Suzuki lecture-slides (1)
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N-1
Cross-Coupling Reactions of Organoboranes:
An Easy Way for Carbon-Carbon Bonding
Akira Suzuki
N-2
Conjugated Alkadienes
R'R'
R
R
R'
trans-trans
MY
MYR
R
trans-cis
+ X R'
R'
+ X
R'R R
cis-trans cis-cis
MR
R'
R'M
R
M : transition metal catalyst
N-3
Syntheses of (E)- and (Z)-1-Alkenylboranes
R HRC CH + HBY 2
O
Y2 = (Siamyl)2 ,O
HBY2 R X
RC CXH BY2
H BY2
trans > 99 %
t-BuLi R BY2
H H
cis > 98 %
X = I or Br Y=Siamyl, Cyclohexyl
N-4
X H
R H
H BY 2
R BY
H H
Pd
base
Pd
base 2
H R'
X R'
H H
H R'
X H
H H
X R'
R HH
HH R'
R HR'
HH H
H R'R
HH H
H HR
R'H H
(trans, trans)
(trans, cis)
(cis, trans)
(cis, cis)
N-5Common Catalytic Cycle Involving Sequential Oxidative
Addition (a), Transmetalation (b), and Reductive Elimination (c)
MR-X
(a)
R-R
(c)
Atomic charge in 0.01 e.u.
(Gropen & Haaland, 1973)
+ 12
CH3 CH3 B
R-M-X
(b)
R'-M' (R3B)
R M R'
R R B OR'
R
CH3 -4
- 12
CH3
CH3 B CH3
CH3
- 22
N-6
Bu
1
BX2+ Br Ph
2
Bu Ph3
1a)Catalystb)
(mol %)Base(equiv / 2)
Yield (%)Solvent React.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
Oa)1a, X2 = (Sia)2 1b, X2 = b) L = PPh 3
O
N-7
1-Alkenylborane 1-Alkenyl Bromide Product Yield (%)[Purity (%)]
BuB
Bu B
Bu B
BuB
Bu B
Ph
b)
a)
a)
b)
a)
b)
PhBr PhBu
BuBrPh Ph
Br Ph BuPh
HexBr HexBu
Br Hex BuHe
x
Ph
86 [98]
49 [99]
42 [89]
88 [99]
49 [98]
89 [98]B Br Ph Ph
Reaction conditions: 1-3 mol % of Pd(PPh3)4 / NaOEt / Benzene / Reflux 2ha) Disiamyl b) 1,3,2-Benzodioxaboryl
N-8
Bu BY2P
d(PPh3)4+ RXNaOEt / benzene
reflux, 2 h
Bu R
BY2 RX Product Yield (%) Purity (%)
B(Sia)2
B(OPri)2 Br
BuHex Hex
49 >98
87 >99
B(Sia)2
B( ) 2 PhI
B(OPri)2
58 >94
Bu Ph 49 >83
98 >97
B(Sia)2 Bu 54 >92I
B(OPri)2 87 >99
N-9OH
H2N
O
HO N NH H
O
O Me
OHMe
Me
OO OH
OHO
HOHO
OHHO
OH MeHO
OOH
O HO
O Me
HOHO
OHM
eOH
OH
OH
OH
OHOHOH
OHOH
HO
OHOH
OH
O OHOH
HOO
HOHO
Me OH
HOHO
"Palytoxin" C129H223N3O54 (MW. 2678.6)
O
OHOHOHOH
OH
Synthesis: Kishi et al., J. Am. Chem. Soc, 1989, 111, 7525, 7530
Reaction Mechanism:
Me
N-10
PdL4Bu +
BrB(Sia)2
BuPh Ph9 %
Cl Cl
Cl Cl
Cl Cl
PdL4
Fitton (1968)
H
ex
+
Cl Cl
Cl PdCl·L2
O
BO
NaOMe
Otsuka (1976)
without baser.t./17 h
Cl Cl
Cl PdOMe·L2
no reaction
Cl PdCl·L2
Cl Cl+
Cl PdOMe·L 2
Hex O B O
NaOMe
r.t./2 h
without base
r.t./15 min
without base
r.t./1 h
Cl Cl
Cl89 % Hex
66 %
97 %
Catalytic Formulation of the Vinyl-Vinyl Cross-Coupling
R
R Pd(0)
X
F. Maseras et al., JACS,2005, 127, 9298 R
R Pd
N-11
R"
R"B
R'ONa
R" OR'B
A. Monteiro et al., J. Braz.Chem. Soc. 2007, 18
PdX
R
NaX
R"
R" OR'PdOR‘ B
N-12
Reaction of B-Alkylboranes
R1 R3
+ R4X
R2 B
R4 : 1-AlkenylAryl1-AlkynylAllyl
Benzyl
R B + R4X
R : Alkyl
Pd(0)
Base
R1 R3
R2 R4
R R4
N-13
PdCl2(dppf) (3 mol%)I
Br
Br
Br
+
+
+
+
B C8H17NaOMe / THF, reflux
B PdCl2(dppf) (3 mol%)
NaOMe / THF, reflux
B (CH2)3 OMe
OMe
PdCl2(dppf) (3 mol%)B C8H17NaOMe / THF, reflux
C8H17
98 %
88 %
(CH2)3 OMe
OMe
87 %
C8H17
94 %
N-14
