A novel,one-step annulation process for the synthesis of ring-fused 2-cyclopentenones

The reaction of the dilithio derivative of dimethyl cis-4-cyclohexen-1,2-dicarboxylate with 3-substituted propiolic acid phenyl esters proceeds via an unusual mechanistic path to generate fused bicyclic 2-cyclopentenones in a single step.     

Synthesis of Silolide Dianions via Reduction of Dichlorosiloles: Important Role of the Solvent

The reduction of 1,1-dichloro-2,5-bistrimethylsilyl-3,4-diphenylsilole to silolide dianion by alkali metals was investigated. As previously demonstrated, the outcome of the reaction depends strongly on the applied alkali metal, solvent, reaction conditions, and substituent pattern. We showed that lithium is a powerful reducing agent in THF or DME solvents, the reaction is even faster than the same reaction with sodium. The X-ray structures of the corresponding dilithio and disodium silolide dianion were investigated, interestingly recrystallization of the dilithio salt results in a coordination polymer. In order to support the synthetic work DFT calculations were performed.     

Synthesis of secoisoquinoline alkaloids : Total synthesis of cryptopleurospermine

Cryptopleurospermine ( ), a 1,2-secobenzylisoquinoline alkaloid was synthesized from hydrastinine derivative and isovanillin 1,3-propylene dithioacetal . The formation of C-C bond between these two synthons involved addition of dilithio salt of dithian to aldehyde group in . Reduction and hydrolysis of the masking group in addition product furnished the synthesis.     

Diverse reactions of 1,4-dilithio-1,3-dienes with nitriles: facile access to tricyclic Delta1-bipyrrolines, multiply substituted pyridines, siloles, and (Z,Z)-dienylsilanes by tuning of substituents on the butadienyl skeleton

Addition cyclization of 1,2,3,4-tetrasubstituted 1,4-dilithio-1,3-dienes (Type I) with four equivalents of various aromatic nitriles in the presence of hexamethylphosphoramide (HMPA) gives exclusively fully substituted pyridines in moderate to good yields. Similarly, trisubstituted pyridines can be prepared by the reaction of 2,3-dialkyl- or diaryl-substituted 1,4-dilithio-1,3-dienes (Type II) with nitriles. However, five- or six-membered-ring fused 2,3-disubstituted 1,4-dilithio-1,3-dienes (Type III) reacted with various aromatic and aliphatic nitriles without alpha-hydrogen atoms to afford tricyclic Delta1-bipyrrolines in high yields. The reaction of six-membered-ring fused 2,3-disubstituted 1,4-dilithio-1,3-diene (Type III) with 2-cyanopyridine afforded the corresponding pyridine, and no tricyclic Delta1-bipyrroline was observed. Seven-membered-ring fused dilithiodienes reacted with PhCN or trimethylacetonitrile to afford the corresponding pyridines in good yield. When 1,2,3,4-tetrasubstituted dilithio reagents (Type I) were treated with Me3SiCN, a tandem silylation/intramolecular substitution process readily occurred to yield siloles, whereas the reaction of 2,3-disubstituted dilithio reagents (Types II and III) with Me3SiCN gave rise to (Z,Z)-dienylsilanes with high stereoselectivity. These results revealed that the formation of tricyclic Delta1-bipyrrolines, pyridines, siloles, and (Z,Z)-dienylsilanes are strongly dependent on the substitution patterns of the dilithio butadienes and the nature of the nitriles employed.     

A regiospecific synthesis of (±)-decarbomethoxyaklavinone

Condensation of the dilithio derivative of 3-methoxybenzanilide with the bicyclic ketoaldehyde $\text{12}$ leads to a convergent and 100% regiospecific synthesis of (±)-decarbomethoxyaklavinone ($\text{19}$).     

