Mild Metal-free Conditions Research Articles

Metal-free synthesis of 2-difluoromethylated quinolines via DBU-promoted cascade michael addition / cyclization of methyl 4,4-difluorobut-2-ynoate with 2-aminobenzonitriles

A facile synthesis of 2-difluoromethylated quinolines via DBU-promoted cascade Michael addition/cyclization between functionalized 2-aminobenzonitriles and methyl 4,4-difluorobut-2-ynoate has been developed. Various highly functionalized quinolines were assembled in moderate to good yields under mild metal-free reaction conditions.

2-(5-Arylterphenyl-4-yl)quinolines from 2-methylquinoline and 1-(het)aryl-3-phenylprop-2-yn-1-ones in just a one step: A miracle of molecular interplay

2-Methylquinoline reacts with 1-(het)aryl-3-phenylprop-2-yn-1-ones under mild transition metal-free conditions (55–60 °C, 20 mol% KOH, H2O, MeCN) to afford 2-{5’-(het)aryl[1,1’ : 3’,1”]terphenyl-4’-yl}quinolines in up to 35% yield. The reaction likely proceeds via the intermediate 1,3-dipole followed by the double nucleophilic vinylation of the methyl group with two molecules of ynone and subsequent elimination of (het)arenecarboxylic acid.

Direct oxidative C-H alkynylation of N-carbamoyl tetrahydroisoquinolines and dihydroisoquinolines.

An efficient oxidative C-H alkynylation of N-carbamoyl tetrahydroisoquinolines mediated by a TEMPO oxoammonium salt has been established. A variety of electronically varied N-carbamoyl tetrahydroisoquinolines reacted with a range of alkynyl potassium trifluoroborates smoothly under mild metal-free conditions. Dihydroisoquinolines were also suitable components for the reaction. The synthetic applicability of the method for facile access to structurally diverse bioactive molecules was further demonstrated.

Stereoselective Vinylation under Mild Metal-Free Conditions to Synthesize N-Vinylazoles

Stereoselective Vinylation under Mild Metal-Free Conditions to Synthesize <i>N</i>-Vinylazoles

Highly crystalline poly(heptazine imides) by mechanochemical synthesis for photooxidation of various organic substrates using an intriguing electron acceptor – Elemental sulfur

Low-defect potassium poly(heptazine imide) (PHIK-BM) was engineered for application in photocatalytic oxidation of organic substrates. Mechanochemical pretreatment of a mixture of 5-aminotetrazole in LiCl/KCl eutectics using high-energy ball milling afforded a highly homogeneous mixture that, upon sequential thermolysis at 600°C, gave nanosized particles of PHIK–BM. The photocatalytic activity of the free-standing PHIK–BM plates was assessed in the oxidation of benzyl alcohol to benzaldehyde under visible light irradiation using elemental sulfur as an electron acceptor. Both quantitative conversion (>99%) of benzyl alcohol and selectivity (>98%) with respect to benzaldehyde were achieved. The developed method was extended to aliphatic alcohol oxidation coupled with multicomponent Hantzsch 1,4-dihydropyridine synthesis. These 1,4-dihydropyridines were also photocatalytically oxidized by PHIK–BM to the corresponding substituted pyridines, with very good yields and under mild metal-free conditions.

Regio- and Stereoselective Oxysulfonylation of Allenes.

A highly regio- and stereoselective oxysulfonylation of allenes was developed that provided direct access to 2-sulfonyl allylic alcohols in good yields. By means of dioxygen activation, selective difunctionlization of allenes could be successfully achieved under mild metal-free conditions. Preliminary mechanistic investigation disclosed that this transformation probably goes through a radical process.

DBU-mediated metal-free oxidative cyanation of α-amino carbonyl compounds: using molecular oxygen as the oxidant.

A novel DBU-mediated oxidative cyanation of α-amino carbonyl compounds by using air as the sole oxidant was developed under mild metal-free conditions for the first time. The reaction involves a tandem oxidation/Strecker reaction/oxidation process and provides a new and efficient method for the construction of α-iminonitriles in good to high yields in a single step.

Easy and mild fluoride-mediated direct mono- and dialkoxylation of perylenediimides

The reaction of perylenediimides with alcohols in the presence of fluoride anions yields 1-alkoxy- or 1,6(7)-dialkoxyperylenediimides under very mild metal-free conditions. The reaction can also be applied to bay- and ortho-brominated perylenediimides.

Metal-free direct 1,6- and 1,2-difunctionalization triggered by radical trifluoromethylation of alkenes.

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.

ChemInform Abstract: Metal‐Free Oxidative Olefination of Primary Amines with Benzylic C—H Bonds Through Direct Deamination and C—H Bond Activation.

An oxidative olefination reaction between aliphatic primary amines and benzylic sp3 C–H bonds has been achieved using N-bromosuccinimide as catalyst and tert-butyl hydroperoxide as oxidant. The olefination proceeds under mild metal-free conditions through direct deamination and benzylic C–H bond activation, and provides easy access to biologically active 2-styrylquinolines with (E)-configuration.

Base-promoted oxidative C-H functionalization of α-amino carbonyl compounds under mild metal-free conditions: using molecular oxygen as the oxidant.

A base-mediated aerobic oxidation of the C-H bond adjacent to the N-atom of a secondary amine to form an imine intermediate under mild metal-free basic conditions has been developed. Accordingly, this new strategy has been successfully applied to the synthesis of various di-, tri-, and tetra-substituted α-aminocyclopentenones through a tandem aerobic oxidative [4 + 1] carbocyclization reaction of N-aryl α'-amino-α,β-unsaturated ketones as C4 1,4-dielectrophiles with active methylenes, including ethyl isocyanoacetate, nitroalkanes, and ethyl cyanoacetate, as C1 components.

