Regioselective Synthesis of 3-Substituted Isocoumarin-1-imines via Palladium-Catalyzed Denitrogenative Transannulation of 1,2,3-Benzotriazin-4(3H)-ones and Terminal Alkynes.

A palladium-catalyzed denitrogenative transannulation strategy to access various 3-substituted isocoumarin-1-imine frameworks using 1,2,3-benzotriazin-4(3H)-ones and terminal alkynes is described. The reaction is highly regioselective and tolerates a wide range of functional groups. The reaction is believed to proceed via a five-membered palladacycle intermediate extruding environmentally benign molecular nitrogen as a by-product. The utility of this method was showcased through the one-pot synthesis of biologically relevant 3-substituted isocoumarin scaffolds.

Convenient Synthesis of Salicylanilide Sulfonates from 1,2,3-Benzotriazin-4(3H)-ones and Organosulfonic Acids via Denitrogenative Cross-Coupling.

An efficient and straightforward approach to synthesize salicylanilide aryl and alkyl sulfonates from 1,2,3-benzotriazin-4(3H)-ones and organosulfonic acids is described. This protocol is operationally simple and scalable, exhibits a broad substrate scope with high functional group tolerance, and affords the desired products in good to high yield. Application of the reaction is also demonstrated by converting the desired product to synthetically useful salicylamides in high yields.

Sustainable Bioengineering of Gold Structured Wide-Area Supported Catalysts for Hand-Recyclable Ultra-Efficient Heterogeneous Catalysis.

Metal nanoparticles grafted within inert and porous wide-area supports are emerging as recyclable, sustainable catalysts for modern industry applications. Here, we bioengineered gold nanoparticle-based supported catalysts by utilizing the innate metal binding and reductive potential of eggshell as a sustainable strategy. Variable hand-recyclable wide-area three-dimensional catalysts between ∼80 ± 7 and 0.5 ± 0.1 cm2 are generated simply by controlling the size of the support. The catalyst possessed high-temperature stability (300 °C) and compatibility toward polar and nonpolar solvents, electrolytes, acids, and bases facilitating ultra-efficient catalysis of accordingly suspended substrates. Validation was done by large-volume (2.8 liters) dye detoxification, gram-scale hydrogenation of nitroarene, and the synthesis of propargylamine. Moreover, persistent recyclability, monitoring of reaction kinetics, and product intermediates are possible due to physical retrievability and interchangeability of the catalyst. Finally, the bionature of the support permits ∼76.9 ± 8% recovery of noble gold simply by immersing in a royal solution. Our naturally created, low-cost, scalable, hand-recyclable, and resilient supported mega-catalyst dwarfs most challenges for large-scale metal-based heterogeneous catalysis.

Trifluoroacetic Acid-Mediated Denitrogenative ortho-Hydroxylation of 1,2,3-Benzotriazin-4(3H)-ones: A Metal-Free Approach.

An efficient trifluoroacetic acid-mediated denitrogenative hydroxylation of 1,2,3-benzotriazin-4(3H)-ones is described. This metal-free approach is compatible with a wide range of 1,2,3-benzotriazin-4(3H)-ones, affording ortho-hydroxylated benzamides in good to high yields with a short reaction time. The reaction is believed to proceed via a benzene diazonium intermediate. The synthetic utility of the reaction was successfully demonstrated by the preparation of an antimicrobial drug, Riparin C, and benzoxazine-2,4(3H)-diones in good yields.

Palladium/Copper-Catalyzed Denitrogenative Alkylidenation and ortho-Alkynylation Reaction of 1,2,3-Benzotriazin-4(3H)-ones.

An efficient palladium-catalyzed approach to access various functionalized (Z)-3-benzylidene-isoindoline-1-ones and (Z)-3-benzylidene(imino)isobenzofuranones via a denitrogenative tandem alkynylation/cyclization reaction of 1,2,3-benzotriazin-4(3H)-ones with aromatic terminal alkynes is described. Furthermore, a denitrogenative ortho-alkynylation reaction of 1,2,3-benzotriazinones with aliphatic terminal alkynes is also developed. The reaction proceeds through a five-membered azapalladacyclic intermediate with the extrusion of a nitrogen molecule. The significance of the reaction is also demonstrated by a one-pot synthesis of (Z)-3-benzylideneisobenzofuran-1(3H)-one derivatives in good to high yields.