Magnesiacyclopentadienes as Alkaline‐Earth Metallacyclopentadienes: Facile Synthesis,Structural Characterization,and Synthetic Application

Metallacyclopentadienes have attracted much attention as building blocks for synthetic chemistry as well as key intermediates in many metal‐mediated or metal‐catalyzed reactions. However, metallacyclopentadienes of the alkaline‐earth metals have not been reported, to say nothing of their structures, reaction chemistry, and synthetic applications. In this work, the first series of magnesiacyclopentadienes, spiro‐dilithio magnesiacyclopentadienes, and dimagnesiabutadiene were synthesized from 1,4‐dilithio 1,3‐butadienes. Single‐crystal X‐ray structural analysis of these magnesiacycles revealed unique structural characteristics and bonding modes. Their reaction chemistry and synthetic application were preliminarily studied and efficient access to amino cyclopentadienes was established through their reaction with thioformamides. Experimental and DFT calculations demonstrated that these magnesiacyclopentadienes could be regarded as bis(Grignard) reagents wherein the two Mg? C(sp²) bonds have a synergetic effect when reacting with substrates.     

Lithiation of 2-Alkyl-3-amino- and 2-Alkyl-3-(methylamino)-4(3H)-quinazolinones(1)

3-Amino-2-methyl-4(3H)-quinazolinone has been doubly lithiated, on nitrogen and in the 2-methyl group, with n-butyllithium. The lithium reagent thus obtained reacts with a variety of electrophiles (D(2)O, benzophenone, cyclohexanone, cyclopentanone, acetophenone, benzaldehyde, tetraisopropylthiuram disulfide (TITD)) to give the corresponding 2-substituted derivatives in very good yields. Reactions of the dilithio reagent with 2 molar equiv of methyl iodide or phenyl isocyanate give disubstituted derivatives. Double lithiation of the 2-ethyl and 2-propyl analogues have been achieved using LDA, and subsequent reactions with most electophiles are then similar. In the reaction of the dianion of the 2-ethyl compound with TITD, deamination from position 3 takes place with the formation of the 2-substituted derivative. In reactions with prochiral ketones, the dianion of the 2-ethyl compound gives very high diastereoselectivity. Lithiation and subsequent reactions of 3-(methylamino) analogues take place in a similar manner, thus providing access to a range of substituted 3-(methylamino)-2-alkyl-4(3H)-quinazolinones by a general procedure. Lithiation of 3-(dimethylamino)-2-ethyl-4(3H)-quinazolinone did not take place under similar conditions. Lithiation of 3-amino-2-unsubstituted-4(3H)-quinazolinone was also unsuccessful.     

Reactions of ketone dilithio α,β-dianions with imines and hydrazones: an anionic access to γ-amino ketones

The reactions of ketone dilithio α,β-dianions with imines and hydrazones were investigated. The nucleophilic addition reaction to C-N double bonds took place selectively at the β-position of dianions to form lithium Z-enolates containing a lithium amide portion, which is then transformed into γ-amino ketones and related compounds by the subsequent reaction with electrophiles.     

Generation and carbonyl addition reactions of Z-dilithiohex-3-ene-1,5-diyne

The reaction of the title dilithio salt with carbonyl compounds leads to products bearing substructures found in recently discovered enediyne antibiotics. The bis condensation product with benzaldehyde undergoes a novel cycloaromatization reaction.     

Dianions as Formal Oxidants: Synthesis and Characterization of Aromatic Dilithionickeloles from 1,4‐Dilithio‐1,3‐butadienes and [Ni(cod)2]

Organolithium compounds can behave as reductants but never as oxidants in redox reactions. Reported herein is that 1,4‐dilithio‐1,3‐butadienes reacted with [Ni(cod)₂] (cod=1,5‐cyclooctadiene) to deliver dilithionickeloles. Single‐crystal X‐ray structural analysis revealed a coplanar structure of dilithionickeloles with an averaging of bond lengths. XPS data confirmed the oxidation state of Ni in dilithionickeloles was Ni²⁺. ⁷Li NMR spectra of dilithionickeloles and theoretical calculations revealed a considerable aromatic character. In this redox reaction, the dilithio dianionic compounds behaved as formal oxidants, thus oxidizing Ni⁰ into Ni²⁺. These results demonstrated that organolithium compounds with π‐conjugation could be used as oxidants and could continue to accept extra electrons.     

