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M.C. White, Chem 153 Hydroformylation -204- Week of October 29, 2002
Monohydride catalysts
H2Rh(CO)(PPh3)n
Cl
H
H
δ−
δ+
HCl
σ-bond metathesis
external amine base may drive the rxn forward by forming insoluble amine hydrochloride salts
Ph3P
Rh(I)
Ph3P PPh3
Cl
CO
Addition of CO, a strong π-acid, enhances the electrophilic character of the Rh promotingheterolytic σ-bond metathesis with H2.
Rh(I)PPh3
PPh3
Cl
CO
Ph3P Rh(I)PPh3
PPh3
H
CO
Ph3P
commercially availablehydroformylation pre-catalyst
COPPh3
Rh(I)PPh3
PPh3
H
CO
OC
PPh3
OC
Rh(I)H PPh3
CO
active monohydride catalyst
A dihydride catalyst may result inreductive elimination of theintermediate metal alkyl with a second hydride (favored over CO insertion).This would result in undesiredhydrogenation product.
Hydroformylation proceeds with RhCl(PPh3)3, however there is an induction period. It was shown that in thepresence of a base the induction period is removed. What is the role of the base? Indicate the active catalyst for this process and specify how it is formed under the reaction conditions. (Question 3, Q&A pg. 200).
Ph3P
Rh(I)
Ph3P PPh3
Cl
C3H7 C3H7
O
Hcat.
H2:CO (1:1, 100 atm), 70oC
16 h, >99% conversion
C3H7
O
H+
linear: branched (2.7:1)
M.C. White, Chem 153 Hydroformylation -205- Week of October 29, 2002
Isomerization/hydroformylationA rhodium hydroformylation catalyst was reported that hydroformylates internal alkenes to produce linear aldehydes preferentially. Provide a detailed mechanism for this transformation. Rationalize the effect of the bulky phosphineligand in the observed regioselectivity. (note: Question 5; Q&A pg. 202)
O
HC5H11 C5H11
Rh(I)CO
COO
O
R
R 0.1 mol%
Ligand, 1 mol%
H2/CO (20 atm), 80oC, toluene
18h n
+ mixture of branched aldehydes
iso
O
t-But-Bu
O
P
O
P
1
Ligand
PPh3
1
n:iso
0.9
9.2
% 1-nonanal
46%
90%
H2
Rh(I)H CO
COR
O
OH
R
sigma-bond metathesis?
1O
t-But-Bu
R
RPR
R
P
Rh(I)
H CO
note: formationof the dihydridewould result incompetitive hydrogenation
R
RPR
R
P
Rh(I)
HR'
R
RPR
R
P
Rh(I)
R'
H
R
RPR
R
P
Rh(I)R'
H
R
RPR
R
P
Rh(I)
OC
R
R
RPR
R
P
Rh(I)
OC
O
R
R
CO
H2
n-aldehyde
bulky ligand may promote hydrometallation to form less sterically hindered primary Rh alkyl.
Proposed mechanism
CO
CO
CO
CO
via Rh(III) dihydride
van Leeuwen ACIEE 1999 (38) 336.
M.C. White, Chem 153 Hydroformylation -206- Week of October 29, 2002
One-Pot Hydroaminomethylation
Rh(I) (BF4-)
R RN
P
P
F3C CF3CF3
CF3
CF3
CF3F3C CF3
+
+ Ligand
0.1 mol%0.4 mol%
H2:CO (50 atm:10 atm), piperdine (1 eq), tol/THF,
120oC, 24h R= Me, 97% yieldn:iso (90:10)
Subtle ligand effects observed.Comparable ligand with p-CF3substituted aryls gave only 11% yield of the amine products. The majorside product was the enamine.
Non-cyclic 1o and 2o amines also resulted in high yields of linearhydroaminomethylated products.
Beller Science 2002 (297) 1676.
R
R
RPR
R
P
Rh(I)
H CO
R
R CHO
R
CHO
R
CHO
R
NR2
RNR2
R
NR2
R
NR2
RNR2
R
RPR
R
P
Rh(I)
H CO
H2
H2
H2
R
NR2
possible monohydride catalyst
olefin isomerization
H2/CO
H2/CO
hydroformylation
hydroformylation
HNR2
HNR2
HNR2
non-catalyzed
non-catalyzed
non-catalyzed
Most hydroformylation catalysts showlow isomerization activity in the presenceof strong σ-donor ligands such as amines. This constitutes the first report of olefinisomerization/ hydroformylation in thepresence of amines.
possible monohydride catalyst
linear amines are valuable chemical feedstocks.
Thermodynamic equilibrium mixturecontains less than <5% of terminal olefin,indicating that hydroformylation of theterminal olefin must occur at significantly higher rates than the process with internalolefins and with high n-selectivity
M.C. White, Chem 153 Hydroformylation -207- Week of October 29, 2002
Hydroformylation of alkynesAcetylenes have lower reactivities than alkenes towards hydroformylation. This is attributed largely to formation of stable metal-acetylene complexes that resist hydroformylation under typical conditions.
(OC)3Co Co(CO)3
C
C
O
O
(OC)4Co Co(CO)4
R'R
+2 CO
(OC)3Co Co(CO)3
R R'
Takahashi Bull. Chem. Soc. Jpn. 1988 (61) 4353.
Under forcing conditions of high CO pressure and high temperatures, terminal acetylenes are converted to fully saturated aldehydes.
CH3H3C
Rh(I)PPh3
PPh3
H
CO
Ph3PO
O
PPh2
PPh2
H
H
+
(0.01 mol%) (0.05 mol%)
H2/CO (1:1, 100 atm), 80oC, 24 hrs, 20% conversion CHO32%
CHO
(S) +
68%
CHO
H2/CO H2hydroformylation of cis-2-butene gave analdehyde with the same configuration. Theisolation of (E)-2-methylbutenal is taken tobe the strongest evidence that the fullysaturated aldehyde arrises via hydrogenation of an initially formed unsaturated aldehydeintermediate.
internal alkynes
terminal alkynes
HC6H13
Rh(I)PPh3
PPh3
H
CO
Ph3PO
O
PPh2
PPh2
H
H
+
(0.01 mol%) (0.05 mol%)
H2/CO (1:1, 100 atm), 80oC, 24 hrs, 78% conversion C6H13
CHO
(S)
27%C6H13 73%
CHO+
no 1-octenal or 2-methyloctenal was observed, suggesting that the fully saturated aldehydes arrise via hydroformylation of highlyreactive alkene intermediates. However, when 1-octene washydroformylated under these conditions, (R)-2-methyloctanal wasformed as the major enantiomer.Salomon TL 1974 (49) 4285.
