Synthesis Enabled by E-to-Z Isomerization Using CBZ6 as Energy Transfer Photocatalyst.

The reactions of Z-isomers and E-isomers usually are different in consideration of the regioselectivity of chemoselectivity. The syntheses of Z-isomers are not feasible in many cases. The energy transfer (EnT) E/Z-photoisomerization might yield the Z-isomers. In this work, CBZ6 was proven to be an EnT photocatalyst for the E → Z-isomerization of C-C or C-N double bonds. The transformations of in situ generated Z-isomers of oximes and stilbenes consequently afforded the desired reversed Beckmann rearrangement products and phenanthrenes, respectively.

Photocatalytic Redox-Neutral Alkoxyacylation of Alkenes.

ß-Alkoxyketones are important building blocks in organic synthesis. By utilizing CBZ6, with an oxidative potential of -2.16 V (vs the saturated calomel electrode), as a redox-neutral photocatalyst, alkoxyacylation of olefins was accomplished under the irradiation of visible light via a cationic intermediate. It involves the addition of an acyl radical to olefin to form a radical intermediate and the following oxidation of the radical intermediate to the benzyl cationic intermediate that is captured by alkoxy anions. This process provides concise and practical access to the ß-functionalized ketones.

Transalkylation via C-N Bond Cleavage of Amines Catalyzed by Super Organophotoreductant CBZ6.

The super organoreductant CBZ6-catalyzed tandem transalkylation-cyclization using amines as traceless radical donors and stabilizer is reported. The later-stage breaking of an N-C bond enables the transalkylation with a secondary amine as the leaving moiety. A wide range of tertiary amines were used as alkyl radical donors for the C1-C8 alkyls. This traceless stabilizer also enabled the transalkylation with methyl radical, which is normally not possible because of the instability of methyl radical.

Synthesis of α-Hydroxyl and α-Amino Pyridinyl Esters via Photoreductive Dual Radical Cross-Coupling.

A method for the synthesis of α-hydroxyl and α-amino pyridinyl esters via photoreductive dual radical cross-coupling catalyzed by the super-organoreductant CBZ6 has been developed. A wide range of 2-pyridinylation and 4-pyridinylation of either α-ketoesters or imine derivatives has been achieved. The applications in the synthesis of pyridinyl amino-hydroxyl acids as well as a new chiral oxazoline ligand have also been accomplished.

Salicylaldehyde as an SET-HAT Bifunctional Photocatalyst for the Intermolecular Transalkylation of Phthalimide.

Salicylaldehyde works as an efficient photocatalyst for the intermolecular transalkylation of phthalimide. The well-designed dimethyl N-hydroxyphthalimide ester proves to be a good alkylation reagent. It inhibits the competing intramolecular alkylation of alkylating reagent, enabling the site-specific synthesis of N-substituted phthalimide.

Iron-Catalyzed Aerobic α,ß-Dehydrogenation.

An iron-catalyzed direct aerobic α,ß-dehydrogenation of carbonyls has been reported. The combination of tert-butyl nitrite and N-hydroxyphthalimide worked as the organo cocatalyst system; thus, no extra transition metal reagents are required. A large variety of lactams and flavanones as well as lactone and thiochromen-4-one could be produced via this method in high yields.

Transcriptomic and physiological analysis of the effect of octanoic acid on Meloidogyne incognita.

Root knot nematodes are the most devastating root pathogens, causing severe damage and serious economic losses to agriculture worldwide. Octanoic acid has been reported as one of the nematicides, and its mode of action is not fully understood. The main objective of this study was to elucidate the effect of octanoic acid on Meloidogyne incognita by transcriptomic analysis combined with physiological and biochemical assays. In the toxicity assays with octanoic acid, the threshold concentration with nematicidal activity and the maximum concentration to which nematodes could respond were 0.03 µL/mL and 0.08 µL/mL respectively. Microscopic observation combined with protein and carbohydrates assays confirmed that the structure of the second-stage juveniles (J2s) was severely disrupted after 72 h of immersion in octanoic acid. Transcriptome analysis has shown that octanoic acid can interfere with the nematode energy metabolism, lifespan and signaling. Although the effects are multifaceted, the findings strongly point to the cuticle, lysosomes, and extracellular regions and spaces as the primary targets for octanoic acid. In addition, nematodes can withstand the negative effects of low concentration of octanoic acid to some extent by up-regulating the defense enzyme system and heterologous metabolic pathways. These findings will help us to explore the nematicidal mechanism of octanoic acid and provide important target genes for the development of new nematicides in the future.

Ambient Temperature Dehydrogenative C(Ar)-H Carbonylative Lactamization of 2-Arylanilines Using DMF as C1-Source.

