Download Carbonylation as a Method for Synthesizing

Carbonylation as a Method for
Synthesizing Organic Intermediates and
Substrates from Epoxides and Aziridines
Venkata A. Kallepalli
Michigan State University
Feb. 15th, 2006
Seminar Outline
•
•
•
•
•
Introduction
Carbonylation
Early Examplesof Epoxides
Carbonylation
of Aziridines
Scope and Limitations
Conclusion
Industrial Applications
Acknowledgments
Oxo synthesis : Otto Roelen (1938)
CHO
Co catalyst
R
CO / H2
R
Developed by Reppe, Heck, Tsuji
CHO
+
R
Carbonylation of methanol to acetic acid
CH3OH
+
catalyst
CO
CH3COOH
H = -33kcal/mol
(Co, Rh, Ir, Ni)
I-
CH3OH
Co2(CO)8
H2O
CO
-CO2
CH3Co(CO)4
HI
-H2O
2HCo(CO)4
CH3I
H2
O
Co(CO)4-
CH3C
Co(CO)3
CO
CH3COI
O
H2O
CH3COOH
CH3C
I-
Hohenshutz, H.; Kutepow,N.; Himmele, W. Hydrocarbon Process 1966, 45, 141
Co(CO)4
Scope of the Reaction
Ketones, Aldehydes, Carboxylic acids,
Esters, Amino acids, Polyketones, Polycarbonates
Olefins
Alkynes
Dienes
Carboxylic acids,
Carboxylic acids
Alcohols/ Phenols
Organic halides
Keto acids
Carbonylation
Organic carbonates
Esters, Keto esters
Amines
Nitro compounds
Isocyanates, Ureas
Isocyanates, Ureas
Carbamates
Carbamates
Scope of the Carbonylation Reaction
• Economical and Ecologically safe
Cl
CN
NaCN
COCl
1.H2O
Cl
COOR'
R'OH
COOR'
+ R'OH
2. SOCl2
R
R
R
cat
CO
R
R
R
Phenyl acetic acid
• Tandem reactions
Cl
+
+
CO
+
COOR
ROH
Capric acid ester
• Easy access to important precursors and intermediates
O
O
Br
NR'2
+ 2CO + R'2NH
R
R
Phenyl Pyruvic amide
Limitations
• High pressure
O
Co2(CO)8, CO (3500 psi)
O
CH3OH, 4 h, 130 oC, 20-40%
• High temperature
• Poor selectivity
• Large amount of byproducts
OH
O
Carbonylation Reaction in Industrial Processes
Process
Catalyst
Company
Methanol to acetic acid
Co2(CO)8
BASF
[Rh(CO)I2]-
Monsanto
IrCl3-RuCl3
BP
Acetylene to acrylic acid
NiBr2-CuBr2
BASF
Ethylene to propionic acid
Ni(OCOC3H5)2
BASF
Butadiene to adipic acid
HCo(CO)4
BASF
Isobutylphenyl ethanol to
Ibuprofen
PdCl2(PPh3)2
Hoechst
Celanese
Propylene to methyl
Methacrylate
Pd-pyridyl
Phosphine
Shell
Ethylene copolymerization
to polyketones
Pd(OAc)2/dppp
TsOH
Shell
Produces more than 8 million tons of carbonylation products
Lactic Acid via Alkoxycarbonylation
O
MeO
PdCl2(PPh3)2, CO (1000psi)
O
OH
O
O
o
MeOH, 100 C, 44 h
O
O
OH
81.6%
Methyl-2-acetoxy propionate
Vinyl acetate
dl - lactic acid
OCOCH3
OCOCH3
PdX2L2
HPdXL2
ROH
-HX
[ROPdXL2]
CO
OCOCH3
[Pd(COOR)XL2]
ROH
[HPdXL2]
H
PdXL2
(RO)2CO
MeO
O
CO
O
OCOCH3
O
H
MeOH
O
PdXL2
Kiyoshi, K.; Yuiji, O.; Koichi, M.; Sadayuki, M.; Koichi, K.; Nobuyuki, S. Bull. Chem. Soc. Jpn. 1996, 69, 1337-1345
Seminar Outline
•
•
•
•
•
Introduction
Carbonylation of Epoxides
Stoichiometric of
Reactions
Carbonylation
Aziridines
Catalytic Reactions
Conclusion
Theoretical Study of -Lactone formation
Acknowledgments
Dicarbonylation Reactions
Carbonylation of Cyclic Ethers
Co(OAc)2
O
Co(OAc)2
CO / H2
200 oC, 200 atm
O
O
O
CO / H2O
200 oC, 250 atm
O
O
55%
35-45%
Reppe, W.; Kroper,H.; Pistor, H. J.; Weissbarth, O. Justus Liebigs Ann Chem. 1953, 582, 87
Khumataveeporn, K.; Alper, H.; Acc. Chem. Res. 1995, 28, 414
O
Co2(CO)8, CO (3500 psi)
O
CH3OH, 4 h, 130 oC, 20-40%
OH
O
Eisenmann, J. L.; Yamartino, R. L.; Howard, J. F. J. Org. Chem. 1961, 26, 2102
R
R
n
O
n = 1,2
R = H, Me
HCo(CO)4
R
CO
R
Co(CO)4
n
OH
O
N(Cy)2Et
n=2, R=H
O
O
+
[(Cy)2NHEt]+ [Co(CO)4]Heck, R. F. J. Am. Chem. Soc. 1963, 85, 1460
Carbonylation of Epoxides
R
R = aryl, vinyl
O
a
O
b
R
R
CO, [M]
O
O
O
• Why Epoxides?
