Research On Asymmetric α-hydroxylation Of β-Keto Esters Catalyzed By Chiral Naphthalenyloxy Aminopropanols

The asymmetric hydroxylation product of β-dicarbonyl compounds was an important structural unit, which widely presented in natural products, medicines, agricultural chemicals, fine chemicals and synthetic intermediates. The methods to prepare such compounds were asymmetric organometallic catalysis and asymmetric organocatalysis. The research on asymmetric hydroxylation ofβ-dicarbonyl compounds by organometallic catalysts was adequate and systematic. However, there were few reports on organocatalysis. An efficient, safe, inexpensive system was waiting to be discovered in the field of organocatalysis.Chiralβ-amino alcohols were used as catalysts for many types reactions, such as:Aldol reaction, Michael addition reaction, epoxidation reaction, etc. Based on out previous work, in this paper, we developed and screened a series of novel napthalenyloxy aminopropanol catalysts through the model reaction of a-hydroxylation of methyl5-chloro-1-indone carboxylate. Naphthol derivatives were synthesized form naphthalene-2,7-diol. Chiral naphthalenyloxy aminopropanols A1-A8were synthesized from naphthol derivatives. Structures of these compounds were checked through IR, NMR spectrum and HR-MS. Compound A8-c was checked through X-Ray Diffraction.Through the screening of the moded reaction, we found A5was the best catalyst. Under the optimal condition, the corresponding product2a was obtained in good yield of99%and63%ee. The scope of the reaction was demonstrated for15substrates and the transition state of a-hydroxylation of la was proposed.