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Microsoft powerpoint - chatani (no 7)

Cross-Coupling Reaction
catalyst
Tamao-Kumada-Corriu
Murahashi
Suzuki-Miyaura
Migita-Kosugi-Stille
Al, Zr, In, Bi.
Reaction Mechansim
oxidative
transmetallation
reductive
addition
elimination
Tamao-Kumada-Corriu Coupling
NiCl2(dppp)
R = Ar, vinyl, benzyl
R' = Ar, vinyl, ally, alkyl
X = I, Br, Cl
還元的脱離 R R'
The first reports
NiCl2(dppe)
Et2O
reflux, 20 h

Tamao, K.; Sumitani, K.; Kumada, M. J. Am. Chem. Soc. 1972, 94, 4374.
Ni(acac)
Corriu, R. J. P.; Masse, J. P. J. Chem. Soc., Chem. Commun. 1972, 144.
Mg (12.2 g, 0.50 mol)
Et2O (200 mL)
1-bromobutane (68.5 g, 0.5 mol) in Et2O (50 mL)

NiCl2(dppp)
0 °C reflux
(30.0-31.5 g)
NiCl2(dppp) (0.25 g, 0.5 mmol)
1,2-dichlorobenzene (29.5 g, 0.21 mol)
Et2O (150 mL)

Kumada, M.; Tamao, K.; Sumitani, K. Org. Synth. 1988, Coll. Vol. 6, 407.
cf. Buck, J. R.; Park, M.; Wang, Z.; Prudhomme, D. R.; Rizzo, C. J.
Org. Synth
. 1999, Vol. 77, 153.
Organic Synthesis Website: http://www.orgsyn.org/
NiCl2/L*
Et2O
0 °C, 2 d

(-)-DIOP
R = iPr
(S)-(R)-PPFA
t-Leuphos
<16% ee
R = tBu
(R)
(S)
Hayashi, T.; Konishi, M.; Fukushima, M.; Kanehira, K.; Hioki, T.; Kumada, M.
J. Org. Chem
. 1983, 48, 2195.
Et2O, 0 °C
ibuprofen 81%ee
Hayashi, T.; Konishi, M.; Fukushima, M.; Mise, T.; Kagotani, M.; Tajika,
M.; Kumada, M. J. Am. Chem. Soc
. 1982, 104, 180.
PhMgBr/LiBr
Et2O/toluene
- 30 °C, 40 h

87% (93%ee)
Hayashi, T.; Niizuma, S.; Kamikawa, T.; Suzuki, N.; Uozumi, Y.
J. Am. Chem. Soc.
1995, 117, 9101.
NiCl2/1,3-butadiene
C10H21 Br +
C10H21 Bu
THF, 0 °C, 30 min
Terao, J.; Watanabe, H.; Ikumi, A.; Kuniyasu, H.; Kambe, N.
J. Am. Chem. Soc.
2002, 124, 4222.
+ tBuMgCl
C8H17 But
25 °C, 6 h
Br > F > Cl
Terao, J.; Ikumi, A.; Kuniyasu, H.; Kambe, N. J. Am. Chem. Soc. 2003, 125, 5646.
NiCl2(PPh3)2
C6H6
rt, 72 h

Wenkert, E.; Michelotti, E. L.; Swindell, C. S.; Tingoli, M.
J. Org. Chem
. 1984, 49, 4894.
NiCl2(PPhCy2)2
tAmOMe/Et2O
23 °C, 15 h

Dankwardt, J. W. Angew. Chem., Int. Ed. 2004, 43, 2428.
cf. Dallaire, C.; Kolber, I.; Gingras, M. Org. Synth. 2000, Vol. 78, 42.
Iron-Catalyzed Grignard Cross-Coupling
Fe(acac)3
RMgBr

