Studies Leading to the Development of a Single-Electron Transfer (SET) Photochemical Strategy for Syntheses of Macrocyclic Polyethers, Polythioethers, and Polyamides

Abstract

Organic photochemists began to recognize in the 1970s that a new mechanistic pathway involving excited-state single-electron transfer (SET) could be used to drive unique photochemical reactions. Arnold's seminal studies demonstrated that SET photochemical reactions proceed by way of ion radical intermediates, the properties of which govern the nature of the ensuing reaction pathways. Thus, in contrast to classical photochemical reactions, SET-promoted excited-state processes are controlled by the nature and rates of secondary reactions of intermediate ion radicals. In this Account, we discuss our work in harnessing SET pathways for photochemical synthesis, focusing on the successful production of macrocyclic polyethers, polythioethers, and polyamides. One major thrust of our studies in SET photochemistry has been to develop new, efficient reactions that can be used for the preparation of important natural and non-natural substances. Our efforts with α-silyl donor-tethered phthalimides and naphthalimides have led to the discovery of efficient photochemical processes in which excited-state SET is followed by regioselective formation of carbon-centered radicals. The radical formation takes place through nucleophile-assisted desilylation of intermediate α-silyl-substituted ether-, thioether-, amine-, and amide-centered cation radicals. Early laser flash photolysis studies demonstrated that the rates of methanol- and water-promoted bimolecular desilylations of cation radicals (derived from α-silyl electron donors) exceeded the rates of other cation radical α-fragmentation processes, such as α-deprotonation. In addition, mechanistic analyses of a variety of SET-promoted photocyclization reactions of α-silyl polydonor-linked phthalimides and naphthalimides showed that the chemical and quantum efficiencies of the processes are highly dependent on the lengths and types of the chains connecting the imide acceptor and α-silyl electron donor centers. We also observed that reaction efficiencies are controlled by the rates of desilylation at the α-silyl donor cation radical moieties in intermediate zwitterionic biradicals that are formed by either direct excited-state intramolecular SET or by SET between the donor sites in the intervening chains. It is important to note that knowledge about how these factors govern product yields, regiochemical selectivities, and quantum efficiencies was crucial for the design of synthetically useful photochemical reactions of linked polydonor-acceptor substrates. The fruits of these insights are exemplified by synthetic applications in the concise preparation of cyclic peptide mimics, crown ethers and their lariat- and bis-analogs, and substances that serve as fluorescence sensors for important heavy metal cations.

Copper(II)-salt-promoted oxidative ring-opening reactions of bicyclic cyclopropanol derivatives via radical pathways

“…In principle, radical intermediates in ET-promoted reactions have a tendency to participate in further ET processes to generate ionic species when stoichiometric amounts of redox reagents are used (Scheme 1) [1–10]. In contrast, radical intermediates formed by a photoinduced ET (PET) are less likely to undergo these secondary reactions, because steady-state concentrations of PET-generated redox reagents are low [11–19]. When radical intermediates and ions derived from their precursor radical ions undergo different rearrangement reactions, it is often possible to distinguish respective reaction pathways of radicals and ions by examining the product distributions of the reactions of substrates that contain appropriate probe moieties (Scheme 2).…”

Catalytic Carbocation Generation Enabled by the Mesolytic Cleavage of Alkoxyamine Radical Cations

“…[5,[6] In certain cases these bonds are sufficiently weakened such that they undergo spontaneous scission, resulting in the formation of two new intermediates – a neutral free radical and a carbocation. While pioneering studies from Arnold, [7] Floreancig, [8] Mariano, [9] and Albini [10] have demonstrated the feasibility and value of these methods, mesolytic cleavage-based strategies for simple carbocation generation remain underutilized.…”

Direct and indirect single electron transfer (SET)-photochemical approaches for the preparation of novel phthalimide and naphthalimide-based lariat-type crown ethers

“…These fragmentation reactions produce neutral radicals, which then participate in typical radical reactions, including C–C bond formation and addition to unsaturated centers. Because of their importance, α-heterolytic fragmentation reactions of radical anions and cations have been intensively studied from synthetic and mechanistic perspectives [11–34]. …”

“…Previous studies [31–34 62–67] in our laboratories resulted in the development, mechanistic elucidation, and synthetic application of various kinds of SET-promoted photocyclization reactions of α-trialkylsilyl donor-linked imide acceptor systems and led to an understanding of the factors controling the chemical selectivities and efficiencies. For example, we have demonstrated that intramolecular SET-photochemical reactions of linked α-trimethylsilyl n-electron donor-phthalimides/naphthalimides produce functionalized macrocyclic poly-ethers, -thioethers, -amides, and -peptides via the intermediacy of interconverting zwitterionic biradicals 21 and 22 .…”