Studies Based On Multi-component Reactions And Cycloaddition Reactions With Diazo Compounds

Multicomponent reactions (MCRs) are considered a powerful and atom-efficient strategy to form multiple chemical bonds from three or more starting materials in one step. In the case of MCRs in which two or more stereogenic centers are produced, control of both diastereo-and enantioselectivity is of the utmost importance. With the co-catalytic strategy, adjust the reactivity of electrophile, the selectivity of the multi-component reactions was controlled efficiently and high enantioselectivity of the products achieved. Here, we discussed a new yilde trapped multi-component coupling reaction to produce the β-amino-α-hydroxyl acid and P-hydroxy-a-amino acid derivatives via the change of the starting materials. The efficient synthetic method was demonstrated in the synthesis of pharmaceutically interesting molecules and nature products. Additionally, we described a new ammounium ylide trapped multi-component oxidation reaction to synthesis the N-alkoxycarbonyl aryl a-imino esters. Finally, we described metal catalyzed cycloaddition reactions with enol diazocompound.Chapter1is an overview of relevant literatures, including:a) introduction of co-catalysis (dual-catalysis), b) introduction of the diazo compound, carbene and yilde chemistry, c) ylide trapped multi-component reactions. At the end of this chapter is the presentation about design strategies and a brief introduction of this dissertation.In chapter2, We discussed a new approach to synthesize optically active β-amino-a-hydroxyl acid derivatives via chiral Br(?)nsted acid-Rh2(OAc)4co-catalyzed three-component reactions of diazo acetates with alcohols and imines. A matched reaction system was identified to give the products in good yield (61%-73%yield) moderate diastereoselectivity (up to82:18dr) and good enantioselectivity (up to91%ee). The key to the success is to find a matched system among the components and the catalysts. The efficient synthetic method was demonstrated in the synthesis of a taxol side chain and (-)-epi-cytoxazone. This is the first time that the highly efficient ylide trapping process is applied for the synthesis of pharmaceutically interesting molecules.In chapter3, we described a highly enantioselective three-component reactions of diazo compounds with imines and water in the presence of Rh2(OAc)4and a chiral Br(?)nsted acid to produce the desired products in good yield (64%-86%) and excellent diastereoselectivity (up to98:2dr) and enantioselectivity (up to97%ee). The reaction represents one the few catalytic asymmetric procedures using water as a reactant and provides an efficient method for the synthesis of the β-amino-a-hydroxyl acid derivatives from three readily available starting materials under mild reaction conditions.In chapter4, we discussed an enantioselective four-component reaction of diazoacetophenone, water, amines and glyoxylatein the presence of Rh2(OAc)4and a chiral Br(?)nsted acid to produce the desired products β-hydroxy-a-amino acids in good yield (61%-88%) and high diastereoselectivity (up to89:11dr) and enantioselectivity (up to96%ee). Successful use of acceptor carbenoids derived from diazoacetophenones in the coupling reaction and the scope of the diazo coumpound was first expanded to alkyl diazo-ketones nicely.In chapter5, we described a new strategy for the synthesis of N-alkoxycarbonyl aryl a-imino esters in the presence of Rh2(OAc)4to produce the desired compounds in high yield (up to96%) under mild reaction conditions. The application of the N-alkoxycarbonyl aryl a-imino esters have been demonstrated in the enantioselective reduction and Friedel-Crafts reaction of indoles to afford corresponding chiral aryl glycines (up to98%yield,94%ee) and indole derivatives (99%yield,99%ee), respectively, in both high yield and excellent ee.In chapter6, a highly diastereoselective synthesis of bicyclic pyrazolidinone derivatives by rhodium(â…¡) acetate catalyzed [3+3]-annulation with enoldiazoacetates and azomethine imines has been achieved in high yield. Vinylogous reaction of the azomethine imine with the metal enol carbene initiates [3+3] cycloaddition whereas reaction at the carbene center effects N-N-cleavage of the azomethine imine. Transition-metal catalysts direct1,2-Câ†'C,-Oâ†'C籆, and-Nâ†'C migrations from β-methylene-β-silyloxy-β-amido-a-diazoacetates with high selectivity. The key to achieving this unique display of differential selectivities relies on steric and stereoelectronic control by their catalytically generated metal carbenes.In chapter7, Copper(II) hexafluoroantimonate catalyzes the formal [3+3] cycloaddition of Lewis acid activated nitrones and vinyl diazoacetates to produce3,6-dihydro-1,2-oxazines in yields of up to96%and diastereoselectivities greater than20:1. This process compliments the metal carbene pathway that is catalyzed by rhodium(II) species.