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CO O
The Pauson-Khand Reaction: The inter- or intramolecular cobalt-catalyzed synthesis of cyclopentenones via coupling of an alkyne, an alkene, and carbon monoxide.
Co2CO8 cat. CO atmC
O O
Co
Co
R1COOC
COCOOC
OCΔΔ
Stoichiometric Catalytic
R
R1 R1R1
R2R2 R2R2
•Alkyne-hexacarbonyldicobalt complexes are kinetically competent intermediates. The complexes are verystable and often utilized as alkyne protecting groups
Co CoOC
OCCOCO
COOC
CODissociativeSubstitution Co CoOC
COCO
COOC
R
R
Co CoCOCO
CO
R
COOC
InsertionCo CoCOCO
CO
R
COOCO
CO
R
ReductiveElimination
O
R
Mechanism: The currently accepted mechanism was originally proposed by Magnus in the context of intramolecular Pauson-Khand reactions: Magnus, P.; Principe, M.; Tet. Lett. 1985, 26, 4851-4854.
•Typically requires elevated temperatures (>60 °C) and long reaction times•The intermolecular variant is mostly limited to reactive alkenes such as norbornene•The carbon monoxide pressure is dependent on the reaction conditions and may vary from 0-40 atm•Pregenerated alkyne-hexacarbonyldicobalt complexes are used for stoichiometric processes
AlkeneInsertion
CO atm
Co2CO8
2 CO
Regioselectivity: Formation of2-substituted cyclopentenones is favored when terminal alkynesare utilized
Diastereoselectivity for internal alkynes
O
R2
H3CH3C
R1O
H
O
R2
H3CH3C
HR1Syn
CO
R2
Co CoOC
OCOC
COCO
CO
R
DMEor
Isooctane
CoOC COCoOC
OCCo
R2
Co COCO
CoOC CO
C CO O
Khand, I. U.; Knox, G. R.; Pauson, P. L.; Watts, W. E. Chem. Comm. 1971, 36
"In addition to the above products, the reaction of norbornadiene with complexes (I) yields hydrocarbon and ketonic products derived from norbornadiene, acetylene, and carbon monoxide."
(I)R = H, Ph
The History of the Pauson-Khand Reaction: An investigation of the chemistry between alkyne Co2CO6 complexes and norbornadiene led to the formation of interesting cobalt complexes and an interesting observation.....
Co CoOC
OCOC
COCO
CO
a) Khand, I. U.; Knox, G. R.; Pauson, P. L.; Watts, W. E. J. Chem. Soc. Perk. Trans. 1 1973, 975-977. b) Khand, I. U.; Knox, G. R.; Pauson, P. L.; Watts, W. E.; Foreman, M.I. J. Chem. Soc. Perk. Trans. 1 1973, 977-981.
9.4 mol% Co2CO8Iso-octane
C2H2:CO (1:1)
60-70 °C74% yield
•A catalytic reaction was also reported where increased yields relative to the stoichiometric process were observed.
52% yield
Cyclopentenone synthesis: Co2CO6 complexes of ethyne, propyne, phenylacetylene, diphenylacetylene and hex-3-yne
•The above work is often referenced as the first report of the Pauson-Khand reaction even though the ketone containing products were unidentified at the time.
O H
H
O H
H
The Intramolecular Pauson-Khand: Schore's report on the first intramolecular Pauson-Khand reaction rekindled interest in the transformation and served as basis for the intense research activity that followed.
O O
1.0 equiv Co2CO81 atm CO
CO purgedtrimethylpentane
95 °C, 4 d31% yield
1.0 equiv Co2CO81 atm CO
CO purgedtrimethylpentane
95 °C, 4 d60% yield
Schore, N. E.; Croudace, M. C. J. Org. Chem. 1981, 46, 5436-5438
O
H3C CH3Co2CO6
adsorbed on silica gel
O2
45 °C, 30 minO O
75% yield
H3C CH3
Simonian, S. O.; Smit, W. A.; Gybin, A. S.; Shashkov, A. S.; Mikaelian, G. S.; Tarasov, V. A.; Ibragimov, I. I.; Caple, R.; Froen, D. E. Tet. Lett. 1986, 27, 1245-1248.
