Eva Hevia

University of Strathclyde, Glasgow, Scotland, United Kingdom

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Publications (78)479.79 Total impact

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    ABSTRACT: Expanding the synthetic potential of Mg–Zn hybrid organyl reagents (generated via transmetallation reactions), this study uncovers a versatile approach, involving a sequence of direct Zn–I exchange and Pd catalysed cross-coupling reactions which grants access to a wide range of asymmetric bis(aryls). By combining X-ray crystallography with ESI-MS and non-deuterium NMR spectroscopic studies, new light is shed on the heterobimetallic constitution of the intriguing organometallic species [(THF)4MgCl2Zn(tBu)Cl] (1) and [{Mg2Cl3(THF)6}+{ZntBu3}−] (2), formed through transmetallation of tBuMgCl with n equivalent amounts of ZnCl2 (n = 1 and 3 respectively). Operating by cooperative effects, alkyl-rich hybrid 2 can effectively promote direct Zn–I exchange reactions with aromatic halides in short periods of time at room temperature in THF solution. The structural elucidation of key organometallic intermediates involved in some of these Zn–I exchanges, provides new reactivity insights into how these bimetallic systems operate. Thus, while the reaction of 2 with 3 equivalents of 2-iodoanisole (3b) gives magnesium dizincate [{Mg(THF)6}2+{Zn(o-C6H4-OMe)3}2−] (4) which demonstrates the 3-fold activation of the tBu groups attached to Zn in 2, using 2-iodobenzonitrile (3i), only two tBu groups react with the substrate, affording [(THF)4MgCl(NC-o-C6H4)ZnI(o-C6H4-CN)(THF)] (7). In 7 Mg and Zn are connected by an aryl bridge, suggesting that the formation of contacted ion-pair hybrids may have a deactivating effect on the outcome of the Zn–I exchange process. A wide range of homoleptic tris(aryl) zincate intermediates have been prepared in situ and used as precursors in Pd catalysed cross-coupling reactions, affording bis(aryls) 6a–s in excellent yields under mild reaction conditions without the need of any additive or polar cosolvent such as NMP or DMI.
    Chemical Science 06/2014; · 8.31 Impact Factor
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    ABSTRACT: Using an interlocking co-complexation approach, a homologous series of unsolvated alkali-metal zincates [MZn(CH2SiMe3)3] (M = Li , Na , K ) was prepared by reacting equimolar amounts of Zn(CH2SiMe3)2 with the relevant alkali-metal alkyl M(CH2SiMe3) employing non-coordinating hexane as a solvent. X-ray crystallographic studies reveal that these heterobimetallic compounds exhibit unprecedented supramolecular assemblies made up exclusively of a three-fold combination of M-CH2, Zn-CH2 and MMe interactions. Revealing an important alkali-metal effect, displays a linear chain structure; whereas and form much more intricate 3D and 2D coordination networks respectively. Shedding new light into the formation of these solvent-free zincates, DFT calculations indicate that the infinite degree of aggregation observed in plays a major role in thermodynamically driving the co-complexation reactions of their homometallic precursors. NMR spectroscopic studies suggest that in C6D6 solution exist as discrete contacted ion-pair species, where the alkali-metal is partially solvated by molecules of deuterated solvent. The supramolecular assemblies of can be easily deaggregated by adding the polydentate N-donors PMDETA (N,N,N',N'',N''-pentamethyldiethylenetriamine) or TMEDA (N,N,N',N'-tetramethylethylenediamine), affording monomeric [(PMDETA)LiZn(CH2SiMe3)3] () and [(TMEDA)2NaZn(CH2SiMe3)3] ().
    Dalton Transactions 06/2014; · 3.81 Impact Factor
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    ABSTRACT: Despite their enormous synthetic relevance, the use of polar organolithium and Grignard reagents is greatly limited by their requirements of low temperatures in order to control their reactivity as well as the need of dry organic solvents and inert atmosphere protocols to avoid their fast decomposition. Breaking new ground on the applications of these commodity organometallics in synthesis under more environmentally friendly conditions, this work introduces deep eutetic solvents (DESs) as a green alternative media to carry out chemoselective additions of ketones in air at room temperature. Comparing their reactivities in DES with those observed in pure water suggest that a kinetic activation of the alkylating reagents is taking place, favoring nucleophilic addition over the competitive hydrolysis, which can be rationalized through formation of halide-rich magnesiate or lithiate species.
