Synthesis of CF3-Isoquinolinones and Imidazole-Fused CF3-Isoquinolinones Based on C-H Activation-Initiated Cascade Reactions of 2-Aryloxazolines.

Presented herein are novel syntheses of CF3-isoquinolinones and imidazole fused CF3-isoquinolinones based on the cascade reactions of 2-aryloxazolines with trifluoromethyl imidoyl sulfoxonium ylides. The formation of CF3-isoquinolinone involves an intriguing cascade process including oxazolinyl group-assisted aryl alkylation through C(sp2)-H bond metalation, carbene formation, migratory insertion, and proto-demetalation followed by intramolecular condensation and water-promoted oxazolinyl ring-scission. With this method, the isoquinolinone scaffold tethered with valuable functional groups was effectively constructed. By taking advantage of the functional groups embedded therein, the products thus obtained could be readily transformed into imidazole-fused CF3-isoquinolinones or coupled with some clinical drugs to furnish hybrid compounds with potential applications in drug development. In general, the developed protocols feature expeditious and convenient formation of valuable CF3-heterocyclic skeletons, broad substrate scope, and ready scalability. In addition, studies on the activity of selected products against some human cancer cell lines demonstrated their potential as lead compounds for the development of novel anticancer drugs.

Divergent synthesis of pyrrolizine derivatives through C-H bond functionalization of pyrroles.

Presented herein is the synthesis of diversely functionalized pyrrolizines from the reaction of N-alkoxycarbamoyl pyrroles with CF3-ynones. The formation of the product is based on a C-H bond activation-initiated cascade process including N-alkoxycarbamoyl group-directed alkenylation of the pyrrole scaffold followed by simultaneous intramolecular nucleophilic addition along with cleavage and transfer of the directing group. By taking advantage of the rich chemistry of the transferred alkoxycarbamoyl moiety, the products could be transformed into a series of structurally and biologically interesting pyrrolizine derivatives. To our knowledge, this is the first example in which the N-alkoxycarbamoyl unit acted as a transferable and transformable directing group for the divergent synthesis of pyrrolizines.

Synthesis of Naphtho[1',2':4,5]furo[3,2-b]pyridinones via Ir(III)-Catalyzed C6/C5 Dual C-H Functionalization of N-Pyridyl-2-pyridones with Diazonaphthalen-2(1H)-ones.

Presented herein is an unprecedented synthesis of naphtho[1',2':4,5]furo[3,2-b]pyridinones via Ir(III)-catalyzed C6/C5 dual C-H functionalization of N-pyridyl-2-pyridones with diazonaphthalen-2(1H)-ones. This protocol forms C-C and C-O bonds in one pot in which diazonaphthalen-2(1H)-ones serve as bifunctional reagents, providing both alkyl and aryloxy sources. To the best of our knowledge, this is the first example of an Ir(III)-catalyzed synthesis of the title compounds by using diazonaphthalen-2(1H)-ones as bifunctional substrates. Notably, this method features operational simplicity, good functional group tolerance, high efficiency, and high atom economy.

Selective Synthesis of Pyrazolonyl Spirodihydroquinolines or Pyrazolonyl Spiroindolines under Aerobic or Anaerobic Conditions.

Presented herein is a condition-controlled selective synthesis of pyrazolonyl spirodihydroquinolines or pyrazolonyl spiroindolines through formal [5 + 1] or [4 + 1] spiroannulation of 2-alkenylanilines with diazopyrazolones. Mechanistically, the formation of the title products involves initial generation of a pyrazolonyl spiro-fused seven-membered ruthenacycle species serving as a key intermediate through Ru(II)-catalyzed C-H/N-H bonds metalation, carbene formation, and its migratory insertion. When the reaction is carried out under air, the key intermediate undergoes reductive elimination to afford spirodihydroquinoline. When the reaction is run under argon, the key intermediate undergoes protonation and intramolecular nucleophilic addition to furnish spiroindoline. This work provides an atom-economical protocol for the effective functionalization of alkenyl C(sp2)-H bond, allowing rapid and selective assembly of valuable spiroscaffolds with a broad range of substrates.

Synthesis of N-Arylindoles from 2-Alkenylanilines and Diazonaphthalen-2(1H)-ones through Simultaneous Indole Construction and Aryl Introduction.

In this paper, an efficient synthesis of N-arylindoles through the cascade reaction of 2-alkenylanilines with diazonaphthalen-2(1H)-ones is presented. Mechanistically, this reaction involves the generation of a Ru-carbene complex from diazonaphthalen-2(1H)-one, followed by carbene N-H bond insertion with 2-alkenylaniline, intramolecular cyclization, and oxidative aromatization. In this reaction, the Ru(II) complex acts as a multifunctional catalyst to promote not only the carbene formation but also the intramolecular cyclization and the dehydrogenative aromatization. Meanwhile, air acts as a green and cost-effective oxidant. To our knowledge, this is the first example in which N-arylindoles were synthesized through simultaneous introduction of the N-aryl unit and construction of the indole scaffold. Notable advantages of this method include readily accessible and halide-free substrates, additive-free reaction conditions, good efficiency, excellent atom economy, and compatibility with diverse functional groups. In addition, the utility of the product thus obtained was showcased by its diverse structural transformations.

Synthesis of Indolyl-Tethered Spiro[cyclobutane-1,1'-indenes] through Cascade Reactions of 1-(Pyridin-2-yl)-1H-indoles with Alkynyl Cyclobutanols.

