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The Preparation of Organolithium Reagents and Intermediates

Organolithium Compounds (2004)

  1. Frédéric Leroux1,
  2. Manfred Schlosser2,
  3. Elinor Zohar3,
  4. Ilan Marek3

Published Online: 15 DEC 2009

DOI: 10.1002/9780470682531.pat0305

Patai's Chemistry of Functional Groups

Patai's Chemistry of Functional Groups

How to Cite

Leroux, F., Schlosser, M., Zohar, E. and Marek, I. 2009. The Preparation of Organolithium Reagents and Intermediates. Patai's Chemistry of Functional Groups. .

Author Information

  1. 1

    Université Louis Pasteur (ECPM), Laboratoire de stéréochimie, Strasbourg, France

  2. 2

    Swiss Federal Institute of Technology, Institute of Molecular and Biological Chemistry, Lausanne, Switzerland

  3. 3

    Technion—Israel Institute of Technology, Department of Chemistry and Institute of Catalysis, Science and Technology, Haifa, Israel

Publication History

  1. Published Online: 15 DEC 2009
Table 1. A Survey of the Standard Methods Applied to the Preparation of Organometallic Compounds: Three Crosses Mean ‘Generally Applicable’, Two ‘Restricted, Though Important Scope of Applicability’ and One ‘Narrow Scope’
Reductive insertionZ (leaving group)Permutational interconversion
inline image inline image inline imageX (halogen) inline image inline image inline image
inline image inline imageY (chalcogen) inline image
inline image inline imageQ (metalloid) inline image inline image
inline imageC (carbon) inline image
inline imageH (hydrogen) inline image inline image inline image
Table 2. Primary Alkyllithiums Li[BOND]R (Including Neopentylic Ones) by Metal Insertion into Halides R[BOND]X: Yields as Determined by Titration1e or after Trapping with an Electrophile El[BOND]X′
Li[BOND]RXSνaProductEl[BOND]X′Reference
  1. a

    Solvent Sν: PET = petroleum ether (pentanes, hexanes, heptanes), DEE = diethyl ether, THF = tetrahydrofuran.

  2. b

    Various electrophiles.

Li[BOND]CH3Cl, Br, IDEEca 80%titration 3, 4
Li[BOND]C2H5Cl, BrPET50%titration 5-9
Li[BOND]C3H7ClPETca 80%titration 5, 10
Li[BOND]C4H9Cl, BrPETca 95% b 11, 12
Li[BOND]C6H13ClDEE≥90%titration 13
Li[BOND]C8H17ClTHF94%H2O 14
Li[BOND]C12H25ClDEE77%titration 15, 16
Li[BOND]CH2C(CH3)3ClPET; DEE71%[(H3C)2CH]2CO 17, 18
Li[BOND]CH2Si(CH3)3ClPET; DEE90%isol. by sublim. 19
Table 3. Secondary and Tertiary Alkyllithiums Li[BOND]R: Yields of Trapping Products as a Function of the Precursor Halide X and the Electrophile El[BOND]X′ Used
Li[BOND]RXSνaProductEl[BOND]X′Reference
  1. a

    Solvent Sν : PET = petroleum ether (pentanes, hexanes, heptanes), DEE = diethyl ether.

  2. b

    inline image

  3. c

    inline image

  4. d

    inline image

  5. e

    inline image

Li[BOND]CH(CH3)2BrPET45%titration 5
Li[BOND]CH(CH3)C2H5ClPET50%titration 20
Li[BOND]C(CH3)3ClPET62%CO2 21
   89%titration 22-24
Li[BOND]CH(CH2)2bBrDEE88%SnCl4 25
Li[BOND]CH(CH2)5cClDEE70%GeCl4 26
Li[BOND]C7H11dClPET51%CO2 27
Li[BOND]C10H15eClPET82%D2O 28
Table 4. 1-Alkenyllithiums Li[BOND]R: Yields of Trapping Products as a Function of the Precursor Halide X and the Electrophile El[BOND]X′ (Common Temperature Range: +25 °C to +50 °C)
Li[BOND]RXSνaProductEl[BOND]X′Reference
  1. a

    Solvent Sν: DEE = diethyl ether, THF = tetrahydrofuran.

