Organic Phosphoric Acid-catalyzed Synthesis Of Chiral Heterocyclic Compounds

The synthesis of chiral heterocyclic compounds has become a popular field in organic synthesis.In recent years,there have been great progresses in asymmetric synthesis of organic compounds using organic small molecules such as alkaloid derivatives,amino acid derivatives and chiral phosphoric acids as the catalysts.As the bifunctional catalysts,chiral phosphoric acids activate the substrates through the hydrogen-type bonding with the Br?nsted acid site（P-OH）,the interaction of the Lewis base site（P=O）and the well-defined,tunable chiral binding pocket formed by the aryl side chains in the 3,3’-positions of chiral phosphoric acids to perform the asymmetric reactions of substrates.In this dissertation,the asymmetric synthesis of naphtho[2,1-b]furan and benzimidazole derivatives was investigated,and some results were obtained as follows:A new method has been developed for two kinds of naphtho[2,1-b]furan derivatives via coupling of N-Boc propargyldiamines withβ-naphthols leading to N-Boc propargylamines and subsequent intramolecular cycloaddition giving the target products mediated by 2,6-lutidine/Ag OAc and 1,8-diazabicyclo[5.4.0]undec-7-ene（DBU）,respectively.The first step of the protocol provides N-Boc propargylamines with high yields in the presence of chiral phosphoric acids.Next,The N-Boc propargylamines were treated with 20 mol%2,6-lutidine and 10 mol%Ag OAc at 30 ^oC for 20 min affording chiral naphtho[2,1-b]furan derivatives in high yields.Meanwhile,naphtho[2,1-b]furan derivatives were provided in high yields under the treatment of 1.2eq of DBU at 70 ^oC for 2 h.The establishment of this method enriches the species of chiral naphthalene furans and provides a basis for further research on the biological activity of naphthalene furanA novel method for the atroposelective synthesis of axially chiral N-aryl benzimidazoles has been developed via chiral phosphoric acid-catalyzed reactions of multi-carbonyl compounds with o-phenylenediamines.The protocol uses multi-carbonyl compounds and o-phenylenediamines as the substrates,CPA as the catalysts,3?molecular sieve as the additive,and the reaction was performed in toluene at 60 ^oC for20 h providing axially chiral N-aryl benzimidazoles in high yields with excellent enantioselectivity.For uncyclic multi-carbonyl compounds,the cleavage of C-C bonds led to the formation of the target products with of one fragment leaving.For cyclic multi-carbonyl compounds,the reaction underwent a ring opening process for the synthesis of the target compound.This method gives the cyclized products efficiently and quickly with the cleavage of C（C=O）-C（sp³）bond in multi-carbonyl compounds,which not only expands the diversity of axial chiral benzimidazole,but also provides a research basis for further exploring the biomedical activity of axial chiral benzimidazole compounds.A new method for synthesis of axially chiral benzimidazoles has been developed via chiral phosphoric acid/Ag₂CO₃-co-catalyzed reactions of o-phenylenediamines with acetylenic ketones.The protocol uses o-phenylenediamines and acetylenic ketones as the substrates,CPA and Ag₂CO₃ as the co-catalysts,and the reaction was carried out in methyl tert-butyl ether（MTBE）at 50 ^oC for 6 h providing axially chiral N-aryl benzimidazoles in high yields with excellent enantioselectivity.Additionlly,we found that the yields and enantioselectivity decreased with elongation of alkyl chains.A possible reason is that it is disadvantageous to enter the chiral pocket of CPA for the alkyl chains with bigger steric hindrance.The present method provides another new pathway to the axial chiral benzimidazole skeleton and complements the diversity of the axial chiral benzimidazole,in which the transformation involves in the C（C=O）-C（sp）bond cleavage of the acetylenic ketones.