Reactions for Organic Synthesis Tristan Lambert MacMillan Group Meeting May 23, 2002 Non-Metathesis Ruthenium-Catalyzed I. Properties of Ruthenium II. Reductions III. Oxidations IV. Isomerizations V. C-C bond forming reactions Murahashi, Chem. Rev., 1998, 2599. Trost, Toste, Chem. Rev., 2001, 2067.
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Reactions for Organic Synthesis
Tristan Lambert
MacMillan Group Meeting
May 23, 2002
Non-Metathesis Ruthenium-Catalyzed
I. Properties of Ruthenium
II. Reductions
III. Oxidations
IV. Isomerizations
V. C-C bond forming reactions
Murahashi, Chem. Rev., 1998, 2599.
Trost, Toste, Chem. Rev., 2001, 2067.
Properties of Ruthenium
Ru4d75s1
Ruthenium has the widest range of accessible oxidation states of any element in the periodic table
Ru(CO)42- RuO4
Ru-II RuVIIIRu0
Ruthenium complexes of each oxidation state can assume several coordination geometries
Oxidation Coordinationnumber Geometry Examples
Ru0
RuII
RuIII
RuVI
RuVII
RuVIII
5
5
6
6
4
4
4
trigonal bipy. Ru(CO)5
trigonal bipy. RuHCl(PPh3)3
octahedral
octahedral [Ru(NH3)5Cl]2+
tetrahedral RuO42-
tetrahedral RuO4-
tetrahedral RuO4
state
Cotton, 5th Ed.
Ru complexes are generally characterized as
having high electron transfer ability, high Lewis
acidity, low redox potentials, and the ability to
stabilize reactive species such as oxometals,
metallacycles, and metal carbene complexes.
The wide range of oxidation states, coordination
geometries, and tunable properties result in the
ability of Ru complexes to catalyze a remarkable
range of chemical transformations
RuCl2CO(PR3)3
Regioselective Reduction of Unsymmetrical Cyclic Anhydrides
O
Me
Me
O
O
O
Me
Me
O
O
Me
Me
O
RuCl2(PPh3)3
2 mol%
reducing agent
reducing agent
LiAlH4
A B
yield % A : B
70
72
1 : 19
9 : 1H2
Morand and Kayser, J.C.S., Chem. Comm., 1976, 314.
O
MeO
MeO
OMe
OMe
O
O
O
MeO
MeO
OMe
OMe
O
Ru2Cl4(dppb)3
H2 (15 atm), 160 oC
88%
Ikariya, Tetrahedron Lett., 1986, 365.
Asymmetric Hydrogenation of Prochiral Olefins
MeO
CO2H
MeO
Me
CO2HRu(OAc)2[(S)-BINAP]
cat.
H2 (135 atm)
(S)-naproxen
97% eeNoyori, J. Org. Chem., 1987, 3176.
O
O
O
Me
O
{RuCl[(S)-BINAP] (benzene)} Cl
0.1 mol%
H2 (100 atm)
Et3N
92% eeTakaya, J. C. S., Chem. Comm., 1992, 1725.
O O
O
Me
Me
O O
O
Me Me
MeRu(OCOCF3)2[(R)-BINAP]
0.5 mol%
H2 (20 atm)
95% ee
Bruneau and Dixneuf, J. Org. Chem., 1996, 8453.
NCHO
MeO
MeO
OMe
OMe
NMe
MeO
MeO
OMe
OMe
(R)-laudanosine >99.5% ee
Ru(OAc)2[(R)-BINAP]
1 mol %
H2 (4 atm)
LiAlH4
Noyori, JACS, 1986, 7117.
Enantioselective Reduction of Ketones
MeOH
ORuCl2[(R)-BINAP]
0.5 mol%
H2 (93 atm) MeOH
OH
100% yield
92% ee
MeNMe2
O 0.1 mol%
H2 (50 atm)Me
NMe2
OH
72% yield
96% ee
Ru(OAc)2[(S)-BINAP]
NTs
HNTs
84% ee
Ru(OAc)2[(S)-BINAP]
5 mol%
80% yield
Charette, Tetrahedron Lett., 1996, 6669.
Noyori, JACS, 1988, 629.
Me Me
O O
Me Me
OH OH{Ru2[(R)-BINAP]2Cl4}NEt3
0.15 mol %
H2 (80 atm)
100% yield
99% ee
Me OMe
O O
Me OMe
OH ORuCl2[(R)-BINAP]
0.05 mol %
H2 (100 atm)
99% yield
99% ee
Noyori, JACS, 1988, 629.
Noyori, JACS, 1987, 5856.
