Aromatic Lithiation Research Articles

Asymmetric Synthesis of Concentricolide

AbstractA practical strategy for the synthesis of both (–)‐ and (+)‐concentricolide from salicylic acid has been developed. The key feature of the approach is sequential aromatic lithiation and condensation with an aldehyde directed by a chiral oxazoline unit derived either from L‐ or D‐phenylalaninol, which is employed as an auxiliary.

Aryl and Heteroaryllithium Compounds by Metal - Halogen Exchange. Synthesis of Carbocyclic and Heterocyclic Systems

The aromatic metalation - cyclization sequence is a valuable protocol for the regiospecific construction of carbocyclic and heterocyclic systems. Aromatic lithiation can be carried out by lithium - hydrogen or lithium - halogen exchange. The latter procedure, though mechanistically controversial, is the method of choice to introduce specifically a lithium atom into a given, non-activated position of the aromatic ring. Once generated, the aryllithiums may react with external or internal electrophiles and thus give rise to cyclization reactions, which are known as Parham cyclization. In addition to the carbon - carbon bond formation, the aromatic lithiation allows the introduction of further functionality to the molecule. Therefore, strategies based aromatic lithiation can play a crucial role in natural products synthesis. In this review we will survey some recent advances on the application of the aromatic lithiation - cyclization sequence for the synthesis of different types of carbocycles and heterocycles. We have limited it to the metalation reactions, where the aryl and hetero-aryllithium intermediates are generated by the metal - halogen exchange reaction. Major emphasis will be placed on stereoselectivity of the metalation - cyclization sequence, since it has received only sporadic attention.

ChemInform Abstract: Heteroatom‐Directed Aromatic Lithiation: A Versatile Route to the Synthesis of Organochalcogen (Se, Te) Compounds

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

An HF and DFT ab initio Study on the Mechanism of ortho-Directed Lithiation of Hydric and Nonhydric Aromatic Compounds Incorporating Aggregation and Discrete Solvation: The Role of N,N,N′,N′-Tetramethylethane-1,2-diamine (TMEDA) in Lithiation Reactions

An HF and DFT ab initio study was set up to decipher the roles of aggregation and solvation in the ortho-directed lithiation of aromatics (hydric and nonhydric), as well as to shed light on the much debated question of precomplexation in the mechanism of lithiation. Ab initio (HF/6-31-G*) calculations on the lithiation of non-hydric aromatics have uncovered several competitive routes operating as a function of the aggregation state of the organolithium base used. Specifically, two competitive routes were found for the lithiation of the anisole model 2 by organolithium dimers 1-dim, namely the so-called cyclic-dimer and open-dimer routes, whereas, for organolithium tetramers 1-tet, the corresponding cyclic route is the only one operative, and, for monomers 1-mon, several optional routes seem to be available. Precomplexation is, in all cases, a requirement. According to the computational data presented, the mysterious rate acceleration experimentally observed for lithiations carried out in TMEDA can be assigned to an aggregation effect on the intermediate open-dimer species, which subsidiarily give rise to several so-called s-monomer routes, of which the dimerization-driven s-monomer route s-m3b is the one having the lowest energy barrier. The relevant species characteristic of both the open-dimer and s-monomer routes are the so-called open dimers, i.e., high-energy intermediates (actually, spiro dimeric aggregates), resulting from cleavage-induced associative complexation of the aromatic substrate upon the fully solvated organolithium dimer. DFT calculations (B3LYP/6-31+G*) also revealed that the peri-lithiation (i.e., Li at C(8)) of 1-naphthol model 3 is a slow process taking place preferentially through the open-dimer route.

Heteroatom-directed aromatic lithiation: a versatile route to the synthesis of organochalcogen (Se, Te) compounds.

Chiral and achiral organochalcogen compounds bearing a heteroatom in close proximity are easily accessible via the directed aromatic lithiation route. The lithium chalcogenolates prepared by the insertion of selenium or tellurium into the C-Li bond are used to synthesize various chalcogen compounds such as Se/Te, N donor ligands, dichalcogenides, monomeric metal chalcogenolates, and macrocycles. The differences in the stability and reactivity of the organochalcogen compounds derived from various substrates are described in terms of electronic and stereochemical properties of donor atoms.