    Angewandte Chemie International Edition 04/2014; · 11.34 Impact Factor
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    ABSTRACT: Despite their enormous synthetic relevance, the use of polar organolithium and Grignard reagents is greatly limited by their requirements of low temperatures in order to control their reactivity as well as the need of dry organic solvents and inert atmosphere protocols to avoid their fast decomposition. Breaking new ground on the applications of these commodity organometallics in synthesis under more environmentally friendly conditions, this work introduces deep eutetic solvents (DESs) as a green alternative media to carry out chemoselective additions of ketones in air at room temperature. Comparing their reactivities in DES with those observed in pure water suggest that a kinetic activation of the alkylating reagents is taking place, favoring nucleophilic addition over the competitive hydrolysis, which can be rationalized through formation of halide-rich magnesiate or lithiate species.
    Angewandte Chemie 04/2014;
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    ABSTRACT: The pivalates RZnOPiv⋅Mg(OPiv)X⋅n LiCl (OPiv=pivalate; R=aryl; X=Cl, Br, I) stand out amongst salt-supported organometallic reagents, because apart from their effectiveness in Negishi cross-coupling reactions, they show more resistance to attack by moist air than conventional organometallic compounds. Herein a combination of synthesis, coupling applications, X-ray crystallographic studies, NMR (including DOSY) studies, and ESI mass spectrometric studies provide details of these pivalate reagents in their own right. A p-tolyl case system shows that in [D8 ]THF solution these reagents exist as separated Me(p-C6 H4 )ZnCl and Mg(OPiv)2 species. Air exposure tests and X-ray crystallographic studies indicate that Mg(OPiv)2 enhances the air stability of aryl zinc species by sequestering H2 O contaminants. Coupling reactions of Me(p-C6 H4 )ZnX (where X=different salts) with 4-bromoanisole highlight the importance of the presence of Mg(OPiv)2 . Insight into the role of LiCl in these multicomponent mixtures is provided by the molecular structure of [(THF)2 Li2 (Cl)2 (OPiv)2 Zn].
    Angewandte Chemie International Edition 01/2014; · 11.34 Impact Factor
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    ABSTRACT: Exploring the reactivity of sodium butylmagnesiate reagent [{Na(THF)6}(+){(Ph2Si(NAr*)2)Mg(Bu)(THF)}(-)] () supported by the bulky chelating silyl(bisamido) ligand {Ph2Si(NAr*)2}(2-) (Ar* = 2,6-iPr2-C6H3) towards N-methylbenzimidazole (bIm(Me)), pyrrole and 2,6-diisopropylaniline (NH2Ar*), this study provides new insights into the ability of this bimetallic base to facilitate direct Mg-H exchange reactions as well as to exhibit polybasicity. Thus effectively promotes the deprotomagnesiation of bIm(Me) under mild reaction conditions to give the α-metallated intermediate [{Na(THF)5}2(+){(Ph2Si(NAr*)2)Mg(bIm(Me)*)}2(-)] () (bIm(Me)* = 2-N-methylbenzimidazolyl). Analysis of crystallographic and NMR data of combined with DFT calculations show that the metallated C in the bIm(Me)* ligands possesses a significant carbenic character. Contrasting with previous studies of benzothiazole (btz), does not react with an excess of bIm(Me) even under forcing refluxing conditions. Contrastingly, the amination reactions of equimolar amounts of with pyrrole and 2,6-diisopropylaniline allowed the isolation of [{(Ph2Si(NAr*)(NHAr*))Mg(NC4H4)2(THF)Na(THF)2}] () and [{Na(THF)6}(+){(Ph2Si(NAr*)(NHAr*))Mg(NHAr*)2(THF)}(-)] () respectively as crystalline solids. Highlighting the ability of to act as a polybasic reagent, and are formed as the result of the deprotonation of two molecules of the relevant amine via its butyl group and one amido arm of the silyl(bisamido) ligand. Similarly, the reactions of with 3 molar equivalents of the relevant amine yielded homoleptic tris(amido) compounds [(THF)2NaMg(NC4H4)3] () and [{Na(THF)6}(+){Mg(NHAr*)3}(-)] (), with the concomitant formation of bis(amine) Ph2Si(NHAr)2, as a result of the complete amination of using its three basic sites. The structures in the solid state of and were elucidated by X-ray crystallography. Despite their similar constitution, these heteroleptic tris(amido)magnesiates adopt contrasting structures, with the former displaying a contacted ion-pair structure, where Na and Mg are connected by two bridging pyrrolyl anions, whereas the latter gives rise to a solvent-separated ion pair motif. To the best of our knowledge represents the first crystallographically characterized magnesium compound containing an anionic non-substituted form of pyrrole. Noticeably, Mg interacts exclusively with the N atoms of the pyrrolyl ligands, forming strong σ-bonds, whereas Na prefers to engage with the π-systems of both NC4-rings.