0 °C rt, 5 min
PhMgBr (28%)
6H13MgBr (91%)
X = Cl (91%) OTf (87%) OTs (83%) Br, I (<40%)
6H13MgBr:
Fe(acac)
0 °C rt, 5 min
14H29MgBr (95%) PhMgBr (73%)
Furstner, A.; Leitner, A.; Mendez, M.; Krause, K. J. Am. Chem. Soc. 2002, 124, 13856.
Furstner, A.; Leitner, A. Angew. Chem. Int. Ed.
2002, 41, 609.
NiCl2(dppp)
C4H9MgBr

reflux, 6 h
Fe(acac)3
C6H13MgBr

0 °C, 5 min
Fe(acac)3
1) Me2CHCH2MgBr

2) C14H29MgBr
THF/NMP, 0 °C
1) 3 min
2) 5 min

RCH2CH2CH2CH2R
4 RCH2CH2MgX
[R Fe(MgX)]
[Fe(MgX)
[R Fe(MgX)2]
Negishi Coupling
R = Ar, vinyl, alkyl
R' = Ar, vinyl, alkyl
generaion of Zn reagents
inert to ketone, esters, amino and
R'MgX + ZnCl
cyano goups
R'Li + ZnCl2
R'3Al + ZnCl2

I + Zn(Cu)
iodine-zinc exchange
Pd(PPh3)4
tBuLi
THF, rt, 1 h
THF, rt, 5 h
-78 °C, 1 h
rt, 1h
o-iodotoluene (26.2 g, 120 mmol)
Pd(PPh3)4 (1.16 g, 1 mmol)
Et2O (60 mL)
THF (100 mL)
1.56M tBuLi in hexane (154 mL, 240 mmol)
1-bromo-4-nitrobenzene (20.2 g, 100 mmol)
THF (80 mL)
ZnCl2 (16.3 g, 120 mmol)
THF (60 mL)

Negishi, E.; Takahashi, T.; King, A. O. Org. Synth. 1993, Col. Vol. 8, 430.
Pd(PPh3)4, LiCl
t
THF, reflux, 18 h
-78°C, 30 min
1.75M tBuLi in pentane (52 mL, 91.0 mmol)
THF (80 mL)
2-bromopyridine (7.13 g, 45.1 mmol)
ZnCl2 (13.3 g, 97.4 mmol)

5-methylpyridyl triflate (8.95 g, 37.1 mmol)
LiCl (3.18g, 75.2 mmol)
Pd(PPh3)4 (1.75 g, 1.5 mmol)

Smith, A. P.; Savage, S. A.; Love, J. C.; Fraser, C. L. Org. Synth. 2000, Vol. 78, 51.
Zn(Cu) (1.71 g, 26 mmol)
C6H6 (60 mL)
HMPA (7.7 mL)

4-iodo-1-phenylbutan-1-one (5.48 g, 20 mmol)
Pd(PPh3)4
40 °C, 1 h
(E)-1-iodohexene (3.88 g, 18.5 mmol)
Pd(PPh3)4 (711 mg, 0.62 mmol)
C6H6 (30 mL)

Tamaru, Y.; Ochiai, H.; Nakamura, T.; Yoshida, Z. Angew. Chem., Int. Ed. Eng.
1987, 26
, 1157.
iPr2Zn (1.1 equiv)
Li(acac) (10 mol%)

Pd(0) or Cu(I)
(FG Ar)2Zn
Et2O/NMP (1:10)
25 °C, 12 h
high functional group compatibility
ester, ketone, cyano, aldehyde, isothiocyanate

Pd(dba)2/TFP
Kniesel, F. F.; Dochnahl, M.; Knochel, Angew. Chem. Int. Ed. 2004, 43, 1017.
decyne (22.6 mL, 125 mmol)
hexane (80 mL)

HAl(iBu)2
HAl(iBu)
hexane, 50-60 °C, 6 h
2 (22.3 mL, 125 mmol)
Pd(PPh3)4
Al(Bui)2
(Z)-hezenyl iodide (21.0 g, 100 mmol)
(14.5-15.8 g)
ZnCl2 (13.6 g, 100 mmol)
Pd(PPh3)4 (1.15 g, 1 mmol)
THF (100 mL)

Negishi, E.; Takahashi, T.; Baba, S. Org. Synth. 1993, Coll. Vol.8, 295.
Cp2ZrCl2 (7.01 g, 24 mmol)
ClCH2CH2Cl (100 mL)
1-buten-3-yne (12.48 g, 120 mmol) in xylene

Cp2ZrCl2
2M Me3Al (120 mL, 240 mmol) in toluene
Me3Al
ClCH2CH2Cl
rt, 12 h

Pd(PPh3)4
THF
rt, 6 h

16.70 g (83%)
geranyl chloride (17.25 g, 100 mmol)
Pd(PPh3)4 (1.15 g, 1 mmol)
THF (100 mL)

