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A NiH-catalyzed intermolecular dearomative hydroalkylation of indoles has been developed, which assembles an array of structurally diverse C2-alkylated indolines with moderate to excellent yields. This protocol exhibits good functional group tolerance, allowing for late-stage functionalization of complex drug molecules.

Highly enantioselective palladium-catalyzed dearomative reductive Heck and domino Heck–Suzuki reactions of 2-CF3-indoles have been developed towards the synthesis of indolines bearing trifluoromethyl quaternary stereocenters.

Carbene insertion reactions initiated with diazo compounds have been widely used to develop unnatural enzymatic reactions. However, the alternative functionalization of diazo compounds in enzymatic processes has been unexploited. Herein, we developed a photoenzymatic strategy for the radical-mediated stereoselective hydroalkylation with diazo compounds. This method generates carbon-centered radicals via an ene-reductase catalyzed photoinduced electron transfer process from diazo compounds, enabling the synthesis of γ-chiral carbonyl compounds in good yields and stereoselectivities. This work further expands the reaction patterns in photo-biocatalysis and offers a new approach to solving the selectivity challenges of radical-mediated reactions.

Highly enantioselective and diastereoselective 1,2-diarylation and 1,2-arylalkynylation of trisubstituted alkenes are reported via the palladium-catalyzed Heck/Suzuki or Heck/Sonogashira domino seq...

The extensively developed ene-type enantioselective cycloisomerization of classical 1,6- and 1,7-enynes provides an efficient approach to chiral cyclic 1,4-dienes. In contrast, catalytic asymmetric heteroarenyne (heteroarene-alkyne) cycloisomerization involving dearomative transformation of endocyclic aromatic C=C bonds remains unknown. Herein, we communicate a PdH-catalyzed enantioselective heteroarenyne cycloisomerization reaction of alkyne-tethered indole substrates (formal 1,5- and 1,6-enynes). Based on this strategy, a variety of structurally diverse chiral spiro- and fused- indoline derivatives bearing quaternary stereocenters and exocyclic C=C bonds are afforded in moderate to excellent yields and excellent enantioselectivities (up to 98% ee). The classical ene-type enantioselective 1,5-enyne cycloisomerization of N -vinylpropiolamides is also developed to afford chiral 2-pyrrolones in good to excellent ee values.

Dearomative functionalization reactions represent an important strategy for the synthesis of valuable three-dimensional molecules from simple planar aromatics. Naphthalene is a challenging arene towards transition-metal-catalyzed dearomative difunctionalization reactions. Reported herein is an application of naphthalene as a masked conjugated diene in a palladium-catalyzed dearomative 1,4-diarylation or 1,4-vinylarylation reaction via tandem Heck/Suzuki sequence. Three types of 1,4-dihydronaphthalene-based spirocyclic compounds are achieved in excellent regio- and diastereoselectivities. Key to this transformation is the inhibition of a few competitive side reactions, including intramolecular naphthalenyl C-H arylation, intermolecular Suzuki cross-coupling, dearomative 1,2-difunctionalization, and dearomative reductive-Heck reaction. Density functional theory (DFT) calculations imply that the facile exergonic dearomative insertion of a naphthalene double bond disrupts the sequence of direct Suzuki coupling, leading to the tandem Heck/Suzuki coupling reaction. The observed regioselectivity towards 1,4-difunctionalization is due to the steric repulsions between the introduced aryl group and the spiro-scaffold in 1,2-difunctionalization., Naphthalene is a challenging arene towards transition-metal-catalyzed dearomative difunctionalization. Here, the authors show that naphthalene may act as a masked conjugated diene in palladium-catalyzed dearomative 1,4-diarylation or 1,4-vinylarylation via a tandem Heck/Suzuki sequence.

