The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Jonathan Clayden - One of the best experts on this subject based on the ideXlab platform.
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Polycyclic Indoline Derivatives by Dearomatizing Anionic Cyclization of Indole and Tryptamine-Derived Ureas
2018Co-Authors: Jessica E. Hill, Quentin Lefebvre, Laura A. Fraser, Jonathan ClaydenAbstract:The base-promoted dearomatizing cyclization of anionic indole-containing urea derivatives provided tri- or tetracyclic indoline-containing scaffolds from lithiated urea intermediates. 3-Substituted indoles, including tryptamine derivatives, generally underwent the reaction in high yield and with excellent diastereoselectivity. In situ IR spectroscopy suggests a deprotonation–Carbolithiation–reprotonation mechanism
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Carbolithiation of S‑Alkenyl‑N‑aryl Thiocarbamates: Carbanion Arylation in a Connective Route to Tertiary Thiols
2016Co-Authors: Daniele Castagnolo, Daniel J Foley, Hatice Berber, Renzo Luisi, Jonathan ClaydenAbstract:S-Alkenyl-N-arylthiocarbamates are formed from allylic alcohols by sigmatropic rearrangement and isomerization or CC bond cleavage. They undergo Carbolithiation with a range of organolithium reagents, generating benzyllithium intermediates in a stereospecific manner which may undergo N to C aryl migration to yield thiocarbamates with tertiary substituents. A simple base-promoted alcoholysis reveals a series of hindered tertiary thiols with branched carbon skeletons
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Tertiary Alcohols by Tandem β-Carbolithiation and N→C Aryl Migration in Enol Carbamates
2016Co-Authors: Anne M Fournier, Jonathan ClaydenAbstract:Enol carbamates (O-vinylcarbamates) derived from aromatic or α,β-unsaturated compounds and bearing an N-aryl substituent undergo Carbolithiation by nucleophilic attack at the (nominally nucleophilic) β position of the enol double bond. The resulting carbamate-stabilized allylic, propargylic, or benzylic organolithium rearranges with N→C migration of the N-aryl substituent, creating a quaternary carbon α to O. The products may be readily hydrolyzed to yield multiply branched tertiary alcohols in a one-pot tandem reaction, effectively a polarity-reversed nucleophilic β-alkylation–electrophilic α-arylation of an enol equivalent
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2,2- and 2,6-diarylpiperidines by aryl migration within lithiated urea derivatives of tetrahydropyridines
2015Co-Authors: Michael Tait, Sam Butterworth, Jonathan ClaydenAbstract:2-Aryltetrahydropyridines formed by anionic cyclization or ring-closing metathesis were converted to their N′-aryl urea derivatives. Depending on the position of the unsaturation within the tetrahydropyridine ring, metalation by deprotonative lithiation or Carbolithiation led to migration of the N′-aryl substituent to the 2- or 6-position via intramolecular nucleophilic attack of a benzylic organolithium on the aryl ring. The products are a range of 2,2-, 2,2,3-, and 2,6-polysubstituted piperidine derivatives. Related chemistry was observed in pyrroline homologues.
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enantioselective Carbolithiation of s alkenyl n aryl thiocarbamates kinetic and thermodynamic control
2015Co-Authors: Daniele Castagnolo, Renzo Luisi, Leonardo Degennaro, Jonathan ClaydenAbstract:The addition of n-butyllithium to alkenylthiocarbamates in the presence of (−)-sparteine or the (+)-sparteine surrogate leads to asymmetric Carbolithiation, and returns enantiomerically enriched thiocarbamate derivatives of secondary thiols. In THF, with the (+)-sparteine surrogate, in situ aryl migration leads to an enantiomerically enriched tertiary thiol derivative. Remarkably, the two pseudoenantiomeric chiral ligands do not always give enantiomeric products, probably as a result of a complex interplay of kinetic and thermodynamic control. In situ IR and NMR studies of a stable, hindered lithiated thiocarbamate demonstrated its chemical and configurational stability over a period of hours at 0 °C.
Dieter Hoppe - One of the best experts on this subject based on the ideXlab platform.
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synthesis of 2 alkylidene cycloalkane 1 3 diols via enantioselective intramolecular Carbolithiation
2003Co-Authors: Gabriele Gralla, Birgit Wibbeling, Dieter HoppeAbstract:The lithiodestannylation and intramolecular anti-selective Carbolithiation of α-lithiated ω-carbamoyloxy-1-alkynyl carbamates have been used to synthesize highly enantioenriched protected 2-alkylidene-cycloalkane-1,3-diols.
