Ready; Catalysis
The Oxo
R
Hydroformylation
-developed in 1938 by Otto Roelen
process
-Principle method for hydroformylation of terminal alkenes industrially
-more that 4 million tons aldehyde annually
-linear aldehydes more desirable
O
H
Co2(CO)8
O
H2/CO (200-300 atm)
chemical feed stocks
o
120-170 C
+
linear alcohols (detergents)
R
H
R
linear (normal) branched (iso)
your name here
O
1/2
(OC)3Co
Co(CO)3
Δ
1/2
(OC)4Co
H
Co(CO)4
R
H
O
Stable convenient form of Co,
but inert at rt (why?)
H
H2
O
R
R
H2
pKa = ~1 (H2O), 8 (CH3CN)
R
(CO)4CoH
CO
R
σ-bond
met. ?
R
(OC)3Co
Heck and Breslow
Jacs, 1961, 4023
Sommer, Jacs,
1969, 7051
(OC)3Co
H
(OC)3Co
O
regiodetermining
Ready; Catalysis
(OC)4Co
iso
R
R
CO
(OC)3Co
H2
hydrogenation
Hydroformylation
1
Ready; Catalysis
Hydroformylation
Asymmetric Hydroformylation: under-developed
O
PCl
PPh2
O
4 steps
high yield
OH
OH
O
O
P
PPh2
O
OH
Hayashi
JOC, 1993, 1945
(S,R)-BINAPHOS
0.5-0.1 mo% Rh(acac)(CO)2
BINAPHOS (4x [Rh])
H2/CO (100 atm)
R
CHO
n:i selectivity "beyond the discussion here"
Nozaki, JACS, 1997, 4413
R
CH3
CH3
% ee
i:n
Ph
92
88:12
4-OMe-Ph
88
87:13
4-ClPh
93
87:13
4-CF3-Ph
93
96:4
93
88:12
85
89:11
R
OHC
CH3
O
91:9 i:n
96:4 d.r.
OH
OH
O
N
CH3
H
HO2C
PivO
O
O
R
R
?
*
Ready; Catalysis
see Breit, Eur. JOC, 1998, 1123,
CHO Buchwald, JACS, 2011, 19080
R'
R'
Hydroformylation
O
R
1. H2N-NH2
O
R
N
(±)-
P
N
2. succinyl chloride,
CO2H
CH3
CH3
H3C
(+)-Ambruticin Jacobsen, JACS, 2001, 10772
O
O
CH3
O
P
N
R
R
O
PH2
R = CO2H
O
A: R =
N
N
H
O
(resolve diastereomers)
~30%
PH2
500 psi H2/CO
Rh(acac)CO2/A (0.02 mol%)
60 oC
R
R
CHO
CH3
CHO
CHO
NC
CH3
CHO
Boc
CH3
CH3
4.8:1 b:l
100% conv
87% ee
30:1 b:l
100% conv
89% ee
AcO
H
N
CHO
CH3
40:1 b:l
100% conv
95% ee
33:1 b:l
99% conv
99% ee
Cbz
H
N
CHO
CH3
51:1 b:l
99% conv
94% ee
OAc
TBSO
CHO
CH3
2:1 b:l
99% conv
96% ee
BzCHN
CHO
CH3
4.4:1 b:l
99% conv
86% ee
AcO
CHO
CH3
7:1 b:l
99% conv
93% ee
Landis, Klosin, JACS, 2005, 5040
Stahl, Landis, JACS, 2010, 14027
2
Ready; Catalysis
Hydroformylation-4
dpm
t-Bu
O
Rh(CO)2
0.1 mol%
O
t-Bu
1 mol% ligand
C5H11
C5H11
Mixture of
branched isomers
CHO
i
n
H2/CO
n:i
ligand
0.9:1
PPh3
t-Bu
t-Bu
9.2:1
O
P
P
O
Can you explain how and why??
van Leeuwen, ACIEE, 1999, 336
O
Ready; Catalysis
Hydroformylation
Alkyne hydroformylation/silylformylation: Unsolved, but would be nice
PdCl2(PCy3)2
Co2(CO)8
NEt3, H2/CO
R
R
R
R'
150 oC
R
Role of Co is not clear. Many other metal carbonyls
accelerate rxn. Cocatalyst could help carbonyl
insertion. However, rate dependent on H2 pressure,
suggesting hydrogenolysis may be rate determining.
