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Macmillan Lecture 1 The Advent and Development of the Field of Enantioselective Organocatalysis Organocatalysis ! Organocatalysis: the use of small organic molecules to catalyze organic transformations The Advent and Development of the Field of Enantioselective Organocatalysis Organocatalysis ! Organocatalysis: the use of small organic molecules to catalyze organic transformations The Advent and Development of the Field of Enantioselective Organocatalysis Organocatalysis ! Organocatalysis: the use of small organic molecules to catalyze organic transformations ! Between 2000 and 2008, more than 2000 ! Transformations that employ organic catalysts manuscripts on >150 discrete reaction types sporadically documented over last 100 years ! Used for enantioselective construction of C–C, ! Organocatalysis google page hits = 137,000 C–N, C–O, C–S, C–P, C–halogen bonds Olefin metathesis google page hits = 253,000 Gold catalysis google page hits = 28,600 ! Now 3rd major branch of catalysis ! The field of organocatalysis was born 1998-2000 The Advent and Development of the Field of Enantioselective Organocatalysis Organocatalysis ! Organocatalysis: the use of small organic molecules to catalyze organic transformations ! Between 2000 and 2008, more than 2000 ! Transformations that employ organic catalysts manuscripts on >150 discrete reaction types sporadically documented over last 100 years ! Used for enantioselective construction of C–C, ! Organocatalysis google page hits = 137,000 C–N, C–O, C–S, C–P, C–halogen bonds Olefin metathesis google page hits = 253,000 Gold catalysis google page hits = 28,600 ! Now 3rd major branch of catalysis ! The field of organocatalysis was born 1998-2000 The Advent and Development of the Field of Enantioselective Organocatalysis Organocatalysis ! Organocatalysis: the use of small organic molecules to catalyze organic transformations ! Between 2000 and 2008, more than 2000 ! Transformations that employ organic catalysts manuscripts on >150 discrete reaction types sporadically documented over last 100 years ! Used for enantioselective construction of C–C, ! Organocatalysis google page hits = 137,000 C–N, C–O, C–S, C–P, C–halogen bonds Olefin metathesis google page hits = 253,000 Gold catalysis google page hits = 28,600 ! Now 3rd major branch of catalysis ! The field of organocatalysis was born 1998-2000 The Advent and Development of the Field of Enantioselective Organocatalysis Organocatalysis ! Organocatalysis: the use of small organic molecules to catalyze organic transformations ! Between 2000 and 2008, more than 2000 ! Transformations that employ organic catalysts manuscripts on >150 discrete reaction types sporadically documented over last 100 years ! Used for enantioselective construction of C–C, ! Organocatalysis google page hits = 137,000 C–N, C–O, C–S, C–P, C–halogen bonds Olefin metathesis google page hits = 253,000 Gold catalysis google page hits = 28,600 ! Now 3rd major branch of catalysis ! The field of organocatalysis was born 1998-2000 The Advent and Development of the Field of Enantioselective Organocatalysis Organocatalysis ! Organocatalysis: the use of small organic molecules to catalyze organic transformations ! Between 2000 and 2008, more than 2000 ! Transformations that employ organic catalysts manuscripts on >150 discrete reaction types sporadically documented over last 100 years ! Used for enantioselective construction of C–C, ! Organocatalysis google page hits = 137,000 C–N, C–O, C–S, C–P, C–halogen bonds Olefin metathesis google page hits = 253,000 Gold catalysis google page hits = 28,600 ! Now 3rd major branch of catalysis ! The field of organocatalysis was born 1998-2000 The Advent and Development of the Field of Enantioselective Organocatalysis Organocatalysis ! Organocatalysis: the use of small organic molecules to catalyze organic transformations ! Between 2000 and 2008, more than 2000 ! Transformations that employ organic catalysts manuscripts on >150 discrete reaction types sporadically documented over last 100 years ! Used for enantioselective construction of C–C, ! Organocatalysis google page hits = 137,000 C–N, C–O, C–S, C–P, C–halogen bonds Olefin metathesis google page hits = 253,000 Gold catalysis google page hits = 28,600 ! Now 3rd major branch of catalysis ! The field of organocatalysis was born 1998-2000 The Advent and Development of the Field of Enantioselective Organocatalysis Organocatalysis ! Organocatalysis: the use of small organic molecules to catalyze organic transformations ! Between 2000 and 2008, more than 2000 ! Transformations that employ organic catalysts manuscripts on >150 discrete reaction types sporadically documented over last 100 years ! Used for enantioselective construction of C–C, ! Organocatalysis google page hits = 137,000 