C5H11 Co2CO6
•Rate acceleration observed only for ether containingsubstrates
•The authors speculate that a more reactive conformation is induced by interation with the silica gel surface
•Hydrogen bonding between the silica gel Si-OH andether oxygen may cause bond angle compression(i.e. Thorpe-Ingold effect).
+ O O
O
H
HToluene
100 °C, 24 h
Standard conditions, 47% yieldUltrasonic Irradiation, 52% yield73 mol% Bu3PO, 64 % yield
5.9 equivBillington, D. C.; Helps, I. M.; Pauson, P. L.; Thomson, W.; Willison, D. J. Organomet. Chem. 1988, 354, 233-242
Milder Conditions and Expanded Substrate Scope
Silica Gel Adsorbtion:
Sonication and Phosphine Oxide Additives
Amine-N-Oxide Promoters: The Schreiber N-methylmorpholine-N-oxide modification of the Pauson-Khand reactionallows the process to be effected at room temperature with a wide variety of substrates resulting in excellent yields and high diastereoselectivity.
Shambayati, S.; Crowe, W. E.; Schreiber, S. L. Tet. Lett. 1990, 31, 5289-5292
O
OSi(CH3)3
6.0 equiv NMO
CH2Cl2, rt8-16 h
4O
OSi(CH3)3
4
O
H
O6.0 equiv NMO
CH2Cl2, rt8-16 h
Co2CO6
70% yield4:1 dr
O O
H HH
98% yield>25:1 dr
H3C
TBSOO
H
TBSO
H3CH3CH3C
6.0 equiv NMO
CH2Cl2, rt8-16 h
87% yield5:1 dr
•Interestingly, in their 1988 report, Billington and Pauson stated that trimethylamine-N-oxide gave erratic results.
Co CoCOCOOC
OC
OCCo CoOC
OC
OC OO
CO
Co CoOCOC
OC OO
CO
R3N + CO2
Co CoCOCOOC
OC
OC
OR3N
R R
COCO
R3N R3N
R
COR
Amine-N-Oxides Oxidize CO to CO2 and Create Vacant Sites on Cobalt:
Schreiber Concludes his Paper with an Interesting Statement: "However, it is unclear whether or not the N-oxide or the tertiary amine produced during the reaction, can also act as ligands for one of the cobalt-containing intermediates, thereby diverting the steric and electronic course of the reaction away from that ofthe classical, thermal Pauson-Khand."
HO
H3C CH3Co2CO6 +
6.0 equivBrucine-N-oxide
THF, –70 °C, 5 d
O
HO
H3C CH3
76% yield (BORSM)44% ee
N
O
N
O
H
H
H
H
O
H3CO
H3CO
Brucine-N-oxideKerr, W. J.; Kirk, G. G.; Middlemiss, D. Synlett 1995, 1085-1086
Ph
CH3
Co2CO6 3.5 equivcyclohexylamine
DCE, 83 °C, 10 min89% yield
Ph
O
CH3H
The Following Results may be an Indication that Amines do in Fact Bind to Cobalt:
Asymmetric stoichiometric Pauson-Khand reaction with a chiral amine-N-oxide
Cyclohexylamine and ammonia afford large rate accelerations in the stoichiometric Pauson-Khand reaction
O
Ph
Co2CO6
1,4-dioxane 2M NH4OH(aq)
100 °C, 45 min75% yield
O
Ph
O
H H H
Sugihara, T.; Yamada, M.; Ban, H.; Yamaguchi, M.; Kaneko, C. Angew. Chem. Int. Ed. 1997, 36, 2801-2804
H
H
Lewis Basic Promoters: Sulfur as Part of the Side Chain
TsN Co2CO6
3.5 equivcyclohexylamine
1,2-Dichloroethane83 °C, 30 min
HNTs
15% yield
3.5 equivn-BuSCH3
1,2-Dichloroethane83 °C, 30 min
TsN O
79% yield
+Ph
Co2CO6
O
Ph
H
H
Toluene