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stereoselective intermolecular Carbolithiation of open chain and cyclic 1 aryl 1 alkenyl n n diisopropylcarbamates coupled with electrophilic substitution observation of p carboxylation in a benzyllithium derivative
2002Co-Authors: Jan Georg Peters, Roland Frohlich, Birgit Wibbeling, Michael Seppi, Dieter HoppeAbstract:1-Aryl-1-alkenyl N,N-diisopropylcarbamates (1) are obtained from alkyl aryl ketones and N,N-diisopropylcarbamoyl chloride (CbCl) by heating with excess pyridine. These undergo facile syn-Carbolithiation by alkyllithium/diamine and produce configurationally stable lithiated benzyl carbamates, which have been trapped with different electrophiles. If the reaction is carried out in the presence of chiral diamines, such as (-)-sparteine or (-)-α-isosparteine, moderate enantiofacial differentiation is observed.
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sparteine mediated stereoselective intramolecular Carbolithiation of 4 substituted 5 hexynyl carbamates synthesis of enantiopure 1 3 difunctionalized alkylidene cyclopentanes
1999Co-Authors: Martin Oestreich, Roland Frohlich, Dieter HoppeAbstract:The stereoselective Carbolithiation of alkynes with external chiral induction has been achieved for the first time by fusing the concepts of the asymmetric deprotonation (A) with s-BuLi/(−)-sparteine (s-BuLi/1) and the intramolecular Carbolithiation (B). Several 4-functionalized 5-hexynyl carbamates with different terminal substituents have been prepared and efficiently cyclized providing enantiopure highly substituted alkylidene cyclopentanes. The presence of a sterically demanding substituent in the propargylic position is the essential feature of these cyclizations in order to suppress the abstraction of the remaining propargylic proton. Furthermore, in dependence on the terminal substituent, the 6-phenyl-substituted precursors undergo an intramolecular Carbolithiation whereas for the 6-trimethylsilyl-substituted alkynes a subsequent migration of the O-carbamoyl group onto the vinylic carbanionic center follows.
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sparteine mediated asymmetric intramolecular Carbolithiation of alkenes synthesis of enantiopure cyclopentanes with three consecutive stereogenic centers
1999Co-Authors: Dieter Hoppe, Martin Oestreich, Michael J Woltering, Roland FrohlichAbstract:An asymmetric intramolecular Carbolithiation reaction was developed by combining the (−)-sparteine-mediated enantiotopos-differentiating deprotonation and the anionic 5-exo-trig cyclization. Achiral 6-phenylhex-5-enyl carbamates were efficiently cyclized furnishing regio-, diastereo- (dr >99 : 1), and enantioselectively (er >98 : 2) 1,2-trans-substituted cyclopentanes. The intermediate primary benzylic lithium-carbanion pairs were – in spite of their configurative lability – diastereoselectively substituted by versatile electrophiles creating a third consecutive stereogenic center. Additionally, some 4-functionalized 6-phenylhex-5-enyl carbamates were also cyclized in high yield to provide enantiomerically pure cyclopentanes incorporating three adjacent stereogenic centers.
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sparteine mediated stereoselective intramolecular Carbolithiation of alkynes
1998Co-Authors: Martin Oestreich, Roland Frohlich, Dieter HoppeAbstract:Abstract The asymmetric deprotonation mediated by the chiral base s-butyllithium/(−)-sparteine of 4-substituted 5-hexynyl carbamates permits the synthesis of enantioenriched carbanionic pairs which undergo a regioselective 5-exo-dig ring closure with the triple bond acting as an internal electrophile. The functionalized five-membered rings are formed with complete stereoselectivity in high yields.
Jacques Maddaluno - One of the best experts on this subject based on the ideXlab platform.
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intramolecular Carbolithiation of heterosubstituted alkynes an experimental and theoretical study
2015Co-Authors: Rudy Lhermet, Maha Ahmad, Catherine Fressigne, Muriel Durandetti, Clémence Hauduc, Jacques MaddalunoAbstract:Lithiation of 2-iodophenyl-propargylethers (I) results in a 5-exo-dig cyclization to yield products (II) selectively.
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Intramolecular Carbolithiation of Heterosubstituted Alkynes: An Experimental and Theoretical Study.
