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Pt(II) Catalyzed Reorganization ofEnynes: What Can You Do With aPlatinum Carbene Intermediate?
Russell SmithDenmark Group Meeting
11-28-2006
Skeletal Reorganization of 1,6 and 1,7-EnynesE
E
cat. PtCl2
toluene, 80 °C
E = CO2Et
E
E3 h, 86 %
Murai, Organometallics, 1996, 15, 901.
E
E
Ph
E
E
Ph
1 h, 97 %
E
ECl
E
ECl
5 h, 70 %
E
E
E
E1 h, 97 %
E
E4 d, 40 %
E
E
Enyne Type “Metathesis” Using Platinum
• Many structural variations and functional groups are tolerated• Even polyunsaturated compounds undergo metathesis process
Fürstner, J. Am. Chem. Soc., 2001, 123, 11863.
Efforts Toward the Synthesis of Streptorubin B
Formation of propargylicester and ketone wasperformed to allow forfurther functionalization
Fürstner, J. Am. Chem. Soc., 1998, 120, 8305
Cyclization of Keto-enyne Using PlatinumChloride
Palladole complex previously used for similar skeletal RAR (Trost)
Fürstner, J. Am. Chem. Soc., 1998, 120, 8305
Interestingly, strong Lewis acids (BF3·Et2O) also promote cyclization
Mechanistic Insight By Scaling-Up a Reaction?
MAJOR79 %
1 %5 %2 %
Provide a mechanism that accounts for each observed product!(think of a common intermediate)
Simple “Wagner-Meerwein” Cationic Process;NOT Metal Catalyzed
Fürstner, J. Am. Chem. Soc., 1998, 120, 8305
Another Side Product Leads to A DifferentReaction Pathway
Can this cyclopropanation process be made general?
Fürstner, J. Am. Chem. Soc., 2000, 122, 6785.
Formation of Cyclopropane Derivatives fromHetero-substituted Enynes
Ability for Pt to catalyze two different process of similarsubstrates may indicate a similar reactive intermediate
Fürstner, J. Am. Chem. Soc., 2000, 122, 6785.
Mechanistic Proposal
Deuterium labeling study
The carbenoid species undergoes 1,2-hydride stabilization faster than insertion
Further Evidence for Cationic IntermediatesMurai
InoueE
E
[Pt(dppe)(PhCN)2](BF4)2
CHCl3, rt
E = CO2Et
E
E
Two different skeletal reorganizations appear to be operative
Labeling Studies Further Suggest Two ReactionPathways
Inoue, Organometallics, 2001, 20, 3704.
Both types of rearrangements can occur
Cross-over Experiment
CC
C C
C
C
C C
OR
CC
The rearrangement of the homoallyl cation canexplain the change in the skeletal RAR
Mechanistic Picture Involving Homoallyl Cations
The substitution of the enyne helps to stabilize thecarbocation intermediates
CC
C
C
E
E
X Pt2+ CC
C
C
E
E
X
Pt+2
C
C
CE
EY
C
Pt+
Y
X
C
CE
E
C
C
Pt+
X
C
CE
E
C
Pt+ X
CY
YA
B
C
CE
E
C C
YPt+X
A
B
C
CE
E
C C
XY
2+PtC
CE
E
C C
XY
2+Pt
Y
Extension to Cycloisomerization of 1,5-Enynes
cat. PtCl2
toluene/CH3CN
80 °C
MeOTBS
Me
Ph
Ph
MeMe
OTBS
66 %
78 %
81 %
73 %
77 %
72 %
Kozmin, J. Am. Chem. Soc., 2006, 128, 9705.
A wide range of terminal, internal,and arene conjugated systemsparticipate in cyclization
Intramolecular Carbocyclization of Allylsilanesand Allylstannanes
Y
E
E
R1 PtCl2
acetone OR MeOH reflux
E
E
R1
R2
R2
PhO2S
PhO2S
Me
94 %
PhO2S
PhO2S62 %
Y = SiMe3 Y = SnBu3
MeO2C
MeO2C
43 %(81 %)*
Y = SnBu3
MeO2C
MeO2C 50 %
Y = SiMe3
CO2Et
Me
PhO2S
PhO2S87 %
Y = SiMe3
Ph
Reaction is regio-complementary with Lewis Acid promoted cyclizationEchavarren, J. Am. Chem. Soc., 2000, 122, 1221.
