One-Pot Acid-Catalyzed Ring-Opening/Cyclization/Oxidation of Aziridines with N-Tosylhydrazones: Access to 1,2,4-Triazines

A new, three-step, telescoped reaction sequence for the regioselective conversion of N-tosyl hydrazones and aziridines to 3,6-disubstituted and 3,5,6-trisubstituted 1,2,4-triazines is described. The process involves an efficient nucleophilic ring opening of the aziridine, giving access to a wide range of aminohydrazones, isolated with excellent yields. A “one-pot” procedure, combining the ring opening with a cyclization and an oxidation step, allows the preparation of diversified triazines in good yields.This work was supported by a postdoctoral fellowship from Pfizer (L.C.) and EPSRC Grant Nos. EP/K009494/1 and EP/M004120/1 (S.V.L.). We also thank Dr. Andrew D. Bond for conducting X-ray crystallographic analysis

Contra-thermodynamic E → Z isomerization of cinnamamides via selective energy transfer catalysis

A bio-inspired, photocatalytic E → Z isomerization of cinnamides is reported using inexpensive (−)-riboflavin (vitamin B2) under irradiation at λ = 402 nm. This operationally simple transformation is compatible with a range of amide derivatives including –NR2, –NHSO2R and N(Boc)2 (up to 99:1 Z:E). Selective energy transfer from the excited state photocatalyst to the starting E-isomer ensures that directionality is achieved: The analogous process with the Z-isomer is inefficient due to developing allylic strain causing chromophore deconjugation. This is supported by X-ray analysis and Stern-Volmer photo-quenching studies. Preliminary validation of the method in manipulating the conformation of a simple model Leu-enkephalin penta-peptide is disclosed via the incorporation of a cinnamamide-based amino acid

Mechanistic Insights into the Triplet Sensitized Photochromism of Diarylethenes

Operating photoswitchable molecules repetitively and reliably is crucial for most of their applications, in particular in (opto)electronic devices, and related to reversibility and fatigue resistance, which both critically depend on the photoisomerization mechanism defined by the substitution pattern. Two diarylethene photoswitches bearing biacetyl triplet sensitizers either at the periphery or at the core were investigated using both stationary as well as transient UV/Vis absorption spectroscopy ranging from the femtosecond to the microsecond time scale. The diarylethene with two biacetyl moieties at the periphery is switching predominantly from the triplet excited state, giving rise to an enhanced fatigue resistance. In contrast, the diarylethene bearing one diketone at the photoreactive inner carbon atom cyclizes from the singlet excited state and shows significantly higher quantum yields for both cyclization and cycloreversion.Peer Reviewe

Vitamin Catalysis: Direct, Photocatalytic Synthesis of Benzocoumarins via (−)-Riboflavin-Mediated Electron Transfer

An operationally simple protocol is disclosed to facilitate entry to benzo-3,4-coumarins directly from biaryl carboxylic acids without the need for substrate prefunctionalization. Complementary to classic lactonization strategies, this disconnection relies on the oxidation competence of photoactivated (−)-riboflavin (vitamin B₂) to generate the heterocyclic core via photoinduced single electron transfer. Collectively, the inexpensive nature of the catalyst, ease of execution, and absence of external metal additives are a convincing endorsement for the incorporation of simple vitamins in contemporary catalysis

Boron-Enabled Geometric Isomerization of Small Alkene Fragments via Selective Energy Transfer Catalysis

The mammalian visual cycle epitomizes the importance of complex polyenes in biology. However, isomerization-based strategies to enable the sterodivergent construction of these important biomolecules from geometrically defined alkene linchpins remain conspicuously underdeveloped. Mitigating the thermodynamic constraints inherent to isomerization is further frustrated by the considerations of atom efficiency in idealized low molecular precursors. Herein, we report a general ambiphilic C3 scaffold that can be isomerized and bi-directionally extended. Predicated on highly efficient triplet energy transfer, the selective isomerization of β-15 borylacrylates is contingent on the participation of the boron p-orbital in the substrate chromophore. Rotation of the C(sp2)-B bond by 90° in the product renders re-excitation inefficient and endows directionality. This subtle stereoelectronic gating mechanism enables the stereocontrolled syntheses of well-defined retinoic acid derivatives.<br /

An Asymmetric Aromatic Finkelstein Reaction: A Platform for Remote Diarylmethane Desymmetrization

A first-of-its-kind enantioselective aromatic Finkelstein reaction is disclosed for the remote desymmetrization of diarylmethanes. The reaction operates through a copper-catalyzed C‒I bond forming event and high levels of enantioselectivity are achieved through the deployment of a tailored guanidinylated peptide ligand. Strategic use of transition-metal mediated reactions enabled the chemoselective modification of the aryl iodide, thus, the synthesis of a diverse set of otherwise difficult-to-access diarylmethanes in excellent levels of selectivity is realized from a common intermediate. A mixed experimental/computational analysis of steric parameters and substrate conformations identifies the importance of remote conformational effects as a key to achieving high enantioselectivity in this desymmetrization reaction

Supporting research data for "One-Pot Acid-Catalyzed Ring-Opening/Cyclization/Oxidation of Aziridines with N-Tosylhydrazones: Access to 1,2,4-Triazines"

Characterisation data for all compounds synthetised and described in the manuscript

Light-Enabled Deracemization of Cyclopropanes by Al-Salen Photocatalysis

Privileged chiral catalysts continue to transform the reactivity landscape, but achieving parity in excited state paradigms remains a frontier in contemporary synthesis. Whilst the interception of photogenerated intermediates by ground state cycles has partially addressed this challenge, single, chiral photocatalysts that simultaneously regulate reactivity and selectivity remain conspicuously scarce. Existing strategies leverage precision donor-acceptor recognition motifs to orchestrate enantioinduction. Expanding the latitude of this emerging branch of photocatalysis to incorporate simple, ubiquitous recognition units would be highly enabling but requires a suite of privileged photocatalysts. Motivated by the well-defined photo-physical properties of chiral Al-salen complexes, the efficiency of this privileged catalyst has been investigated and validated in the highly enantioselective deracemization of cyclopropyl ketones (up to 98:2 e.r.)

One-Pot Acid-Catalyzed Ring-Opening/Cyclization/Oxidation of Aziridines with <i>N</i>‑Tosylhydrazones: Access to 1,2,4-Triazines

A new, three-step, telescoped reaction sequence for the regioselective conversion of <i>N</i>-tosyl hydrazones and aziridines to 3,6-disubstituted and 3,5,6-trisubstituted 1,2,4-triazines is described. The process involves an efficient nucleophilic ring opening of the aziridine, giving access to a wide range of aminohydrazones, isolated with excellent yields. A “one-pot” procedure, combining the ring opening with a cyclization and an oxidation step, allows the preparation of diversified triazines in good yields