Rh(III)-Catalyzed C-H Functionalization/Annulation of 1-Arylindazolones: Divergent Synthesis of Fused Indazolones and Allyl Indazolones.

Rh(III)-catalyzed C-H/N-H annulation and C-H allylation of phenylindazolones have been realized by employing 5-methylene-1,3-dioxan-2-one and 4-vinyl-1,3-dioxolan-2-one as scalable cross-coupling partners, delivering functionalized indazolone fused heterocycles and branched and linear allyl indazolones respectively in moderate to high yield. These divergent synthesis protocols showcase mild conditions, broad substrate scope, and high functional-group compatibility. In addition, scale-up synthesis and preliminary mechanistic exploratory were also accomplished.

Synthesis of Indole-Substituted Trifluoromethyl Sulfonium Ylides by Cp*Rh(III)-Catalyzed Diazo-carbenoid Addition to Trifluoromethylthioether.

The indole-substituted trifluoromethyl sulfonium ylide has been developed via Cp*Rh(III)-catalyzed diazo-carbenoid addition to trifluoromethylthioether and is the first example of an Rh(III)-catalyzed diazo-carbenoid addition reaction with trifluoromethylthioether. Several kinds of indole-substituted trifluoromethyl sulfonium ylide were constructed under mild reaction conditions. The reported method exhibited high functional group compatibility and broad substrate scope. In addition, the protocol was found to be complementary to the method disclosed by a Rh(II) catalyst.

Rhodium(III)-catalyzed regioselective C(sp2)-H activation of indoles at the C4-position with iodonium ylides.

Herein, we report a Rh(III)-catalyzed C4-selective activation of indoles by using iodonium ylides as carbene precursors. This protocol proceeded under redox neutral reaction conditions and provided important coupling products with good tolerance of functional groups and high yields. In addition, one-pot synthesis and scale-up and mechanistic studies were also conducted.

Thioether-directed Rh(III)-catalyzed peri-selective acyloxylation of arenes.

A thioether directed acyloxylation of arenes has been realized via Cp*Rh(III)-catalyzed C-H activation and subsequent coupling with carboxylic acids. This new method showed high functional group compatibility and broad substrate scope. Primary mechanistic studies have been conducted and a tentative reaction mechanism was proposed. It represents the first example of a thioether-directed Cp*Rh(III)-catalyzed C(sp2)-H acyloxylation reaction.

Mild Synthesis of 3,4-Dihydroisoquinolin-1(2H)-ones via Rh(III)-Catalyzed Tandem C-H-Allylation/N-Alkylation Annulation with 2-Methylidenetrimethylene Carbonate.

A tandem rhodium(III)-catalyzed system was established to access 3,4-dihydroisoquinolin-1(2H)-one by coupling of N-methoxy-3-methylbenzamide with 2-methylidenetrimethylene carbonate. This one-pot synthesis protocol processed smoothly under mild reaction conditions. Moreover, a total of 28 examples, broad substrate scope, and high functional-group compatibility were observed. Preliminary mechanism studies were also conducted and demonstrated that the rhodium(III) catalyst played a vital role in the C-H-allylation and N-alkylation cyclization process.

Rhodium(III)-catalyzed oxidative alkylation of N-aryl-7-azaindoles with cyclopropanols.

An efficient Rh(iii)-catalyzed C-H oxidative alkylation of N-aryl-7-azaindoles with cyclopropanols by merging tandem C-H and C-C cleavage was developed. This transformation features mild reaction conditions, high regioselectivity, and excellent functional group compatibility. The resulting ß-aryl ketone derivatives can be readily transformed into 7-azaindole-containing π-extended polycyclic heteroarenes.

Correction: Rhodium(iii)-catalyzed oxidative alkylation of N-aryl-7-azaindoles with cyclopropanols.

Correction for 'Rhodium(iii)-catalyzed oxidative alkylation of N-aryl-7-azaindoles with cyclopropanols' by Jidan Liu et al., Org. Biomol. Chem., 2021, DOI: .

Access to acridones by tandem copper(I)-catalyzed electrophilic amination/Ag(I)-mediated oxidative annulation of anthranils with arylboronic acids.

An efficient and practical approach for the synthesis of medicinally important acridones was developed from anthranils and commercially available arylboronic acids by a tandem copper(I)-catalyzed electrophilic amination/Ag(I)-mediated oxidative annulation strategy. This new and straightforward protocol displayed a broad substrate scope (25 examples) and high functional group tolerance. What's more, a possible mechanistic proposal was also presented.

