Transition metal-facilitated C-C and C-F bond forming

Chapter 1. Copper-Catalyzed Asymmetric Addition of Olefin-Derived Nucleophiles to Ketones A copper (I) catalyzed coupling olefins and ketones has been developed for the diastereo- and enantioselective generation of homopropargyl alcohols bearing vicinal stereocenters. This method allows for the generation of enantioenriched tertiary alcohols with a high degree of functional group compatibility. The utility of the process is further illustrated by a large scale synthesis with extremely low catalyst loading as well as the late stage modification of several pharmaceuticals. Chapter 2. Copper-Catalyzed Enantioselective Addition of Styrene-Derived Nucleophiles to Imines We describe the catalytic generation of amines bearing vicinal stereocenters with a moderate degree of diastereoselectivity. The stereoselective hydrocupration of an unactivated olefinic component is followed by nucleophilic addition of the organocuprate to an N-phosphinoyl protected imine. The mild and general process tolerates a broad-range of functionality, and the process was shown to be successful at a gram-scale synthesis. Chapter 3. Palladium-facilitated Regioselective Nucleophilic Fluorination of Aryl and Heteroaryl Halides. The preliminary findings regarding an aryl and heteroaryl halide fluorination process facilitated by palladium as a reagent is described. Stoichiometric studies illustrate the utility of the method in producing aryl fluorides with unprecedented regioselectivity, and preliminary studies into the fluorination of five- and six-membered heteroaryl bromides are described. Halogen atom substitution as a route to irreversible oxidative addition of aryl and heteroaryl halides is discussed. This strategy may serve to facilitate the fluorination of particularly problematic heteroaryl bromide and chloride substrates.

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Chemistry.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2017

Author dc:creator

• Perry, Ian B. (Ian Brooks)

Advisor dc:contributor.advisor

• Stephen L. Buchwald.

• Chemistry.

Statement dc:rights

• MIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written 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/1721.1/112449

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/112449