Amines lithiation

Ort/jo-substituted bromovinylferrocenes 157 were obtained in few steps from Ugi s amine. Lithiation and reaction with tert-butyldichlorophosphine and lithium aluminium hydride afforded secondary phosphines 158 as epimeric... 

Poly(phenylene oxide)s undergo many substitution reactions (25). Reactions involving the aromatic rings and the methyl groups of DMPPO include bromination (26), displacement of the resultant bromine with phosphoms or amines (27), lithiation (28), and maleic anhydride grafting (29). Additional reactions at the open 3-position on the ring include nitration, alkylation (30), and amidation with isocyanates (31). 

H-Dibenz[6,/]azepine, 10,11-dihydro-acylation, 7, 511 alkylation, 7, 511 amination, 7, 512 lithiation, 7, 528 PE spectrum, 7, 502 pharmacological properties, 7, 546 reactions... 

An indole protected by a Mannich reaction with formaldehyde and dimethyl-amine is stable to lithiation. The protective group is removed with NaBH4 (EtOH, THE, reflux). The related piperidine analogue has been used similarly for the protection of a triazole. ... 

Another class of configurationally stable a-mctallo amines is derived from the N-tert-butoxy-carbonyl-protected piperidines 32 and 3516, l7. Addition of the lithiated piperidines to aldehydes leads to mixtures of the anti- and. yin-diastereoiners. Although the diastereoselectivity is low, the diastereomers can be readily separated by chromatography since the. vyn-isomer is often in a cyclized form 34. The stereochemistry of the products obtained from piperidines 32 are consistent with an equatorial a-lithiation followed by addition to the aldehyde with retention of configuration. However, with piperidine 35 selective axial lithiation is observed. 

Alkylation can also be carried out, in certain compounds, at positions a to other heteroatoms, for example, at a position a to the nitrogen of tertiary amines. Alkylation a to the nitrogen of primary or secondary amines is not generally feasible because an NH hydrogen is usually more acidic than a CH hydrogen. a-Lithiation of... 

These phosphinous amide anions are presumably responsible for the formation of the by-products AT-phosphino phosphinous amides 11 and mono-phosphazenes derived from diphosphanes 12 in the sequential treatment of primary amines with n-BuLi and chlorophosphanes for preparing NH phosphinous amides [75,88] (Scheme 14). Compounds 11 and 12 are presumably derived from anions 9 and 10, respectively, generated by deprotonation of the newly formed phosphinous amide with the lithiated amine R NHLi. In solution, 9 can establish a metallotropic equilibrium with 10. 

Reaction conditions can be modified to accelerate the rate of lithiation when necessary. Addition of tertiary amines, especially TMEDA, facilitates lithiation53 by coordination at the lithium and promoting dissociation of aggregated structures. Kinetic and spectroscopic evidence indicates that in the presence of TMEDA lithiation of methoxybenzene involves the solvated dimeric species (BuLi)2(TMEDA)2.54 The reaction shows an isotope effect for the o-hydrogcn, establishing that proton abstraction is rate determining.55 It is likely that there is a precomplexation between the methoxybenzene and organometallic dimer. 

After a fluorine/chlorine exchange, a lithiated aminochlorosilane is obtained. Lithium is bound to nitrogen, the strongest Lewis base in this compound. The SiN bond is enlarged (164.2 pm) and the SiNC angle of 138.7° shows the character of the amine.17,18... 

The highly diastereoselective 1,4-addition of lithiated chiral amines to a-, (1-unsaturated esters, followed by hydrogenolysis of the benzylic-type C-N... 

Benzotriazole-related methodology publications appeared in 2006. Reaction of 1-formylbenzotriazole with triphenylphosphine/carbon tetrachloride afforded l-(2,2-dichlorovinyl)benzotriazole, where lithiation followed addition of electrophiles gave a variety of functionalized M-(ethynyl)benzotriazoles <06T3794>. Novel mono- and symmetrical di-/V-hydroxy- and IV-aminoguanidines were readily prepared from the reaction of diverse hydroxylamines or hydrazines with reagent classes di(benzotriazol-l-yl)methanimine, (bis-benzotriazol-1 -y 1-methy lene)amines, benzotriazole-1 -carboxamidines, benzotriazole-1 -... 

Acyl hydrazides are useful precursors for the synthesis of 1,2,4-triazoles. Reaction of acyl hydrazides 149 with imidoylbenzotriazoles 148 in the presence of catalytic amounts of acetic acid under microwave irradiation afforded 3,4,5-trisubstituted triazoles 150 <06JOC9051>. Treatment of A-substituted acetamides with oxalyl chloride generated imidoyl chlorides, which reacted readily with aryl hydrazides to give 3-aryl-5-methyl-4-substituted[ 1,2,4]triazoles <06SC2217>. 5-Methyl triazoles could be further functionalized through a-lithiation and subsequent reaction with electrophiles. ( )-A -(Ethoxymethylene)hydrazinecarboxylic acid methyl ester 152 was applied to the one-pot synthesis of 4-substituted-2,4-dihydro-3//-1,2,4-triazolin-3-ones 153 from readily available primary alkyl and aryl amines 151 <06TL6743>. An efficient synthesis of substituted 1,2,4-triazoles involved condensation of benzoylhydrazides with thioamides under microwave irradiation <06JCR293>. 

Addition of Lithiated Sulfoxides and Sulfones Nucleophilic addition of lithiated methylaryl sulfoxides (384) to nitrones of various structures proceeds easily and in good yields (622). The reactions are applied to the synthesis of optically active a-substituted and a,a-disubstituted hydroxylamines, to secondary amines (623), and to enantioselective syntheses of alkaloids (624). The preferred approach to (+ )-euphococcinine is based on the use of homochiral 3-sullinyl nitrones (385) (Scheme 2.167). 

Qudguiner s group enlisted a combination of directed metalation and a Pd-catalyzed crosscoupling reaction for the construction of heteroaryl natural products [49]. One example was the total synthesis of bauerine B (64), a -carboline natural product [50], Or/fio-lithiation of 2,3-dichloro-A-pivaloylaminobenzene (61) was followed by reaction with trimethylborate to provide boronic acid 62 after hydrolysis. The Suzuki reaction between 62 and 3-fluoro-4-iodopyridine led to the desired biaryl product 63 contaminated with the primary amine (ca. 30%), both of which were utilized in the total synthesis of bauerine B (64). Another p-carboline natural product, the antibiotic eudistomin T (65), and a few other hydroxy p-carbolines have also been synthesized in the same fashion [3,51]. 

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