PHOTOCATALYSIS: FORMATIONS OF RINGS Zachery Matesich 15 April 2014
Roadmap 2 Photoredox Catalysis Cyclizations Reductive Oxidative Redox-neutral Electron Transfer Conclusion
http://www.meta-synthesis.com/webbook/11_five/five.html Photochemistry: What is it? 3 Use of light (UV or visible) to sensitize a molecule to move an electron to an excited state
Early Pioneer 4 Ciamician (1885) First real investigation into photochemical process Saw the potential for Use of light as the future energy for mankind Roth, H. D. Angew Chem Int Ed 1989, 28 (9), 1193-1207.
Typical Uses of Photochemistry 5 Typically employ UV light (<380 nm) [2+2] Photocycloaddition Electron-Transfer Reaction Cyclopropane Ring Opening Hoffmann, N., Chem. Rev. 2008, 108 (3), 1052-1103.
Visible Spectrum: Why? 6 Visible light (>380 nm) is abundant, yet difficult to harness as most organic molecules do not absorb Yoon, T. P. et al. Science 2014, 343 (6174).
Visible Light Photochemistry: Why? 7 UV photons are similar to C-C bonds in energy 350 nm photon = 81 kcal/mol C-C bond = 85 kcal/mol No special apparatus required Can just leave a reaction in the sun Ideal reagent Non-toxic, generates no waste, renewable sources Yoon, T. P. et al. Science 2014, 343 (6174).
How to Harness the Light 8 Metal-ligand complexes Such as: Organic dyes Such as: Yoon, T. P. et al. Science 2014, 343 (6174). Nicewicz, D. A.; et al ACS Catalysis 2013, 4 (1), 355-360.
Spectral Properties of Ru(bpy) 3 9 Highly suitable for one-electron photoredox chemistry Excited state energy calculation = E 0 [Ru(bpy) 2+/2+* 3 ] = -2.10 V (vs SCE in MeCN) Kalyanasundaram, K., Coord. Chem. Rev. 1982, 46.
Electronics of Ru(bpy) 3 10 Spin-forbidden decay Excited state both better oxidant and reductant than ground E 1/2 III/II = +1.29 V E 1/2 II/I = -1.33 V MacMillan, D. W. C.; et al Chem. Rev. 2013, 113, 5322 5363
Photocatalysts: Redox Potential 11 Wide variety of photocatalysts available Alteration of metal and/or ligands changes potential and therefore role of catalyst MacMillan, D. W. C.; et al Chem. Rev. 2013, 113, 5322 5363
Photocatalysts: Ligand Effects 12 In general, e donating substituents on ligands render complex more strongly reducing Stephenson, C. R. J. et al. J. Org. Chem 2012, 77 (4), 1617-1622.
Photochemical: Mechanism 13 Three mechanisms for metal-ligand systems A) Reductive B) Oxidative & C) Energy Transfer Xiao, W.-J., et al Eur. J. Org. Chem. 2013 (30), 6755-6770.
Early Use of Ru(bpy) 3 14 Use of visible light highly superior over UV method Deronzier, A.; et al. J Chem Soc, Perkin Transactions 2 1984, (6), 1093-1098.
Photoreductive Cyclizations 15 *Ru(bpy) 3 2+ acts as oxidant forming Ru(bpy) 3 +, which is a strong reductant Donates an electron to an acceptor, generating a radical anion
Cyclization through Reduction of C-Br bond 16 [Ru] sufficient for bromomalonate substrates, but not bromo esters Stephenson, Corey R. J.; et al Chem. Commun. 2010, 46 (27), 4985-4987.
Further C-Br Bond Reductions 17 High reduction potential of [Ir] required for less activated C-Br bonds (-1.51 V vs -1.31 V) Stephenson, Corey R. J.; et al Chem. Commun. 2010, 46 (27), 4985-4987.