Olefin functionalization represents one of the most important synthetic transformations in organic synthesis. Over the past decades, palladium-catalyzed enantioselective Heck reactions, and Heck/anion-capture domino sequences through olefin carbopalladation followed by termination of the resulting alkyl-Pd species have been extensively developed. Extension of the coupling partners from classical olefins to other π-components would enable further advances and open new space in this field. Aromatics are important and easily available bulk chemicals. Dearomative transformation of endocyclic aromatic π-bonds via the Heck reaction pathway provides an efficient and straightforward route to structurally diverse alicyclic compounds. Nevertheless, major challenges for this transformation include aromaticity breaking and reactivity and selectivity issues.Recently, we have engaged in developing catalytic enantioselective dearomative Heck reactions and related domino reactions. A range of heteroarenes and naphthalenes have been employed as novel π-coupling partners in these reactions. Through dearomative migratory insertion of endocyclic aromatic C-C π-bonds followed by interception of the transient alkyl-Pd species, enantioselective Heck reactions, reductive Heck reactions, Heck/anion-capture difunctionalization reactions, and heteroarenyne cycloisomerization reactions have been established. Relying on β-H elimination of the alkyl-Pd intermediate, we realized enantioselective dearomative Heck reactions with a range of aromatic partners, including heterocyclic indoles, pyrroles, furans, benzofurans, and more challenging carbocyclic naphthalenes. In order to avoid the utilization of organohalide electrophiles, heteroarenyne cycloisomerization reaction was developed by merging intermolecular alkyne hydropalladation with intramolecular dearomative Heck reaction. Cycloisomerization of alkyne-tethered indoles delivered chiral indolines in excellent enantioselectivities with 100% atom economy. On the other hand, Heck/anion-capture domino sequences were established through nucleophilic trapping of the alkyl-Pd intermediate. When HCO

A Pd-catalyzed dearomative arylvinylation reaction of indoles with N-arylsulfonylhydrazones as coupling partners is developed, which proceeds via a domino sequence involving dearomative carbopallad...

A palladium-catalyzed domino Larock annulation/dearomative Heck reaction is developed, which delivers a range of tetracyclic indoline derivatives in moderate to excellent yields through a Larock annulation of N-bromobenzoyl o-iodoanilines with alkynes and a subsequent intramolecular dearomative Heck reaction. This protocol provides a straightforward route to structurally diverse indolines from readily available starting materials by forming two new rings and three chemical bonds in a single step.

A palladium-catalyzed dearomative arylphosphorylation reaction of indoles involving C–C/C–P bond formation is developed. Through the intramolecular dearomative carbopalladation of indoles followed by an intermolecular benzyl–Pd termination with dialkylphosphite, a range of unique indolines bearing vicinal tetrasubstituted and phosphate-containing trisubstituted stereocenters are obtained in good yields. Synthetic transformations of the product show practical utilities of the reaction.

A palladium-catalyzed dearomative arylborylation of indoles is reported, which provides straightforward access to structurally diverse indolines bearing vicinal tetrasubstituted and borylated trisubstituted stereocenters in moderate to good yields with excellent diastereoselectivities. By using a BINOL-based chiral phosphoramidite ligand and an sp2–sp3 mixed-boron reagent, an enantioselective dearomative arylborylation was achieved and chiral boron-containing products were accessed in up to 94% ee. Synthetic tranformations of the resulting organoborons were conducted to afford a number of unique indoline derivatives.

Lilium longiflorum is a wild Lilium, and its flowering transition requires a long period of cold exposure to meet the demand of vernalization. The responses of different sized bulbs to cold exposure and photoperiod are different, and the floral transition pathways of small and large bulbs are different. In this study, small and large bulbs were placed in cold storage for different weeks and then cultured at a constant ambient temperature of 25 °C under long day (LD) and short day (SD) conditions. Then, the flowering characteristics and expression patterns of key genes related to the vernalization and photoperiod pathways in different groups were calculated and analyzed. The results showed that the floral transition of Lilium longiflorum was influenced by both vernalization and photoperiod, that vernalization and LD conditions can significantly improve the flowering rate of Lilium longiflorum, and that the time from planting to visible flowering buds’ appearance was decreased. The flowering time and rate of large bulbs were greatly influenced by cold exposure, and the vernalization pathway acted more actively at the floral transition stage. The floral transition of small bulbs was affected more by the photoperiod pathway. Moreover, it was speculated that cold exposure may promote greater sensitivity of the small bulbs to LD conditions. In addition, the expression of LlVRN1, LlFKF1, LlGI, LlCO5, LlCO7, LlCO16, LlFT1, LlFT3 and LlSOC1 was high during the process of floral transition, and LlCO13, LlCO14 and LlCO15 were highly expressed in the vegetative stage. The expression of LlCO13 and LlCO14 was different under different lighting conditions, and the flowering induction function of LlCO9 and LlFT3 was related to vernalization. Moreover, LlFKF1, LlGI, LlCO5, LlCO16, LlSOC1 and LlFT2 were involved in the entire growth process of plants, while LlCO6, LlCO16 and LlFT1 are involved in the differentiation and formation of small bulblets of plants after the inflorescence stage, and this process is also closely related to LD conditions. This study has great significance for understanding the molecular mechanisms of the vernalization and photoperiod flowering pathways of Lilium longiflorum.

