Demethylenative cyclization of 1,7-enynes using α-amino radicals as a traceless initiator enabled by Cu(I)-photosensitizers.

A rare type of demethylenative intramolecular cyclization of 1,7-enynes to access quinoline-2-(1H)-ones has been successfully developed under the catalysis of P/N-heteroleptic Cu(I)-photosensitizers. Preliminary mechanistic experiments revealed that the key to the success of this protocol lay in the α-amino radical addition-triggered tandem process of intramolecular radical cyclization/1,5-HAT/ß-fragmentation. This protocol provides a new avenue for the deconstructive cyclization of alkene derivatives.

Cu(I)-Photosensitizer-Catalyzed Olefin-α-Amino Radical Metathesis/Demethylenative Cyclization of 1,7-Enynes.

A demethylenative En-Yne radical cyclization of 1,7-enynes has been successfully developed to chemoselectively afford 3,4-dihyroquinolin-2-ones or quinolin-2-ones under the catalysis of Cu(I) photosensitizers PS3 and PS6 with different redox potentials. The preliminary mechanistic experiments revealed that the reaction underwent an unprecedented olefin-α-amino radical metathesis-type process. A reasonable mechanism was proposed to illustrate the catalyst-controlled chemoselectivity of the reaction based on preliminary mechanistic experiments and DFT calculations.

P/N-heteroleptic Cu(I)-photosensitizer-catalyzed domino radical relay annulation of 1,6-enynes with aryldiazonium salts.

A visible-light driven photocatalytic construction of benzo[b]fluorenones from 1,6-enynes and aryldiazonium salts has been achieved via a P/N-heteroleptic Cu(I)-photosensitizer-catalyzed domino radical relay annulation process. Preliminary mechanistic studies revealed that the aryl radicals in situ generated from aryldiazonium salts with the excited state of the Cu(I)-photosensitizer played a dual role of a radical initiator and a radical terminator in the concise construction of the highly fused benzo[b]fluorenone scaffold.

Approach to Access Benzo[j]phenanthridinones from 1,7-Enynes and Aryldiazonium Salts via a Domino Radical Relay Process Enabled by a P/N-Heteroleptic Cu(I)-Photosensitizer.

A mild approach for the synthesis of benzo[j]phenanthridin-6(5H)-one derivatives from 1,7-enynes and aryldiazonium salts has been successfully developed involving a domino radical relay process enabled by a heteroleptic Cu(I)-photosensitizer under visible-light-driven photocatalytic conditions. Mechanistic studies disclosed that the oxidative quenching of the excited state of PS 4 with aryldiazonium salts via an SET process generated aryl radicals, which could play a radical initiator-terminator dual role within the whole radical relay process, namely, at the initial step acting as a radical donor to trigger the radical addition to the olefin moieties of 1,7-enynes while at the final stage serving as a radical acceptor to complete the cyclization.

Aryl boronic acid-controlled divergent ring-contraction and ring-opening/isomerization reaction of tert-cyclobutanols enabled by nickel catalysis.

In this work, we wish to present a nickel-catalyzed divergent ring-contraction and ring-opening/isomerization reaction of tert-cyclobutanols. The key to control these two different reaction pathways is to choose appropriate boronic acid, where the use of phenylboronic acid and pyrimidin-5-ylboronic acid enables a ring-contraction and ring-opening reaction/isomerization, respectively. Both cyclopropyl aryl methanones and 1-aryl butan-1-ones could be selectively obtained.

Nickel-catalyzed divergent formylation and carboxylation of aryl halides with isocyanides.

Herein, we describe a nickel-catalyzed divergent formylation and carboxylation reaction of aryl halides with isocyanides. A rich array of aromatic aldehydes and carboxylic acids can be, respectively, accessed in moderate to good yields. Some sensitive functional groups such as hydroxyl, iodine, cyano, and indolyl are fairly tolerant of nickel catalysis. In the carboxylation reactions, the combination of isocyanide and H2O is first employed as a promising carbonyl surrogate instead of gaseous CO and CO2.

Nickel-catalyzed cascade hydrosilylation/cyclization of 1,7-enynes leading to silyl-containing quinolinones.

