A general and unprecedented gold-catalyzed tandem dual heterocyclization reaction of enynones with 1,3,5-triazines has been developed, which provides bicyclic fused furans in high to excellent yields under mild reaction conditions. In addition, mechanistic studies indicate that the reaction goes through a stepwise [3+2+2]-cycloaddition of furanyl gold intermediate, which is generated from gold-catalyzed cyclization of enynone, with two molecules of formaldimines derived in situ from 1,3,5-triazine, instead of formal [4+3]-cycloaddition.

A gold-catalyzed cyclization/carbonylation cascade reaction of 1,6-diynes is reported. The reaction goes through 6-exo-dig and 6-endo-dig cyclizations in sequence, followed by hydration to provide the β,γ-unsaturated ketones with moderate to high yields under mild reaction conditions. This is the first example of intercepting the postulated 1,3-oxazine vinylgold intermediate with another pendant alkyne, which not only verifies the proposed mechanism but also provides the ketone products with cyclized 1,2,3,6-tetrahydropyridine or 3,6-dihydro-2H-pyran frameworks from corresponding diynes.

•Thermally induced reaction of diazoamides with isatins.•Mild approach to the 3,3′-bioxindole derivatives.•Good to high yields with excellent diastereoselectivity.•gem-Difunctionalization of diazo compounds via a non-carbene process under catalyst-free conditions.An efficient and thermally induced reaction of diazoamide with isatin under mild reaction conditions is described, which provides a complementary approach to the 3,3′-bioxindole in high yields with excellent diastereoselectivity. In comparison to the metal-catalyzed versions, this is the only example under catalyst-free conditions via a non-carbene reaction pathway.Download high-res image (85KB)Download full-size image

A copper-catalyzed novel carbene/alkyne metathesis cascade reaction with alkyne-tethered diazo compounds is described. The whole transformation features a dual-functionalization of alkyne to install one C═N and one C═C bond on each carbon with azide and diazo groups, respectively, in one reaction, which represents a practical synthetic alternative to the multisubstituted 4-carboxyl quinoline derivatives and with most of them in high to excellent yields.Keywords: alkyne functionalization; azide; carbene/alkyne metathesis; cascade reaction; diazo compound; quinoline

Catalyst-dependent [4 + 2]-cycloaddition reactions of azoalkenes from α-halohydrazones with enol diazoacetates have been developed. A [4 + 2]-cycloaddition of enol diazoacetates with in situ formed azoalkenes produces tetrahydropyridazinyl-substituted diazoacetates promoted by only Cs2CO3. In contrast, donor–acceptor cyclopropenes, which are formed in situ from enol diazoacetates by Rh2(OAc)4-catalyzed dinitrogen extrusion, undergo [4 + 2]-cycloaddition with azoalkenes to yield bicyclo[4.1.0]tetrahydropyridazines. These stable cycloaddition products undergo subsequent one-step transformations to form 6-alkylidenetetrahydropyridazines and 4,5,6,7-tetrahydro-1,2-diazepine derivatives in good yields.

A general and unprecedented thermally induced formal [3 + 2] cycloaddition has been developed that provides a general access to fused lactam derivatives in high to excellent yields with broad substrate scope. In comparison with the reported metal-catalyzed carbene/alkynyl metathesis, this is the only example in this area under catalyst-free conditions with excellent selectivity. Mechanistic studies indicate that the 3H-pyrazole is the key intermediate in this cascade reaction, which is confirmed spectroscopically for the first time.

A synthetically useful transformation arises from NBS-mediated dinitrogen extrusion of N-aryl diazoacetamides under catalyst-free conditions, which gives 3-bromooxindoles in high to excellent yields with high selectivity via a non-carbene process.

An efficient transition-metal-free fluoroarylation reaction of N-aryl diazoacetamides with NFSI (N-fluorobenzenesulfonimide) is described. This reaction directly provides 3-fluorooxindole derivatives in yields of 67–93% with high selectivity via a carbene-free process under mild reaction conditions.

A general and transition-metal-free access to the fused polycyclic pyrazoles via an intramolecular 1,3-dipolar cycloaddition reaction of alkyne-tethered tosylhydrazones has been reported. The pure solid products could be obtained without column chromatography in high to excellent yields, and the obtained products are useful bioactive molecules or could be used as the key intermediate for synthesis of these compounds in one or two steps. Additionally, a [3+2]-cycloaddition followed by a direct H-shift aromatization reaction mechanism was proposed, which is different from the previously reported aryl or alkyl sequential [1,5]-sigmatropic rearrangement pathway.

β-Lactam derivatives are produced through intermediate donor–acceptor cyclopropene intermediates in high yield, exclusive cis-diastereoselectivity, and high enantiocontrol in a chiral dirhodium carboxylate catalyzed intramolecular C–H functionalization reaction of enoldiazoacetamides.