C–N, C–O, C–S, C–P, C–halogen bonds Olefin metathesis google page hits = 253,000 Gold catalysis google page hits = 28,600 ! Now 3rd major branch of catalysis ! The field of organocatalysis was born 1998-2000 The Advent and Development of the Field of Enantioselective Organocatalysis Organocatalysis ! Organocatalysis: the use of small organic molecules to catalyze organic transformations ! Why did the field of chemical synthesis overlook the use of organic catalysts for more than eighty years? ! Why did the field of organocatalysis initiate so rapidly at the beginning of the 21st century The Advent and Development of the Field of Enantioselective Organocatalysis Organocatalysis ! Organocatalysis: the use of small organic molecules to catalyze organic transformations ! Why did the field of chemical synthesis overlook the use of organic catalysts for more than eighty years? ! Why did the field of organocatalysis initiate so rapidly at the beginning of the 21st century The Advent and Development of the Field of Enantioselective Organocatalysis ! Why did the field of chemical synthesis overlook the use of organic catalysts until the beginning of the 21st century? Dieter Seebach: A 1990 essay on the future of organic synthesis: Angew. Chem. Int. Ed. 1990, 29, 1320. “New synthetic methods are most likely to be encountered in the fields of biological and organometallic chemistry.” Why did Seebach omit organocatalysis from his vision of the future of organic synthesis? One perspective: It is impossible to overlook a field that does not yet exist (in much the same way that you cannot work on a problem that has not yet been defined) The Advent and Development of the Field of Enantioselective Organocatalysis ! Why did the field of chemical synthesis overlook the use of organic catalysts until the beginning of the 21st century? Dieter Seebach: A 1990 essay on the future of organic synthesis: Angew. Chem. Int. Ed. 1990, 29, 1320. “New synthetic methods are most likely to be encountered in the fields of biological and organometallic chemistry.” Why did Seebach omit organocatalysis from his vision of the future of organic synthesis? One perspective: It is impossible to overlook a field that does not yet exist (in much the same way that you cannot work on a problem that has not yet been defined) The Advent and Development of the Field of Enantioselective Organocatalysis ! Why did the field of chemical synthesis overlook the use of organic catalysts until the beginning of the 21st century? Dieter Seebach: A 1990 essay on the future of organic synthesis: Angew. Chem. Int. Ed. 1990, 29, 1320. “New synthetic methods are most likely to be encountered in the fields of biological and organometallic chemistry.” Why did Seebach omit organocatalysis from his vision of the future of organic synthesis? One perspective: It is impossible to overlook a field that does not yet exist (in much the same way that you cannot work on a problem that has not yet been defined) The Advent and Development of the Field of Enantioselective Organocatalysis ! Why did the field of chemical synthesis overlook the use of organic catalysts until the beginning of the 21st century? Dieter Seebach: A 1990 essay on the future of organic synthesis: Angew. Chem. Int. Ed. 1990, 29, 1320. “New synthetic methods are most likely to be encountered in the fields of biological and organometallic chemistry.” Why did Seebach omit organocatalysis from his vision of the future of organic synthesis? One perspective: It is impossible to overlook a field that does not yet exist (in much the same way that you cannot work on a problem that has not yet been defined) The Early Use of Organic Catalysts in Enantioselective Synthesis: Hajos-Parrish ! Intramolecular Aldol: Hajos–Parrish J. Org. Chem. 1974, 39, 1615 O O O 3 mol% Me N CO2H catalyst H Me Me O catalyst DMF OH O (S)-proline 97% ee ! Extraordinary result that was well received by the chemical synthesis community ! Viewed as a unique chemical reaction, not part of a larger interconnected field ! Manuscript emphasis never placed on the benefits of organocatalysts or new catalysis concepts ! General lessons were never extrapolated thereby stalling potential application over multiple reaction types (Agami mechanistic red herring) ! The value of a general over-arching field that used organic catalysts was never recognized ! Between 1960 and 2001, no review articles on the collective use of organic catalysts The Early Use of Organic Catalysts in Enantioselective Synthesis: Hajos-Parrish ! Intramolecular Aldol: Hajos–Parrish J. Org. Chem. 1974, 39, 1615 O O O 3 mol% Me N CO2H catalyst H Me Me O catalyst DMF OH O (S)-proline 97% ee ! Extraordinary result that was well received by the chemical synthesis community ! Viewed as a unique chemical reaction, not part
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