• Efficient way to -Lactones
• Availability of the Epoxides
• Reactivity of the Epoxides
Tokunaga, M.; Larrow, J. F.; Kakiuchi, F.; Jacobsen, E. N. Science 1997, 277, 936-938
R = alkyl, ether, ester, amide
Why -Lactones?
O
OH
R''2N
O
R
R'
O
R
R'
+ CO2
R
R''
R'
NHR2''
1.LDA
2.R''I
O
O
R'
R
LnM-OR
(R = CH2R')
O
MgBr2
O
NaN3
O
R'
R
R'
O
O
R
R'
N3
HO
R'
Getzler, Y. D. Y. L.; Schmidt, J. A. R.; Coates, G. W. Journal of Chemical Education 2005, 82, 621-624
n
Natural -Lactones
NHCHO
O
NHCOCH3
O
O
O
O
H2N
O
O
O
O
C6H13
Lipstatin
C6H13
Esterastin
O
O
O
HH
OCOCHCH2(CH3)2
O
O
O
H
Spongiolactone
Pommier, A.; Pons, J. M. Synthesis 1995, 729-744
O
O
Guaiagrazielolide
Photocarbonylation of Epoxide
2
3
R
O
1
2
R
Fe(CO)5
R
3
C6H6, hv,
-CO
R4
O
R
2
1
R
2
3
R
Fe(CO)4
R
R
O
Fe
(CO)3
O
O
O
O
R1
2
R
O
3
R
R4
O
R4
R1
R
3
R1
+
R
O
Fe
(CO)3
2
R1
syn-isomer
C4 H9
NHCHO
R
IV
3
O
R4
Ce
O
R4
3
C6H13
R
R4
2
O
R1
R
R
O
R4
O
Fe
(CO)3
anti-isomer
Isolated : Streptomyces albolongus
C9H19
Esterase inhibitor
OH
O
Valilactone
O
Malyngolide
Frohlich, K.; Ring, H.; Aumann, R. Angew. Chem. Int. Ed. Engl. 1974, 13, 275
Annis, G. D.; Ley, S. V. J. Chem. Soc. Chem. Commun, 1977, 581
Annis, G. D.; Ley, S. V.; Self, C. R.; Sivaramakrishnan, R. J. Chem. Soc., Perkin Trans. 1 1981, 270
O
Isolated : Lyngbya majuscula
Antibacterial agent
Synthesis of Valilactone
C4H9
C5H11
C4H9
Zn/Cu/Ag, MeOH-H2O
C5H11
50 oC. 90%
OH
OH
O
VO(acac)2, tBuOOH
O
(OC)3Fe
OH
C5H11
A
1
..
