Enone Photochemistry: Fundamentals and Applications

Enone Photochemistry: Fundamentals and Applications

Initial Discovery Ciamician and Silber were the first to report a 2 2 light-induced cycloaddition in 1908: Italian sunlight, one year carvone camphorcarvone Buchi and Goldman confirmed the structure originally proposed for camphorcarvone in 1957. Ciamician, G.; Silber, P. Ber., 1908, 41, 1928. Buchi, G.; Goldman, I. M. J. Am. Chem. Soc., 1957, 79, 4741.

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. R6 R 5 R 1R2 R 4 R 3

chanism, 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. E = = (hl) / c ground state configuation p * p * n first excited state n p p 1 (p 2 n 2 ) 1 (p 2 n 1 p* 1 ) What next? Scster, D. I. "The Photochemistry of Enones," (p. 629-635) in: Patai, S., Rappoport, Z. The Chemistry of Enones, John Wiley & Sons Ltd., 1989.

chanism, 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 * p * first excited state (singlet) n p first excited state (triplet) n p 1 (p 2 n 1 p* 1 ) 3 (p 2 n 1 p* 1 ) Scster, D. I. "The Photochemistry of Enones," (p. 629-635) in: Patai, S., Rappoport, Z. The Chemistry of Enones, John Wiley & Sons Ltd., 1989.

chanism, Part 3 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. Scster, D. I. "The Photochemistry of Enones," (p. 629-635) in: Patai, S., Rappoport, Z. The Chemistry of Enones, John Wiley & Sons Ltd., 1989.

Evidence for Similar Rates of Initial Bond Formation, Part 1, 2 Se, ratio of b to a bonded cyclopentyls is 8.2 to 9.0 astings, D. J.; Weedon A. C. J. Am. Chem. Soc., 1991, 113, 8525.

Evidence for Similar Rates of Initial Bond Formation, Part 2 Et Et Et, 2 Se, 5.7 1.0 Et Et Et Et 3.2 3.5 astings, D. J.; Weedon, A. C. J. Am. Chem. Soc., 1991, 113, 8525.

Regioselectivity, Part 1 26.5% 6.5% 65% 55% Corey, E. J.; Bass, J. D.; LeMahieu, R.; Mitra, R. B. J. Am. Chem. Soc. 1964, 86, 5570.

Regioselectivity, Part 2 Cl F F Cl F F CClF 2 CClF 2 Corey's exciplex model correctly predicts regiochemical outcomes: d- d, d d- EWG R d d d- R, d- EDG R R R R EWG EDG Crimmins, M. T.; Reinhold, T. L. rg. Reactions, 1993, 44, 297.

Regioselectivity, Part 3 ther 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: TBS TBS C 2 C2 Crimmins, M. T.; Reinhold, T. L. rg. 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. Ac Bu Ac Crimmins, M. T.; Reinhold, T. L. rg. Reactions, 1993, 44, 297.

Stereochemistry, Part 2 64% 1 : 1 MM MM 82% 94:6 facial selectivity C 2 bornyl Ph Ph Ph 2 C Ph 2 C C 2 bornyl 94% ee Crimmins, M. T.; Reinhold, T. L. rg. Reactions, 1993, 44, 297.

Total Synthesis, Part 1 TsCl, py steps C 2 S C 2 steps Ph 3 PBr TsCl, py then S dl-caryophyllene Corey, E. J.; Mitra, R. B.; Uda,. J. Am. Chem. Soc. 1964, 86, 485.

Total Synthesis, Part 3 C 2 Et C2 Et TES tbu TES tbu 100% many, many steps A tbu dl-ginkgolide B Crimmins, M. T. et al. J. Am. Chem. Soc. 2000, 122, 8453.

Total Synthesis, Part 4, p-tsa C 2 3 steps smallest known inside outside bicycle (1988) Winkler, J. D.; ey, J. P. J. Am. Chem. Soc., 1986, 108, 6425.

Total Synthesis, Part 5 R 16% R 4 steps TBS many steps dl-ingenol Winkler, J. D. et al. J. Am. Chem. Soc., 2002, 124, 9726.

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. Scster: 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.. E. Zimmerman: explained triplet electronics and reactivity using M theory. G. S. ammond and N. J. Turro: carried out experiments that suggested enone triplets werereactive intermediates.