Equivalents Of N-butyllithium Research Articles

Synthesis, structures and oxidative addition reactions of new thermally stable silylenes; crystal structures of [ [formula omitted](CH 2tBu)} 2C 6H 4-1,2] and [( [formula omitted](CH 2tBu)} 2C 6H 4-1,2)(μ-E)] 2 (E = Se or Te)

Treatment of the N,N′-dineopentyl-1,2-phenylenediamine 4-RC 6H 3[NH(CH 2 tBu)] 2-1,2 (R = H or Me) with successively two equivalents of n-butyllithium and one of SiCl 4 yields the appropriate N,N′-dineopentyl-1,2-phenylenediaminodichlorosilane Si[{N (CH 2 tBu)} 2C 6H 3-1,2-R-4]Cl 2 (R = H, 1, or R = Me, 2). The thermally stable, yellow, diamagnetic, volatile, crystalline silylene Si[{N (CH 2 tBu)} 2C 6H 3-1,2-R-4] (R = H, 3, or R = Me, 4) is obtained from 1 or 2 by reaction with potassium in refluxing tetrahydrofuran. The silylene 3 undergoes oxidative addition with (i) Mel or EtOH to give [ Si{N (CH 2 tBu)} 2C 6H 4-1,2](X)Y (X = Me and Y = 1. 5. or X = OEt and Y = H. 6), or (ii) a chalcogen E to afford [( Si{N (CH 2 tBu)} 2C 6H 4-1,2)(μ-E)] 2 (E = S. 7. Se. 8 or Te. 9). Spectroscopic data are provided for compounds 1–9 and single crystal X-ray diffraction results for compounds 3, 8 and 9. The average SiN distances are 1.750(4) Å for the silylene 3. 1.719(4) Å for the cyclodisilaselenane 8 and 1.729(3) Å for the cyclodisilatellurane 9, the NSiN′ angles being 88.2(1)° for 3, 93.5(2)° for 8 and 93.7(1)° for 9.

Dilithiated ( E)- N-isobutyl-4-tosyl-2-butenamide: An allyl sulfone dianion for the regiospecific γ-functionalization of crotonamide dianion

( E)- N-Isobutyl-4-tosyl-2-butenamide ( 5) (prepared from vinylacetic acid by stereoselective iodosulfonylation-dehydroiodination and further amidation) has been lithiated with two equiv of n-butyllithium at −78°C in the presence of DMPU leading to the corresponding allyl dianion 6. This intermediate reacts with electrophiles (alkyl bromides, aldehydes and electrophilic olefins) regiospecific and stereoselectively at the γ-position to afford γ-substituted ( E)- N-isobutyl-4-tosyl-2-butenamides 7. Desulfonylation of compounds 7 occurs stereoselectively to provide ( E)- β, γ-unsaturated amides 9. This methodology has been applied to the synthesis of dienamides such as naturally occurring N-isobutyl-(2 E,4 E)-decadienamide (pellitorine).

( E)- N-Isopropyl-5-tosyl-4-pentenamide: A vinyl sulfone as precursorv of a new δ-acyldienyl anion equivalent

( E)- N-Isopropyl-5-tosyl-4-pentenamide ( 7b), prepared from 4-pentenoic acid by stereoselective iodosulfonylation-dehydroiodination and further amidation with oxalyl chloride and isopropylamine, reacts with two equiv of n-butyllithium at −78°C and then with aldehydes affording stereoselectively (2 E,4 E)-6-hydroxy-2,4-hexadienamides 9. In the case of carboxylic acid chlorides or cyclohexyl isocyanate, dilithiated lactam 8c undergoes acylation to afford the corresponding lactam derivatives 10.

Reaction of 3-cyanopyridine-2(1H)-thiones with N-butyllithium

The reaction of 3-cyanopyridine-2(1 H)-thiones with BuLi in ether was studied. It was found that the metallation proceeds initially at the sulfur atom. The resulting lithium salts add a second equivalent of n-butyllithium at the CN group. The hydrolysis of the dilithium derivatives leads to 3 pentanoylpyridine-2(IH)-thiones.