R
CHO
Hidai, JACS, 1997, 6448
R = alkyl, 88-95%
R = Ph, 53% (much stilbene)
R = Ph, 77% (w/o Cobalt)
R = Ph, Me, 85%, 3:2 regio (w/o Cobalt)
Rh4(CO)12 (1mol%)
Me2PhSiH (1 equiv)
NEt3, CO (29 atm)
R
R'
CsF
R
R'
o
100 C
PhMe2Si
CHO
CHO
R = Me, Pr, Ph, cHex, allyl
R' = H, Me, Ph, CO2M2
yields mostly >70%
Often poor E/Z
Matsuda, JACS, 1989, 2332
3
Ready; Catalysis
Hydroformylation
Tandem hydroformylation/reductive amination or hydroaminomethylation
+
R
[Rh(cod)2]BF4 (0.1mol %)
Xantphos (0.4 mol%)
MeOH/Tol
CO/H2 (1:5, 40 bar) 125 oC
R2NH
R2N
R
Olefins
O
HO
Xantphos ($17/g Aldrich)
i
Beller
JACS, 2003, 10311
HN
HNMe2
n
PPh2
R
n:i 9:1 - 99:1
y: most >90%
Amines
alkyl
PPh2
+
NR2
n
H2N
RO
OH
n
OR
NH2
R
R = H, Me, Ph
Ready; Catalysis
Hydrosilylation
Hydrosilylation
What:
R
SiR3
R
H-SiR3
catalyst usually = Pt, Rh, Pd, Ir
catalyst
R
O
why:
R
[O]
SiR3
R
SiR3
O
OH
R
or as adhesives, surfactants
(major applications industrially)
To retire rich, young and famous:
R
R
How:
OH
+ H2O
O
SiR3
R
=
R
H-OH
C=C
120
60
O-C
-90
C-H
-100
!H ~ -10 kcal/mol
HSiR3
Mn
SiR3
SiR3
X
or
protected alcohol
XSiR3
H
OH
Mn+2
SiR3
H
H
Mn+2
Mn+2
Note in some cases X-Si
bond formation precedes
H-C bond formation
H
X
X
4
Ready; Catalysis
Hydrosilylation
Rhodium [Rh(I) - Rh(III)]
RhCl(PPh3)3
SiMe2Ph
PhMe2SiH
+
80%
SiMe2Ph
RhCl(PPh3)3
PhMe2SiH
75 %
RhCl(PPh3)3
low yield
PhMe2SiH
n
RhCl(PPh3)3
HSiR3
R
SiR3
H
Rh
Cl
R3Si
RhCl(PPh3)2
SiR3
P
R
P
Rh
P
P
Cl
Chalk JOMC, 1970 (21) 207
+
R
SiR3
Rh
R
R
Ready; Catalysis
Cl
P
P
Hydrosilylation
Platinum [very active, Pt(II) - Pt(IV)]
2007: 5.6 metric tons of platinum used for hydrosilylation
H2PtCl6 6H2O
0.005 mol%
MeCl2Si-H
SiCl2Me
Has been suggested that Pt colloids are the real
catalyst. These are suspensions of fine particles
10-1000 A radius. These solutions appear
homogeneous and are able to pass through filters.
93%
H2PtCl6 6H2O
0.5 mol%
MeCl2Si-H
SiCl2Me
98%
H2PtCl6 6H2O
0.5 mol%
MeCl2Si-H
H
quant.
SiCl2Me
O
54%
H
OBn
O
H
OH
O
O
O
SiMe2
1. (Me2HSi)2NH;
H2PtCl6
2. TBAF
87:13
10 mol% HMDS
2 mol% H2PtCl6 6H2O
>80 %yield
O
OMe
O
OSiMe2H
BnO
OH
OMe
OBn
O
O
8 steps
BnO
H
H
O
Leucascandrolide A
Kozmin, OL, 2001, 755
Jatrophatrione
Paquette, JACS, 2002, 6542
5
Ready; Catalysis
Hydrosilylation
also OBn, OiPr, Et
Palladium: asymmetric synthesis of 2o alcohols
OMe
PPh2
1. 0.1-0.01 mol% [Pd(allyl)Cl]2,
yield
R = n-alkyl 60's
OH
HSiCl3
R
2. EtOH, Et3N
3. H2O2
R = cHex
R
45
%ee
95-97
i:n
5:1 - 20:1
96
3:1
Hayashi, JACS, 1991, 9887
Note: they propose MOP accelerates R.E.; Insertion is rate determining, so get kinetic product
Note: w/ BINAP (and other chelating phosphines) no reaction, propose inert 16e s.p. complex:
P
P
SiR3
Pd
P
vs.
