InI3‐ or ZnI2‐Catalyzed Reaction of Hydroxylated 1,5‐Allenynes with Thiols: A New Access to 3,5‐Disubstituted Toluene Derivatives

Transition‐metal‐activated alkynes or allenes can accept nucleophilic attack and undergo direct addition of the nucleophiles to the unsaturated bonds or trigger subsequent rearrangement reactions. This chemistry has witnessed increasing development in recent years. In this report, we have focused on the metal‐catalyzed reactions of a variety of substituted propargyl allenic alcohols and thiophenols using indium(III) and zinc(II) catalysts, which can activate both the alcohol and alkyne. In this reaction, thio groups play the role of a nucleophile and trigger subsequent rearrangements to give benzene derivatives. The products can be further transformed into various 1,3,5‐trisubstituted aromatic compounds by nickel‐catalyzed coupling reactions through the cleavage of the C? S bonds.     

Copper‐Catalyzed Cyclization/aza‐Claisen Rearrangement Cascade Initiated by Ketenimine Formation: An Efficient Stereocontrolled Synthesis of α‐Allyl Cyclic Amidines

An efficient and convenient synthesis of α‐allyl cyclic amidines has been achieved by applying a novel cascade reaction. Copper(I)‐mediated in situ N‐sulfonyl ketenimine formation from the reaction of a terminal alkyne with sulfonyl azide is followed by an intramolecular nucleophilic attack on the central carbon atom by an allylic tertiary amine, and then an aza‐Claisen rearrangement takes place through a chair transition state to furnish the titled amidines with complete stereocontrol.     

Synthesis of N‐Arylated 1,2‐Dihydroheteroaromatics Through the Three‐Component Reaction of Arynes with N‐Heteroaromatics and Terminal Alkynes or Ketones

The reaction of benzynes with N‐heteroaromatics including quinolines, isoquinolines, and pyridines and various terminal alkynes or ketones with an α‐hydrogen in the presence of KF and 18‐crown‐6 in THF at room temperature for 8 h gave various N‐arylated 1,2‐dihydroheteroaromatics in good to moderate yields. Some of these product structures are found in various naturally occurring and biologically active heterocyclic compounds. The reaction involves an unusual multiple construction of new C? C, C? N, and C? H bonds and the cleavage of a C? H bond in one pot. It is likely that the three‐component coupling proceeds through the nucleophilic addition of quinoline to benzyne, which generates a zwitterionic species. The latter then attracts a proton from terminal alkyne (or ketone) to generate an N‐arylated quinolinium cation and an acetylide anion. Further reaction of these two ions provides the final substituted 1,2‐dihydroquinolines. In the reaction, the terminal alkyne acts first as a proton donor and then as a nucleophile. The application of a three‐component coupling reaction product, 1,2‐dihydro‐2‐pyridinyl alkyne in a stereospecific [4+2] Diels–Alder cycloaddition reaction with N‐phenyl maleimide to give an isoquinuclidine derivative, an important core present in various natural products, is demonstrated.     

A Facile synthesis of n,n′‐oligomethylenebis(4,5‐dihydrofuran‐3‐carboxamide)s using manganese(III)‐based radical cyclization of n,n′‐oligomethylenebis(3‐oxobutanamide)s with 1,1‐diarylethenes

The reaction of N,N′‐oligomethylenebis(3‐oxobutanamide)s with 1,1‐diarylethenes in the presence of manganese(III) acetate in acetic acid at 100° produced N N′‐oligomethylenebis(2‐methyl‐5,5‐diaryl‐4,5‐dihydrofuran‐3‐carboxamide)s. Similarly, the reaction of 3‐oxobutanamidoethyl 3‐oxobutanoate or N,N′‐(3,6‐dioxaoctamethylene)bis(3‐oxobutanamide) with 1,1‐diphenylethene gave (2‐methyl‐5,5‐diphenyl‐4,5‐dihydrofuran‐3‐amido)ethyl 2‐methyl‐5,5‐diphenyl‐4,5‐dihydrofuran‐3‐carboxylate or N,N′‐(3,6‐dioxa‐octamethylene)bis(2‐methyl‐5,5‐diphenyl‐4,5‐dihydrofuran‐3‐carboxamide) in moderate yields.     

