Norrish-Yang Reaction Research Articles

Formation of Multiple Naturally Occurring Meroterpenoid Scaffolds by Norrish–Yang Reaction of a p‐Benzoquinone

The Norrish–Yang reaction, as a typical example, demonstrates the inherent ability of photochemical reaction to facilitate formation of sterically congested C‐C bonds, efficiently crafting intricate ring structure in complex organic molecules.Herein we report for the first time a unified synthesis using quinone‐based acid‐promoted Norrish–Yang photocyclization for the stereoselective construction of multiple avarane‐type meroterpenoid natural products.

Formation of Multiple Naturally Occurring Meroterpenoid Scaffolds by Norrish-Yang Reaction of a p-Benzoquinone.

The Norrish-Yang reaction, as a typical example, demonstrates the inherent ability of photochemical reaction to facilitate formation of sterically congested C-C bonds, efficiently crafting intricate ring structure in complex organic molecules.Herein we report for the first time a unified synthesis using quinone-based acid-promoted Norrish-Yang photocyclization for the stereoselective construction of multiple avarane-type meroterpenoid natural products.

Visible-Light-Mediated Activation of Remote C(sp3)-H Bonds by Carbon-Centered Biradical via Intramolecular 1,5- or 1,6-Hydrogen Atom Transfer.

In this study, we introduce a novel intramolecular hydrogen atom transfer (HAT) reaction that efficiently yields azetidine, oxetane, and indoline derivatives through a mechanism resembling the carbon analogue of the Norrish-Yang reaction. This process is facilitated by excited triplet-state carbon-centered biradicals, enabling the 1,5-HAT reaction by suppressing the critical 1,4-biradical intermediates from undergoing the Norrish Type II cleavage reaction, and pioneering unprecedented 1,6-HAT reactions initiated by excited triplet-state alkenes. We demonstrate the synthetic utility and compatibility of this method across various functional groups, validated through scope evaluation, large-scale synthesis, and derivatization. Our findings are supported by control experiments, deuterium labeling, kinetic studies, cyclic voltammetry, Stern-Volmer experiments, and density functional theory (DFT) calculations.

Unusually Chemoselective Photocyclization of 2-(Hydroxyimino)aldehydes to Cyclobutanol Oximes: Synthetic, Stereochemical, and Mechanistic Aspects.

Photocyclization of carbonyl compounds (known as the Norrish-Yang reaction) to yield cyclobutanols is, in general, accompanied by fragmentation reactions. The latter are predominant in the case of aldehydes so that secondary cyclobutanols are not considered accessible via the straightforward Norrish-Yang reaction. A noteworthy exception has been reported in our laboratory, where cyclobutanols bearing a secondary alcohol function were observed upon UV light irradiation of 2-(hydroxyimino)aldehydes (HIAs). This reaction is here investigated in detail by combining synthesis, spectroscopic data, molecular dynamics, and DFT calculations. The synthetic methodology is generally applicable to a series of HIAs, affording the corresponding cyclobutanol oximes (CBOs) chemoselectively (i.e., without sizable fragmentation side-reactions), diastereoselectively (up to >99:1), and in good to excellent yields (up to 95%). CBO oxime ether derivatives can be purified and diastereomers isolated by standard column chromatography. The mechanistic and stereochemical picture of this photocyclization reaction, as well as of the postcyclization E/Z isomerization of the oxime double bond is completed.

Total Synthesis of (+)-Cyclobutastellettolide B.

A convenient enantioselective total synthesis of (+)-cyclobutastellettolide B via a strategy that involves a diastereoselective Johnson-Claisen rearrangement, a regioselective cyclopropoxytrimethylsilane ring-opening reaction, and a Norrish-Yang cyclization is described. The results of computational and experimental studies indicate that the regio- and stereoselectivity of the Norrish-Yang reaction are controlled by the C-H bond dissociation energy and restricted rotation of the C13-C14 bond.

Structural reasons for the formation of multicomponent products and the influence of high pressure.