Carbon-Carbon Bond Formation by Reductive Coupling with Titanium(II) Chloride Bis(tetrahydrofuran)

Titanium(II) bis(tetrahydrofuran) 1, generated by the treatm ent of TiCl4 in THF with two equivalents of n-butyllithium at -78 °C, has been found to form carbon-carbon bonds with a variety of organic substrates by reductive coupling. Diphenylacetylene is dimerized to exclusively (E,E)-1,2,3,4-tetraphenyl-1,3-butadiene; benzyl bromide and 9-bromofluorene give their coupled products, bibenzyl and 9,9'-bifluorenyl, as do benzal chloride and benzotrichloride yield the 1,2-dichloro-1,2-diphenylethanes and 1,1,2,2-tetrachloro-1,2-diphenylethane, respectively. Styrene oxide and and cis-stilbene oxide undergo deoxygenation to styrene and fra/«-stilbene, while benzyl alcohol and benzopinacol are coupled to bibenzyl and to a mixture of tetraphenylethylene and 1,1,2,2-tetraphenylethane. Both aliphatic and aromatic ketones are smoothly reductively coupled to a mixture of pinacols and/or olefins in varying proportions. By a choice of experimental conditions either the pinacol or the olefin could be made the predom inant product in certain cases. The reaction has been carried out with heptanal, cyclohexanone, benzonitrile, benzaldehyde, furfural, acetophenone, benzophenone and 9-fluorenone. In a remarkable, multiple reductive coupling, benzoyl chloride is converted into 2,3,4,5-tetraphenylfuran in almost 50% yield. The stereochemical course of two such couplings, that of diphenylacetylene to yield exclusively (E,E)-1,2,3,4-tetraphenyl-l,3-butadiene and that of acetophenone to produce only racemic-2,3-diphenyl-2,3-butanediol, is interpreted to conclude that the couplings proceed via two electron transfer pathways (TET) involving titanium (IV) cyclic intermediates of the titanirene and the oxatitanacyclopropane type, respectively.

The Formation of a Mixed Organolithium Aggregate Li4R2nBu2 during the Heteroatom‐Assisted Lithiation of 1,3‐Bis(dimethylaminomethyl)‐2,4,6‐trimethylbenzene (R = 2,6‐(CH2NMe2)2‐3,5‐Me2C6HCH2)

Lithiated 1 and unreacted n-butyllithium in a 2:2 ratio make up the title aggregate 2, which is formed in the reaction of 1 with two equivalents of n-butyllithium (shown below). Species such as 2 can be regarded as intermediates in heteroatom-facilitated lithiation reactions.

エノレート化学を基盤とする新しい不斉合成法の開発 : β-ラクタム合成と不斉記憶

Two topics are described concerning asymmetric synthesis utilizing enolate chemistry. The first one is stereoselective β-lactam synthesis through oxidative coupling of dienolates generated from acyclic tertiary amides. Amides 4 were converted into dienolates by treatment with two equivalents of n-butyllithium or t-butyllithium, and the dienolates were oxidized with N-iodosuccinimide (NIS) or Cu (II) acetate to form β-lactams 5 stereoselectively. The stereochemistry of β-lactam formation depends on the oxidant : NIS is cis-selective, whereas Cu (II) acetate is slightly trans-selective. By the use of optically active 1-phenylethyl-amine as a chiral auxiliary, asymmetric induction of 90% de is achieved. The product 11 was transformed to an intermediate for the synthesis of monobactam antibiotic carmonam. Chemoselective epimerization of cis-β-lactam 13 was accomplished with trifluoroacetic acid, and the resulting trans-isomer 14 was converted into an intermediate of monobactam antibiotic aztreonam. The second topic is asymmetric alkylation of enolates based on a new concept, memory of chirality. An optically active ketone 20 was treated with potassium hydride and a series of alkyl halides in the presence of 18-crown-6 to furnish optically active alkylated ketones 21 in 48-73% ee without any external chiral source. These findings contravene the accepted view that chirality at the α-carbon to carbonyl groups is lost in the corresponding enolates because the enolates themselves are achiral. To explain this phenomenon, we propose a novel concept that chirality at the α-carbon to the carbonyl group is memorized as dynamic axial chirality in the intermediate enolate, and is then regenerated as central chirality in the reaction products (memory of chirality). This mechanism was supported by trapping the enolate as methyl enol ether 27 of 65% ee. The present concept was successfully applied to the development of the asymmetric α-alkylation reactions of α-amino acid derivatives. Thus, phenylalanine derivative 33 was found to undergo asymmetric α-alkylation in up to 88% ee when treated with lithium 2, 2, 6, 6-tetramethylpiperidide followed by alkyl halides.

