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A palladium-catalyzed dearomatizing [2+2+1] spiroannulation of indoles with two molecular internal alkynes is developed in the presence of Cu(OAc)

Ferrocenes with planar chirality have emerged as an important class of scaffolds for ligands in asymmetric catalysis; however, ferrocene molecules with polychiral structures have not been well explored. Herein, both axially and planar chiral ferrocenes were synthesized via palladium/chiral norbornene cooperative catalysis and axial-to-planar diastereoinduction. In this work, chiral norbornene was used to stereoselectively control the aromatic axial chirality, and further selectivity induced C(sp

We described a novel palladium-catalyzed C-H glycosylation of indole or tryptophan for a one-pot stereoselective synthesis of 2,3-diglycosylindoles and tryptophan-C-glycosides. In this strategy, the use of air and base-free and ligand-free conditions provided a highly efficient route to construct C-glycosides. The method can be applied to a wide range of cost-effective and convenient glycosyl chloride donors. Mechanistic studies indicated that the indole 2,3-diglycosylation sequence was C3 and then C2.

We describe a new strategy for aminoarylation of alkenes by copper-catalyzed smiles rearrangement using

The direct Pd-catalyzed β-C-H arylation of aldehydes and ketones was developed by using 2-amino-N,N'-diisopropylsuccinamide as a novel transient directing group (TDG). The TDG showed good versatility in functionalizing unactivated β-C-H bonds of aldehydes and ketones. It was effective not only for aliphatic aldehydes and ketones but also for aromatic aldehydes and ketones. Besides, it was applicable to o-methylbenzaldehydes.

Herein, we describe the copper-catalyzed arylalkylation of activated alkenes via hydrogen-atom transfer and aryl migration strategy. The reaction was carried out through a radical-mediated continuous migration pathway using

We have described a copper-catalyzed radical 1,2-carbotrifluoromethylselenolation of alkenes using the readily available alkyl halides and (Me4N)SeCF3 salt. Critical to the success is the use of a proline-based N,N,P-ligand to enhance the reducing capability of copper for easy conversion of diverse alkyl halides to the corresponding radicals via a single-electron transfer process. The reaction features a broad substrate scope, including various mono-, di-, and trisubstituted alkenes with many functional groups.

A copper-catalyzed highly

A novel photocatalytic decarboxylative [2 + 2 + m] cyclization of 1,7-enynes with alkyl N-hydroxyphthalimide (NHP) esters, using tricyclohexylphosphine and potassium iodide as redox catalysts, is reported for the construction of functional polycyclic compounds. This protocol tolerates primary, secondary, and tertiary alkyl NHP esters through a single reaction via decarbonylation, radical addition, C-H functionalization, and cyclization under mild conditions.

A general and practical cross-dehydrogenative coupling protocol between readily available trisubstituted α,β-dehydro α-amino carboxylic esters and H-phosphites is described. This C(sp2)–H phosphory...

Herein, we have developed two types of photoredox-catalyzed cascade reactions using diaryliodonium salts for the concise synthesis of norascyronone A and β-eudesmol. A rationally designed photoredox-catalyzed arylation/cyclization/Friedel-Crafts cascade reaction of enone was exploited to generate the norascyronone polycyclic skeleton. A visible-light-induced radical cyclization/acyloxy-migration reaction was explored to forge the decalin skeleton of eudesmol, and mechanistic studies indicated the reaction was initiated by one-electron oxidation of the enol ester.

A novel photocatalytic decarboxylative [2 + 2 +

A general and practical cross-dehydrogenative coupling protocol between readily available trisubstituted α,β-dehydro α-amino carboxylic esters and H-phosphites is described. This C(sp

A diphenyl-diselenide-mediated Claisen-type rearrangement/cyclization of propargylic aryl ethers under metal-free conditions is developed, affording various naphthofuran-2-carboxaldehydes in moderate to excellent yield. The broad substrate scope and excellent functional group compatibility suggest that it can be a straightforward and powerful method to access naphthofuran-2-carboxaldehydes in a highly regioselective manner. Moreover, this reaction can be scaled up to the gram scale.

