Linear allylic C-H oxidation: methods and utility

Vermeulen, Nicolaas

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Description

Title

Linear allylic C-H oxidation: methods and utility

Author(s)

Vermeulen, Nicolaas

Issue Date

2012-02-01T00:45:07Z

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

White, Maria C.

Doctoral Committee Chair(s)

White, Maria C.

Committee Member(s)

• Hergenrother, Paul J.
• Moore, Jeffrey S.
• Nuzzo, Ralph G.

Department of Study

Chemistry

Discipline

Chemistry

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• C-H Oxidation
• Catalytic Palladium oxidation

Abstract

The installation of complex functional groups through the use of C-H oxidation methodologies has the potential to dramatically increase the efficiency of synthetic sequences with respect to resources, time and overall steps to key intermediates. This work describes methods that target complex intermediates to show the scope, wide functional group tolerance, and streamlining utility of our allylic C-H oxidation chemistry. In general, functional groups are installed in complex molecules through the advent of sequential C-C bond forming reactions. This chemistry is not only well known, but has been employed for decades, resulting in the wide array of reaction conditions and electrophile/nucleophile pairs seen in the literature today. In contrast, the deliberate installation of functional groups through unactivated C-H bonds represents a new strategy for the construction of complex intermediates. Previously, we have reported that the use -olefins, as an inert and readily available functional group handle, allows for the direct installation of allylic acetates via a Pd(II) catalysis. A clever implementation of this strategy shows its utility and ability to streamline the synthesis of known molecules (e.g. L-galatose). Further exploration of this reaction manifold gives rise to a linear allylic oxidation method requiring only coupling levels of almost any carboxylic acid to render linear (E)-allylic esters. A significant problem with the Pd(II) allylic C-H oxidation reaction is the need for super-stoichiometric amounts of the oxidant benzoquinone. By employing a Co(II)Salophen catalyst, hydroquinone (the byproduct of benzoquinone oxidation) can be converted to benzoquinone using only molecular oxygen as terminal oxidant. This second catalytic system was found to be compatible with our allylic C-H oxidation reaction conditions and allows for the use of only catalytic amounts of the palladium-specific oxidant, thereby greatly reducing reaction waste. This process appears to be a general solution and can also be employed with the intera- and inter-molecular allylic C-H amination reactions developed in our lab.

Graduation Semester

2011-12

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Copyright and License Information

Copyright 2011 Nicolaas Vermeulen

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