  2. b

    Various electrophiles El[BOND]X′.

Li[BOND]CH[DOUBLE BOND]CH2ClTHF70–80% b 23, 29, 30
Li[BOND]CH[DOUBLE BOND]C(CH3)2BrDEE30%H5C6CHO 31, 32
inline imageBrDEE75%H3CCOOC2H5 33
inline imageClDEE40%H5C6CHO 31, 32
Table 5. Aryllithiums Li[BOND]R Lacking Hetero-Substituents by Metal Insertion into Haloarenes, the Reactions Being Generally Conducted in Diethyl Ether and in the Temperature Range of 0 °C to +40 °C (Refluxing Ether)
Li[BOND]RXaProductEl[BOND]X′bReference
  1. a

    X = Halogen in the starting material, being displaced by metal.

  2. b

    The concentration of the organometallic solution prepared was determined either by the titration1e of an aliquot or by isolation of the product formed upon the trapping of an aliquot using an electrophilic reagent El[BOND]X′.

  3. c

    In diethyl ether or tetrahydrofuran.

inline imageCl, Brcca 85%CO2 34-38
inline imageBr93%Titration 39
inline imageBr86%Titration 39
inline imageBr95%Titration 34-37, 39
inline imageI50% inline image 40
inline imageBr, Ica 75%CO2 41, 42
inline imageBr72%Titration 41
inline imageBr87%Titration 41, 43
inline imageBr75%Titration 44
inline imageBr85%CO2 45, 46
Br44%Titration 
inline imageBr80%Titration 39
inline imageBr81%SiCl4 39, 47
Table 6. Aryllithiums Li[BOND]R Carrying Amino and Alkoxy Substituents Prepared in Diethyl Ether by Metal Insertion into the Corresponding Bromoarene
Li[BOND]RProductEl[BOND]X′aReference
  1. a

    El[BOND]X′ = electrophilic trapping reagent.

  2. b

    inline image; then oxidation with CrO3.

inline image0%(H5C6)3PbCl 48
inline image58%(H5C6)3SiCl 49, 50
inline image65%CO2 22, 51
inline image22%R′COOC2H5b 52
inline image85%titration 53
inline image66%titration 53
Table 7. Butyllithium in the Presence of Butyl Chloride, Bromide and Iodide (0.50 M Initial Concentrations): Half-Lives τ1/2 (in Hours) as a Function of the Solvent Benzene (BNZ) or Diethyl Ether (DEE) at Ambient Temperature54
H9C4[BOND]X + LiC4H9inline image (in hours)inline image (in hours)
X = I3<0.1
X = Br40 0.5
X = Cl>10040
Table 8. Primary Aliphatic Organolithiums Li[BOND]R by Halogen/Metal Permutation between Haloalkanes X[BOND]R and tert-Butyllithium in Diethyl Ether at −75 °C
Li[BOND]RXaProductEl[BOND]X′bReference
  1. a

    X = halogen displaced by the metal.

  2. b

    El[BOND]X′ = electrophilic trapping reagent.

  3. c

    Using butyllithium rather than tert-butyllithium.

  4. d

    C10H15 = 2-adamantyl.

  5. e

    At −45 °C rather than −75 °C.

