![Page 1: C-C Bond Formation - Organometallic Coupling Reactions (McM 7th ed. 10.8, Lab ex 10 ... · C-C Bond Formation - Organometallic Coupling Reactions (McM 10.9, Lab ex 10) C + XC CC Reagents](https://reader036.vdocument.in/reader036/viewer/2022062507/5fe11fc8c997642c2230eac9/html5/thumbnails/1.jpg)
C-C Bond Formation - Organometallic Coupling Reactions(McM 7th ed. 10.8, Lab ex 10)
Alkenes(McM 7th ed. 11.8 – 11.9)
Dienes(McM 7th ed. 14.1 – 14.3)
![Page 2: C-C Bond Formation - Organometallic Coupling Reactions (McM 7th ed. 10.8, Lab ex 10 ... · C-C Bond Formation - Organometallic Coupling Reactions (McM 10.9, Lab ex 10) C + XC CC Reagents](https://reader036.vdocument.in/reader036/viewer/2022062507/5fe11fc8c997642c2230eac9/html5/thumbnails/2.jpg)
C-C Bond Formation - Organometallic Coupling Reactions(McM 10.9, Lab ex 10)
C + X C C C
No nu subst if C sp2 or spReagents often unstableDifficult to makeStrong bases
R HNaNH2
R
pKa ca 25
CH3IR CH3
Br
Na
RH
H
C H
Br
Elimination
pKa ca 44
pKa ca 60
pKa NH3 35
![Page 3: C-C Bond Formation - Organometallic Coupling Reactions (McM 7th ed. 10.8, Lab ex 10 ... · C-C Bond Formation - Organometallic Coupling Reactions (McM 10.9, Lab ex 10) C + XC CC Reagents](https://reader036.vdocument.in/reader036/viewer/2022062507/5fe11fc8c997642c2230eac9/html5/thumbnails/3.jpg)
Grignard reagents and Organolithium reagents
Reacts with carbonylsStrong bases
RMgX or RLi does not react well with alkyl halides in substitutions
R-XMg
R-Mg-X
R: prim, sek, tert alkyl alkenyl aryl
NucleophileStrong base
O
R1 R2
R2R1
R OMgX
R-HBase
R
R-X2 Li
R--Li + LiX
R: prim, sek, tert alkyl alkenyl aryl
NucleophileStrong base
OR1 R2
R2R1
R OLi
BuLi used a lot as strong base
![Page 4: C-C Bond Formation - Organometallic Coupling Reactions (McM 7th ed. 10.8, Lab ex 10 ... · C-C Bond Formation - Organometallic Coupling Reactions (McM 10.9, Lab ex 10) C + XC CC Reagents](https://reader036.vdocument.in/reader036/viewer/2022062507/5fe11fc8c997642c2230eac9/html5/thumbnails/4.jpg)
Organocuprates (McM 10.8)
2 R-Li + CuI R2Cu Li + LiI
2 R-MgX + CuI R2CuMgX + IMgX
Gilman reagentDialkylcuprate
Participate in substitution with alkylhalides (Cl, Br, I)
(R: alkyl, alkenyl, alkynyl, aryl)
R2Cu Li + R-X R-R
alkylhalide
+ RCu + LiX
less reactiveAlkylcopper(i)
Mech. see next slide
![Page 5: C-C Bond Formation - Organometallic Coupling Reactions (McM 7th ed. 10.8, Lab ex 10 ... · C-C Bond Formation - Organometallic Coupling Reactions (McM 10.9, Lab ex 10) C + XC CC Reagents](https://reader036.vdocument.in/reader036/viewer/2022062507/5fe11fc8c997642c2230eac9/html5/thumbnails/5.jpg)
R2Cu Li
I R
I
R'
R
R'
R Cu R+ CuR
+ CuRR Cu R
R'
Also reaction with alkenyl halides and arylhalides (sp2)Not SN1 or SN2