An example of a transition-metal-free, direct, and efficient acetamidosulphenylation reaction of alkenes using nitriles as the nucleophiles via a radical process is presented. This reaction shows a broad substrate scope and high regioselectivity and provides straightforward access to acetamidosulfide derivatives in moderate to high yields.

A one-pot cascade process of benzyl enoldiazoacatates, initiated by dirhodium(II)-catalyzed intramolecular cyclopropene formation, occurs via a subsequent Buchner reaction and Cope rearrangement to provide straightforward access to bicyclo[3.2.2]nonatriene derivatives in high yields and selectivities.

A new type of intramolecular carbene cascade reaction of alkynyl-tethered styryl diazoesters is presented, which is terminated with a formal [3 + 2] cycloaddition to give the bicyclic cyclopentadiene derivatives in high yields and selectivity. Additionally, it was found that the β-H shift is the dominating process in the case of alkyl alkyne-tethered substrates.

A Cu-catalyzed direct cyanation of terminal alkynes was reported with broad substrate generality in moderate to high yield, and AMBN (azobisisoamylonitrile)/AIBN (azobisisobutyronitrile) were used as less toxic and effective cyanating sources in open air. Interestingly, addition products were selectively achieved as the major product under the same conditions in argon.

A transition metal free oxidative C–H bond functionalization/esterification of α-alkoxy alkanes with acids is described in this report. This method is effectively mediated by NCS instead of traditional oxidants, like TBHP or its derivatives, and directly generates the esterification products in moderate to high yield under mild conditions. This tranformation constitutes a practical and general approach toward various α-acyloxy ethers with broad substrate generality; alkyl-, aryl-, alkenyl- and alkynyl-carboxylic acids are all well tolerated.

A direct and convenient CN bond formation reaction was reported, which was a de-tetra-hydrogenative cross-coupling (DTCC) reaction between N,N-dimethyl aniline and sulfamide under transition-metal-free conditions, and to give sulfonyl amidine derivatives in moderate to high yields.

β,γ-Unsaturated α-diazocarbonyl compounds possess two reactive sites for electrophilic addition – one at the diazo carbon and the other at the vinylogous γ-position. Controlled by catalyst, divergent transformations are achieved starting from the same starting materials, either by Lewis acid-catalyzed addition or by dirhodium-catalyzed metal carbene reactions. In select cases two catalysts working in combination or in sequence provide a relay for cascade transformations. In this review, we summarize advances in catalyst-dependent divergent transformations of β,γ-unsaturated α-diazocarbonyl compounds and highlight the potential of this exciting research area and the many challenges that remain.β,γ-Unsaturated α-diazocarbonyl compounds possess two reactive sites for electrophilic addition – one at the diazo carbon and the other at the vinylogous γ-position. Controlled by catalyst, divergent transformations are achieved starting from the same starting materials, either by Lewis acid-catalyzed addition or by dirhodium-catalyzed metal carbene reactions.

A chiral dirhodium(II) carboxylate complex catalyzed enantioselective cyclopropanation reaction of N-Boc diazooxindoles with olefins, including aryl, alkyl, cyclic, and disubstituted olefins, under mild conditions is described. This reaction provides complementary access to the corresponding chiral spirocyclopropyloxindole products in good to high yields with good to excellent enantioselectivities.

A novel cascade reaction of alkynyl-tethered α-iminodiazoacetates has been developed, which provides a general access to both multi-substituted and fused pyrroles in high yields with a broad substrate scope. The γ-imino carbene is proposed as the key intermediate in this divergent reaction and followed by unpresented transformations.

A transition metal free oxidative C–H bond functionalization/esterification of α-alkoxy alkanes with acids is described in this report. This method is effectively mediated by NCS instead of traditional oxidants, like TBHP or its derivatives, and directly generates the esterification products in moderate to high yield under mild conditions. This tranformation constitutes a practical and general approach toward various α-acyloxy ethers with broad substrate generality; alkyl-, aryl-, alkenyl- and alkynyl-carboxylic acids are all well tolerated.

A Cu-catalyzed direct cyanation of terminal alkynes was reported with broad substrate generality in moderate to high yield, and AMBN (azobisisoamylonitrile)/AIBN (azobisisobutyronitrile) were used as less toxic and effective cyanating sources in open air. Interestingly, addition products were selectively achieved as the major product under the same conditions in argon.

β-Lactam derivatives are produced through intermediate donor–acceptor cyclopropene intermediates in high yield, exclusive cis-diastereoselectivity, and high enantiocontrol in a chiral dirhodium carboxylate catalyzed intramolecular C–H functionalization reaction of enoldiazoacetamides.