Photoredox Catalysis of Polypyridyl Transition Metal Complexes

Using Visible Light as a Reagent in Organic Synthesis

Methods for Photoredox Catalysis

Properties of Ru(bpy)32+

d6 (RuII); D3 symmetry (“pinwheel” chirality)

s-donating; p-donating, accepting ligands (bpy)

Photochemistry (N.B. potentials v. SCE)

Campagna, S.; Puntoriero, F.; Nastasi, F.; Bergamini, G.; Balzani, V. Top. Curr. Chem. 2007, 280, 117-214; Juris, A.; Balzani, V.; Barigelletti, F.; Campagna, S.; Belser, P.; von Zelewsky, A. Coord. Chem. Rev. 1988, 84, 85-277; Kalyanasundaram, K. Coord. Chem. Rev. 1982, 46, 159-244

Nature of MLCT

Electronic Absorption Spectrum (Ground State)

Electronic Emission Spectrum @77K (solid), rt (dashed)

Emission Lifetime v. T Consistent with MLCT, not LC

Campagna, S.; Puntoriero, F.; Nastasi, F.; Bergamini, G.; Balzani, V. Top. Curr. Chem. 2007, 280, 117-214; Juris, A.; Balzani, V.; Barigelletti, F.; Campagna, S.; Belser, P.; von Zelewsky, A. Coord. Chem. Rev. 1988, 84, 85-277

Methods for Photoredox Catalysis

SOMO Catalysis: Photochemical Advances a-Alkylation, Trifluoroalkylation, Benzylation of Aldehydes

Nicewicz, D.A.; MacMillan, D.W.C. Science 2008, 322, 77-80; Nagib, D.A.; Scott, M.E.; MacMillan, D.W.C. J. Am. Chem. Soc. 2009, 131, 10875-10877; Shih, H.; Vander Wal, M.N.; Grange, R.L.; MacMillan, D.W.C. J. Am. Chem. Soc. 2010, 132, 13600-13603

Ru(bpy)32+

Photo-Trifluoromethylation of Silyl Enol Ethers

Pham, P.V.; Nagib, D.A.; MacMillan, D.W.C. Angew. Chem. Int. Ed. 2011, 50, 6119-6122

Reductive Intermolecular C-H Alkylation

Furst, L.; Matsuura, B.S.; Narayanam, J.M.R.; Tucker, J.W.; Stephenson, C.R.J. Org. Lett. 2010, 12, 3104-3107

Proposed Mechanism

Tucker, J.W.; Narayanam, J.M.R.; Krabbe, S.W.; Stephenson, C.R.J. Org. Lett. 2010, 13, 368-371; Furst, L.; Matsuura, B.S.; Narayanam, J.M.R.; Tucker, J.W.; Stephenson, C.R.J. Org. Lett. 2010, 12, 3104-3107

Arylation of Dehalogenation Radical: Total Synthesis of Gliocladin C 10 Steps, 30% Yield from Boc-D-Tryptophan Methyl Ester

Key Photoarylation step:

Furst, L.; Narayanam, J.M.R.; Tucker, J.W.; Stephenson, C.R.J. Angew. Chem. Int. Ed. 2011, 50, 9655-9659

Methods for Photoredox Catalysis

Reductive Dehalogenation

Narayanam, J.M.R.; Tucker, J.W.; Stephenson, C.R.J. J. Am. Chem. Soc. 2009, 131, 8756-8757