Synthesis and biological evaluation of novel indole-pyrazoline hybrid derivatives as potential topoisomerase 1 inhibitors.

A series of novel indole-pyrazoline hybrid derivatives were designed, synthesized, and evaluated for topoisomerase 1 (Top1) inhibitory activity. Top1-mediated relaxation assays showed that our synthesized compounds had variable Top1 inhibitory activity. Among these compounds, 3-(5-(naphthalen-1-yl)-1-phenyl-4,5-dihydro-1H-pyrazol-3-yl)-1-(phenylsulfonyl)-1H-indole (6n) was found to be a strong Top1 inhibitor with better inhibitory activity than CPT and hit compounds. Our further experiments rationalized the mode of action for this new type of inhibitors, which showed no significant binding to supercoiled DNA.

Decarboxylative Negishi Coupling of Redox-Active Aliphatic Esters by Cobalt Catalysis.

A cobalt-catalyzed decarboxylative Negishi coupling reaction of redox-active aliphatic esters with organozinc reagents was developed. The method enabled efficient alkyl-aryl, alkyl-alkenyl, and alkyl-alkynyl coupling reactions under mild reaction conditions with no external ligand or additive needed. The success of an in situ activation protocol and the facile synthesis of the drug molecule (±)-preclamol highlight the synthetic potential of this method. Mechanistic studies indicated that a radical mechanism is involved.

Experimental and Theoretical Studies on Rhodium-Catalyzed Coupling of Benzamides with 2,2-Difluorovinyl Tosylate: Diverse Synthesis of Fluorinated Heterocycles.

Fluorinated heterocycles play an important role in pharmaceutical and agrochemical industries. Herein, we report on the synthesis of four types of fluorinated heterocycles via rhodium(III)-catalyzed C-H activation of arenes/alkenes and versatile coupling with 2,2-difluorovinyl tosylate. With N-OMe benzamide being a directing group (DG), the reaction delivered a monofluorinated alkene with the retention of the tosylate functionality. Subsequent one-pot acid treatment allowed the efficient synthesis of 4-fluoroisoquinolin-1(2H)-ones and 5-fluoropyridin-2(1H)-ones. When N-OPiv benzamides were used, however, [4 + 2] cyclization occurred to provide gem-difluorinated dihydroisoquinolin-1(2H)-ones. Synthetic applications have been demonstrated and the ready availability of both the arene and the coupling partner highlighted the synthetic potentials of these protocols. Mechanistically, these two processes share a common process involving N-H deprotonation, C-H activation, and olefin insertion to form a 7-membered rhodacycle. Thereafter, different reaction pathways featuring ß-F elimination and C-N bond formation are followed on the basis of density functional theory (DFT) studies. These two pathways are DG-dependent and led to the open chain and cyclization products, respectively. The mechanistic rationale was supported by detailed DFT studies. In particular, the origins of the intriguing selectivity in the competing ß-F elimination versus C-N bond formation were elucidated. It was found that ß-F elimination is a facile event and proceeds via a syn-coplanar transition state with a low energy barrier. The C-N bond formation proceeds via a facile migratory insertion of the Rh-C(alkyl) into the Rh(V) amido species. In both reactions, the migratory insertion of the alkene is turnover-limiting, which stays in good agreement with the experimental studies.

Rh(III)-catalyzed C(sp2)-H functionalization/[4+2] annulation of oxadiazolones with iodonium ylides to access diverse fused-isoquinolines and fused-pyridines.

In this study, a Rh(III)-catalyzed C-H/N-H [4+2] annulation of oxadiazolones with iodonium ylides has been developed, which afforded a series of diverse fused-isoquinolines and fused-pyridines in moderate to high yields. These divergent synthesis protocols featured mild conditions, broad substrate scope, and functional-group compatibility. In addition, scale-up synthesis, related applications and preliminary mechanistic explorations were also accomplished.

A Platform for the Synthesis of Diverse Phosphonyl and Thiofunctionalized Sulfoxonium Ylides.

A practical strategy for the construction of diverse phosphonyl and thiofunctionalized sulfoxonium ylides via controllable monofunctionalization of hybrid I(III)/S(VI) ylides is presented. This process allows efficient P-H insertion of I(III)/S(VI) ylides under Cu catalysis, enabling the synthesis of phosphonyl sulfoxonium ylides, whereas reaction with sulfur-containing reagents including AgSCF3, KSC(S)OR, and KSCN under mild conditions resulted in α-trifluoromethylthiolation, dithiocarbanation, and thiocyanation of sulfoxonium ylides accordingly. Of note, wide substrate compatibility (108 examples), excellent efficiency (up to 99% yield), gram-scale experiments, and various product derivatizations highlight the synthetic utility of this protocol.

