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Chem 1140; Ring-Closing Metathesis (RCM) and Ring-Opening Metathesis (ROMP)
• Introduction• RCM• Cross-Metathesis• ROMP
History of RCM
From the point of view of organic synthesis, the first noteworthy, but largely ignored, example of a ring closing diene metathesis reaction appeared in 1980:
History of RCM
O
O
20 mol% WClO4 + 24 mol% Cp2TiCl2
21O
O
12%
Tsuji, J.THL 1980, 21, 2955
Important Technical Applications
Phillips triolefin process
+ +
Shell higher olefin process
+10-20
2-7
9-13
[Mo]
[cat]
SHOPR
R
R
Important Technical Applications
Norsorex process
n[W]
ROMP
n
Hüls-Vestenamer process
[cat]n
n
ROMP
Molybdenum-Based Olefin Metathesis
MoO2Cl2(THF)2 + ArNH(TMS)2
lutidineTMSClDME
Mo(NAr)2Cl2(DME)RCH2MgCl2
Mo(NAr)2(CH2R)2
TfOHDME Mo(NAr)(CH2R)(OTf)2(DME) LiOR'2
Mo(NAr)(CH2R)(OR')2 R: C(Me)2PhR': OC(Me)2CF3
Schrock, JACS 1990, 112, 3875
Molybdenum-Based Ring-Closing Olefin Metathesis
O
P h
M o
N
O
O
F3
C
F3
C
C F3
F3
C
P h
A (5 mol%)
O
P h
93%
Molybdenum-Based Ring-Closing Olefin Metathesis
Xu, Z.; Johannes, C. W.; Salman, S. S.; Hoveyda, A. H. J. Am. Chem. Soc. 1996, 118, 10926.
A (25 mol%)
60%
HN
O
OTBMS
HN
O
OTBMS
>98% Z
Ruthenium-Based Olefin Metathesis
The synthesis of ruthenium vinylcarbene complexes allowed the development of well-defined, late transition metal, low oxidation state complexes that catalyze olefin metathesis. Ruthenium carbene complexes are significantly easier to make and handle than the Schrock molybdenum complex.In addition to the metathesis of strained cyclic and exocyclic olefins, the remarkable functional group tolerance (alcohols, aldehydes, carboxylic acids) and stability toward air, water, and acid has made this class of compounds particularly attractive for practical applications (Grubbs, R. H.; Miller, S. J.; Fu, G. C. Acc. Chem. Res. 1995, 28, 446).
Ruthenium-Based Olefin Metathesis: Mechanism
Dias, E. L.; Nguyen, S. T.; Grubbs, R. H. J. Am. Chem. Soc. 1997, 119, 3887.
Ruthenium-Based Olefin Metathesis: Mechanism
Mechanistically, the major pathway (>95%) was found to involve phosphine dissociation from the metal center, such that a minor associative pathway in which both phosphines remain bound can be considered to operate only at higher phosphine concentrations. The formation of the 14-electron metallacyclobutane intermediate is the rate-determining step. The rate and catalyst activity are directly proportional to (a) K1, the equilibrium constant for olefin binding, (b) K2, the equilibrium constant for phosphine dissociation, (c) k3, the rate constant for metallacyclobutane formation from the monophosphine olefin complex I2.
Ruthenium-Based Olefin Metathesis: Applications
N NH
N
N
H
OH
N
NCO2EtOPh
H CO2Me
N
NO
H CH2OBDPS
O
O
N
N
HCH2OBDPS
OO
O
N
NOPh
HCO2Me
O N
NOPh
HCO2Me
O
Manzamine A
B, 1equiv. rt, 5 days
30%
Pandit, THL 1994, 35, 3191
Martin, THL 1994, 35,691
A, benzene50°C, 63%
(Z only)
Cross-Metathesis
Challenges for successful cross-metathesis include:
control of olefin geometry
suppression of homodimer formation
extending functional group compatibility
OO
CO2Me
MoNAr
RF6ORF6O
H
CMe2Ph
A
CN
OO
CO2Me
CN5 mol% 92% yield
exclusively Z
Cross-Metathesis
Chatterjee, A. K.; Morgan, J. P.; Scholl, M.; Grubbs, R. H., "Synthesis of functionalized olefins by cross and ring-closing metathesis." J. Am. Chem. Soc. 2000, 122, 3783.