Alcohols to Halides: Phosphorus-Free Appel Reactions Original Appel Reaction

Arrow-Pushing Mechanism

Alcohols to Halides: Phosphorus-Free Appel Reactions

Dai, C.; Narayanam, J.M.R.; Stephenson, C.R.J. Nature Chem. 2011, 3, 140-145

Proposed Mechanism: Appel Reaction

Photochemical Cycle

Dai, C.; Narayanam, J.M.R.; Stephenson, C.R.J. Nature Chem. 2011, 3, 140-145

Proposed Mechanism: Appel Reaction

Fate of Imidate

Product obtained as racemate

Side product obtained during interrupted cycle, sterically encumbered alcohols

Dai, C.; Narayanam, J.M.R.; Stephenson, C.R.J. Nature Chem. 2011, 3, 140-145

Methods for Photoredox Catalysis

Oxidative [2+2] Cycloadditions

Ischay, M.A. ; Lu, Z.; Yoon, T.P. J. Am. Chem. Soc. 2010, 132, 8572-8574

Proposed Mechanisms: Oxidative [2+2]

Ischay, M.A. et al. J. Am. Chem. Soc. 2010, 132, 8572-8574; Teply, F. Collect. Czech. Chem. Commun. 2011, 76, 859-917

Reductive [2+2] Intramolecular Cycloadditions

Ischay, M.A.; Anzovino, M.E.; Du, J.; Yoon, T.P. J. Am. Chem. Soc. 2008, 130, 12886-12887

Proposed Mechanisms: Reductive [2+2]

Ischay, M.A.; Anzovino, M.E.; Du, J.; Yoon, T.P. J. Am. Chem. Soc. 2008, 130, 12886-12887; Teply, .F. Collect. Czech. Chem. Commun. 2011, 76, 859-917

Crossed Intermolecular [2+2] Cycloadditions

Key Challenges to Previous Precedent:

Unproductive Events: Cis-trans isomerization

Self-reaction: Efficiently Generates Homodimers

Morrison, H.; Rodriguez, O. J. Photochem. 1974/75, 3, 471-474; Ischay, M.A.; Anzovino, M.E.; Du, J.; Yoon, T.P. J. Am. Chem. Soc. 2008, 130, 12886-12887

Crossed Intermolecular [2+2] Cycloadditions

Du, J.; Yoon, T.P. J. Am. Chem. Soc. 2009, 131, 14604-14605

Control and Scalability

Attempt for Direct Access to Photoexcited Enone

Cis-trans isomerization disfavors direct photochemical coupling

Scalability

Du, J.; Yoon, T.P. J. Am. Chem. Soc. 2009, 131, 14604-14605

Du, J.; Yoon, T.P. J. Am. Chem. Soc. 2009, 131, 14604-14605

Methods for Photoredox Catalysis

An Interesting Observation

Hurtley, A.E.; Cismesia, M.A.; Ischay, M.A.; Yoon, T.P. Tetrahedron, 2011, 67, 4442-4448

Reductive Formal [4+2] Heterocycloadditions

Hurtley, A.E.; Cismesia, M.A.; Ischay, M.A.; Yoon, T.P. Tetrahedron, 2011, 67, 4442-4448

Mechanism: Formal [4+2]

Hurtley, A.E.; Cismesia, M.A.; Ischay, M.A.; Yoon, T.P. Tetrahedron, 2011, 67, 4442-4448

Learning from Observation

Hurtley, A.E.; Cismesia, M.A.; Ischay, M.A.; Yoon, T.P. Tetrahedron, 2011, 67, 4442-4448

Reductive Cyclizations of Enones

Du, J.; Espelt, L.R.; Guzei, I.A.; Yoon, T.P. Chem. Sci. 2011, 2, 2115

Mechanism: Reductive Enone Cyclization

Du, J.; Espelt, L.R.; Guzei, I.A.; Yoon, T.P. Chem. Sci. 2011, 2, 2115

Where Can We Go From Here?

Reductive Formal [3+2] Cycloadditions

Lu, Z.; Shen, M.; Yoon, T.P. J. Am. Chem. Soc. 2011, 133, 1162-1164

Proposed Mechanism: Formal [3+2]

Lu, Z.; Shen, M.; Yoon, T.P. J. Am. Chem. Soc. 2011, 133, 1162-1164

Intermolecular Formal 3+2 Cycloadditions?