+
C4H9
Fe2(CO)9, THF. 80%
C4H9
C5H11
4
O
OH
C5H11
C4H9
B
CH2Cl2, 0 oC to r.t., 73%
O
(OC)3Fe
OH
Bates, R.W.; Fernandez-Moro.; Ley, S. V. Tetrahedron Lett
1991, 32, 2651
O
Bates, R.W.; Fernandez-Moro.; Ley, S. V. Tetrahedron
1991, 47, 9929
CAN, EtOH,
r.t. 26%
C4H9
C5H11
O
O
OH
N-Cbz-L-valine, DCC,
CH2Cl2, 0 oC, then DMF,
DMAP, r.t., 56%
H2/Pd/C, THF, then
AcOCHO, CH2Cl2, 62%
C6H13
C4H9
NHCHO
O
O
O
O
Synthesis of Malyngolide
OH
KHSO4, toluene, 48 h;
COOMe then DBU, r.t., 24 h,
OH
then LiAlH4 in ether
added at 0 oC
C9H19
O
BuOOH, VO(acac)2
OH
benzene, 10 mins
C9H19
C9H19
Fe2(CO)9,
THF
O
B
Fe(CO)3
A
CO(300atm), 90 oC, 24 h
C9H19
O
+
O
C9H19
OH
O
O
C9H19
O
OH
OH
PtO2/H2, MeOH
PtO2/H2, MeOH
LDA, -78 oC, H+ work-up
C9H19
O
OH
O
69% conversion
C9H19
O
OH
O
Horton, A. M.; Ley, S. V. J. Organomet. Chem. 1985, 285, C17
Catalytic Carbonylation of Epoxides
O
O
2 mol % [Rh(COD)Cl]2
CO (150atm), CCl4,
70 oC, 50 h
O
(75%)
Ph
Ph
2-3 mol% RhCl(CO)(PPh3)2
O
O
CO (400psi)
O
(67%)
Ph
CH2OMOM
O
5 mol% Pd2(C4H7)2Cl2
CO (30atm), EtOH, r.t.
i-Pr2NEt, NaBr
maleic anhydride
Ph
CH2OMOM
Ph
+
O
O
(14%)
Aumann, R.; Ring, H.; Angew. Chem. Int. Ed. Engl. 1977, 16, 50
Kamiya, Y.; Kawato, K.; Ohta, H. Chem. Lett. 1980, 1549
Shimizu, I.; Maruyama, T.; Makuta, T.; Yamamoto, A. Tetrahedron Lett. 1993, 34, 2135
CH2OMOM
(44%)
Carbonylation of Epoxides:
Co2(CO)8, CO (60atm),
75 oC,6 h
O
O
OH
N
+
O
93% conversion
90% selectivity
cat + LA
2 - 4 mol%
CO
80-110 oC, 24 - 48 h
O
O
O
cat
LA
[PPN][Co(CO)4]
BF3 . Et2O
[PPN][Co(CO)4]
B(C6F5)3
Drent, E.; Kragtwijk, E. Eur. Pat. Appl. EP 577206
Lee, J. T.; Thomas, P. J.; Alper, H. J. Org. Chem. 2001, 66, 5424-5426
(PPN = Ph3P
N
PPh3)
Substrate Scope of [PPN][Co(CO)4] Catalyst
substrate
LA
product (% isolated yield)
O
(66)
BF3 . Et2O
3
3
Cl
O
BF3 . Et2O
.
BF3 Et2O
O
HO
O
O
BF3 . Et2O
O
i PrO
O
O
BF3 . Et2O
(86)
i PrO
O
O
- (no reaction)
(57)
HO
(83)
O
B(C6F5)3
Ph
O
(20)
O
BF3 . Et2O
O
(63)
O
O
B(C6F5)3
(PPN = Ph3P
product (% isolated yield)
O
Cl
O
LA
O
O
O
substrate
N
PPh3)
Lee, J. T.; Thomas, P. J.; Alper, H. J. Org. Chem. 2001, 66, 5424-5426
O
(24)
Salen Based Catalysts
O
R1
1-2 mol% catalyst,
CO (900psi)
50o - 80 oC
O
O
R1
R2
R2
catalyst
R1
R2
time
yield(%)
[PPN][Co(CO)4/BF3.Et2O
H
Me
24
77
[nBu4N][Co(CO)4]
H
Me
16
0
[Na][Co(CO)4]
H
Me
16
6
1
H
Me
1
95
1
Me
Me
1
83
L
N
t
Bu
O
t
Bu
+
Al
Co(CO)4-
N
t
O
L
O
O
Bu
But
L=THF
1mol% 1, CO (880psi)
50 oC, neat, 1h
95% (96% ee)
1
Getzler, Y. D. Y. L.; Mahadevan, V.; Lobkovsky, E. B.; Coates, G. W. J. Am. Chem. Soc. 2002, 124, 1174
O
Stereochemistry of carbonylation
O
L
N
t
Bu
O
Co(CO)4-
N
+
Al
t
O
t
Bu
+
O
1
CO
O
Bu
racemic
t
Bu
L
L=THF
O
1
+
O
1
CO
O
racemic
racemic
L
N
t
Bu
O
t
Bu
+
Al
Co(CO)4-
N
t
O
L
Bu
But
L=THF
O
O
+
2
CO
racemic
Getzler, Y. D. Y. L.; Mahadevan, V.; Lobkovsky, E. B.; Coates, G. W. Pure Appl. Chem. 2004, 76, 557
2
O
O
+
O
Enantiomerically-enriched
44 % ee
LA Promoted Carbonylation Mechanism
M + Ln
O
O
Co(CO)4
Ln M O
Co(CO)4
[LnM][Co(CO)4]
O
CO
O
O
Ln M O
Co(CO)4
Getzler, Y. D. Y. L.; Mahadevan, V.; Lobkovsky, E. B.; Coates, G. W. J. Am. Chem. Soc. 2002, 124, 1174
Molnar, F.; Luinstra, G. A.; Allmendinger, M.; Reiger, B. Chem. – Eur. J. 2003, 9, 1273-1280.