Intramolecularly Coordinated Diorganyl Ditellurides: Thiol Peroxidase-like Antioxidants

A series of diaryl ditellurides with and without coordinating amino/imino groups are synthesized by using either the Grignard route or the heteroatom-directed aromatic lithiation route. The chiral ditelluride (R),(R)-bis[2-(4-ethyl-2-oxazolinyl)phenyl] ditelluride is synthesized in an enantiomerically pure form by stereoselective ortho-lithiation. The thiol peroxidase activity of the ditellurides is studied by using H2O2 as a substrate and PhSH as a cosubstrate. The initial rates for the reduction of H2O2 catalyzed by diaryl ditellurides are much higher than those catalyzed by the corresponding diselenides. A comparison of the activities between various diorganyl ditellurides and diselenides shows that the presence of basic amino groups in the close proximity of tellurium enhances the reduction rates and the effect of amino groups on the activity is more pronounced in the case of ditellurides as compared to the corresponding diselenides. On the other hand, a correlation between the strength of Te···N intr...

The tert-butylchlorideȁlithium naphthalene radical anion and tert-butyllithiumȁnaphthalene systems. Mechanism of metallation

A mechanism of lithiation of aromatics has been inferred from a comparative study of the systems tert-butyl chlorideȁlithium naphthalene radical anion and tert-butyllithiumȁnaphthalene. Both systems give tert-butyldihydronaphthyllithiums, naphthyllithiums and tert-butylnaphthalenes. Although tert-butyllithium is a reaction product in the former system, it has been shown not to be involved in the formation of the products. In the system tert-butyllithiumȁnaphthalene the distribution of products is markedly dependent upon the strength of the catalyzing Lewis base. Weak Lewis bases favor formation of tert-butylnaphthalene (mainly the 2-isomer) as well as tert-butyldihydronaphthyllithiums, whereas strong Lewis bases favor metallation. Mechanisms are proposed which postulate the involvement of a tert-butyl radicalȁnaphthalene donorȁacceptor complex in the fundamental elementary reaction.

ChemInform Abstract: Mechanisms of Aromatic Lithiation: Influence of Aggregation and Directing Groups.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Mechanisms of aromatic lithiation: Influence of aggregation and directing groups

High level ab initio calculations (MP2(fc)/6-31+ G*/MP2(fc)6-31G*Δ+ZPE/6-31IG* show that the reaction of aromatic compounds with methyllithium is not an electrophilic substitution, but a hydrogen transfer along an almost linear path, with the (coordinatively highly unsaturated) “active” lithium cation bridging the methyl carbanion and the carbon atom being lithiated. Aggregation (modelled with lithium hydride) does not change the mechanism. However, intra-aggregate bonding stabilizes the “active” lithium ( i.e., the one directly undergoing transfer). The mixed dimer of methyllithium and lithium hydride is predicted to be more reactive than methyllithium monomer in the lithiation of benzene, due to interaction of the “passive” lithium with the aromatic π-system and the carbon atom being lithiated. The accelerating and ortho-directing effect of Lewis base substituents is due to stabilization of the “active” lithium in the transition state by intramolecular coordination and favorable electrostatic interactions. These stabilizing effects are strongest for reaction of a monomer, but are also significant in the reaction of anisole with the mixed dimer of methyllithium and lithium hydride.

CNDO/II treatment of proton abstraction step in aromatic lithiation reaction

All valence MO calculation employing CNDO/II treatment for hydrogen abstraction step in aromatic ortho lithiation reaction is done. The predicted proton abstraction is supported by experimental observation. The lithiation of N-methyl-β-naphthamide occurs at the 1 position and not at the 3 position.

ChemInform Abstract: Aromatic Lithiation Directed by the Carboxylic Acid Groups. Synthesis of 9‐Substituted Dibenzodioxin‐1‐carboxylic Acids and 6‐Substituted Phenoxathiin‐4‐carboxylic Acids.

AbstractRegioselective lithiation of the acids (I) and subsequent quenching with carbon dioxide followed by esterification yield the corresponding diesters (IV).

ChemInform Abstract: Synthesis of 4,7‐Disubstituted Spirobenzofuran‐2(3H)‐cyclohexanes.

AbstractA general strategy is shown for the preparation of the title compounds (VII) and (VIII) and some of their derivatives using successive, regioselective heteroatom‐facilitated aromatic lithiation reactions and subsequent reaction with electrophiles.