Li[BOND]CH3cBr64%titration 64-66
Li[BOND]C4H9I91%H9C4CH[DOUBLE BOND]O 67
Li[BOND]C8H17I93%H3CCOCH3 67
Li[BOND]C10H15d, eI66%CO2 68
inline imageI91%CO2 67
Li[BOND](CH2)2C6H5I91%CO2 67-69
Li[BOND]CH2C(CH3)3I89%H7C3CH[DOUBLE BOND]O 67
Li[BOND](CH2)2CH[DOUBLE BOND]CH2I88%ClSn(CH3)3 69
Li[BOND](CH2)3CH[DOUBLE BOND]CH2I87%CO2 70
Li[BOND](CH2)2C[TRIPLE BOND]C[BOND]C4H9I80%ClSn(CH3)3 69
Li[BOND](CH2)4C[TRIPLE BOND]C[BOND]C6H5I87%D2O 71
Table 9. Cyclopropyl- and Other Cycloalkyllithiums Li[BOND]R by Halogen/Metal Permutation between Haloalkanes X[BOND]R and Reagents Li[BOND]R′ in Diethyl Ether (DEE)
Li[BOND]RLi[BOND]R′XaTbProductEl[BOND]X′cReference
  1. a

    X = halogen which is displaced by the metal.

  2. b

    Exchange and trapping temperature.

  3. c

    El[BOND]X′ = electrophilic trapping reagent.

  4. d

    In tetrahydrofuran (THF) rather than DEE.

inline image dLiCH(CH3)3Br−75 °C91%(H5C6)2CO 72, 73
inline imageLiCH(CH3)2Br

0 °C

15%CO2 74
inline imageLiC(CH3)3I−60 °C60–90%H5C6CHO 75
inline imageLiC(CH3)3I−70 °C60–90%H5C6CHO 75
inline imageLiC(CH3)3I−70 °Cca 70%H5C6CHO 76
inline imageLiC4H9Br+25 °C41%CO2 77, 78
Table 10. α-Fluoro-, α-Chloro-, α-Bromo- and α-Iodoalkyllithiums Li[BOND]R by Halogen/Metal Permutation Using Organometallic Reagents Li[BOND]R′
Li[BOND]RLi[BOND]R′XaTProductEl[BOND]X′bReference
  1. a

    X = halogen being displaced.

  2. b

    El[BOND]X′ = electrophilic trapping reagent.

  3. c

    Halogen/metal exchange performed in the presence (in situ) of the electrophile.

  4. d

    The isolated product emanated from a subsequent reaction.

  5. e

    Detected by NMR.

  6. f

    Diethyl ether (DEE) rather than THF as the solvent.

  7. g

    Or butyllithium.

Li[BOND]CH2CLiC4H9I−75 °C88%H5C6CHOc 79-82
Li[BOND]CH2ILiC4H9I−75 °C89% inline image d 83
Li[BOND]CH(CH3)ClLiCH(CH3)C2H5Br−115 °C63%H5C6CHO 84
Li[BOND]CH(CH3)BrLiCH(CH3)C2H5Br−115 °C59%H5C6CHO 84
Li[BOND]C(CH3)2BrLiCH(CH3)C2H5Br−115 °C41%H5C6CHO 84
Li[BOND]C(C6H5)2ClLiC4H9Cl−100 °C75%CO2 85
Li[BOND]CBr2CH3LiC4H9Br−100 °C e 60
Li[BOND]C2F5LiCH3c, fI−75 °C88%H5C2CHO 86
Li[BOND]C3F7LiCH3c, fI−40 °C54%(H5C6)2CO 87, 88
Li[BOND]C7F15LiC4H9cI−90 °C38%CO2 89
Li[BOND]CF(CF3)2LiCH3c, fI−75 °C53%H5C6CHO 90
Li[BOND]CCI3LiC4H9Cl−100 °C76%CO2 85, 91
Li[BOND]CBr3LiC6H5gBr−110 °C91%CO2 60, 92
Table 11. α- or β-Alkoxy- and α-Halocyclopropyllithiums Li[BOND]R by Halogen/Metal Permutation between Bromocyclopropanes and Organolithium Reagents Li[BOND]R′ Followed by Trapping with Electrophiles El[BOND]X′
Li[BOND]RLi[BOND]R′SνaTProductEl[BOND]X′bReference
  1. a

    Solvent (Sν): DEE = diethyl ether, THF = tetrahydrofuran.

  2. b

    El[BOND]X′ = electrophilic trapping reagent.

