Download Multiple Metal-Carbon Bonds for

Multiple Metal-Carbon Bonds for
Catalytic Metathesis Reactions
Nobel Lecture
December 8, 2005
1
Metal-carbon double and triple bonds in which the
transition metal is in a "low oxidation state"
were discovered by E. O. Fischer.
CO
OC
Cr
δ-
CO OCH
C δ+
CO
CO
3
Br
W
C
OC
OC
CO
CO
1964
"carbene"
1973
"carbyne"
2
Beta hydride elimination in an ethyl complex
H
H
C
H
H C
L1
M
L2
H
L3
H
L1
M
L3
+
H
H
C C
H
H
L2
3
Known Group 4 Peralkyl Complexes (M = Ti, Zr, Hf) in 1973.
H
H
H
Me
β
H
α CH2
C6H5CH2
C6H5CH2
H
M
CH2C6H5
β Si
α CH2
M
Me3SiCH2
Me3SiCH2
Me
Me
Me
CH2SiMe3
β C Me
α CH2
Me3CCH2 M
Me3CCH2
Me
CH2CMe3
All alkyls lack one or more hydrogen atoms
on the atom β with respect to the metal.
4
The first relatively stable permethyl complex
Me
pentane
WCl6 + 6 AlMe3
Me
Me
W
Me
Me
Me
4
Ti
Zr
Hf
5 6 7 8
V Cr Mn Fe
Nb Mo Tc Ru
Ta W Re Os
A. J. Shortland and G. Wilkinson
J. Chem. Soc., Dalton Trans. 1973, 872.
“*Note added in proof. Hexamethylrhenium (K. Mertis and G. Wilkinson)
and pentamethyl[t]antalum (R. Schrock, DuPont, Wilmington, private
communication) have recently been synthesized.”
Geoffrey Wilkinson, Nobel Lecture, December 11, 1973
5
Synthesis of tantalum pentaalkyls
pentane
2 LiMe
TaMe3Cl2
TaCl5 + 1.5 ZnMe2
- 1.5 ZnMe2
H H H
C
ether
(Juvinall)
H3C
H3C
Ta
CH3
CH3
Decomposes above 0 °C
bimolecularly
TaCl5 + 5 Me3SiCH2MgCl
1/2
Me3SiCH2
Me3SiCH2
SiMe3
C
CH2SiMe3
Ta
Ta
CH2SiMe3
C
SiMe3
"It is assumed that a penta-alkyl complex cannot exist for steric reasons."
(Mowat, W.; Wilkinson, G. J. Chem. Soc, Dalton Trans. 1973, 10, 1120.)
6
Neopentyls yield a stable product of α hydrogen abstraction.
2 LiCH 2CMe3
Ta(CH 2CMe3) 3Cl2
- CMe 4
t-BuCH2
t-BuCH2
t-BuCH2
H
Ta
C
CMe3
J. Am. Chem. Soc. 1974, 96, 6796
Distills in a good vacuum at 75°C.
CH2-t-Bu
(t-BuCH2)3Ta
α hydrogen
activation
H
C H
t-Bu
δ+
(t-BuCH2)3Ta
δCH2-t-Bu
H δ+
δ- C H
t-Bu
δ+
- CMe4
δ+ δ- H
(t-BuCH2)3Ta C
t-Bu
α hydrogen
abstraction
(deprotonation)
7
Alkylidenes can be deprotonated to yield
tantalum-carbon triple bonds.
t-BuCH2
t-BuCH2
t-BuCH2
δ+
δ+
δ-
Ta
C
H
LiButyl
CMe3
- ButylH
t-BuCH2
t-BuCH2
t-BuCH2
Li+
Ta C CMe3
Guggenberger, L. J.; Schrock, R. R. J. Am. Chem. Soc. 1975, 97, 2935.
8
Alkylidenes decompose bimolecularly.