reflux, 3 d23% yield2.0 equiv
4.0 equivn-BuSCH3
1,2-Dichloroethane83 °C, 30 min
85% yield
6.0 equiv NMO
CH2Cl2, 23 °C, 10 min
Co2CO6
SC2H5Toluene
71 °C, 0.15 h74% yield
O
SC2H5
10 equiv NMO•H2O
CH2Cl2, rt, 0.13 h39% yield
10 equivNMO•H2O
CH2Cl2, rt79% yield
Co Co
H3CS
OCOCOC
COCO
COCo Co
COCO
CO
COOCS
H3C
Krafft, M. E.; Scott, I. L.; Romero, R. H.; Feibelmann, S.; Van Pelt, C. E. J. Am. Chem Soc. 1993, 115, 7199-7207
10 equiv NMO•H2O
CH2Cl2, rt, 5 d35% yield
O
SCH3•Rate accelerations were observed with heteroatom containing side chains (sulfur being optimal)•Certain chain lengths allowed for stable, isolable complexes to be formed
+Ph
Sugihara, T.; Yamada, M.; Yamaguchi, M.; Nishizawa, M. Synlett 1999, 771-773
•Sugihara's system effects intermolecular Pauson-Khand reactions with cyclic alkenes such as cyclohexene and cycloheptene as well as terminal alkenes. Intermolecular Pauson-Khand reactions are problematic with N-oxide promoted systems sincealkyne-Co2CO6 complexes undergo rapid decomplexation when treated with N-oxides in the absence of alkenes
Lewis Basic Promoters: Sulfur Containing Additives
N
OO
H
CH3
Co2CO6
N
O
O
O
HH
H3C
(CH3)3NO
93% yieldNTs
OTMS
HH
H3C
H
OMOMNH
CO2H
CO2HH
(–)-α-Kainic acidYoo, S.-E.; Lee, S. H. J. Org. Chem. 1994, 59, 6968-6972
Si(CH3)3
CH3
OOH
Co2CO6 + Δ
86% yield
CH3
OOHO
(H3C)3Si
H
H
sole product
CH3
H
H
H3C HH3C
H
H3C CH3
(13Z)-Spata-13(15),17-dieneDauben, W. G.; Kowalczyk, B. A. Tet. Lett. 1990, 31, 635-638
Hexane, 42 °C, 12 h
55% yield5-6:1 dr
H3CH3C
Co2CO6
O
Ph
CH3
H3CH3C O
CH3
ORH3CH3C
H HH
H3CH
(+)-Hirsutene
Total Synthesis of (–)-α-Kainic acid Via an Intramolecular Pauson-Khand Reaction
A Highly Regioslective Intermolecular Pauson-Khand Reaction: Synthesis of (13Z)-Spata-13(15),17-diene
Chiral Auxiliary-Based Intramolecular Pauson-Khand Reaction: Formal Synthesis of (+)-Hirsutene
Castro, J.; Sorensen, H.; Riera, A.; Morin, C.; Moyano, A.; Pericas, M. A.; Greene, A. E. J. Am. Chem. Soc. 1990, 112, 93889389
O
N CH3
H
H H
CH3H3CO
(–)-DendrobineCH3H3C
CH3N CH3
OAc
1)Co2CO82) NMO•H2O
CH3CN
3) Pd/C, H251% yield
N CH3
H
H H
CH3H3C
O
OAc
Cassayre, J.; Zard, S. Z. J. Am. Chem. Soc. 1999, 121, 6072-6073
Co Co
O
H3C CH3SCH3
COCO
COOCOC
OC
+ Δ
82% yield24:1 dr
OO
RO
H
H H
HH
CH3
OTBS
O
H
CH3
OTBS
CO2C4H9HO
H
HO
O
CH3
(+)-Brefeldin A
Bernardes, V.; Kann, N.; Riera, A.; Moyano, A.; Pericas, M. A.; Greene, A. E. J. Org. Chem. 1995, 60, 6670-6671
N CH3
H
H H
CH3H3C
OAcNC
The Intramolecular Pauson-Khand Reaction in the Total Synthesis of (–)-Dendrobine
Chiral Auxiliary Approach for Intermolecular Pauson-Khand Reactions: Total Synthesis of (+)-Brefeldin A
Co
H
H
H3C
Si(CH3)3
O
O CH3CH3
CH3
H
1:1 mixture of diastereomers
H
H
H3C
Si(CH3)3
O
OCo2CO6 CH3
CH3
CH3
HCo2CO8 (C2H5)2AlCl
CH2Cl2, –78 °C82% yield (2 steps)
> 20:1 dr
H3C H
H
CoOC CO
COCO
COCO
O
