Application of a palladium/tri-tert-butylphosphine catalyst system towards mild and general methods for carbon-carbon bond formation

Our research over the last four years has been focused on the development of mild and general methods for conducting palladium-catalyzed carbon-carbon bond forming reactions utilizing the bulky and electron-rich trialkylphosphine, tri-tert-butylphosphine (P(t-Bu)3). We have concentrated on the utilization of aryl chlorides as substrates due to their lower cost and greater availability compared to traditionally employed aryl bromides, iodides, and triflates. The Suzuki reaction was the first reaction that we investigated, and we were able to develop a first-generation protocol for coupling aryl chlorides with aryl-boronic acids utilizing Pd2(dba)3/P(t-Bu)3 as catalyst and Cs2CO3 as base. A second-generation protocol utilizing KF as base offered significant improvements and provided an opportunity to expand the scope of the reaction. Electron-deficient aryl chlorides underwent Suzuki reaction at room temperature. Hindered substrates and unactivated vinyl chlorides could be coupled efficiently, and turnover numbers as high as 9,700 could be achieved. In addition, we discovered a highly unusual selective coupling of an aryl chloride in preference to an aryl triflate. The next reaction that we examined was the Heck reaction, and we were able to develop a method for coupling aryl chlorides with olefins using Pd/P(t-Bu)3 as catalyst and Cs2CO3 as base. A significant improvement in terms of scope and mildness of conditions was realized with the replacement of Cs2CO3 with Cy2NMe, which allowed for the coupling of sterically and electronically diverse aryl bromides at room temperature, as well as the first room-temperature Heck couplings of aryl chlorides.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Chemistry.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2002

Author dc:creator

• Littke, Adam F. (Adam Francis), 1974-

Advisor dc:contributor.advisor

• Gregory C. Fu.

• 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/1721.1/8049

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/8049