    Dalton Transactions 11/2013; · 3.81 Impact Factor
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    ABSTRACT: Aiming to shed new light on the stability and constitution of the organometallic intermediates involved in direct ortho-metalation processes, using trifluoromethylbenzene (1) as a case study, this paper investigates the deprotonation of 1 using group 1 alkyl bases tBuLi and nBuNa in the presence of the Lewis donors TMEDA (N,N,N′,N′-tetramethylethylenediamine), THF, and PMDETA (N,N,N′,N″,N″-pentamethyldiethylenetriamine). A systematic and comprehensive study combining structural, spectroscopic, and theoretical studies reveals that these donors strongly influence the final outcome of the reactions, not only by activating the alkali-metal bases and facilitating deprotonation of 1 but also by tuning the regioselectivity of the reaction. Thus, while using tBuLi/TMEDA, ortho-metalation of 1 is preferred, switching to THF gives a complex mixture of products with the meta-regioisomer being the major species crystallizing from hexane solution. This donor effect is significantly reduced when nBuNa is employed, as ortho-regioselectivity is observed almost exclusively using THF, TMEDA, or PMDETA. DFT calculations computing the relative energies of the ortho-, meta-, and para-regioisomers obtained from these metalating systems have also been carried out. Reinforcing the experimental findings, these theoretical studies show that although in all cases the product of ortho-metalation is the most thermodynamically preferred, the energy difference between the three possible modeled regioisomers is much larger for the Na systems than for the Li ones. The structures of key reaction intermediates [(TMEDA)·Li(C6H4-CF3)]2 (2), [(TMEDA)·Na(C6H4-CF3)]2 (3), and [(PMDETA)·Na(C6H4-CF3)]2 (4) have been elucidated by X-ray crystallographic studies. All compounds exhibit a similar dimeric arrangement with a four-atom core constituting a {MCMC} ring. Interestingly for Na derivatives 3 and 4 unusual Na···F dative interactions are found, which appear to contribute to the overall stability of these compounds, therefore favoring ortho-metalation of 1, as the meta or para structures do not contain these additional interactions.
    Organometallics 09/2013; · 4.15 Impact Factor
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    ABSTRACT: Lithium 2,2,6,6-tetramethylpiperidide (LiTMP), one of the most important polar organometallic reagents both in its own right and as a key component of ate compositions, has long been known for its classic cyclotetrameric (LiTMP)4 solid-state structure. Made by a new approach through transmetalation of Zn(TMP)2 with tBuLi in n-hexane solution, a crystalline polymorph of LiTMP has been uncovered. X-ray crystallographic studies at 123(2) K revealed this polymorph crystallises in the hexagonal space group P63 /m and exhibited a discrete cyclotrimeric (C3h ) structure with a strictly planar (LiN)3 ring containing three symmetrically equivalent TMP chair-shaped ligands. The molecular structure of (LiTMP)4 was redetermined at 123(2) K, because its original crystallographic characterisation was done at ambient temperature. This improved redetermination confirmed a monoclinic C2/c space group with the planar (LiN)4 ring possessing pseudo (non-crystallographic) C4h symmetry. Investigation of both metalation and transmetalation routes to LiTMP under different conditions established that polymorph formation did not depend on the route employed but rather the temperature of crystallisation. Low-temperature (freezer at -35 °C) cooling of the reaction solution favoured (LiTMP)3 ; whereas high-temperature (bench) storage favoured (LiTMP)4 . Routine (1) H and (13) C NMR spectroscopic studies in a variety of solvents showed that (LiTMP)3 and (LiTMP)4 exist in equilibrium, whereas (1) H DOSY NMR studies gave diffusion coefficient results consistent with their relative sizes.