The direct dehydrogenative C-H cleaving carbonylative lactamization of 2-arylanilines promoted by visible light and potassium bases is reported. Solvent DMF acts as the sole carbonyl source in the absence of an oxidant. The irreversible release of hydrogen gas drags this reaction to the stable phenanthridinone products. This work provides a direct conversion of a broad range of 2-arylanilines to various phenanthridinones. This method could be applied in the synthesis of bioactive molecules and organic optoelectronic materials.

Endo/Exo-Controllable Photocyclization by EnT-SET-Switch.

CBZ6, a redox-neutral non-donor-acceptor-type organo-photocatalyst, presents a strong reductive potential with an oxidative potential of -2.16 V (vs SCE). It can work as a photosensitizer for both single-electron transfer and triplet energy transfer processes. This feature enables site-selective control in the intramolecular hydroarylation of acrylamides. Both 5-exo-trig and 6-endo-trig cyclization products could be prepared regiospecfically under mild conditions. No transition metal, halogen-containing reagents, or additional reductant or oxidant is involved. This process provides a concise and environmentally sustainable access to a series of oxindoles and dihydroquinolinones.

Reductive Cleavage of C-X or N-S Bonds Catalyzed by Super Organoreductant CBZ6.

The reductive cleavage of C(Ar)-X bonds is the key step for the cross coupling of Ar-X with other groups. In this work, under the irradiation of 407 nm LEDs using sodium formate as reductant and thiol as hydrogen atom transfer agent, a variety of (hetero)aryl chlorides, bromides, and iodides could be reduced to corresponding (hetero)arenes. The key intermediates, aryl radicals, could be trapped by either hydrogen, phosphite, or borates. The same reduction conditions can be extended to the deprotection of sulfonamides.

Synthesis of carbinoxamine via α-C(sp3)-H 2-pyridylation of O, S or N-containing compounds enabled by non-D-A-type super organoreductants and sulfoxide- or sulfide HAT reagents.

The radical cations of tertiary amines (R3N) have been well-established as the precursors of HAT reagents in photochemical transformations. Similarly, thiols and thioacids bearing SH groups have also been widely applied as HAT reagents. Despite the fact that sulfoxides (R2SO) and sulfides (RSR) also bear lone pairs of electrons, these compounds have been barely reported as HAT reagents in photocatalysis. On the other hand, the α-C-H 4-pyridylation of O or N-containing compounds has been documented, whereas 2-pyridylation remains challenging. However, the antihistamine and anticholinergic agent carbinoxamine is an ether bearing 2-pyridyl, which has not been obtained by the existing α-photoarylation of ether. In this work, we report the discovery of a non-donor-acceptor (D-A) type organic photoreductant CBZ6 and sulfoxide/sulfide synergistically catalyzed general α-C(sp3)-H arylation of ethers, thioethers and amines. By using as low as 1 mol% of CBZ6 as a recyclable organic photoreductant and sulfoxides or sulfides as a new type of HAT reagent, the 2- or 4-pyridylation of O, N, or S-containing compounds has been accomplished. This is the first base-free version of α-C-H 2-/4-pyridylation of O, N, or S-containing compounds. It is the first example of sulfoxides or sulfides working as HAT reagents. It is also the first general method for photocatalytic HAT 2-pyridylation of various ethers, amines or thioethers.

Direct Synthesis of ß-Amino Aldehydes from Linear Allylic Esters Using O2 as the Sole Oxidant.

A tandem isomerization-anti-Markovnikov oxidation of linear allylic imidic esters is developed using bis(benzonitrile)palladium chloride as the catalyst and O2 as the sole oxidant, regiospecifically giving ß-amino aldehydes as the product. tert-Butyl nitrite works as a simple, and the only, redox cocatalyst. tBuOH proves to be a crucial solvent for achieving excellent yield and specificity toward anti-Markovnikov aldehyde products.

tert-Butyl Nitrite as a Twofold Hydrogen Abstractor for Dehydrogenative Coupling of Aldehydes with N-Hydroxyimides.

A synthetically practical transition metal/catalyst/halogen-free dehydrogenative coupling of aldehydes with N-hydroxyimides promoted solely by tert-butyl nitrite under mild conditions was developed. tert-Butyl nitrite generates two radicals (tBuO and NO) and thus works as a twofold hydrogen abstractor. A diverse array of N-hydroxyimide esters were prepared from either aliphatic or aromatic aldehydes. Benzoyl-substituted aldehydes such as 2-oxo-2-phenylacetaldehyde are also suitable.

CBZ6 as a Recyclable Organic Photoreductant for Pinacol Coupling.