2015Co-Authors: Rudy Lhermet, Maha Ahmad, Catherine Fressigne, Muriel Durandetti, Clémence Hauduc, Jacques MaddalunoAbstract:A series of heterosubstitued alkynes was successfully submitted to the intramolecular Carbolithiation of their triple bond. We show that the addition is stereoselective because of the control exerted by the terminal substituent X on the geometry of the transition state. A complementary DFT study suggests that the addition is anti when a strong Li–X interaction occurs.
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Carbolithiation of chloro substituted alkynes a new access to vinyl carbenoids
2015Co-Authors: Rudy Lhermet, Maha Ahmad, Catherine Fressigne, Bernard Silvi, Muriel Durandetti, Jacques MaddalunoAbstract:Intramolecular Carbolithiation of chloro-substituted alkynes such as (I), (III), and (V) provides access to exocyclic alkylidene carbonoids.
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Carbolithiation of chloro substituted alkynes a new access to vinyl carbenoids
2014Co-Authors: Rudy Lhermet, Maha Ahmad, Catherine Fressigne, Bernard Silvi, Muriel Durandetti, Jacques MaddalunoAbstract:The intramolecular Carbolithiation of a series of chloro-substituted alkynes leads to exocyclic alkylidene carbenoids of which both nucleophilic and electrophilic characters can be drove. A sole stereoselective 5-exo-dig addition takes place, probably because of a strong and persisting Li-Cl interaction arising before the transition state.
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Influence of the Acetylenic Substituent on the Intramolecular Carbolithiation of Alkynes: A DFT Theoretical Study
2013Co-Authors: Catherine Fressigné, Rudy Lhermet, Muriel Durandetti, Annelise Girard, Jacques MaddalunoAbstract:A theoretical study of the intramolecular 5-exo-dig Carbolithiation of substituted propargyl o-lithioaryl ethers, leading to dihydrobenzofurans, has been performed. The results show that a DFT description of the reaction (B3P86, 6-31G**) matches the experimental data provided that an explicit solvation by two molecules of THF is considered. To take place, the cyclization also implies that the acetylenic chain adopts a conformation in which a significant interaction arises between the lithium and the CC triple bond. Reaching the cyclization TS requires the passage of an activation barrier that should not be higher than 12–13 kcal mol–1. From a thermodynamic point of view, the reaction is exothermic whatever the substituent R (from approximately −40 to −62 kcal mol–1). In the starting substrate, a supplementary interaction between the Li and a substituent at the propargylic position can develop, influencing the future double-bond configuration. Thus, derivatives exhibiting an R–Li interaction tend to provide E olefins. In contrast, when no coordination between the lithium cation and the terminal R occurs, syn Carbolithiation takes place, and the configuration of the exocyclic olefin is likely to be Z. This hypothesis accounts for most of the experimental results published before
Donal F Oshea - One of the best experts on this subject based on the ideXlab platform.
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mechanistic insight into stereoselective Carbolithiation
2011Co-Authors: Viktoria H Gessner, Annemarie L Hogan, Stephan G Koller, Carsten Strohmann, Donal F OsheaAbstract:This article addresses the mechanistic features of asymmetric car- bolithiation of b-methylstyrenes. While often the presence of functional groups is required to obtain high enantioselec- tivities in Carbolithiation reactions, simple b-methylstyrene also gives high selectivities in ()-sparteine-mediated addition of alkyl lithium compounds. Computational studies on the carboli- thiation of b-methylstyrene with ()- sparteine show that the observed selec- tivities are the result of repulsion ef- fects in the diastereomeric transition states between the ()-sparteine·alkyl lithium adduct and the b-methylstyr- ene, upon approximation of the two re- actants. In contrast, for the ortho- amino b-methylstyrene (E)-benzyl(2- propenylphenyl)amine (4) X-ray struc- ture analyses of intermediate lithium amides indicate a Carbolithiation mech- anism in which one side of the double bond is shielded by the amide moiety, leaving only one side free for approach of the chiral alkyl lithium adduct.
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synthetic applications of Carbolithiation transformations
2008Co-Authors: Annemarie L Hogan, Donal F OsheaAbstract:Carbolithiation reactions are exceptionally versatile transformations which have been utilised in a remarkably diverse and creative manner. In this review we outline the background and scope of these reactions and then focus on their use in organic synthesis with a particular emphasis on literature examples published since 2000.