Cp*Rh(III)-catalyzed regioselective cyclization of aromatic amides with allenes.

A new Cp*Rh(III)-catalyzed regioselective cyclization reaction of aromatic amides with allenes is reported. The use of allenyl derivatives bearing a directing-group assistant as a reaction promoter was the key to the success of this protocol. In this catalytic system, N-(pivaloyloxy)benzamide substrates react with allenes via Rh-σ-alkenyl intermediates, while N-(pivaloyloxy) indol substrates react via Rh-π-allyl intermediates. These reactions were characterized by mild reaction conditions, a broad substrate scope, and high functional-group compatibility to yield several high-value isoquinolinone and pyrimido[1,6-a]indol-1(2H)-one skeleton-containing compounds. The synthetic applications and primary mechanisms were also investigated.

Cp*Rh(III)-Catalyzed ortho-Alkylation/Alkenylation of Nitroarenes.

Cp*Rh(III)-catalyzed nitro-directed C-H alkylation/alkenylation of nitroarenes has been reported for the first time. This protocol is associated with the features of high efficiency, broad substrate scope, and good functional group compatibility. Additionally, gram-scale experiments and synthetic applications proved the practicability of the method. Moreover, preliminary mechanistic investigations consistently revealed C-H bond cleavage as the rate-limiting step.

Divergent Synthesis of Tetrasubstituted Phenols via [3 + 3] Cycloaddition Reaction of Vinyl Sulfoxonnium Ylides with Cyclopropenones.

Two categories of tetrasubstituted phenols were prepared via the cycloaddition reaction of vinyl sulfoxonnium ylides with cyclopropenones in a switchable manner. Copper carbenoid was proposed as the active intermediate in the process of 2,3,4,5-tetrasubstituted phenols formation, while 2,3,5,6-tetrasubstituted phenols were generated via the direct [3 + 3] annulation of vinyl sulfoxonnium ylides with cyclopropenones under metal-free conditions. Further synthetic applications were also demonstrated.

Rh(III)-Catalyzed Dienylation and Cyclopropylation of 1,2,3-Benzotriazinones with Alkylidenecyclopropanes.

Rh (III)-catalyzed dienylation and cyclopropylation of 1,2,3-benzotriazinones with alkylidenecyclopropanes (ACPs) has been achieved. Different from the previous reports of 1,2,3-benzotriazinones, the triazinone ring remained intact in this C-H bond functionlization reaction. Also, the denitrogenative cyclopropylation could also be realized by changing the reaction temperature. This protocol is featured with high E selectivity, wide substrate scope, and divergent structures of products.

Access to Branched Allylarenes via Rhodium(III)-Catalyzed C-H Allylation of (Hetero)arenes with 2-Methylidenetrimethylene Carbonate.

A rhodium(III)-catalyzed C-H allylation of (hetero)arenes by using 2-methylidenetrimethylene carbonate as an efficient allylic source has been developed for the first time. Five different directing groups including oxime, N-nitroso, purine, pyridine, and pyrimidine were compatible, delivering various branched allylarenes bearing an allylic hydroxyl group in moderate to excellent yields.

Iridium-catalyzed B-H insertion of sulfoxonium ylides and borane adducts: a versatile platform to α-boryl carbonyls.

Iridium-catalyzed boron-hydrogen bond insertion reactions of trimethylamine-borane and sulfoxonium ylides have been demonstrated, furnishing α-boryl ketones in moderate to excellent yields in most cases (51 examples; up to 84%). This practical and scalable insertion reaction showed broad substrate scope, high functional-group compatibility and could be applied in late-stage modification of structurally complex drug compounds. Further synthetic applications were also demonstrated.

Regioselective Synthesis of 5-Aminooxazoles via Cp*Co(III)-Catalyzed Formal [3 + 2] Cycloaddition of N-(Pivaloyloxy)amides with Ynamides.

A simple and efficient protocol for the regioselective synthesis of 5-aminooxazoles is disclosed. The reaction, catalyzed by a cheap Cp*Co(III) catalyst, starts from easily accessible N-(pivaloyloxy)amides and ynamides. Mild reaction conditions, a broad substrate scope, good functional group tolerance, and good to excellent yields were observed.