Late-Stage C–H Methylation

In this episode we discuss a report from the Hartwig lab on an enantioselective hydroamination reaction. Through rational catalyst design, a cationic iridium complex was discovered that adds an amine N–H bond across a range of unactivated, internal alkenes.    DOI: 10.1038/s41586-020-2919-z   Xi, Y.; Ma, S.; Hartwig, J. F. Catalytic asymmetric addition of an amine N–H bond across internal alkenes. Nature 2020.   Nguyen, T. M.; Manohar, N.; Nicewicz, D. A. anti-Markovnikov Hydroamination of Alkenes Catalyzed by a Two-Component Organic Photoredox System: Direct Access to Phenethylamine Derivatives. Angew. Chem. Int. Ed. 2014, 53, 6198–6201.     Musacchio, A. J.; Lainhart, B. C.; Zhang, X.; Naguib, S. G.; Sherwood, T. C.; Knowles, R. R. Catalytic intermolecular hydroaminations of unactivated olefins with secondary alkyl amines. Science, 2017, 355, 727–730.     Huang, L.; Arndt, M.; Gooßen, K.; Heydt, H.; Gooßen, L. J. Late Transition Metal-Catalyzed Hydroamination and Hydroamidation. Chem. Rev. 2015, 115, 2596–2697.    Gurak, J. A.; Yang, K. S.; Liu, Z.; Engle, K. M. Directed, Regiocontrolled Hydroamination of Unactivated via Protodepalladation. J. Am. Chem. Soc. 2016, 138, 5805–5808.    Vanable, E. P.; Kennemur, J. L.; Joyce, L. A.; Ruck, R. T.; Schultz, D. M.; Hull, K. L. Rhodium-Catalyzed Asymmetric Hydroamination of Allyl Amines. J. Am. Chem. Soc. 2019, 141, 739–742.    Zhang, J.; Yang, C.-G.; He, C. Gold(I)-Catalyzed Intra- and Intermolecular Hydroamination of Unactivated Olefins. J. Am. Chem. Soc. 2006, 128, 1798–1799.    Zhang, Z.; Lee, S. D.; Widenhoefer, R. A. Intermolecular Hydroamination of Ethylene and 1-Alkenes with Cyclic Ureas Catalyzed by Achiral and Chiral Gold(I) Complexes. J. Am. Chem. Soc. 2009, 131, 5372– 5373.    Zhou, J.; Hartwig, J. F. Intermolecular, Catalytic Asymmetric Hydroamination of Bicyclic Alkenes and Dienes in High Yield and Enantioselectivity. J. Am. Chem. Soc. 2008, 130, 12220–12221.   Sevov, C. S.; Zhou, J.; Hartwig, J. F. Iridium-Catalyzed Intermolecular Hydroamination of Unactivated Aliphatic Alkenes with Amides and Sulfonamides. J. Am. Chem. Soc. 2012, 134, 11960–11963.    Hanley, P. S.; Hartwig, J. F. Intermolecular Migratory Insertion of Unactivated Olefins into Palladium-Nitrogen Bonds. Steric and Electronic Effects on the Rate of Migratory Insertion. J. Am. Chem. Soc. 2011, 133, 15661–15673.    Pan, S.; Endo, K.; Shibata, T. Ir(I)-Catalyzed Intermolecular Regio- and Enantioselective Hydroamination of Alkenes with Heteroaromatic Amines. Org. Lett. 2012, 14, 780–783.    Casalnuovo, A. L.; Calabrese, J. C.; Milstein, D. Rational design in homogeneous catalysis. Iridium(I)-catalyzed addition of aniline to norbornylene via nitrogen-hydrogen activation. J. Am. Chem. Soc. 1988, 110, 6738–6744.

In this episode we interview Mark Levin, an Assistant Professor at UChicago. We discuss his recent publication with the Jacobsen group, life as a new professor, and places to eat in Chicago.

In this episode we discuss a report from the Jacobsen lab on an enantioselective synthesis of difluorinated alkyl bromides catalyzed by a chiral iodoarene. Linear free energy relationships between experimental enantioselectivities and computed catalyst parameters helped elucidate the origins of enantioselectivity.  DOI: 10.1021/jacs.0c07043

In this episode we interview Marshall Brennan, the founder and Senior Product Manager of ChemRxiv. We discuss open-access publishing, alternative chemistry careers, and much more.

In this episode we interview Dr. Daniele Leonori, who is a professor of chemistry at the University of Manchester. We discuss his recent paper on dehydrogenative aniline synthesis, differences between the UK and US academic system, and much more.

In this episode we discuss a report from the Leonori lab on a photochemical dehydrogenative strategy for aniline synthesis. Photoredox and cobalt catalysis are combined to transform cyclohexanones into anilines. DOI: 10.1038/s41586-020-2539-7

In this episode we interview Dr. M. Christina White, who is a professor of chemistry at the University of Illinois. We discuss her recent paper on C–H methylation as well as her program on site-selective C–H oxidation chemistry.

In this episode we discuss a report from the White lab on a new method for late-stage C–H methylation adjacent to heteroatoms.  DOI: 10.1038/s41586-020-2137-8

In this episode we discuss the total synthesis of (–)-maximiscin reported by the Baran lab. The route takes advantage of a convergent fragment coupling strategy with a late-stage formation of the central pyridone ring.  DOI: https://doi.org/10.1021/jacs.0c03202

In this episode we discuss a report from the Knowles lab on a method for catalytic deracemization using visible light. This strategy benefits from two independent stereoselective steps resulting in a highly enantioselective transformation. DOI: 10.1126/science.aay2204.