    Chemistry 09/2013; · 5.93 Impact Factor
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    ABSTRACT: Mixed-metal reagents [NaMg(CH2SiMe3)3] () and [(THF)NaMg(NPh2)3(THF)] [] can act as precatalysts to selectively promote the hydroamination/trimerization of isocyanates (RNCO) depending on the steric bulk of the R substituent.
    Chemical Communications 08/2013; · 6.38 Impact Factor
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    ABSTRACT: Merging two evolving areas in synthesis, namely cooperative bimetallics and N-heterocyclic carbenes (NHCs), this study reports the isolation of the first intermediates of alkali-metal-mediated zincation (AMMZn) of a free NHC and a Zn–NHC complex using sodium zincate [(TMEDA)NaZn(TMP)(tBu) 2 ] (1) as a metallating reagent. The structural authentication of (THF) 3 Na[:C{[N(2,6-iPr 2 C 6 H 3)] 2 CHCZn(tBu 2)}] (2) and [Na(THF) 6 ] + [tBu 2 Zn:C{[N(2,6-iPr 2 C 6 H 3)] 2 CHCZn(tBu 2)}] À (4), resulting from the reactions of 1 with unsaturated free NHC IPr (IPr ¼ 1,3-bis(2,6-di-isopropylphenylimidazole-2-ylidene) and NHC complex ZntBu 2 IPr (3) respectively demonstrates that in both cases, this mixed-metal approach can easily facilitate the selective C4 zincation of the unsaturated backbone of the NHC ligand. Furthermore, the generation of anionic NHC fragments enables dual coordination through their normal (C2) and abnormal (C4) positions to the bimetallic system, stabilising the kinetic AMMZn intermediates which normally go undetected and provides new mechanistic insights in to how these mixed-metal reagents operate. In stark contrast to this bimetallic approach when NHC-complex 3 is reacted with a more conventional single-metal base such as tBuLi, the deprotonation of the coordinated carbene is inhibited, favouring instead, co-complexation to give NHC-stabilised [IPr$LiZntBu 3 ] (5). Showing the potential of 2 to act as a transfer agent of its anionic NHC unit to transition metal complexes, this intermediate reacts with two molar equivalents of [ClAu(PPh 3)] to afford the novel digold species [ClAu:C{[N(2,6-iPr 2 C 6 H 3)] 2 CHCAu(PPh 3)}] (6) resulting from an unprecedented double transmetallation reaction which involves the simultaneous exchange of both cationic (Na +) and neutral (ZntBu 2) entities on the NHC framework.