H3CH3C
NMOCH2Cl2
rt
70% yield11:1 dr
H3C H
HO CH3
CH3H
O
H
H3C H
HO CH3
CH3H
H
NCH3CO
H
H3C H
HO CH3
CH3H
H
H3C
H
Jamison, T. F.; Shambayati, S.; Crowe, W. E.; Schreiber, S. L. J. Am. Chem. Soc. 1994, 116, 5505-5506Jamison, T. F.; Shambayati, S.; Crowe, W. E.; Schreiber, S. L. J. Am. Chem. Soc. 1997, 119, 4353-4363
Tandem Nicholas/Pauson-Khand Reaction in the Total Synthesis of (+)-Epoxydictymene
(+)-Epoxydictymene
CH3
100 atm CO, 40 atm C2H40.22 mol% Co2CO8
Toluene, 150 °C, 16 h47-49% yield
OCH3
Rautenstrauch, V.; Megard, P.; Conesa, J.; Kuster, W. Angew. Chem. Int. Ed. Engl. 1990, 29, 1413-1416
The Catalytic Pauson-Khand Reaction: Even though Pauson and Khand reported a catalytic variant of the reaction in their initial publication, the next catalytic Pauson-Khand reaction appeared only 17 years later.
•Although low catalyst loadings areutilized, prohibitively high pressures ofcarbon monoxide and ethene are required as well as elevated temperatures
A trans-dihydrojasmonate precursor (important to the perfume industry)
2 Co2CO8 Co4CO12 + 4 CO
2-Pentylcyclopent-2-en-1-one Via a Catalytic Pauson-Khand Reaction:
Co4CO12-Catalyzed Inter- and Intramolecular Pauson-Khand Reactions:
•At 50 °C, Co2CO8 is converted to Co4CO12 which is inactive towards alkynes•The equilibrium shifts to the left under high CO pressures
+
0.5 mol% Co4CO1210 atm CO
CH2Cl2, 150 °C, 6 h75% yield O
TsN
0.5 mol% Co4CO1210 atm CO
CH2Cl2, 150 °C, 6 h75% yield
TsN O
•The intermolecular Pauson-Khand reactionsare limited to norbornene and norbornadiene.
Kim, J. W.; Chung, Y. K. Synthesis, 1998, 142-144
Cobalt-Catalyzed Intramolecular Pauson-Khand Reactions: A Very Narrow Thermal Window
TsN7.5 mol% Co2CO8
1 atm CO
DME
TsN O
80 °C, 41%, 3 h60 °C, 86%, 12 h
5 mol% Co2CO81 atm CO
DME
O
50 °C, 50%, 24 h60 °C, 83%, 12 h
EtO2CEtO2C
C2H5O2CC2H5O2C
Only substrate
•Catalytic Pauson-Khand reactions may be performed under one atmosphere of CO with high purity Co2CO8 at 60-65 °CBelanger, D. B.; O'Mahony, D. J. R.; Livinghouse, T. Tet. Lett. 1998, 39, 7637-7640
Alternative Cobalt Catalysts in the Pauson-Khand Reaction: Attempts to replace the toxic and pyrophoric Co2CO8
Co
(1,5-cyclooctadiene)(Indenyl)Cobalt(I)-Catalyzed Pauson-Khand Reactions:
HO +
1.0 mol% 115 atm CO
DME, 100 °C, 40 h96% yield O
HOH
H
(COD)(Indenyl)Co(I)
1
•Negligible reactivity was observed with CpCo(CO)2 and CpCo(COD)•Less reactive and/or strained alkenes such as ethene, cyclopentene, allyl alcohol, and methyl acrylate are not viable substrates
Lee, B. Y.; Chung, Y. K. J. Am. Chem. Soc. 1994, 116, 8793-8794
•Complex 1 is moderately stable and can bestored in the freezer for a prolonged period of time
TsN TsN O
2.0 mol% 115 atm CO
DME, 100 °C, 40 h94% yield
Co2CO8 + Ph3P
THFrt, 30 min65% yield
Co CoPh3P COOC
CO
OC CO
COOC
•Purified by silica gel chromatography!