Getzler, Y. D. Y. L.; Mahadevan, V.; Lobkovsky, E. B.; Coates, G. W. Pure Appl. Chem. 2004, 76, 557
Theoretical Study of -Lactone Synthesis
O
O
catalyst, CO
O
• Multisite
Catalysts
Single-Site
Catalysts
[Lewis
acid][Co(CO)
-]
4]
Co,
Rh, Pd
catalysts, Co[CO
4
Opens
a
low
energy
pathway
trans opening
No low energy pathway for ring for
opening
Effect
of Lewisformation
acid (BF3is, Me
3Al,
-allyl
complex
a
must
• Multisite
Catalysts
Et2Al+. diglyme & Me3Al/Co2(CO)8)
[Lewis
acid][Co(CO)
CO insertion
& uptake
4]
LA
O
OC
(CO)3 Co
LA
O
O
CO insertion
(OC)3Co
R
LA
O
CO uptake
O
(OC)4Co
R
Molnar, F.; Luinstra, G. A.; Allmendinger, M.; Reiger, B. Chem. – Eur. J. 2003, 9, 1273-1280.
R
Porphyrin Based Catalyst
O
O
Ph
N
Ph
N
R1
R2
Co(CO)4-
3
L
N
t
Bu
O
t
Bu
Al+
R1
R2
R2
substrate:
catalyst
yield (%)
3
1
nBu
H
350:1
>99
40
tBu
H
800:1
>99
0
H2C=CH(CH2)2
H
250:1
>99
40
TBDMSOCH2
H
400:1
>99
30
trans-CH3
CH3
75:1
>99
74
cis-CH3
CH3
75:1
56
20
Co(CO)4-
N
t
O
L
neat, 60 C, 6 h
Ph
N
O
O
o
N
Cr+
R1
Ph
O
catalyst, CO (900 psi)
But
L=THF
Bu
1
Schmidt, J.A.; Mahadevan, V.; Getzler, Y. D. Y. L.; Coates, G. W. Org. Lett. 2004, 6, 373
Highly Active and Versatile Catalyst
substrate
O
substrate/4
product
O
O
O
3500
N
N
Cr+
N
O
4500
> 99%
3
O
3
Co(CO)4-
O
O
4
O
10000
> 99%
9
O
Ph
N
Ph
N
N
O
O
O
3
O
5000
tBu
N
Cr+
9
> 99%
t Bu
Ph
O
O
3500
Ph
> 99%
O
O
N
yield
O
Co(CO)4-
> 99%
O
O
450
Schmidt, J. A.; Lobkovsky, E. B.; Coates, G. W. J. Am. Chem. Soc. 2005, 127, 11426
O
88%
Expanding the Range of Glycidyl Ethers
substrate
product
substrate/4
yield
O
O
O
MeO
N
N
N
O
750
MeO
O
O
Cr+
t
N
BuMe2SiO
O
O
2500
t
O
4
O
1800
PhH2CO
>99%
PhH2CO
O
O
O
250
O
>99%
O
O
O
O
O
O
>99%
BuMe2SiO
O
Co(CO)4-
>99%
O
250
Schmidt, J. A.; Lobkovsky, E. B.; Coates, G. W. J. Am. Chem. Soc. 2005, 127, 11426
O
88%
Esters and Amides are Tolerated
substrate
substrate/4
product
conditions
O
O
O
300
O
40 oC
6h
O
O
O
O
250
O
40 oC
6h
O
O
O
O
Pr
3500
2
60 oC
6h
O
n
Pr
O
O
O
Pr0
1500
60 oC
6h
O
n
> 99%
Pr0
O
O
O
O
Me2N
> 99%
O
2
O
n
97%
O
Ph
O
n
> 99%
O
O
Ph
yield
O
75
7
60 oC
6h
O
Schmidt, J. A.; Lobkovsky, E. B.; Coates, G. W. J. Am. Chem. Soc. 2005, 127, 11426
O
Me2N
> 99%
O
7
O
Rearrangement of -Lactone to -lactone
