N-heterocyclic carbene-catalyzed reactions / Pei-Chen Chiang.

Format:

Book

Manuscript

Thesis/Dissertation

Author/Creator:

Chiang, Pei-Chen.

Contributor:

Bode, J. W. (Jeffrey W.), advisor.

University of Pennsylvania.

Language:

English

Subjects (All):

Penn dissertations--Chemistry.

Chemistry--Penn dissertations.

Local Subjects:

Penn dissertations--Chemistry.

Chemistry--Penn dissertations.

Physical Description:

xxxi, 460 pages : illustrations ; 29 cm

Production:

2011.

Summary:

The discovery of new carbon--carbon bond-forming reactions is still a formidable challenge in the continuing development of efficient, sustainable chemical processes. In this regard, N-heterocyclic carbenes (NHCs) have become useful organocatalysts in asymmetric reactions as they can open new modes of reactivity, especially for substrates such as aldehydes, enals, and their surrogates. This thesis describes the use NHCs in the development of a novel cyclopentene annulation strategy, the use of alpha'-hydroxyenones as surrogates for enals, and an investigation of NHC-catalyzed oxidation of aldehydes.

Chiral NHCs are shown to promote cyclopentene-forming annulations between enals and 4-oxoenoates with excellent levels of enantioinduction and preference for the cis-1,3,4-trisubsitituted cyclopentene diastereomer. Mechanistic and stereochemical investigations support a tandem sequence of intramolecular cross-benzoin reaction followed by an NHC-catalyzed oxy-Cope rearrangement.

The facile preparation of a diverse array of annulation products utilizing NHCs is contingent on the difficult preparation of enal starting materials. It has been successfully demonstrated that alpha'-hydroxyenones, which can be prepared in a single convenient step from aromatic and heteroaromatic aldehydes, could serve as effective surrogates for enals in the annulation reactions. As a further extension, alpha'-hydroxyenones could be converted to saturated amides through NHC-catalyzed internal redox reactions. This was proposed to occur by beta-protonation of the Breslow intermediate, followed by nucleophilic attack of an amine to the resulting activated acyl azolium.

The apparent NHC-catalyzed oxidation of aldehydes under CO2 atmosphere actually involved exogenous O2 as the stoichiometric oxidant. The effect of CO2 appeared to lie in a diminution of the side products formed by aldehyde dimerization or oligomerization under the reaction conditions.

Notes:

Adviser: Jeffrey W. Bode.

Thesis (Ph.D. in Chemistry) -- University of Pennsylvania, 2011.

Includes bibliographical references.