Solvent-controlled bifurcated cascade process for the selective preparation of dihydrocarbazoles or dihydropyridoindoles.

A solvent-controlled cascade process has been identified for the dual purpose of the preparation of either dihydrocarbazoles or dihydropyridoindoles from identical N-aryl-α,β-unsaturated nitrones and electron-deficient allene starting materials. These reactions proceed smoothly under mild metal-free conditions affording a range of two types of skeletally distinct indole-based heterocycles in high yield and diastereoselectivity. These transformations demonstrate the use of a bifurcated cascade process that hinges on the ring-opening event of a benzazepine intermediate for the synthesis of skeletally diverse heterocyclic products and rapid access to biologically-significant, indole-based structures.

Metal-free regioselective hydrobromination of alkynes through C[sbnd]H/C[sbnd]Br activation

A metal-free regioselective hydrobromination of alkynes has been developed to provide the Markovnikov-type vinyl bromides in good yields using dibromomethane/N,N-dimethylaniline as in-situ ‘HBr’ source. This protocol also represents an elegant example of the activation of sp2 CH and CBr bonds in one pot, in which ‘HBr’ is generated and transferred under mild metal-free conditions. D-incorporated experiments were employed to investigate the reaction mechanism and a plausible reaction path was proposed.

ChemInform Abstract: Bicyclization of Diazomethanes: A Synthetic Strategy for Fused Pyrazoles.

On the terminal diazo nitrogen atom, two CN bonds are formed in the bicyclization reaction of the readily available acyclic substrates with diazomethanes as 1,3-dipoles. The tandem 1,3-dipolar cycloaddition/intramolecular aza-addition/oxidative aromatization reaction can tolerate a variety of functional groups and proceeds under mild metal-free conditions to give substituted analogues of withasomnine alkaloids in good to high yields in a single step.

ChemInform Abstract: Metal‐Free Phosphorylations of 1,3,4‐Oxadiazoles and Related Heterocycles.

Abstract2‐Substituted 1,3,4‐oxadiazoles are phosphorylated at C‐5.

Metal-Free Phosphorylations of 1,3,4-Oxadiazoles and Related Heterocycles

1,3,4-Oxadiazoles have been phosphorylated at C5 in yields of >90% under mild metal-free reactions conditions using triethylamine as base. Other azoles undergo analogous phosphorylations albeit in lower yields.

Diversity-Oriented Synthesis Based on the DPPP-Catalyzed Mixed Double-Michael Reactions of Electron-Deficient Acetylenes and β-Amino Alcohols

In this study, we prepared oxizolidines through 1,3-bis(diphenylphosphino)-propane (DPPP)–catalyzed mixed double-Michael reactions of β-amino alcohols with electron-deficient acetylenes. These reactions are very suitable for the diversity-oriented parallel syntheses of oxizolidines because: (i) they are performed under mild metal-free conditions and (ii) the products are isolated without complicated work-up. To demonstrate the applicability of mixed double-Michael reactions for the preparation of five-membered-ring heterocycles, we prepared 60 distinct oxazolidines from five β-amino alcohols and 12 electron-deficient acetylenes. We synthesized 36 of these 60 oxazolidines in enantiomerically pure form from proteinogenic amino acid–derived β-amino alcohols.

Mild and selective boronic acid catalyzed 1,3-transposition of allylic alcohols and Meyer–Schuster rearrangement of propargylic alcohols

Boronic acid catalysis (BAC) was applied to the 1,3-transposition of allylic alcohols and the related Meyer–Schuster rearrangement of propargylic alcohols using highly electron deficient polyfluoroarylboronic acids as catalysts under mild metal-free conditions. A wide range of synthetically useful products are formed in E : Z selectivities superior to that of metal-catalyzed methods. A mechanism is proposed involving partial or full ionization into an allylic (or propargylic) carbocation, and additional possibilities for multicatalytic tandem reactions are exemplified.

Three‐Component Reactions of Isochromenylium Tetrafluoroborates via Non‐Classical [4+2]‐Intermediates: Mild One‐Step Metal‐Free Synthesis of Functionalized Dihydronaphthalenes and Tetrahydronaphthalenes

Two novel types of elegant three-component reactions of stable isochromenylium tetrafluoroborates (ICTBs) have been developed under mild metal-free conditions in this work. Mechanistically, these reactions are commonly initiated by a [4+2]-cycloaddition between the non-classical isochromenylium diene and the aldehyde-enol, and terminated by the following addition of weak nucleophiles, including nitriles or the second equivalent of aldehydes, in a one-pot fashion. The developed methodologies exhibit excellent chemoselectivity, regioselectivity, and diastereoselectivity, and provide a new convenient access to functionalized dihydronaphthalenes and tetrahydronaphthalenes.

Diphosphine-catalyzed mixed double-Michael reaction: a unified synthesis of indolines, dihydropyrrolopyridines, benzimidazolines, tetrahydroquinolines, tetrahydroisoquinolines, dihydrobenzo-1,4-oxazines, and dihydrobenzo-3,1-oxazines.

Seven different types of benzannulated N-heterocycles-indolines, dihydropyrrolopyridines, benzimidazolines, dihydrobenzo-3,1-oxazines, benzomorpholines, tetrahydroquinolines, and tetrahydroisoquinolines-can be obtained from simple dinucleophiles and electron-deficient acetylenes in one synthetic step. This powerful methodology was made possible through the use of diphenylphosphinopropane (DPPP) as the catalyst, with acetic acid and sodium acetate used as additives in some cases. The benzannulated N-heterocycles were isolated in excellent yields under mild metal-free conditions; they were purified without the need for aqueous workups.