Arylboration and arylsilylation reactions of N-(2-iodoaryl)acrylamides with bis(pinacolato)-diboron (B2pin2) or PhMe2Si-Bpin are developed by using simple CuOAc as the sole catalyst. A range of bor...

A highly enantioselective intramolecular dearomatizing olefination of indoles has been developed through a Pd-catalyzed reductive Heck reaction. This protocol provides efficient access to optically active tetracyclic indolines bearing C2-alkenylated quaternary stereocenters in good yields with excellent enantioselectivities.

The photoperiodic flowering pathway is essential for plant reproduction. As blue and ultraviolet-A light receptors, cryptochromes play an important role in the photoperiodic regulation of flowering. Lilium × formolongi is an important cut flower that flowers within a year after seed propagation. Floral induction is highly sensitive to photoperiod. In this study, we isolated the CRYPTOCHROME2 gene (LfCRY2) from L. × formolongi. The predicted LfCRY2 protein was highly homologous to other CRY2 proteins. The transcription of LfCRY2 was induced by blue light. LfCRY2 exhibits its highest diurnal expression during the floral induction stage under both long-day and short-day photoperiods. Overexpression of LfCRY2 in Arabidopsis thaliana promoted flowering under long days but not short days, and inhibited hypocotyl elongation under blue light. Furthermore, LfCRY2 was located in the nucleus and could interact with L. × formolongi CONSTANS-like 9 (LfCOL9) and A. thaliana CRY-interacting basic-helix-loop-helix 1 (AtCIB1) in both yeast and onion cells, which supports the hypothesis that LfCRY2 hastens the floral transition via the CIB1-CO pathway in a manner similar to AtCRY2. These results provide evidence that LfCRY2 plays a vital role in promoting flowering under long days in L. × formolongi.

Palladium-catalyzed intramolecular dearomative reductive-Heck reaction of C2-substituted indoles is developed, which provides access to structurally diverse 3,2'-spiropyrrolidine oxindoles. By changing the hydride source to AcONa base, direct C3-arylation products [2,3-b]quinolinones are achieved in good yields. The reaction of C2-substituted benzofuran is also realized, delivering the desired spiro-product.

An efficient palladium-catalyzed intramolecular deacetylative dearomatization reaction of 3-acetoxyindoles has been developed. A range of tetracyclic indolin-3-ones bearing C2-quaternary stereocenters are achieved in good yields, showing a wide substrate scope for this reaction. A preliminary enantioselective reaction is established to furnish the product in 63% ee by using (R,R,R)-phosphoramide-PE as a chiral ligand.

A highly enantioselective Friedel-Crafts alkylation of indoles with N-sulfonylaziridines as alkylating agents has been developed by utilizing the complex of Cu(CH3CN)4BF4/(S)-Segphos as a catalyst. A range of optically active tryptamine derivatives are obtained in good to excellent yields and enantioselectivities (up to >99% ee) via a kinetic resolution process.

A Friedel-Crafts alkylation reaction of styrenes with trifluoropyruvates has been developed, which delivered allylic alcohols in excellent yields (up to 98%) using the Ni(ClO4)2·6H2O/bipyridine complex as a catalyst. The asymmetric reaction was catalyzed by the chiral Cu(OTf)2/bisoxazoline complex to afford the corresponding chiral allylic alcohols bearing trifluoromethylated quaternary stereogenic centers in moderate enantioselectivities (up to 75% ee).