We herein describe a nickel-catalyzed cascade hydrosilylation/cyclization reaction of 1,7-enynes with bulky triphenylsilane. A series of silyl-containing quinolinone derivatives are obtained in good to excellent yields under mild reaction conditions. This reaction also features excellent chemoselectivity, broad functional group tolerance, and gram-scale synthesis.

P/N-Heteroleptic Cu(I)-Photosensitizer-Catalyzed [3 + 2] Regiospecific Annulation of Aminocyclopropanes and Functionalized Alkynes.

We report here a regiospecific [3 + 2] annulation between aminocyclopropanes and various functionalized alkynes enabled by a P/N-heteroleptic Cu(I) photosensitizer under photoredox catalysis conditions. Thus, a divergent construction of 3-aminocyclopentene derivatives including methylsulfonyl-, arylsulfonyl-, chloro-, ester-, and trifluoromethyl-functionalized aminocyclopentenes could be achieved with advantages of high regioselectivity, broad substrate compatibility, and mild and environmentally benign reaction conditions.

Nickel-catalyzed cyanation reaction of aryl/alkenyl halides with alkyl isocyanides.

We herein describe a nickel-catalyzed cyanation reaction of aryl/alkenyl halides with alkyl isocyanides. Both aryl/alkenyl iodines and bromides were found to be competent electrophiles that reacted with alkyl isocyanides, affording nitrile compounds in moderate to good yields. A range of functional groups including halogens as well as hydroxyl, formyl, and acetamino groups were fairly compatible with the nickel catalysis. This protocol featured broad functional group tolerance, simple reaction conditions, and gram-scale synthesis.

Deconstructive isomerization of azetidinols via C-C bond cleavage enabled by N-heterocyclic carbene (NHC) catalysis.

Herein, we describe an N-heterocyclic carbene (NHC)-catalyzed deconstructive isomerization of azetidinols via an inert C-C bond cleavage. It provides a direct and supplementary pathway to access α-amino ketone and oxazol-2-one derivatives in moderate to good yields. DFT calculation supports the proposed mechanism in which NHC undergoes a concerted proton transfer and ring-opening process. This reaction features non-metal catalysis, simple reaction operation, excellent regioselectivity and gram-scale synthesis.

Reactivity Umpolung of the C═N Bond in Quinoxaline Scaffold Enabling Direct Nucleophilic Attack of Alkyl Grignard Reagents at the N-Terminus.

The reactivity umpolung of the C═N bond in the quinoxaline scaffold has been successfully realized for the first time by introduction of a formyl or an acyl group adjacent to the C-position of the C═N moiety. The reversed reactivity of the C═N bond thus enabled direct nucleophilic attack of alkyl Grignard reagents at the N-terminus rather than the C-terminus, thereby providing an unprecedented and efficient method for the synthesis of quinoxalin-2(1H)-one derivatives involving a tandem N-alkylation/C─C bond cleavage process.

Azetidine synthesis enabled by photo-induced copper catalysis via [3+1] radical cascade cyclization.

Azetidines are an important type of saturated, highly strained, four-membered, nitrogen-containing heterocyclic compound. These compounds serve as important raw materials, intermediates, and catalysts in organic synthesis, as well as important active units in amino acids, alkaloids, and pharmaceutically active compounds. Thus, the development of an efficient and concise method to construct azetidines is of great significance in multiple disciplines. In this work, we reported on the photo-induced copper-catalyzed radical annulation of aliphatic amines with alkynes to produce azetidines. This reaction occurred in a two- or three-component manner. The alkynes efficiently captured photogenerated α-aminoalkyl radicals, forming vinyl radicals, which initiated tandem 1,5-hydrogen atom transfer and 4-exo-trig cyclization. Density functional theory calculations indicated that the tertiary radical intermediate was critical for the success of cyclization. In addition, the resulting saturated azetidine scaffolds possessed vicinal tertiary-quaternary and even quaternary-quaternary centers.

Nickel-catalyzed cyclization of 1,7-enynes for the selective synthesis of dihydrocyclobuta[c]quinolin-3-ones and benzo[b]azocin-2-ones.

