enone photochemistry: fundamentals and applications · 2008-05-12 · iii) predictable...
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Enone Photochemistry:
Fundamentals and Applications
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Initial Discovery
OMe
Me
MeMeO
Ciamician, G.; Silber, P. Ber., 1908, 41, 1928.Buchi, G.; Goldman, I. M. J. Am. Chem. Soc., 1957, 79, 4741.
Italian sunlight,one year
Ciamician and Silber were the first to report a 2 + 2 light-induced cycloaddition in 1908:
Buchi and Goldman confirmed the structure originally proposed for camphorcarvonein 1957.
carvone camphorcarvone
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Significance
Why should we be interested in enone photochemistry?
1. It is theoretically interesting.
2. For its synthetic utility:
i) Efficient cyclobutane synthesis;
ii) Regiochemical control;
iii) Predictable stereochemistry at the ring fusion(s);
iv) Great method for accessing medium sized rings via fragmentation.
O R6
R5
R1R2
R4R3
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Mechanism, Part 1
What happens when an enone is irradiated with UV radiation?
If the radiation is of appropriate wavelength (i.e. frequency, energy), excitation will occur.
ground stateconfiguation first excited state
1(p2n1p*1)
p* p*
n n
p p
1(p2n2)
What next?
E = hu = (hl) / c
Schuster, D. I. "The Photochemistry of Enones," (p. 629-635) in:Patai, S., Rappoport, Z. The Chemistry of Enones, John Wiley & Sons Ltd., 1989.
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Mechanism, Part 2
An enone in the first excited state (singlet) can:
1. Return to the singlet ground state (fluorescence);
2. Undergo internal conversion to the ground state via "trickle down" energy loss;
3. Undergo intersystem crossing (ISC; a.k.a. spin flip) to give the lower energy triplet and proceed to the next step of product formation;
4. Skip ISC altogether and proceed to the next step.
p*
n
p
3(p2n1p*1)
p*
n
p
first excitedstate (singlet)
first excitedstate (triplet)
Schuster, D. I. "The Photochemistry of Enones," (p. 629-635) in:Patai, S., Rappoport, Z. The Chemistry of Enones, John Wiley & Sons Ltd., 1989.
1(p2n1p*1)
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Mechanism, Part 3
Schuster, D. I. "The Photochemistry of Enones," (p. 629-635) in:Patai, S., Rappoport, Z. The Chemistry of Enones, John Wiley & Sons Ltd., 1989.
The excited enone (triplet state) can proceed to the next set of events:
1. Exciplex formation with the alkene.
The exciplex has a lifetime of 10 to 100's of ns. In this time it can:
1. Initiate carbon-carbon bond formation at either the a or b carbon of the enone;
2. Revert to starting materials. All intermediates up to the 1, 4 diradical are suceptible to this process.
If the diradical survives long enough, it may revert to a singlet state via ISC to give an excited singlet state which can then form the second bond and give the product.
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Evidence for Similar Rates of Initial Bond Formation, Part 1
O
O O
O O O
hu, H2Se,
ratio of b to a bonded cyclopentyls is 8.2 to 9.0
Hastings, D. J.; Weedon A. C. J. Am. Chem. Soc., 1991, 113, 8525.
+
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Evidence for Similar Rates of Initial Bond Formation, Part 2
Hastings, D. J.; Weedon, A. C. J. Am. Chem. Soc., 1991, 113, 8525.
O hu, H2Se,
O O O
OOO
5.7 1.0
3.2 3.5
OEt
OEt
OEt
OEt OEt
EtOEtO
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Regioselectivity, Part 1
O
O
O
MeO OMe
O O
MeMe Me
Me
+
O
O
OMeOMe
Corey, E. J.; Bass, J. D.; LeMahieu, R.; Mitra, R. B. J. Am. Chem. Soc. 1964, 86, 5570.
hu
hu
hu
26.5% 6.5%
65%
55%
H
+
+
+
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Regioselectivity, Part 2
O
O
MeMe
Me Me O
O
MeMe
O
O
MeMe Cl
F F
Cl
FF O
O
O
R
R
CClF2CClF2
EWG
EDG
hu,
Corey's exciplex model correctly predicts regiochemical outcomes: O
R
R
O
R
R
EWG
EDG
hu
hu
hu,
d+d-
d+d-
d+
d+
d-
d-
Crimmins, M. T.; Reinhold, T. L. Org. Reactions, 1993, 44, 297.
