A new DTBP/Mg(NO3)2-mediated bicyclization cascade of o-arylalkynylanilines with secondary arylphosphine oxides has been developed, enabling dual C(sp2)–H functionalization along with the cleavage of the C–N bond. The combination between regioselective P-centered radical-triggered [3 + 2] cyclization and C-centered radical-induced cross-coupling in a one-pot manner delivered 27 examples of tribenzo[b,e,g]phosphindole oxides with generally high regioselectivity. A reasonable mechanism for forming such products involving radical addition–cyclization cascade is proposed.

The combination of AgTFA and Sc(OTf)3 enables the bimetallic synergistic catalysis of β-alkynyl ketones and para-quinone methides (p-QMs), allowing direct synthesis of 17 examples of benzo[c]xanthenes with generally good yields through a benzannulation/1,6-addition/cyclization sequence. Exchanging p-QMs for quinone imine ketal resulted in 10 examples of tetracyclic naphtho[1,2-b]benzofurans via a similar benzannulation/1,4-addition/cyclization cascade. During these reaction processes, AgTFA and Sc(OTf)3 could be perfectly compatible, together with the realization of C(sp3)-H functionalization adjacent to carbonyl group on the β-alkynyl ketone unit.

A new Ag/Brønsted acid co-catalyzed spiroketalization of β-alkynyl ketones with para-quinone methides (p-QMs) has been established, enabling multiple C–C and C–O bond-forming events to access densely functionalized spiro[chromane-2,1′-isochromene] derivatives with generally excellent diastereoselectivity and good yields. A reasonable mechanism for forming these 6,6-dibenzannulated spiroketals involving 6-endo-dig oxo-cyclization and 1,6-addition-cyclization cascades is proposed.

A new and highly eco-friendly approach to diverse and functionalized oxazolo[5,4-b]indoles with good yield and high diastereoselectivity (up to >99:1) has been disclosed from simple and readily available arylglyoxals with cyclic enaminones and amino acids. These microwave-assisted transformations in environmentally compatible ethanol resulted in continuous multiple bond-forming events including C–C, C–N, and C–O bonds, enabling catalyst-free multicomponent bicyclizations to rapidly build up functional N,O-heterocycles.

A new Ag-catalyzed oxidative bicyclization of N-tethered 1,7-enynes with alkylcarboxylic acids for forming 41 examples of polycyclic 3,4-dihydroquinolin-2(1H)-ones has been established using readily accessible K2S2O8 as an oxidant. The reaction pathway involves a silver-catalyzed decarboxylation/in situ-generated C-center radical-triggered α,β-conjugated addition/6-exo-dig cyclization/H-abstraction/5-endo-trig cyclization/SET sequence, allowing direct site-selective decarboxylative C(sp3)–H functionalization toward the formation of multiple C–C bonds and rapid construction of complex spiroheterocycles.

A novel I2-mediated benzannulation of 1,7-diyne-involved 1,4-oxo-migration was established, providing a range of unexpected 1-aroyl-2-naphthaldehydes with a 1,4-dicarbonyl unit. The resulting 1-aroyl-2-naphthaldehydes were successfully applied in the synthesis of benzo[e]isoindol-3-ones and benzo[e]benzo[4,5]imidazo[2,1-a]isoindoles using aromatic amines and benzene-1,2-diamines as nucleophiles, respectively. The mechanisms for the formation of these compounds were proposed.

•A p-TsOH-promoted dehydroxylated [3+2] cyclization of β-hydroxy ketones is established.•The mechanism involves dehydration/Michael addition/cyclization-dehydration.•This method provides a new entry for regioselective formation of 1,5,6,7-tetrahydro-4H-indol-4-ones.A new p-TsOH-promoted dehydroxylated [3+2] cyclization strategy has been established, allowing a flexible, practical and regiospecific approach to 23 examples of 1,5,6,7-tetrahydro-4H-indol-4-ones from low-cost and readily accessible β-hydroxy ketones and cyclic enaminones. Notably features of this work include broad functional group compatibility, mild reaction conditions and good reaction yields.Download high-res image (101KB)Download full-size image

AbstractNew silver-catalyzed tunable dimerization and trimerization reactions of β-alkynyl ketones have been established, enabling multiple C−C bond-forming events to selectively access skeletally diverse spiroisochromenes with generally good yields. The silver-enabled bicycloaddition of β-alkynyl ketones with water offered hydroxylated spiroisochromenes. Without water, spiroisochromenes with a methylene moiety were obtained through catalytic 6-endo-dig oxo-cyclization/[4+2] cycloaddition cascades by using pyridine as additive whereas employment of 1,1′-binaphthyl-2,2′-diyl hydrogen phosphate (BiNPO4H) as a Brønsted acid catalyst rendered the unprecedented dispiro trimerization products through double C(sp3)–H functionalization.

Silver-mediated C(sp3)–H functionalization and 6-endo-dig oxo-cyclization of conjugated β-alkynyl ketones have been established under oxidative conditions. The reaction leads to the concise formation of a wide range of isochromenes via C(sp3)–H bond-breaking and radical addition steps. Dual and monofunctional isochromene products were selectively controlled by using either electron-rich or electron-deficient radical sources.

Synergistic rhodium/copper catalysis enables new three-component coupling reactions of terminal alkynes and α-diazoketones and/or arylamines, allowing dediazotized carbene C–H insertion for the synthesis of functionalized 1,3-enynes and N-aryl enaminones with high stereoselectivity. The synthetic utility of these transformations results in subsequent C–C or/and C–N bond-forming reactions to effectively build up functional molecules with potential significance.

