lower-energy visible light provides access to the
reactivity of electronically excited alkenes that
are less susceptible to photoinduced degradation. For example, the cyclobutane cannabanoid
cannabiorcicyclolic acid can be synthesized by
using a clean, high-yielding [2+2] cycloaddition
under photocatalytic conditions. Direct irradiation with UV light, however, results in substantial photodecomposition of the product after
5 hours, and only 19% yield of the cycloadduct
is formed along with 9% of unreacted starting
Conclusions and Outlook
Synthetic organic chemistry benefits greatly when
it can incorporate developments from intellectually adjacent disciplines to advance. For instance,
organotransition metal chemistry, biocatalysis,
and computational chemistry have all been rapidly adopted and are now tools used by synthetic
chemists on a routine basis. Photochemistry has
the potential to have an equally substantial impact
on the field of chemical synthesis by providing
a complementary strategy for the activation of
organic substrates; the prospect of doing so with
renewable solar radiation has motivated photochemists for over a century and seems increasingly
relevant as the chemistry community becomes
more cognizant of its environmental responsibilities. The growing recognition that operationally
facile visible light–induced photochemical reactions can be conducted by using transition metal
photocatalysts is bringing us closer to this long-standing goal.
The pace of development in this area has been
remarkable. Recent research in visible light photocatalysis has yielded a generalizable rubric for
how organic substrates can undergo photoactivation by transition metal complexes. Both electron-transfer and energy-transfer photocatalysis have
been used to generate classes of reactive intermediates whose general reactivity patterns are
well understood, inspiring the design of a wide
range of new chemical reactions.
Therefore, the immediate goals within this area
are to continue advancing the utility of photocatalytic synthesis by exploiting the reactivity of
photogenerated intermediates in the construction
of increasingly complex organic targets. Current
research is also expanding the range of reactive
intermediates that are available using photocatalytic activation, which should increase the diversity of transformations accessible to synthetic
chemists interested in photochemical activation
strategies (70). Last, as has been the case with
many other advances in synthetic chemistry, the
advantages of visible light photocatalysis are
being recognized by researchers with interests in
areas as diverse as materials science, chemical
biology, and drug discovery, suggesting that research in photochemical synthesis will continue
to grow in synergistic relationship with intellectually adjacent fields (32, 71, 72). It seems clear
that the future of photochemical synthesis remains bright.
References and Notes
1. G. Ciamician, The photochemistry of the future. Science
36, 385–394 (1912). doi: 10.1126/science.36.926.385;
2. V. Balzani, A. Credi, M. Venturi, Photochemical
conversion of solar energy. ChemSusChem 1, 26–58
(2008). doi: 10.1002/cssc.200700087; pmid: 18605661
3. K. Kalyanasundaram, Photochemistry of Polypyridine and
Porphyrin Complexes (Academic Press, London, 1992).
4. S. Protti, S. Manzini, M. Fagnoni, A. Albini, “The
contribution of photochemistry to green chemistry,”
in Eco-Friendly Synthesis of Fine Chemicals, R. Ballini, Ed.
(2009), pp. 80–111.
5. P. Esser, B. Pohlmann, H. D. Scharf, The photochemical-synthesis of fine chemicals with sunlight. Angew. Chem.
Int. Ed. Engl. 33, 2009–2023 (1994). doi: 10.1002/
6. T. Bach, J. P. Hehn, Photochemical reactions as key steps
in natural product synthesis. Angew. Chem. Int. Ed. 50,
1000–1045 (2011). doi: 10.1002/anie.201002845;
7. N. Hoffmann, Photochemical reactions as key steps in
organic synthesis. Chem. Rev. 108, 1052–1103 (2008).
doi: 10.1021/cr0680336; pmid: 18302419
8. C. K. Prier, D. A. Rankic, D. W. MacMillan, Visible
light photoredox catalysis with transition metal
complexes: Applications in organic synthesis. Chem. Rev.
113, 5322–5363 (2013). doi: 10.1021/cr300503r;
9. T. P. Yoon, M. A. Ischay, J. Du, Visible light photocatalysis
as a greener approach to photochemical synthesis.
