Intermolecular [2π+2σ]-photocycloaddition enabled by triplet energy transfer.

For more than one century, photochemical [2+2]-cycloadditions have been used by synthetic chemists to make cyclobutanes, four-membered carbon-based rings. In this reaction, typically two olefin subunits (two π-electrons per olefin) cyclize to form two new C-C σ-bonds. Although the development of photochemical [2+2]-cycloadditions has made enormous progress within the last century, research has been focused on such [2π+2π]-systems, in which two π-bonds are converted into two new σ-bonds1,2. Here we report an intermolecular [2+2]-photocycloaddition that uses bicyclo[1.1.0]butanes as 2σ-electron reactants3-7. This strain-release-driven [2π+2σ]-photocycloaddition reaction was realized by visible-light-mediated triplet energy transfer catalysis8,9. A simple, modular and diastereoselective synthesis of bicyclo[2.1.1]hexanes from heterocyclic olefin coupling partners, namely coumarins, flavones and indoles, is disclosed. Given the increasing importance of bicyclo[2.1.1]hexanes as bioisosteres-groups that convey similar biological properties to those they replace-in pharmaceutical research and considering their limited access10,11, there remains a need for new synthetic methodologies. Applying this strategy enabled us to extend the intermolecular [2+2]-photocycloadditions to σ-bonds and provides previously inaccessible structural motifs.

Amidative ß-Scission of Alcohols Enabled by Dual Catalysis of Photoredox Proton-Coupled Electron Transfer and Inner-Sphere Ni-Nitrenoid Transfer.

The photoredox/Ni dual catalysis is an appealing strategy to enable unconventional C-heteroatom bond formation. While significant advances have been achieved using this system, intermolecular C(sp3)-N bond formation has been relatively underdeveloped due to the difficulty in C(sp3)-N reductive elimination. Herein, we present a new mechanistic approach that utilizes dioxazolones as the Ni(II)-nitrenoid precursor to capture carbon-centered radicals by merging proton-coupled electron transfer (PCET) with nickel catalysis, thus forming synthetically versatile N-alkyl amides using alcohols. Based on mechanistic investigations, the involvement of (κ2-N,O)Ni(II)-nitrenoid species was proposed to capture photoredox PCET-induced alkyl radicals, thereby playing a pivotal role to enable the C(sp3)-N bond formation.

Visible-Light Induced C(sp2 )-H Amidation with an Aryl-Alkyl σ-Bond Relocation via Redox-Neutral Radical-Polar Crossover.

We report an approach for the intramolecular C(sp2 )-H amidation of N-acyloxyamides under photoredox conditions to produce δ-benzolactams with an aryl-alkyl σ-bond relocation. Computational studies on the designed reductive single electron transfer strategy led us to identify N-[3,5-bis(trifluoromethyl)benzoyl] group as the most effective amidyl radical precursor. Upon the formation of an azaspirocyclic radical intermediate by the selective ipso-addition with outcompeting an ortho-attack, radical-polar crossover was then rationalized to lead to the rearomative ring-expansion with preferential C-C bond migration.

Tuning Triplet Energy Transfer of Hydroxamates as the Nitrene Precursor for Intramolecular C(sp3)-H Amidation.

Reported herein is the design of a photosensitization strategy to generate triplet nitrenes and its applicability for the intramolecular C-H amidation reactions. Substrate optimization by tuning physical organic parameters according to the proposed energy transfer pathway led us to identify hydroxamates as a convenient nitrene precursor. While more classical nitrene sources, representatively organic azides, were ineffective under the current photosensitization conditions, hydroxamates, which are readily available from alcohols or carboxylic acids, are highly efficient in accessing synthetically valuable 2-oxazolidinones and γ-lactams by visible light. Mechanism studies supported our working hypothesis that the energy transfer path is mainly operative.

Photochemical single-step synthesis of ß-amino acid derivatives from alkenes and (hetero)arenes.

ß-Amino acids are frequently found as important components in numerous biologically active molecules, drugs and natural products. In particular, they are broadly utilized in the construction of bioactive peptides and peptidomimetics, thanks to their increased metabolic stability. Despite the number of methodologies established for the preparation of ß-amino acid derivatives, the majority of these methods require metal-mediated multistep manipulations of prefunctionalized substrates. Here we disclose a metal-free, energy-transfer enabled highly regioselective intermolecular aminocarboxylation reaction for the single-step installation of both amine and ester functionalities into alkenes or (hetero)arenes. A bifunctional oxime oxalate ester was developed to simultaneously generate C-centred ester and N-centred iminyl radicals. This mild method features a remarkably broad substrate scope (up to 140 examples) and excellent tolerance of sensitive functional groups, and substrates that range from the simplest ethylene to complex (hetero)arenes can participate in the reaction, thus offering a general and practical access to ß-amino acid derivatives.

Living ß-selective cyclopolymerization using Ru dithiolate catalysts.

Cyclopolymerization (CP) of 1,6-heptadiyne derivatives is a powerful method for synthesizing conjugated polyenes containing five- or six-membered rings via α- or ß-addition, respectively. Fifteen years of studies on CP have revealed that user-friendly Ru-based catalysts promoted only α-addition; however, we recently achieved ß-selective regiocontrol to produce polyenes containing six-membered-rings, using a dithiolate-chelated Ru-based catalyst. Unfortunately, slow initiation and relatively low catalyst stability inevitably led to uncontrolled polymerization. Nevertheless, this investigation gave us some clues to how successful living polymerization could be achieved. Herein, we report living ß-selective CP by rational engineering of the steric factor on monomer or catalyst structures. As a result, the molecular weight of the conjugated polymers from various monomers could be controlled with narrow dispersities, according to the catalyst loading. A mechanistic investigation by in situ kinetic studies using 1H NMR spectroscopy revealed that with appropriate pyridine additives, imposing a steric demand on either the monomer or the catalyst significantly improved the stability of the propagating carbene as well as the relative rates of initiation over propagation, thereby achieving living polymerization. Furthermore, we successfully prepared diblock and even triblock copolymers with a broad monomer scope.