A new copper-catalyzed sulfur-enabled dehydrobicyclization of 1,6-enynes using potassium sulfide as a sulfurating reagent has been established, providing a straightforward access toward arylated indeno[1,2-c]thiophenes with moderate to good yields. This sulfur incorporation pathway involves Michael addition, 5-exo-dig/5-endo-trig bicyclization and dehydrogenation sequence, resulting in continuous multiple bond-forming events including C–S and C–C bonds to rapidly construct functional organic molecules.

A new cascade bicyclization of o-alkynyl aldehydes with thiazolium salts is described, in which 25 examples of densely functionalized indeno[2,1-b]pyrroles are achieved in a functional-group-compatible manner. Thiazole carbenes generated in situ from thiazolium salts play dual roles as reaction partners and as NHC catalysts. The synthetic utility of these bicyclization reactions results in subsequent C–C bond-forming events to rapidly build up molecular complexity.

The combination of Co(acac)2 and AgOTf enables the bimetallic relay catalysis reaction of 2-ethynylanilines and isocyanides, allowing easy and low-cost access to new densely functionalized pyrrolo[2,3-b]indoles. The reaction pathway involves a Co(acac)2-catalyzed double isocyanide insertion followed by a silver-enabled 1,3-dipolar cycloaddition. The synthetic utility of these bicycloaddition reactions results in subsequent C–C and C–N bond-forming events to rapidly build up molecular complexity.

A base-promoted [3 + 2] cycloaddition for the construction of multi-functionalized imidazo[1,2-a]indole derivatives with good yields has been accomplished. This transformation provides an easy and facile protocol for the formation of diverse imidazo[1,2-a]indoles of chemical and biomedical importance using preformed 3-sulfonyl-2-sulfonyldiazenyl-1H-indoles and readily available but-2-ynedioates under mild conditions.

A new TBHP/TBAI-mediated reaction of propargyl alcohols with sulfonyl hydrazides in the presence of HOAc has been established, in which a wide variety of allenyl sulfones were obtained in moderate to excellent yields. Mechanistic studies indicate that this transformation involves HOAc-promoted sulfonohydrazide intermediate formation, sequential C–O, C–N, and N–S bond cleavage, and C–S bond formation. Significantly, this sulfonohylation proceeds in a radical process and shows highly functional group compatibility and excellent regioselectivity, with a short reaction time and inexpensive reagents.

A palladium-catalyzed isocyanide insertion-cyclization using low-cost and readily accessible 2-haloanilines, 2-iodophenylethanones, and isocyanides for efficient synthesis of 3-iminoindol-2-amine and cyclic enaminone derivatives has been developed. The method features low-cost and readily accessible starting materials, reliable scalability, and bond-forming efficiency as well as simple one-pot operation, which makes this strategy highly attractive. A reasonable mechanism for forming 3-iminoindol-2-amine involved double isocyanide insertion/cyclization process is proposed.

Base-promoted transannulation of heterocyclic enamines and 2,3-epoxypropan-1-ones has been successfully achieved, providing a new access to structurally diverse fused pyridines and pyrroles with excellent regio- and stereoselectivity. Treatment with N-aryl 4-aminofuran-2(5H)-ones and 2,3-epoxypropan-1-ones under microwave heating resulted in functional furo[3,2-b]pyridines in good yields. The N-aryl 4-aminopyrrol-2(5H)-ones bearing an electron-withdrawing group engaged in the reaction afforded pyrrolo[3,2-b]pyridines, whereas their counterparts with an electron-neutral or an electron-donating group underwent a different reaction pathway to form pyrrolo[3,2-b]pyrroles through C–C bond cleavage.

A new three-component bicyclization for the efficient synthesis of a fused pyrano[2,3-b]pyridine library has been developed. The syntheses were achieved by reacting diverse C,O-containing nucleophiles, aldehydes, and 2-aminoprop-1-ene-1,1,3-tricarbonitrile under microwave irradiation, providing 50 examples of chemically and biomedically significant pyrano[2,3-b]pyridine analogues with the concomitant formation of two new rings and four σ bonds. This procedure features short reaction times, low-cost, and easily available starting materials, reliable scalability and mild reaction conditions, as well as operational simplicity.Keywords: bis-pyrans; microwave irradiation; pyrano[2,3-b]pyridines; three-component bicyclization

A novel I2-mediated benzannulation of 1,7-diyne-involved 1,4-oxo-migration was established, providing a range of unexpected 1-aroyl-2-naphthaldehydes with a 1,4-dicarbonyl unit. The resulting 1-aroyl-2-naphthaldehydes were successfully applied in the synthesis of benzo[e]isoindol-3-ones and benzo[e]benzo[4,5]imidazo[2,1-a]isoindoles using aromatic amines and benzene-1,2-diamines as nucleophiles, respectively. The mechanisms for the formation of these compounds were proposed.

The combination of Co(acac)2 and AgOTf enables the bimetallic relay catalysis reaction of 2-ethynylanilines and isocyanides, allowing easy and low-cost access to new densely functionalized pyrrolo[2,3-b]indoles. The reaction pathway involves a Co(acac)2-catalyzed double isocyanide insertion followed by a silver-enabled 1,3-dipolar cycloaddition. The synthetic utility of these bicycloaddition reactions results in subsequent C–C and C–N bond-forming events to rapidly build up molecular complexity.

A new cascade bicyclization of o-alkynyl aldehydes with thiazolium salts is described, in which 25 examples of densely functionalized indeno[2,1-b]pyrroles are achieved in a functional-group-compatible manner. Thiazole carbenes generated in situ from thiazolium salts play dual roles as reaction partners and as NHC catalysts. The synthetic utility of these bicyclization reactions results in subsequent C–C bond-forming events to rapidly build up molecular complexity.