Date of Award

5-31-2016

Document Type

Campus Access Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry/Organic Chemistry

First Advisor

Wei Zhang

Second Advisor

Béla Török

Third Advisor

Jason Evans

Abstract

Michael addition-initiated cascade asymmetric synthesis is powerful for the construction of molecules bearing multiple stereocenters. Organofluorine molecules play an important role in medicinal chemistry and agricultural chemistry. Presented in this thesis is my effort on the development of Michael addition-based cascade reaction sequences for the synthesis of fluorinated and other asymmetric molecules with biological interest. Organocatalysts, especially recyclable fluorous catalysts such as cinchona alkaloid/thiourea have been used for the reactions. This thesis covers following projects: 1) Michael addition reaction of α-fluoro-β-ketoesters with maleimides to afford two adjacent stereocenters including a fluorinated chiral tertiary carbon; 2) One-pot Michael addition-based cascade reactions including double cascade Michael/aldol reactions for monofluoro- and difluorocyclohexanones; 3) One-pot triple cascade Michael/aza-Henry/lactamization sequence for fluorinated 2-piperidinones bearing four stereocentres; 4) One-pot quadruple cascade fluorination/Michael/Michael/aldol sequence for fluorinated cyclohexanes bearing six stereocentres; and 5) One-pot Michael/Mannich/cyclization reactions for asymmetric synthesis of 5- and 6-membered spirooxindoles bearing up to four stereocenters. Most of above mentioned projects are conducted as one-pot synthesis and using recyclable organocatalysts to afford compounds in good to excellent yields and stereoselectivties. They have green synthetic advantages of pot, atom and step economy (PSAE), minimal intermediate separation, toxic transition metal-free catalysis; and catalyst recovery.

Comments

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