TBSO OMe
O
Ru
PCy3
ClCl
NN
Ru
PCy3
ClCl
NN
AcO
H
O
AcO CHO
TBSO OMe
O
5 mol%
(2 equiv)
CH2Cl2, 45 °C,
91%; 4.5:1 E:Z
5 mol%
(0.5 equiv)
CH2Cl2, 45 °C,
92%; 20:1 E:Z
Cross-Metathesis: Applications
Wipf, P.; Spencer, S. R. "Asymmetric total syntheses of tuberostemonine, didehydrotuberostemonine, and 13-epituberostemonine." J. Am. Chem. Soc. 2005, 127, 225-235.
H
H
NHO
CO2Me
NH2
HOCO2H
NOCbz
H
H
CO2Me
Tuberostemonine
Tyrosine
HH
H
N
O
O
O O
H
82
Cross-Metathesis: Applications
O OH
HO
O
N
H
H
Br OO
O
NCO2Me
O
H
H
Ph
NCO2Me
H
HO
N N
Ru
MesMes
PhPCy3
ClCl
O
O OO
N
H
HTBSO
NCO2Me
H
HO
N
H
HTBSO N
O
OMe
O
H
ON
H
HHO H
CH2Cl2; 92%
THF, -78 °C; 81%
1. PhSH, TEA2. (Ph3P)3RhCl, H2
3. DBU, THF; 76%
1. NaBH4, CeCl3; 75%2. TBS-Cl, Im.; 79%
3. MeONHMe•HCl, Me2AlCl; 94%
, LiDBB1. L-Selectride2. TsOH, MeOH
75%
Cross-Metathesis: Applications
O
H
ON
H
HHO H
N
OH
O
O OH
H
H
N N
Ru
MesMes
PhPCy3
ClCl
NHTr
O
Me2N
N
H
O OH
H
H
HN
OH
O
O OH
H
NN
Mes
Mes
Ru
OCl
Cli-Pr
N,N-Dimethyl-acetamide
dimethyl acetal
xylenes; 79%
CH2Cl2; H2C=CH2;then Pd/C, H2, MeOH; 80%
1. PhSeCl, MeCN/H2O, 0 °C; 67%2. AIBN, allyltriphenyltin, 95 °C; 70%
3. LDA•HMPA, THF; MeI 76%
toluene; 85%
27 steps/1.1% yieldfrom Cbz-tyrosine
HH
H
N
O
O
O O
HTuberostemonine!
ROMP
Ru
Cy3P
PhCl
NN
Cl
(2)
Ru ca ta lys t 2
ROMP Polymer
M CHR RCH CHR'+M
R' R
R
M CHR'
RCH CHR
ROMP
• A way of making polymers from cyclic olfins
• Condition for prepare living polymers a. monomer is highly strained (irreversible) b. R2 is slow c. organometallic intermediates in the polymerization reaction are stable
• Advantages of ROMP a. very narrow molecular weight distribution can be obtained: Mw/Mn approaching 1.0 b. living ROMP catalyst can tolerate a range of functionalities: most catalysts are destroyed in other types of living polymerization reactions c. new materials can be prepared under controlled
design conditions
Living Ring Opening Metathesis Polymerization (ROMP)
Brief history
• Calderon (1967) : the discovery WCl6/EtAlCl2/EtOH “olefin metathesis” • Grubbs (1986): the first report of living ROMP of a
cyclic olefin• Richard R. Schrock (1980’s): molybdenum &
tungsten catalystsLiving Polymerizations • Absence of chain termination and chain transfer reaction provides polymers whose molecular weights are precisely predicted and controlled by stoichiometry of polymerization
Mn = (g monomer) / (moles of initiator)
• Polydispersity will decrease with increasing molecular weight
• Synthesis of macromonomers that retain the reactive chain ends when all the monomer has been consumed
ROMP
Wakamatsu, H.; Blechert, S. "A new highly efficient ruthenium metathesis catalyst." Angew. Chem. Int. Ed. 2002, 41, 2403-2405
ROMP
Why Carbene Ligands?
The nucleophilic carbenes are ‘phosphine-mimics’ and yet they are much more. They reside at the upper end of the Tolman electronic and steric parameter scales. From solution calorimetric studies, it became clear that nucleophilic carbenes (most of them) are better donors than the best donor phosphines.
Why Carbene Ligands?
Don’t Miss….
Thursday, March 03, 20052:30 PM, Chevron Science Center 12 B
Professor Paul Hanson University of Kansas
Metathesis Enabled Combinatorial Chemistry for Drug Discovery
![Opening Metathesis Polymerization of Dendritic Urethane ... · polyurethanes [9], and aerogels derived via Ring Opening Metathesis Polymerization (ROMP), including polynorbornene](https://img.pdfslide.net/doc/110x75/5ed92a686714ca7f476944b0/opening-metathesis-polymerization-of-dendritic-urethane-polyurethanes-9-and.jpg)