Reduction of C-Br Bond: Mechanism 18 Both operative under CFL light, but [Ru] more efficient with blue LED Stephenson, Corey R. J.; et al Chem. Commun. 2010, 46 (27), 4985-4987.
Tandem Cyclization-VCP Rearrangement 19 Insensitive to electronic effects, yet non-selective Five-membered ring strain required for transformation Stephenson, Corey R. J.; et al Org. Lett., 2011, 13, 5468
Tandem Reaction: Mechanism 20 Mechanistic data points away from path a, but did not distinguish between b and c Stephenson, Corey R. J.; et al Org. Lett., 2011, 13, 5468
Cyclization through Reduction of C-I bond 21 Reduction of C-I bond requires even higher reduction potential (-1.73 V) Stephenson, Corey R. J.; et al Nat Chem 2012, 4 (10).
Photooxidative Cyclizations 22 *Ru(bpy) 3 2+ acts as reductant forming Ru(bpy) 3 3+, which is a strong oxidant Accepts an electron from a donor, generating a radical cation
Oxidative Cyclization 23 Requirement for base Li, P., et al Org. Lett., 2012, 14, 98
Oxidative Cyclization: Substrates 24 Mild generation of 2-substituted benzothiazoles Li, P., et al Org. Lett., 2012, 14, 98
Believed to go through oxidative mechanism, but reductive mechanism could not be ruled out Li, P., et al Org. Lett., 2012, 14, 98 Oxidative Cyclization: Mechanism 25
AzomethineYlide [3+2] Cycloaddition 26 Facile formation of pyrrolo isoquinolines from a variety of dipolarophiles Xiao, W. et al Angew. Chem. Int. Ed. 2011, 50, 7171 7175
[3+2] Cycloaddition: Mechanism 27 Generation of iminium ion prior to cyclization NBS employed to form 3 exclusively Xiao, W. et al Angew. Chem. Int. Ed. 2011, 50, 7171 7175
Photoredox Neutral Cyclizations 28 Prior reactions require a stoichiometric amount of a compound to act as source/reservoir of electrons In this case, substrate undergoes both a singleelectron oxidation and reduction in the mechanism
[2+2] Enone Cyclization 29 Presence of 1 aryl enone required Electronics of aryl group are tolerated Yoon, T. et al J. Am. Chem. Soc. 2008, 130 (39), 12886-12887.
Group Problem 30 Based on the mechanisms thus far seen, predict the mechanism for this net-redox neutral reaction No reaction in absence of ipr 2 NEt No reaction in absence of LiBF 4 Na + and Bu 4 N + show low reactivity Yoon, T. et al J. Am. Chem. Soc. 2008, 130 (39), 12886-12887.
Group Problem Answer 31 BF 4 - required for solubility of Ru(bpy) 3 Yoon, T. et al J. Am. Chem. Soc. 2008, 130 (39), 12886-12887.
[2+2] Cyclization: Redox Auxiliaries 32 Use of 2-imidazolyl ketone allowed facile reaction of non-aryl substrates Yoon, T. P.; et al Org. Lett., 2012, 14, 1110-1113
Radical Diels-Alder Cycloadditions 33 Electron rich dienophile becomes electron poor through formation of radical cation Yoon, T. P.; et al J. Am. Chem. Soc. 2011, 133, 19350-19353
Radical Diels-Alder: Heitziamide A 34 Intrinsic regiochemical preference is opposite Radical process allows for formation of other isomer Yoon, T. P.; et al J. Am. Chem. Soc. 2011, 133, 19350-19353
[2+2+2] in Formation of Endoperoxides 35 Electron donating group required Intermolecular unsuccessful, but other tethers (CH 2, NTs) are possible Yoon, T. P.; et al Org. Lett., 2012, 14, 1640-1643
Organic Dye Mediated Process 36 High relative stereocontrol of C3 and C4 in anti-markovnikov formation of furan rings Nicewicz, D. A.; et al Angew. Chem. Int. Ed. 2013, 52 (14), 3967-3971.
