The development and synthetic applications of Ti- and Pd-catalyzed processes

Chapter 1. Ti-Catalyzed Asymmetric Reduction of Aromatic Heterocycles A method for the highly selective asymmetric reduction of quinoxalines and quinazolines was developed. This complements technologies developed by others for the asymmetric reduction of other aromatic heterocycles. This chemistry utilizes a Ti catalyst based on the C2-symmetricansa-metallocene scaffold. In these studies, we utilized a novel silane as a reducing reagent that showed superior properties in the reduction of difficult substrates. We then used this chemistry to prepare a variety of tetrahydroquinoxalines and tetrahydroquinazolines in up to >99% ee. Chapter 2. A Method for the Pd-Catalyzed y-Arylation of Ketones and its Application to a One-Pot Synthesis of Tricyclic Indolines The Pd-catalyzed ca-arylation of enolates is a rapidly growing area of chemistry due its usefulness in constructing key C-C bonds. After thorough optimization, we have identified a catalyst system for the regioselective y-arylation of ketone dienolates, allowing for a convenient preparation of quaternary y-aryl ca,-unsaturated ketones. A key finding was the influence of the supporting ligand on the observed regioselectivity. Bidentate ligands with a small bite angle such as dppe allow for exclusive arylation at the y-position. As a novel application of this chemistry, we also developed a one-pot domino reaction of 2-bromoanilines with P,y-unsaturated ketones for the preparation of indolines. Further, use of the chiral ligand DTBM-SegPhos allows for asymmetric induction with excellent levels of enantioselectivity.

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Chemistry

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2009

Author dc:creator

• Hyde, Alan M. (Alan Michael)

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/1721.1/49746

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/49746