    Chemical Science 08/2013; 4:4259. · 8.31 Impact Factor
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    ABSTRACT: Opening-up new synthetic applications of β-diketiminate stabilised magnesium complexes, this case study compares the ability of the alkyl [{Ar*NC(Me)CHC(Me)NAr*}Mg(Bu)(THF)] (1) and the amido reagent [{Ar*NC(Me)CHC(Me)NAr*}Mg(TMP)] (2) (Ar* = 2,6-i-Pr2-C6H3) to promote direct Mg–H exchange towards the series of 1,3-benzoazoles: benzoxazole (boz), benzothiazole (btz) and N-methyl benzimidazole (bImMe). Both reagents deprotonate boz at room temperature to yield [{Ar*NC(Me)CHC(Me)NAr*}Mg{O(o-C6H4)NC}(THF)] (3) via the C–O bond cleavage of a putative C2-magnesiated-benzoxazolyl intermediate. Structurally tracking the reactivity of 1 and 2 towards less acidic btz and bImMe showed that the behaviour of reagents 1 and 2 diverged dramatically. Kinetically activated TMP-reagent 2 effectively promotes the deprotonative magnesiation of btz and bImMe under mild reaction conditions, giving the alpha-metallated intermediates [{Ar*NC(Me)CHC(Me)NAr*}2Mg2{btz*}2] (4) and [{Ar*NC(Me)CHC(Me)NAr*}2Mg2{bImMe*}2] (7) (btz* = 2-benzothiazolyl; bImMe* = 2-N-methylbenzimidazolyl). Analysis of crystallographic and NMR data revealed that in 4 and 7 the metallated carbon atoms display a markedly carbenic character and that in solution these species exist at room temperature solely as the ring-closed products, without any observable equilibration to the acyclic isomers. Contrastingly, alkyl reagent 1 decreases the magnesiation rate of btz facilitating an intriguing new cascade activation process of two molecules of substrate involving a sequence of deprotonation/coordination/C–C coupling and ring-opening reactions to yield [{Ar*NC(Me)CHC(Me)NAr*}Mg{(btz*)C(H)N(o-C6H4)S}] (5). Hydrolysis of 5 followed by addition of the radical oxidant TEMPO ultimately produces the homocoupled product bis(benzothiazole) 6 in a 72% isolated yield. Thus, this establishes a novel transition-metal-free method to prepare homocoupled thiazoles. More straightforwardly, the coordination product [{Ar*NC(Me)CHC(Me)NAr*}Mg(Bu)(bImMe)] (8) was obtained when equimolar amounts of bImMe and 1 were reacted, illustrating the kinetic stubbornness of the Mg–C bond in butyl derivative 1. Complex 8 can be envisaged as a valuable guide to the constitution of a premetallation complex (in relation to the complex-induced proximity effect, CIPE).
    Chemical Science 03/2013; 4(4):1895-1905. · 8.31 Impact Factor
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    ABSTRACT: Exploring the co-complexation reactions between the gallium alkyl Ga(CH2SiMe3)3 and alkali-metal alkyl MCH2SiMe3 (M = Li, Na, or K) using an arene/hexane solvent mixture has allowed the isolation of solvent-free alkali-metal tetraorganogallates [{MGa(CH2SiMe3)4}∞] (M = Li, 1; Na, 2) and related benzene adduct [{(C6H6)2KGa(CH2SiMe3)4}∞] (3). By combining X-ray crystallography, NMR spectroscopy, and DFT calculations, this study sheds new light on the constitution of these mixed-metal species. X-ray crystallographic studies reveal that all gallates exhibit novel polymeric arrangements, with 1 and 2 sharing the same linear chain structure, made up exclusively of M–C and Ga–C bonds, whereas 3 displays a significantly more open structural motif, where the K and Ga atoms are connected by a single alkyl bridge and propagation occurs via weaker K···Me electrostatic interactions of a methyl from a SiMe3 group of an alkyl ligand from one monomer to the potassium from a neighboring monomeric unit. Multinuclear NMR spectroscopic studies suggest that in deuterated benzene solutions 1–3 exist as discrete solvent-separated ion-pair species where the alkali-metal is solvated by the arene solvent. DFT calculations show that while the infinite aggregation of these polymeric structures is key for thermodynamically favoring the formation of 1 and 2, in the case of 3 the solvation of unsaturated potassium by two molecules of benzene, via π-electrostatic interactions, appears to be the major contributor to its overall stability.
    Organometallics 01/2013; 32(2):480–489. · 4.15 Impact Factor
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    ABSTRACT: New coordination complexes of the neutral tripodal tetra-amine Me(6)TREN with tBu(3)Ga or tBu(2)Zn have been synthesised and studied with their molecular structures revealing, for the first time, coordination to metal centres via an η(1) or η(2) mode, adding to previously reported η(3) and η(4) ligated examples.