Cascade radical cyclization of alkynyl ketones with various carbon- and heteroatom-centered radical precursors via a sequential radical addition/1,5-H radical shift/5-exo-trig/radical cyclization process was realized for the first time. This method provides a strategically novel and step-economical protocol for diversity-oriented synthesis of a wide range of carbocyclic and heterocyclic 6(5)-6-5 fused ring systems with three contiguous stereocenters, including a quaternary carbon in high yields with excellent chemo- and diastereoselectivity.

An unprecedented Lewis acid catalyzed, protection-free, and high-efficiency synthesis of valuable 3,4-dihydro-2H-2,4-methanochromans via cycloaddition of propargylic alkynols with 2-vinylphenol is described. This cycloaddition protocol, which tolerates a wide variety of functional groups, provides practical, versatile, and atom-economical access to a new class of appealing bridged-ring products in satisfactory yields. Compared with the reported reaction conditions for bridged-ring skeletons synthesis, the present reaction conditions are neutral, mild, and without any additives.

A new method for the AgSCF3-mediated radical cascade difunctionalizing trifluoromethythiolation of alkynes with dearomatization is developed. This protocol provides a novel route to SCF3-substituted spirocyclic compounds via the formation of one C-SCF3 bond, one C-C bond, and one C-O double bond in a single step.

Two classes of azido-modified pyrimidine nucleosides were synthesized as potential radiosensitizers; one class is 5-azidomethyl-2′-deoxyuridine (AmdU) and cytidine (AmdC), while the second class is 5-(1-azidovinyl)-2′-deoxyuridine (AvdU) and cytidine (AvdC). The addition of radiation-produced electrons to C5-azido nucleosides leads to the formation of π-aminyl radicals followed by facile conversion to σ-iminyl radicals either via a bimolecular reaction involving intermediate α-azidoalkyl radicals in AmdU/AmdC or by tautomerization in AvdU/ AvdC. AmdU demonstrates effective radiosensitization in EMT6 tumor cells.

The synthsis of fluorinated isoxazolidines in bicyclic settings has been realized via Ru(II)-catalyzed C–H activation of aryl nitrones with perfluoroalkyl-substituted olefins as the coupling partner. The reaction proceeded via initial chelation-assisted C(aryl)–H allylation followed by regio- and diastereoselective intramolecular dipolar addition between the nitrone directing group and the olefin unit.

A palladium-catalyzed aryldifluoroalkylation of alkynes with ethyl difluoroiodoacetate and arylboronic acids as reaction partners is described. The alkyne difunctionalization process provides various aryldifluoroalkylated products in one pot under mild reaction conditions. A wide range of alkynes and diverse arylboronic acids are compatible with these reaction conditions. High reaction efficiency and broad substrate scope are the notable features of this transformation. Preliminary mechanistic investigations indicate that a difluoroalkyl radical addition pathway is involved in this transformation.

A metal-free direct remote C-H functionalization triggered by radical trifluoromethylation of alkenes was explored, realizing highly selective 1,6-difunctionalization of alkenes toward valuable trifluoromethyl α-hydroxycarbonyl compounds. Furthermore, a metal-free direct intermolecular regioselective 1,2-oxytrifluoromethylation of alkenes is also disclosed. With Togni's reagent as both the CF3 source and oxidant, the reaction exhibits a broad substrate scope with excellent functionality tolerance under mild metal-free conditions, thus showing great potential for synthetic utility.

A metal-free catalytic strategy for the facile synthesis of biologically relevant molecular architectures indolizines and imidazopyridines has been developed. The process is promoted by amine and N-heterocyclic carbene (NHC) relay catalysis via Michael addition-[3 + 2] fusion of simple azaarenes and α,β-unsaturated aldehydes. The preparative power is demonstrated in the synthesis of anxiolytic drug saripidem via two simple one-pot operations with overall 45% yield.