Intramolecular Carbocyclization of Allylsilanesand Allylstannanes
Y
E
E
R1 PtCl2
acetone OR MeOH
reflux
E
E
R1
R2
R2
Could the use of an external nucleophile be used to trap carbocation?
Alkoxycyclization of Enynes Catalyzed byPlatinum
Z
Z
cat. PtCl2
ROH
Z
Z
OR
Z = SO2Ph, CO2Me R = Me, Et, allyl, H64-88 %
Ph
Z
Z
cat. PtCl2
MeOH
Z
Z
Ph
OMeH
Z
Z
cat. PtCl2
MeOH
Z
Z
Ph
OMeH
Ph
Echavarren, J. Am. Chem. Soc., 2000, 122, 11549.
Reaction is highly stereoselective with concomitant formation of C-Cand C-O bonds
DFT Calculations Indicate a CyclopropylIntermediate
• Terminal alkyne Clies closer to Pt• Electrophilic center isinternal C (polarized)• Pt-C bond of XXVI isrel. short (1.88 Å)
A platinum carbene is a possible intermediateEchavarren, J. Am. Chem. Soc., 2001, 123, 10511.
Asymmetric Pt-catalyzed Hydroxycyclization
100 %0 % ee
100 %5 % ee
91 %20 % ee (85 %)*
91 %13 % ee
* When 0.25 equiv of Ag salts were added, then enantioselectivitysignificantly improved
Use of Ag removes chlorine ligands from Pt ->more electrophilic metal center
Michelet, Pur Appl. Chem., 2006, 78, 397.
Intramolecular O->C Shift Reactions ViaCycloisomerization
Fürstner, J. Am. Chem. Soc., 2001, 123, 11863.
Intramolecular O->C Shift Reactions ViaCycloisomerization
Fürstner, J. Am. Chem. Soc., 2001, 123, 11863.
Cross-over experiment indicates that the allyl group istransferred intramolecularly
Phenol Formation from a Pt-carbeneIntermediate?
OO
cat. PtCl2
acetone, refluxO
HO
O
OH
+ 60 %(2.75:1.0)
OO
O
OH
75 %
O HO
OH
+ 70 %(3.4:1.0)
CO2Me
CO2Me
E
E
E
Can you propose a mechanism for the formation of these phenols?
Echavarren, J. Am. Chem. Soc., 2003, 125, 5757.
Possible Reactions of Furans with Alkynes
Only III could be found for an energy minimum for Friedel-Craft reactionEchavarren, J. Am. Chem. Soc., 2003, 125, 5757.
Formation of Oxepins Create Last C-C Bond
Calc show that the formationof 72 is high in energy
TS most likely occurs viaattack of O on carbene C
Echavarren, J. Am. Chem. Soc., 2003, 125, 5757.
Interception of Carbocationic Species by OtherAromatic Systems
OMe
E
E
E = CO2Me
cat. PtCl2
toluene, 80 °C
E
E
OMe
+
E
E
OMe
76 % yield (99:1)
E
E
Me
+
E
E
Me
47 % (96:4)
E
E
66 % (58:42)
Cl
E
E NR
Ruthenium also catalyzes process albeit with lower selectivityMurai, J. Org. Chem., 2000, 65, 4913.
CHALLENGEBased on knowledge obtained of Pt-cycloisomerization chemistry,prepare the 8-membered carbocycle
HO
O
O
OH
1,5-Enyne Cyclization Mechanism
R1 R3
R2
R4
Pt R1 R3
R2
R4
Pt
R3
R2R1
R4
Pt-
R2R3
Pt
R4
R1Pt-R1
R4
R3R2R1
R4
Pt-
R2
R2
Pt
R1
R4
R3
R2-M R1
R4
R3
R2
Kozmin, J. Am. Chem. Soc., 2006, 128, 9705.
Conclusions• Use of Pt(II) catalysts can serve as a versatile promoter
for of a number of reactions• A common intermediate has been found which is a
cyclopropyl platinum carbene• DFT calculations have been performed for a number of
platinum catalyzed reactions which has supported theplatinum carbene character of these systems
• The highly efficient atom economy of these processesmake them attractive reactions– Including the high diversity in which similar compounds can
be manipulated• These works may help to provide insight into similar
metal-catalyzed systems (e.g. Au, Ru, Rh)