Alkyl-Vinyl Coupling:Total Synthesis of Polycyclic Ether Natural Product
M. Sasaki, Bull. Chem. Soc. Jpn. 2007, 80, 856
TfO O
O 9-BBNR1O OP
H
OH9-BBN
R1OOP
OR2
Pd(0)aq. base
H HO O
R1O OR 2
OP
acetal
1. hydroboration
2. oxidation
OR1O
O
P
H H
OOR2
O
formationR1O
O O OR2
OH OH
N-15
Polycyclic Ether Marine Natural Products:
HO
HO
O
Me Me H HO O
O
HO H
HO HH H H H H
Gambierol
HO
MeMe O
H
O
OHMe
OHC
Me
H
H HH
OO O O
H H H H
OHH
O HMe
O
H OH
H H H H HO O HO H
O O OH H H H Me
Gymnocin-AH
HO
OH
Me
N-16
Aromatic-Aromatic Cross-Coupling Reactions
ZB(OH)2 + Br
Pd(PPh3)4Z
aq Na2CO3
benzene, reflux
Suzuki Coupling:
B(OH)2
+ XR
B(OH)2
+ XR
Ullmann Reaction:
X
+
XR
R Pd(0), base
R' Pd(0), base
R' Cu, high temp
N-17
R R
R R'
R R
R R'
R' R'
N-18
Valsartan (Novartis): Antihypertensive
CH3
CH3 CH3
O
N COOHN N
HN N
Suzuki Coupling
3.5 million users in Japan
22 million users in the whole world
N-19
Angiotensin II Receptor Antagonist (Losartan)
CPh3
N N NN N N
HO
CPh3
N N
Cl
N
NC4H9 N
N
HO Cl
CPh3 NN N N C 4H91. BuLi
2. B(OPri)3
3. IPA-NH4Cl-H 2 O
B(OH)2
90%
Br
Pd(OAc)2 / 3 PPh3
aq. K2CO3
THF / DMEreflux 93%
Losartan(Antihypertensive)
Merck , J. Org. Chem. 59, 6391 (1994)
Suzuki coupling is a shortcut to biaryls (BASF's Boscalid Process)
OCH3PRE-SUZUKI ROUTE
COOHN
5 Synthetic steps
N-20
O
N
HCl
ClBoscalid
Multi-purpase Fungicide
CN
1 Step
CatalystBase
for Specialty Crops
SUZUKI ROUTE
CN
Cl + (HO)2B
N-21
Boscalid; Agrochemicals (BASF, Germany)
N Cl
O
H N
Cl
Boscalid
N-22
Liquid crystal:
Chisso (Japan)
C5H11 B(OH)2
Pd catalyst / base
Merck (Germany)
F F
R OCF3
F
+ I F
F
C5H11
C3H7
LC
Glass substrate
F
F
F
F
OC
F3
F
N-23
EL Polymer materials
Br Br
C8H17 C8H17
(HO)2B B(OH)2
Pd(PPh3)4Na2CO3 (solid)DMAc, 120 °C
C8H17 C8H17n
N-24
B
B
B
B
B
B
XPd cat+ base
Pd cat+ X
base
Pd cat+ X
base
XPd cat+ base
XPd cat+ base
XPd cat+ (base)
(1979)
(1980)
(1981)
(1985)
(1992)
Fu 2001-2002
Soderquist andFürstner 1995
N-25
Advantages of the Cross-Coupling Reaction betweenOrganoboron Compounds and Organic Electrophiles:
1. Ready availability of reagents: hydroboration and transmetalation2. Mild reaction conditions: base problem
3. Water stability4. Easy use of the reaction both in aqueous and heterogeneous
conditions5. Toleration of a broad range of functional groups6. High regio- and stereoselectivity of the reaction
7. Insignificant effect of the steric hindrance8. Use of a small amount of catalysts9. Application in one-pot synthesis
10. Nontoxic reaction11. Easy separation of inorganic boron compounds
ReferencesScientific 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. 18213) 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
1)Royal Swedish Academy of Sciences, http://kva.se, and at http://nobelprize.org.2)Prezi.com3)www.openaccesschemistry.com
Acknowledgement
Nobelprize.org
Principal, Jawaharlal nehru Technological University Hyderabad
Dr. Pramod Kumar Dubey
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