A Convenient and Efficient Approach for the Synthesis of New 2‐N‐substituted 2,5‐dihydrofuran‐3‐carboxamides

In order to obtain potent biological active compounds, a convenient and efficient method for the synthesis of compounds comprising 2‐imino‐2,5‐dihydrofuran, aromatic, sulfamoyl, and heterocyclic fragments has been presented. This environmentally friendly method was based on the reaction of 2‐imino‐2,5‐dihydrofuran‐3‐carboxamides with analgesic and sulfanilamide drugs and 4‐aminoantipyrine in glacial acetic acid and afforded high yields of the products.     

Brønsted Acid‐Catalyzed Cascade Reactions Involving 1,2‐Indole Migration

A cascade reaction of indoles with propargylic diols involving an unprecedented metal‐free 1,2‐indole migration onto an alkyne was carried out. DFT calculations support a mechanism consisting of a concerted nucleophilic attack of the indole nucleus with loss of water, followed by the 1,2‐migration and subsequent Nazarov cyclization. This Brønsted acid‐catalyzed protocol affords indole‐functionalized benzofulvene derivatives in high yields.     

Theoretical study on the mechanism of reaction between 3‐hydroxy‐3‐methyl‐2‐butanone and malononitrile catalyzed by magnesium ethoxide

The mechanism of reaction between 3‐hydroxy‐3‐methyl‐2‐butanone and malononitrile for the synthesis of 2‐dicyanomethylene‐4,5,5‐trimethyl‐2,5‐dihydrofuran‐3‐carbonitrile catalyzed by magnesium ethoxide was investigated by density functional theory (DFT). The geometries and the frequencies of reactants, intermediates, transition states, and products were calculated at the B3LYP/6–31G(d) level. The vibration analysis and the IRC analysis demonstrated the authenticity of transition states, and the reaction processes were confirmed by the changes of charge density at bond‐forming critical point. The results indicated that magnesium ethoxide is an effective catalyst in the synthesis of 2‐dicyanomethylene‐4,5,5‐trimethyl‐2,5‐dihydrofuran‐3‐carbonitrile from malononitrile and 3‐hydroxy‐3‐methyl‐2‐butanone. The activation energy of reaction with magnesium ethoxide decreased by 102.37 kJ mol^?1 compared with that of the reaction without it. The mechanism of reaction with catalyst magnesium ethoxide differs from that of reaction without it. © 2008 Wiley Periodicals, Inc. Int J Chem Kinet 41: 227–235, 2009     

1,3-Dipolar Addition of Methyl α-Diazoacetoacetate to Enamines： A New Synthetic Route to 5-Amino-4,5-dihydrofurans

The reaction of methyl α-diazoacetoacetate with enamines catalyzed by dirhodium and copper complexes underwent formal 1,3-dipolar addition to give 5-amino-4,5-dihydrofurans in moderate yields. The reaction was suggested to proceed via a nucleophilic addition of enamines to rnetal-carbenes and a subsequent intramolecular cyclization of the resulting zwitterionic intermediates.     

Gold(I)‐Catalyzed Cascade Cyclization Reactions of Allenynes for the Synthesis of Fused Cyclopropanes and Acenaphthenes

A gold‐catalyzed reaction of phenylene‐tethered allenynes with benzofurans gave 1‐(naphth‐1‐yl)cyclopropa[b]benzofuran derivatives, whereas the reaction of 1‐allenyl‐2‐ethynyl‐3‐methylbenzene derivatives in the absence of benzofurans gave acenaphthenes in good yields. These results can be rationalized by nucleophilic attack of the alkyne moiety on an activated allene to form a vinyl cation intermediate.     

Copper‐Catalyzed Amine–Alkyne–Alkyne Addition Reaction: An Efficient Method For the Synthesis of γ,δ‐Alkynyl‐β‐amino Acid Derivatives

A simple and efficient method for the synthesis of γ,δ‐alkynyl‐β‐amino acid derivatives by a copper‐catalyzed three‐component amine–alkyne–alkyne addition reaction was developed. Various γ,δ‐alkynyl‐β‐amino acid derivatives were synthesized in moderate to good yields in one step. With chiral prolinol derivatives employed as the amine component, excellent diastereoselectivities (up to >99:1 diastereomeric ratio (dr)) were obtained. The scope of the reaction and further transformations of the resulting amino acid derivatives, such as deprotection and cyclization are also described.     

