Photochemical phenol oxidation strategies in the total synthesis of natural products Matthew C Carson

Format:

Book

Thesis/Dissertation

Author/Creator:

Carson, Matthew C., author.

Contributor:

University of Pennsylvania. Chemistry., degree granting institution.

Language:

English

Subjects (All):

Organic chemistry.

Physical chemistry.

Inorganic chemistry.

0490.

0800.

0488.

0494.

Local Subjects:

Organic chemistry.

Physical chemistry.

Inorganic chemistry.

0490.

0800.

0488.

0494.

Genre:

Academic theses

Physical Description:

1 online resource (839 pages)

Contained In:

Dissertations Abstracts International 87-12B

Place of Publication:

Ann Arbor : ProQuest Dissertations and Theses, 2026

Language Note:

English

Summary:

1.A photocatalytic method to selectively synthesize 4-hydroperoxy-2,5-cyclohexadienones from para-alkyl phenols is disclosed. This photosensitized singlet oxygen approach functionalized a variety of electronically diverse para-alkyl phenols in 27-99% isolated yields. Utilizing this dearomative oxidation, (±)-stemenone B and (±)-parvistilbine B were synthesized in 9 and 11 steps, respectively, from commercially available starting materials. Additional experiments revealed the dramatic influence of base and solvent on the selectivity while providing insight into the mechanism of this transformation.2. A dual photocatalytic system to synthesize phenol-pyridinium salts using visible light has been discovered. Utilizing both electron donor-acceptor (EDA) complex and iridium(III) photocatalytic cycles, the C-N cross-coupling of unprotected phenols and pyridines proceeds in the presence of oxygen to furnish pyridinium salts. Photocatalytic generation of phenoxyl radical cations also enabled a nucleophilic aromatic substitution (SNAr) of a fluorophenol with an electron-poor pyridine. Spectroscopic experiments were conducted to probe the mechanism and reaction selectivity. The unique reactivity of these phenol-pyridinium salts were displayed in several derivatization reactions, providing rapid access to a diverse chemical space.3. A photochemical method for the amination of phenols (C-H) and halophenols (SNAr) has been developed. Dual catalytic pathways involving both iridium(III) photocatalysis and phenol-pyridinium electron donor-acceptor complexation are involved. By incorporating a pyridinium additive, efficient C-N coupling was achieved between phenols and diverse aromatic nitrogen nucleophiles, delivering high yields (up to 99%) across a wide range of substrates, including pharmaceuticals and natural products. The reaction selectivity and substrate compatibility/limitations was investigated through a combination of experimental and computational techniques. Moreover, the synthetic versatility of the amination products was highlighted through various late-stage functionalizations including the grafting of two different heteroarenes onto one phenol scaffold.4.Aporphine alkaloids are important natural products with uses ranging from traditional Chinese herbal medicine to modern clinical applications. These compounds are isolated from a variety of plants and possess many powerful biological properties. Inspired by the biomimetic coupling of reticuline, a novel synthetic approach was designed to construct the corytuberine (8-2' coupling) and isoboldine (8-6' coupling) aporphine cores using a key photochemical intermolecular oxidative phenol coupling. With a short and efficient synthetic sequence telescoping of intermediates (no chromatography) and minimal use of transition-metals, these natural products were functionalized into a variety of synthetic analogues. These derivatives fueled biological evaluation of the natural products and their derivatives for binding affinity at the serotonin 5-HT2 and adrenergic α1A receptors.5. Developing sustainable methods for C(sp2)-C(sp2) bond formation that avoid transition-metals and prefunctionalized substrates remains a central goal in synthetic chemistry. Phenols and N-heteroarenes (azines) are abundantly available, yet their cross-coupling is hindered by mismatched redox properties and chemoselectivity issues. Herein, a photochemical strategy that couples phenols with heteroaryl halides under redox-neutral conditions using an organic dye photocatalyst and base is disclosed. Concurrent oxidation of the phenol component and reduction of the azine component generates complementary radicals that cross-couple efficiently, delivering moderate to high yields (up to 91%) with high functional group tolerance. Mechanistic experiments and density functional theory (DFT) studies elucidate the radical reaction pathways, while substrate clustering, high-throughput experimentation (HTE), and machine learning (ML) enable prediction of C-C versus SNAr reactivity across broad chemical space

Notes:

Source: Dissertations Abstracts International, Volume: 87-12, Section: B.

Advisors: Kozlowski, Marisa C. Committee members: Trauner, Dirk; Huryn, Donna M.; McCallum, Monica E.

Ph.D. University of Pennsylvania 2026

Vendor supplied data

Local Notes:

School code: 0175

ISBN:

9798247979920

Access Restriction:

Restricted for use by site license