M.C. White, Chem 153 Hydroformylation -208- Week of October 29, 2002
Hydroformylation of internal alkynesC3H7C3H7
C3H7 C3H7
CHO
C3H7 C3H7
CHO
C3H7C3H7C3H7 C3H7
CHO
C3H7 C3H7
CHO
PdCl2(PCy3)2 (2mol%), NEt3 (60 mol%)
H2/CO (1:1, 35 atm), benzene 150oC, 1h
20% conv. 1, 16 % 2, <1 %
PdCl2(PCy3)2- Co2(CO)8 (2mol%)
NEt3 (60 mol%), H2/CO (1:1, 35 atm)
benzene 150oC, 1h100% conv. 1, 95 % 2, 2 %
note: after 6 hrs, reaction went to 84% conversion generating 83% 1 and <1 % of 2.
Co metal is thought to promote the CO insertion into the Pd-Cbond of the vinylpalladiumintermediate to form anacylpalladium species.
+
+
A possible mechanism:
ClPd(II)
(Cy)3P Cl
P(Cy)3 ClPd(II)
(Cy)3P H
P(Cy)3
H2 HCl
heterolytic cleavage
ClPd(II)
(Cy)3P HR
R
P(Cy)3
ClPd(II)
(Cy)3P
R
R
(OC)4CoPd(II)
(Cy)3P
(OC)4CoPd(II)
(Cy)3P
R
R
O
R
R
(OC)4CoPd(II)
(Cy)3PH
(OC)3CoPd(II)
(Cy)3PR
R
C
O
(OC)4CoPd(II)
(Cy)3P HR
R
migratoryinsertion
[Co(CO)4]-
H2
P(Cy)3
P(Cy)3
PCy3
CO
σ-bondmetathesis
Because the productselectivity obtained for themonometallic Pd catalyst andthat of the heterobimetalliccatalytic system are similar,the chemistry is thought toproceed on the Pd center.The Co2(CO)8 accelerates the rate of the reaction. It's rolemay be to deliver CO to thePd center, therebyaccelerating CO insertion.
Hidai J. Chem. Soc. DaltonTrans. 1995 3489. Reaction ofPdPh(PMe3)3(OTf) with[Co(CO)4]- results in facile COinsertion into the P-aryl bond togive (PMe3)2(PhCO)PdCo(CO)4.
Hidai JACS 1997 (119) 6448. For a Rh system w/bulky ligand see: Buchwald ACIEE 1995 (34) 1760.
M.C. White, Chem 153 Silylformylation -209- Week of October 29, 2002
Silylformylation of alkynes
Me H
Me H
SiMe2PhOHC
CsFEtOH
Me H
HOHC
C3H7 Me
C3H7 Me
SiMe2PhOHC
CsFEtOH
C3H7 Me
HOHC
Rh4(CO)12 (1 mol%)
Me2PhSiH (1 eq)
NEt3 (1 eq), CO (29 atm)
2h, 100oC
terminal sp C is selectively silylated
99% yieldZ:E (80:20)
Z-isomer is the kinetic product. E-isomer arises from isomerization under thecarbonylation conditions.
terminal alkynes:
internal alkynes:
Formal product ofhydroformylation ofterminal alkynes withopposite regioselectivity.
Rh4(CO)12 (1 mol%)
Me2PhSiH (1 eq)
NEt3 (1 eq), CO (29 atm)
2h, 100oC85% yield
Z:E (70:30)sp C bearing thebulkier substituent isselectively formylated
tri-substituted olefin
Other substituents tested: Ph, CO2R.
Matsuda JACS 1989 (111) 2332.
Matsuda OM 1997 (16) 4327.
Rh4(CO)12metal CO clusters are known todecompose to lower nuclearity metal CO complexes under CO pressureR3SiH
(CO)4Rh(I) SiR3
(CO)3Rh(I ) SiR3
R'
(CO)4Rh(I)
R'
R3Si
(CO)3Rh(I)
O
R'
R3Si
(CO)3(SiR3)Rh(III)
O
R'
R3Si
H
R' H
SiR3OHC
CO
COR3SiH
oxidativeaddition
migratory insertion
migratoryinsertion
When R3Si-D was used,alkenal deuterated at theformyl carbon was produced >98%. When deuteratedalkyne was used, alkenaldeuterated at the vinylcarbon was selectivelyisolated (>94%).
M.C. White, Chem 153 Silylformylation -210- Week of October 29, 2002
Silylformylation of epoxides
Murai JOC 1993 (58) 4187.
OCRh
OC Cl
ClRh
CO
COCl[Rh] SiR3
H
HSiR3exact structurenot known
O
O SiR3
+
[RhI II]
OSiR3
RhIII
OSiR3
H
H
O
RhIII HCl
Cl
Cl
CO
[RhI]Cl
HSiR3
OSiMe2Ph
CHO
nucleophilic epoxide ring
opening
stereospecificmigratory insertion
Proposed mechanism:
O
n= 0,1
OCRh
OC Cl
ClRh
CO
CO1 mol%
HSiMe2Ph (1.2 eq), CO (50 atm)
N
N 40 mol% n= 0,1
OSiMe2Ph
O
H
Stereospecific epoxide ring opening: no cis product observed.
n = 0, 72% 1, 82%
O
OCRh
OC Cl
ClRh
CO
CO1 mol%
HSiMe2Ph (1.2 eq), CO (50 atm)
N
N 40 mol%
CHO
OSiMe2Ph+
OSiMe2Ph
CHO
60% yieldlinear: branched (77:23)
note: 1-methylpyrazole is essential toring-opening silylformylation. w/out it cyclopentanol silyl ether is the mainproduct observed. Although NEt3 waseffective at promoting the rxn withcyclohexene, 1-methylpyrazole wasuniquely effective at promotingring-opening silylformylation over awide range of substrates (other aminestried: pyridine, pyrrole, DBU failed).Itis suggested that 1-methylpyrazolepromotes CO incorporation, howeverno discussion of it's mechanism ofaction is presented (perhaps it's actingas a ligand to the Rh).
Co2(CO)8 was alsotried; however yieldswere significantlylower (51% based onsilane, 17% based onepoxide which wasused in 3-fold excess).
Muria Synlett 1996 414.