Nickel-Catalyzed Denitrogenative Cross-Coupling Reaction of 1,2,3-Benzotriazin-4(3 H)-ones with Organoboronic Acids: An Easy Access to Ortho-Arylated and Alkenylated Benzamides.

A novel nickel-catalyzed approach to synthesize ortho-arylated and alkenylated benzamides in good to high yields via a denitrogenative cross-coupling reaction of 1,2,3-benzotriazin-4(3 H)-ones with organoboronic acids is described. The reaction proceeds through a five-membered azanickelacyclic intermediate with the extrusion of a nitrogen molecule. Moreover, the resulting ortho-arylated benzamides were successfully converted into synthetically useful substituted fluorenones and ortho-arylated benzylamine derivatives in high yields.

Ligand-Controlled Divergent C-H Functionalization of Aldehydes with Enynes by Cobalt Catalysts.

We describe a highly step and atom economical cobalt-catalyzed cyclization of 1,6-enynes with aldehydes to synthesize functionalized pyrrolidines and dihydrofurans with high chemo- and stereoselectivity. The catalytic reaction plausibly proceeds via the cobaltacycle intermediate generated from the reaction of enyne substrate with cobalt catalyst, followed by switchable C-H functionalization of weakly coordinating aldehydes depending on the electronic nature of the ligand.

Palladium(0)/NHC-Catalyzed Reductive Heck Reaction of Enones: A Detailed Mechanistic Study.

We have studied the mechanism of the palladium-catalyzed reductive Heck reaction of para-substituted enones with 4-iodoanisole by using N,N-diisopropylethylamine (DIPEA) as the reductant. Kinetic studies and in situ spectroscopic analysis have provided a detailed insight into the reaction. Progress kinetic analysis demonstrated that neither catalyst decomposition nor product inhibition occurred during the catalysis. The reaction is first order in the palladium and aryl iodide, and zero order in the activated alkene, N-heterocyclic carbene (NHC) ligand, and DIPEA. The experiments with deuterated solvent ([D7]DMF) and deuterated base ([D15]Et3N) supported the role of the amine as a reductant in the reaction. The palladium complex [Pd(0)(NHC)(1)] has been identified as the resting state. The kinetic experiments by stopped-flow UV/Vis also revealed that the presence of the second substrate, benzylideneacetone 1, slows down the oxidative addition of 4-iodoanisole through its competing coordination to the palladium center. The kinetic and mechanistic studies indicated that the oxidative addition of the aryl iodide is the rate-determining step. Various scenarios for the oxidative addition step have been analyzed by using DFT calculations (bp86/def2-TZVP) that supported the inhibiting effect of substrate 1 by formation of resting state [Pd(0)(NHC)(1)] species at the cost of further increase in the energy barrier of the oxidative addition step.

Cobalt-catalyzed hydroarylative cyclization of 1,6-enynes with aromatic ketones and esters via C-H activation.

A highly chemo- and stereoselective cobalt-catalyzed hydroarylative cyclization of 1,6-enynes with aromatic ketones and esters to synthesize functionalized pyrrolidines and dihydrofurans is described. A mechanism involving cobaltacycle triggered C-H activation of aromatic ketones and esters was proposed.

Alkene-assisted nickel-catalyzed regioselective 1,4-addition of organoboronic acid to dienones: a direct route to all-carbon quaternary centers.

A nickel-catalyzed highly regioselective 1,4-addition reaction of boronic acids to dienones to form products with an all-carbon quaternary center is described. The 3-alkenyl group of dienones is the key for the reaction to proceed smoothly. A mechanism involving the coordination of the dienyl group to the nickel center is proposed.

Nickel-catalyzed chemo- and stereoselective alkenylative cyclization of 1,6-enynes with alkenyl boronic acids.

Discover nickel! A nickel-catalyzed alkenylative cyclization of 1,6-enynes and alkenyl boronic acids affording substituted pyrrolidines and dihydrofurans is described (see scheme; cod = 1,5-cyclooctadiene, Ts = p-toluene sulfonate). The reaction is highly chemo- and stereoselective. A possible reaction mechanism involving a nickelacyclopentene intermediate is proposed.

Nickel-catalyzed regio- and diastereoselective intermolecular three-component coupling of oxabicyclic alkenes with alkynes and organoboronic acids.