(S)-(-)-1-Phenylethanaminium 4-(2,4,6-triisopropylbenzoyl)benzoate (S-PEATPBB) undergoes a photochemical reaction in its crystalline form upon UV irradiation and forms three different products: the first product is the result of a Yang cyclization with the participation of the δ-H atom of o-isopropyl (product D) and the second and third products are obtained via a Norrish-Yang reaction with the involvement of the γ-H atom of 2-isopropyl (product P) and 6-isopropyl (product Z). These products are formed in different proportions (D > P >> Z). The path and kinetics of the reaction were monitored step-by-step using crystallographic methods, both under ambient and high-pressure conditions. The reactivity of S-PEATPBB depends strongly on the geometry of the reaction centre and the volume of the reaction cavity. Due to the geometrical preferences making the cyclization reaction easier to proceed, product D dominates over the other products, while the formation of product Z becomes difficult or almost impossible at high pressure. The reaction proceeds with an increase of the unit-cell volume, which, suppressed by high pressure, results in a significant decrease of the reaction rate. The crystal lattice of S-PEATPBB shows high elasticity. The quality of the partially reacted crystal remains the same after decompression from 0.75 GPa to 0.1 MPa.

The Reasons for Different Kinetics of the Norrish-Yang Reaction in Crystals. Structural and Spectroscopic Studies

The kinetics of the photochemical Norrish-Yang reaction in single crystals was studied using the example of 1,3,5,7-tetraazatricyclo[3.3.1.13,7]decane 4-(2,4,6-triisopropylbenzoyl)benzoate by X-ray...

Selective C-C Bond Scission of Ketones via Visible-Light-Mediated Cerium Catalysis

Summary Here, we report a general catalytic manifold for the selective C–C bond scission of ketones via the exploitation of the ligand-to-metal charge transfer (LMCT) excitation mode. Through a cooperative utilization of Lewis acid catalysis and LMCT catalysis, the C–C bond of ketones could be selectively and effectively cleaved, enabling the installation of different functionalities at each carbon of the cleaved C–C bond through a sequential and orthogonal manner. This reaction manifold serves as a photocatalytic alternative to the Norrish type I reaction with the combination of visible light and inexpensive cerium salts. Under operationally simple conditions, a wide range of acyclic and cyclic ketones, from simple strained cyclobutanones to complex androsterone with less strained cyclopentanone moiety, could be successfully transformed into versatile chemical building blocks.

Synthesis of Naphthocyclobutenes from α-Naphthyl Acrylates by Visible-Light Energy-Transfer Catalysis.

Methyl (α-naphthyl) acrylates bearing an ortho-substituent with a hydrogen atom produce naphthocyclobutenes upon Ir(Fppy)3-mediated photosensitization. This reaction can be described as a carbon analogue of the Norrish-Yang reaction: upon triplet excitation of the acrylate a 1,5-HAT results in a 1,4-diradical which forms the cyclobutene. Diastereoselectivities up to >20:1 were observed for the ring-closure reaction.

Structural Transformations in Crystals Induced by Radiation and Pressure. Part 7. Molecular and Crystal Geometries as Factors Deciding about Photochemical Reactivity under Ambient and High Pressures

We studied the photochemical reactivity of salts of 4-(2,4,6-triisopropylbenzoyl)benzoic acid with propane-1,2-diamine (1), methanamine (2), cyclohexanamine (3), and morpholine (4), for compounds (1), (3), and (4) at 0.1 MPa and for compounds (1) and (2) at 1.3 GPa and 1.0 GPa, respectively. The changes in the values of the unit cell parameters after UV irradiation and the values of the intramolecular geometrical parameters indicated the possibility of the occurrence of the Norrish–Yang reaction in the case of all the compounds. The analysis of the intramolecular geometry and free spaces revealed which o-isopropyl group takes part in the reaction. For (1), the same o-isopropyl group should be reactive at ambient and high pressures. In the case of (2), high pressure caused the phase transition from the space group I2/a with one molecule in the asymmetric unit cell to the space group P1¯ with two asymmetric molecules. The analysis of voids indicated that the Norrish–Yang reaction is less probable for one of the two molecules. For the other molecule, the intramolecular geometrical parameters showed that except for the Norrish–Yang reaction, the concurrent reaction leading to the formation of a five-membered ring can also proceed. In (3), both o-isopropyl groups are able to react; however, the bigger volume of a void near 2-isopropyl may be the factor determining the reactivity. For (4), only one o-isopropyl should be reactive.