M.C. White, Chem 153 Silylformylation -211- Week of October 29, 2002
“Silylformylation” of alkenes
Observed product: silyl enol ether of formylated alkene
C4H9
RhCl(PPh3)3 (1.3 mol%)
HSiEt2Me (1 eq)
Et3N (3 mol%), CO (x atm),
benzene, 140oC, 20h
C4H9
OSiEt2Me
88%
linear:Z: 56%; E: 23%
+
C4H9
MeEt2SiO
branched:Z: 18%; E : 13%
linear alkenes
cyclic alkenes
Similar product ditributions were obtained with CO2(CO)8, Ru3(CO)12; however theoverall yields were lower (57% and 40%respectively).
Murai ACIEE 1977 (16) 881.
Co2(CO)8 (0.7 mol%)
HSiEt2Me (1 eq)
CO (X atm)
benzene, 140oC, 20h
OSiEt2Me
89%
OSiEt2Me
product appears if rxncarried out at highertemperatures or with a high concentration ofcatalyst
Murai ACIEE 1977 (16) 174.
Desired silylformylation product:
Rcatalyst*
CO, R3Si-H R
O
H
SiR3
R
O
H
OH* *Tamao
oxidation
acetate aldol equivalentpolyacetate polyol
M.C.White Chem 153 Silylformylation -212- Week of October 29, 2002
MechanismOSiEt2Me
DCo2(CO)8 (0.7 mol%)
DSiEt2Me (1 eq)
CO (X atm)
benzene, 140oC, 20h
91% incorporation of the deuterium in the vinylicposition
Proposed mechanism:
(OC)3Co Co(CO)3
C
C
O
O
(OC)4Co Co(CO)4
D SiR3
(OC)4Co Co(CO)4
σ-bond metathesis
D-SiEt2Me DCo(CO)4+ R3SiCo(CO)4
catalyst activation:
1st catalytic cycle:
DCo(CO)4D-SiEt2Me HCo(CO)4
OSiEt2Me
D
D
+ CO (X atm) +
catalytic cycle:
HCo(I )(CO)4H
Co(CO)4
O
Co(CO)3
O
Co(III)SiR3(CO)3
D
O
D
R3Si Co(CO)4Co(CO)4
SiR3
O
D
OSiR3
Co(CO)4
D
H
OSiEt2Me
D
+
DSiR3
Muria ACIEE 1979 (18) 837.
M.C. White, Chem 153 Silylformylation -213- Week of October 29, 2002
Intramolecular alkene silylformylation
Alkyl
OSi
Ph Ph
H
Alkyl
O SiPh2 O
H
ORh(I)O CO
CO
alkyl = Me allyl i-Pr -CH2CH2OTBS
alkyl = Me, 67%, 4.5:1 (cis: trans) allyl, 64%, 4:1 i-Pr, 79%, 6:1 -CH2CH2OTBS, 60%, 4:1
1 mol%
1000 psi CO,
benzene, 60oC
i-Pr
OSi
i-Pr i-Pr
H ORh(I)
O CO
CO1 mol%
i-Pr CH3
O SiPh2
1000 psi CO,
benzene, 60oC
Silylformylation reactivity depends on the natureof the silicon substituents. If isopropyl is replacedfor Ph in this system, hydrosilylation results.Interestingly, when phenyl homoallylic alcoholsare used as substrates, phenyl substituted silaneslead to hydrosilylation whereas diisopropyl silanes result in silylformylated products.
R groups on Si in conjunction w/R' maydictate which olefin binding mode ispreferable. Binding perpendicular toRh-Si bond results in poor orbitalalignment with Rh-Si but good orbitalalignment w/Rh-H. This may lead topreferential migratory insertion of H that results in hydrosilylated product.
Leighton JACS 1997 (119) 12416.
Proposed mechanism:
R'
OSi
R R
H
ORh(I)O CO
CO
ORh(Iii)
O
H
CO
R2Si
OR'
ORh(Iii)
O
H
CO
CO
O
R2Si
R'
ORh(Iii)
OH
CO
OR2Si R'
O
R'
O SiR2 O
H
silane migratory insertion
oxidative addition
CO migratoryinsertion
reductive elimination
ORh(Iii)
O
H
CO
R2Si
OR'
or
i-Pr CH3
O SiPh2
M.C. White, Chem 153 Silylformylation -214- Week of October 29, 2002
Intramolecular silylformylation-allylsilylation
i-Pr
OSi
HO
Rh(I)O CO
CO1 mol%
1000 psi CO,
benzene, 60oC
i-Pr
O Si O
H i-Pr
O Si O
H Hi-Pr
OH OHOHH2O2,NaHCO3MeOH
alkenes
59% overall yield77:23 (syn,syn triol: rest)
Leighton JACS 2000 (122) 8587.
i-Pr
OSi
HO
Rh(I)O CO
CO1 mol%
1000 psi CO,
benzene, 60oC
i-Pr
O Si O
H i-Pr
O Si O
i-Pr
OAc OAc
1. TBAF2. Ac2O
alkynes
70% overall yield23:1 (1,5-anti: 1,5-syn)
Leighton ACIEE 2001 (40) 2915.
Leighton JACS 2001 (123) 341.Schreiber JACS 1993 (115) 3360.
OTIPSOSi
HO
Rh(I)O CO
CO
H2O2, NaHCO3MeOH
OTIPSOHOHOHOPMB O O O O O O O O OH1 mol%
1000 psi CO, benzene, 60oC1.
2.55% overall yield
Formal synthesis of Mycoticin A
Schreiber intermediate to Mycoticin A
M.C. White, Chem 153 Hydrocarbonylation -215- Week of October 29, 2002
Hydroesterification
CO (300 atm), MeOH
100oCMe Me
EtPh3P
Pd(II)Cl PPh3
Cl catalytic
Me Me
CO2MeH
Et
only source of hydrogen is protic solvent
94:6 dr ( hydroesterification is predominantly cis)
High pressure conditions:
Consiglio Gazz. Chim. Ital. 1975 (105) 1133.
Ph3P
Pd(II)Cl PPh3
Cl
Ph3P
Pd(II)Cl PPh3
O
Cl
Ph3P
Pd(II)Cl PPh3
O
OMe
HCl
Pd(II)Cl PPh3
O
OMeR'
Pd(II)Ph3P Cl
R'
CO2Me
PPh3
MeOH
PPh3
HCl
RCO2Me
Proposed carboxylate insertion mechanism:
Stille Comprehensive Organic Synthesis 1993; Volume 4; Chapter 4.5
Insertion of the esteroccurs at the leaststerically hinderedolefinic carbon
M.C. White, Chem 153 Hydrocarbonylation -216- Week of October 29, 2002
CO (150-400 atm), H2NR'
150-200oC
catalytic
only source of hydrogen is H2NR'
Natta JACS. 1952 (74) 4496.