δ+ Ta
2
Me
H
C δH
Me CH
2
Cp2Ta
L
TaCp2
CH2
Me
Me
Ta
Me
CH2
+
Ta
L
CH2
18 electrons
L = CO, C2H4 , PR3
-
H+
base
[Cp2TaMe3]+
Schrock, R. R. J. Am. Chem. Soc. 1975, 97, 6577.
Bimolecular decomposition of alkylidenes, especially methylenes,
is difficult to prevent, especially in electron deficient species.
9
Olefin metathesis and the Chauvin mechanism (1971)
2 RCH=CHR'
RCH=CHR + R'CH=CHR'
+ RCH=CHR' - R'CH=CHR'
+ RCH=CHR'
M=CHR
R H
M
R
H
- RCH=CHR
M=CHR'
H R'
M = Mo, W, or Re
10
Alkyne metathesis and the metalacyclobutadiene mechanism
R'C≡CR' + RC≡CR
2 RC≡CR'
R
RC
M
CR
R
CR'
- RC
M
R
M
R'
R
CR
M
CR'
R'
(suggested by
T. Katz; 1975)
M = Mo, W
11
Reaction of tantalum alkylidenes with olefins.
2 RCH=CH2
Cl Ta
Cl
Cl Ta
CH2
Cl
CHR
CH-t-Bu
CH-t-Bu
βH
RCH=CHCH2-t-Bu
+
RCH2CH=CH-t-Bu
βH
CH2=CHRCH2-t-Bu
+
CH3CHR=CH-t-Bu
CH2
CpCl2Ta
+ 4 olefins
CHR
CH-t-Bu
CHR
CpCl2Ta
CH2
12
Modification of Nb and Ta yields metathesis catalysts
M(CH-t-Bu)L2 Cl 3 + H2 C=CHR
4 products of rearrangement
of metallacyclobutanes
M = Nb or Ta
L = PMe3
M(CH-t-Bu)(O-t-Bu)2Cl(PMe3) + olefins
also metathesis products
(~35 turnovers for cis-2-pentene)
Alkoxides "prevent reduction" and "promote metathesis."
J. Molec. Catal. 1980, 8, 73; J. Am. Chem. Soc. 1981, 103, 1440.
13
An oxo neopentylidene complex of tungsten
t-Bu
O
C
Cl
Ta
L
t-Bu
H
H
Cl
Cl
+
t-BuO
t-BuO
W
C
Cl
O-t-Bu
O-t-Bu
t-BuO
t-BuO
Ta
O-t-Bu
O-t-Bu
L
+
Cl
L
W
Cl
L = a phosphine, e.g. PEt3
t-Bu
H
C
Cl
L
W
Cl
L
R
H
C
RCH=CHR
O
- t-BuCH=CHR
Cl
L
W
L
O
Cl
(AlCl3 cat)
Even R = H
14
L
O
A sterically demanding diisopropylphenyl imido
group might be a desirable "ancillary" ligand.
i-Pr
X
RO
RO
X = N
W
CH-t-Bu
i-Pr
The OR group should be a sterically demanding tertiary alkoxide.
15
A sterically demanding diisopropylphenyl imido
group might be a desirable "ancillary" ligand.
i-Pr
i-Pr
N
(CF3)2MeCO
(CF3)2MeCO
W
CH-t-Bu
Hexafluoro-t-butoxide was chosen as a highly electron withdrawing alkoxide.
16
Synthesis of a tungsten neopentylidyne complex
t-Bu
Cl
MeO
MeO
C
Cl
W
OMe
Cl
+ 6 ClMgCH2-t-Bu
W
CH2
t-Bu
CH2
CH2
t-Bu
t-Bu
Volatile yellow crystals.
Thermally stable, distilling
at 75°C in a good vacuum.
(1978)
17
Tungsten-carbon triple bonds and alkyne metathesis
t-Bu
t-Bu
C
W
CH2
t-Bu
3 HCl in dme
CH2
CH2 t-Bu
- 3 CMe4
t-Bu
C
Cl
W
Me O
Cl
Cl
O
Me
t-Bu
C
3 LiO-t-Bu
W
O
t-Bu
O
O
t-Bu
t-Bu
purple crystals
The tri-t-butoxide compound is a powerful catalyst
for the alkyne metathesis reaction.