A recyclable organic photoreductant (1 mol % CBZ6)-catalyzed reductive (pinacol) coupling of aldehydes, ketones, and imines has been developed. Irradiated by purple light (407 nm) using triethylamine as an electron donor, a variety of 1,2-diols and 1,2-diamines could be prepared. The oxidation potential of the excited state of CBZ6 is established as -1.92 V (vs saturated calomel electrode (SCE)). The relative high reductive potential enables the reductive coupling of carbonyl compounds and their derivatives. CBZ6 can be prepared in gram scale and is acid/base- or air-stable. It could be applied in large-scale photoreductive synthesis and recovered in high yield after the reaction.

Iron-Catalyzed α,ß-Dehydrogenation of Carbonyl Compounds.

An iron-catalyzed α,ß-dehydrogenation of carbonyl compounds was developed. A broad spectrum of carbonyls or analogues, such as aldehyde, ketone, lactone, lactam, amine, and alcohol, could be converted to their α,ß-unsaturated counterparts in a simple one-step reaction with high yields.

Discovery of Oxygen α-Nucleophilic Addition to α,ß-Unsaturated Amides Catalyzed by Redox-Neutral Organic Photoreductant.

The conjugate additions of oxygen-centered nucleophiles to conjugate acceptors are among the most powerful C-O bond formation reactions. The conjugate addition normally takes place at the ß-position carbon to the electron-withdrawing group, resulting in the formation of a stabilized carbanion intermediate that can be quenched by proton or electrophiles to form the ß-addition (i.e., hetero-Michael addition) products. On the contrary, the formation of α-hydroxyl or alkoxyl amides through conjugate addition needs an α,ß-inverse addition. Nevertheless, a regio-inversed nucleophilic α-addition of oxygen-centered nucleophiles to α,ß-unsaturated carbonyl compounds still remains less explored because of the electronic mismatch. In this research, we discovered the first α-specific nucleophilic addition of α,ß-unsaturated amides with oxygen and fluoride nucleophiles. This region-inversed nucleophilic addition is enabled by the catalysis of a novel redox-neutral nondonor-acceptor organic photoreductant (CBZ6). As low as 0.5 mol % of visible light photoreductant was employed. The mechanistic insights were also explored. The oxidative potential of the excited state of CBZ6 is obtained in -1.92 V (vs SCE), presenting a stronger reductive potential than representative metal-cored or organic photoredox catalysts. This feature enabled the umpolung of α,ß-unsaturated amides to take place α-nucleophilic addition other than the normal ß-addition.

tBuOK-Promoted Cyclization of Imines with Aryl Halides.

A transition-metal-free indole synthesis using radical coupling of 2-halotoluenes and imines via the later-stage C-N bond construction was reported for the first time. It includes an aminyl radical generation by C-H cleaving addition of 2-halotoluenes to imines via the carbanion radical relay and an intramolecular coupling of aryl halides with aminyl radicals. One standard condition can be used for all halides including F, Cl, Br, and I. No extra oxidant or transition metal is required.

Visible-Light-Induced, Base-Promoted Transition-Metal-Free Dehalogenation of Aryl Fluorides, Chlorides, Bromides, and Iodides.

We report a simple and efficient visible-light-induced transition-metal-free hydrogenation of aryl halides. The combined visible light and base system is used to initiate the desired radical-mediated hydrogenation. A variety of aryl fluorides, chlorides, bromides, and iodides could be reduced to the corresponding (hetero)arenes with excellent yields under mild conditions. Various functional groups and other heterocyclic compounds are tolerated.

CuSO4-Catalyzed dual annulation to synthesize O, S or N-containing tetracyclic heteroacenes.

In this work, CuSO4 is utilized as a practical redox catalyst for tandem dual annulation in the synthesis of indole-fused tetracyclic heteroacenes, which are important skeletons in both medicinal chemistry and materials chemistry. The preparation of such skeletons in a convenient and efficient manner is in high demand. This method realizes the modular synthesis of benzofuro-, benzothieno-, and indoloindoles from abundant feedstocks such as 2-halobenzyl halides and nitrile derivatives in up to 99% yields, providing a rapid access to diverse indole-fused heteroacenes with biological or optoelectronic properties.

Deprotonated Salicylaldehyde as Visible Light Photocatalyst.

Salicylaldehyde is established as an efficient visible light photocatalyst for the first time. Compared to other simple aldehyde analogies, salicylaldehyde has a unique deprotonative red-shift from 324 to 417 nm and gives rise to the remarkable increase of fluorescence quantum from 0.0368 to 0.4632, thus enabling salicylaldehyde as a visible light (>400 nm) photocatalyst. The experimental investigations suggest that the reactive radical species are generated by sensitization of the substrates by the deprotonated salicylaldehyde through an energy-transfer pathway. Consequently, the C-C cleaving alkylation reactions of N-hydroxyphthalimide esters proceed smoothly in the presence of as low as 1 mol % of salicylaldehyde under the visible-light irradiation, affording desired alkylation products with up to 99% yields. Application in visible-light induced aerobic oxidation of N-alkylpyridinium salts is also reported.