Jacques Mortier

Directed Remote Aromatic Metalations: Mechanisms and Driving Forces

Directed remote aromatic metalations are useful synthetic transformations allowing for rapid regioselective access to elaborate highly substituted carbocyclic aromatic and heteroaromatic systems. This review unravels the tangle of data reported on directed remote aromatic metalations. Through a careful analysis of critically selected examples, advanced rationalizations of remote metalation regioselectivities are presented. These extend beyond the complex-induced proximity effect (CIPE). Mechanisms, driving forces, and parameters influencing remote metalations are discussed. An understanding of these metalation mechanisms enables more accurate predictability of justification of regiochemical outcomes of these useful synthetic transformations.

On the mechanism of the directed ortho and remote metalation reactions of N,N-dialkylbiphenyl 2-carboxamides.

A study concerning the mechanism of the LDA-mediated ortho and remote metalation of N,N-dialkyl-2-biphenyl carboxamides (e.g., 4a) is reported. On the basis of site-selective lithiation/electrophile quench experiments, including deuteration, the LDA metalation of 4 is proposed to involve initial amide-base complexation (CIPE) and equilibrium formation of 5, whose fast reaction with an in situ electrophile (TMSCl) to afford 6 prevents its equilibration with 7. In the absence of an electrophile, 5 undergoes equilibration via 4a with 7, whose fate is instantaneous cyclization to a stable tetrahedral carbinolamine oxide 8 which, only upon hydrolysis, affords fluorenone (3).

Diels-Alder reactions of 1,3-dienylborate salts with activated dienophiles

Abstract 1,3-Dienylborate 3 is found to be a very reactive diene for the Diels-Alder reaction to produce functionalized cyclic allylborates in good yields.

Synthèse d'analogues structuraux de thaxtomines, phytotoxines responsables de la gale de la pomme de terre

Abstract Cross coupling reactions of lithiated 2,5-piperazinedione anions with gramine methosulfate and alkylhalides were shown to be catalyzed by copper reagents, e.g. dilithium tetrachlorocuprate and copper (I) iodide. Based on this findings, the results of the first method for preparation of racemic thaxtomins are reported. Compound 1c , chosen as a synthetic model, was prepared in five steps in 19% overall yield. The key step was reaction of the lithiated anion of sarcosine anhydride with gramine methosulfate in the presence of a catalytic amount of dilithium tetrachlorocuprate in THF. The remainder of the sequence involved protection of the indole NH, aldol condensation with 3-benzyloxybenzaldehyde, bromohydrin formation and catalytic hydrogenation.

The Meyers Reaction (1994-2010)

Abstract: The Meyers reaction, i.e. the nucleophilic aromatic substitution reaction between aryloxazolines with organolithium and organomagnesium reagents is a very efficient and reliable method for the formation of new carbon-carbon and carbon-heteroatom bonds. The aim of this review is to present a general overview of this reaction in chiral and racemic form, emphasizing its scope and limitations. The literature is covered since 1994.

An Improved Synthesis of 3-Substituted 1,2,4-Triazolo[4,3-a]pyridines and 1,2,4-Triazolo[4,3-b]pyridazines

Abstract The preliminary results of a simple and versatile one-pot procedure for the preparation of 3-substituted 1,2,4-triazolo[4,3-a] pyridines and 1,2,4-triazolo[4,3-b]pyridazines are described. Intramolecular cyclization of nitrile imine ylides are carried out by treatment of 2-pyridyl- and 3-pyridazinylhydrazones with chloramine T.

Combined directed ortho metalation—intramolecular Friedel–Crafts connections. Regiospecific route to 1-substituted fluoren-9-ones

Abstract ortho -Substituted-2-biphenyl carboxylic acids of the type 3a – j were prepared by the tandem metalation sequence from 2-biphenyl carboxylic acid 1 with sec -butyllithium in THF at −78°C followed by quenching with electrophiles. The carboxylic acids 3a – f were converted into 1-substituted fluorenones 4a – f upon treatment with methanesulfonic acid.

Lithium Bis-(diisopropylamino)boracetylide [LiCCB(NiPr2)2]. A new reagent for the preparation of terminal alkynes

Abstract Terminal alkynes RCCH [R = PhCO, PhCH 2 OCO, (CH 3 ) 2 CHCH 2 OCO, Et 2 NCO, (EtO) 2 P(O), PhCH 2 , H 2 CCHCH 2 , and PhCH(OH)] may be prepared in satisfactory yield in a one-pot process by reaction in THF at −78 °C of the titled reagent with electrophiles followed by acidic workup with dilute HCl.

ortho-Lithium/magnesium carboxylate-driven aromatic nucleophilic substitution reactions on unprotected naphthoic acids.

Substitution of an ortho-fluoro or methoxy group in 1- and 2-naphthoic acids furnishing substituted naphthoic acids occurs in good to excellent yields upon reaction with alkyl/vinyl/aryl organolithium and Grignard reagents, in the absence of a metal catalyst without the need to protect the carboxyl (CO(2)H) group. This novel nucleophilic aromatic substitution is presumed to proceed via a precoordination of the organometallic with the substrate, followed by an addition/elimination.

Synthesis of N-Aryl and N-Alkyl Anthranilic Acids via SNAr Reaction of Unprotected 2-Fluoro- and 2-Methoxybenzoic Acids by Lithioamides

Substitution of the fluoro or methoxy group in unprotected 2-fluoro- and 2-methoxybenzoic acids to afford N-aryl and N-alkyl anthranilic acids occurs upon reaction with lithioamides under mild conditions in the absence of a metal catalyst.