Negishi, E.; Matsushita, H. Org. Synth. 1990, Coll. Vol.7, 245.
Suzuki-Miyaura Coupling
R = Ar, vinyl, alkynyl, alkyl
R' = Ar, vinyl, ally, alkyl
X = I, Br, Cl, OTs
high functional group compatibility
non-toxicity of boronic acids
stability of boronic acids to heat, air, and moisture
easy separation of inorganic boron from reaction mixture

Reaction Mechansim
oxidative
transmetallation
reductive
addition
elimination
role of base
ate complex
The first paper
cat. Pd(PPh3)4
NaOEt
benzene/EtOH

reflux, 2 h
Miyaura, N.; Yamada K.; Suzuki, A. Tetradedron Lett. 1979, 3437.
Alkyl-Alkyl coupling
Pd(PPh3)4
K3PO4
dioxane
60 °C, 24 h

Ishiyama, T.; Abe, S.; Miyaura, N.; Suzuki, A. Chem. Lett. 1992, 691.
Pd(OAc)2, PPh3
PrOH, H2O, reflux, 45 min
4-bromobenzaldehyde (50.0 g, 0.270 mol)
benzeneboronic acid (34.6 g, 0.284 mol)
1-propanol (485 mL)

Pd(OAc)2 (0.182 g, 0.811 mmol)
PPh3 (0.638 g, 2.43 mmol)
1M Na2CO3 (162 mL, 0.324 mol)
H2O (95.0 mL)

Huff, B. E.; Koenig, T. M.; Mitchell, D.; Staszak, A. Org. Synth. 1997, Col. Vol. 75, 53.
Pd(OAc)2, K2CO3
acetone, H2O
reflux, 2 h

o-tolylboronic acid (10.0 g, 73.6 mmol)
4-iodoanisole (16.8 g, 71.8 mmol)
acetone (200 mL)

K2CO3 (25.0 g, 0.180 mol) in H2O (200 mL)
Pd(OAc)2 (3.30 mg, 0.02 mmol) in acetone (10 mL)
Goodson, F. E.; Wallow, T. I.; Novak, B. M. Org. Synth. 1997, Vol. 75, 61.
2(PhCN)2, AsPh3
THF/H2O, 25°C, 1 h
2-iodo-2-cyclohexen-1-one (10.69 g, 70.4 mmol)
4-methoxyphenylboronic acid (16.72 g, 72.1 mmol)
Ag2O (0.85 g, 2.8 mmol)
AsPh3 (0.53 g, 1.4 mmol)
PdCl2(PhCN)2 (0.53 g, 1.4 mmol)
THF (200 mL)
H2O (25 mL)

Ruel, F. S.; Braun, M. P.; Johnson, C. R. Org. Synth. 1997, Vol. 75, 69.
hexyne (4.9 g, 60 mmol)
60-70 °C
catecholborane (6.7 mL, 60 mmol)
2(PPh3)2
reflux, 3 h
(Z)-β-bromostyrene (8.4 g, 46 mmol)
2M NaOEt in EtOH (50 mL)
PdCl2(PPh3)2 (0.28 g, 0.4 mmol)

Miyaura, N.; Suzuki, A. Org. Synth. 1993, Col. Vol. 8, 532.
Pd2(dba)3
aq. KOH, THF
-78 °C rt
Yasuda, N.; Xavier, L.; Rieger, D. L.; Li, Y.; DeDamp, A. E.; Dolling, U. H.
Tetrahedron Lett
. 1993, 34, 3211.
TESO H H Me
Pd(dba)2
THF, H2O, Et3N
30 °C, 2-3 h
Yasuda, N.; Huffman, M. A. et al
J. Org. Chem. 1998, 63, 5438.
2.00 kg (70%)
Palytoxin caboxylic acid
Kishi, Y. et.al. J. Am. Chem. Soc. 1989, 111, 7525.
Recent Advances in Cross-Coupling Reactions
Design of Ligand
bulky and electron-rich phosphine
N
-heterocyclic carbene
For a review on Pd-catalyzed coupling reactions of aryl chlorides:
Fu, G. C. Angew. Chem. Int. Ed.
2002, 41, 4176.
For a review on monoligated Pd species:
Christmann, U.; Vilar, R. Angew. Chem. Int. Ed
. 2005, 44, 366.
Pd2(dba)3/PBut3
THF, KF
rt

intermolecular competition experiment : kAr-Cl / kAr-OTf >20
Pd(OAc)2/PCy3
THF, KF
rt