Generation of ketone dilithio α,β-dianions and their reactions with electrophiles

Ketone dilithio α,β- and α,β′-dianions can be generated by a tin-lithium exchange reaction of the lithium enolate of β-tributyltin substituted ketones. A chelation-aided approach, which employs β-dichlorobutyltin substituted ketones and n-BuLi, is also useful for the generation of ketone α,β-dianions having the Z-geometry at the alkene. The generated dianions can be transformed into substituted ketones by reaction with various carbon electrophiles.     

Magnesiacyclopentadienes as Alkaline‐Earth Metallacyclopentadienes: Facile Synthesis,Structural Characterization,and Synthetic Application

Metallacyclopentadienes have attracted much attention as building blocks for synthetic chemistry as well as key intermediates in many metal‐mediated or metal‐catalyzed reactions. However, metallacyclopentadienes of the alkaline‐earth metals have not been reported, to say nothing of their structures, reaction chemistry, and synthetic applications. In this work, the first series of magnesiacyclopentadienes, spiro‐dilithio magnesiacyclopentadienes, and dimagnesiabutadiene were synthesized from 1,4‐dilithio 1,3‐butadienes. Single‐crystal X‐ray structural analysis of these magnesiacycles revealed unique structural characteristics and bonding modes. Their reaction chemistry and synthetic application were preliminarily studied and efficient access to amino cyclopentadienes was established through their reaction with thioformamides. Experimental and DFT calculations demonstrated that these magnesiacyclopentadienes could be regarded as bis(Grignard) reagents wherein the two Mg C(sp²) bonds have a synergetic effect when reacting with substrates.     

Studies on isoxazole and pyrazole formation by the reaction of trifluoromethyl-substituted anilines with oxime and hydrazone dianions

5-(2-Aminophenyl)isoxazoles are obtained in good yields by the reaction of 2-(trifluoromethyl)aniline with dilithio derivatives of oximes of acetone, 3-pentanone, propiophenone, and cyclohexanone. An analogous synthesis of a substituted isoxazole from 4-(trifluoromethyl)aniline and 3-pentanone oxime and the synthesis of a substituted pyrazole from 2-(trifluoromethyl)aniline and 3-pentanone hydrazone are less efficient.     

Synthesis of 2,9‐diacyl‐1, 10‐phenanthrolines

A convenient high yield synthetic route leading to 2,9‐diacyl‐1,10‐phenanthrolines has been developed. The reaction of bis‐amide 1 with 2‐pyridyllithium, 6‐bromo‐2‐pyridyllithium or 2‐thienyllithium led to the diacyl compounds 5,6 and 7 , respectively. Attempts to prepare 8 by intramolecular coupling of 6 or by treatment of 1 with dilithio analogue 9b were unsuccessful. Treatment of 1 with butyllithium or aryllithium reagents led to 10a, 10b and 10c.     

A facile solid-phase synthesis of substituted 2(5H)-furanones from polymer-supported alpha-selenocarboxylic acids

The synthesis of polystyrene-supported alpha-selenoacetic acid, alpha-selenopropionic acid, and alpha-selenophenylacetic acid is described. The reaction of the dilithio derivatives of polymer-supported alpha-selenocarboxylic acids with racemic epoxides or optically active styrene oxide afforded polystyrene-supported gamma-substituted alpha-selenobutyrolactones. The alpha-alkylation reaction of gamma-substituted polystyrene-supported alpha-selenobutyrolactones provided another route for the synthesis of polystyrene-supported alpha,gamma-disubstituted alpha-selenobutyrolactones. Subsequent oxidation-elimination with an excess of 30% hydrogen peroxide at room temperature afforded substituted (3- and 5-mono-; 3,4- and 3,5-di) 2(5H)-furanones in high yields and good purities.     