  3. c

    Product isolated after subsequent transformation.

  4. d

    7,7-Diiodonorcarane as the starting material.

  5. e

    Detected by NMR.

  6. f

    Bn = CH2C6H5.

inline imageLiC(CH3)3DEE−75 °C92% inline image 93
inline imageLiC(CH3)3DEE−75 °C85%H13C6CHO 93
inline imageLiC(CH3)3DEE−75 °C81% inline image c 94
inline imageLiC4H9THF−135 °C9%H2O 95
inline imageLiC4H9THF−110 °C64%Br2 58, 95
inline imageLiC4H9THF−100 °C39% inline image 96-99
inline image dLiC4H9THF−80 °C e 92
inline imageLiC4H9THF−100 °C70%(H3C)2CO 100
inline imageLiC4H9THF−100 °C60%(H3C)2CO 100, 101
inline imageLiC4H9THF−100 °C80%H9C4CHO 100
inline image fLiC4H9DEE−95 °C83%HOC2H5 102-104
inline imageLiCH3DEE−80 °C88%CO2 105
inline imageLiCH3DEE−80 °C65%CO2 105
Table 12. 1-Alkenyllithiums Li[BOND]R by Halogen/Metal Permutation
Li[BOND]RXaLi[BOND]R′SνbTProductEl[BOND]X′cReference
  1. a

    X = halogen displaced by the metal.

  2. b

    Solvent (Sν): PET = petroleum ether (pentanes, hexanes, heptanes), DEE = diethyl ether, THF = tetrahydrofuran.

  3. c

    El[BOND]X′ = electrophilic trapping reagent.

  4. d

    Or LiC(CH3)3.

  5. e

    Or LiC2H5.

inline imageBrLiC(CH3)3THF−115 °C74%(SC6H5)2 106, 107
inline imageILiC(CH3)3PET+25 °C71%H5C6CHO 106, 107
inline imageILiC4H9dPET+25 °C71%H5C6CHO 106, 108
inline imageILiC4H9eDEE−50 °C91%H3CCHO 109
inline imageILiC(CH3)3PET+25 °C74%H5C6CHO 110
inline imageILiC(CH3)3PET+25 °C77%H5C6CHO 110
inline imageBrLiC(CH3)3DEE−80 °C24%c-(H2C)5CO 111
inline imageILiC4H9eDEE−50 °C91%(H5C2)2CO 109
Table 13. 1-Cycloalkenyllithium Compounds Li[BOND]R by Halogen/Metal Permutation
Li[BOND]RXaLi[BOND]R′SνbTProductEl[BOND]X′cReference
  1. a

    X = halogen displaced by the metal.

  2. b

    Solvent (Sν): DEE = diethyl ether, THF = tetrahydrofuran.

  3. c

    El[BOND]X′ = electrophilic trapping reagent.

  4. d

    Prepared in situ from trihalocyclopropanes.

  5. e

    Bis(trimethylsilyl)peroxide.

  6. f

    59% with CO2.

 CldLiCH3DEE+25 °C72%CO2 112
inline imageBrdLiCH3DEE+25 °C78%CO2 113
inline imageBrLiC(CH3)3THF−75 °C73%I2 106
inline imageBrLiC(CH3)3THF−75 °C52% e 106
inline imageBrLiC(CH3)3THF−75 °C93%ClSi(CH3)3 106
inline imageBrLiC(CH3)3THF−75 °C83%(SCH3)2 114
inline imageBrLiC4H9THF−60 °C7%fFClO3 115, 116
Table 14. Hetero (β-Amino, β- or γ-Alkoxy, β- or γ-Silyloxy, α- or β-Halo) Substituted 1-Alkenyllithiums Li[BOND]R by Halogen/Metal Permutation
Li[BOND]RXaLi[BOND]R′bSνcTProductEl[BOND]X′dReference
  1. a

    X = halogen in the precursor.

  2. b

    Exchange reagent Li[BOND]R′: LIT = LiC(CH3)3, LIC = LiC4H9, LIM = LiCH3.