substrate
substrate/4
product
conditions
O
O
O
300
O
40 oC
6h
O
O
O
O
250
40 oC
6h
O
Ph
O
97%
O
O
O
O
550
O
60 oC
24h
O
O
O
Ph
> 99%
O
O
Ph
yield
O
250
60 oC
24h
O
Schmidt, J. A.; Lobkovsky, E. B.; Coates, G. W. J. Am. Chem. Soc. 2005, 127, 11426
Ph
O
> 99%
O
> 99%
O
O
O
O
Rearrangement of -Lactone to -lactone
O
n
Pr
O
O
O
N
N
N
Cr
+
+
N
O
-
O
4 Co(CO)4 ,
CO
O
n
Pr
4+
O
nPr
O
4+
O
O
O
O
4+
O
O
Pr
Schmidt, J. A.; Lobkovsky, E. B.; Coates, G. W. J. Am. Chem. Soc. 2005, 127, 11426
nPr
O
O
O
+
O
O
O
4
Bicyclic -Lactones
substrate
substrate/catalyst
product
yield
O
O
O
> 99%
100
O
O
O
250
> 99%
O
O
O
> 99%
100
O
O
O
100
Schmidt, J. A.; Lobkovsky, E. B.; Coates, G. W. J. Am. Chem. Soc. 2005, 127, 11426
57%
Mechanism of Stereoretention
-
OEP = octaethyl porphyrin
(OEP)CrO
Co(CO)4
+
O
(OEP)CrO
Co(CO)4
(OEP)CrO
Co(CO)4
[(OEP)Cr][Co(CO)4]
O
O
CO
O
(OEP)Cr
O
Schmidt, J. A.; Lobkovsky, E. B.; Coates, G. W. J. Am. Chem. Soc. 2005, 127, 11426
Co(CO)4
Dicarbonylation of Epoxides
R
Ph
Ph
R
O
Co2(CO)8, CTAB, MeI
NaOH (0.5M), C6H6,
r.t.., CO (1atm)
H
O
HO
O
1 (R=H)
Alper, H.; Arzoumanian, H.; Petrignani, J.F.; Maldonado, M. S. J. Chem. Soc., Chem. Commun. 1985, 340
Mechanism of Dicarbonylation
O
Co(CO)4-
MeI
Me
CO
Co(CO)4
Me
O
Co(CO)4
1
Ph
O
Me
Co(CO)4
CO
Ph
O
O
HO
Ph
O
O
O
Co(CO)4
O
Ph
O
O
Me
Co(CO)4
HO
O
Me
Ph
CO
HO
O
Co(CO)4
Me
Dicarbonylation of Epoxides
O
O
O
1 mol% 1, CO (880psi)
O
O
O.45 mol% 1, CO (200psi)
1 h, 50 oC, neat
24 h, 55 oC, toluene
99% ee
Proposed Mechanism
O
O
O
O
[LnAl]+[Co(CO)4]-
O
O
LnAl
O
Co(CO)4
O
LnAl
O
O
CO
Getzler, Y. D. Y. L.; Kundnani, V.; Lobkovsky, E. B.; Coates, G. W. J. Am. Chem. Soc. 2004, 126, 6842
Co(CO)4
O
Seminar Outline
• Introduction
• Carbonylation of Epoxides
• Carbonylation of Aziridines
• Inversion of Stereochemistry
• Effect of EWG groups
• Bimetallic catalysts
Carbonylation of Aziridines
Me
R
Me
Ph
Ph
[Rh(CO)2Cl]2
N
N
a
R'
O
Pr
R
N
CO, 20atm
90o, C6H6
i
Pr
i
O
CO, [M]
N
Et
R'
H
Et
R
b
N
CH2CH2Ph
N
O
Ph
O
Boc
Pd2(dba)3. CHCl3
PPh3, CO, 1 atm
r.t., 3days
N
R
N
DME, CO (33 atm)
100 oC, 24 h
PhH2CH2C
O
R'
Boc
N
H
Co2(CO)8 (8 mol%)
Ph
N
Ph
O
(51%)
CO
N
R
Pd
L2
N
R
O
(55-83%)
Hamel, N.; Alper, H. Tetrahedron Lett 1987, 28, 3237.
