title: A General Approach to Catalytic Alkene Anti-Markovnikov Hydrofunctionalization Reactions via Acridinium Photoredox Catalysis.
abstract: The development of methods for anti-Markovnikov alkene hydrofunctionalization has been a focal point of catalysis research for several decades. The vast majority of work on the control of regioselectivity for this reaction class has hinged on transition metal catalyst activation of olefin substrates. While progress has been realized, there are significant limitations to this approach, and a general solution for catalysis of anti-Markovnikov hydrofunctionalization reactions of olefins does not presently exist. In the past several years, this research lab has focused on alkene activation by single electron oxidation using organic photoredox catalysts to facilitate anti-Markovnikov hydrofunctionalization. By accessing reactive cation radical intermediates, we have realized a truly general approach to anti-Markovnikov olefin hydrofunctionalization reactions. We have identified a dual organic catalyst system consisting of an acridinium photooxidant, first reported by Fukuzumi, and a redox-active hydrogen atom donor that accomplishes a wide range of hydrofunctionalization reactions with complete anti-Markovnikov regiocontrol. This method relies on single electron oxidation of the alkene to reverse its polarity and results in the opposite regioselectivity for hydrofunctionalization. In 2012, we disclosed the anti-Markovnikov hydroetherification of alkenols employing an acridinium photocatalyst and a hydrogen atom donor that proceeds via interwoven polar and radical steps. This general catalyst system has enabled several important reactions in this area, including anti-Markovnikov alkene hydroacetoxylation, hydrolactonization, hydroamination, and hydrotrifluoromethylation reactions. More recently, we have also delineated conditions for intermolecular anti-Markovnikov hydroamination reactions of alkenes using either triflamide or nitrogen-containing heteroaromatic compounds such as pyrazole, indazole, imidazole, and 1,2,3-triazole. Further development led to a method for the anti-Markovnikov addition of mineral acids to olefins using lutidinium halide salts as convenient reagents to deliver the mineral acids. Acids including HCl, HF, H3PO4, and MeSO3H all participate in the hydrofunctionalization reactions, even with alkenes that are highly prone to polymerization. A combination of transient and steady-state absorption spectroscopy tools were employed to observe alkene cation radicals and the resultant acridine radical, lending support for an electron transfer mechanism. The origin of the anti-Markovnikov selectivity in these reactions is likely the result of a reversible addition of the nucleophile to the alkene cation radical resulting in a greater population of the more stable radical. Loss of a proton followed by reaction of the radical intermediate with the hydrogen atom donor completes the transformations. Again, by means of transient absorption spectroscopy, oxidative turnover of the acridine radical was observed to complete the dual catalytic cycle mechanistic picture.
authors: Department of Chemistry, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599-3290, United States.
authors: Kaila A
authors: KA
authors: Margrey
authors: Department of Chemistry, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599-3290, United States.
authors: David A
authors: DA
authors: Nicewicz
mesh_terms: D000166:Acridines / Q000737:chemistry* / Q000528:radiation effects; D000475:Alkenes / Q000737:chemistry*; D002384:Catalysis / Q000528:radiation effects; D002412:Cations / Q000737:chemistry; D003500:Cyclization; D005609:Free Radicals / Q000737:chemistry; D006859:Hydrogen / Q000737:chemistry; D007536:Isomerism; D008956:Models, Chemical; D015394:Molecular Structure; D010084:Oxidation-Reduction
chemical_list: D000166:Acridines; D000475:Alkenes; D002412:Cations; D005609:Free Radicals; D006859:Hydrogen