Organic Dye Mediated Process 37 Redox-neutrality due to redox-active hydrogenatom donor 2 Nicewicz, D. A.; et al Angew. Chem. Int. Ed. 2013, 52 (14), 3967-3971.
Energy Transfer Cyclizations 38 Energy of triplet state much lower than UV photons Often larger substrate scope as more mild Yoon, T. P. et al. Science 2014, 343 (6174).
[2+2] via Energy Transfer 39 Successful application of formerly unreactive styrene Yoon, T. et al. Angew. Chem. Int. Ed. 2012, 51, 10329.
[2+2] via Energy Transfer 40 Unique reactivity over other radical methods Yoon, T. et al. Angew. Chem. Int. Ed. 2012, 51, 10329.
Energy Transfer in Natural Product Synthesis 41 Direct irradiation of 35 with UV light (254 nm) only gave 19% of product with 9% rsm Yoon, T. et al. Angew. Chem. Int. Ed. 2012, 51, 10329.
Conclusions 42 Using light as the reagent greatly decreases effort to perform the reaction Ability to generate a diverse array of intermediates via single-electron transfer Construction of complex molecules with complementary regiochemistry to current methods Metal catalysts can be tuned to substrates and type of reaction Use of organic dyes increasing in utility as well while avoiding the use of transition metals Scope of photocatalysis expands even beyond cyclizations and continues to do so
Concluding Thoughts 43 On the arid lands there will spring up industrial colonies without smoke and without smokestacks; forests of glass tubes will extend over the plains and glass buildings will rise everywhere; inside of these will take place the photochemical processes that hitherto have been the guarded secret of the plants, but that will have been mastered by human industry which will know how to make them bear even more abundant fruit than nature, for nature is not in a hurry and mankind is. And if in a distant future the supply of coal becomes completely exhausted, civilization will not be checked by that, for life and civilization will continue as long as the sun shines! -Giacomo Ciamician (1912) Ciamician, G. Science 1912, 36 (926), 385-394.
References 44 Roth, H. D. Angew Chem Int Ed 1989, 28 (9), 1193-1207. Hoffmann, N., Chem. Rev. 2008, 108 (3), 1052-1103. Yoon, T. P. et al. Science 2014, 343 (6174). Nicewicz, D. A.; et al ACS Catalysis 2013, 4 (1), 355-360. Yoon, T. et al. Angew. Chem. Int. Ed. 2012, 51, 10329. Kalyanasundaram, K., Coord. Chem. Rev. 1982, 46. MacMillan, D. W. C.; et al Chem. Rev. 2013, 113, 5322 5363 Stephenson, C. R. J. et al. J. Org. Chem 2012, 77 (4), 1617-1622. Xiao, W.-J., et al Eur. J. Org. Chem. 2013 (30), 6755-6770. Deronzier, A.; et al. J Chem Soc, Perkin Transactions 2 1984, (6), 1093-1098. Stephenson, Corey R. J.; et al Chem. Commun. 2010, 46 (27), 4985-4987. Stephenson, Corey R. J.; et al Org. Lett., 2011, 13, 5468 Stephenson, Corey R. J.; et al Nat Chem 2012, 4 (10). Li, P., et al Org. Lett., 2012, 14, 98 Xiao, W. et al Angew. Chem. Int. Ed. 2011, 50, 7171 7175 Yoon, T. et al J. Am. Chem. Soc. 2008, 130 (39), 12886-12887. Yoon, T. P.; et al Org. Lett., 2012, 14, 1110-1113 Yoon, T. P.; et al J. Am. Chem. Soc. 2011, 133, 19350-19353 Yoon, T. P.; et al Org. Lett., 2012, 14, 1640-1643 Nicewicz, D. A.; et al Angew. Chem. Int. Ed. 2013, 52 (14), 3967-3971. Ciamician, G. Science 1912, 36 (926), 385-394.