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以商业化易得的具有碱性氮原子的手性药物为有机催化剂,用于催化β-酮酸酯不对称α-羟基化反应,发现以噻吗洛尔或普萘洛尔为催化剂,反应对映选择性分别可达32%和18%.对噻吗洛尔和普萘洛尔进行结构修饰,合成了12个洛尔药物类似物,并考察了其催化效果,发现在优化的反应条件下,以30mol%(R)-1-叔丁胺基-3-(2-萘氧基)-2-丙醇(7f)为催化剂,20mol%β-环糊精为助催化剂,叔丁基过氧化氢为氧化剂,正己烷为溶剂,反应对映选择性最高可达57%,收率92%.不对称α-羟基化产物(S)-5-氯-2-羟基-1-茚酮-2-甲酸甲酯(2a)在乙酸乙酯中一次重结晶后,对映体光学纯度可达99%,收率68%.
A commercially available chiral drug with a basic nitrogen atom is an organic catalyst used to catalyze the asymmetric α-hydroxylation of β-ketoacid esters. It was found that using timolol or propranolol as a catalyst, the reaction The enantioselectivities were up to 32% and 18% respectively.Thylogolol and propranolol were structurally modified and 12 aldol analogues were synthesized, and their catalytic effects were investigated. It was found that under optimized reaction conditions , 30 mol% (R) -1-tert-butylamino-3- (2-naphthyloxy) -2-propanol (7f) was used as a catalyst, 20 mol% β-cyclodextrin was used as a cocatalyst, Hydrogen as oxidant and n-hexane as solvent, the enantioselectivity of the reaction was up to 57% and the yield was 92% .Asymmetric α-hydroxylation product (S) -5-chloro-2-hydroxyindanone-2 After the methyl formate (2a) was recrystallized from ethyl acetate, the enantiomeric purity was 99% and the yield was 68%.