Calet, S.; Urso, F.; Alper, H. J. Am. Chem. Soc. 1989, 111, 931.
Spears, G. W.; Nakanishi, K.; Ohfune, Y. Synlett 1991, 91.
Marcelo, E. P.; Alper, H. J. Am. Chem. Soc. 1996, 118, 111.
O
N
CO
O
Pd(PPh3)4
CH2Cl2, RT, CO,1atm
Boc
Pd
Inversion of stereochemistry
R2
R3
H
H
N
R1
R2
Co2(CO)8 (8 mol%)
or NaCo(CO)4
DME, CO (33 atm)
100 oC, 24 h
R3
H
N
R2
H
N
R1
R2
H
H
R3
R1
O
R3
R1
R2
R3
isolated
yield
PhCH2CH2
Et
H
94
PhCH2
Et
H
64
p-MeOPh
t-Bu
H
50
i-Pr
H
Ph
42
i-Pr
Me
Ph
94
Co(CO)4
R1
CO
Co(CO)4
R2
R3
Co(CO)4
R2
H
H
R3
R1
N
N
R1
O
O
Marcelo, E. P.; Alper, H. J. Am. Chem. Soc. 1996, 118, 111.
Effect of EWG Substituents
Me
Me
Me
Co2(CO)8 (8 mol%)
N
DME, CO (33 atm)
100 oC, 24 h
O
Ph
+
N
N
O
O
Ph
(55%)
O
O
Ph
(37%)
SET Mechanism:
O
N
Ph
Me
OCo(CO)4
O
O
Co(CO)4
-
SET
H
N
+
Co(CO)4
Ph
Me
Me
H
Ph
+
C
ON
N
Me
H
Co(CO)4
O
Me
C
H
N
O
Ph
Marcelo, E. P.; Alper, H. J. Am. Chem. Soc. 1996, 118, 111.
Co(CO)4
O
Co(CO)4
O
Me
C
H
N
-
Me
Ph
C
H
N
OPh
Ph
Substituents at 2-Position
Ph
R
Ph
R
Co2(CO)8 (8 mol%)
N
Ph
N
DME, CO (500 psi)
100 oC, 14 h
Aziridines
O
R
Stereochemistry
Ph
ß-Lactams
Stereochemistry Yield(%)
cis
COOCH3
-
-
cis
COCH3
-
-
cis
CHO
-
-
cis
CH2OH
trans
79
cis
CH2OTBDMS
trans
96
cis
CH2OAc
trans
86
cis
CH2NH2
trans
68
trans
CH2OH
-
-
trans
CH2OTBDMS
cis
40
Davoli, P.; Forni, A.; Moretti, I.; Torre, G.; Prati, F. Tetrahedron 2001, 57, 1801-1812.
Effect of Intramolecular H-Bonding
Ph
H3C
OH
HN
Co2(CO)8 (8mol%)
N
DME, CO (500psi)
100 oC, 14h
Ph
O
O
Mechanism
Ph
H3C
HN
N
[Co(CO)4]
O
OH
O
Ph
Ph
N
(OC)4Co
H
(OC)4Co
O
Ph
O
CO
Davoli, P.; Forni, A.; Moretti, I.; Torre, G.; Prati, F. Tetrahedron 2001, 57, 1801-1812.
N
O
H
Bimetallic Catalysts
Substrate
Catalyst
Yield[%]
Product
1
N
O
Ti+
Ph
Bu
O
t
Bu
Al+
1
80
2
<5
_
+
N
Ph
Ph
t
O
Bu
But
L
2
L=THF
N
O
Co(CO)4-
N
50
N
O
O
L
t
2
Ph
[Co(CO)4]-
1
N
90
1
TBSO
95
TBSO
_ N
+
_ N
+
O 19
Ph
Ph
..
1
TBSO
_
+
O
Mahadevan, V.; Getzler, Y. D. Y. L.; Coates, G. W. Angew. Chem. Int. Ed. 2002, 6, 2781
Ph
Conclusions
• Mild and Efficient route to Lactones and
Lactams
• Access to Bicyclic systems
• Mechanistic study helps in the design of
new catalysts
Acknowledgement
• Dr. Smith
• Dr. Wagner
• Smith’s Group
Abbas, Aparajita, Edith, Sulagna,
Washington
• Doug, Kapil, Sandeep, Nicki, Gwenn, Sue