Generation of organometal species

1. Organo halide + Metal
R-X + 2M = RM + MX

M = 1 electron donor(Li, Na, K, Cu, SmI2 ...)

R-X + M = RMX

M = 2 electron donor(Mg, Ca, Ba, Zn ...)

Wurtz coupling
occurred easily
with reactivesubstrates

Sterechemistry

Reactivity of R-X
F << Cl < Br < I

Depend on substrates andreactivty of metals

Activation of metals to facilitate halogen-metal exchange.

alkali metal arenide
MeN

Me< LiLiLN(lithium naphtalenide)<t-BuLDMAN(lithium 1-dimethylaminonaphtalenide)SPht-BuLDBB(lithium 4,4'-di-tert-butylbiphenylide)Li++2 LN

LiSPh +2 C10H8Rieke metals (Mg, Zn, Ba, Cu etc...)naphtalene cat.
MXn + nK (or nNa)

M* + nKX (or nNaX)
Highly active metal(0) is generated.
R. D. Rieke Acc. Chem. Res. 1977, 10, 301.
A. Furstner Angew. Chem. Int. Ed. 1993, 32, 164.

nC8H17F + Mg*

nC8H17MgF

2. Halogen-Metal exchange
RX + R'M

RRM + R'X

X R'

M
via ate complex

X = halogen, Se, Te...

Anion of RM should be more stable than R'M.

+N

iPrMgBr
NBr+MgBr

iPrBr

3. Metal-Metal exchange
RM' + R'M

M
R M' R'
via ate complex

RM + R'M'
Anion shold bethermodynamicaly more stable.

M' = Sn, B etc... (easily form ate complex)
R'M High polarity
tBu

BR2+tBu

Me2Zn

ZnMe

MeBR2

retention of configuration

4. Hydrogen-Metal exchange (Metalation)
RH + R'M+

RM + R'H

difference in pKa >2 ~3basicity of R'M
Cs > Rb > K > Ba > Na > Ca > Li > Mg
smalllargeelectronegativity

lowhighnature of covalent bonding

mixture of nBuLi and tBuOK super base (Schlosser base)
KnBuLi, tBuOK

Kretention

ortho metalation
effect of directing group
SO2NR2 > SO2Ar > CONR2 > CONHR > CH2NMe2 > OR > NHAr > SR > NR2 > CR2O-

5. Others
RM' + M

electronegativity M < M'

RM + M'
Et2Zn + 2Cs

2 EtCs + Zn

RM + 1/2 H2

RH + Msalt free organic metals

NaRM' + X'M+ 1/2 H2Na

M'X' ... driving force

RM + M'X'
RLi + CeCl3

RCeCl2 + LiCl+M* accepts one electron
radical anion ... potent 1 electron
donor (metal arenide)

M+ Mg
Mg
R+ R-M

hydrometalation
carbometalation

MHMeMeH + nPrCu(MgBr2)(SMe2)

Cu

Feature of organo metalic species5) Ligand effect6) Aggregation
7) Steric factor

1) How ionic?
2) Stability of carbanion3) 1, 3, 54) Lewis acidity of the metal
LiNanPrKBe

Mg

CaBaB

Al Tl

Cu

Zn

lantanoid

electron negativity ( M)

1.0 0.9 0.8 1.5 1.2

1.0 0.9 2.0 1.5 1.8 1.9

1.6 1.1~1.2

ionic nature (%)

43 47

4318C(sp)electron negativity ( M)

3.29

51 2234C(sp2)
2.75

47

622 12 9C(sp3)
2.5basicity
nucleophilicity(steric factor)-conjugated system (allyl, benzyl etc...) showed exceptional reactivity.

38~34

Li, Na, K, Rb, Cs, Fr (mainly Li)
aggregation statelarge Rhigh s character
highly coordinating solvent

LiMeMeLi
Li
MeLiMeLiMeMe LiLiMeLi
Melower aggregation state
multiple coordination
TMEDA ...

dimer or trimer

or THF etc...
NNMe2 MeL... monomer
NMe2(PMDTA)

4-center-2-electron-conjugated system (allyl, benzyl etc...) ... lower aggregation statelithium amide ... dimer
lithium enolate ... tetramer
reaction pathdissotiation path
LinBuLi

nBuLi
TMEDA
maintain aggregation

LiO
Li
O
Li
O
O
Li
O

Li
O
O
Li
LiO
O
Li
O

H

H

Li
O
Li
O
Li
O
Li
O
O
H

Half-life of organo lithium
solvent

temp.