A Stable Heptacarbonyl(triphenylphosphine)dicobalt(0) Catalyst:5 mol% (Ph3P)Co2(CO)7
1.05 atm CO
DME, 75 °C, 4 h85% yield
H3CO2CH3CO2C CH3 OH3CO2C
H3CO2C
CH3
Ph +
O
Ph
H
H5 mol% (Ph3P)Co2(CO)71.05 atm CO
DME, 75 °C, 4 h96% yield
-CO
•Norbornadiene was the only alkene utilized for intermolecular reactions•The system allows both intra- and intermolecular Pauson-Khand reactions under mild conditions
Gibson, S. E.; Johnstone, C.; Stevenazzi, A. Tetrahedron 2002, 58, 4937-4942
•Identical results are obtained with a catalyst stored at 4 °C for 18 months under an atmosphere of air
Catalytic Asymmetric Pauson-Khand Reaction: A first!
X
20 mol% Co2CO820 mol% (S)-BINAP
1.0 atm CO
DME, reflux, 24 h
PPh2PPh2
(S)-BINAP
X O
53% yield90% ee
31% yield63% ee
R1R2
R1
R2
H3CO2CH3CO2C O
H H3CO2CH3CO2C O
H
CH3
H3CO2CH3CO2C O
CH3
CH3
90% yield0% ee
60% yield93% ee
13% yield62% ee
•Limited substrate scope
•Enantioselectivity varies fromexcellent to non existentdepending on the substituents
TsN O
H
TsN O
CH3
36% yield82% ee
TsN O
CH3
a) Hiroi, K.; Watanabe, T.; Kawagishi, R.; Abe, I. Tet. Lett. 2000, 41, 891-895. b) Hiroi, K.; Watanabe, T.; Kawagishi, R.; Abe, I. Tet. As. 2000, 11, 797-808
Catalytic Pauson-Khand Type Reactions: Ruthenium Carbonyl
2.0 mol% Ru3(CO)1215 atm CO
DMAC, 140 °C, 8 h
R
C2H5O2CC2H5O2C
H3CO2CH3CO2C O
R
R = CH3, C2H5, C3H7, C4H9, Si(CH3)3 78-89% yield
•High Temperatures and CO pressures are required•Ruthenium carbonyl is an inexpensive, innocuous ruthenium complex1,1- and 1,2-disubstituted olefins are somewhat challenging substrates
H3CO2CH3CO2C O
C2H5
CH341% yield5.6:1 dr
H3CO2CH3CO2C O
C2H5
CH373% yield
Kondo, T.; Suzuki, N.; Okada, T.; Mitsudo, T-. A. J. Am. Chem Soc. 1997, 119, 6187-6188For another ruthenium carbonyl-based system see: Morimoto, T.; Chatani, N.; Fukumoto, Y.; Murai, S. J. Org. Chem. 1997, 62, 3762-3765
Pauson-Khand Type Reactions: Titanocene-Catalyzed Cyclocarbonylation of Enynes
XR 5-20 mol% Cp2Ti(CO)2
18 psig CO
Toluene, 90 °C, 12-48 hX O
R
C4H9
BnO
O
C4H9
BnO H
C4H9
7.5 mol% cat.
92% yield3.5:1 dr
(i-Pr)3SiO
O
C4H9
H
(i-Pr)3SiO10 mol% cat.