![Page 6: C-C Bond Formation - Organometallic Coupling Reactions (McM 7th ed. 10.8, Lab ex 10 ... · C-C Bond Formation - Organometallic Coupling Reactions (McM 10.9, Lab ex 10) C + XC CC Reagents](https://reader036.vdocument.in/reader036/viewer/2022062507/5fe11fc8c997642c2230eac9/html5/thumbnails/6.jpg)
Palladium catalyzed coupling reactions (Lab ex. 10. McM 10.8, not McM 6th ed)
R-X + R'-Metcat. Pd(0)-complex R-R' + Met-X
-aryl halide-alkenyl halide-alkynyl halide
R': alkynyl, alkenyl, aryl, alkyl-Met; (-MgX), -ZnX, -SnR3,- -B(OR)2,
R’-Met: R’ZnX - Negishi coupling
- Esp. good for R’ = alkyl, R’ZnX generated in situ
R’SnBu3 / R’SnMe3 - Stille coupling -R’ (alkynyl) aryl, alkenyl, organotin comp. tox R’SnBu3 / R’SnMe3 stable
R’B(OH)2 / R’B(OR)2 - Suzuki coupling - R’ (alkynyl) aryl, alkenyl, Green react. R’B(OH)2 / R’B(OR)2 relatively stable
react. requires base
R’MgX - Kumada couplingLess reactive, often Ni-cat. (less stable than Pd-cat)
![Page 7: C-C Bond Formation - Organometallic Coupling Reactions (McM 7th ed. 10.8, Lab ex 10 ... · C-C Bond Formation - Organometallic Coupling Reactions (McM 10.9, Lab ex 10) C + XC CC Reagents](https://reader036.vdocument.in/reader036/viewer/2022062507/5fe11fc8c997642c2230eac9/html5/thumbnails/7.jpg)
General mechanism
Met: -ZnX, -B(OH)2, -SnR3 (-MgX)
Alkenyl or aryl halidesPd complex from alkyl halides unstable
Alkynyl, alkenyl, aryl, alkyl reacts (depending on the metal used)
N
N N
N
X
OCH3
O
Formed by Pd-cat coupling
Highly active against Mycobacterium tuberculosis
PdL4 [Pd(0)]
I
PdL
LI
PdL2
Pd(0)
2L
PdL
L
L: Ligand, often PPh3
Pd(II)Pd(II)
MetMet-I
Oksidative addition[Pd oxs from Pd(0) tto Pd(II)]
Transmetallation(Ph transfered from Met Pd Pdno red ox)
Reduktive eliminationPd redused back to Pd(0)C-C between aryls formed
![Page 8: C-C Bond Formation - Organometallic Coupling Reactions (McM 7th ed. 10.8, Lab ex 10 ... · C-C Bond Formation - Organometallic Coupling Reactions (McM 10.9, Lab ex 10) C + XC CC Reagents](https://reader036.vdocument.in/reader036/viewer/2022062507/5fe11fc8c997642c2230eac9/html5/thumbnails/8.jpg)
The Suzuki reaction
I
PdL
LI
PdL2
Pd(0)
PdL
L
Pd(II)
Pd(II)
B
Oksidative addition
Transmetallation
Reduktive elimination
OH
I
PdL
LHO
(or other base)
OH
OH
OH
B OHOH
OHMore reactive
B(OH)4
Need base
![Page 9: C-C Bond Formation - Organometallic Coupling Reactions (McM 7th ed. 10.8, Lab ex 10 ... · C-C Bond Formation - Organometallic Coupling Reactions (McM 10.9, Lab ex 10) C + XC CC Reagents](https://reader036.vdocument.in/reader036/viewer/2022062507/5fe11fc8c997642c2230eac9/html5/thumbnails/9.jpg)
Special cases - No preformed R’Met
Coupling on alkynes - Sonogashira coupling
Coupling on alkenes - Heck coupling(Somewhat diff. mech.)