High pressure and high temperature conditions:
Co2(CO)8
O
NHR'+
O NHR'
MeOH can also be used under these conditions to obtain the methyl ester
Hydroamidation
The clear limitation of these systemsis the extreme temperatures andpressures that are necessary toeffect the hydrocarbonylative process
Proposed hydride mechanism:
Stille Comprehensive Organic Synthesis 1993; Volume 4; Chapter 4.5
Independently prepared Co-H has beenshown to effect both hydroamidation and hydroesterification processes.
Hemiacetal intermedaite is speculative and basedon the reaction of ananalogous manganesecomplex with alcohols.
(OC)3Co Co(CO)3
C
C
O
O
(OC)4Co Co(CO)4
H2NR'
?
(OC)4Co H
(OC)3Co
RH
R
CO
(OC)3CoR
(OC)4CoR
CO
(OC)4Co R
O
H2RN
(OC)4Co R
O NHRH
R
O
NHR'
M.C. White, Chem 153 Carbonylation -217- Week of October 29, 2002
The palladium catalyzed carboxylation of a variety of aryl iodides can be performed under mild conditions of temperature (rt) and CO pressure (1 atm). Propose a catalytic cycle for this transformation.
I
X
Pd(OAc)2 1 mol%K2CO3 (4 eq), H2O/DMF, rtCO (1 atm)
CO2H
X
X = NO2, 90% Cl, 92% CN, 98% NH2, 68% OH, 92%Pd(Cl)2(PPh3)2 used
Beletskaya JOMC 1988 (358) 563.
Palladium catalyzed carbonylation of Ar-X
PdII
X
I
PdII
IO
X
-OH
PdII
I
X
-O
O
H
PdII
H I
Pd0Ln
L = DMF
Ln
Ln
Ln
Ln
A similar system has been developed that uses aryl triflates:
O
TfO
Pd(OAc)2 3 mol%dppf (6 mol%), NEt3 (2 eq)MeOH,DMF,CO (1 atm)
60oC, 2h
O
MeO2C81%
Treatment with piperdine under the same conditions yielded theamide in 61% yield.
Ortar TL 1986 (27) 3931
Proposed mechanism:
M.C. White, Chem 153 Carbonylation -218- Week of October 29, 2002
Carbomethoxylation of terminal epoxides
(OC)4Co Co(CO)4
?
(OC)4Co H
MeOH
R
O
R
O+
H
Co(CO4)
R
OH
Co(CO4)
R
OH
Co(CO4)
O
MeOH
R
OH
Co(CO4)
O OH
Me
R
OH O
OMe
Proposed mechanism:
Using the same catalyst, the addition of3-hydroxypyridine (based on a patent report)results in significantly improved yields and appearsto allow the system to be run under milderconditions of temperature (55-65oC) and COpressure (41 atm). The role of this co-catalyst is not addressed; however, we've seen this amine"additive"effect before in the ring-openingsilylformylation of epoxides.
3-hydroxypyridine
CO (41 atm), MeOH
55-65oC
5 mol%Co2(CO)8
R
O
R
OH O
OMe
R = CH3, 92% yield C6H13, 96% CH2Cl, 96% CH2OBn, 86%
>99% ee >99% ee
N
OH
10 mol%
Reaction was highly regioselective andstereoretentive. Enantiomerically pure terminalepoxides result in enantiomerically pureβ-hydroxy carbonyls (valuable synthetic building blocks).
CO (238 atm), MeOH
190oC
catalyticCo2(CO)8O
OH O
OMe
β-hydroxybutyrate22% yield
+ < 4% methoxypropanol
The original report:
Eisenmann JACS 1961 (26) 2102.
Jacobsen JOC 1999 (64) 2164.
M.C.White/M.S. Taylor Chem 153 Carbonylation -219- Week of October 29, 2002
Pd catalyzed hydroxycyclization/carbonylation/lactonization
C6H13
OH OH O
OO
H
H
H
C6H13CO
NaOAc / AcOH
PdCl2, CuCl 2
Kitching JOC. 2001 (66) 7487
C6H13
OH OHPdCl2 OH
OHH
H
C6H13
O
OO
H
H
H
C6H13
PdCl2
O
OH
H
H
H
C6H13
Pd
CO O
OH
H
H
H
C6H13
O
PdCl
CO
Wacker-typereaction
carbonylation
NaOAc O
OH
H
H
H
C6H13
PdCl
Cl
+ NaCl, AcOH
O
O
H
H
H
C6H13
O
Pd ClH
+
+ PdHCl
After reductive elimination to Pd0, reoxidation with CuCl2regenerates PdIICl2
Proposed mechanism:
M.C. White, Chem 153 Decarbonylation -220- Week of October 29, 2002
H
O
MePd-C
MeMe
Me
An early report using palladium metal on carbon (heterogeneous catalysis) to effect decarbonylation of aldehydes yielding mixtures of alkene and alkane products..."Recently the usefulness of palladium in organic syntheses has attracted much attention" (1968).
6
190 oC, 2 h
6 6+
57 % 27 %
+ H2 + CO
CH3R
Pd
H
H CO
R
PdLn CO
CO
R
Pd
H Ln
H CO
H2
Pd
H
Ln CO
R
O
HR
Pd
H
O
R
L n
oxidativeaddition
deinsertionreductive
elimination
Pd(0)metallic Pd
β-hydrideelimination
reductiveelimination
Proposed mechanism
The oxidative addition of aldehydesto metallic palladium to form the acyl complex was not a known reaction.This mechanism was proposed byTsuji and coworkers based onestablished analogous reactions withacyl halides. Part of the evidencepresented for this oxidative additionwas that metallic palladium partiallydissolves in acyl halides.
This system has clear limitations including high reaction temperatures, theformation of product mixtures, and heterogeneity which makes it difficultto tune the catalyst's reactivity. Thus a more useful, homogeneouscatalytic system was sought. Based on this postulated mechanism fordecarbonylation with palladium, it was reasoned that a complex that couldeffect this process efficiently should have the following properties: (1) low valent, coordinately unsaturated metal (e.g. 4-coordinate d8 complex) tomake possible the oxidative addition of aldehydes or acid halides and (2)the complex should be able to coordinate carbon monoxide. Wilkinson'scatalyst satisfies both of these requirements.
CO is thought to readily dissociate at
200 oC, thus rendering this process
catalytic in metallic palladium at these
temperatures.
Tsuji TL 1965 4565, JACS 1968 94-98.
