Post on 01-Apr-2018
Catalytic Asymmetric Pauson-Khand Reaction
Won-jin Chung02/25/2003
U. Khand; G. R. Knox; P. L. Pauson; W. E. WattsJ. Chem. Soc. Chem. Commun. 1971, 36
The General Pattern of the Pauson-Khand Reaction
R
OR Co2(CO)8
D
Schore, N. E.; Croudace, M. C.J. Org. Chem. 1981, 46, 5436
• Formal [2+2+1] cycloaddition• Stoichiometric amount of the metal• Long reaction time
R1
R2 Co2(CO)6 (OC)3Co Co(CO)3C C
R2 R1
=
Improved Reaction Conditions
Promoters
• Tertiary amine N-oxides - Room temperature - Generate free coordination sites at cobalt by oxidative removal of CO ligands Shambayati, S.; Crowe, W. E.; Schrieber, S. L. TL 1990, 31, 5289 Jeong, N.; Chung, Y. K.; Lee, B. Y.; Lee, S. H.; Yoo, S.-E. Synlett 1991, 204
• Primary amines as solvent
- Few minutes
Sugihara, T. et al. ACIEE 1997, 36, 2801
PhCo2(CO)6 +
n-Bu S CH3
ClCH2CH2Cl
83oC, 30 min, 79%
O
Ph
Improved Reaction Conditions
• Sulfides - Mild condition
NHp-TsN Co2(CO)6p-Ts83oC, 30 min, 15%
NH2
N Op-TsN Co2(CO)6p-Tsn-Bu S CH3
ClCH2CH2Cl
83oC, 30 min, 79%
Sugihara, T.; Yamada, M.; Yamaguchi, M.; Nishizawa, M. Synlett 1991, 204
Catalytic Pauson-Khand Reactions – Cobalt Catalyzed
• High CO pressure, high temperatureRautenstrauch, V.; Megard, P.; Conesa, J.; Kuster, W. ACIEE 1990, 29, 1413
Co2(CO)8 (3 mol%)
CO (1 atm), DME120oC, 82%
P(OPh)3 (10 mol%)EtO2C
EtO2CO
EtO2C
EtO2C
• The ligands stabilize the active cobalt intermediates.Jeong, N.; Hwang, S. H.; Lee, Y.; Chung, Y. K. JACS 1994, 116, 3159
C5H11
ethylene/CO (310-360 bar)Co2(CO)8 (0.22 mol%)
150oC, 16h, 48%
O
C5H11
Catalytic Pauson-Khand Reactions – Cobalt Catalyzed
(ind)Co(COD) (2 mol%)
DME, 100oC, 64%
CO (15 atm)EtO2C
EtO2CO
EtO2C
EtO2C
Lee, B. Y.; Chung, Y. K.; Jeong, N.; Lee, Y.; Hwang, S. H. JACS 1994, 116, 8793
Co2(CO)8 (5 mol%)CO (1 atm)
hv = 95%D = 83%
EtO2C
EtO2CO
EtO2C
EtO2CDME, 50-55oC
• Photochemical – 8% starting enyne remaining after 14h• Thermal – 15 % starting enyne remaining after 14hPagenkopf, B. L.; Livinghouse, T. JACS 1996, 118, 2285Belanger, D. B.; O’Mahony, D. J. R.; Livinghouse, T. TL 1998, 39, 7637
Co2(CO)8 (2.5 mol%)CO (30 atm), CO2 (112 atm)EtO2C
EtO2CO
EtO2C
EtO2C90oC, 82%
Catalytic Pauson-Khand Reactions – Cobalt Catalyzed
• Super critical fluids promote the reaction.Jeong, N.; Hwang, S. H.; Lee, Y. W.; Lim, J. S. JACS 1997, 119, 10549
Co2(CO)8 (1 mol%)additiveMeO2C
MeO2CO
MeO2C
MeO2CCO (7 atm), toluene120oC
additive yieldDME (4 mol%) 94%H2O (4 mL) 97%
• Hard Lewis BasesSugihara, T.; Yamaguchi, M. Synlett 1998, 1384
Catalytic Pauson-Khand Reactions – Cobalt Catalyzed
Co(acac)2 (5 mol%)NaBH4 (10 mol%)EtO2C
EtO2CO
EtO2C
EtO2CCO (30-40 atm), CH2Cl2100oC, 66%
Lee, N. Y.; Chung, Y. K. TL 1996, 37, 3145
Co4(CO)12 (1 mol%)EtO2C
EtO2CO
EtO2C
EtO2CCO (10 atm), CH2Cl2150oC, 92%
Kim, J. W.; Chung, Y. K. Synthesis 1998, 142
Co3(CO)9(m3-CH) (1 mol%)MeO2C
MeO2CO
MeO2C
MeO2CCO (7 atm), toluene
120oC, 98%
O
R
R
CoBr2 (0.4 eq)
CO (1 atm), 110oC
toluene/t-BuOH
+Zn (0.43 eq)
Catalytic Pauson-Khand Reactions – Cobalt Catalyzed
Sugihara, T.; Yamaguchi, M. JACS 1998, 120, 10782
