Date of Graduation

12-2019

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Chemistry (PhD)

Degree Level

Graduate

Department

Chemistry & Biochemistry

Advisor/Mentor

Nan Zheng

Committee Member

Matthias McIntosh

Second Committee Member

Bill Durham

Third Committee Member

Stefan Kilyanek

Keywords

amines, bond formation, bond cleavage, distonic radical cations, radical cations, ring-opening

Abstract

Recently photoredox catalysis has emerged as a powerful tool in organic synthesis led by Professor McMillan, Stephenson, Yoon. Upon absorption of visible light, photocatalyst can be excited to its singlet state followed by intersystem crossing to form a long lived excited triplet state. While amine serves as electron donor, single electron transfer (SET) can happen between excited triplet photocatalyst and nitrogen atom on amine to give a reduced photocatalyst and amine radical cation.

Cyclopropylamines or cyclobutylamines can be oxidized by excited photocatalyst to generate amine radical cations and due to the ring strain, subsequent C-C bond cleavages can lead to distonic radical cation with an iminium site and a carbon radical site. Prof. Zheng’s group has utilized the distonic radical cation to undergo [3+2] and [4+2] annulations to furnish cyclopentyl or cyclohexylanilines. These reactions are initiated via radical addition to unsaturated bonds such as olefins and alkynes. When a different type of cyclobutylaniline, namely benzo-cyclobutylaniline, is employed as substrate, multisubstituted naphthalenes can be obtained as product as a result of fully aromatization via elimination of the aniline moity. Further exploration to take advantage of the binary reactivity of distonic radical cation revealed a difunctionalization protocol which use TMSCN as nucleophile to react with iminium ion and α- CF3 styrenes as radical acceptors. This protocol also for the first time employed amines instead of anilines as substrates. One of the intrinsic limitations to use amine radical cation to induce α C-C bond cleavge is the tertiary amines which generally are not very active towards ring-opening process. To tackle this long standing issue we devised a two-electron ring-opening system which bypassed the formation of distonic radical cation. Electrophilic iodine was used directly to induce C-C bond cleavage via a SN2 type like pathway and the subsequent β-iodo iminium ion can be intercepted by various nucleophiles such as TMSCN, succinimide and indole.

Amine radical cations can also directly engage in C-N bond formation as an electrophilic species. Intramolecular addition of amine radical cation to tetrasubstituted styrenes followed by 1,2-carbocation shift yielded tetracyclic scaffolds that is commonly seen in akuammiline natural products.

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