H
Pd
but:
Ph
O
(best substrate)
H
1. MeLi, MeI
2. HBF4
3. H2O2
Ph
PhCl2Si-SiMe3
Pd(BINAP)Cl2
SiR3
Me
Ph
SiPhCl2 OSiMe3
OH
70%
54%, 85% ee
SiCl3
0.5mol% [Pd(allyl)Cl]2, HSiCl3
Johannsen
JACS, 2002, 4558
Ph
O
R
P
N
R
O
95-97% ee
e poor or neutral aromatic
Ph
Ready; Catalysis
O
Hayashi, Ito
Tetrahedron, 1994, 335
Hydrosilylation
Cu: an alternative to conjugate addn.
for early work with [(Ph3P)CuH]6 'strykers reagent' see stryker, jacs, 1989, 8818
O
Cu[(tol)-BINAP]Cl (5 mol%)
NaOtBu (5 mol%), PMHS (1.05 equiv)
glovebox
RMgBr; H+
n
n
OEt
TBAF
n
R
H
PMHS = polymethylhydrosiloxane
cheap, safe
O
Si
O
n
Dynamic kinetic resolution
O
1. Cu[(tol)-BINAP]Cl (10 mol%)
NaOtBu (1.7 equiv), PMHS (2.2 equiv)
R
n
R
R
Me
mw = 3200-1700
O
O
OSiR3
O
R
n
y
ee
n-alkyl
1
~80
94-98
iPr
1
88
94
Bu
2
82
87
-(CH2)2Ph
3
82
96
R
2. TBAF
R'
R'
O
O
Me
O
i-Pr
Ph
91% ee
91:9 cis:trans
89% yield
O
Bn
Ph
93% ee
93:7 cis:trans
94% yield
Me
i-Pr
93% ee
92:8 cis:trans
95% yield
Buchwald Jacs, 2000, 6797; 2002, 2892
Ph
91% ee
97:3 cis:trans
90% yield
6
Cu-Catalyzed Hydrosilylation: Mechanism and Application
OSiR3
O
OMe
LnCu
Cl
KOtBu
H
tBuOSiR3
LnCu
MeO
H
O
MeO
EtO2C
SiR3
OMe
(formed in situ from iodide)
O
MeO
OtBu
ClMg
MeO
Me
O
MeO
(±)MeO
O
O
O
OCuLn
H
H
LnCu
OtBu
H
SiR3
MeO-BIPHEP,
NaOtBu (1.2 equiv)
PMHS, tBuOH
>85%, 93%ee
SiR3
O
CH3
O
OMe
O
LnCu
CuLn
H
H
OMe
O
MeO
NaHMDS,
MeI
MeO
O
O
MeO
MeO
MeO
O
O
MeO
O
O
Buchwald, ACIE, 2005, 6177
Ready; Catalysis
Hydrosilylation
7
Ready; Catalysis
Hydrosilylation
Ready; Catalysis
Hydrosilylation
Ketone Hydrosilylation: a remarkable catalyst
some substrates
O
[CpW(CO)2IMes]+[B(C6F5)4]0.2 mol%, HSiMe2Ph
O
R
R
OSiMe2Ph
R
O
R
y ~90
-catalyst soluble in "a few molecules of substrate per molecule of catalyst"
-catalyst precipitates at end of reaction; decant product
-can recycle catalyst:
N
N
cycle
1
TOF(initial) 370
2
780
3
870
4
760
5
620
O
IMes
Dloumaev and Bullock
(Brookhaven National Laboratory)
Nature, 424, 2003, 530
8
Ready; Catalysis
Hydrosilylation
Enantioselective ketone hydrosilylation
OH
+
SiPh2H2
O
L=
OH
OH
O
RhCl3L*
AgBF4;
H3O+
"PyBox"
99% ee
80% ee
Nishiyama
Tet: asym, 1993, 143
O
N
N
5
95% ee
N
R
R
Note: MCl + AgBF4 or AgSbF6
[M][BF4] or [M][SbF6] + AgCl
AgBF4 $72/10g
AgSbF6 $42/5g (aldrich)
In general, hydrogenation works better than hydrosilylation
-usually see silane that does NOT give useful protecting group
-often used as 'benchmark' reaction for new ligands
-compare H2 - 100% atom effecient; HSiPh2H - 0.5% atom effecient
Ready; Catalysis
Hydrosilylation
and now for something different...