    Dalton Transactions 07/2012; 41(34):10141-4. · 3.81 Impact Factor
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    ABSTRACT: Comparing the reactivity of the related lithium zincates [(THF)LiZn(TMP)(t)Bu(2)] (1) and [(PMDETA)LiZn(t)Bu(3)] (2) towards pyrazine discloses two new bimetallic approaches for the selective 2,5-dideprotonation and room temperature C-H alkylation of this sensitive heterocycle.
    Chemical Communications 02/2012; 48(14):1985-7. · 6.38 Impact Factor
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    ABSTRACT: Exploring the reactivity of the mixed-metal reagent [(TMEDA)Na(TMP)Zn(t)Bu(2)] (1) towards substituted metallocene benzoylferrocene 2, this study has found that two competing reactivity pathways are available for the sodium TMP-zincate, namely (i) remote 1,6-nucleophilic addition of a tert-butyl group to the phenyl ring of 2, and (ii) simultaneous alpha-deprotonation of the substituted cyclopentadienyl ring of the metallocene and alkylation (1,2-addition) across the C=O bond of the carbonyl group. A key organometallic intermediate [(TMEDA)Na(μ-TMP)Zn{OC((t)Bu)(Ph)(η(5)-C(5)H(3))Fe(η(5)-C(5)H(5))}] (3), resulting from the latter reaction has been trapped and characterised by X-ray crystallography and multinuclear ((1)H and (13)C) NMR spectroscopy. Its molecular structure revealed a unique two-fold activation of the tert-butyl groups bonded to zinc in the bimetallic base 1, showing for the first time that each alkyl group can exhibit markedly different reactivities (deprotonation vs. 1,2-addition) towards the same substrate molecule. Iodine interception of the organometallic intermediates of the reaction between 1 and 2 allowed the isolation and characterization ((1)H, (13)C NMR and X-ray crystallography) of the ferrocenyl derivatives [PhC(OH)((t)Bu)(η(5)-C(5)H(3)I)Fe(η(5)-C(5)H(5))] (4) and [4-(t)Bu-C(6)H(4)C([double bond, length as m-dash]O)(η(5)-C(5)H(4))Fe(η(5)-C(5)H(5))] (5) in a 29% and 24% isolated yield respectively. The low yield observed for the formation of 5 (resulting from the 1,6-addition reaction followed by spontaneous aerobic oxidation during aqueous workup) could be increased to 41% when the reaction mixture was hydrolysed in the presence of the radical oxidant TEMPO.
    Dalton Transactions 01/2012; 41(1):98-103. · 3.81 Impact Factor
  • Angewandte Chemie International Edition 10/2011; 50(42). · 11.34 Impact Factor
  • Eva Hevia, Robert E. Mulvey
    Angewandte Chemie 09/2011; 123(40).
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    ABSTRACT: This study investigates the ability of the mixed-metal reagent [Li(TMP)Zn(tBu)2] 1 to promote direct Zn–H exchange reactions (zincations) of a wide range of N-heterocyclic molecules. The generated metallated intermediates from these reactions are intercepted with I2 and some of them are also employed as precursors in Pd-catalysed Negishi cross-coupling applications. A comparison with recent precedents in metallation chemistry reveals that for some of these heterocycles, 1 allows improved conversions, under milder conditions and in certain cases, even gives unique regioselectivities.
    Tetrahedron Letters 09/2011; 52(36):4590–4594. · 2.40 Impact Factor
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    ABSTRACT: Ligand domin(o)ated: In contrast to the straightforward deprotonation of benzothiazole using Grignard reagents, treatment of benzothiazole with 1 leads to a novel type of activation. The initial magnesiation initiates an unstoppable domino reaction of CC coupling, ring opening, nucleophilic addition, and deprotonation to give 2. THF=tetrahydrofuran.
    Angewandte Chemie International Edition 07/2011; 50(42):9857-60. · 11.34 Impact Factor
  • Eva Hevia, Robert E Mulvey
    Angewandte Chemie International Edition 07/2011; 50(40):9242-3. · 11.34 Impact Factor