A cascade β-C–H bond trifluoromethylation/C(sp3)–F bond activation/hydrolysis reaction of enamides with Togni’s reagent has been disclosed. This formal C–H bond carbonylation reaction utilizes the CF3 group as a CO surrogate to provide an efficient approach to 1,3-oxazin-6-ones in satisfactory yields. Furthermore, CF3-containing 1,3-oxazin-6-ones could also be accessed using this method by using alkenyl N-ethylamides involving the functionalization of one Csp2–H, one Csp3–H, one Csp2–H, and three Csp3–F bonds. The broad substrate scope of this method enables access to synthetically or pharmaceutically important compounds, which are difficult to access by known methods.

A novel iron-catalyzed aerobic oxidative reaction to synthesize disubstituted isoxazoles from homopropargylic alcohol, t-BuONO, and H2O is developed. The method provides mild conditions to afford a variety of useful substituted heterocycles in an efficient and regioselective manner. The mechanism has been studied and proposed, which indicates that the transformation can be realized through construction of a C═N bond and C═O bond, C-H oxidation, and then cyclization. Moreover, this method can be enlarged to gram scale.

A silver-promoted oxidative cyclization of 1,6-enynes with disubstituted phosphine oxides is developed for the synthesis of fluorene derivatives. The reaction proceeds with high regioselectivity by constructing one C-P bond and two C-C bonds in one step. Moreover, reduction of the pentavalent phosphine enlarges the application scope of the product.

The first example of catalytic B–H activation of azaborines leading to a new family of stilbene derivatives through dehydrogenative borylation is reported. Ten 1,2-azaborine-based BN isosteres of stilbenes have been synthesized using this method, including a BN isostere of a biologically active stilbene. It is demonstrated that BN/CC isosterism in the context of stilbenes can lead to significant changes in the observed photophysical properties such as higher quantum yield and a larger Stokes shift. Direct comparative analysis of BN stilbene 3g and its carbonaceous counterpart 6g is consistent with a stronger charge-transfer character of the excited state exhibited by 3g in which the 1,2-azaborine heterocycle serves as a better electron donor than the corresponding arene.

An organocatalytic asymmetric trifluoromethylthiolation reaction via in situ generation of active electrophilic trifluoromethylthio species involving trichloroisocyanuric acid and AgSCF3 as a practical and easily handled electrophilic SCF3 source for CSP(3)-SCF3 bond formation was developed. Reactions with this one-pot version strategy occurred in good yields and excellent stereoselectivities to access enantiopure oxindoles bearing a SCF3-substituted quaternary chiral center. The straightforward process described here makes use of simple starting materials and proceeds under mild conditions, which will be useful in medicinal chemistry and diversity-oriented syntheses.

A novel domino copper-catalyzed trifluoromethylated Meyer-Schuster rearrangement reaction with Togni's reagent was developed, leading to α-trifluormethyl (CF3) enone products with moderate to good yields. Furthermore, α-CF3 enones can be transformed toward important trifluoromethyl heterocyclic motifs in a one-pot version.

A catalytic radical protocol for 1,2-cyanofunctionalization of unactivated alkenes involving remote cyano migration triggered by addition of diverse carbon- and heteroatom-centered radicals to alkenes has been developed. This powerful strategy provides a diverse platform for the collection of a variety of synthetically important β-functionalized alkyl nitriles bearing densely functionalized carbonyl, cyano, and other various functional groups within the same molecules. The substrates TMS (trimethylsilyl)-protected alkenyl cyanohydrins are straightforwardly accessible via simple cyanosilylation of the corresponding ketones.

The first example of a metal-free direct carbotrifluoromethylation of alkenes using inexpensive TMSCF3 as the CF3 source is described. The methodology not only exhibits high chemoselectivity for this transformation but also expands the substrate scope that is difficult to access by known transition-metal-catalyzed methods.

The two-component, three-molecule reactions between 2,3-dihydroinden-1-ones and aryl chlorides were achieved in the presence of an NHC-Pd(II)-Im complex. Under the optimal conditions, all reactions performed well to give the corresponding products in moderate to high yields.

