Palladium catalyzed reactions of akira suzuki which made him to win nobel prize.

1. N-1
Cross-Coupling Reactions of Organoboranes:
An Easy Way for Carbon-Carbon Bonding
Akira Suzuki

3. N-2
Conjugated Alkadienes
R'
R'
R R R'
R' R R
trans-trans trans-cis cis-trans cis-cis
R M
+ X R
MY R' R'
R' R'
+ X M
MY
R R
M : transition metal catalyst

4. N-3
Syntheses of (E)- and (Z)-1-Alkenylboranes
R H
RC CH + HBY 2
H BY2
O trans > 99 %
Y2 = (Siamyl)2 ,
O
HBY2 R X t-BuLi R BY2
RC CX
H BY2 H H
cis > 98 %
X = I or Br Y=Siamyl, Cyclohexyl

5. N-4
XH
H R' R H
H (trans, trans)
R H Pd H
X R' H R'
H BY 2 base R H
H H
R' (trans, cis)
H
H H
H R'
H R'
X H R
(cis, trans)
H
R BY H H
Pd H H
H H
H H base 2
X R' R
R' (cis, cis)
H H

6. N-5
Common Catalytic Cycle Involving Sequential Oxidative
Addition (a), Transmetalation (b), and Reductive Elimination (c)
M Atomic charge in 0.01 e.u.
R-R
R-X (Gropen & Haaland, 1973)
+ 12
(a) (c)
CH3 CH3
B
CH3 -4
R
M
R-M-X R' - 12
(b)
CH3
R CH3 B CH3
R B OR' CH3
R'-M' (R3B) R - 22

7. N-6
Bu + Br Bu
BX2 Ph Ph
1 2 3
Catalystb) Base Yield (%)
1a) Solvent React.
(mol %) (equiv / 2)
time (h) of 3
1b PdL4 (3) None THF 6 0
1b PdL4 (3) None Benzene 6 0
1a PdL4 (3) 2M NaOEt (2)-EtOH THF 2 73
1b PdL4 (3) 2M NaOEt (2)-EtOH THF 4 78
1b PdL4 (1) 2M NaOEt (2)-EtOH Benzene 2 86
O
a) 1a, X2 = (Sia)2 1b, X2 = b) L = PPh3
O

8. N-7
1-Alkenylborane Yield (%)
1-Alkenyl Bromide Product
[Purity (%)]
Ph
Bu b) Br Ph 86 [98]
B Bu
Bu B a) Bu 49 [99]
Br Ph Ph
Bu B a) Br Ph Bu 42 [89]
Ph
Hex
Bu b) Br Hex 88 [99]
B Bu
Bu B a) Br Hex Bu 49 [98]
Hex
Ph
Ph b) 89 [98]
B Br Ph Ph
Reaction conditions: 1-3 mol % of Pd(PPh3)4 / NaOEt / Benzene / Reflux 2h
a) Disiamyl b) 1,3,2-Benzodioxaboryl

9. N-8
Pd(PPh3)4 Bu R
Bu BY2
+ RX
NaOEt / benzene
reflux, 2 h
BY2 RX Product Yield (%) Purity (%)
B(Sia)2 Bu 49 >98
B(OPri)2 Br Hex Hex 87 >99
B(Sia)2 58 >94
B( ) 2 PhI Bu Ph
49 >83
B(OPri)2 98 >97
B(Sia)2 Bu 54 >92
I
B(OPri) 2 87 >99

10. N-9
OH
H2N O
O O OH
HO OH
HO OH
OH
O HO
OH
HO Me
HO OH
OH
OHOH
OH
HO OH O
O O Me OH MeHO OH
OH OH
HO N N O
H H OH OH OH HO
Me O HO
OH
OH
O
Me O Me OH HO
OH Me OH
O OH
HO OH OH
HO OH OH
"Palytoxin" C129H223N3O54 (MW. 2678.6)
Synthesis: Kishi et al., J. Am. Chem. Soc, 1989, 111, 7525, 7530

11. N-10
Reaction Mechanism:
Me PdL4
Bu + Br Bu
Ph Ph
B(Sia)2
9%
Cl Cl Cl Cl Cl Cl
PdL4 NaOMe
Cl Cl Cl PdCl·L2 Cl PdOMe·L2
Fitton (1968) Otsuka (1976)
Cl Cl Hex O without base
no reaction
+ BO r.t./17 h
Cl PdCl·L2 Cl Cl
NaOMe
r.t./2 h Cl
89 % Hex
Cl Cl Hex O without base
B 66 %
+ r.t./15 min
Cl PdOMe·L 2 O
without base
97 %
r.t./1 h

12. Catalytic Formulation of the Vinyl-Vinyl Cross-Coupling N-11
R
R Pd(0)
R"
X
F. Maseras et al., JACS,
2005, 127, 9298 R
R Pd
R"
B PdX R"
R'ONa
R" OR'
B R
R" OR'
A. Monteiro et al., J. Braz. PdOR‘ B
Chem. Soc. 2007, 18 NaX

13. N-12
Reaction of B-Alkylboranes
R1 R3 Pd(0) R1 R3
+ R4X
R2 B Base R2 R4
R4 : 1-Alkenyl
Aryl
1-Alkynyl
Allyl
Benzyl
R B + R4X R R4
R : Alkyl

14. N-13
PdCl2(dppf) (3 mol%)
I + B C8H17 C8H17
NaOMe / THF, reflux
98 %
B PdCl2(dppf) (3 mol%)
Br +
NaOMe / THF, reflux
88 %
Br B (CH2)3 OMe
+ (CH2)3 OMe
OMe
OMe
87 %
PdCl2(dppf) (3 mol%)
Br + B C8H17 C8H17
NaOMe / THF, reflux
94 %