• In situ generation of the alkyne-Co2(CO)6 complexRajesh, T.; Periasamy, M. TL 1999, 40, 817
TitanoceneO O N
benzene, 45oCPh Me3SiCN
Ph
TMS H3O+
O O
Ph
catalyst mol% yieldCp2Ti(PMe3)2 10 80%Cp2TiCl2 / n-BuLi 10 82%Ni(COD)2 / Ligand 5 60%
catalyst (5 mol%)O
toluene, 90oCPh CO (18 psig)
O O
PhTi CO
OC
catalyst yield eeCp2Ti(CO)2 92% -
85% 96%
Catalytic Pauson-Khand Reactions – Titanium Catalyzed
Berk, S. C.; Grossman, R. B.; Buchwald, S. L. JACS 1993, 115, 4912Berk, S. C.; Grossman, R. B.; Buchwald, S. L. JACS 1994, 116, 8593
Hicks, F. A.; Buchwald, S. L. JACS 1996, 118, 11688Hicks, F. A.; Buchwald, S. L. JACS 1999, 121, 7026
11 solvent yieldMurai dioxane 86%Mitsudo DMAc 78%
Catalytic Pauson-Khand Reactions – Ruthenium Catalyzed
Morimoto, T.; Chatani, N.; Fukumoto, Y.; Murai, S. JOC 1997, 62, 3762Kondo, T.; Suzuki, N.; Okada, T.; Mitsudo, T. JACS 1997, 119, 6187
Ru3(CO)12 (2 mol%)EtO2C
EtO2CO
EtO2C
EtO2CCO (10-15 atm)
solvent, 140-150oC
[RhCl(CO)2]2 (1 mol%)EtO2C
EtO2CO
EtO2C
EtO2CCO (1 atm), dibutyl ether
130oC, 94%Ph
Ph
trans-[RhCl(CO)(dppp)]2 (2.5 mol%)EtO2C
EtO2CO
EtO2C
EtO2CCO (1 atm), toluene
110oC, 99%Ph
Ph
Catalytic Pauson-Khand Reactions – Rhodium Catalyzed
Koga, Y.; Kobayashi, T.; Narasaka, K. CL 1998, 249
Jeong, N.; Lee, S.; Sung, B. K. Organometallics 1998, 17, 3642
SR
O
SHR
O-CO (D), N2
+CO (CO)CoCo
CO
OC
CO
COOC
CO
CoCo
COCO
CO
COOC
Asymmetric Pauson-Khand Reactions – Chiral Auxiliary Approach
• The sulfur ligated complex can be isolated.• The equilibrium can be controlled.• Maximum concentration of complex A - 40% de• Maximum concentration of complex B - 92% de - Could not be used with less reactive olefins
Asymmetric Pauson-Khand Reactions – Chiral Auxiliary Approach
S
O O
O*R
1. Co2(CO)62. NMO
rt, 44h
H(+)-15-nor-pentalenene
dr 9:1
Tormo, J.; Moyano, A.; Pericas, M. A.; Riera, A. JOC 1997, 62, 4851
OS
O
R*S
*
1. Co2(CO)8
2. 65oC, 42hhexanes
OS R*S
O
*
CoCoOC
OC COCO
COCO
*
NMO (6 eq)
CH2Cl2, -20oC28h
4.6 : 1
Asymmetric Pauson-Khand Reactions – Chiral Auxiliary Approach
• In the absence of the chelating sulfur moiety : low diastereoselectivityPericas, M. A.; Riera, A. et al. Tetrahedron 1997, 53, 8651
1.4 : 1
NO2S
O
Co
Co
OC
COOC
COOCOC
R
toluene25-45 oC
orNMO H2O (6 eq)
CH2Cl2
OR
Xc
O
Asymmetric Pauson-Khand Reactions – Chiral Auxiliary Approach
• Thermal conditions - dr 523:1• Oxidative conditions - dr 800:1Pericas, M. A.; Riera, A. et al. JACS 1997, 119, 10225
CoCo
R
S OC COCOCO
OC CO
O
SO
O
R SO
R
O
**
*
*
+
+
Asymmetric Pauson-Khand Reactions – Chiral Auxiliary Approach
• Close proximity• Low reactivity• Low selectivity• The dicobalthexacarbonyl alkynyl sulfoxide complex is configurationally unstable.Pericas, M. A.; Riera, A. et al. TA 1999, 10, 457
SO Co2(CO)8
CH3CN, 80oC44% O
H SO
O
HZn, NH4Cl
THF, rt96% ee
Asymmetric Pauson-Khand Reactions – Chiral Auxiliary Approach
• The chiral sulfoxide moiety was attached to the olefin.• cis and trans vinyl sulfoxides afforded only one isomer upon cyclization.Adrio, J.; Carretero, J. C. JACS 1999, 121, 7411
Co CoP P
OCOC
COCO
Ph H
EXX
XX
OPhtoluene
80oC+
5 eq
Asymmetric Pauson-Khand Reactions – Chiral Complex Approach