Via R' Cu
R-X +cat. Pd(0)-complex
Base, CuXR' H R' R
R-X + cat. Pd(0)-complex
BaseR' R'
R
![Page 10: C-C Bond Formation - Organometallic Coupling Reactions (McM 7th ed. 10.8, Lab ex 10 ... · C-C Bond Formation - Organometallic Coupling Reactions (McM 10.9, Lab ex 10) C + XC CC Reagents](https://reader036.vdocument.in/reader036/viewer/2022062507/5fe11fc8c997642c2230eac9/html5/thumbnails/10.jpg)
Why difficult to couple alkyl halides
XPdL2
ox. addL Pd L
XH
H
β-hydride elimination
L Pd LH
X
Trans metallation
![Page 11: C-C Bond Formation - Organometallic Coupling Reactions (McM 7th ed. 10.8, Lab ex 10 ... · C-C Bond Formation - Organometallic Coupling Reactions (McM 10.9, Lab ex 10) C + XC CC Reagents](https://reader036.vdocument.in/reader036/viewer/2022062507/5fe11fc8c997642c2230eac9/html5/thumbnails/11.jpg)
C-C Bond Formation - Organometallic Coupling Reactions(McM 7th ed. 10.8, Lab ex 10)
Alkenes - Synthesis by elimination react.(McM 7th ed. 11.8 – 11.9)
Dienes(McM 7th ed. 14.1 – 14.3)
![Page 12: C-C Bond Formation - Organometallic Coupling Reactions (McM 7th ed. 10.8, Lab ex 10 ... · C-C Bond Formation - Organometallic Coupling Reactions (McM 10.9, Lab ex 10) C + XC CC Reagents](https://reader036.vdocument.in/reader036/viewer/2022062507/5fe11fc8c997642c2230eac9/html5/thumbnails/12.jpg)
Elimination reactions - Repetition
H
XR
RR'
R'
E2: mechanism
BR' R'
R R+ BH + X
•One step•2. order•Stereospecific
E1: mechanism
H
XR
RR'
R' H
R
RR'
R'
B
+ X
R' R'
R R
+ BH + X
and / orR' R
R R'
•Two steps•1. order•1. step rate limiting•1.step = 1. step in SN1•Not stereospecific
Elimination in competition with substitution
![Page 13: C-C Bond Formation - Organometallic Coupling Reactions (McM 7th ed. 10.8, Lab ex 10 ... · C-C Bond Formation - Organometallic Coupling Reactions (McM 10.9, Lab ex 10) C + XC CC Reagents](https://reader036.vdocument.in/reader036/viewer/2022062507/5fe11fc8c997642c2230eac9/html5/thumbnails/13.jpg)
E2 and stereochemistry (McM 11.9)
Base
H R
RH
H
X
ReactantAnti Periplanar conformation
H R
RH
H
X
Base#
Anti transition state
HR
R
H
Alkene
H
H
H
Cl
H
HClH
HH
H
H
cannot react E2
B
![Page 14: C-C Bond Formation - Organometallic Coupling Reactions (McM 7th ed. 10.8, Lab ex 10 ... · C-C Bond Formation - Organometallic Coupling Reactions (McM 10.9, Lab ex 10) C + XC CC Reagents](https://reader036.vdocument.in/reader036/viewer/2022062507/5fe11fc8c997642c2230eac9/html5/thumbnails/14.jpg)
Deuterium Isotope Effect (McM 11.8)(Kinetic Isotope Effect)
•Important in elucidation of reaction mechanisms•Cleavage of C-H and C-D requires different amount of energy
Hookes Law, Stretching frequencies, IR
ν = 12πc
f(m1+m2)m1m2 m1 m2
ν C-H: ca 3000 cm-1
ν C-D: ca 2200 cm-1
Relationship between Streching frequency (ν) and zero-point energy (E0)E0 = 1/2 hνE0 C-H 18 kJ/molE0 C-D 13 kJ/molHigher activation energy for cleavage of C-DCleavage of C-H will be faster
TS#
![Page 15: C-C Bond Formation - Organometallic Coupling Reactions (McM 7th ed. 10.8, Lab ex 10 ... · C-C Bond Formation - Organometallic Coupling Reactions (McM 10.9, Lab ex 10) C + XC CC Reagents](https://reader036.vdocument.in/reader036/viewer/2022062507/5fe11fc8c997642c2230eac9/html5/thumbnails/15.jpg)
Mechanistic Information from Deuterium Isotope Effect
CH
HCH
BrH
?
H
H
HE2 C-H broken in rate limiting step
CH
HCH
H
Same prod. no info from regio / stereosel.
CH
HCH
BrH
H
H
H
CD
DCH
BrH
H
H
D
Fastest if E2, C-H more easily broken
![Page 16: C-C Bond Formation - Organometallic Coupling Reactions (McM 7th ed. 10.8, Lab ex 10 ... · C-C Bond Formation - Organometallic Coupling Reactions (McM 10.9, Lab ex 10) C + XC CC Reagents](https://reader036.vdocument.in/reader036/viewer/2022062507/5fe11fc8c997642c2230eac9/html5/thumbnails/16.jpg)
C-C Bond Formation - Organometallic Coupling Reactions(McM 7th ed. 10.8, Lab ex 10)
Alkenes(McM 7th ed. 11.8 – 11.9)
Dienes(McM 7th ed. 14.1 – 14.3)
![Page 17: C-C Bond Formation - Organometallic Coupling Reactions (McM 7th ed. 10.8, Lab ex 10 ... · C-C Bond Formation - Organometallic Coupling Reactions (McM 10.9, Lab ex 10) C + XC CC Reagents](https://reader036.vdocument.in/reader036/viewer/2022062507/5fe11fc8c997642c2230eac9/html5/thumbnails/17.jpg)
Dienes (McM 14.1-3)
C C (CH2)n C Cn: 1,2,3... non conjugated dienen=1: Skipped dienen>1: Isolated diene
C C CC conjugated diene
C CC cumulated diene (allene)
•
sp
•Molecular orbitals•Addition react.