Aromatic lithiation directed by the carboxylic acid group. Synthesis of 9-substituted dibenzodioxin-1-carboxylic acids and 6-substituted phenoxathiin-4-carboxylic acids

An efficient procedure has been developed for the regiospecific synthesis of 9-substituted dibenzo[1,4]dioxin-1-carboxylic acid derivatives. Lithiation of dibenzo[1,4]dioxin-1-carboxylic acid forms the lithium carboxylate, which directs subsequent metalation exclusively to the 9-position. Conditions for the controlled mono- and dilithiation of dibenzo[1,4]dioxin itself, leading to the direct synthesis of the corresponding mono- and isomeric dimethyl esters, are also described

Synthesis of 4,7‐disubstituted spirobenzofuran‐2(3H)‐cyclohexanes

AbstractA general synthetic strategy was designed for the preparation of 7‐substituted‐4‐methoxy‐ and 4‐hydroxyspiro[benzofuran‐2(3H)‐cyclohexanes] 5 and 6 (Figure 1) using successive, regioselective hetero‐atom‐facilitated aromatic lithiation reactions and subsequent reaction with various electrophiles.

ChemInform Abstract: Heteroatom Directed Aromatic Lithiation Reactions for the Synthesis of Condensed Heterocyclic Compounds

ChemInformVolume 18, Issue 19 Reviews ChemInform Abstract: Heteroatom Directed Aromatic Lithiation Reactions for the Synthesis of Condensed Heterocyclic Compounds N. S. NARASIMHAN, N. S. NARASIMHAN Garware Res. Centre, Dep. Chem., Univ. Poona, Pune-411007, IndiaSearch for more papers by this authorR. S. MALI, R. S. MALI Garware Res. Centre, Dep. Chem., Univ. Poona, Pune-411007, IndiaSearch for more papers by this author N. S. NARASIMHAN, N. S. NARASIMHAN Garware Res. Centre, Dep. Chem., Univ. Poona, Pune-411007, IndiaSearch for more papers by this authorR. S. MALI, R. S. MALI Garware Res. Centre, Dep. Chem., Univ. Poona, Pune-411007, IndiaSearch for more papers by this author First published: May 12, 1987 https://doi.org/10.1002/chin.198719385Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume18, Issue19May 12, 1987 RelatedInformation

Mechanism of aromatic lithiation reactions—Importance of steric factors

N,N-Dimethyl-1-naphthyIamine and N,N-dimethyl-2-aminobiphenyl do not undergoortho-lithiation although lithiation at a distant, but sterically close, position does occur. The result, although apparently anomalous, can be explained by Roberts-Curtin mechanism, taking into consideration the steric strain present at the transition state corresponding to the proton abstraction process.

ChemInform Abstract: SYNTHESES OF HETEROCYCLIC COMPOUNDS INVOLVING AROMATIC LITHIATION REACTIONS IN THE KEY STEP

Chemischer InformationsdienstVolume 15, Issue 17 Reviews ChemInform Abstract: SYNTHESES OF HETEROCYCLIC COMPOUNDS INVOLVING AROMATIC LITHIATION REACTIONS IN THE KEY STEP N. S. NARASIMHAN, N. S. NARASIMHANSearch for more papers by this authorR. S. MALI, R. S. MALISearch for more papers by this author N. S. NARASIMHAN, N. S. NARASIMHANSearch for more papers by this authorR. S. MALI, R. S. MALISearch for more papers by this author First published: April 24, 1984 https://doi.org/10.1002/chin.198417384AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume15, Issue17April 24, 1984 RelatedInformation

Lithiation of 2-Methyl-2-Phenyl-1,3-Dioxolane with Sutyllithium

Abstract In lithiation of acetophenone ketal by butyllithium in diethyl ether, both aromatic lithiation and ketal ring cleavage are observed.

Syntheses of Heterocyclic Compounds Involving Aromatic Lithiation Reactions in the Key Step

Heteroatom-directed aromatic lithiation reactions for the syntheses of several heterocyclic ring systems and naturally occurring compounds which have not been synthesised or which have been synthesised only through considerably longer routes by the usual methods are reviewed in this article. 1. Introduction 2. Aromatic Lithiation Reactions 3. Synthesis of Basic Heterocyclic Ring Systems 4. Utility of the New Synthetic Methods 5. Strategies to Improve Yields in Aromatic Lithiation Reactions