Two hydrophobic 3D cobalt-cluster based magnetic MOFs, [Co3(pimdc)2(H2O)6]·5H2O (1) and Co2(Hpimdc)2 (2) (H3pimdc = 2-propyl-imidazole-4,5-dicarboxylic acid), have been hydrothermally synthesized and magnetically characterized. Both of them exhibit a regular pcu net with hexagonal Co6 and zigzag Co4 clusters as 6-connected nodes, respectively. The magnetic studies indicate that 1 displays predominant antiferromagnetic interactions within the Co3(pimdc) triangle, while 2 shows spin-canting antiferromagnetic behaviour with larger canting angles. Furthermore, after heating under vacuum conditions, activated 1 exhibits an excellent catalytic selectivity in the allylic oxidation reaction of cyclohexene to form an α,β-unsaturated ketone, which indicates that the opened Co(II) sites play a significant role in the heterogeneous catalytic process.

An enantioselective hydrogenolysis of 3-aryl-3-hydroxyisoindolin-1-ones under H 2 has been developed by using Ir(I)/( R )-MeO-Biphep complex as a catalyst. Cyclic diaryl methylamides were obtained in moderate to excellent yields and up to 92% ee.

Enantioselective intramolecular dearomative Heck reactions have been developed by Pd-catalyzed cross-coupling of aryl halides or aryl triflates with the internal C═C bond of indoles, benzofurans, pyrroles, and furans. A variety of structurally unique spiroheterocycles and benzofused heterocycles having N/O-substituted quaternary carbon stereocenters, and exocyclic olefin moieties were afforded in moderate to excellent yields with good to excellent enantioselectivities, showing a broad scope of the present protocol. A series of new BINOL- and H8-BINOL-based phosphoramidite ligands were synthesized and proved to be efficient chiral ligands in the reactions of C2-tethered substrates to form spiroheterocycles. ( S)-SEGPHOS turned out to be a good ligand for the reaction delivering benzofused indolines and pyrrolines. Synthetic applications based on transformations of the exocyclic double bonds were realized without loss of enantiopurities, including hydrogenation, hydroborylation, and stereospecific ring-expanding rearrangement.

An enantioselective Friedel–Crafts alkylation of indoles with β,β-disubstituted nitroalkenes was developed by using a nickel(II) perchlorate–bisoxazoline complex as a catalyst. A range of nitroalkenes and indoles participated in this reaction, affording chiral indole compounds bearing all-carbon quaternary stereocenters in excellent yields and with moderate to good enantioselectivities (up to 80% ee).

Enantioselective addition of styrenes to cyclic N-sulfonyl α-ketiminoesters was developed using the complex of Ni(ClO4)2 with chiral phosphine complex as a catalyst. A range of chiral benzofused 5-membered sultams bearing alkenylated or allylated α-tetrasubstituted amino ester framework were afforded in excellent enantioselectivities (up to 99% ee) as potential biologically active compounds for drug research.

The enantioselective redox annulation of nitroalkynes with indoles is enabled by gold/chiral phosphoric acid dual catalysis. A range of indolin-3-one derivatives bearing quaternary stereocenters at the C2 position were afforded in good yields and excellent enantioselectivities (up to 96 % ee) from readily available starting materials.

A highly enantioselective intramolecular arylative dearomatization of indoles via palladium-catalyzed reductive Heck reactions was developed. The new strategy led to a series of optically active indolines bearing C2-quaternary stereocenters in modest to good yields with excellent enantioselectivities (up to 99% ee).

A series of metal–organic architectures (compounds 1–5) based on zinc salts and four 4′-substituted 4,2′:6′,4′′-tpys including two new ligands have been synthesized and structurally characterized. The ligands L1–L4 with various 4′-substituents on 4,2′:6′,4′′-tpy react with Zn(OAc)2·2H2O to yield assemblies 1–4 containing either 1-D polymeric chains (1–3) or a discrete dinuclear complex (4). X-ray structural analysis revealed that although similar 1-D polymeric chains were observed in both 1 and 3, the 3-D packing modes were essentially different. The chains in 1 were stacked to form a network structure with microporous channels that were not present in 3. In contrast, 4 was a discrete dinuclear complex containing a paddle-wheel {Zn2(μ-OAc)4} motif, although another minor component possibly coexists in the bulk sample as revealed by the PXRD studies. Crystals of 5 were prepared from the reaction between L4 and ZnI2 and its X-ray structure revealed a 1-D polymeric chain with a wave-like structure. Phase-pure compounds 1–3 and 5 were tested for the catalytic transesterification of phenyl acetate with alcohols, and the results indicated that 1 was the most active catalyst for this reaction, affording the new ester product in 95% yield at 50 °C under neat conditions, while other catalysts also catalysed the reaction with modest yields. Several different alcohols were examined as substrates for 1-catalysed transesterification and it was found that the size of substrates has important influence on the catalytic efficiency. In addition, amine additives were found to remarkably promote the catalytic efficiency of the less active catalyst 3. The structure–catalytic activity relationship was discussed in detail based on the catalytic data obtained.