MeLI

Et2Ortmonths 54 hr 6 days

THF

DME

EtLi

nBuLi

35 oC

31 hrrt

2 hr

0 oC

1 day-30 oC

5 days

25 oC

10 min.

sBuLi

tBuLi

vinyl-Li

PhLi

decomp. > 7 days
12 hr
> 7 days
30 min. decomp.
short timeBe, Mg, Ca, Sr, Ba, Raaggregation state
ex. monomer in variable conc. in THF
low conc. in Et2O

variable

t-Bu
NN

Cl

Mg

Mg
ClEt2O
Mg

NBr

N
1OO

OEt2
Mg
Br
t-Bu

structure

Schlenk equilibrium
XR Mg

Mg RX

R2Mg

XX Mg

2 RMgXMg R
MgX2

RR
X Mg

Mg

RXMg

Mg
X

R

precipitate
in dioxane

X

R
reaction mechenism of Grignard reagent
concerted mechanism

OX

X

Mg R

Mg R
O

O

RMgX +R

1R

2R1

typical example

ORO

R1 2 R
RMg
R

R1R22MgX

X+ RMgXsteric effect is major factor

PhMgBr +Meelectron transfer mechanism

MeX
Mg

O
RMgX +Ph

O
Ph

Ph

R

O
Ph
Ph

Ph

MgX
R

X
Mg

typical example
OO

R

tBuMgX +Ph

Ph

Ph

Ph·ability of electron donor·stability of radical species·steric effectalkali and alkaliearth metals
basicity vs nucleophilicity
O
Ph M
Ph

OM

Ph OM
Ph

PhratioKNa
LiMgBrelectronegativity

061610010094840NucBase

regioselectivity
KMeI

3ratio
K94

6MgBr

892

MgBr
1M

effect of -substituent
RRX

electron withdrawing groupstabilize the anion via conjugation effect
X = COR, CN, NC, NO2, SOR, P(O)(OR)2 etc...
OM
OM
stabilize the anion via inductive effect
X = OR, NR2
OR

OR

OR>
Li>

> nBuLi
>
1R
LiR
Li
Li
R2
OR ... 20~25 kJmol-1 stabilize
R ... 15 kJmol-1
destabilize
G. J. McGarvey et al. J. Am. Chem. Soc. 1988, 110, 842.
MeLi>

1

negative hyperconjugation
X = SiR3, SR, SeR
(C-M)

(X-R)

carbenoid
X = F, Cl, Br, I, OR
both nucleophilicity and electrophilicity at C center
RCR

M

RXRC MC-X bond is longer
than neutral compound.

Xelectrophilic

nucleophilic

H. Ahlbrecht et al. Chem. Ber. 1993, 126, 1887.
A. Maercker et al. Angew. Chem. Int. Ed. 1993, 32, 1023.
BrLiCl
tBuLi

t-Bu
ClLi

tBuLi

t-Bu
H

MeOH
39% ee100% eepartially via carbene
cf. gem-bimetalic species (R2CM2) ... lower nucleophilicity than R2CHM
ref. J. -F. Normant et al. Chem. Rev. 1996, 96, 3241.
inversion of stereochemistry
LiRLiPhPhHPhPh

Ph

Li

LiPh

892

via aggregated state
LiGrignard reagent
stable(hard to form planar TS)

H

slower stereo inversion-alcoxy or amino organometals resist to stereo inversion at low temp.
O

OBnnBuLi

OSn(nBu)3

OBn

Li-SiR3, SR, SeR etc organometals resist to stereo inversion at low temp.
LiPhPhH

SePhPhPhfavorable

Se
LiPhR. W. Hoffmann et al. Angew. Chem. Int. Ed. 1993, 32, 1467.
R. R. Dykstra et al. Angew. Chem. Int. Ed. 1993, 32, 1469.