  3. c

    Solvent (Sν): PET = petroleum ether; DEE = diethyl ether, THF = tetrahydrofuran.

  4. d

    El[BOND]X′ = electrophilic trapping reagent.

  5. e

    NQ2 = 2, 2, 5, 5-tetramethyl-1-aza-2,5-disilolanyl.

  6. f

    SiR″2R″′ = Si(CH3)2C(CH3)3.

  7. g

    Not specified.

  8. h

    R″′ = cis-CH2[BOND]CH = CH[BOND](CH2)3[BOND]COOCH3.

  9. i

    (H2C)5CO = Cyclohexanone; product isolated after acid hydrolysis as an α,β-unsaturated carbonyl compound.

inline image eBrLITDEE−80 °C82%H5C6NCO 117
inline imageBrLITTHF−70 °C100%(H3C)2NCHO 118, 119
inline imageBrLICTHF−75 °C75%H5C6CHO 120-122
inline imageBrLICTHF−75 °C75%(H5C6)2CO 121
inline imageBrLICTHF−75 °C67%(H3C)3SiCl 121, 123
inline imageILICPET−70 °C90%D2O 124
inline imageBrLITTHF−120 °C93%H5C6CHO 125
inline imageBrLITDEE−70 °C97%β-ionone 126
inline imageILITDEE−75 °C70%CO2 127
inline image fILITPET g g inline image h 128, 129
inline imageBrLICDEE−75 °C25%(H2C)5CO 130
inline imageClLICDEE−110 °C90%H2O 131
 ClLICTHF−135 °C82%(H2C)5COi 132
inline imageClLITDEE−60 °C90%(H2C)5COi 133, 134
 BrLIMDEE−75 °C66%(H2C)5COi 135
inline imageBrLICDEE−85 °C51%H5C6COCH3 136
inline imageBrLICTHF−110 °C92%CO2 137
Table 15. 1-Alkenyllithiums Li[BOND]R Carrying Lithiooxy or Lithiooxycarbonyl Groups (at the γ or β Position, Respectively): Generation by Halogen/Metal Permutation Using Exchange Reagents Li[BOND]R′ in Diethyl Ether or, with Respect to the First and Last Two Entries, in Tetrahydrofuran
Li[BOND]RXaLi[BOND]R′TbProductEl[BOND]X′cReference
  1. a

    X = halogen displaced by the metal.

  2. b

    If the temperature at T which the organometallic intermediate was generated varied, only the highest one is given.

  3. c

    El[BOND]X′ = electrophile used to trap the organometallic intermediate.

  4. d

    First the lithium β-bromoenolate was generated from the corresponding α-bromoketone using 2.0 equiv. of LiCH3.

  5. e

    Similar results were obtained with O-tert-butyldimethylsilyl protected 1-alkenyl bromides as the precursors.

  6. f

    Or sec-butyllithium.

  7. g

    Isolated as the lactone.

inline imageBrdLiC(CH3)30 °C88% inline image 138
inline imageBrdLiC(CH3)30 °C64% inline image 138
inline image eBr, ILiC(CH3)3f−75 °C55%H5C6CHO 139
inline image eBr, ILiC(CH3)3−75 °C57%H5C6CHO 139
inline image eBr, ILiC(CH3)3f−75 °C28%H5C6CHO 139, 140
inline image eBr, ILiC(CH3)3−75 °C65%(H3C)3CCHO 139
inline imageBrLiC4H9−100 °C38%H5C6CHOg 141
inline imageBrLiC4H9−100 °C61%H5C6CHOg 141
inline imageBrLiC4H9−100 °C47%H5C6CHOg 138
Table 16. Heteroatom-Free Aryllithiums Li[BOND]R by Halogen/Metal Permutation between Bromo- or Iodoarenes and Butyllithium
Li[BOND]RXaSνbTProductEl[BOND]X′cReference
  1. a

    X = halogen displaced by the metal.