Efficient and atom-economical access to indolizines has been developed by a Cu-catalyzed cyclization of 2-(2-enynyl)pyridines with various nucleophiles through simultaneous formation of a C–N bond and a remote carbon–nucleophile bond. 1,3-Dicarbonyl compounds, indoles, amides, alcohol, and even water, were used as nucleophiles in this reaction. Good to excellent yields of the corresponding indolizines were obtained under mild reaction conditions.

A novel method for the C-C bond cleavage of cyclopropanes was developed by gold-catalyzed cycloisomerization of 2-(1-alkynyl-cyclopropyl)pyridine with nucleophiles, which provides efficient access to structurally diverse indolizines under mild conditions. A series of N-, C- and O-based nucleophiles were involved in this reaction to afford the corresponding indolizines in modest to excellent yields.

Enantioselective alkynylation of cyclic N-sulfonyl α-ketiminoesters with terminal alkynes was developed by using an Ni(ClO4)2/(R)-DTBM-Segphos complex as a catalyst. A range of propargylic amides bearing quaternary stereocenters were afforded in excellent enantioselectivities (up to 97% ee). Theoretical studies revealed that this reaction proceeded via a Friedel-Crafts-type reaction pathway.

Palladium-catalyzed enantioselective dearomative arylalkynylation of N-substituted indoles, through a Heck/Sonogashira sequence, was established using a new BINOL-based phosphoramidite as the chiral ligand. A wide range of 2,3-disubstituted indolines, bearing vicinal quaternary and tertiary stereocenters, were efficiently constructed in one step with excellent enantioselectivities (up to 97 % ee) and diastereoselectivities (>20:1).

Numerous efficient synthetic methods for enantioselective indole functionalizations have emerged in recent years. This review summarizes the major achievements in the transition-metal-catalyzed enantioselective indole functionalization reactions since 2010 and focuses on C–C bond formation processes, including alkylations, arylations, cycloaddition reactions, and other reactions. It intends to give a compendious overview of the significant progress achieved in this area.

A nickel-catalyzed intramolecular addition of vinyl or aryl bromides to ketoamides has been developed. The reactions proceeded efficiently with Ni(bpy)Br 2 as a catalyst and zinc powder as reducing agent, affording 3-hydroxypyrrolidinones, 3-hydroxyoxindoles, and dihydroquinolinones as important heterocyclic compounds in good to excellent yields.

Construction of all-carbon quaternary stereocenter by asymmetric Friedel–Crafts alkylation reaction remains a significant challenge. By the introduction of CF3 group at the β-position of nitroalkene, a highly enantioselective Friedel–Crafts reaction of indoles with β-CF3-β-substituted nitroalkenes was achieved using Ni(ClO4)2-bisoxazoline complex as a catalyst, which afforded indole-bearing chiral compounds with trifluoromethylated all-carbon quaternary stereogenic centers in good yields and excellent enantio­selectivities.

Using a Ni(ClO4)2–bisoxazoline complex as a catalyst, Friedel–Crafts alkylations of 4,7-dihydroindoles with β-CF3-β-disubstituted nitroalkenes were carried out with high enantioselectivities (up to 91%) to give alkylated dihydroindoles bearing trifluoromethylated all-carbon quaternary stereocenters in good yields. The corresponding chiral C2 alkylated indoles were obtained with complete preservation of enantiomeric purity by oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ).

A highly enantioselective Friedel-Crafts alkylation reaction of indoles with β-CF(3)-β-disubstituted nitroalkenes was achieved using a Ni(ClO(4))(2)-bisoxazoline complex as a catalyst, which afforded indole-bearing chiral compounds with trifluoromethylated all-carbon quaternary stereocenters in good yields with excellent enantioselectivities (up to 97% ee). The transformation of one of the products into first a trifluoromethylated tryptamine and then a trifluoromethylated tetrahydro-β-carboline by sequential nitro reduction and Pictet-Spengler cyclization were realized with complete preservation of enantiopurity.