2 RC≡CR'
R'C≡CR' + RC≡CR
18
Metal-metal bonds and "metathesis" reactions.
t-BuO
t-BuO
t-BuO
t-BuO
O-t-Bu
W W
t-BuO
+
O-t-Bu
O-t-Bu
R-C
C-R
W CR
2
t-BuO
(1982)
R
R-C
X3W
WX3
R
R
C-R
X3W
WX3
X3W
WX3
R
19
Synthesis of a tungsten imido alkylidene complex
Ar
N
Me
O
Cl
Ar
H
Cl
W C-t-Bu
O
Me
Et3N catalyst
Me
N
Cl t-Bu
O W C
Cl
H
O
Me
Ar
N
2 LiOR
t-Bu
W C
RO
RO
H
("14 electron" species)
OR = O-t-Bu, OCMe2(CF3), OCMe(CF3)2,
and various bulky phenoxides
W(NAr)(CH-t-Bu)(OR)2 species are "well-defined"
catalysts for the metathesis of olefins and the
activity can be varied systematically by varying OR.
i-Pr
NAr = N
i-Pr
20
Structure of syn-W(NAr)(CH-t-Bu)(O-t-Bu)2
1.87Å
169°
1.76Å
000
000 00
000
00
00
000 000
00
00
145°
21
Tungstenacyclobutanes can be isolated, but can be too
stable toward loss of olefin.
000000000
000000000
00
Molybdacyclobutane intermediates lose an olefin more readily.
22
Two isomers (anti and syn) are available in any system
through rotation about the M=C bond.
R'
N
RO
RO
R'
R'
RO
RO
M
C H
t-Bu
anti
N
ka/s
ks/a
R'
M
C t-Bu
H
syn (usually favored)
23
Olefin metathesis variations
RCM
ROM/CM
- CH2=CH2
+ RCH=CH2
HH
H
H
H
H
H
H
H
H
H
R
H
H
ROMP
(Ring-Opening Metathesis
Polymerization)
x
Control!
24
Polymerization of bistrifluoromethylnorbornadiene via
enantiomorphic site control.
R
R
Ph Me N
Si Me
CMe3
Mo
O
O Me H
Si Me
Ph
CF3
CF3
H
CF3
H
CF3
H
CF3
H
CF3
H
CF3
H
CF3
H
CF3
H
CF3
H
CF3
H
CF3
x
all cis and isotactic through enantiomeric site control when R = CH3
When R = CH(CH3)2 the polymer structure has a relatively random
(71% cis) structure.
25
Alkynes are polymerized to yield polyenes.
EtO2C
EtO2C CO2Et
CO2Et
H
or
CO2Et
CO2Et
H
H
H
head-to-tail
H
H
tail-to-tail
Soluble, highly conjugated (purple), and relatively air-stable;
both rings observed in polymer made with Mo(NAr)(ORF6)2 catalyst.
E E
E E
E E
E E
*
*
E E
E E
E E
>95% 5-membered rings produced with Mo(NAr)(O-t-Bu)2 catalyst.
26
Ring-closing metathesis with Mo catalyst (4-5 mol%)
(Catalyst = Mo(NAr)(CHCMe2Ph)[OCMe(CF3)2]2)
O
O
Ph
Ph
- 2 butene
Me
Me
Me
O
Ph
O
Ph
O
- C2H4
N
15 min, 92%
O
15 min, 92%
Me
O
Ph
N
2 hr at 50°, 81%
Me
- C2H4
Ph
Ph
Me
Me
Me
Me
O
- propylene
Ph
180 min, 93%
Me
Me
Fu, G. C.; Grubbs, R. H. J. Am.Chem. Soc. 1992, 114, 5426; 7324.