Cl
Ru
HP
P
O
O OMe
Me
H
Ru
ClP
P
O
OMe
OMe
S
favored
unfavored
P
P= (R)-BINAP
Me Me
R
Dynamic Kinetic Resolution of !-Keto Esters
R1 OR3
O O
R2
R1 OR3
O O
R2
R1 OR3
OH O
R2
R1 OR3
OH O
R2
H2
Ru-BINAP
H2
Ru-BINAP
acyclic
syn-favored
cyclic
anti-favored
If equilibration is faster than hydrogenation, high ee's can be obtained
Me OMe
O O
NHCOMe
Me OMe
OH O
NHCOMeH2 (100 atm)
RuBr2[(R)-BINAP]
O O
OMe
OH O
OMe
RuCl(C6H6)-
[(R)-BINAP]Cl
H2 (100 atm)
98% ee
93% ee
99 : 1 syn : anti
1 : 99 syn : antiNoyori, JACS, 1989, 9134.
Ru
H
X
OP
P
OOMe
Ru
H
X
OP
P
O
Me
O
H
N
H
Me
O
Me
OMe
O O
OMe
OH O
H2 (100 atm)
RuBr2[(R)-BINAP]Ph Ph
NHBoc NHBoc
0.5 mol%
0.1 mol%
99% ee
0.2 mol%
> 99 : 1 syn : anti
4-Substituted !"keto-esters can be used as well
Noyori, Tetrahedron Lett., 1988, 6327.
Directed Hydrogenation of Allylic and Homoallylic Alcohols
Me
Me Me
OH
Me
Me Me
OH
Me
Me Me
OH
Me
Me Me
OH
Ru[(S)-BINAP]
Ru[(S)-BINAP]
Ru[(R)-BINAP]
geraniol
nerol
(R)-citronellol
(S)-citronellol
98% ee, 97% yield0.2 mol% cat.
Noyori, JACS, 1987, 1596.
Me
Me Me
Me
Me MeRu[(S)-BINAP]
OH OH
Olefins allylic to alcohols can be selectively and asymmetrically hydrogenated
Homoallylic alcohols similarly under slightly more forcing conditions
0.5 mol%
(100 atm H2)
(30 atm H2)
Homo homoallylic alcohols and higher analogs are inert
Me
Me Me
OH no rxnRu[(S)-BINAP]
0.5 mol%
(100 atm H2)
P
P
Ru
O
O
O
O
CH3
CH3
Ph2
Ph2
(R)-homocitronellol
96% yield
92% ee
Ru[(R)-BINAP]
homogeraniol
Oxidation of Diols to Lactones
HOOH
OO
180 oC, acetone
99% yield
HONMe
OHMeN O
O
RuH2(PPh3)4
RuH2(PPh3)4
2 mol%
2 mol%
180 oC, acetone
95% yield
OH
OH O
O
H
H
RuH2(PPh3)4
2 mol%
180 oC, acetone
90% yield
HO OH
Me
MeO
O
O
O
MeMe
MeMe
RuH2(PPh3)4
2 mol%
20 oC, toluene 99.6% yield
0.4% yield
Nozaki, JOMC, 1994, 473, 253.
Saburi and Yoshikawa, JOC, 1986, 2034
Murahashi, JOC, 1987, 4319.
OH
OHO
O[RuCl((S)-BINAP)-
60 oC, toluene 61% yield
23% ee
(C6H6)]Cl
0.2 mol%
H2NOH
NH
O140 oC, DME
RuH2(PPh3)4
2 mol%
hydrogen
acceptor
Murahashi, SynLett, 1991, 693.
Reactions can be performed intermolecularly to form esters and amides
59% yield
PhCH=CHCOCH3
PhCH=CHCOCH3
Oxidative Cleavage of Olefins
O
OAc
AcO
OAc
OCHO
CO2H
OAc
AcO
OAc
97% yield
0.2 mol% RuO2
NaIO4, CCl4-H2O N
CO2Et
Me NCHO
CO2H
CO2Et
Me
0.2 mol% RuO2
NaIO4, CCl4-H2O
96% yield
Torii, JOC, 1985, 4980.
O
Me
H
O
Me
HO
MeO
1. NaIO4, RuCl3
CH3CN / CCl4 / H2O
2. CH2N2
85% yield
OH
H
MeO2C
MeO2C
OH
H1. NaIO4, RuCl3
CH3CN / CCl4 / H2O
2. CH2N2
85% yield
Ghatak, Synthesis, 1983, 746.
Oxidative cleavage of aromatic rings
ORu
O
OO
reactions proceed through
a cyclic ruthenium (VI) diester
In reactions where carboxylic acids are
generated, the addition of CH3CN has
a dramatic effect on rate and efficiency
due to the disruption of insoluble Ru-
carboxylate species
Sharpless, JOC, 1981, 3936.
Oxidation of Ethers, Amines, and Alkanes
Oxidation of !-methylenes of ethers and amines
Me Me
O Ph
Me Me
O Ph
O
0.2 mol% RuO2, NaIO4
CH3CN / CCl4 / H2O
85% yield
Schuda, Tetrahedron Lett., 1983, 3829.
N
Boc OTBS
N
Boc OTBS
O
cat. RuO2, NaIO4
CCl4 / H2O
90% yield
Tanaka, Chem. Pharm. Bull., 1986, 3879.
Amides can be oxidized in a similar manner to imides