Evidence for bromine-lithium exchange in a local high concentration gradient

The product ratios for bromine-lithium exchange of 3,3′-dibromostilbene ( 6) with one equivalent of n-butyl lithium, s-butyl lithium or t-butyl lithium in THF and in Et 2O to give after quenching with methanol 3-bromostilbene ( 7) and stilbene ( 8), have been investigated. In the most reactive cases the ratio of 8:7 is significantly greater than expected for a statistical reaction. The apparently accelerated exchange of 7-Li relative to 6 is attributed to reaction in a high local concentration of the butyl lithium reagent.

Base-catalyzed Electrophilic Substitution in 2(1H)-Quinolinones

Instead of tandem conjugate addition-α-alkylation to C 3 =C 4 double bond of 2(1H)-quinolinones, regioselective C 3 -lithiation and subsequent C 3 - alkylation takes place by reaction with two equivalents of n-butyllithium and several electrophiles

(3,3‐Diphenylallenylidene)trimethylphosphanetitanocene: The First Titanocene Carbene Complex with Three Cumulative Double Bonds

1,2-Dilithiocyclopropene → 1,1-dilithioallene rearrangement results in the formation of compound 2 from 3,3-diphenylcyclopropene (1) and two equivalents of n-butyllithium. Compound 2 reacts further with titanocene dichloride and trimethylphosphane to give the allenylidenetitanocene complex 3. The yields of this one-pot synthesis are 71 %.

Metalation of 1,4-dihydropyridine esters

4-Aryl-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic esters are metalated at the NH and the C-2 methyl positions via tretament with two equivalents of n-butyl lithium. The resulting dilithio species can be treated with a variety of electrophiles to furnish C-2 methyl functionalized dihydropyridine esters.

The regiospecific formation and reactions of 4-lithio-2-(t-butyldimethylsilyl)- 3-(hydroxymethyl)furan: An approach to 3,4-disubstituted furans.

4-Lithio-2-(t-butyldimethylsilyl)-3-(hydroxymethyl)furan, generated by treating 2-(t-butyldimethylsilyl)-3-(hydroxymethyl)furan 2 with 2.2 equivalents of n-butyllithium (DME/0°C/15 min), is trapped by a variety of electrophiles to produce, after desilylation, 3,4-disubstituted furans in good to moderate yields.

A novel synthesis of epoxides and allylic alcohols from carbonyl compounds through α, β-epoxy sulfoxides

Treatment of α,β-epoxy sulfoxides, easily prepared from carbonyl compounds with 1 equivalent of n-butyllithium at −100 °C gave the desulfinated epoxides in good yields. The similar α,β-epoxy sulfoxides having arylmethyl group at α-position, on treatment with excess n-butyllithium at −70 °C afforded 3-aryl allylic alcohols.

Synthesis and mass spectrometric study of condensed thiones: Precursors of thiophene heterofulvalenes

1. Thieno(2,3-d)-1,3-dithiol-2-thione, thieno(2,3-d)-1,3-thioselenol-2-thione, and thieno(2,3-d)-1,3-diselenol-2-thione were prepared by successive treatment of 3-bromothiophene at -70°C with an ether solution of n-butyllithium, sulfur, or selenium, a second equivalent of n-butyllithium, sulfur or selenium, and an ether solution of thiophosgene at −20°C (without separation of intermediate products). 2. Thieno(3,4-d)-1,3-dithiol-2-thione, thieno(3,4-d)-1,3-thioselenol-2-thione, and thieno(3,4-d)-1,3-diselenol-2-thione were prepared by dealkylation of 3,4-bis(ethylmercapto)-,3-ethylseleno-4-ethylmercapto-, and 3,4-bis(methylseleno)thiones with sodium in liquid ammonia and subsequent treatment of the disodium salts formed with thiophosgene in ether. 3. The mass spectra of the thiones synthesized were studied and showed that a C4H2S+. ion (m/z 82), which could correspond to the structure of dehydrothiophene, was formed on decomposition of the molecular ions in all cases.