Palladium-mediated decarbonylation of aldehydes
M.C. White, Chem 153 Decarbonylation -221- Week of October 29, 2002
RhCl PPh3
Ph3P PPh3
O
H
CH2Cl2
RhCl PPh3
Ph3P CO PPh3+ + +
roomtemp
+ H2
78 % Yieldratio of hexane:hexene 6:1
+
dark red solutionin CH2Cl2
yellowcolor change signifies
reaction completion
This reaction is very senstitve to sterics. Whereas primary aldehydes can be decarbonylated at room temperature, secondary aldehydes require high temperatures (>100 oC).
Wilkinson's catalyst
RCH3
RhClPh3P
PPh3
CO
X
RhPh3PPh3P
Cl
RhHPh3P
CO
Cl
PPh3
R
RhCl PPh3
Ph3P PPh3
RhPh3PPh3P
H
Cl O
R
R
O
Hoxidative addition
deinsertionreductiveelimination
CO
Proposed mechanism:
The carbon monoxide ligand does not dissociate atmild temperatures rendering this processnon-catalytic. Attempts to effect CO dissociation viathermal and photochemical approaches met with little success.
Tsuji JACS 1968 99-107.
Decarbonylation of primary aldehydes mediated by Wilkinson's catalyst
M.C. White, Chem 153 Decarbonylation -222- Week of October 29, 2002
Catalytic decarbonylation of primary aldehydes at room temperature
RhCl PPh3
Ph3P CO R N3
O
RhCl PPh3
Ph3P N
CO
N N
O
R
RhCl PPh3
Ph3P N2
R NCO
ON2
RhC
NCl
PPh3
PPh3
O
R
O
O'Connor and coworkers have found a way to close this catalytic cycle (25 years after Tsuji's initial report)...it was known in the literature that chlorocarbonylbis-
(triphenylphosphine)rhodium reacted with butanoyl azide at -70 oC to give the corresponding dinitrogen complex which decomposes in chloroform solution at room
temperature.
+
Ukhin Izv. Akad. Nauk SSSR, Ser. Khim. 1967 957.Collman JACS 1968 90 5430.
O
PN3PhO
PhO
DPPA
RCH3
RhCl
Ph3PPPh3
CO
O
PNCO
PhOPhO
RhH
Ph3P
CO
Cl
PPh3
R
RhPh3P
Ph3PCl
RhCl PPh3
Ph3P PPh3
R
O
H
RhPh3P
Ph3P
H
Cl O
R
oxidativeaddition
deinsertionreductiveelimination
O'Connor and coworkers found that in contrast to other azideswhich were decompsed under the reaction conditions, the relativelystable azide diphenylphosphoryl azide (DPPA) was effective inremoving the CO ligand from chlorocarbonylbis(triphenyl-phosphine)rhodium and was thus able to render thedecarbonylation reaction catalytic with Wilkinson's catalyst.DPPA is a readily available, non-explosive, high-boiling azide used as a reagent in peptide synthesis.
Limitations of this catalytic system include the requirement for theuse of a syringe pump to add the DPPA in addition to the generation of stoichiometric isocyanate byproduct
O'Connor JOC 1992 5075-5077.
M.C. White, Chem 153 Decarbonylation -223- Week of October 29, 2002
Pd-catalyzed decarbonylative olefination of aryl esters
O
ONO2
N
RR
HO
NO2
CO
PdCl2, LiCl
NMP, 160 oC
16 h
++ +
R = p-C(O)CH 3 85 % yieldR = p-Cl 74 % yieldR = m-CH3 52 % yield
Gooβen and coworkers recently reported a method that makes it possible to use aryl esters as substrates in a Heck coupling. As shown above, the reaction is more efficient for substrates with electron withdrawing groups than those with electron donating groups. Propose a detailed catalytic cycle to account for this overall transformation. (Hint: the Pd catalyst formed in this process is capable of inserting into the single carbon-oxygen bond of an ester.
Gooββββen ACIEE 2002 (41) 1237.
PdLL
PdRO
L
PdRO
LH
R'
PdRO
LH
L
ROH
R'
R'
PdRO
L
O
O
R
PdLOR
O
CO
PdRO
L CO
R'
oxidativeaddition
deinsertion
migratoryinsertion
β-hydrideelimination
reductiveelimination
R
H
H
Ph
M.C. White, Chem 153 Hydroacylation -224- Week of October 29, 2002
C4H9
O
H
RhCl PPh3
Ph3P PPh3
+
R
O
H+ R'
catalystR
O
R'
Direct route to di-substituted ketones from unactivated precursors
Observed intermolecularly: decarbonylation
saturatedsolution
CHCl3Rh
Cl PPh3
Ph3P CO+ C5H12
Miller JACS 1976 (98) 1281.
stiochiometric
O
HRh
Cl PPh3
Ph3P PPh3
CHCl3
10 mol%
O
14%
When the solution was saturated w/ethylene, the yield increased to 78%. Thought to occupy free coordinationsite on Rh complex necessary fordecarbonylation.
Hydroacylation
RhCl PPh3
Ph3P PPh3
RhCl PPh3
Ph3P
RhPh3P
Ph3P
H
Cl
RhPh3P
Ph3P
H
Cl
O
O
RhPh3P
Ph3P
Cl O
RhPh3P
Ph3PCl
O
O
H
Proposed mechanism:
An improved process was later developed byLarock which utilizes a Rh(I) catalystwith electron rich trarylphosphines.Larock JACS 1980 (102) 190.
M.C. White, Chem 153 Hydroacylation -225- Week of October 29, 2002
Chelate-assisted intermolecular hydroacylation
R
O
H+
N NH2
N N
2-amino-3-picoline RH
THF, reflux3Å mol. sieves
Rh(I)
Cl PPh3
Ph3P PPh3
THF, 55oC Rh(III)
H
C
N N
RCl
Ph3P
PPh3
R = Ph, >90% p-OMePh, >90% p-ClPh, >90%
isolated and characterized by NMR and IR.
N N
PhH
C6H13
Rh(I)
Cl PPh3
Ph3P PPh3
5 mol%
160oC, THF (sealed)
1.
2. H+ workup
Ph
O
C6H13
10%
+
First report Suggs JACS 1979 (101) 489.
Ph
O
H
C4H9+
Rh(I)
Cl PPh3
Ph3P PPh3
2 mol%
160oC, toluene (sealed)
N NH2 7 mol%
Ph
O
C6H13
72%
One-Pot: Jun JOC 1997 (62) 1200. What's the difference?
R
O
H+ R' R
O
R'R
N
H
masked carbonyl can no longer decarbonylate
A Lewis basic group on thesubstrate binds to the metal and directs it towardsinsertion into the imine C-H .