Reaction of oxabicyclic alkenes with alkynes and organoboronic acids in the presence of Ni(cod)(2), P(t-Bu)(3), and CsF in a binary solvent toluene-methanol (1 : 3) at 75 to 85 °C provided exo-5,6-disubstituted 7-oxanorbornene derivatives in good to excellent yields.

Cobalt(II)-catalyzed 1,4-addition of organoboronic acids to activated alkenes: an application to highly cis-stereoselective synthesis of aminoindane carboxylic acid derivatives.

It all adds up: The 1,4-addition of organoboronic acids to activated alkenes catalyzed by [Co(dppe)Cl(2)] is described. A [3+2]-annulation reaction of ortho-iminoarylboronic acids with acrylates to give various aminoindane carboxylic acid derivatives with cis-stereoselectivity is also demonstrated (see scheme; dppe = 1,2-bis(diphenylphosphino)ethane).

Regio- and enantioselective cobalt-catalyzed reductive [3+2] cycloaddition reaction of alkynes with cyclic enones: a route to bicyclic tertiary alcohols.

Round and round: An unusual cobalt-catalyzed regio- and enantioselective reductive [3+2] cycloaddition of cyclic enones with alkynes affording bicyclic tertiary alcohols is described. A possible mechanism involving the formation of a cobaltacyclopentene intermediate is proposed.

Synthesis of trans-disubstituted alkenes by cobalt-catalyzed reductive coupling of terminal alkynes with activated alkenes.

A cobalt-catalyzed reductive coupling of terminal alkynes, RC≡CH, with activated alkenes, R'CH=CH(2), in the presence of zinc and water to give functionalized trans-disubstituted alkenes, RCH=CHCH(2)CH(2)R', is described. A variety of aromatic terminal alkynes underwent reductive coupling with activated alkenes including enones, acrylates, acrylonitrile, and vinyl sulfones in the presence of a CoCl(2)/P(OMe)(3)/Zn catalyst system to afford 1,2-trans-disubstituted alkenes with high regio- and stereoselectivity. Similarly, aliphatic terminal alkynes also efficiently participated in the coupling reaction with acrylates, enones, and vinyl sulfone, in the presence of the CoCl(2)/P(OPh)(3)/Zn system providing a mixture of 1,2-trans- and 1,1-disubstituted functionalized terminal alkene products in high yields. The scope of the reaction was also extended by the coupling of 1,3-enynes and acetylene gas with alkenes. Furthermore, a phosphine-free cobalt-catalyzed reductive coupling of terminal alkynes with enones, affording 1,2-trans-disubstituted alkenes as the major products in a high regioisomeric ratio, is demonstrated. In the reactions, less expensive and air-stable cobalt complexes, a mild reducing agent (Zn) and a simple hydrogen source (water) were used. A possible reaction mechanism involving a cobaltacyclopentene as the key intermediate is proposed.

Enantioselective synthesis of ß-substituted cyclic ketones via cobalt-catalyzed asymmetric reductive coupling of alkynes with alkenes.

A CoI(2)/(R)-BINAP, Zn, ZnI(2), H(2)O system efficiently catalyzes the intermolecular asymmetric reductive coupling of alkynes with cyclic enones to afford highly regio- and enantioselective ß-alkenyl cyclic ketones. A possible mechanism that involves the formation of a cobaltacyclopentene intermediate from the alkyne and cyclic enone is proposed.

Cobalt-catalyzed regio- and stereoselective intermolecular enyne coupling: an efficient route to 1,3-diene derivatives.

The reaction of alkynes with vinyl arenes or vinyl trimethyl silane in the presence of a cobalt(II) complex, Zn and ZnI(2) in CH(2)Cl(2) at rt to 50 degrees C provides 1,3-dienes in good to excellent yields.

Nickel-catalyzed borylative coupling of alkynes, enones, and bis(pinacolato)diboron as a route to substituted alkenyl boronates.

Three-component coupling reactions of an alkyne, an enone, and a diboron reagent provide access to highly substituted alkenyl boronates in good to excellent yields (see scheme). The coupling is highly regio- and stereoselective, and the products are amenable to further functional-group transformations. R(1),R(2) = H, alkyl, aryl, CO(2)Me; R(3) = alkyl, Ph; R(4),R(5) = H, alkyl.