Seitenkettenmetallierung 2-methylsubstituierter benzylalkohole

Treatment of the benzyl alcohols 1 , 5a , and 7 with two equivalents of n-butyllithium gives the intermdiates 2 , 6 , and 8 . By reaction with various electrophiles, the products 3a - c , 4a , b , and 5b , c are formed.

ChemInform Abstract: NUCLEAR ANALOGS OF β‐LACTAM ANTIBIOTICS. XV. SYNTHESIS OF 6‐SUBSTITUTED 2‐METHYLPENEM‐3‐CARBOXYLIC ACIDS

The synthesis of 6-substituted 2-methylpenem-3-carboxylic acids is described. The dianion 6 was prepared insitu from 2-methylpenem-3-carboxylic acid (5) by the addition of two equivalents of n-butyllithium in THF at −78 °C. This dianion reacted with deuterated acetic acid, acetone, acetaldehyde, benzaldehyde, and methyl thiomethylsulfonate to give 6-deuterio-, 6-(2′-hydroxy-2′-propyl)-, 6-(1′-hydroxyethyl)-, 6-(1′-hydroxybenzyl)-, 6-methylthio-2-methylpenem-3-carboxylic acids and their sodium or potassium salts, 7–11, respectively. The stereochemistry of the products is also discussed.

Nuclear analogs of β-lactam antibiotics. XV. Synthesis of 6-substituted 2-methylpenem-3-carboxylic acids

The synthesis of 6-substituted 2-methylpenem-3-carboxylic acids is described. The dianion 6 was prepared insitu from 2-methylpenem-3-carboxylic acid (5) by the addition of two equivalents of n-butyllithium in THF at −78 °C. This dianion reacted with deuterated acetic acid, acetone, acetaldehyde, benzaldehyde, and methyl thiomethylsulfonate to give 6-deuterio-, 6-(2′-hydroxy-2′-propyl)-, 6-(1′-hydroxyethyl)-, 6-(1′-hydroxybenzyl)-, 6-methylthio-2-methylpenem-3-carboxylic acids and their sodium or potassium salts, 7–11, respectively. The stereochemistry of the products is also discussed.

Polyorganometallic heterocycles. 2,6-dilithiopyridine

Metal—halogen exchange between 2,6-diiodo- and 2,6-dibromopyridine and two equivalents of n-butyllithium gives 2,6-dilithiopyridine. On quenching with either carbon dioxide followed by esterification, methanol or dimethyl disulfide the dilithio compound gives a methyl 2,6-pyridinedicarboxylate, pyridine, or 2,6-dithiomethylpyridine, respectively. A convenient procedure for halogen—halogen exchange is also described.

An efficient synthesis of substituted uranocenes

Dilithium n-butylcyclooctatetraenide is prepared by reaction of 2 equiv of n-butyllithium with 1 equiv of cyclooctatetraene in diethyl ether at 25/sup 0/C. Treatment of this solution with 0.5 equiv of UCl/sub 4/ dissolved in tetrahydrofuran followed by Soxhlet extraction with hexane resulted in a 50% yield of 1,1'-di-n-butyluranocene based on cyclooctatetraene. Treatment of 1,1'-di-n-butyluranocene with nitrobenzene resulted in a 51% yield of azobenzene based on cyclooctatetraene.

A CONVENIENT PREPARATIVE METHOD OF α-CHLORO KETONES

Abstract Rearrangement reaction of 1-substituted 2,2-dichloroethanol has been studied and it has been found that the corresponding α-chloro ketone is obtained in good to excellent yield by treating the alcohol with 2∼3 equivalents of n-butyllithium in dimethoxyethane.