How to do reductions with an oxidant
Usual hydrosilylation requires O.A. to Si-H:
Si
H
Mn
+
Toste et. al. disovered [2+2] with metal oxo
I
OSiR3
R
H
O
PPh3
O
O
H
SiR3
PPh3
I
O Re OSiR3
H
PPh3
PPh3
I
Re OSiR3
PPh3
H
... but here it's
promoting a reduction
R
O
Toste, JACS, 2003, 4056
Alternative mech: Abu-Omar JACS, 2005, 15374
Mn+2
H
PPh3 High valent metal oxo usually
strong oxidizing...
Re O
R
R
Si
R
R
9
Ready; Catalysis
Hydrosilylation
Enantioselective imine hydrosilylation
CN
O
O
Cl Re SMe2
+
Cl
Cl
OPPh3
O
O
N
R
R = 4-tBu-Ph
1
R
P(O)Ph2
N
Ar
N
O
R
Cl
Re Cl
OPPh3
N
NC
HN
R
O
1 (3 mol%)
PhMe2SiH
HN
R
Ar
R
NP(O)Ph2
NP(O)Ph2
NP(O)Ph2
NP(O)Ph2
CH3
Ph
CH3
>98% ee
X = H, OMe, CF3, I
X
P(O)Ph2
TsN
CH3
n
n = 1,3; 95-96% ee
>99% ee
CH3
99% ee
Toste, JACS, 2005, 12462
Ready; Catalysis
Hydrosilylation
alkene silylformylation
OSiPh2H
O
1 mol% Rh(acac)(CO)2
1000 psi CO
SiPh2 OC
H
Rh
R
R
O
O
but
O
Si(iPr)2
as above
R
R
O
R
CO
note Si-C formation preceeds
H-C formation
OSi(iPr)2H
SiPh2
O
H
R
% yield
cis/trans
Me
allyl
iPr
67
64
79
4.5:1
4:1
6:1
CH3
allylic alcohol; can
repeat process
Tandem silylformylation/allylation
O
Si
Rh(acac)(CO)2
(1mol%)
1000 psi CO
H
OH
O
Si
O
O
i-Pr
Si
O
OH
OH
H2O2
i-Pr
i-Pr
59% yield
77:23 syn,syn:rest
i-Pr
O
i-Pr
Si
H
Rh(acac)(CO)2
(1mol%)
1000 psi CO
O
i-Pr
Si
O
1.TBAF
2. Ac2O
OAc
OAc
i-Pr
70% yield
23:1 1,5 anti:1:5 syn
Leighton JACS, 1997; 12416, 2000, 8587; 2001, 341
10
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computer, and then open the file again. If the red x still appears, you may have to delete the image and then insert it again.
Ready; Catalysis
Hydrosilylation
Aldehyde Silylformylation
O
OSiMe2Ph
0.5 mol% [(COD)RhCl]2
PhSi(H)Me2, CO
R
H
R
H
O
O
60%
H
H
H
H3C
OSiMe2Ph
OSiMe2Ph
OSiMe2Ph
O
Me2N
O
AcO
70%
80%
Proposed:
HSiR3
LRhCl
OSiMe2Ph
L
H
R
L
Rh
Cl
H
SiR3
O
R
O
L
L
Rh
H
O
CO
L
Cl
R3SiO
L
R
Rh
Cl
H
H
R
OSiR3
Wright, JACS, 1993, 2059
11
Ready; Catalysis
Hydrozirconation
Hydrozirconation
Cl
Zr
H
Schwartz's reagent
Cl
Zr
2o alkyl zirconium complexes
isomerize to 1o alkyl zirconium species
via β-hydride elimination/insertion sequence.
