INVESTIGATIONS IN IRON, COPPER, AND PALLADIUM –CATALYZED C-H BOND FUNCTIONALIZATION

Transition metal-catalyzed functionalization of C-H bonds has been used as a powerful tool for the construction of C-C and C-heteroatom bonds. Within this dissertation, methods that allow functionalization of C-H bonds via iron and copper catalysis have been developed. Additionally, functionalization of sp3 C-H bonds in amino acid derivatives using auxiliary-assisted palladium-catalyzed methodology is also demonstrated. A method for iron-catalyzed alkylation of arenes and heterocycles containing acidic C-H bonds has been developed. Various heterocycles such as pyridine, furan, thiophene and electron deficient arenes can be coupled with both alkyl bromides and iodides. Magnesium amide base is required for the reaction. Similarly, the deprotonative dimerization of arenes and heterocycles can be effected in the presence of an iron catalyst. Thus, the method allows direct functionalization of arenes and heterocycles. Additionally, the use of an iron catalyst is an advantage compared with existing methods. Methods for copper-catalyzed direct sulfenylation and amination of sp2 C-H bonds have been developed. Using 8-aminoquinoline auxiliary and copper catalyst, ortho C-H bonds of benzoic acid amides can be sulfenylated by disulfides. The method provides an alternative, milder way for the preparation of aryl trifluoromethylsulfides. Furthermore, ortho C-H bonds of benzoic acid amides can be aminated by reaction with simple amines using 8-aminoquinoline directing group and a copper catalyst. Sulfenylation and amination of -C-H bonds of benzyl amine derivatives using picolinic acid auxiliary were also demonstrated. Broad substrate scope, high regioselectivity, and good functional group tolerance were observed. The use of a copper catalyst and a removable directing group are significant improvements compared with the existing methods. Finally, a novel way for synthesis of non-natural amino acids via auxiliary-assisted, palladium-catalyzed C-H functionalization methodology was developed. Under palladium catalysis, 2-methyl thioaniline auxiliary allows the monoarylation of -C-H bonds of alanine derivatives generating, after directing group removal, substituted phenylalanines. In contrast, using 8-aminoquinoline auxiliary, methylene groups in phenylalanine, leucine, and lysine derivatives can be arylated. Methods for alkylation and acetoxylation were also reported. The directing group can be removed without significant erosion of enantiomeric excess. The method provides a straight-forward way to synthesize non-natural amino acids from the chiral pool.

Name thesis:degree_name

Doctor of Philosophy

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Chemistry

Grantor

University of Houston

Year dc:date.issued

2013

Author dc:creator

• Tran, Ly 1985-

Advisor dc:contributor.advisor

• Daugulis, Olafs

Committee members dc:contributor.committeemember

• Ball, Zachary T.
• Guloy, Arnold M.
• May, Jeremy A.
• Thummel, Randolph P.

• C-H bond functionalization

Statement dc:rights

• The author of this work is the copyright owner. UH Libraries and the Texas Digital Library have their permission to store and provide access to this work. Further transmission, reproduction, or presentation of this work is prohibited except with permission of the author(s).

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/10657/925

OAI identifier oai:identifier

oai:uh-ir.tdl.org:10657/925