92% yield8:1 dr
C4H9 10 mol% cat.
86% yield O
C4H9
CH3
t-BuO2Ct-BuO2C
CH35 mol% cat.
94% yieldO
CH3
t-BuO2Ct-BuO2C
CH3
a) Hicks, F. A.; Kablaoui, N. M.; Buchwald, S. L. J. Am. Chem. Soc. 1996, 118, 9450-9451. b) Hicks, F. A.; Kablaoui, N. M.; Buchwald, S. L. J. Am. Chem. Soc. 1999, 121, 5881-5898. c)Buchwald,S. L.; Hicks,F. A. in Comprehensive Asymmetric Catalysis; Jacobsen E. N., Pfaltz, A., Yamamoto,H., Eds; Springer: Berlin, 1999; Vol. II, p 491
Cp2Ti(CO)2X
R
Cp2Ti
R
X
CO
OC
COCp2Ti
R
XXCp2Ti
R
COOCCO
XCp2Ti
O
ROC
CO
Cp2Ti
OR
COX
XCp2Ti
O
OC
R
Cp2Ti
O R
X CO
First proposed mechanism
Second proposed mechanism
COXO
R
•Lower loadings of a commercially available catalyst provide higher yields than previous titanium-based systems developed by Buchwald
•Excellent functional group compatibility: ethers, amines, esters, nitriles, and ketones are tolerated
•1,1- and 1,2-disubstituted olefins are viable substrates but terminal alkynes require 20 mol% catalyst in order for high yields to be obtained
•The mechanism of the reaction is unclear, however, discrepencieshave been observed between a previous system which relied on the extremely unstable Cp2Ti(P(CH3)3)2 as catalyst
Catalytic Asymmetric Pauson-Khand Type Reaction: (S,S)(EBTHI)Ti(CO)2
TiOC CO
(S,S)(EBTHI)Ti(CO)2
XR1
R2
(S,S)(EBTHI)Ti(CO)2 cat.2.0 atm CO
Toluene, 90 °C, 12 hX O
R1
R2
O O
Ph
H20 mol% cat.
85% yield, 96% ee
O
Ph
H20 mol% cat.
70% yield, 87% ee
O
Ph
HC2H5O2CC2H5O2C
7.5 mol% cat.92% yield, 94% ee
O
C3H7
HC2H5O2CC2H5O2C
5.0 mol% cat.94% yield, 89% ee
O
C3H7
HC2H5O2CC2H5O2C
5.0 mol% cat.94% yield, 89% ee
O
CH3
HC2H5O2CC2H5O2C
5.0 mol% cat.90% yield, 87% ee
BnN O
CH3
H15 mol% cat.
82% yield, 92% ee
O
CH3
CH3
t-BuO2Ct-BuO2C
20 mol% cat.90% yield, 72% ee
O
H
Ht-BuO2Ct-BuO2C
20 mol% cat.87% yield, 50% ee
CH3
OC2H5O2CC2H5O2C
20 mol% cat.77% yield, 47% ee
•Low ees are observed with terminal alkynes and 1,7-enynes
•3- or 5-substituted enynes are poor substrates
•Failure to cyclize sterically demanding substrates likely arises from unfavorable steric interactions between the ligand and the substrates
R
C2H5O2CC2H5O2C
R = i-Pr, C5H9, SiH(CH3)2
Substrates wich cannot be cyclized:
Ph
H3CH3C
BnOC4H9
TIPSO C4H9
BnO
Ph
C2H5O2CC2H5O2C
CH3
R
C2H5O2CC2H5O2C
R = CH3, Ph O
Ph CH3
t-BuO2Ct-BuO2C
a) Hicks, F. A.; Buchwald, S. L. J. Am. Chem. Soc. 1996, 118, 11688-11689. b) Hicks, F. A.; Buchwald, S. L. J. Am. Chem. Soc. 1999, 121, 7026-7033. c) Sturla, S. J.; Buchwald, S. L. J. Org. Chem. 1999, 64, 5547-5550