Synthesis of 4,5‐Dihydrofuran‐3‐carbonitrile Derivatives with Electron‐Rich Alkenes in the Presence of Manganese(III) Acetate

Radical cyclization reactions mediated by manganese(III) acetate were carried out with ν‐excessive alkenes ( 2a‐d ) and 3‐oxopropanenitriles ( 1a‐f ) resulting in the formation of 3‐cyano‐4,5‐dihydrofuran derivatives in poor to high yields. A mechanism was proposed for the cyclization reaction. The significance of the study is the formation of the 3‐cyano‐4,5‐dihydrofuran derivatives resembling terfuran, 2‐(2‐thienyl)furan and 2‐(2‐benzofuryl)furyl compounds having the fluorescent properties due to a conjugated ν‐electron system particularly containing the cyano moeity.     

Atom transfer cyclization catalyzed by InCl3 via halogen activation

[reaction: see text] Indium trichloride was found to be an efficient catalyst for the cyclization of allylic halides and alkynes with atom transfer in methylene chloride. Mechanistic evidence supports a cationic reaction pathway with Lewis acid activation of the allylic halogen. Concomitant nucleophilic attack by the alkyne and trapping with halide led to atom transfer cyclization products. Depending on alkyne substitution, a bromine atom was transferred from the substrate or a chlorine atom was transferred from the solvent.     

Preparation of β-hydroxysulfides from 1,2,3-thiadiazoles. Comparison of the effect of phenylmagnesium bromide on α-Thio- and α-selenoketones

Base decomposition of 4-substituted-phenyl-1,2,3-thiadiazoles at 78° resulted in 2-(4-substituted-phenyl)-ethynylthiolate anions which were immediately reacted with α-bromoketones to give a series of α-(2-[4-substituted-phenyf]ethynyl) thioketones. Unlike the selenophilic reaction of the Grignard reagents with α-selenoketones, the carbonyl group was the site of nucleophilic attack and the reaction of the α-thioketones with phenylmagnesium bromide gave the corresponding β-hydroxysulfides. The difference in mode of action toward the Grignard reagents was attributed to the difference in the bond strengths between carbon and the heteroatoms.     

Catalytic Enantioselective Conjugate Alkynylation of α,β‐Unsaturated 1,1,1‐Trifluoromethyl Ketones with Terminal Alkynes

The first catalytic enantioselective conjugate alkynylation of α,β‐unsaturated 1,1,1‐trifluoromethyl ketones has been carried out. Terminal alkynes and 1,3‐diynes were treated with trifluoromethyl ketones in the presence of a low catalytic load of a Cu^I‐MeOBIPHEP complex (2.5 mol %) and triethylamine (10 mol %) to give the corresponding trifluoromethyl ketones bearing a propargylic stereogenic center at the β position with good yields and excellent enantiomeric excesses in most of the cases. No 1,2‐addition products were formed under the reaction conditions. The procedure showed broad substrate scope for alkyne, diyne, and enone. A rationale for the observed stereochemistry has been provided. Finally, the potential application of the reaction products in the synthesis of chiral tetrahydrofurans bearing a trifluoromethylated quaternary stereocenter has been devised.     

Asymmetric [3+2] Annulation Approach to 3‐Pyrrolines: Concise Total Syntheses of (−)‐Supinidine, (−)‐Isoretronecanol,and (+)‐Elacomine

An asymmetric [3+2] annulation reaction to form 3‐pyrroline products is reported. Upon treatment with lithium diisopropylamide, readily available ethyl 4‐bromocrotonate is deprotonated and trapped with Ellman imines selectively at the α‐position to yield enantiopure 3‐pyrroline products. This new method is compatible with aryl, alkyl, and vinyl imines. The efficacy of the method is showcased by short asymmetric total syntheses of (−)‐supinidine, (−)‐isoretronecanol, and (+)‐elacomine. This novel annulation approach also works for an aldehyde, thus providing access to a 2,5‐dihydrofuran product in a single step from simple precursors. By modifying the structure of the carbanion nucleophile, an asymmetric vinylogous aza‐Darzens reaction can be realized.     