27
Synthesis of Fluvirucin-B1
OAc
Me
OAc
Me
N(H)COCF3
O
Mo cat
O
C6H6
NH
Me
Et
H2N
OH
Me
N(H)COCF3
HO
Me
O
OAc
O
AcO Me
O
Et
- CH2=CH2
O
O
Et
Et
HN
O
O
Et
Et
HN
92% yield
Fluvirucin-B1
A. F. Houri, Z. M. Xu, D. A. Cogan, A. H. Hoveyda, J. Am. Chem. Soc. 1995, 117, 2943.
28
Mo or W catalyzed alkyne metathesis reactions are
useful in organic chemistry.
O
O
Hydrog.
W cat
- MeC
O
CMe
W cat = W(CCMe3)(OCMe3)3
+ H2
H
H
Civetone
(Fürstner)
Olefins do not appear to react with M-C triple bonds.
29
Other examples of alkyne metathesis in organic synthesis
O
H2 N
N
S
N
O
OH
N
O
H
O
HO
O
Motuporamine C
PGE2-1,15-lactone
O
O
O
MeO
W cat
Epothilone C
O
O
MeO
O
HO
1. TsOH
O
O
O
2. 9-I-9- BBN
- 2-butyne
MeO
O
OH
MeO
HO
80%
S-(+)-citreofuran
30
An enantiomerically pure Mo catalyst
Alexander, J. B.; La, D. S.; Cefalo, D. R.; Hoveyda, A.; Schrock, R. R.
J. Am. Chem. Soc. 1998, 120, 4041.
31
Asymmetric catalyst design; a modular approach
Imido Groups
Diolates
t-Bu
TRIP
Mes
O
Mo
O
O
Mo
O
TRIP
Mes
N
N
O
Mo
O
Mo
Mo
t-Bu
Me
Me
i-Pr
i-Pr
Mes
CHPh2
O Mo
O
O Mo
O
O
Mo
O
t-Bu
Mes
CHPh2
t-Bu
Cl
Cl
N
N
Mo
Mo
24 catalysts!
32
Asymmetric Ring-Closing Metathesis (ARCM)
Me
N
Me
Me
Mo
O
Ph
O
- propylene
O
Me
Me
Me
O
Me
2 mol % cat
Me
no solvent,
22 °C, 5 min
Me
Me
H
R
99% ee, 93%
R = i-Pr
i-Pr
i-Pr
Me2
Si
O
R
i-Pr
N
O
Mo
O
i-Pr
O
R
Me
Ph
Me
Me
- ethylene
2 mol % cat
Me2
Si
O
Me
Me
no solvent,
60 °C, 4 h
H
Me
>99% ee, 98%
i-Pr
i-Pr
33
Ring-Opening / Ring-Closing Metathesis
i-Pr
i-Pr
N
Me
O
Mo
O
Ph
Me
5 mol %
H
O
C6H6
O
O
O
H
>99% ee, 76%
34
Ring-Opening / Cross Metathesis
i-Pr
i-Pr
N
Me
O Mo
O
Ph
Me
OMOM
OMOM
5 mol %
+
X
C6H6
X = H, OMe, CF3
X
95% yield, >98% ee, >98% trans
D. S. La; J. G. Ford; E. S. Sattely; P. J. Bonitatebus; R. R. Schrock;
A. H. Hoveyda J. Am. Chem. Soc. 1999, 121, 11603.
35
Nitrogen-Containing substrates
R
5 mol %
O
O
N
Mo
R
Me
Ph
Me
Ph
N
22 °C
PhN
- ethylene
20 min
R = Me
>98% ee, 90% yield
36
Enantioselective synthesis of a tertiary ether in a drug
R
R
R
R
O
5 mol %
O
N
Mo
R
Me
Ph
O
Me
R
R
R = i-Pr
R
O
O
C6H6, 50 °C
95% ee, 95% yield
Me
OH
O
H
N
N
CF3
S
O2
O
Cefalo, D. R.; Kiely, A. F.; Wuchrer, M.;
Jamieson, J. Y.; Schrock, R. R.; Hoveyda, A. H.