15. N-14
Alkyl-Vinyl Coupling:
Total Synthesis of Polycyclic Ether Natural Product
M. Sasaki, Bull. Chem. Soc. Jpn. 2007, 80, 856
TfO O
OR2
O OH
9-BBN 9-BBN
R1O R1 O Pd(0)
OP OP aq. base
H H H
O O 1. hydroboration O O
R1O OR 2 R1 O OR2
2. oxidation
OP OP O
H H
acetal
formation O O
R1O OR2
O
H OH

16. N-15
Polycyclic Ether Marine Natural Products:
HO
Me Me H H
H
O O
O H
HO
O O H
H H H H H O OH
Me
Me O
Gambierol H OH
Me
HO
H H OH
H O H
O O H
H Me
OHC O O H H H H H
O O O H
H H H H
Me H O O H
H O O O
H H H H Me H OH
Gymnocin-A HO
Me

17. N-16
Aromatic-Aromatic Cross-Coupling Reactions
Z
B(OH)2 + Br
Pd(PPh3)4 Z
aq Na2CO3
benzene, reflux

18. Suzuki Coupling: N-17
B(OH)2 + X
R Pd(0), base R R
R
B(OH)2 + X
R' Pd(0), base R R'
R
Ullmann Reaction:
R R
X + X
R R' Cu, high temp R R'
R' R'

19. N-18
Valsartan (Novartis): Antihypertensive
CH3 CH3
O
CH3 N COOH
N N
HN N
Suzuki Coupling
3.5 million users in Japan
22 million users in the whole world

20. N-19
Angiotensin II
Receptor Antagonist
(Losartan)
HO Cl
HO Cl
N
CPh3 CPh3 N CPh3 N
N N N N C4H9 N N N
N N N N N N C 4H9
1. BuLi Br
2. B(OPri)3 B(OH)2
Pd(OAc)2 / 3 PPh3
3. IPA-NH4Cl aq. K2CO3
-H 2 O THF / DME
90% reflux 93%
Losartan
(Antihypertensive)
Merck , J. Org. Chem. 59, 6391 (1994)

21. N-20
Suzuki coupling is a shortcut to biaryls
(BASF's Boscalid Process)
O
OCH3
PRE-SUZUKI ROUTE
N
COOH
N Cl H
5 Synthetic steps Cl
Boscalid
Multi-purpase Fungicide
for Specialty Crops
CN
1 Step SUZUKI ROUTE
Catalyst
Base
CN
Cl + (HO)2B

22. N-21
Boscalid; Agrochemicals (BASF, Germany)
N Cl
O
HN
Cl
Boscalid

23. N-22
Liquid crystal:
Chisso (Japan)
F LC
+ I F Glass substrate
C5H11 B(OH)2
F
F
Pd catalyst / base
C5H11 F
F
Merck (Germany)
F F F
R OCF3 C3H7 OCF3
F

24. N-23
EL Polymer materials
(HO)2B B(OH)2
Br Br
Pd(PPh3)4
Na2CO3 (solid) C8H17 C8H17
C8H17 C8H17
DMAc, 120 °C n

25. N-24
X Pd cat
B (1979)
+ base
Pd cat
B + X (1980)
base
Pd cat
B + X (1981)
base
X Pd cat
B (1985)
+ base
X Pd cat
B (1992)
+ base
Fu 2001-2002
B X Pd cat
Soderquist and
+ (base) Fürstner 1995

26. N-25
Advantages of the Cross-Coupling Reaction between
Organoboron Compounds and Organic Electrophiles:
1. Ready availability of reagents: hydroboration and transmetalation
2. Mild reaction conditions: base problem
3. Water stability
4. Easy use of the reaction both in aqueous and heterogeneous
conditions
5. Toleration of a broad range of functional groups
6. High regio- and stereoselectivity of the reaction
7. Insignificant effect of the steric hindrance
8. Use of a small amount of catalysts
9. Application in one-pot synthesis
10. Nontoxic reaction
11. Easy separation of inorganic boron compounds

27. References
Scientific articles
1) Heck, R. F. and Nolley, J. P. J. Org. Chem. 1972 , 37, p. 2320.
2) Negishi, E.-I., King, A. O. and Okukado, N. J. Org. Chem. 1977, 42, p. 1821
3) Miyaura, N. and Suzuki, A. J. Chem. Soc. Chem. Commun., 1979, p 866.
Review articles
1) Negishi, E. A profile of Professor Richard F. Heck Discovery of the Heck reaction. Journal of
Organometallic Chemistry , 1999, 576, p. XV-XVI.
2) Rouhi, M. Chem. & Eng. News, 2004, 82 (36), Sept. 6, p. 49–58. [Article about Suzuki.]
3) de Meijere, A. and Diederich, F. (Eds.), Metal-Catalyzed Cross-Coupling Reactions, 2004,vol. 1 and
2,Wiley-VCH, Weinheim. pp. 916.
4) Buchwald, S. L. (Ed.) Accounts of Chemical Research, 2008 Vol. 41, Nov. 11, p. 1439–1564.
[Special issue on Cross Coupling.]
Online Resources
•Royal Swedish Academy of Sciences, http://kva.se, and at http://nobelprize.org.
•Prezi.com
•www.openaccesschemistry.com

28. Acknowledgement
Nobelprize.org
Principal, Jawaharlal nehru Technological University
Hyderabad
Dr. Pramod Kumar Dubey
My Research Friends