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applications of enantioselective Carbolithiation of ortho substituted β methylstyrenes
2008Co-Authors: Annemarie L Hogan, Thomas Tricotet, Alastair Meek, Shaista S Khokhar, Donal F OsheaAbstract:The enantioselective Carbolithiation of ortho-substituted (E)-beta-methylstyrenes provides access to chiral lithiated intermediates with broad synthetic potential. Specifically, beta-methylstyrenes with o-aminomethyl, ether, and oxazoline groups have been employed in the synthesis of chiral aromatics and heteroaromatics such as isoquinolines, isoquinolinones, benzofurans, and isobenzofuranones.
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Carbolithiation of o amino e stilbenes diastereoselective electrophile substitution with applications to quinoline synthesis
2008Co-Authors: Annemarie L Hogan, Donal F OsheaAbstract:A regioselective Carbolithiation of o-amino-(E)-stilbenes has been achieved with a series of alkyllithiums when THF is employed as the reaction solvent. The use of other solvents, such as diethyl ether or hydrocarbons, leads to a pronounced loss in regioselectivity. Moreover, high levels of diastereoselectivity have been obtained following reaction of the lithiated intermediate in THF with different electrophiles such as MeOD, CO2, and Bu3SnCl. It was shown that diastereoselectivity was influenced by the ortho-amino substituent and the alkyllithium utilized for Carbolithiation with N-Boc substituent and t-BuLi proving optimal. In the case of carbolithiated intermediate 3a, obtained from the reaction of N-Boc substituted stilbene with t-BuLi, 1H and 13C NMR analysis revealed predominantly one diastereoisomer which was stable at room temperature. Application of the Carbolithiation/electrophile reaction methodology to the synthesis of six-membered quinoline ring systems is demonstrated with substituted 3,4-d...
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7 azaindoles via Carbolithiation of vinyl pyridines
2007Co-Authors: Bertrand Cottineau, Donal F OsheaAbstract:The sequential reactions of a pyridine vinylation and alkene Carbolithiation constitutes a new route to substituted 7-azaindoles. The methodology involves a reaction sequence of controlled Carbolithiation of the vinyl double bond, subsequent trapping of the formal di-anion intermediate with a suitable electrophile, followed by an in situ ring closure and dehydration. The reaction sequence allows for aryl, heteroaryl, alkyl and keto substituents to be included at different positions around the heterocycle.
Anne-sophie Castanet - One of the best experts on this subject based on the ideXlab platform.
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Computational Insight into 1,2-Diamine, -Diether, and -Amino Ether Chiral Ligand-Mediated Carbolithiation: A Case of Enantioinduction Reversal.
2020Co-Authors: Hélène Guyon, Anne-sophie Castanet, Anne BoussonnièreAbstract:trans-1,2-Cyclohexanediamine, -diether, and -amino ether were compared as chiral inducers in the asymmetric intramolecular Carbolithiation of olefinic aryllithiums. Switching from diamine to ethereal ligands inverts the sense of asymmetric induction. This reversal of stereoselectivity was investigated through density functional theory calculations. High enantioselectivities observed with diether and amino ether ligands arise from favorable weak interactions between the ligand and the substrate. The relative efficiency of the three ligands and sense of stereoinduction for the most efficient diether and amino ether ligands prove to be foreseeable by modeling the reaction with the parent achiral 1,2-bidentate additives and comparing the diastereomeric transition states stemming from the two half-chair conformations of their lithium chelate.
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Readily Accessible 1,2-Amino Ether Ligands for Enantioselective Intramolecular Carbolithiation
2017Co-Authors: Hélène Guyon, Anne Boussonnière, Anne-sophie CastanetAbstract:A new class of chiral 1,2-amino ether ligands, readily accessible from naturally occurring alpha-amino- or alpha-hydroxy acids, was found to provide high levels of both conversion and stereocontrol (up to 95:5 er) in intramolecular Carbolithiation reactions, outperforming the benchmark ligand (-)-sparteine. The ligand could, be used in a substoichiometric amount (0.25 equiv) without significant loss of enantios electivity.
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Readily Accessible 1,2-Amino Ether Ligands for Enantioselective Intramolecular Carbolithiation
2017Co-Authors: Hélène Guyon, Anne Boussonnière, Anne-sophie CastanetAbstract:A new class of chiral 1,2-amino ether ligands, readily accessible from naturally occurring α-amino- or α-hydroxy acids, was found to provide high levels of both conversion and stereocontrol (up to 95:5 er) in intramolecular Carbolithiation reactions, outperforming the benchmark ligand (−)-sparteine. The ligand could be used in a substoichiometric amount (0.25 equiv) without significant loss of enantioselectivity