Catalytic Asymmetric Pauson-Khand Type Reactions: Rhodium
3 mol% [(CO)2RhCl]29 mol% (S)-BINAP
12 mol% AgOTf
0.5-3 atm COTHF, 90-130 °C, 3-20 h
XR
X O
R
H
PPh2PPh2
(S)-BINAP
O
CH3
HC2H5O2CC2H5O2C
93% yield71% ee
O
CH3
Hi-PrO2Ci-PrO2C
40% yield90% ee
O
Ph
HC2H5O2CC2H5O2C
67% yield61% ee
O
Ph
H61% yield51% ee
O O
CH3
H40% yield96% ee
O O
Ph
H88% yield81% ee
O O
C4H9
H60% yield65% ee
TsN O
CH3
H80% yield84% ee
TsN O
Ph
H93% yield74% ee
Jeong, N.; Sung, B. K.; Choi, Y. K. J. Am. Chem. Soc. 2000, 122, 6771-6772. b) Jeong, N.; Lee, S.; Sung, B. K. 1998, 17, 3642-3644For other rhodium-catalyzed systems see: Kobayashi, T.; Koga, Y.; Narasaka, K. J. Organomet. Chem. 2001, 624, 73-87
[(CO)2RhCl]2
2 (S)-BINAP2 AgOTf
2 AgCl
RhCO
COP
P
RhCO
XR
Rh
XR
HCO
PP
PP
CO
RhPP
XO
CO
H
X O
R
H
Plausible Mechanism
•Limited to unsubstituted alkenes•Enantioselectivity and yields range from modest to excellent
CO
CO
XR
CO
CO
Catalytic Asymmetric Pauson-Khand Type Reactions: Iridium
5.0 mol% [(COD)IrCl]210 mol% (S)-tolBINAP
1 atm COToluene, reflux, 20-72 h
XR
X O
R PAr2PAr2
(S)-tolBINAP
[(COD)IrCl]2
2 (S)-tolBINAP
2 COD
IrCO
ClP
P
IrCl
XR
Ir X
R
Cl
PP
PP
IrPP
XO
Cl
XR
X O
R
Plausible Mechanism
Ar = 4-tolyl
O
O
H3CO80% yield96% ee
O O
CH3
75% yield97% ee
O
O
54% yield90% ee
Ph
TsN O
Ph
85% yield95% ee
O
Ph
74% yield84% ee
C2H5O2CC2H5O2C
O O
Ph
30% yield88% ee
CH3
+ CO
OC
Ph
CH3+
5.0 mol% [(COD)IrCl]210 mol% (S)-tolBINAP
1 atm COToluene, reflux, 20-72 h
32% yield, 93% ee
O
Ph
CH3
•Low CO Pressure yet lengthy reaction times and high catalyst loadings of an expensive iridium complex are required
•May be performed intermolecularly with excellent ee albeit at the expense of yield
•1,1-disubstituted olefins are sluggish but product is obtained with good ee
•No examples of 1,2-disubstituted olefins
Shibata, T.; Takagi, K. J. Am. Chem. Soc. 2000, 122, 9852-9853
CO
COCO
Expanding the Scope of the Pauson-Khand Reaction:
CH3
O 10 mol% Cp2Ti(PMe)218 psig CO
Toluene, 105 °C, 15-18 h98% yield
O OH3C
H
γ-Butyrolactones from Enones
H3C
O
CO2C2H5
1.1 equiv Cp2Ti(PMe)215 psig CO
70 °C90% yield
OO
H3C CO2C2H5
Kablaoui, N. M.; Hicks, F. A.; Buchwald, S. L.; J. A. Chem. Soc. 1996, 118, 5818-5819
H3CO2CH3CO2C CH3 1.0 mol% (Ph3P)2RhCl(CO)
1.0 mol% AgSBF6
DCE, rt, 24 h96% yield
O
CH3
H3CO2CH3CO2C
The Dienyl Pauson-Khand Reaction
Wender, P. A.; Deschamps, N. M.; Gamber, G. G. Angew. Chem. Int. Ed. 2003, 42, 1853-1857