Pd2(dba)3/PBut3
Littke, A. F.; Dai, C.; Fu, G.C. J. Am. Chem. Soc. 2000, 12
Pd(OAc)2
K3PO4
toluene

90 °C, 12 min
increases steric bulk
oxygen lone pair may
stabilize Pd complex
prevents cyclometalation
increases electron density
in biaryl backbone

Pd(OAc)2
K3PO4
toluene

110 °, 18 h
Walker, S. D.; Barder, T. E.; Martineli, J. R.; Buchwald, S. L.
Angew. Chem. Int. Ed.
2004, 43, 1871.
Barder, T. E.; Walker, S. D.; Martinelli, J. R.; Buchwald, S. L.
J. Am. Chem. Soc. 2005, 127, 4685.
iPr
Pri
t
Pri
t
THF, K3PO4
80 °C, 3 h

Nguyen, H. N.; Huang, X.; Buchwald, S. L. J. Am. Chem. Soc. 2003, 125, 11818.
Ni(cod)2/PCy3
THF, K3PO4
rt, 8 h

Tang, Z.-Y.; Hu, Q.-S. J. Am. Chem. Soc. 2004, 126, 3058.
NiCl2(dppe)/PPh3
toluene, K3PO4
80 °C, 14 h

Percec, V.; Golding, G. M.; Smidrkal, J.; Weichold, J. Org. Chem. 2004, 69, 3447.
Gstottmayr, C. W. K.; Bohm, V. P. W.; Herdtweck, E.; Grosche, M.;
Herrmann, W. A. Angew. Chem. Int. Ed.
2002, 41, 1363.
Pd(OAc)2
K3PO4
THF/toluene

110 °C, 16 h
Altenhoff, G.; Goddard, R.; Lehmann, C. W.; Glorius, F.
J. Am. Chem. Soc.
2004, 126, 15195.
NaOBut
i
PrOH
rt, 75 min
Ar = 2,6-(iPr)2C6H3
i
[IPrPd(0)]
Navarro, O.; Kelly, R. A.; Nolan, S. P. J. Am. Chem. Soc. 2003, 125, 16194.35
Migita-Kosugi-Stille Coupling
R = Ar, vinyl, ally, alkyl
R' = Ar, vinyl, allyl
X = I, Br, Cl, OTf
R' = alkynyl > vinyl > aryl > benzyl, allyl > acetonyl > CH3
SE2 (cyclic)
SE2 (open)
Espinet, P. et. al. J. Am. Chem. Soc. 2000, 122, 11771.
Angew. Chem. Int. Ed. Engl. 2004, 43, 4704.
The first papers
+ Bu3SnBr
benzene
100 °C, 20 h

Kosugi, M.; Sasazawa, K.; Shimizu, Y.; Migita, T. Chem. Lett. 1977, 301.
Pd(PPh3)4
+ Me3SnCl
benzene
140 °C, 5 h

Kosugi, M.; Shimizu, Y.; Migita, T. Chem. Lett. 1977, 1423.
2Pd(PPh3)2Cl
+ Me3SnCl
HMPA, 65 °C, 10 min
Milstein, D.; Stille, J. K. J. Am. Chem. Soc. 1978, 100, 3636.
Removal of R3Sn-X
Pd(PPh3)4
0.23 g (0.20 mmol)

toluene (20 mL)
reflux, 4 h
(10.1 mmol)
(11.0 mmol)
pyridine (4.4 mL), 1.2 N pyridinium fluoride solution (9.3 mL)
stirred for 16 h at rt
extraction by Et2O

McKean, D. R.; Parrinello, G.; Renaldo, A. F.; Stille, J. K.
J. Org. Chem
. 1987, 52, 422.
PdCl2(PPh3), LiCl
DMF, 100-105 °C, 2.5 h
DMF (300 mL)
4-nitrophenyl trifluoromethanesulfonate (15.0 g, 55.4 mmol)
tributyl(4-methoxyphenyl)stannane (27.8 g, 70.0 mmol)
LiCl (7.5 g)
PdCl2(PPh3)2 (1.6 g)

vaccum-filterd through the pad of Celite 521, washed with EtOAc
removal of EtOAc, the brown liquid is slowly poured into H2O (1.5 L)
and collect the preciptate after standing for 8 h
the solid is dissolved in CH3CN (500 mL), washed with hexane (3 x
300 mL), 24 g of crude product as a brown solid
column chromatography (Rf = 0.26, hexane:EtOAc = 95:5), 6.9 g (a
yellow solid)
dissolved in EtOAc and stirred over saturated, aqueous KF for 24 h
recrystalization from EtOH, 6.1 g (yellow needles)

