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The Diels-Alder Reaction
James Partridge August 27th, 2010
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Easy Question
+
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Diels-Alder Reaction
Otto Diels 1876-1952 Kurt Alder 1902-1958
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Diels-Alder Reaction
• Identified products of quinnone and cyclopentadiene reaction.
• Paper-1928 • Nobel prize 1950
O
O
+
O
O
H
H
O
O
H
H
H
H
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O. Diels, K. Alder, Justus Liebigs Ann. Chem. 1928, 460, 98 ± 122
Diels Alder quotes • “Thus it appears to us that the possibility of synthesis
of complex compounds related to or identical with natural products such as terpenes, sesquiterpenes, perhaps even alkaloids, has been moved to the near prospect.”
• “We explicitly reserve for ourselves the application of the reaction developed by us to the solution of such problems.”
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What is the Diels Alder Reaction?
• Thermal π4s +π2s cycloadition reaction • Concerted and stereospecific • 200°, 17h, 90 ATM, 18%
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+
DIene Dieneophile 6 memebered ring
L.M. Joshel, L.W.Butz, J. Am. Chem. Soc., 63,3350, (1941)
What Makes Diels Alder reactions work?
• Frontier Orbital theory
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DIeneophile DIene
HOMO
LUMOLUMO
HOMO
ΔE
The Endo rule
• Ewoks, small race of primative mamals, live only on the forest moon of Endor
• ………Wait, that the Endor rule
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The REAL endo rule • Provide answers, explain stereochemistry
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MeO
CO2Me
CO2Me
MeO+
+
O
MeO
MeO
CO2Me
CO2Me
Diastereospecific!
O
H
H
O
main product
(+/-)
The REAL endo rule
• Secondary orbital overlap accounts for endo selectivity
• Will be converted thermally to exo
• If no 2ndary orbital overlap, exo ts is dominant
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O
Lots of cycloaddition • Hint: 2+2+2, then retro 2+2, then 4+2
R. L. Funk, K. P. C. Vollhardt, J. Am. Chem. Soc. 1979, 100, 215- 217;
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OMe TMSTMSCpCo(CO)2
136°C, 41 h[2+2+2]
decane174°C 20h
71%
TMS
TMS
Me O
H H
H
HO
Me
H H
H
Estrone
intermediate
TMS
TMS
O
Me
TMS
TMS
Me O
Retro Diels Alder
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P. A. Jacobi, C. A. Blum, R. W. DeSimone, U. E. S. Udodong, Tetrahedron Lett. 1989, 30, 7173 - 7176.
N O
Me OMe
NH+TBSO
O
TMS
O
OMe
TMS
ON
H
TBSO
O
N
H
O
H
(-) norsecurinine
50% overall
Michael NO
Me
OMe
N
OTBS
O
TMS
DA
NO
Me OMe
TMS
ON
H
OTBS
Retro Diels Alder-MeCN
NO
Me OMe
TMS
ON
H
OTBS
Review from last week
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N
OPG
CO2Me
Br
NBocO
OPG
SnBu3Pd(PPh3)4
toluene110°C, 30h N
O NBoc
OPG
CO2MeH
OPG68%
NH
N
N
N
OH
H
H
H
manzamine A
RXNName, product,
N
OPG
NBocO
OPG
MeO2C
S. F. Martin, J. M. Humphrey, A. Ali, M. C. Hillier, J. Am. Chem. Soc. 1999, 121, 866 ± 867
Boger Diels-Alder
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D. L. Boger, S. Ichikawa, H. Jiang, J. Am. Chem. Soc. 2000, 122, 12 169 - 12 173.
O
O
N
MeOMeO
nPrMe
O
OMeMe O
O
NMeO
MeO
nPr Me
OMeMe
H
H
H
HO
97%100% EXO
N MenPr
O O
OHHO
rubrolone aglyconO
OO
OMeMe
Boger puts off gas
D. L. Boger, C. M. Baldino, J. Am. Chem. Soc. 1993, 115, 11418-11425 ; H. H. Wasserman, R. W. DeSimone, D. L. Boger, C. M. Baldino, J.
Am. Chem. Soc. 1993, 115, 8457-8458.
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OMe
OMeMeO
MeO
+ NN N
N
CO2Me
CO2Me
60°C
CHCl35 Days
NN
NNR
R
MeOR
ROMe
N
N Me
Me
CO2HCO2H
MeO
MeO
CO2Me
MeO2C
2 eq
NN
NN
NN
NNR
ROMeOMe
MeOMeO
R
R
R=CO2Me
-2N2
NN
NNR
ROMeOMe
MeOMeO
R
R
-2MeOH65%
O2, Rose Bengal, hν
colidine:H2O: iPrOH2:6:1
O
O
Cl Cl
Cl
Cl
O
I
I IOH
I
HO
Rose Bengal
OO
NOON
MeO2C
OOH
O
OH
MeO2CMeO
OMe
Boger puts off MORE gas
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OO
NOON
MeO2C
OOH
O
OH
MeO2CMeO
OMe
N
N
OO
MeO2C
HO CO2Me
HOMeO
MeO
isochrysohermidin