  2. b

    Solvent (Sν): PET = petroleum ether, DEE = diethyl ether.

  3. c

    El[BOND]X′ = electrophilic trapping reagent.

  4. d

    Or in benzene or in diethyl ether.

  5. e

    In DEE in the range of −75 °C to +40 °C (reflux), in pure hydrocarbon media at +25 °C.

  6. f

    In the presence of N,N,N′,N′-tetramethylethylenediamine (TMEDA).

inline imageBr, IPETd e65%CO2 142-145
inline imageBrDEE+50 °C84%CO2 142, 143
inline imageBrDEE+50 °C65%CO2 142, 143
inline imageBrPET+25 °C86%CO2 142, 143
inline imageIDEE−70 °C76%CO2 146
inline imageBrDEE+25 °C62%CO2 142-145, 147
inline imageBrDEE−75 °C60%Cl3SiBr 148, 149
inline imageBrDEE+25 °C87%crystallized 150
inline imageBrDEE+25 °C97%CO2 151, 153
inline imageBrDEE+25 °C77%CO2 151
inline image fBrDEE+40 °C51%CO2 154
inline imageBrPET+25 °C72%CO2 155
Table 17. Amino-, Cyano- and Nitro-Substituted Aryllithiums Li[BOND]R by Halogen/Metal Permutation Using Butyllithium or Phenyllithium
Li[BOND]RLi[BOND]R′aSνbTProductEl[BOND]X′cReference
  1. a

    Li[BOND]R′ = organometallic exchange reagent.

  2. b

    Solvent (Sν): DEE = diethyl ether, THF = tetrahydrofuran.

  3. c

    El[BOND]X′ = electrophilic trapping reagent.

inline imageLiC4H9THF−75 °C83%(H5C6)2CO 156
inline imageLiC4H9DEE+49 °C32%CO2 157
inline imageLiC4H9DEE+40 °C56%CO2 157, 158
inline imageLiC4H9DEE0 °C80%(H5C6)2CO 159
inline imageLiC4H9THF−80 °C75%H5C6CHO 160
inline imageLiC4H9DEE+40 °C71%CO2 161
inline imageLiC4H9THF−100 °C72% inline image 162
inline imageLiC4H9DEE−70 °C17%CO2 163
inline imageLiC4H9THF−100 °C97%CO2 164
inline imageLiC6H5THF−100 °C61%CO2 164
inline imageLiC6H5THF−100 °C41%CO2 164
inline imageLiC6H5THF−100 °C82%CO2 164
Table 18. Alkoxy- and Acetal-Substituted Aryllithiums Li[BOND]R by Halogen/Metal Permutation between Bromo- or Iodoarenes and Butyllithium
Li[BOND]RXaSνbTProductEl[BOND]X′cReference
  1. a

    X = halogen displaced by the metal.

  2. b

    Solvent (Sν): PET = petroleum ether; DEE = diethyl ether, THF = tetrahydrofuran, BNZ = benzene.

  3. c

    El[BOND]X′ = electrophilic trapping reagent.

  4. d

    Or using phenyllithium in DEE at +25 °C.

  5. e

    Not specified.

  6. f

    OTHP = (2-tetrahydropyranyl)oxy.

  7. g

    1-p-Anisyl-3-phenyl-2-butanone.

  8. h

    N-Benzyl-6-aza-2-bicyclo[2.2.2]octanone.

inline image dBr, IDEE+25 °C90%(H5C6)2CO 165-167
inline imageBrTHFd−75 °C52%CO2 168, 169
inline imageBr, IBNZ+25 °C82%CO2 142-144
inline imageBrPET+25 °C eD2O 170
inline imageBrTHF−75° eD2O 170
inline image fBrTHF−75 °C80% g 171
inline imageBr, IDEE−75 °C42% h 172
inline imageBrTHF−75 °C52% inline image 173, 174
inline imageBrTHF−75 °C38% inline image 175
inline imageBrTHF−75 °C75% inline image 176
Table 19. Lithiooxy-Substituted Aryllithiums Li[BOND]R by Halogen/Metal Permutation between Butyllithium and O-Lithiated Bromophenols, Bromobenzyl Alcohols, Bromo-2-Phenethyl Alcohols and Bromobenzoic Acids
Li[BOND]RaSνbTProductEl[BOND]X′cReference
  1. a

    OLi by deprotonation of OH prior to the halogen/metal permutation.

