催化反应的过渡态中脒基部分的分子内氢键辅助活化。