LB
H2OM
M.C. White, Chem 153 Hydroacylation -226- Week of October 29, 2002
Chelate-assisted intermolecular hydroacylation
Ph
O
H
C4H9+
Rh(I)
Cl PPh3
Ph3P PPh3
2 mol%
160oC, toluene (sealed)
N NH2 7 mol%
Ph
O
C6H13
72%
Proposed mechanism:
One-Pot: Jun JOC 1997 (62) 1200. What's the difference?
N NH2
Ph
O
H
N N
Ph
Rh(I)
Cl PPh3
Ph3P PPh3
H
Rh(III)
H
N N
PhCl
Ph3P
PPh3
Rh(III)
H
N N
PhCl
Ph3P
R
Rh(III)
N N
PhCl
Ph3P
R
N N
PhR
oxidativeaddition
H2O
H2O
Ph
O
C6H13
+
M.C. White, Chem 153 Hydroacylation -227- Week of October 29, 2002
Hydroacylation of 1-alkynes with aldehydes: chelation assistance
R H
OMe
H
NH2N
Rh(PPh)3Cl (5 mol%)
OH
O
R
O
Me+
40 mol%
20 mol%
Toluene, 80 oC, 12 h
R = Ph 92 % yieldR = p-CF3C6H4 95 % yieldR = p-MeOC6H4 76 % yield
best substrates are aromatic aldehydes (non-aromatic aldehydes givemixtures of branched and unbranchedproducts.
R H
O
N N
RH
H2O
Rh(I) PPh3Cl
PPh3
Ph3P
N N
RMe
R
O
Me
N NH2
H2O
Rh(III)Cl
PPh3
Ph3PNN
RH
Rh(III)Cl
Ph3PNN
R
Me
Rh(III)Cl
Ph3PNN
RH
Me
Me
H
migratory insertion to give moresterically hindered metal alkenyl. It is unclear why this regioselectivity isobserved.
Jun ACIEE 2002 (41) 2146
M.C. White, Chem 153 Hydroacylation-228- Week of October 29, 2002
Synthesis of cyclopentenones: Rh-catalyzed intramolecular trans hydroacylation of an alkyne
R
Me O
H
O
Me
R
R = n-C6 H13 75% yieldR = Ph 88% yield
[Rh(dppe)]2(BF4)2
acetone, CH3CN
rt (R = n-C6 H13)
100 oC (R = Ph)
LnRh(I) H
O
Rh(III)
O
HRh(III)
H
O
O
H
oxidativeaddition
trans hydrometalation?
reductive elimination
it is unclear how the observed trans hydrometalation is achieved
Ln
Proposed mechanism The following studies support this mechanistic proposal
n-C6 H13
Me O
D
O
Me
n-C6 H13
D
[Rh(dppe)]2(BF4)2
acetone, CH3CN100 oC
n-C6 H13
O
H
n-C6 H13
Me O
D
Me
O
n-C6 H13
H [Rh(dppe)]2(BF4)2
acetone, CH3CN100 oC
O
Me
n-C6 H13
D
1:1
Me
none of the crossover products were observed, supporting the hypothesis that this transfer process proceeds intramolecularly
aldehde proton (deuterium) istransfered cleanly to the βposition of the cyclopentenone
Fu JACS 2001 46 11492-11493..
M.C. White, Chem 153 Hydrovinylation -229- Week of October 29, 2002
Hydrovinylation of vinyl arenes
X X1 atm
+[Ni(CH3CN)6](BF4-)2, 0.25 mol%
PPh3 (1 mol%), AlEt2Cl (1.25 mol%)CH2Cl2, rt
+ linear product isomerized product
branched productX = H, 87% 3-Me, 82% 4-OMe, >5% 4-Cl, NR
Monteiro TL 1996 (37) 1157.
NiBr
NiBr
X X
0.35 mol%PPh3/AgOTf (0.35 mol%)
CH2Cl2, -56oC1 atm
+
branched productX = H, >95% 3-Me, >95% 4-OMe, >95% 4-Cl, 81% 4-Br, >95%
RajanBabu JACS 1998 (120) 459.
elimination of a Lewisacid in this system isthought to increase thereaction scope to include substrates with Lewisbasic fuctionality.
Hydride insertion gives thebranched product which canbe electronically stabilized asan η-3 intermediate. Note that this is a common trend inhydrometallations of arylolefins.
Bulky phosphine ligand may promote binding of ethylenevs. binding of another arylolefin which would result inoligomerization product
RajanBabu JACS 1998 (120) 459.
Ni
Br
Ni
Br
pre-catalyst
PPh3Ni(II)
Br
PPh3
AgOTfNi(II)
OTf
PPh3
Ni(II)
PPh3
+(OTf-)
metathesis
insertion
NiPPh3
OTf
H
Ni(II)
OTf
PPh3
H
nickel hydridecatalytically active
species
Ni(II)
OTf
PPh3H
Ni(II)
OTf
PPh3
Ni(II)
OTf
PPh3
Ni(II)
OTf
PPh3
Ni(II)
OTf
PPh3
H
M.C. White, Chem 153 Hydrovinylation -230- Week of October 29, 2002
Hemilabile bidentate chelation/counterion effects
NiBr
Ni
Br0.35 mol%
L/AgX (0.35 mol%)
CH2Cl2, -56oC1 atm
+MeO MeO
P
A systematic study in the hydrovinylation of styrene:
Counterion Yield
OTfClO4SbF6BARF
94%95%<2%<2%
ligand w/outhemilabile substituent
P
CH2OCH2Ph Counterion Yield
OTfClO4SbF6BARF
<4%<2%94%97%
ligand w/ hemilabilesubstituent
RajanBabu JACS 1999 (121) 9899.
With ligands devoid of hemilabile bidentatechelation, weakly coordinatng counterions must beused to prevent catalyst deactivation. Counterionssuch as OTf or ClO4 are small enough to transientlyoccupy a site of coordinative unsaturation on the Nicomplex. Because of their highly diffuse electrondensity, OTf and ClO4 weakly coordinate to the Nicomplex and can be readily displaced by ethyene.Alternatively, bulky counterions such as BARF orSbF6 cannot enter the coordination sphere of the Nicomplex and lead to rapid complex decomposition.The use of a hemilabile bidentate ligand inconjunction with coordinating counterion generates acatalytically inactive Ni complex. This may be due todiminished binding of the ethylene to the Ni complex.
