Synthesis, study and application of silyl ketene imines in Lewis base catalyzed carbonyl addition

Wilson, Tyler

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https://hdl.handle.net/2142/29486 Copy

Description

Title

Synthesis, study and application of silyl ketene imines in Lewis base catalyzed carbonyl addition

Author(s)

Wilson, Tyler

Issue Date

2012-02-01T00:48:54Z

Director of Research (if dissertation) or Advisor (if thesis)

Denmark, Scott E.

Committee Member(s)

• Hergenrother, Paul J.
• Burke, Martin D.
• Rauchfuss, Thomas B.

Department of Study

Chemistry

Discipline

Chemistry

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• Silyl Ketene Imines
• Lewis Base Catalysis
• Enantioselective Synthesis

Abstract

The activation of Lewis acids by chiral Lewis bases has allowed for the development of a robust and highly selective catalyst system for the addition of silylated nucleophiles to carbonyl compounds. In general, aldolate-type products containing secondary and tertiary stereogenic centers are obtained in high yield and with excellent stereoselectivities. Despite the breadth of reactivity that has been observed for additions to aldehydes under this mode of catalysis certain structural motifs, such as quaternary carbons and tertiary alcohols have remained unsolved problems. This deficiency is further underscored by the dearth of general methods for the catalytic, asymmetric preparation of fully substituted stereogenic carbon centers. To address these challenges, and empower Lewis base catalysis for the asymmetric synthesis of tetrasubstituted carbons a range of disubstituted N-silyl ketene imines has been investigated as latent nucleophiles for additions to carbonyl compounds. In the presence of silicon tetrachloride and a catalytic amount of chiral bis-phosphoramide, N-silyl ketene imines underwent extremely rapid additions to aldehydes, providing aldol products containing quaternary stereogenic centers in excellent yields and stereoselectivities. Further extension of this chemistry to catalytic, enantioselective Michael-type reactions and vinylogous aldol additions has also been realized, by introduction of a double bond into the aldehyde acceptor or N-silyl ketene imine donor. The reactions of these unsaturated species occurred with excellent site selectivity and provide products with a 1,5-disposition of oxygen and nitrogen heteroatoms in moderate to excellent enantioselectivity. Finally, a new class of N-silyl oxyketene imines derived from protected cyanohydrins has been developed. These nucleophiles serve as acyl anion equivalents in Lewis base catalyzed aldol addition reactions and allow for the preparation of cross-benzoin and glycolate-aldol products in high yield and with exceptional diastereo- and enantioselectivities.

Graduation Semester

2011-12

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http://hdl.handle.net/2142/29486

Copyright and License Information

Copyright 2011 Tyler Wilson

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