Photoinduced Structural Changes as the Factor Influencing the Direction of the Photochemical Reaction in the Crystal

The path of the Norrish–Yang reaction of methylammonium 4-(2,4,6-triisopropylbenzoyl)benzoate was studied by means of X-ray structure analysis. The following parameters influenced by this photochemical reaction were monitored: (a) intramolecular distances and angles in the reaction center, (b) the size of the free space near the reactive atoms, (c) the mutual orientation of molecular fragments, (d) the cell parameters, and (e) the product content. Product molecules were created in two modes, namely, by the reaction of the 2-isopropyl or 6-isopropyl group, which has not been revealed previously for other 2,4,6-triisopropylbenzophenones. The 2-isopropyl group took part in the photochemical reaction during the whole crystal transformation, whereas the reaction of the 6-isopropyl group started with a delay and ceased before the total crystal conversion. The reason for such behavior was explained by the analysis of changes in the free space near both o-isopropyl groups with the crystal phototransformation.

The reasons for the photochemical behaviour of propylamine 4-(2,4,6-triisopropylbenzoyl)benzoate during the Norrish–Yang reaction

Intermolecular interactions are responsible for the direction of the Norrish–Yang reaction.

Structural transformations in crystals induced by radiation and pressure. Part 3. The pressure-induced structural changes versus the rate of the Norrish-Yang reaction in crystals

Abstract The X-ray diffraction studies of the salt of 6,6-diethyl-5-oxo-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid with (1 S )-1-(4-methylphenyl)ethylamine were carried out at high pressure. The compound underwent the Norrish-Yang reaction in crystals brought about by UV–vis radiation. In order to understand the photoreactivity of the compound at high pressure, the structures of pure reactant crystals at 0.1 MPa and 1.8 GPa were compared in terms of the intramolecular geometrical parameters, the intermolecular interactions, the free space, the size of the reaction cavity and the cell parameters, which all changed with pressure. The course of the photochemical reaction was monitored at 1.0 GPa and 1.8 GPa. The changes in the unit cell parameters indicated that the reaction proceeded faster at 1.0 GPa than at 1.8 GPa, which was connected with the decrease of the volume of the reaction cavity and the increase of the intermolecular interactions at high pressure.

Monitoring Photochemical Reactions in Single Crystals by X-ray Diffraction: Practical Aspects

The influence of external stimuli on the decrease of crystal diffracting power and hence the quality of diffraction patterns and determined structures was studied in the case of the Norrish-Yang photochemical reaction of methyl 2-{[4-(2,4,6-triisopropylbenzoyl)benzoyl]amino}-3-phenylpropanoate, compound 1. The reaction was conducted in a single-crystal-to-single-crystal homogeneous manner. The calculated rate constant at 75 °C was 1.6 × 10−3 s−1. In a quantitative way we illustrated a relationship between the reduction of the crystal diffracting power and the content of reactant molecules in the crystal and quantitatively showed that reactant molecules are responsible for this reduction. We observed that there is no correlation between the energy of UV–vis radiation applied to induce the photochemical reaction and the degree of the decrease of crystal diffracting power. We also showed in the case of the studied crystals that some change in temperature does not influence the degree of the decrease of the crystal diffracting power under the influence of UV–vis radiation. The unknown structures of the crystals containing pure reactant and product for compound 1 were also presented. The influence of different external stimuli on the reduction of diffracting power of crystals was monitored quantitatively during and after the Norrish-Yang photochemical reaction.

The crystal and molecular structure of sodium 4-(2,4,6-triisopropylbenzoyl)benzoate in terms of the photochemical behaviour of the anion.

Contrary to the known 4-(2,4,6-triisopropylbenzoyl)benzoate salts, di-μ-aqua-bis[tetraaquasodium(I)] bis[4-(2,4,6-triisopropylbenzoyl)benzoate] dihydrate, [Na2(H2O)10](C23H27O3)2·2H2O, (1), does not undergo a photochemical Norrish-Yang reaction in the crystalline state. In order to explain this photochemical inactivity, the intermolecular interactions were analyzed by means of the Hirshfeld surface and intramolecular geometrical parameters describing the possibility of a Norrish-Yang reaction were calculated. The reasons for the behaviour of the title salt are similar crystalline environments for both the o-isopropyl groups in the anion, resulting in similar geometrical parameters and orientations, and that these interaction distances differ significantly from those found in salts where the photochemical reaction occurs.

