Carbon-trifluoromethyl bond forming reactions and palladium-catalyzed cyanation of (hetero)aryl halides

Chapter 1 Nucleophilic trifluoromethyl sources were systematically examined in stoichiometric palladium experiments to determine the most efficient class of reagents for transmetallation. In conjunction with reductive elimination studies, this led to the development of the first system for the trifluoromethylation of aryl chlorides. Chapter 2 A method for the oxidative trifluoromethylation of (hetero)aryl boronic acids is reported. Bench top setup and visual reaction monitoring makes this process particularly well suited to medicinal and academic chemists. Fast reaction times allow for the trifluoromethylation of heterocyclic boronic acids that are prone to facile protodeboronation. Chapter 3 A trifluoromethylation of potassium vinyl trifluoroborates via iron catalysis has been developed. Excellent E:Z ratios are observed for styryl trifluoroborates. Initial investigations suggest a mechanistic pathway that diverges from our previous (hetero)aryl trifluoromethylation systems. Chapter 4 A highly efficient system for the palladium-catalyzed cyanation of (hetero)aryl halides is disclosed. By employing palladacycle precatalysts, cyanide binding during catalyst formation is minimized, allowing for low catalyst loadings even with unactivated aryl chlorides. The method utilizes a non-toxic cyanide source and exhibits excellent functional group tolerance, particularly of free N-H groups and typically challenging five membered heterocycles.

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Chemistry.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2013

Author dc:creator

• Senecal, Todd D. (Todd Dale)

Advisor dc:contributor.advisor

• Stephen L. Buchwald.

• Chemistry.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/82321

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/82321