Cephalosporolide B (Ces-B) was efficiently synthesized and exploited for the first time as a versatile biomimetic synthetic precursor for the chemical syntheses of not only cephalosporolides C, G, and (4-OMe-) G via a challenging diastereoselective oxa-Michael addition but also the structurally unprecedented cephalosporolides E and F via a novel biomimetic ring-contraction rearrangement. These findings provide the first direct chemical evidence that Ces-B may be the true biosynthetic precursor of cephalosporolides.

A novel, four-component synthetic strategy to synthesize a series of β-difluoroalkyl unsaturated esters/amides with high regioslectivity is described. This Pd-catalyzed difluoroalkylation and carbonylation reaction can be carried out with simple starting materials. Through this protocol, two new C–C bonds (including one C–CF2 bond) and one C–O(N) bond are constructed simultaneously in a single step. The synthetic utility of this reaction system has been certified by the applicability to a wide scope of alkynes and nucleophiles. Preliminary mechanistic studies suggest that the difluoroalkyl radical pathway is involved in this reaction.

An efficient and selective gold-catalyzed cascade reaction for the synthesis of oxanorbornenes and naphthalene derivatives from easily prepared hydroxy enynes has been developed. Divergent products could be obtained from the same substrates by different gold catalytic systems.

Diiodinated carbocycles and oxygen heterocycles can be readily synthesized by electrophilic carbocyclization of aryl propargylic alcohols in moderate to good yields under mild conditions. The resulting diiodide can be further exploited by subsequent oxidizing and coupling reactions. Both the iodine anion and cation generated from I(2) are used effectively. The presence of a trace amount of water is essential for this electrophilic cyclization.

A novel method for the selective synthesis of (Z)-1,5-dien-2-yl esters has been developed though Pt(II)-catalyzed tandem 1,2-acyl and 1,2-hydride migration, along with an allyl migration reaction of propargylic carboxylates with electronically unbiased internal alkynes. The unusual selectivity of 1,2-acyloxy migration was realized.

[reaction: see text] Indene or naphthalene derivatives are readily prepared in moderate to excellent yields with high regio- and stereoselectivity under very mild reaction conditions by the reaction of acetylenic malonates and ketones with I2, ICl, or NIS. The resulting iodides can be further elaborated using palladium-catalyzed coupling reactions.

An entirely metal-free catalyst system consisting of an easily prepared recyclable new TEMPO derived sulfonic salt catalyst, and mineral acids (NaNO2 and HCl) has been developed for selective aerobic oxidation of structurally diverse benzylic sp(3) C-H bonds of ethers and alkylarenes. The mild reaction conditions allow for the generation of synthetically and biologically valued isochromanones and xanthones from readily accessible alkyl aromatic precursors in good yields.

A novel and convenient Pd-catalyzed radical cascade iododifluoromethylation/cyclization of 1,6-enynes with ethyl difluoroiodoacetate is demonstrated. The proposed transformation presents high stereoselectivity under mild and facile reaction conditions, thereby allowing an efficient access to a variety of iodine-containing difluoromethylated pyrrolidines. A possible radical pathway for the transformation is proposed on the basis of the results of control experiments and relevant literature reviews.

A AgSCF3-mediated radical cascade cyclization/trifluoromethylthiolation of 1,6-enynes triggered by a C-C triple bond is developed. This protocol also provides another opportunity to construct a valuable trifluoromethylthio-substituted polycyclic fluorene system through the formations of one C-SCF3 bond and two C-C bonds in a single step.

Palladium-catalyzed direct C–H arylations of 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) with 3,4-ethylenedioxythiophene (EDOT) derivatives at relatively low temperature (60 °C) provide moderate to good yields (47%–72%) of products having potential applications in fluorescent bioimaging and organic optoelectronics.

A strategy for the synthesis of iodocarbazoles through a tandem iodocyclization with migration and aromatization is presented. This sequential cascade process is concisely conducted at room temperature and in a short time. Moreover, the obtained halides can be further applied to palladium-catalyzed coupling reactions, which act as the important intermediates for building other valuable compounds.