O
PPh2
Ni
+
(BARF-)
97% isolated yield80% ee
Ph
PPh2 BARF = BAr4Ar = 3,5-(CF3)-Ph
Ni
+
(BARF-)
12% conversion0% ee
Hemilabile ether substituent on themonophosphine ligand stabilizescoordinatively unsaturated intermediates in the absence of coordinatingcounterions or solvents and readilydissociates to to bind ethylene andinitiate the formation of the active Ni-Hcatalyst. In the absence of hemilabileligation by the ligand, NMR studiesindicate that the highly dissociatedBARF complex readily decomposes.
hydrovinylation of 2-methoxy-6-vinylnaphthalene
M.C. White, Chem 153 Hydrovinylation -231- Week of October 29, 2002
Asymmetric hydrovinylation
NiBr
NiBr
0.35 mol%L/AgX (0.35 mol%)CH2Cl2, low temp
1 atm+
X X
Monodentate phosphporus ligands (bidentate phosphines lead to catalytically inactive species)
O
PPh2
Ph
P
CH2OCH2Ph
P
N
Ph
2
OO
O
OBnNH
Ac
OAr2P
1 2 3 4 (monophosphite)
O
O
P N
5
X = i-Bu, 40% ee X = H, 50% ee X = H, 86% ee X = H, 81% ee Br, 89% ee i-Bu, 74% ee
X = H, 95% ee Br, 92% ee i-Bu, 68% ee
(monophosphoamidite)
Asymmetric synthesis of (R)-ibuprofen
Br
NiBr
NiBr
0.35 mol%4/NaBARF (0.35 mol%)
CH2Cl2, low temp1 atm
+
Br
98% yield>99% selectivity for iso89% ee
(dppp)NiCl21.6 mol%i-BuMgCl
i-Bu i-Bu
O
O3, MeOHMe2S
KMnO4
acetone95% 96% 66%
i-Bu
O
HO
(R)-ibuprofen89% ee
i-Bu
? Takaya's asymmetric hydroformylation?(see hydroformylation -194-)
High levels of asymmetric induction inhydrovinylation with the current catalytic systemsappears to be limited to electron-neutral or deficient styrenes. 4-isobutylstyrene undergoeshydrovinylation with 4 in high yield (99%) butmodest ee (74%).
RajanBabu JACS 1999 (121) 9899. Ligand 1.RajanBabu JACS 2002 (124) 734. Ligand 4.Leitner JACS 2002 (124) 736. Ligand 5.
M.C. White, Chem 153 Hydrocyanation -232- Week of October 29, 2002
Hydrocyanation
OO
O
MeO MeO
CN Very narrow substrate scope reportedcomprised primarily of isomericvinylnaphthalene substrates. Yieldsrarely reported and typical runs were runwith substiochiometric amounts of HCN. Zerovalent nickel phosphite catalyst areknown to undergo irreversible oxidationwith HCN to Ni(CN)2. Since catalystdeactivation is second order in HCN,slow addition of HCN is required foroptimal yields.
OPh
O
PAr2
OAr2P
Ph
Proposed catalytic cycle:
Ni0
OO
O OPh
O
PAr2
OAr2P
Ph
COD
PNi0
P*
PNiIIP H
CN
*
PNi0
P*
COD
HCNCOD
PNiIIP*
H
CN Ar
Ar
PNiIIP*
CN
CN
CN
HCN
Ar
HCN
ligated Ni0 complex
observed by NMR
RajanBabu JACS 1992 (114) 6265.
RajanBabu JACS 1994 (116) 9869.
Nugent JOC 1985 (50) 5370. Ni0[(P(O-o-tolyl)3]4.
HCN
H2, L
NiII(CN)2
Ar = 3,5(CF3)2-Phnote when Ar = 3,5-(CH3)2-Ph, 16% ee
Industrial hydrocyanation to form adiponitrile:
Ni[P(O-o-tolyl)3]3 cat.
HCN, LA (e.g.AlCl3, ZnCl2) NiLCN LA
Spectroscopic studies indicate that the LA coordinates to the Ni cyanide intermedaites via the CN nitrogen . Coordination is thought to enhance both the rate and selectivity (n:iso) of reductive elimination. Selectivity is enhanced by destabilizing therelatively bulky branched alkyl intermediates.
5 mol%L (6.5 mol%)
benzene, low temp
+ Ni0(COD)2HCN (2.5 eq)
>99% regioselectivity85 % yield
85% eeL =
aimed towards synthesis of Naproxin and it's derivatives
η3-organo nickel intermedaite identified by NMR
NCNi(0)
NC
isomerizationhydrocyanation
hydrocyanationNC
CNadiponitrile: key
intermediate in Nylon-6,6Houpis Tetrahedron 2000 (56) 817.
Tolman OM 1984 (3) 33.
M.C. White,Q. Chen Chem 153 Q&A -233- Week of October 29, 2002
Hydrogenation: dihydride mechanism
CoH P(OMe)3
P(OMe)3
H
P(OMe)3
< 1 atm H2, 25 °C, rt.
cat.
Mild hydrogenation of benzene can be achieved with the cobalt complex below. Also, the rate of cyclohexadiene reduction is similar to the rate of benzene hydrogenation while cyclohexene is reduced at three to four timesslower than benzene. Propose 2 mechanisms for the arene hydrogenation.
Similar rates for benzene and cyclohexadiene suggests an η4-benzene complex is involved.
Muetterties JACS 1975, 97, 237.
CoIIIH P(OMe)3
P(OMe)3
H
P(OMe)3
HH
CoIII(MeO)3P HCo(MeO)3P Co(MeO)3P
HH
Co(MeO)3P
HCo(MeO)3PCo(MeO)3PCo(MeO)3P
H
H
Co(MeO)3P
P(OMe)3
H Co(MeO)3P
P(OMe)3
P(OMe)3
CoH P(OMe)3
P(OMe)3
H
P(OMe)3
H2
P(OMe)3
P(OMe)3
-C6H12
H2
H2
-2 P(OMe)3
η4-benzene, 18 e-
Dihydride mechanism:
H
H
H
H
H
H
M.C. White/Q. Chen Chem 153 Q&A -234- Week of October 29, 2002
CoH P(OMe)3
P(OMe)3
H
P(OMe)3
< 1 atm H2, 25 °C, rt.
cat.
Hydrogenation: monohydride mechanism
CoH P(OMe)3
P(OMe)3
H
P(OMe)3
CoP(OMe)3
P(OMe)3
H
P(OMe)3
P(OMe)3CoH
P(OMe)3
P(OMe)3Co
P(OMe)3
P(OMe)3Co
P(OMe)3
H HP(OMe)3CoH
P(OMe)3
P(OMe)3Co
P(OMe)3
H H
CoP(OMe)3
P(OMe)3
H
P(OMe)3
P(OMe)3
-C6H12
H2
Monohydride mechanism:
16e-
-2P(OMe)3
η4-benzene, 18 e-
repeat
The following experimental evidence supports the dihydride mechanism: HCo(P(OMe)3)3 has been independently synthesized and is inactive for the hydrogenation of arenes. Additionally, propene evolution is not observed in presence of arene, and the original Co allyl complex can be recovered in almost quantitative yield after the hydrogenation.
