We present here a review of the photochemical and electrochemical applications of multi-site proton-coupled electron transfer (MS-PCET) in organic synthesis. MS-PCETs are redox mechanisms in which both an electron and a proton are exchanged together, often in a concerted elementary step. As such, MS-PCET can function as a non-classical mechanism for homolytic bond activation, providing opportunities to generate synthetically useful free radical intermediates directly from a wide variety of common organic functional groups. We present an introduction to MS-PCET and a practitioner's guide to reaction design, with an emphasis on the unique energetic and selectivity features that are characteristic of this reaction class. We then present chapters on oxidative N-H, O-H, S-H, and C-H bond homolysis methods, for the generation of the corresponding neutral radical species. Then, chapters for reductive PCET activations involving carbonyl, imine, other X═Y π-systems, and heteroarenes, where neutral ketyl, α-amino, and heteroarene-derived radicals can be generated. Finally, we present chapters on the applications of MS-PCET in asymmetric catalysis and in materials and device applications. Within each chapter, we subdivide by the functional group undergoing homolysis, and thereafter by the type of transformation being promoted. Methods published prior to the end of December 2020 are presented.

Photochemical and Electrochemical Applications of Proton-Coupled Electron Transfer in Organic Synthesis.

The past decade has witnessed the emergence of N-(acyloxy)phthalimides (NHPI esters) and its derivatives at the forefront of synthetic methods facilitating the construction of diverse molecular fra...

Single Electron Transfer-Induced Redox Processes Involving N-(Acyloxy)phthalimides

The mainstream applications of visible-light photoredox catalysis predominately involve outer-sphere single-electron transfer (SET) or energy transfer (EnT) processes of precious metal RuII or IrIII complexes or of organic dyes with low photostability. Earth-abundant metal-based Mn Ln -type (M=metal, Ln =polydentate ligands) complexes are rapidly evolving as alternative photocatalysts as they offer not only economic and ecological advantages but also access to the complementary inner-sphere mechanistic modes, thereby transcending their inherent limitations of ultrashort excited-state lifetimes for use as effective photocatalysts. The generic process, termed visible-light-induced homolysis (VLIH), entails the formation of suitable light-absorbing ligated metal-substrate complexes (Mn Ln -Z; Z=substrate) that can undergo homolytic cleavage to generate Mn-1 Ln and Z. for further transformations.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/anie.202100270

Visible-Light-Induced Homolysis of Earth-Abundant Metal-Substrate Complexes: A Complementary Activation Strategy in Photoredox Catalysis.

For molecules with a singlet ground state, the population of triplet states is mainly possible (a) by direct excitation and subsequent intersystem crossing or (b) by energy transfer from an appropriate sensitizer. The latter scenario enables a catalytic photochemical reaction in which the sensitizer adopts the role of a catalyst undergoing several cycles of photon absorption and subsequent energy transfer to the substrate. If the product molecule of a triplet-sensitized process is chiral, this process can proceed enantioselectively upon judicious choice of a chiral triplet sensitizer. An enantioselective reaction can also occur in a dual catalytic approach in which, apart from an achiral sensitizer, a second chiral catalyst activates the substrate toward sensitization. Although the idea of enantioselective photochemical reactions via triplet intermediates has been pursued for more than 50 years, notable selectivities exceeding 90% enantiomeric excess (ee) have only been realized in the past decade. This review attempts to provide a comprehensive survey on the various photochemical reactions which were rendered enantioselective by triplet sensitization.

Enantioselective Photochemical Reactions Enabled by Triplet Energy Transfer.

Phosphine-Free NNN-Manganese Complex Catalyzed α-Alkylation of Ketones with Primary Alcohols and Friedländer Quinoline Synthesis

This study reports a nickel-catalyzed sustainable synthesis of polysubstituted quinolines from α-2-aminoaryl alcohols by a sequential dehydrogenation and condensation process that offers the advantages of a low catalyst loading and wide substrate scope. In contrast to earlier reported methods, this strategy allows the use of both primary as well as secondary α-2-aminoaryl alcohols in combination with either ketones or secondary alcohols for desired product formation. Using this methodology, 30 substituted quinoline derivatives were synthesized with up to 93% isolated yields.

Synthesis of Polysubstituted Quinolines from α-2-Aminoaryl Alcohols Via Nickel-catalyzed Dehydrogenative Coupling

This study reveals cobalt-catalyzed sustainable synthesis of benzimidazoles by redox-economical coupling of o-nitroanilines and alcohols. The major advantage of this report is the use of a commerci...

Cobalt-Catalyzed Sustainable Synthesis of Benzimidazoles by Redox-Economical Coupling of o-Nitroanilines and Alcohols.

Nickel(II) Tetraphenylporphyrin as an Efficient Photocatalyst Featuring Visible Light Promoted Dual Redox Activities

An organophotoredox catalyzed efficient and robust approach for the synthesis of highly important 3-alkyl substituted chroman-4-one scaffold is developed using visible light induced radical cascade cyclization strategy. The reaction is initiated through the generation of alkyl radicals from N-(acyloxy)phthalimides under photoredox conditions, which subsequently undergo intermolecular cascade radical cyclization on 2-(allyloxy)arylaldehydes to afford chroman-4-one scaffolds. The presented strategy is attractive with regard to mild reaction conditions, operational simplicity, high functional group tolerance and broad substrate scope.

Organophotoredox-Catalyzed Cascade Radical Annulation of 2-(Allyloxy)arylaldehydes with N-(acyloxy)phthalimides: Towards Alkylated Chroman-4-one Derivatives.

Sanju Das

Papers

Single Electron Transfer-Induced Redox Processes Involving N-(Acyloxy)phthalimides

Synthesis of Polysubstituted Quinolines from α-2-Aminoaryl Alcohols Via Nickel-catalyzed Dehydrogenative Coupling

Cobalt-Catalyzed Sustainable Synthesis of Benzimidazoles by Redox-Economical Coupling of o-Nitroanilines and Alcohols.

Nickel(II) Tetraphenylporphyrin as an Efficient Photocatalyst Featuring Visible Light Promoted Dual Redox Activities

Organophotoredox-Catalyzed Cascade Radical Annulation of 2-(Allyloxy)arylaldehydes with N-(acyloxy)phthalimides: Towards Alkylated Chroman-4-one Derivatives.