Ultimate formation of strongest Zr-C bond
Zr
R
Cl
H
not favored: Zr(IV) (d0) can't
backbond
Cp
Cl
Cp
H
Zr
Zr
Cp
Cl
Cp H
Zr
Cl
H
Zr
slight excess
(usually 1.1 equiv)
Schwartz JACS, 1974, 8115
1975, 679;
With 1 equiv ZrH
with 1.1 equiv ZrH
Ready; Catalysis
+
16
2
Cl
Zr
84
98
:
Hydrozirconation
Electrophilic Functionalization
HCl
H
Br2 or NBS
Zr
Cl
Zr
Cl
Br
R
AcCl
Cl
Reactions are stereospecific:
Maintain olefin geometry or
stereochemistry
R
Br
R
R
O
Br
Schwartz JACS, 1975,
228; ACIEE 1976, 333
Review: Labinger, Com.
Org Syn vol 8, 667
R
H2O2, NaOH
HO
R
CO insertion, functionalization
O
HCl
H
Zr
Cl
CO (1.5atm)
Zr
Br2/MeOH
Cl
MeO
R
O
O
BF3 Et2O
R
H
LnM-X
Cl
R
M
stereospecific
M = Al, B, Cu, Hg, Ni, Pd, Sn, Zn
R
+
R
O
R
R
OH
Transmetallation (most common application. Great way to make vinyl organometallics)
Zr
R
O
Zr
Cl
X
Wipf, tetrahedron, 1996, 12853
12
Ready; Catalysis
TIPSO
Hydrozirconation
TIPSO
1. Cp2Zr(H)Cl (3eqiv)
2. NBS
MeO
1. tBuLi
2. MgBr2
3. Me
CHO
Me
MeO
Br
TIPSO
intermediate in synthesis of FK506.
Schreiber jacs, 1990, 5583
1. Cp2Zr(H)Cl ClZn
2. ZnCl2
O
survived
I
R3SiO
O
Me
O
Me
1. Cp2Zr(H)Cl
2. I2
3. steps
O
HO
R
OH
I
R3SiO
Me
MeO
Me
O
Me
O
I
N3
Me
Pd(PPh3)3
6.5 mol%
Me
Me
N3 reduced by ZrH
Free OH OK
Me
Me
O
O
N3
Me
R3SiO
O
Intermediate in syn of FR901464
Jacobsen, JACS, 2000 10482
Ready; Catalysis
I
Hydrozirconation
R'
no added ligand
HZr(Cl)Cp2
R
Br
H
H
+
Zr(Cl)Cp2
R
Pd(OAc)2
LiBr
R
R'
H
β-H, but no elimination
Fu, JACS, 2004, 82
O
EtO
H
O
5
99%
Ph
EtO
OTBDPS
5
99%
BnO
O
NC
3
68%
Ph
N
O
O
5
77%
Ph
OTHP
5
73%
EtO
Et
Et
5
85%
13
Ready; Catalysis
Hydroacylation
Hydroacylation
O
O
Desired Reaction/obstacle:
R
H
+
R
R
M
increased CO pressure would decrease
decarbonylation but would also retard CH
insertion
R
H
N
R
O
150 oC, 24 h
+ R'
R
RH
(20 mol %)
R
13 egs
R = H, Alkyl
R' = aryl, alkyl
R'
49-92%y
NH2
pyridine recruits aldimine to Rh;
accelerates CH activation
-H2O
N
R
H
(PPh3)3RhCl (5 mol%)
O
O
O
M
N
H
P
N
Rh
Cl
R
H
H
N
-P
P R
P2RhCl
N
NH2
N
P
+P
O
R
N
H2O
R'
Cl
N
P
R'
Cl
Jun JOC, 1997, 1200
with alkynes: ACIEE, 2002,
2146
R
H
N
R
N
Rh
R
N
Rh
R
R
Ready; Catalysis
Hydroacylation
Intramolecular hydroacylation
O
20 mol% [Rh(dppe)][ClO4],
H
O
O
RhLn
RhLn
ethylene, 65oC
O
H
O
O
O
PO
2
65%
cis: 63%
trans: 65%
58%
Shair, JACS, 2000, 12610
O
Me
O
Me
[Rh(dppe][BF4]
H
R
??
RhH
R
O
R
O
Rh
R
Me
H
Me
R = n-Hex 75%
R = Ph
88%
Fu, JACS, 2001, 11492
14
Ready; Catalysis
H-X Additions to Olefins
15