The Development Of New Methods For The Synthesis Of Quaternary Oxindoles Featuring A C3All-carbon Or N-containing Carbon Center

This thesis focuses on the efficient construction of quaternary oxindoles featuring a C3all-carbon or èV-containing carbon center, which includes the development of a new strategy for the enantioselective synthesis of all-carbon quaternary oxindoles via the catalytic desymmetrization of oxindole based1,6-heptadiynes; the improvement in the catalytic asymmetric direct amination reaction of3-substituted oxindoles, allowing unprotected3-aryl,3-alkyl and3-heteroatom substituted oxindoles to readily react with di-terf-butyl azodicarboxylate (DBAD), which greatly facilitates product elaboration; the diverse synthesis of quaternary oxindoles via acid catalyzed Friedel-Crafts and Ritter reaction of3-substituted3-hydroxyoxindoles. It is divided into the following three parts.1) The first highly enantioselective Cu(I)-catalyzed alkyne-azide cycloaddition (CuAAc) reaction via asymmetric desymmetrization of oxindole based1,6-heptadiynes is developed, which is also the first highly enantioselective catalytic asymmetric intermolecular desymmetrization of prochiral1,6-dialkynes. Using2,5-hexadione as solvent, a chiral Cu(I) complex derived from Pybox and CuCl allowed the synthesis of quaternary oxindoles bearing both an alkyne and a1,2,3-triazole moiety at the C3position with up to82%yield and98%ee. The thus obtained quaternary oxindoles can be readily elaborated via transformations based on the alkyne group. Based on the NMR studies and negative non-linear effect, a stereochemical model is proposed containing a dinuclear copper intermediate as the catalytically active species.2) The first example of highly enantioselective direct amination of both unprotected3-aryl and3-alkyloxindoles with DBAD is developed. It is found that the reaction can be efficiently catalyzed by chiral bifunctional tertiary amine-thiourea catalyst with up to98%ee achieved using1,2-dichloroethane (DCE) as solvent and5A MS as additive. The amination adducts can be easily further elaborated.The highly enantioselective direct amination of3-heteractom substituted oxindoles is also developed for the first time furnishing the3,3-disubstituted oxindoles featuring both sulfur (or oxygen) and nitrogen atoms at C3position. The3-thiooxindoles or3-alkoxyoxindoles can react with DBAD efficiently with moderate to excellent yields and ee values in the presence of β-ICD or (DHQD)2PYR as the catalyst, respectively. The thus obtained amination adducts can be readily transformed to a novel spirocyclic oxindole without the loss of enantioselectivity.3) The highly efficient Friedel-Crafts reaction of3-aliphatic or aromatic-substituted3-hydroxyoxindoles with a variety of (hetero)aromatic compound, such as phenol,1,3-dimethoxybenzen, indole, furan, thiophene and pyrrole, is developed using only5mol%of Hg(ClO4)2·3H2O as catalyst to synthesis a series of unsymmetrical3,3-diaryloxindoles and3-alkyl-3-aryloxindoles. Mechanism research reveals that the high catalytic property of Hg(ClO4)2·3H2O is originated from the unprecedented dual activation effects of aromatic mercuration, which can generate a strong protic acid to facilitate the generation of carbocation at the C3position of oxindoles and simultaneously form the more reactive nucleophilic reaction partner.The first Ritter reaction of3-substituted3-hydroxyoxindoles with nitriles, catalyzed by inexpensive and convenient HClO4, is also developed, which enables the synthesis of3-substituted3-aminooxindoles in25-95%yield with rich diversity.