Installing CSP3-Rich Motifs via Visible Light-Mediated Transformations / Weizhe Dong.

Format:

Book

Thesis/Dissertation

Author/Creator:

Dong, Weizhe, author.

Contributor:

University of Pennsylvania. Chemistry, degree granting institution.

Language:

English

Subjects (All):

Chemistry.

Organic chemistry.

Pharmacology.

Chemistry--Penn dissertations.

Penn dissertations--Chemistry.

Local Subjects:

Chemistry.

Organic chemistry.

Pharmacology.

Chemistry--Penn dissertations.

Penn dissertations--Chemistry.

Physical Description:

1 online resource (505 pages)

Distribution:

Ann Arbor : ProQuest Dissertations & Theses, 2023

Contained In:

Dissertations Abstracts International 84-12B.

Place of Publication:

[Philadelphia, Pennsylvania] : University of Pennsylvania, 2022.

Language Note:

English

Summary:

Studies have found that the three-dimensionality of a drug candidate has a positive correlation with success in clinical trials, which revitalizes general interest in installing CSP3-containing fragments. To satisfy the ever-increasing demand for complexity in drug discovery, visible-light mediated transformations have stood out to become a powerful tool for the installation of CSP3-containing fragments, or alkyl groups, with intricate functional groups via radical pathways. Furthermore, the merger of these processes with metal catalysis has significantly broadened the chemical space of cross-couplings, enabling novel bond formation events. Nonetheless, engaging aliphatic amines, especially unprotected ones, in photoredox catalysis to construct CSP2-CSP3 bonds remains challenging due to the undesired over-oxidation, C-N coupling, and many other side reactions. Chapter 2 describes a solution using the easily accessible α-silylmethylamine to generate α-amino radicals regioselectively under mild reaction conditions and engage them in a rate-matched Ni/photoredox dual catalytic process to generate benzylamines. Subsequent efforts toward installing alkyl substrcutures was focused on the synthesis of bicyclo[1.1.1]pentane (BCP), which is a bioisostere of phenyl-, alkyl- and alkynyl groups. Although in many cases, BCP has brought promising improvement to drug candidates, limitations in synthetic methods to access this unusual motif have become a main hurdle for their application. Chapter 3 describes a transition metal-free approach to 1,3-disubstituted BCP boronates, a class of highly versatile BCP building blocks, from [1.1.1]propellane using carboxylic acid and organohalide feedstock materials. Chapter 4 describes the discovery of a highly selective Ni-catalyzed cyanation process that enables the synthesis of alkyl-, sulfonyl- and carbamoyl-substituted BCP nitriles, another useful BCP building block, in a single-step from [1.1.1]propellane.

Notes:

Source: Dissertations Abstracts International, Volume: 84-12, Section: B.

Includes supplementary digital materials.

Advisors: Molander, Gary A.; Schelter, Eric J.; Committee members: Huryn, Donna M.; Chenoweth, David M.

Department: Chemistry.

Ph.D. University of Pennsylvania 2023.

Local Notes:

School code: 0175

ISBN:

9798379758738

Access Restriction:

Restricted for use by site license.