Study Based On Asymmetric Co-catalysis Multi-component Ylide Trapping Reactions For Effective Construction Of Poly-functional Compounds

Asymmetric Multi-component Reactions (AMCRs) is a novel methodology for efficient synthesis of chiral poly-functional compound from simple materials (three or more substrates) in one-pot. The selectivity of the multi-component reactions can efficiently achieved by the co-catalytic strategy, which is using two or more catalysts which parallel act on the corresponding substrate or catalytic cycle, thereby achieving an ordered assembly of various substrates in the reaction system and smoothly delivered the designed product. Thus, these reactions possess the advantages of high efficiency, economy, green, and offer an efficient and convenient entry to construct diversity molecules. The research and application of this field also demonstrates the value of academic and economic.In this dissertation, we designed and implemented two types of ylide trapping multi-component reactions based on the asymmetric co-catalytic strategy, One was based on the asymmetric co-catalytic multi-component reactions of oxonium ylides with imines to construct chiral (syn-)α-hydroxy-β-amino ester derivatives; the other was based on the co-catalytic 3+2 cycloaddition reactions of carbonyl ylides with imines to build multi-substituted oxazolidine derivatives with diverse configurations. In addition, the author also found a one-pot tandem reaction of allyl alcohol derivatives and diazo compounds for selective construction of poly-substituted tetrahydrofuran derivatives.Chapter 1 is the short review of relevant literatures, including co-catalysis; diazo compound, carbene and yilde chemistry; ylide involved multi-component reactions, etc. At the end of this chapter is a brief introduction of design strategies and content of this dissertation.In chapter 2, for the first time we achieved the enantioselective three-component reaction of a-aryl diazo acetate, alcohol, and imine, which was asymmetric co-catalyzed by combination of chiral organic molecule and non-chiral rhodium acetate. The research showed that BINOL-derived chiral phosphonic acid catalyst can effectively activate the substrate imine, and introduce of chirality at the same time. The activated imine will efficiently capture the active oxonium ylide intermediate which is in situ generated from an alcohol and a metal carbenoid. The corresponding (syn-)α-hydroxy-β-amino ester derivatives were successfully synthesized in a highly selective pattern, and the enantioselectivity up to 99%.The research of chapter 3 was based on the previously asymmetric co-catalyzed three-component reaction. We designed an asymmetric co-catalyzed four-compound reaction by in situ generate imine substrate from corresponding aldehyde and amine. Based on principle that the amine and aldehyde will quickly generate imine in acidic anhydrous conditions, our study of four-compound reaction could be smoothly achieved by optimization the reaction conditions and suppress of possible side reactions. Via this methodology, lots of chiral (syn-)α-hydroxy-β-amino ester derivatives with diverse structures could be conveniently synthesized from simple materials.In chapter 4, for the first time, we achieved the asymmetric co-catalyzed multi-component reactions by introducing the single acceptor substituted diazo compounds as substrates. With the optimized reaction conditions, the generality of the substrates was well demonstrated:including extended diazo compounds to 1-aryl-2-diazo ketone derivatives, and imines derived from aromatic aldehydes extended to alkyl aldehydes, etc., which provided a very effective methodology for construction of chiral (syn-)α-hydroxy-β-amino ester derivatives with diverse structure.Chapter 5 was based on the 3+2 cycloaddition reaction of carbonyl ylide with imine. For the first time, we successfully introduced lewis acid or br(?)nsted acid as co-catalyst and achieved the diastereoselectivity control of the 3+2 cycloaddition of carbonyl ylide (in situ generated from metal carbenoid and aldehyde) and imine. This study is the first successful example of co-catalyzed 3+2 cycloaddition of the intermolecular carbonyl ylide and imine. In these co-catalysis conditions, the addition pattern of the addition intermediate will be adjustable by changing the property of the co-catalyst, and provided multi-substituted oxazolidine derivatives with different configurations:Oxazolidine derivatives generated fromα-aryl diazo acetate provided two (cis-and trans-) diastereoisomers with different co-catalyst, and by a simple hydrolysis manipulation (syn-and anti-)α-hydroxy-β-amino ester derivatives were obtained respectively; Oxazolidine derivatives generated from diazo acetate could provided steric hindrance (cis-) product. This result was a successful complementary of the above three-or four-components ylide trapping research, which yield the product with set (syn-) configuration.In chapter 6, we have designed an efficient pattern of one-pot tandem reaction for poly-substituted tetrahydrofuran derivatives from allyl alcohol derivatives and diazo compounds. This was the first highest diastereoselectivity OH insertion reaction (dr> 99:1). This insertion product was followed by an intramolecular Michael reaction to provide a tetrahydrofuran derivative. This reaction was a highly selective methodology, which was an effective way to obtain poly-substituted tetrahydrofuran derivatives with fully trans-aryl-substituted structure.