2026-09-19T17:50:51Zhttps://dspace.mit.edu/server/oai/requestoai:dspace.mit.edu:1721.1/1050482026-06-16T18:16:28Zcom_1721.1_7582com_1721.1_7581col_1721.1_131022
Stephen L. Buchwald.
Ruiz-Castillo, Paula
Massachusetts Institute of Technology. Department of Chemistry.
Massachusetts Institute of Technology. Department of Chemistry
2016-10-25T19:51:19Z
2016-10-25T19:51:19Z
2016
2016
http://hdl.handle.net/1721.1/105048
959712444
Thesis: Ph. D. in Organic Chemistry, Massachusetts Institute of Technology, Department of Chemistry, 2016.
Cataloged from PDF version of thesis.
Includes bibliographical references (pages 375-410).
Chapter 1: This chapter describes a general method for the of the Pd-catalyzed N-arylation of hindered [alpha],[alpha],[alpha]-trisubstituted primary amines. The reaction utilized catalysts based on two biaryl phosphine ligands, which were developed via kinetics-based mechanistic analysis and rational design. These studies led to the first example of catalyst based on a hybrid (alkyl)aryl biaryl phosphine ligand that provides better results that its dialkyl- or diarylbiaryl analogues. The C-N coupling was efficient for a wide range of (hetero)aryl chlorides and bromides under mild conditions. Chapter 2: This chapter relates the development of the Pd-catalyzed C-O coupling of primary alkyl alcohols. The reaction of primary aliphatic alcohols bearing [beta]-hydrogen atoms can lead to undesired [beta]-hydride elimination pathways instead of the target reductive elimination from the [LPd(Ar)OAlk] intermediate, especially when using electron-rich aryl halides. Additionally, aryl chlorides have been shown to be more challenging coupling partners than the corresponding aryl bromides. The use of catalysts based on commercially available ligand t-BuBrettPhos and a novel hybrid ligand, AdCyBrettPhos, have allowed the C-O coupling reaction to proceed effectively at room temperature, minimizing the side reaction. A variety of functionalized primary alcohols have been successfully coupled with (hetero)aryl bromides and chlorides giving rise to medicinally interesting products. Chapter 3: This chapter is a compilation of the applications of Pd-catalyzed C-N coupling in various fields of chemical research since 2008. This work includes the reactions of nine classes of nitrogen-based coupling partners in the 1) synthesis of heterocycles, 2) medicinal chemistry, 3) process chemistry, 4) synthesis of natural products, 5) organic materials and chemical biology, and 6) synthesis of ligands. The large number of applications highlights the versatility and utility of this transformation both in academic and industrial settings.
by Paula Ruiz-Castillo.
Ph.D. in Organic Chemistry
410 pages
eng
Massachusetts Institute of Technology
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.
http://dspace.mit.edu/handle/1721.1/7582
Chemistry.
Palladium-catalyzed C-N and C-O cross-coupling reactions
Thesis
application/pdf
Publication
unknown
unknown
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<Abstract>Chapter 1: This chapter describes a general method for the of the Pd-catalyzed N-arylation of hindered [alpha],[alpha],[alpha]-trisubstituted primary amines. The reaction utilized catalysts based on two biaryl phosphine ligands, which were developed via kinetics-based mechanistic analysis and rational design. These studies led to the first example of catalyst based on a hybrid (alkyl)aryl biaryl phosphine ligand that provides better results that its dialkyl- or diarylbiaryl analogues. The C-N coupling was efficient for a wide range of (hetero)aryl chlorides and bromides under mild conditions. Chapter 2: This chapter relates the development of the Pd-catalyzed C-O coupling of primary alkyl alcohols. The reaction of primary aliphatic alcohols bearing [beta]-hydrogen atoms can lead to undesired [beta]-hydride elimination pathways instead of the target reductive elimination from the [LPd(Ar)OAlk] intermediate, especially when using electron-rich aryl halides. Additionally, aryl chlorides have been shown to be more challenging coupling partners than the corresponding aryl bromides. The use of catalysts based on commercially available ligand t-BuBrettPhos and a novel hybrid ligand, AdCyBrettPhos, have allowed the C-O coupling reaction to proceed effectively at room temperature, minimizing the side reaction. A variety of functionalized primary alcohols have been successfully coupled with (hetero)aryl bromides and chlorides giving rise to medicinally interesting products. Chapter 3: This chapter is a compilation of the applications of Pd-catalyzed C-N coupling in various fields of chemical research since 2008. This work includes the reactions of nine classes of nitrogen-based coupling partners in the 1) synthesis of heterocycles, 2) medicinal chemistry, 3) process chemistry, 4) synthesis of natural products, 5) organic materials and chemical biology, and 6) synthesis of ligands. The large number of applications highlights the versatility and utility of this transformation both in academic and industrial settings.</Abstract>
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