Structural transformations in crystals induced by radiation and pressure. Part 2. The path of a photochemical intramolecular reaction in crystals at different pressures

Studies have revealed how pressure influences the path of one photochemical reaction in crystals. The single-crystal-to-single-crystal Norrish–Yang reaction of 4-(2,4,6-triisopropylbenzoyl)benzoate benzylammonium, compound 1, was studied at high pressures of 0.3 and 0.9 GPa. X-ray structure analysis was used in order to monitor the kinetics of the reaction and the structural changes induced by UV radiation and pressure. The reaction rate is lower at higher pressure: the rate constants are 5.3 × 10−5 s−1 and 4.3 × 10−6 s−1 at 0.3 and 0.9 GPa, respectively. This was rationalized by: (a) the decrease in the size of voids near the reaction centre and in the unit cell with pressure, (b) the increase of intermolecular interactions in which the photoreactive o-isopropyl group takes part along with pressure and (c) the structural changes brought about by the photochemical reaction itself, for example, the increase of the unit cell volume. Pressure significantly reduced these structural changes and even halted some of them.

Steering photochemical reactivity of 2,4,6-triisopropylbenzophenonate anion in a crystalline state

The Norrish–Yang reaction was conducted in crystals of benzylammonium, pyrrolidinium and ammonium 4-(2,4,6-triisopropylbenzoyl)benzoates (1–3). The crystal structures of 1–3, six structures of the partly reacted crystals of these compounds and the structure of the pure product crystal for 1 were determined. The content of the product in the partly reacted crystals allowed to calculate the values of the rate constants and the orders of the reaction for 1 and 3 by the JMAK model. The results indicated that the Norrish–Yang reaction proceeded homogeneously for 3 and according to a hybrid mechanism for 1. The rate constant was much higher for 3 than for 1. The differences in the reactivity were explained by the intramolecular geometrical parameters and intermolecular interactions mapped onto the Hirshfeld surfaces. The results showed that it is possible to largely change reactivity of the one organic species, even several hundred times, by modifying the crystal lattice in which it is embedded.

Photo-induced structural transformations in crystals at high pressure. Part 1. The crystallographic studies of the photochemical reaction at high pressure

Abstract The preliminary results of high-pressure X-ray diffraction studies of the intramolecular photochemical Norrish–Yang reaction in single crystals of the salt of 6,6-diethyl-5-oxo-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid and (1S)-1-(4-methylphenyl)ethylamine are presented. The photo-induced changes in the cell parameters at high pressure along with the time of UV irradiation and the changes in the cell parameters along with pressure are discussed. The percentage change in the cell parameters brought about by the photochemical reaction at high pressure is similar to that at normal pressure. The cell volume decreases non-linearly with increasing pressure. The crystals lose their crystallinity above 2 GPa. This is the first paper in scientific literature on monitoring photochemical reactions in crystals at high pressure by X-ray diffraction.

Photo-induced structural changes in two crystal forms with different numbers of independent molecules

Structural changes brought about by the Norrish-Yang reaction proceeding in two crystal forms of methyl 2-{[4-(2,4,6-triisopropylbenzoyl)benzoyl]amino}-3-phenylpropanoate were monitored by X-ray structure analysis. The S-enantiomer and the racemic mixture of the compound crystallize in the space groupsP212121 with one molecule in the asymmetric unit and Pna21 with two symmetrically independent molecules, respectively. The changes in the cell volume for both crystal forms are of different kinds. They were attributed not only to the photochemical reaction but additionally to a loss of translational order in the racemic crystal. The structures determined for the partly reacted racemic crystal revealed that two symmetrically independent molecules react at different rates. This fact was explained quantitatively by means of differences in the free space and in the geometry of both molecules. It was also shown that only a single o-isopropyl group took part in the reaction.

Photochemical synthesis of benzoyl spiro[2.2]pentanes

In the present study, we describe the photochemical behaviour of 2-mesyloxy phenyl ketones 8 and 12 bearing a cyclopropane moiety in the side-chain. Irradiation of 8 and 12 leads to the corresponding benzoyl spiro[2.2]pentanes as a consequence of an initial gamma-H-shift, subsequent elimination of MsOH (accompanied by a spin-center shift) and cyclization of the resulting 1,3-diradicals. In contrast, a corresponding phenyl ketone without a mesyloxy group in the 2-position, and thus a potential reactant of the "classical" Norrish-Yang reaction, shows no photochemical reaction. By means of quantum chemical calculations we discovered that in the presence of a mesyloxy group the activation barrier for the photochemical gamma-H-shift is substantially decreased. Furthermore, a photoinduced skeletal rearrangement of benzoyl spiro[2.2]pentane to 2-cyclobutylidene-acetophenone could be observed. Compared to the common methods used to synthesize spiro[2.2]pentanes, the photochemical preparation of benzoyl spiro[2.2]pentane presented herein is the first example where a bond between the spiro atom and an adjacent atom is formed.