The use of small organic molecules as catalysts has been known for more than a century. But only in the past decade has organocatalysis become a thriving area of general concepts and widely applicable asymmetric reactions. Here I present my opinion on why the field of organocatalysis has blossomed so dramatically over the past decade.
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Berkessel, A. & Groeger, H. Asymmetric Organocatalysis: from Biomimetic Concepts to Applications in Asymmetric Synthesis (Wiley-VCH, 2005).
Seebach, D. Organic synthesis — where now? Angew. Chem. Int. Edn Engl. 29, 1320–1367 (1990).
Hajos, Z. G. & Parrish, D. R. Asymmetric synthesis of optically active polycyclic organic compounds. German patent DE 2102623 (1971).
Eder, U., Sauer, G. R. & Wiechert, R. Optically active 1,5–indanone and 1,6–naphthalenedione derivatives. German patent DE 2014757 (1971).
Hajos, Z. G. & Parrish, D. R. Asymmetric synthesis of bicyclic intermediates of natural product chemistry. J. Org. Chem. 39, 1615–1621 (1974).
Tu, Y., Wang, Z. & Shi, Y. An efficient asymmetric epoxidation for trans–olefins mediated by a fructose derived ketone. J. Am. Chem. Soc. 118, 9806–9807 (1996).
Denmark, S. E., Wu, Z., Crudden, C. & Matsuhashi, H. Catalytic epoxidation of alkenes with oxone. 2. Fluoro ketones. J. Org. Chem. 62, 8288–8289 (1997).
Yang, D. et al. A C2 symmetric chiral ketone for catalytic asymmetric epoxidation of unfunctionalized olefins. J. Am. Chem. Soc. 118, 491–492 (1996).
Sigman, M. & Jacobsen, E. N. Schiff base catalysts for the asymmetric Strecker reaction identified and optimized from parallel synthetic libraries. J. Am. Chem. Soc. 120, 4901–4902 (1998).
Corey, E. J. & Grogan, M. J. Enantioselective synthesis of α–amino nitriles from N-benzhydryl imines and HCN with a chiral bicyclic guanidine as catalyst. Org. Lett. 1, 157–160 (1999).
Miller, S. J. et al. Kinetic resolution of alcohols catalyzed by tripeptides containing the N–alkylimidazole substructure. J. Am. Chem. Soc. 120, 1629–1630 (1998).
List, B., Lerner, R. A. & Barbas, C. F. III. Proline-catalyzed direct asymmetric aldol reactions. J. Am. Chem. Soc. 122, 2395–2396 (2000).
Ahrendt, K. A., Borths, C. J. & MacMillan, D. W. C. New strategies for organic catalysis: the first highly enantioselective organocatalytic Diels–Alder reaction. J. Am. Chem. Soc. 122, 4243–4244 (2000).
King, H. D. et al. Enantioselective synthesis of a highly potent selective serotonin reuptake inhibitor. An application of imidazolidinone catalysis to the alkylation of indoles with an α,β-disubstituted α,β-unsaturated aldehyde. Org. Lett. 7, 3437–3440 (2005).
List, B. The direct catalytic asymmetric three-component Mannich reaction. J. Am. Chem. Soc. 122, 9336–9337 (2000).
Wenzel, A. G. & Jacobsen, E. N. Asymmetric catalytic Mannich reactions catalyzed by urea derivatives: enantioselective synthesis of β–aryl–β–amino acids. J. Am. Chem. Soc. 124, 12964–12965 (2002).
Mukherjee, S., Yang, J. W., Hoffmann, S. & List, B. Asymmetric enamine catalysis. Chem. Rev. 107, 5471–5569 (2007).
Hiemstra, H. & Wynberg, H. Addition of aromatic thiols to conjugated cycloalkenones, catalyzed by chrial β–hydroxy amines. A mechanistic study on homogeneous catalytic asymmetric synthesis. J. Am. Chem. Soc. 103, 417–430 (1981).
Oku, J. I. & Inoue, S. Asymmetric cyanohydrin synthesis catalyzed by a synthetic cyclic dipeptide. J. Chem. Soc. Chem. Commun. 229–230 (1981).
Dolling, U. H., Davis, P. & Grabowski, E. J. J. Efficient catalytic asymmetric alkylations. 1. Enantioselective synthesis of (+)–indacrinone via chiral phase-transfer catalysis. J. Am. Chem. Soc. 106, 446–447 (1984).
Doyle, A. G. & Jacobsen, E. N. Small-molecule H-bond donors in asymmetric catalysis. Chem. Rev. 107, 5713–5743 (2007).
Lelais, G. & MacMillan, D. W. C. Modern strategies in organic catalysis: the advent and development of iminium activation. Aldrichim. Acta 39, 79–87 (2006).
Narasaka, K., Okauchi, T., Tanaka, T. & Murakami, M. Generation of cation radicals from enamines and their reactions with olefins. Chem. Lett. 92, 2099–2102 (1992).
Beeson, T. D., Mastracchio, A., Hong, J., Ashton, K. & MacMillan, D. W. C. Enantioselective organocatalysis using SOMO activation. Science, 316, 582–585 (2007).
Jang, H., Hong, J. & MacMillan, D. W. C. Enantioselective organocatalytic singly occupied molecular orbital activation: the enantioselective α–enolation of aldehydes. J. Am. Chem. Soc. 129, 7004–7005 (2007).
Kim, H. & MacMillan, D. W. C. Enantioselective organo–SOMO catalysis: the α–vinylation of aldehydes. J. Am. Chem. Soc. 130, 398–399 (2008).
Raheem, I., Thiara, P. S., Peterson, E. A. & Jacobsen, E. N. Enantioselective Pictet–Spengler-type cyclizations of hydroxylactams: H-bond donor catalysis by anion binding. J. Am. Chem. Soc. 129, 13404–13405 (2007).
Reisman, S. E., Doyle, A. G. & Jacobsen, E. N. Enantioselective thiourea-catalyzed additions to oxocarbenium ions. J. Am. Chem. Soc. 130, 7198–7199 (2008).
Huang, Y., Walji, A. M., Larsen, C. H. & MacMillan, D. W. C. Enantioselective organo-cascade catalysis. J. Am. Chem. Soc. 127, 15051–15053 (2005).
Enders, D., Grondal, C. & Huttl, M. R. M. Asymmetric organocatalytic domino reactions. Angew. Chem. Int. Edn Engl. 46, 1570–1581 (2007).
I thank the National Institute of General Medical Sciences (grant number R01 GM078201-01-01) for financial support, and Merck Research Laboratories and Bristol-Myers Squibb for gifts. I also thank H. Kim, R. Knowles, D. Carerra and J. Van Humbeck for their help in the preparation of the manuscript.
The author declares no competing financial interests.
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MacMillan, D. The advent and development of organocatalysis. Nature 455, 304–308 (2008). https://doi.org/10.1038/nature07367
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