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Regioselectivity, Part 3
Crimmins, M. T.; Reinhold, T. L. Org. Reactions, 1993, 44, 297.
Other factors that affect regiochemistry:
1. Less polar solvents favor products predicted by the Corey exciplex model;
2. Lower temperatures have the same effect;
3. In general, two to four membered tethers set regiochemistry. Examples:
OMe Me
OTBS
OMeMe
CO2MeO
OMe Me
OTBS
OMeMe
O CO2Me
hu
hu
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Crimmins, M. T.; Reinhold, T. L. Org. Reactions, 1993, 44, 297.
Stereochemistry, Part 1
General considerations:
1. Cyclopentenones and smaller enones give cis fused products;
2. Cyclohexenones give significant amounts of trans product;
3. Strained enones or strained cyclobutane products preclude trans products
4. trans Fused products are easily epimerized to cis.
Me MeO OAc
Me MeO
AcO Me
O
Bu
O O
Me Me
+
+hu
hu
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Crimmins, M. T.; Reinhold, T. L. Org. Reactions, 1993, 44, 297.
Stereochemistry, Part 2
OMe
Me Me O
H
H
Me
Me Me
H
H
Me
Me Me
O
O
O
Me
MOMO
O
O
Me
MOMO H
H
CO2bornyl
MeO2C
Ph
Ph
Ph
CO2bornyl
Ph
MeO2C
+ +
+
+
hu
64%
hu
hu
82%
94:6 facial selectivity
94% ee
1 : 1
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Total Synthesis, Part 1
Corey, E. J.; Mitra, R. B.; Uda, H. J. Am. Chem. Soc. 1964, 86, 485.
O O H
MeMe
MeMe
OH
O
CO2MeMe
O
CO2Me
HHO
MeMe
O
O
Me
O
MeMe
Me
H
Me
+
Me
O
MeMe
H
Me
O
hu stepsSO
TsCl, py
MePh3PBr
MeOOHH
HO
MeMe
Mesteps
SO
TsCl, pythen
dl-caryophyllene
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Total Synthesis, Part 3
O
OO
O CO2EtCO2Et
tBuTESO TESO tBu
OA
OO
MeH H
HO HtBu
O
O
O
HHOHO
HH
dl-ginkgolide B
hu
100%
many, many steps
Crimmins, M. T. et al. J. Am. Chem. Soc. 2000, 122, 8453.
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O
Total Synthesis, Part 4
OO
Me Me
OO
O
Me Me
H
CO2Me
O
H
H
O
H
H
smallest knowninside outsidebicycle (1988)
hu MeOH, p-TSA
3 steps
Winkler, J. D.; Hey, J. P. J. Am. Chem. Soc., 1986, 108, 6425.
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Me
R
OO
MeMe
O
MeR
OO
O
Me MeMe O
OTBS
hu
16%
4 steps
many steps
Me O
HO HOHO OH
MeMeH
H
Me dl-ingenol
Total Synthesis, Part 5
Winkler, J. D. et al. J. Am. Chem. Soc., 2002, 124, 9726.
H
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Main Contributors to Enone Photochemistry's Development
P. E. Eaton: discovered that cyclopentenone and cyclopentadiene reaction under photochemical conditions; synthesized cubane to exemplify utility.
E. J. Corey: established the usual stereochemistry of 2 + 2 photochemical cycloadditions; advanced the notion of an exciplex to explain regioselectivity.
P. de Mayo: established that intermolecular 2 + 2 was feasible; invented a method for the preparation of 1, 5 diones by photochemical means, postulated that the first triplet state is the reactive one in enones; found that intermediates could revert to starting materials.
D. I. Schuster: determined lifetimes of reactive intermediates thereby disproving Corey's exciplex mechanism; in particular, he determied that rate constants for enones triplet quenching were previously overestimated; proved that enone triplets were reactive intermediates.
A. C. Weedon: determined that regioselectivity is goverend by diradical lifetimes.
H. E. Zimmerman: explained triplet electronics and reactivity using HMO theory.
G. S. Hammond and N. J. Turro: carried out experiments that suggested enone triplets werereactive intermediates.