Muetterties JACS 1975, 97, 237.
M.C. White/M.S. TaylorChem 153 Q&A -235- Week of October 29, 2002
CO2H
NHAc
H2 (1 atm), 25oC, MeOH
CO2Et
NHAc
N-acetyl-(R)-phenylalanine>95% ee
(R)
Rh(I)P
P
(ClO4-)
+
H3C
H3C
(S,S-CHIRAPHOS)
Rh(I)P
P O
NH
(ClO4-)
+
H3C
H3C
MeO2C
Ph
olefin bound to Rh via its
si-face
stereospecific H migratory insertion /stereospecific H/C reductive elimination
both to the olefin face bound to Rh
minor diastereomer formednone detected by NMR (must be less than 5% present in solution)
Rh(I)P
PO
HN
(ClO4-)
+
CH3
CH3
CO2Me
Ph
olefin boundto Rh via its
re-face
major diastereomer formedin solution (identified by NMR
and x-ray crystallography)
It was concluded from kinetic measurements thatthe minor diastereomer was 580 fold more reactivetowards H2 oxidative addition (recall the RDS at rt). This factor offsets its lower concentration insolution and results in a 60:1 product ratio in favorof the R enantiomer.
Halpern's seminal mechanistic studies on the Rh+ - DIPAMP system for asymmetric dehydroamino acid hydrogenation permitted improvement of the reaction conditions to
increase enantiomeric excess. Provide a rationalization for the following observations, in light of Halpern's results.i) Decreasing the H2 pressure of the reaction increases the enantiomeric excess.
ANSWER: Oxidative addition of hydrogen to the DIPAMPRh-enamide complex is the rate-determining and ee determining step in this catalytic cycle. At low H2 pressures,the rate of interconversion between the major and minor diatstereomeric enamides is faster than the reaction of either complex with H2 (recall that the minor diastereomericenamide complex leads to the formation of the major product). As the hydrogen pressure is increased, the rate of oxidative addition of H2 becomes competitive with themajor/minor interconversion. Because it is present in excess amount, the reaction with the major diastereomer (leading to the minor enantiomer) becomes more favorable.Stated differently, at high H2 pressures the minor Rh-enamide diastereomer (which leads to the major product enantiomer, and exists in very low concentration) exhibitssaturation kinetics while the major Rh-enamide diastereomer (which leads to the undesired product enantiomer) is consumed at a rate which increases linearly with H2 pressure.
ii) Increasing the reaction temperature increases the enantiomeric excess.
The enthalpies of activation for oxidative additionH2 to the Rh-enamide complexes is lower than theenthalpic barrier for diastereomer interconversion(requires enamide dissociation). Thus as thetemperature of the reaction is increased, theequilibration between the major and minordiastereomeric enamide complexes is promotedmore than the oxidative addition of H2. Thus, it ispredicted that increasing the temperature will offset the effect of increasing the H2 pressure and lead toan enhancement in enantioselectivity.
Halpern JACS 1987, 109, 1746.Blackmond JACS 1996, 118, 1348.
M.C. White/Q. Chen Chem 153 Q&A -236- Week of October 29, 2002
Si(OiPr)3
OSi
OiPrOiPr
2%
Rh
Si(OiPr)3(PrOi)3Si
Rh(I)
Cp*
Si(OiPr)2
O
Me Me
Rh(III)
Cp*
Si(OiPr)2H
O
Me
Si O
Rh(III)
Me
OiPr
OiPr
Cp*
Si O
Rh(III)
OiPr
OiPr
Cp* H
Me
O
Me
SiOiPr
OiPr
Me liganddissociation
migratoryinsertion
β-hydrideelimination
reductive elimination
oxidative addition(C-H activation)
Si(OiPr)3
Rh
Si(OiPr)3(PrOi)3Si
Vinyl silane isomerization via C-H activationThe rhodium complex below catalyzes the isomerization of vinyl silanes to silyl enol ethers. Propose a mechanism for the transformation.
Brookhart JACS 1999 (121) 4385.
M.W. Kanan/M.C. White, Chem 153 Q&A -237- Week of October 29, 2002
Question 1
Pt
N
N Me
Me
Me
Me Me
iPr
iPr
Pt
N
N D
Me
Me iPr-d7
iPr-d7
iPr-d7CD3
DD
1
Provide a mechanism for the formation of 2-d27. Note that very little CH3D is formed under the reaction conditions.
iPr
iPr
C6D6 150°C
10 min.
2-d27
+ C2H6, CH4
M.W. Kanan/M.C. White, Chem 153 Q&A -238- Week of October 29, 2002
O
TESO
OH
ROTf
O
TESO
OH
R
OTf
Pd(PPh3)4800 psi CO
i-Pr2NEt, PhCN65 to 110°C
or
O
O
O
R
TESO
Provide a mechanism for this one-pot transformation. Explain why both the E- and Z-tetrasubstituted enol triflates react to form the desired product in comperable yields.
Question 2
Q. Chen/M.C. White, Chem 153 Q&A -239- Week of October 29, 2002
R
O
HN
O
N
H
CH3
H
H3C
NN
O
O
CH3
H3C
R+ PdBr2(PPh3)2 (0.25 mol %)
30% LiBr, 1% H2SO4, CO
Substituted hydrantions can be prepared by the ureidocarbonylation of an aldehyde in the presence of LiBr and H2SO4. Provide a mechansim for this transformation.
Question 3
Q. Chen/M.C. White, Chem 153 Q&A -240- Week of October 29, 2002
Question 4
Hn-Hex n-HexPPh2
O
Hn-HexPPh2
O
n-Hex
Hydrophosphinylation of internal and terminal alkynes with Ph2P(O)H can be catalyzed by a variety of palladium sources. Pd(PPh3)4 is selective for the anti-Markovnikovproduct. Propose a mechanism for the hydrophosphinylation of 1-octyne below.
The regioselectivity of the hydrophosphinylation can be completely reversed by usingPdMe2(dmpe) (dmpe = dimethylphosphinoethane) and the phosphinic acid, Ph2P(O)OH.Propose a mechanism for the formation of the Markovnikov product under these conditions.
+ Ph2P(O)H5% Pd(PPh3)4
+ Ph2P(O)H5% PdMe2(dmpe)
5% Ph2P(O)OH
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