• E=NMe : 3-5 days, 90-98% yield• E=(-)-a- methyl-benzylamine : 16% eeGreene, A. E. et al.JOC 1999, 64, 3492
N N O
HR 10-15 mol% (S,S)-(EBTHI)TiMe2
14 psig CO, toluene, 12-45 h, 95oCR
Asymmetric Pauson-Khand Reactions – Chiral Auxiliary Approach
• Chiral mixed metal complex• Thermally stableRutherford, D. T.; Christie, S. D. R. TL 1998, 39, 9805
OCo
Mo
OC COOC
H
COCO
toluene61%
O
O
100% de
Sturla, S. J.; Buchwald, S. L. JOC 1999, 64, 5547
Asymmetric Pauson-Khand Reactions – Chiral Auxiliary Approach
Jeong, N.; Sung, B. K.; Choi, Y. K. JACS 2000, 122, 6771
Asymmetric Pauson-Khand Reactions – Chiral Auxiliary Approach
Shibata, T.; Takagi, K. JACS 2000, 122, 9852
Asymmetric Pauson-Khand Reactions – Chiral Promoter Approach
Co CoOC CO
OC CO
OC CO
RH
• Chiral promoter should be able to differentiate between the enantiotopic ligands.• Chiral N-oxides were used.• Maximum ee 33%Kerr, W. J.; Kirk, G. G.; Middlemiss, D. Synlett 1995, 1085Derdau, V.; Laschat, S.; Jones, P. G. Heterocycles 1998, 48, 1445
TMS
Cr(CO)3MeO
TMSLi
Br
1.
2.
3. TsOH
TMSO
TMS
OO
TMS
HH
H
1. Co2(CO)8
2. NMO (10 eq)88%
Asymmetric Pauson-Khand Reactions – Chiral Precursor Approach
Quattropani, A. et al. JACS 1997, 119, 4773
OMeOMe
O
O
HO
HO
OO
OHHO
HO
HO
or R2
R1O
R1O
O
R2
R1O
R1O
H
O
R2
R1O
R1O
H1. Co2(CO)8
2. D or TMANO or NMO
Asymmetric Pauson-Khand Reactions – Chiral Precursor Approach
• Depending on R groups, yields ranged from 0 to 96%.• The product ratio ranged from 1:1 to 100:0.Mukai, C.; Hanaoka, M. et al. JCS PT1 1998, 2903Mukai, C.; Hanaoka, M. et al. TL 1998, 39, 7909
OEt
O
TMSH
H
H
HCo
Co
OC COCO
CO
COCO
OH
1. Co2(CO)8
2. Et2AlCl, -78oC82% 2 steps
O
O
H
H
H
HO
H
H
H
H
H
H
CH3CN, airreflux, 15 min
85% (5:1)
NMO, CH2Cl270% (11:1)
ultrasoundCH3CN, 40oC
45% (3:1)
or
or
(+)-epoxydictymene
Asymmetric Pauson-Khand Reactions – Chiral Precursor Approach
Schreiber, S. L. et al. JACS 1994, 116, 5505Schreiber, S. L. et al. JACS 1997, 119, 4353
Pauson-Khand reaction - Mechanistic Studies
• The currently accepted mechanistic pathwayMagnus, P.; Principe, L. M. TL 1985, 26, 4851
• Beyond the fact that a hexacarbonyldicobalt-alkyne complex is involved, little is actually known about the mechanism.• No group has observed any of the proposed intermediates.
Co CoOC CO
R R'
COCO
OCOC
R''Co CoOC CO
R R'
COOCOC R''
Co CoOC
OC
RR'
COCO
OC R''
Co CoOC
OC
RR'
COOC
O
R''CoOC
OC
RR'
OCR''
CoCOO
R''R
R'
-Co2(CO)5
O
OC OC
OCCO
CoCo
R
OCOC
CO
COCO
CO CoCo
R
OC CO
COCO
CO CoCo
R
OC CO
COCO
CO
CoCo
R
L CO
COCO
CO
OO
Co
R
CO
COCo
LCO
L
CO
OR
-CO
O2
Pauson-Khand reaction - Mechanistic Studies
• The reaction was interrupted by exposing the reaction mixture to an oxygen containing atmosphere.Krafft, M. E. et al. JACS 1996, 118, 6080
Pauson-Khand reaction - Summary
• The P-K reaction allows for a rapid increase in molecular complexity from relatively simple starting materials.• Several promoters can make the reaction efficient.• Many kinds of metal complexes can be used as catalysts.• High levels of enantioselectivity can be achieved.• The reaction mechanism is not clear.