See also cycloadditions (Diels Alder etc)chapter 30 - lecure 4 & 5
![Page 18: C-C Bond Formation - Organometallic Coupling Reactions (McM 7th ed. 10.8, Lab ex 10 ... · C-C Bond Formation - Organometallic Coupling Reactions (McM 10.9, Lab ex 10) C + XC CC Reagents](https://reader036.vdocument.in/reader036/viewer/2022062507/5fe11fc8c997642c2230eac9/html5/thumbnails/18.jpg)
153 Å147 Å
Conjugated dienes
[red] [red]ΔHohydrog -253 kJ/mol ΔHo
hydrog -236 kJ/mol
Less energy difference - conjugated diene more stable
Ho
![Page 19: C-C Bond Formation - Organometallic Coupling Reactions (McM 7th ed. 10.8, Lab ex 10 ... · C-C Bond Formation - Organometallic Coupling Reactions (McM 10.9, Lab ex 10) C + XC CC Reagents](https://reader036.vdocument.in/reader036/viewer/2022062507/5fe11fc8c997642c2230eac9/html5/thumbnails/19.jpg)
Energy
H 1s orbital H 1s orbital
H-H Binding MO (filled)
H-H Antibinding MO (unfilled)
Molecular orbitals of H2 (cf fig 1.17) - σ-bond
Molecular orbitals of π-bond (cf fig. 1.18)
Energy
2 p orbitals
π Bonding MO
π Antibonding MO
Node
![Page 20: C-C Bond Formation - Organometallic Coupling Reactions (McM 7th ed. 10.8, Lab ex 10 ... · C-C Bond Formation - Organometallic Coupling Reactions (McM 10.9, Lab ex 10) C + XC CC Reagents](https://reader036.vdocument.in/reader036/viewer/2022062507/5fe11fc8c997642c2230eac9/html5/thumbnails/20.jpg)
Energy
H 1s orbital H 1s orbital
H-H Binding MO (filled)
H-H Antibinding MO (unfilled)
Molecular orbitals of H2 (cf fig 1.17) - σ-bond Molecular orbitals of π-bond (cf fig. 1.18)
Energy
2 p orbitals
π Bonding MO
π Antibonding MO
Node
Energy
4 p orbitals
Bonding MO - 0 nodes
Bonding MO - 1 node
Antibonding MO - 2 nodes
Antibonding MO - 3 node
MO 1,3-butadienecf fig 14.2
4 π electron in 2 bonding orbitals(ground state)
HOMO
LUMOhν1 e-
Energy absorbUV spectra
π Molecular orbitals
delvis dobbeltbind. karakter
![Page 21: C-C Bond Formation - Organometallic Coupling Reactions (McM 7th ed. 10.8, Lab ex 10 ... · C-C Bond Formation - Organometallic Coupling Reactions (McM 10.9, Lab ex 10) C + XC CC Reagents](https://reader036.vdocument.in/reader036/viewer/2022062507/5fe11fc8c997642c2230eac9/html5/thumbnails/21.jpg)
Long conjugated systems - colored compounds
β-Carotene
![Page 22: C-C Bond Formation - Organometallic Coupling Reactions (McM 7th ed. 10.8, Lab ex 10 ... · C-C Bond Formation - Organometallic Coupling Reactions (McM 10.9, Lab ex 10) C + XC CC Reagents](https://reader036.vdocument.in/reader036/viewer/2022062507/5fe11fc8c997642c2230eac9/html5/thumbnails/22.jpg)
Electrophilic addition to conjugated dienes
Termodyn prod: High activation barrier, most stable prod. Vigorous cond. (high temp), reversibleKinetic prod: Low activation barrier, less stable prod. Mils cond, (low temp,) irreversible
H-Br
sec, allylic cation
prim. cat.
BrBr
H
H H
1,2-add. prod.kinetic prod.
+H
Br
1,4-add. prod.termodyn. prod.