  2. b

    Solvent (Sν): DEE = diethyl ether, THF = tetrahydrofuran.

  3. c

    El[BOND]X′ = electrophilic trapping reagent.

  4. d

    Using tert-butyllithium rather than butyllithium.

  5. e

    (1) SO2, (2) HO3SONH2.

inline imageDEE+25 °C67%CO2 177-181
inline image dTHF0 °C61% e 182
inline imageDEE,THF+25 °C75%CO2 177-181
inline image dTHF0 °C61%H5C6CN 183
inline imageDEE+25 °C32%CO2 162
inline imageDEE+25 °C18%CO2 162
inline imageDEE+25 °C45%CO2 162
inline imageDEE+25 °C52%CO2 162
inline imageDEE−75 °C35%CO2 161, 177-181
inline imageDEE−75 °C62%CO2 166, 177-181, 184
Table 20. Fluoro- and Trifluoromethyl-Substituted Arylithium Li[BOND]R by Halogen/Metal Permutation between Bromoarenes and Butyllithium
Li[BOND]RSνaTProductEl[BOND]X′bReference
  1. a

    Solvent (Sν): DEE = diethyl ether, BNZ = benzene.

  2. b

    El[BOND]X′ = trapping electrophile.

  3. c

    R′2 = 4,4-Dimethyl-2,2′-biphenyldiyl.

inline imageDEE−70 °C84%(H5C6)2CO 185
inline imageDEE−40 °C65%CO2 186
inline imageBNZ+25 °C50%CO2 144
inline imageDEE−75 °C83%CO2 187, 188
inline imageDEE−75 °C77%CO2 189
inline imageDEE−75 °C51%H2O 190, 191
inline imageDEE+25 °C61%CO2 192
inline imageDEE−50 °C64%CO2 193
inline imageDEE0 °C48%Cl2C = CF2 194
inline imageDEE−75 °C94%CO2 195
inline imageDEE−70 °C78%R′4As+Ic 196
Table 21. Chloro-, Bromo- and Iodo-Substituted Aryllithiums Li[BOND]R by Halogen/Metal Permutation between Bromoarenes and Butyllithium in Diethyl Ether
Li[BOND]RTProductEl[BOND]X′aReference
  1. a

    El[BOND]X′ = electrophilic trapping reagent.

  2. b

    Also from the corresponding iodoarenes and also in benzene rather than diethyl ether.

  3. c

    From hexachlorobenzene.

  4. d

    Nucleophilic addition of 3-bromophenyllithium to the 4-position of pyrimidine followed by the elimination of lithium hydride.

  5. e

    R′2 = 4,4′-dimethyl-2,2′-biphenyldiyl.

  6. f

    From 1,4-diiodobenzene.

inline image−90 °C93%CO2 197
inline image b+25 °C42%CO2 142, 143, 184
inline image b+25 °C90%CO2 142-144
inline image c−10 °C71%(H5C6)2CO 198, 199
inline image−100 °C38%CO2 142, 143, 200
inline image+35 °C44% inline image d 201, 202
inline image+25 °C90%CO2 144, 203, 204
inline image−75 °C93%F7C3COOC2H5 205
inline image−15 °C16%CO2 122
inline image+25 °C67%H2O 142, 143
inline image−70 °C30%R′4P+Ie 196
inline image f+25 °C80%(H5C2)3GeBr 206
Table 22. Pyridyl- and Quinolyllithiums Li[BOND]R by Halogen/Metal Permutation Using Butyllithium as the Exchange Reagent
Li[BOND]RXaSνbTProductEl[BOND]X′cReference
  1. a

    X = halogen displaced by the metal.