In development, but similar challenges to intermolecular [2+2]

Lu, Z.; Shen, M.; Yoon, T.P. J. Am. Chem. Soc. 2011, 133, 1162-1164

Methods for Photoredox Catalysis

Possible Future Directions

Enantioselective Perfluoroalkylation of Chiral Ketenamines

Photoredox Substitution of Unactivated 1o & 2o Alcohols

Acknowledgements

Prof. Teshik Yoon & Prof. Corey Stephenson

Photographs

Prof. M. Christina White & CHEM 535

Prof. Martin D. Burke & the Burke Group

Methods for Photoredox Catalysis

ASAPs

Radical Cation [4+2] Cycloadditions of Unactivated Dienes

Oxidative C-H Arylation with Diazobenzene Using Pd(OAc)2/Ru(bpy)3Cl2

Lin, S.; Ischay, M.A.; Fry, C.G.; Yoon, T.P. J. Am. Chem. Soc. 2011 ASAP; Kalyani, D.; McMurtrey, K. B.; Neufeldt, S. R.; Sanford, M. S. J. Am. Chem. Soc. 2011 ASAP

Ru(bpz)32+

Reductive Intramolecular C-H Alkylation

Sn-Free Reductive Radical Cyclizations of p-Rich Heteroaromatics

Tucker, J.W.; Narayanam, J.M.R.; Krabbe, S.W.; Stephenson, C.R.J. Org. Lett. 2010, 13, 368-371

Radical Cascade Cyclizations

Mechanistic Evidence: Reductive Dehalogenation

Internal Radical Clock

Deuterium Incorporation

Proposed Mechanism

Narayanam, J.M.R.; Tucker, J.W.; Stephenson, C.R.J. J. Am. Chem. Soc. 2009, 131, 8756-8757

Mechanistic Evidence: Appel Reaction

Evidence for involvement of DMF

Evidence against carbene mechanism

Dai, C.; Narayanam, J.M.R.; Stephenson, C.R.J. Nature Chem. 2011, 3, 140-145

Mechanistic Evidence: Appel Reaction

Dai, C.; Narayanam, J.M.R.; Stephenson, C.R.J. Nature Chem. 2011, 3, 140-145

Evidence against solvolysis of oxyiminium ion

Figure taken from reference

Mechanistic Evidence: Oxidative Cycloaddition

Ischay, M.A. et al. J. Am. Chem. Soc. 2010, 132, 8572-8574

Fast erosion of EZ/EE; Fast Olefin Isomerization Relative to Cyclization

Erosion of EZ corresponds to Formation of Minor Diastereomer; Stereospecific Cyclization; Cycloaddition

Rxn charged with pure EZ

Mechanistic Evidence: Formal [3+2] Cycloaddition

No reaction if photocatalyst, Lewis acid, amine (reductive quencher), or light source is omitted

MgSO4 not necessary, contributes to reproducibility, slightly increased yield (ca. 5%)

Diastereomeric cyclopropanes stereoconvergent in cyclization

Lu, Z.; Shen, M.; Yoon, T.P. J. Am. Chem. Soc. 2011, 133, 1162-1164

Early Examples

Photocatalytic Pschorr Reaction (Cano-Yelo, 1984)

Debromination of dibromostilbene (Willner, 1983)

Cano-Yelo, H.; Deronzier, A. J. Chem. Soc. Perkin Trans. 2; 1984, 1093-1098; Maidan, R.; Goren, Z.; Becker, J.Y.; Willner, I. J. Am. Chem. Soc. 1984, 106, 6217; Goren, Z.; Willner, I. J. Am. Chem. Soc. 1983, 105, 7764

Early Examples

Radical Addition Of Selenosulfonates to Olefins (Barton, 1994)

Barton, D.H.R.; Csiba, M.A.; Jaszberenyi, J.C. Tet. Lett. 1994, 35, 2869