Cu
CuX + RM

R = TMSCH2

CuR + MX

Lewis acid (MgX2, TMSCl etc.)
Lewis base (R3P, R2S etc.)
coordinative solvent
cuprateR Cu R
Cu

improves the reactivity

R Cu R
3-center-2-electron

MCuR2 + MX

CuX + 2RM

solv

Gillman reagent
higher stability
higher reactivity
higher solubility

Cu

R Li R
Cu

than CuR

Cu

R Li Rheterocuprate
CuZ + RM

MCuRZ

higher stability
lower reactivity

Z = CN, SPh, NR'2, OR'less transferable group than R

than MCuR2
SR

TMS

are also
less transferable gloup

higher order cuprateNC

M2CuR2(CN)CuCN + 2RM
higher reactivity
higher stability

reaction of cuprate

Li Li
than MCuR2
R Cu R(proposed structure)
N. Krause et al. J. Am. Chem. Soc. 1996, 118, 4149.

O[LiCuR2]

SETO

O

O

LiO

reductive
elimination

Li+CuR

CuR2RCuR-coordination-3d
SN2 type substitution
LiCuR2 + B

XC

reductiveelimination

AS N2AR2CuBCLiARBC

SET process is also plausible in some cases.

RZn
R Zn R ... monomer, linear structure, low reactivity
Zn-C has lower polarization.
Not reactive in the absence of ligand.
Et2O
distorted the linear structure
improves the reactivity

ligandRZn

Me145 oR

MeRZn

NR3NR32RR
ate complexes show higher reactivity

Zn

R

R Zn RR

R = alkynyl, O, N, X, carbonyl compound ... various aggregation state
Simmons-Smith reaction

ZnIZnIC
H2 I

CH2I2 + Zn-Cu
I
carbenoid+ ZnI2

accelerate the reaction

OH group directs the reaction

E. Nakamura et al. J. Am. Chem. Soc. 1998, 120, 5844.
R2Zn or R3Al can also promote the reaction.

R2Cd ... monomer, linear structure, lower reactivity than R2Zn
R4Cd2- ... unstable due to low Lewis acidity
R2Hg, RHgX ... monomer, linear structure, stable in water and O2 atmosphere
Hg-C bond ... almost covalent bondsolvomercuration
Y

R+ YH + HgX2R'R
anti-addition R'

NaBH4HgX

YRR'H

B, Al, Ga, In, Tl
R3M ... planar structure
Lewis acidity
MCl3B > Al > Ga > In > Tl
MMe3

Al > B > Ga > In > Tl

B

H

H

hyperconjugation stabilizes monomer species
conjugation effect of hetero atoms

Cl < S < O < F < Ncarbaborane
Hborazine
R'diborane
H
H
H
B
B
H
H
H

R

3-center-2-electron
R'

R2HB

R2B

N
B

B
NN
B

RC
C

H

easilydeprotonatedR'electron acceptor

R
R3B ... stable in water
R is generated under mild O2 oxidationAl
less effective stabilization by hyperconjugation
PhPh
MeMeMePh AlAl AlAl PhMeMe MePh
3-center-2-electron
Ph-coordinationt-Bu
MeO

Br
BrAl

Br
BrAlBrBr

2-center-2-electron

t-Bu

Al

t-Bu RO

Mebulky substituents prefermonomeric species

t-Bu

rapid equibrium
R13Al + R23Al

R12R2Al + R1R22Al.....

ate complex
AlEt3 + LiEt

LiAlEt4

coordination profile
Me3N > Me3P > Me3As > Et2O > Me2S > Me2Se > Me2Te..... mixturehydroboration
H BR2HH

H BR2H
H

R

R

H

H

BR2H
H

H
R

H

antiMarkovnikov(Coordination of solvent promotes dissociation of dimer.)
O
BH

BH

BH

BH2O

22(Sia)2BH

less reactivetexylborane

enantioselective

sensitive to steric effecthydroalumination
Similar mechanism as hydroboration is proposed.
electronic effect > steric effectt-Bu

t-Bu>n-Bu

n-Bu

20-fold faster
Z + DIBAL

PhZ = Me2N(1900) > Me3Si(431) > tBu(28) > EtS(25) > H(12) > Me(1.2) > Ph(1)Lanthanoid
Sc, Y, Lanthanide
normally M3+(M3+/M reduction voltage Eo = -2.25~-2.52V)

other than M3+ ion
Ce4+ (f0)
Eu2+ (f7)
f0, f7, f14 ions are rather stable
2+ 14
Yb (f )
lanthanide contraction
LaLuionic radiusless efficient shield effect of 4f orbitallarge ionic radiushigher coordination number (6 ~ 10)

small interaction between CO, alkene ( -backdonation type ligand)shift reagent ... through pseudocontact shift