Presented herein is an efficient and unprecedented synthesis of indolyl-tethered spiro[cyclobutane-1,1'-indenes] through the cascade reaction of 1-(pyridin-2-yl)-1H-indoles with alkynyl cyclobutanols. Mechanistic experiments implicate a sequential process in which 1-(pyridin-2-yl)-1H-indole first undergoes an alkenylation with alkynyl cyclobutanol followed by an intramolecular Friedel-Crafts reaction to give the title products. The utility of this novel protocol was reflected by the ample substrate scope, high chemo- and regioselectivity, removable directing group, and scalable preparation. In addition, the product thus obtained can be further derivatized quite efficiently.

Synthesis of Dihydroquinolinone Derivatives via the Cascade Reaction of o-Silylaryl Triflates with Pyrazolidinones.

Presented herein is a novel synthesis of dihydroquinolinone derivatives through an unprecedented cascade reaction of o-silylaryl triflates with pyrazolidinones. Mechanistically, the formation of the title products is believed to involve a cascade procedure including in situ formation of aryne and its addition with pyrazolidinone followed by N-N bond cleavage and intramolecular C-C bond formation/annulation. Compared with literature methods for the synthesis of dihydroquinolinones, this protocol has advantages such as multistep transformations accomplished in one pot, broad substrate scope, mild reaction conditions, and good tolerance of diverse functional groups. In addition, the products thus obtained demonstrated significant in vitro antiproliferative activity in selected human cancer cell lines.

Selective Synthesis of Dihydrophenanthridine and Phenanthridine Derivatives from the Cascade Reactions of o-Arylanilines with Alkynoates through C-H/N-H/C-C Bond Cleavage.

In this paper, an unprecedented selective synthesis of dihydrophenanthridine and phenanthridine derivatives through the cascade reactions of 2-arylanilines with alkynoates is presented. Mechanistic studies showed that the formation of the dihydrophenanthridine scaffold involves an initial C(sp2)-H alkenylation of 2-arylaniline with alkynoate followed by an intramolecular aza-Michael addition. When this reaction is carried out at elevated temperature, the in situ formed substituted dihydrophenanthridine readily undergoes a retro-Mannich-type reaction to give the corresponding phenanthridine through C-C bond cleavage. Compared with literature methods, this novel protocol has advantages such as easily obtainable substrates with a free amino group, pharmaceutically privileged products, cheap catalysts, and conveniently controllable selectivity.

Selective Synthesis of Pyrazolo[1,2-a]pyrazolones and 2-Acylindoles via Rh(III)-Catalyzed Tunable Redox-Neutral Coupling of 1-Phenylpyrazolidinones with Alkynyl Cyclobutanols.

An unprecedented divergent synthesis of pyrazolo[1,2-a]pyrazolones and 2-acylindoles via Rh(III)-catalyzed [4 + 1] or [3 + 2] annulation of 1-phenylpyrazolidinones with alkynyl cyclobutanols through redox-neutral multiple bond activation by using -NH and -OH units as directing groups is presented. Notably, different annulation reactions were selectively achieved by simply adjusting the reaction conditions. With features such as simple procedures, easily accessible substrates, and high regio/chemoselectivity, these methods may find wide applications in related areas.

Synthesis of benzoazepine derivatives via Rh(iii)-catalyzed inert C(sp2)-H functionalization and [4 + 3] annulation.

In this paper, a novel and sustainable synthesis of the hitherto unreported 5H-benzo[c]imidazo[1,2-a]azepine-6-carboxylic acids via the cascade reactions of 2-arylimidazoles (1) with methylene-oxetanones (2) is presented. Mechanistically, the formation of the title compounds is triggered by a Rh(iii)-catalyzed C(sp2)-H alkenylation of 1 with 2 followed by an intramolecular N-nucleophilic substitution. With this method, a series of hybrid compounds combining the biologically promising imidazole and benzoazepine moieties decorated with a synthetically versatile carboxyl group were prepared in moderate to good efficiency. In addition, the utility of the products thus obtained was remarkably showcased by their efficient transformations into some otherwise difficult-to-obtain pentacyclic compounds.

Metal-Free Synthesis of 2-Aminobenzothiazoles via Iodine-Catalyzed and Oxygen-Promoted Cascade Reactions of Isothiocyanatobenzenes with Amines.

In this paper, a highly efficient and sustainable synthesis of 2-aminobenzothiazoles through the cascade reactions of isothiocyanatobenzenes with primary or secondary amines by using iodine as a catalyst and oxygen as an oxidant is presented. Mechanistically, the formation of the title compounds involves the in situ formation of the required benzothiourea intermediate followed by its intramolecular cross dehydrogenative coupling of a C(sp2)-H bond and a S-H bond. To our knowledge, this should be the first example in which 2-aminobenzothiazoles are efficiently prepared from simple and cheap isothiocyanates and amines under metal-free conditions by using iodine as a catalyst and molecular oxygen as an oxidant with water as the byproduct. Compared with literature protocols, this method eliminates the use of ortho-halo-substituted precursors, expensive transition-metal catalysts, and hazardous oxidants.

Synthesis of 2,2'-biphenols through direct C(sp(2))-H hydroxylation of [1,1'-biphenyl]-2-ols.

A novel synthesis of diversely substituted 2,2'-biphenols through Pd(ii)-catalyzed, (t)BuOOH-oxidized, and hydroxyl-directed C(sp(2))-H hydroxylation of [1,1'-biphenyl]-2-ols has been developed. Notably, this finding is distinct from previous reports in which [1,1'-biphenyl]-2-ols underwent an intramolecular C-H activation and C-O bond formation to afford dibenzofurans under the promotion of Pd(ii) but in the absence of (t)BuOOH.