The scalable procedure provides tryptamine derivatives in high yields and with high enantioselectivities.

A palladium-catalyzed indole dearomative bisfunctionalization via a domino arylation/alkynylation sequence has been developed, which provides a reliable approach to a series of structurally diverse tetracyclic indolines bearing vicinal tertiary and quaternary stereocenters in moderate to good yields and excellent diastereoselectivities.

A highly enantioselective palladium/l-proline-catalyzed α-arylative desymmetrization of cyclohexanones was developed. The new strategy for α-arylation reaction led to a series of optically active morphan derivatives bearing α-carbonyl tertiary stereocenters in good yields with excellent enantioselectivities (up to 99% ee).

A Friedel-Crafts alkylation reaction of styrenes with trifluoropyruvates has been developed, which delivered allylic alcohols in excellent yields (up to 98%) using the Ni(ClO4)2·6H2O/bipyridine complex as a catalyst. The asymmetric reaction was catalyzed by the chiral Cu(OTf)2/bisoxazoline complex to afford the corresponding chiral allylic alcohols bearing trifluoromethylated quaternary stereogenic centers in moderate enantioselectivities (up to 75% ee).

An enantioselective Friedel–Crafts alkylation of indoles with β,β-disubstituted nitroalkenes was developed by using a nickel(II) perchlorate–bisoxazoline complex as a catalyst. A range of nitroalkenes and indoles participated in this reaction, affording chiral indole compounds bearing all-carbon quaternary stereocenters in excellent yields and with moderate to good enantioselectivities (up to 80% ee).

Highly enantioselective Friedel–Crafts C2-alkylation reactions of 3-substituted indoles with α,β-unsaturated esters and nitroalkenes were developed using chiral Lewis acids as catalysts, which afforded chiral indole derivatives bearing C2-benzylic stereogenic centers in good to excellent yields (up to 99%) and enantioselectivities (up to 96% ee).

The enantioselective redox annulation of nitroalkynes with indoles is enabled by gold/chiral phosphoric acid dual catalysis. A range of indolin-3-one derivatives bearing quaternary stereocenters at the C2 position were afforded in good yields and excellent enantioselectivities (up to 96 % ee) from readily available starting materials.

Very high asymmetric inductions result in the Pd-catalyzed intramolecular arylation of amides to give 3,3-disubstituted oxindoles when new in situ-generated chiral N-heterocyclic carbene (NHC*) ligands are employed. Structural studies show that conformational locking to minimize allylic strain is the key to understanding the function of these ligands. New applications of these ligands in the frontier area of asymmetric coupling reactions involving C(sp3)–H bonds are detailed. Highly enantioenriched fused indolines are accessible using either preformed- or in situ-generated Pd-NHC* catalysts. Remarkably, this occurs at high temperature (140–160 °C) via excellent asymmetric recognition of an enantiotopic C–H bond in an unactivated methylene unit.

Mesoporous MCM-41 silica functionalized with sulfonic acid groups (SO 3 H-MCM-41) was prepared through the condensation of MCM-41 with benzyl alcohol followed with sulfonation, which was characterized by XRD, FT-IR and nitrogen adsorption analyses. One-pot Fischer indole synthesis of tryptophols under the catalysis of SO 3 H-MCM-41 was reported with phenylhydrazine hydrochlorides and 2,3-dihydrofuran. The acidity and amount of sulfur loading were surveyed and also were the catalytic performance of SO 3 H-MCM-41. The results showed that higher amount of sulfur loading leads to higher acidity and consequently better yields of tryptophols. Moreover, SO 3 H-MCM-41 displayed good shape-selectivity in Fischer indole synthesis and inhibited the production of bulky byproduct polyindoles which were generally found in traditional acid catalysis. A series of tryptophols were synthesized with SO 3 H-MCM-41 in better yields than those of conventional methods reported.

An sp(2)/sp(3) get-together: A novel and efficient method can be used to synthesize 3,3-disubstitued oxindoles by the direct intramolecular oxidative coupling of an aryl C(sp(2))-H and a C(sp(3))-H center (see scheme; DMF = N,N-dimethylformamide).