Cross-Coupling Reactions of Organoboranes: p g g An Easy Way for ...
Transcript of Cross-Coupling Reactions of Organoboranes: p g g An Easy Way for ...
N-1
Nobel Lecture, December 8, 2010
Cross-Coupling Reactions of Organoboranes:p g g
An Easy Way for Carbon-Carbon Bondingy y g
Akira SuzukiS
Conjugated AlkadienesN-2
RR'
R'
R'RR' R
RR
R
trans trans trans cis cis trans cis cistrans-trans trans-cis cis-trans cis-cis
+RMY X R
R' R'M
+MY
XR' R'M
RMY
R
M : transition metal catalyst
N-3
Syntheses of (E)- and (Z)-1-Alkenylboranes
R H
Syntheses of (E)- and (Z)-1-Alkenylboranes
R
H
H
BY2
+ HBY2RC CH
O
O
trans > 99 %
(Siamyl)2,=Y2O
R
H
X
BY2
R
H
BY2
H
t-BuLiHBY2RC CX
H BY2 H H
X = I or Br Y = Siamyl Cyclohexyl
cis > 98 %
X = I or Br Y = Siamyl, Cyclohexyl
N-4
HX
H
HX
R' HRH (trans trans)
H
HR
BY2
Pd R'XH
H R'HRbase
(trans, trans)
2 H H
H
HR
H
R'
H
(trans, cis)
H H
X
R'H
H RR'H
BY2R
X H
Pd HH H
R
HH
HH
(cis, trans)
H H X R'
H
R
H
base HH
R' (cis, cis)H H
N-5Common Catalytic Cycle Involving Sequential Oxidative Addition (a), Transmetalation (b), and Reductive Elimination (c)
R R' Atomic charge in 0.01 e.u.
( ), ( ), ( )
MR-X R-R
( ) (c)
(Gropen & Haaland, 1973)
+ 12
CH3 BCH3
(a) (c)
CH3 - 4
MR
R'R M X
BCH3
CHCH
(b)- 12R'R-M-X
B OR'R
RR
B CH3CH3CH3
R'-M' (R3B) - 22R -M (R3B)
N-6
Bu Br Bu+BuBX2
BrPh
BuPh+
31 2
THF
Catalystb)
(mol %)1a) Base
(equiv / 2)
1b PdL (3) N
Solvent React.time (h)
Yield (%)of 3
6 0THF1b PdL4 (3) None
1b PdL4 (3) None Benzene
6
6
0
0
THF
THF
1a PdL4 (3)
1b PdL4 (3)
2M NaOEt (2)-EtOH
2M NaOEt (2)-EtOH
2
4
73
78THF1b PdL4 (3)
1b PdL4 (1)
2M NaOEt (2)-EtOH
2M NaOEt (2)-EtOH Benzene
4
2
78
86
O
O
a) 1a, X2 = (Sia)2 1b, X2 = b) L = PPh3
O
N-7
1-Alkenyl Bromide Product Yield (%)1-Alkenylborane
BuB
Br PhBu
Ph
1-Alkenyl Bromide Product [Purity (%)]
b) 86 [98]
1 Alkenylborane
B
Bu B BrPh
Bu
BuPha) 49 [99]
Bu B Br Ph
Ph Ph
BuPh
a) 42 [89]
Br Hex
Ph
BuHex
b) 88 [99]BuB
Br Hex BuHex
a) 49 [98]Bu B
PhB Br Ph Ph
Phb) 89 [98]
Reaction conditions: 1-3 mol % of Pd(PPh3)4 / NaOEt / Benzene / Reflux 2h a) Disiamyl b) 1,3,2-Benzodioxaboryl
N-8Bu BY2 RX
Pd(PPh3)4 Bu R+ RX
BY
NaOEt / benzenereflux, 2 h
(%) P it (%)
Bu
BY2 RX Product Yield (%) Purity (%)
B(Sia)2 49 >98Br Hex HexB(OPri)2 87 >99
B(Si ) 8 >94
Bu PhPhI
B(Sia)2
B( )2
58 >94
49 >83
B(OPri)2 98 >97
IBu
B(OPri)2
B(Sia)2 54 >92
87 >99B(OPr )2 87 >99
N-9
H N
OHO
OH
OH
HOHO OH
OHO
H2N OO
O
HOHO
OH
OHMe
OH
HO
HO OH
O
OHOH
OHOH
HOM HOOHMOO OH OHOH
HOHO
O
HOMeHO
OHNH
OHMe
OH
O
NH
O
HO
OH
OH
OHMe O
O OH
OHO
Me
MeOH
OHMe
O
O OH MeHO
O
HOHOOH
OHOH OHOH
"P l t i " C H N O (MW 2678 6)"Palytoxin" C129H223N3O54 (MW. 2678.6)Synthesis: Kishi et al., J. Am. Chem. Soc, 1989, 111, 7525, 7530
N-10
M PdL
Reaction Mechanism:
BuB(Sia)2
Me BrPh Bu
Ph+ PdL4
9 %
Cl
ClCl
Cl
Cl
PdCl LCl
Cl NaOMe Cl
PdOMe·L2Cl
ClPdL4
Cl Cl
Hex O
PdCl·L2Cl PdOMe L2ClFitton (1968) Otsuka (1976)
without baseCl
PdCl·L2Cl
Cl HexBO
O
N OMCl Cl
+ r.t./17 hwithout base no reaction
Hex O
NaOMeCl
Hex89 %r.t./2 h
Cl
PdOMe·L2Cl
Cl HexBO
O+ r.t./15 min 66 %
without base
r.t./1 h97 %
without base
N-11Catalytic Formulation of the Vinyl-Vinyl Cross-Coupling
RR
R"Pd(0)
XR
RF. Maseras et al., JACS,2005, 127, 9298
R
PdX
Pd
R"R"
B
R'ONa
RR" OR'
R"B
OR'