Asymmetric [3+2] Annulation Approach to 3‐Pyrrolines: Concise Total Syntheses of (−)‐Supinidine, (−)‐Isoretronecanol,and (+)‐Elacomine

An asymmetric [3+2] annulation reaction to form 3‐pyrroline products is reported. Upon treatment with lithium diisopropylamide, readily available ethyl 4‐bromocrotonate is deprotonated and trapped with Ellman imines selectively at the α‐position to yield enantiopure 3‐pyrroline products. This new method is compatible with aryl, alkyl, and vinyl imines. The efficacy of the method is showcased by short asymmetric total syntheses of (?)‐supinidine, (?)‐isoretronecanol, and (+)‐elacomine. This novel annulation approach also works for an aldehyde, thus providing access to a 2,5‐dihydrofuran product in a single step from simple precursors. By modifying the structure of the carbanion nucleophile, an asymmetric vinylogous aza‐Darzens reaction can be realized.     

α,α‐Dibromotoluene as a monomer for poly (substituted methylene) synthesis: Magnesium‐mediated polycondensation of α,α‐dibromotoluene and magnesium/copper‐mediated copolycondensation of α,α‐dibromotoluene with 1,6‐dibromohexane

α,α‐Dibromotoluene 1 was found to be polymerized by the reaction with excess Mg to give poly(phenylmethylene)s 2 , whose main chains were partially dehydrogenated to carbon–carbon double bonds (C?C). The C?Cs in 2 can be brominated by treatment with Br₂. The polymerization mechanism was presumed to include the formation of Grignard reagents of various species with benzylic C? Br bonds and the nucleophilic attacks of the Grignard reagents to various compounds with benzylic C? Br bonds. Copolymerization of 1 with dichlorodimethylsilane successfully proceeded. Mg/Cu‐mediated copolycondensation of 1 with 1,6‐dibromohexane proceeded to give polymers that have similar compositions to those of random copolymers of ethylene and styrene. © 2006Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 5661–5671, 2006     

Nucleophilic Cyclopropanation Reaction with Bis(iodozincio)methane by 1,4‐Addition to α,β‐Unsaturated Carbonyl Compounds

Treatment of α,β‐unsaturated ketones with an electrophilic site at the γ‐position in the presence of trimethylsilyl cyanide with bis(iodozincio)methane afforded the (Z)‐silyl enol ether of the β‐cyclopropyl substituted ketone in good yields. The reaction proceeds by 1,4‐addition to form an enolate, and its sequential intramolecular nucleophilic attack to an adjacent electrophilic site. The reaction of γ‐ethoxycarbonyl‐α,β‐unsaturated ketone and bis(iodozincio)methane in the presence of trimethylsilyl cyanide afforded 1‐ethoxy‐1‐trimethylsiloxycyclopropane derivatives, which can be regarded as the homoenolate equivalent. Additionally, reaction of the obtained homoenolate equivalents with imines give 1‐(E)‐alkenyl‐2‐(1‐aminoalkyl)alkanols diastereoselectively.     

A 1‐Aza‐2‐silacyclobut‐3‐ene and an Alkyne from [Li{Si(SiMe3)3}(thf)3] and the Isocyanide 2,6‐Me2C6H3NC

The novel zwitterionic heterocycle 1 was unexpectedly obtained from the reaction between [Li(SiR₃)(thf)₃] and ArNC. Upon heating 1 underwent an interesting ring opening to give the alkyne 2 . Hence the C≡C bond effectively arises from the C−C coupling of two ArNC moieties. R=SiMe₃, Ar=2,6‐Me₂C₆H₃, tmeda=N,N,N′,N′‐tetramethylethylenediamine.     

A new ruthenium-catalyzed cyclopropanation of alkenes using propargylic acetates as a precursor of vinylcarbenoids

[RuCl₂(CO)₃]₂ catalyzes intermolecular cyclopropanation of various alkenes with propargylic acetates to give vinylcycloropanes in good yields. The key intermediate of this reaction is a vinylcarbene complex generated by nucleophilic attack of the carbonyl oxygen of the acetate to an internal carbon of alkyne activated by the ruthenium complex.