Nat. Chem. 2, 527–532 (2010). doi: 10.1038/
nchem.687; pmid: 20571569
10. M. Pirtsch, S. Paria, T. Matsuno, H. Isobe, O. Reiser,
[Cu(dap)2Cl] as an efficient visible-light-driven
photoredox catalyst in carbon-carbon bond-forming
reactions. Chemistry 18, 7336–7340 (2012).
doi: 10.1002/chem.201200967; pmid: 22581462
11. G. Revol, T. McCallum, M. Morin, F. Gagosz, L. Barriault,
Photoredox transformations with dimeric gold complexes.
Angew. Chem. Int. Ed. 52, 13342–13345 (2013).
doi: 10.1002/anie.201306727; pmid: 24133051
12. A. Juris et al., Ru(II) polypyridine complexes:
Photophysics, photochemistry, eletrochemistry, and
chemiluminescence. Coord. Chem. Rev. 84, 85–277
(1988). doi: 10.1016/0010-8545(88)80032-8
13. K. Kalyanasundaram, Photophysics, photochemistry and
solar energy conversion with tris(bipyridyl)ruthenium(II)
and its analogues. Coord. Chem. Rev. 46, 159–244
(1982). doi: 10.1016/0010-8545(82)85003-0
14. H. Takeda, O. Ishitani, Development of efficient photocatalytic
systems for CO2 reduction using mononuclear and
multinuclear metal complexes based on mechanistic
studies. Coord. Chem. Rev. 254, 346–354 (2010).
doi: 10.1016/ j.ccr.2009.09.030
15. O. S. Wenger, Proton-coupled electron transfer with
photoexcited metal complexes. Acc. Chem. Res. 46,
1517–1526 (2013). doi: 10.1021/ar300289x;
16. D. R. Weinberg et al., Proton-coupled electron
transfer. Chem. Rev. 112, 4016–4093 (2012).
doi: 10.1021/cr200177j; pmid: 22702235
17. T. Bach, Stereoselective intermolecular [2+2]-photocycloaddition
reactions and their application in synthesis. Synthesis
1998, 683–703 (1998). doi: 10.1055/s-1998-2054
18. A. Albini, Photosensitization in organic-synthesis. Synthesis
1981, 249–264 (1981). doi: 10.1055/s-1981-29405
19. M. Fagnoni, D. Dondi, D. Ravelli, A. Albini, Photocatalysis for
the formation of the C-C bond. Chem. Rev. 107, 2725–2756
(2007). doi: 10.1021/cr068352x; pmid: 17530909
20. S. Fukuzumi, S. Mochizuki, T. Tanaka, Photocatalytic
reduction of phenacyl halides by 9,10-dihydro-10-
methylacridine - control between the reductive and
oxidative quenching pathways of tris(bipyridine)
ruthenium complex utilizing an acid catalysis. J. Phys.
Chem. 94, 722–726 (1990). doi: 10.1021/j100365a039
21. F. Alonso, I. P. Beletskaya, M. Yus, Metal-mediated
reductive hydrodehalogenation of organic halides. Chem.
Rev. 102, 4009–4092 (2002). doi: 10.1021/cr0102967;
22. D. A. Nicewicz, D. W. MacMillan, Merging photoredox
catalysis with organocatalysis: The direct asymmetric
alkylation of aldehydes. Science 322, 77–80 (2008);
10.1126/science.1161976. doi: 10.1126/
science.1161976; pmid: 18772399
23. S. Mukherjee, J. W. Yang, S. Hoffmann, B. List, Asymmetric
enamine catalysis. Chem. Rev. 107, 5471–5569 (2007).
doi: 10.1021/cr0684016; pmid: 18072803
24. T. D. Beeson, A. Mastracchio, J. B. Hong, K. Ashton,
D. W. C. Macmillan, Enantioselective organocatalysis
using SOMO activation. Science 316, 582–585
(2007); 10.1126/science.1142696. doi: 10.1126/
science. 1142696; pmid: 17395791
25. T. D. Beeson, D. W. C. Macmillan, Enantioselective
organocatalytic a-fluorination of aldehydes. J. Am.