PdOR'R
BOR
NaXA. Monteiro et al., J. Braz.Chem. Soc. 2007, 18
N-12
Reaction of B-Alkylboranes
R4XPd(0)
Reaction of B Alkylboranes
+R1 R3 R1 R3
R4XBase
R4 : 1-Alkenyl
+R2 B R2 R4
R : 1 Alkenyl Aryl 1-Alkynyl
AllylAllyl Benzyl
R B R4X R R4+
R : Alkyl
N-13
PdCl2(dppf) (3 mol%)I B C8H17 C8H17+
PdCl2(dppf) (3 mol%)NaOMe / THF, reflux
98 %
BrB
+PdCl2(dppf) (3 mol%)
88 %
NaOMe / THF, reflux
Br OMe
88 %
+ (CH2)3 (CH2)3 OMeB
OMe
87 %
( 2)3
OMe
Br B C8H17 C8H17
87 %
+PdCl2(dppf) (3 mol%)
NaOMe / THF, refluxNaOMe / THF, reflux94 %
N-14
Alkyl-Vinyl Coupling:Total Synthesis of Polycyclic Ether Natural Product
M. Sasaki, Bull. Chem. Soc. Jpn. 2007, 80, 856
O
OTfOOR2
O HO
OP
9-BBNR1O
Pd(0)aq. base
O
OPR1O
9-BBN
O OH1 hydroboration O OH H
O
OPR1O
OOR2
1. hydroboration
2. oxidation
O
OPR1O
OOR2
O
O OH H
R1O OR2
acetalformation
OH OH
N-15Polycyclic Ether Marine Natural Products:
HOMe Me H H
O
O
O
O
OO
OH H H H H M
HO
Me Me H HH
HH H
OH H H H H Me
MeH OH
MeGambierol
OHH H
HHO OH
OO O
O
OO O O
OH H H HH
HH
H
HHHHHMeH
HHM
OHC
OO O O
O
O
HH
H H H H Me HH
OH
HMe
Gymnocin-AMe
y
N-16
Aromatic-Aromatic Cross-Coupling Reactions
ZB(OH)2 Br+
Z
Pd(PPh ) ZPd(PPh3)4
aq Na2CO3benzene, reflux
Z
N-17Suzuki Coupling:
B(OH)2 + XR Pd(0), baseR R R
B(OH)2 + XR Pd(0) bR' R R'R Pd(0), baseR R R'
Ullmann Reaction:R R
X + XR Cu high tempR' R R'R Cu, high temp.R R R'
R' R'
N-18
V l t (N ti ) A tih t iValsartan (Novartis): Antihypertensive
CH3 CH3O
CHN COOH
CH3
NNN
HN
Suzuki Coupling
3.5 million users in Japan22 million users in the whole world
N-19Angiotensin II R t A t i t Receptor Antagonist (Losartan)
ClHO
NNCPh3
NNCPh3
NNCPh3
NN
ClHO
NN
C4H9N
NNN N
NNN
B(OH)2
NNN
NN
C4H9
4 9
1. BuLi
2 B(OPri)3
Br
Pd(OAc) / 3 PPh2. B(OPr )3
3. IPA-NH4Cl -H2O 90%
Pd(OAc)2 / 3 PPh3aq. K2CO3THF / DMEreflux 93%
Losartan(Antihypertensive)
reflux 93%
(Antihypertensive)Merck , J. Org. Chem. 59, 6391 (1994)
N-20Suzuki coupling is a shortcut to biaryls (BASF's Boscalid Process)
OCH3PRE-SUZUKI ROUTE
O
(BASF s Boscalid Process)
COOHPRE-SUZUKI ROUTE
N
N
ClH
5 Synthetic steps ClBoscalid
CNMulti-purpase Fungicidefor Specialty Crops
1 Step
C t l tSUZUKI ROUTE
CatalystBase
CN
Cl (HO)2B+
N-21
Boscalid; Agrochemicals (BASF Germany)Boscalid; Agrochemicals (BASF, Germany)
N
O
Cl
HN
ClB lidBoscalid
N-22
Liquid crystal:q y
Chisso (Japan)
C5H11 B(OH)2 I F
F
+
( p )
LC
Glass substrate5 11 ( )2
FF
Pd catalyst / baseC5H11 F
F
Pd catalyst / base
FFF
Merck (Germany)
C3H7 OCF3
F
R OCF3
N-23
EL Polymer materials
Br Br Pd(PPh )
(HO)2B B(OH)2
Br Br
C8H17 C8H17C8H17 C8H17 n
Pd(PPh3)4Na2CO3 (solid)DMAc, 120 °C
N-24
BX
+Pd cat
base (1979)
B X (1980)+ Pd cat
base
XB + (1981)Pd catbase
BX+ (1985)
Pd catbase
BX+ (1992)
Pd catbase
F 2001 2002
B X+ Soderquist andFürstner 1995
Pd cat(base)
Fu 2001-2002
Fürstner 1995
N-25
Ad t f th C C li R ti b t 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 problem3 Water stability 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 I i ifi t ff t f th t i hi d 7. Insignificant effect of the steric hindrance 8. Use of a small amount of catalysts9. Application in one-pot synthesis 9. Application in one pot synthesis
10. Nontoxic reaction11. Easy separation of inorganic boron compounds