Asymmetric Allylic Alkylation Of 3-cyano Phthalides And Synthetic Application

Phthalides are frequently found in naturally occurring substances which exhibit a broad spectrum of biological activities and also act as useful building blocks in organic synthesis. 3-Cyano phthalides are excellent nucleophilic reagents which can be used for the construction of highly functional phthalides compounds. Nevertheless,these compounds have seldom been employed in an asymmetric organocatalytic transformation to construct enantiomerically pure chiral frameworks. Efficient strategy to form carbon-carbon bond has always been a central theme in the field of organic synthesis, especially for the construction of the chiral frameworks bearing adjacent stereocenters. In this thesis, we studied Lewis base-catalyzed asymmetric allylic alkylation reaction between 3-cyano phthalides and Morita-Baylis-Hillman adducts, and also investigated the synthetic application of the resultant chiral compounds on asymmetric sulfa-Michael triggered cascade reaction. The main content is as follows:1. Asymmetric synthesis of 3,3-disubstituted phthalides bearing contiguous quaternary and tertiary stereocenters can be achieved with excellent yields and stereoselectivities via bifunctional chiral phosphines catalyzed allylic alkylation reaction between 3-cyano phthalides and traditional Morita-Baylis-Hillman adducts under neutral and mild conditions.2. Asymmetric synthesis of 3,3-disubstituted oxindoles bearing contiguous all-carbon-substituted quaternary stereocenters can be successfully accomplished with good yields and stereoselectivities via the quinine catalyzed-allylic alkylation reaction between 3-cyano phthalides and isatin Morita-Baylis-Hillman.3. On the basis of these, a novel asymmetric sulfa-Michael triggered cascade reaction has been developed, which provided enantioenriched functionalized dihydroquinones incorporating adjacent quaternary and tertiary stereocenters in good yields and high stereoselectivities. The broad scope and versatility of the process were demonstrated.