Stille, J. K.; Echavarren, A. M.; Williams, R. M. Org. Synth. 1998, Col. Vol. 9, 553.
Pd/C, Cul, AsPh
NMP, 95°C, 24 h
4-iodoacetophenone (10.0 g, 40. 6 mmol)
CuI (770 mg, 4.1 mmol)
1-methyl-pyrroldinone (150 mL)
2-(tributylstannyl)thiophene (14.1 mL, 44.7 mmol)
10% Pd/C (215 mg, 0.2 mmol)

EtOAc (300 mL), saturated aqueous NaF (200 mL), stirred
vigorously for 30 min
the green-yellow hetergeneous mixture is passed
through a sand pad

Liebeskind, L. S.; Pena-Cabrera, E. Org. Synth. 1999, Vol. 77, 135.
(-)-Macrolactine A
Smith, A. B., III; Ott, G. R. J. Am. Chem. Soc. 1998, 120, 3935.
(-)-Macrolactine A
Smith, A. B., III; Ott, G. R. J. Am. Chem. Soc. 1998, 120, 3935.
Sanglifehrin A (SFA)
Nicolau, K. C. et. al. J. Am. Chem. Soc. 2000, 122, 3830.
Hiyama Coupling
Y = Cl, F, H, OMe, cyclobutyl, thienyl, OH .
R = Ar, vinyl, alkynyl, allyl
R' = Ar, vinyl, allyl, alkynyl
X = I, Br, OTf
[(η3-C3H5)PdCl]2
(Et

2N)3S+Me3SiF2 (TASF)
HMPA, 50 °C, 2 h
Hatanaka, Y.; Hiyama, T. J. Org. Chem. 1988, 53, 918.
Alkyl-Alkyl Coupling
undesired
β-hydride
elimination

Alkyl-Alkyl Coupling
Pd(OAc)2/PCy3
K

THF, rt, 16 h
Netherton, M. R.; Dai, C.; Neuschutz, K.; Fu, G. C. J. Am. Chem. Soc. 2001, 123, 10099.
Pd2(dba)3/PCy3
CsOH.H2O
dioxane, 90 oC
Kirchhoff, J. H.; Dai, C.; Fu, G. C. Angew. Chem. Int. Ed. 2002, 41, 1945.
Pd2(dba)3/P(cC5H9)3
THF/NMP, NMI
80 °C, 14 h
Zhou, J.; Fu, G. C. J. Am. Chem. Soc. 2003, 125, 12527.
Pd(acac)2
55 °C, 24 h
Wiskur, S. L.; Korte, A.; Fu, G. C. J. Am. Chem. Soc. 2003, 125, 82.
PMetBu2
Si(OMe)3
THF, r.t.
Lee, J.; Fu, G. C. J. Am. Chem. Soc. 2003, 125, 5616.
[(π-ally)PdCl]2
PCy(pyrrolidinyl)2
Tang, H.; Menzel, K.; Fu, G. C. Angew. Chem. Int. Ed. 2003, 42, 5079.
sBu-Pybox
Bus
Bus
Ni(cod)2
DMA, r.t., 20 h
Zhou, J.; Fu. G. C. J. Am. Chem. Soc. 2003, 125, 14726.
Ni(cod)2
sbutanol, KOBut
60 oC, 5 h
Zhou, J.; Fu, G. C. J. Am. Chem. Soc. 2004, 126, 1340.
Si: Powell, D. A.; Fu, G. C. J. Am. Chem. Soc. 2004, 126, 7788.
Sn: Powell, D. A.; Maki, T.; Fu, G. C. J. Am. Chem. Soc. 2005, 127, 510.

Source: http://ocw.osaka-u.ac.jp/engineering-jp/synthetic-organic-chemistry-adv-jp/no-7.pdf

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