J. Am. Chem. Soc. 2001, 123, 3139.
Me
tipranavir (HIV protease inhibitor)
37
A bis amido alkylidene catalyst precursor.
CHPh2
OH
OH
Ar
Ar
CHPh2
N
CHPh2
Ph2N
CH-t-Bu
Ph2N
Mo
O
Mo
N
CH-t-Bu
O
- 2 Ph2NH
CHPh2
In situ
Amido ligands deactivate the metal
toward metathesis reactions.
O
In situ catalyst prepared with
gives same ee (93-94%) as
5 mol% [Mo]
C6D6, 22 oC
O
H
the isolated catalyst.
38
Dineopentyl species were examined as bisalkoxide catalyst precursors.
Ar
Ar
N
N
Mo
t-Bu
t-Bu
+ ROH
- CMe4
t-Bu
Ar = 2,6-i-Pr2C6H3
t-Bu
Mo
t-Bu
O
R
OR = OCH(CF3)2 , OAdamantyl,
OCMe3, or OAr
Preliminary results suggest that monoalkoxides are at least as active as bisalkoxides!
(Surprising since dineopentyl species are essentially inactive.)
39
"Well-defined" catalysts can be prepared on a silica surface.
Ar
N
Ar
t-Bu
N
OH
t-Bu
CH2
t-Bu
t-Bu
Mo
CH2
C
H
+
CH2
O
C
H
Si
Si
Silica (SiO2)
Ar = 2,6-i-Pr2C6H3
- CMe4
t-Bu
Mo
Silica (SiO2)
Bimolecular decomposition of alkylidenes is not possible.
Frédéric Blanc, Anne Baudouin, Christophe Copéret, Jean Thivolle-Cazat, Jean-Marie Basset,
Anne Lesage, Lyndon Emsley, Amritanshu Sinha, Richard R. Schrock, Angew. Chem. Int. Ed., in press.
40
Well-defined catalysts can be prepared on a silica surface
using other "clean" neopentyl sources.
R
N
M
t-Bu
C
t-Bu
H
H
C
Ta
CH2
t-Bu
t-Bu
CH2
CH2
t-Bu
t-Bu
Ta(V)
CH2
CH2
t-Bu
t-Bu
C
M
CH2
t-Bu
t-Bu
C
t-Bu
Re
C
H
CH2
CH2
t-Bu
t-Bu
CH2
CH2
t-Bu
t-Bu
Re(VII)
M(VI)
(M = Mo, W)
Cóperet, C.; Chabanas, M.; Saint-Arroman, R. P.; Basset, J.-M.
Angew. Chem. Int. Ed. 2003, 42, 156.
41
The principles of high oxidation state alkylidene and
alkylidyne chemistry extend to Re(VII)
t-Bu
R
t-Bu
N
C
t-Bu
W
C
H
O
O
R
W(VI)
Re
C
R
H
O
O
R
R
Re(VII)
Olefins react with the Re=CHR bond selectively, not the Re≡C-t-Bu bond.
These Re species are active olefin metathesis catalysts.
42
Present and future challenges
1. Prevent catalyst decomposition completely and/or
find ways to regenerate catalysts from
decomposition products.
2. Find ways to generate and evaluate all catalysts
in situ from one precursor.
3. Synthesize new catalysts and aim for additional
selectivity and efficiency in metathesis reactions.
43
44
"Unsupported" M=M bonds are formed in bisalkoxide systems
Me
Me
N
N
(CF3)Me2CO
(CF3)Me2CO
Me
Me
MeCH=CHEt
W
CH-t-Bu
(CF3)Me2CO
(CF3)Me2CO
W
W
OCMe2(CF3)
OCMe2(CF3)
N
Me
Me
A W=W species (W=W = 2.49 Å)
that does not contain
bridging groups.
45