  2. b

    Solvent (Sν): DEE = diethyl ether, THF = tetrahydrofuran, TOL = toluene.

  3. c

    El[BOND]X′ = electrophilic trapping reagent.

inline imageBrDEE−15 °C69%H5C6CHO 207-209
inline imageBrDEE−35 °C62%CO2 207-212
inline imageBrDEE−75 °C55%(H5C6)2CO 211-213
inline imageBrTHF−60 °C80%H3CI 214
inline imageBrDEE−40 °C82%H3CCON(CH3)2 215-219
inline imageBrTOL−75 °C79%(H3C)2CO 220
inline imageBrTHF−100 °C85%D2SO4 221
inline imageClDEE−35 °C84%H2O 222
inline imageIDEE−35 °C65%CO2 223
inline imageClDEE−75 °C29%CO2 224-226
inline imageBrDEE−75 °C16%CO2 227
inline imageBr, IDEE−50 °C50%(H5C6)2CO 228, 229
inline imageBrDEE−45 °C48%CO2 184, 207-213
Table 23. Pyrryl-, Indolyl-, Pyrazolyl- and Imidazolyllithiums Li[BOND]R by Halogen/Metal Permutation between a Five-Membered Bromoheterocycle and Butyllithium in an Ethereal Solvent
Li[BOND]RSνaTProductEl[BOND]X′bReference
  1. a

    Solvent (Sν): DEE = diethyl ether, THF = tetrahydrofuran; in case of mixtures (containing, e.g., petroleum ether) only the most polar component is indicated.

  2. b

    El[BOND]X′ = trapping electrophile.

  3. c

    SiR′2R″ = Si(CH3)2C(CH3)3.

  4. d

    tert-Butyllithium instead of butyllithium.

  5. e

    4-Iodo-1-triphenylmethylimidazole as the starting material.

  6. f

    Plus 7% 2-isomer.

  7. g

    Plus 14% 5-isomer.

inline imageTHF−75 °C83%(H3C)3SiCl 230
inline imageTHF−75 °C88%CO2 231, 232
inline image c, dTHF−75 °C94%(H3C)3SnCl 233-235
inline image dDEE−100 °C77%CO2 236
inline imageDEE−30 °C74%(H5C6)2CO 237
inline imageDEE−30 °C81%CO2 237
inline imageDEE+25 °C97% inline image 238
inline imageDEE−30 °C80%CO2 237
inline image eTHF−75 °C51%f(H3C)2NCHO 239
inline imageTHF−100 °C42%CO2 240
inline imageDEE−75 °C54%g(H3CS)2 241-243
Table 24. Furyl-, Thienyl-, Benzothienyl- and Selenophenyllithiums Li[BOND]R by Halogen/Metal Permutation between Haloheterocycles and Butyllithium in Diethyl Ether
Li[BOND]RXaTProductEl[BOND]X′bReference
  1. a

    X = halogen in the precursor.

  2. b

    El[BOND]X′ = electrophilic trapping reagent.

  3. c

    Using sec-butyllithium instead of butyllithium.

  4. d

    Using phenyllithium instead of butyllithium.

  5. e

    Using ethyllithium instead of butyllithium.

inline imageBr−70 °C63%(H9C4O)3B/H2O 244-248
inline imageBrc−70 °C78%H5C6N(CH3)CHO 249
inline imageBr−45 °C49%H3CCON(CH3)2 246-248
inline imageBr−80 °C65%H2O 249
inline imageBr−45 °C61%(H9C4O)3B/H2O 246-248, 250
inline imageI+25 °C58%CO2 251
inline imageI−70 °C78%CO2 252, 253
inline imageBr−75 °C51%(H3C)2NCHO 254
inline imageBr−70 °C90%CO2 253
inline imageCl0 °C69%CO2 255, 256
inline imageBrd+40 °C65%CO2 257
inline imageIe−100 °C51%CO2 258