Metalation reactions—VIII Metalation of 1,4-enynes and protonation of their anions

A series of 1,4-enynes was prepared and the compounds metalated with butyllithium in ether. The formation of the mono- and dilithio derivatives was studied by PMR and UV. Protonation of the dilithio compounds gave vinylallenes, 1,3- and 1,4-enynes. Isomerisation of the 1,4-enynes in DMSO using dimsylsodium gave vinylacetylenes from compounds containing a terminal double bond and vinylallenes from those with an internal double bond. The sequence of the H—D exchange of the various protons was also studied.     

Synthesis,Spectra Characterization,Electrochemical Behavior of Silyl Derivatives of Ferrocene

Ferrocenyl‐substituted silanes via the reaction between mono and dilithio‐ferrocene with trimethyl, trietheyl, vinyldimethyl or t‐butyldimethyl chlorosilanes is prepared. The electrochemical behaviors of these compounds were investigated by cyclic voltammetry. This work describes the electrochemical and electrocatalytic properties of carbon ceramic electrode (CCE) modified with ferrocene composites as a new electrocatalyst material.     

1,3‐Butadienyl Dianions as Non‐Innocent Ligands: Synthesis and Characterization of Aromatic Dilithio Rhodacycles

Herein we report that 1,4‐dilithio‐1,3‐butadienes, a type of 1,3‐butadienyl dianion, can act as non‐innocent ligands, taking electrons from low‐valent transition metals. Dilithio reagents reacted with [{RhCl(cod)}₂] to give dilithio rhodacycle 3 a . Single‐crystal X‐ray structural analysis revealed the structure of 3 a with averaged bond lengths. XPS data suggested that the oxidation state of Rh in 3 a was more likely to be Rh³⁺. CDA/ECDA confirmed the electron‐transfer process. ⁷Li NMR spectra of 3 a and theoretical calculations revealed a considerable aromatic character. In this process, the dilithio compounds behaved as non‐innocent ligands and formal oxidants. These results demonstrated that organolithium compounds with suitable π‐conjugation could be used as electron acceptor.     

Photostimulated reactions of phenylacetic acid dianions with aryl halides. Influence of the metallic cation on the regiochemistry of arylation

[reaction: see text]Phenylacetic acid dianions react via what appears to be an S(RN)1 process with aryl halides under photostimulation to afford aryl substitution products 5 and 6. When the counterion is K+, only 4-biphenylacetic acids 5 are obtained. Both alpha- and para-coupling occurs with Na+ to give a mixture of 5 and 6, while exclusive formation of diphenylacetic acids 6 is observed with the dilithio salt of 1.     

An Unusual Rearrangement of a Lithiated N-Acyl-tetrahydroisoquinoline to an Amino-indan Skeleton and Structural Comparison of 3-Amino-2-methylindan- and -tetrahydronaphthalene-2-carboxylic Acids as Possible Building Blocks for Peptide-Turn Mimics

Lithium 1-lithio-6,7-dimethoxy-3-methyl-2-pivaloyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylate rearranges to the dilithio derivative of 5,6-dimethoxy-2-methyl-1-(pivaloylamino)indan-2-carboxylic acid ( 2 , [1,2]-sigmatropic shift with retention of configuration) by 1,2-migration resembling the Wittig rearrangement of deprotonated ethers (Scheme 2). The structure, including absolute configuration of the rearrangement product, was determined by X-ray diffraction. Structural conditions for the rearrangement to occur are tested by subjecting various other tetrahydroisoquinoline derivatives ( 6 , 7 , 10 , 15 ) to the metalating conditions. Only one other compound was found to undergo the same rearrangement ( 15 → 16 ). Possible mechanisms of the rearrangement are discussed ( B–G ). Due to the presence of a tetrasubstituted C-atom, the indan-type β-amino-acid derivative 2 has a conformationally locked structure (N? C? C? CO₂R dihedral angle 44°). For comparison, the corresponding tetralin-type β-aminoacid derivatives 19–22 were prepared, and it was shown by X-ray analysis (of the ester 21 ) that these have larger dihedral angles (ca. 60°). It is proposed that β-amino acids of the type described here could be incorporated into peptides, providing bents of known angles along the peptide backbone.