One-Pot Transition-Metal-Free Alkyne Synthesis and Palladium-Catalyzed Synthesis of Alpha-Arylated Ketones Yu Wu

Format:

Book

Thesis/Dissertation

Author/Creator:

Wu, Yu, author.

Contributor:

University of Pennsylvania. Chemistry., degree granting institution.

Language:

English

Subjects (All):

0485.

0490.

Local Subjects:

0485.

0490.

Physical Description:

1 electronic resource (463 pages)

Contained In:

Dissertations Abstracts International 87-07B

Place of Publication:

Ann Arbor : ProQuest Dissertations and Theses, 2025

Language Note:

English

Summary:

Alkynes are key motifs in chemistry, serving as precursors in many organic reactions toward the synthesis of bioactive compounds, polymers, and new materials. Methods to synthesize terminal alkynes with an extension of the carbon skeleton involve harsh and/or dangerous reagents. Further derivatization of terminal alkynes to other types of alkynes largely rely on the popular Sonogashira coupling. This thesis reports a one-pot approach to alkynes under transition-metal-free conditions from feedstock chemicals. The disclosed methods are expected to be complementary to the state-of-the-art by streamlining the synthesis of alkynes, reducing the costs of production of these valuable building blocks, and increasing the sustainability of the synthesis of alkynes. In Chapter 1, a one-pot transition-metal-free method to make diaryl alkynes is reported. A simple, convenient, and economical pathway employs petroleum feedstocks toluenes and methyl benzoates under basic conditions to form C-C bonds and generate enolate intermediates. Trapping with either TBS-Cl or Nf-F is followed by elimination to furnish alkynes. Initial results indicate that this method can be extended to the one-pot synthesis of enynes. In Chapter 2, a one-pot method to make alkynyl amides is reported. This method provides an access to a broad range of alkynyl amides, including alkyl alkynyl amides, with the chirality in functional groups preserved. This tandem reaction involves reversible deprotonation of weakly acidic acetamides and their reactions with methyl benzoates or aliphatic esters to form C−C bonds and generate enolate intermediates. Trapping of the enolate intermediates with chlorophosphate is followed by elimination to furnish alkynyl amides. The method is also successful with thioamides to produce thioamide alkynes and has been applied to the one-pot synthesis of benzo[b]thiophenes with C−C and C−S bond-formation. In Chapter 3, a one-pot method for the synthesis of terminal alkynes and TMS-alkynes through a one-carbon homologation of pronucleophiles with DMF promoted by LiN(SiMe3)2/Cs+ is reported. This method utilizes readily available feedstock chemicals to assemble all three bonds of the alkyne in one vessel without transition-metal catalysts. The selectivity between terminal alkyne and TMS-alkyne was tuned by choice of activating reagent and base. Additionally, the method is successful in TMS-propiolamide syntheses. The synthesis of α-arylated ketones has been extensively studied, because of the importance of α-arylated carbonyl moieties in many organic compounds which possess interesting pharmaceutical and biological properties. In Chapter 4, a new and efficient process that allows highly selective one-pot palladium-catalyzed α-arylation from methyl benzoates, methyl pyridines and aryl bromides. This method enable the direct construction of α-arylated ketones from simple, readily available starting materials in a one-pot process, while minimizing the use of toxic reagents and improving compatibility with industrial conditions

Notes:

Advisors: Walsh, Patrick Committee members: Zahrt, Andrew; Trauner, Dirk; Chenoweth, David

Source: Dissertations Abstracts International, Volume: 87-07, Section: B.

Ph.D. University of Pennsylvania 2025

Vendor supplied data

Local Notes:

School code: 0175

ISBN:

9798276007397

Access Restriction:

Restricted for use by site license