We herein described a nickel-catalyzed cyclization of N-(o-ethynylaryl)acrylamides for the selective synthesis of dihydrocyclobuta[c]quinolin-3-ones and benzo[b]azocin-2-ones. The two varied products could be easily obtained by tuning the reaction temperature. This reaction features easy temperature-control, high efficiency, and gram-scale synthesis.

Nickel-catalyzed remote hydrosilylation of unconjugated enones with bulky triphenylsilane.

Herein we describe a nickel-catalyzed remote hydrosilylation of unconjugated enones with bulky triphenylsilane. A range of Z-silyl enol ethers are obtained as major isomers due to the process of nickel triggered alkene isomerization. Notably, some specific alkyl silyl enol ethers can be prepared from this protocol, which are not easily accessed by the traditional strategy using a strong base and chlorosilane. This reaction features 100% atom economy, simple reaction conditions, and good yields.

NHC-catalyzed Truce-Smiles rearrangement of N-aryl methacrylamides for the synthesis of trans-cinnamides.

Herein we describe a NHC-catalyzed Truce-Smiles rearrangement of N-aryl methacrylamides which enables the cleavage of an inert aryl C-N bond. A range of trans-cinnamides could be obtained by the direct construction of a C(aryl)-C(alkenyl) bond and functional groups such as Br, Cl, CN, and pyridinyl are compatible with NHC catalysis. The reaction features high atom-economy, transition-metal free catalysis, and easily available substrates.

Selective cine-arylation of tert-cyclobutanols with indoles enabled by nickel catalysis.

In previous literature, tert-cyclobutanols are widely studied for C-C bond activation exclusively leading to the formation of ordinary γ-substituted ketones. Herein, we first report a nickel-catalyzed cine-arylation of tert-cyclobutanols with indoles to access ß-aryl ketones with an unusual site-selectivity at the C3-position of tert-cyclobutanols. The reaction features earth-abundant nickel catalysis, excellent regioselectivity, high atom-economy, and broad substrate scope.

Single Cu(I)-Photosensitizer Enabling Combination of Energy-Transfer and Photoredox Catalysis for the Synthesis of Benzo[b]fluorenols from 1,6-Enynes.

An efficient, mild, and atom-economical synthesis of benzo[b]fluorenols from 1,6-enynes has been developed under photocatalytic conditions. A single P/N heteroleptic Cu(I)-photosensitizer might exhibit both energy-transfer and photoredox catalytic activities in the formation of benzo[b]fluorenols.

Nickel-Catalyzed Arylation/Alkenylation of tert-Cyclobutanols with Aryl/Alkenyl Triflates via a C-C Bond Cleavage.

Herein, we first present a nickel-catalyzed arylation and alkenylation of tert-cyclobutanols with aryl/alkenyl triflates via a C-C bond cleavage. An array of γ-substituted ketones was obtained in moderate-to-good yields, thus featuring earth-abundant nickel catalysis, broad substrate scope, and simple reaction conditions. Preliminary mechanistic experiments indicated that ß-carbon elimination pathways might be involved in the catalytic cycle.

Tertiary Amines Acting as Alkyl Radical Equivalents Enabled by a P/N Heteroleptic Cu(I) Photosensitizer.

An unprecedented exploration of tertiary amines as alkyl radical equivalents for cross-coupling with aromatic alkynes to access allylarenes has been achieved by a P/N heteroleptic Cu(I)-based photosensitizer under photoredox catalysis conditions. Mechanistic studies reveal that the reaction might undergo radical addition of in situ-generated α-amino radical intermediates to alkynes followed by 1,5-hydrogen transfer, C-N bond cleavage, and concomitant isomerization of the resulting allyl radical species.

Bifunctional phosphine ligand-enabled gold-catalyzed direct cycloisomerization of alkynyl ketones to 2,5-disubstituted furans.

An efficient synthesis of 2,5-disubstituted furans directly from alkynyl ketones has been developed via tandem gold(i)-catalyzed isomerization of alkynyl ketones to allenyl ketones and cycloisomerization. The key to the success of this chemistry is the use of a biphenyl-2-ylphosphine ligand featuring a critical remote tertiary amino group.