enone photochemistry: fundamentals and applications contributors to enone photochemistry's...
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Enone Photochemistry:
Fundamentals and Applications
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
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
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.
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)
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.
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.
+
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
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
+
+
+
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.
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
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
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
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
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.
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.
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
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.