Chem. Soc. 127, 8826–8828 (2005). doi: 10.1021/
ja051805f; pmid: 15954790
26. H. W. Shih, M. N. Vander Wal, R. L. Grange, D. W. MacMillan,
Enantioselective a-benzylation of aldehydes via photoredox
organocatalysis. J. Am. Chem. Soc. 132, 13600–13603
(2010). doi: 10.1021/ja106593m; pmid: 20831195
27. P. V. Pham, D. A. Nagib, D. W. MacMillan, Photoredox
catalysis: A mild, operationally simple approach to the
synthesis of a-trifluoromethyl carbonyl compounds.
Angew. Chem. Int. Ed. 50, 6119–6122 (2011).
doi: 10.1002/anie.201101861; pmid: 21604347
28. L. Furst, B. S. Matsuura, J. M. Narayanam, J. W. Tucker,
C. R. Stephenson, Visible light-mediated intermolecular
C-H functionalization of electron-rich heterocycles
with malonates. Org. Lett. 12, 3104–3107 (2010).
doi: 10.1021/ol101146f; pmid: 20518528
29. L. Furst, J. M. Narayanam, C. R. Stephenson, Total synthesis
of (+)-gliocladin C enabled by visible-light photoredox
catalysis. Angew. Chem. Int. Ed. 50, 9655–9659 (2011).
doi: 10.1002/anie.201103145; pmid: 21751318
30. C. J. Wallentin, J. D. Nguyen, P. Finkbeiner, C. R. Stephenson,
Visible light-mediated atom transfer radical addition via
oxidative and reductive quenching of photocatalysts. J. Am.
Chem. Soc. 134, 8875–8884 (2012). doi: 10.1021/
ja300798k; pmid: 22486313
31. J. D. Nguyen, E. M. D’Amato, J. M. Narayanam,
C. R. Stephenson, Engaging unactivated alkyl, alkenyl
and aryl iodides in visible-light-mediated free radical
reactions. Nat. Chem. 4, 854–859 (2012). doi: 10.1038/
nchem.1452; pmid: 23001000
32. B. P. Fors, C. J. Hawker, Control of a living radical
polymerization of methacrylates by light. Angew. Chem.
Int. Ed. 51, 8850–8853 (2012). doi: 10.1002/
anie.201203639; pmid: 22807122
33. Y. Ye, S. A. Künzi, M. S. Sanford, Practical method for the
Cu-mediated trifluoromethylation of arylboronic acids
with CF3 radicals derived from NaSO2CF3 and tert-butyl
hydroperoxide (TBHP). Org. Lett. 14, 4979–4981 (2012).
doi: 10.1021/ol3022726; pmid: 22984900
34. D. Kalyani, K. B. McMurtrey, S. R. Neufeldt, M. S. Sanford,
Room-temperature C-H arylation: Merger of Pd-catalyzed
C-H functionalization and visible-light photocatalysis.
J. Am. Chem. Soc. 133, 18566–18569 (2011).
doi: 10.1021/ja208068w; pmid: 22047138
35. J. W. Tucker, C. R. Stephenson, Shining light on
photoredox catalysis: Theory and synthetic applications.
J. Org. Chem. 77, 1617–1622 (2012). doi: 10.1021/
jo202538x; pmid: 22283525
36. L. Shi, W. Xia, Photoredox functionalization of C-H
bonds adjacent to a nitrogen atom. Chem. Soc. Rev.
41, 7687–7697 (2012). doi: 10.1039/c2cs35203f;
37. U. C. Yoon, P. S. Mariano, Mechanistic and synthetic
aspects of amine enone single electron-transfer
photochemistry. Acc. Chem. Res. 25, 233–240 (1992).
38. E. A. Mitchell, A. Peschiulli, N. Lefevre, L. Meerpoel,
B. U. Maes, Direct a-functionalization of saturated
cyclic amines. Chemistry 18, 10092–10142 (2012).
doi: 10.1002/chem.201201539; pmid: 22829434
39. K. R. Campos, Direct sp3 C-H bond activation adjacent to
nitrogen in heterocycles. Chem. Soc. Rev. 36, 1069–1084
(2007). doi: 10.1039/b607547a; pmid: 17576475
40. P. Kohls, D. Jadhav, G. Pandey, O. Reiser, Visible light
photoredox catalysis: Generation and addition of
www.sciencemag.org SCIENCE VOL 343 28 FEBRUARY 2014 1239176-7