Iron-Catalyzed C(sp3)–H Alkylation through Ligand-to-Metal Charge Transfer

Abstract

We report the FeCl3-catalyzed alkylation of nonactivated C(sp3)–H bonds. Photoinduced ligand-to-metal charge transfer at the iron center generates chlorine radicals that then preferentially abstract hydrogen atoms from electron-rich C(sp3)–H bonds distal to electron-withdrawing functional groups. The resultant alkyl radicals are trapped by electron-deficient olefins, and the catalytic cycle is closed by Fe(II) recombination and protodemetalation.

Iron-Catalyzed C(Sp3)–H Borylation, Thiolation, and Sulfinylation Enabled by Photoinduced Ligand-to-Metal Charge Transfer

“…Metal complexes and organocatalytic systems that are able to release chlorine radical species have been exploited in C­(sp 3 )–H functionalization reactions. In general, these reactions are affected by the thermodynamic preference of chlorine radicals for weaker C–H bonds, leading to site selectivities that follow the trend of 3° > 2° > 1°. ,, Since the chlorine radical-mediated HAT step has proved to be not turnover-limiting through our KIE experiment, we hypothesized that the afforded regioselectivity is highly dependent on the choice of radical acceptors. To testify our hypothesis, we chose 2,3-dimethylbutane (DMB), a branched isomer of hexane that was recently utilized to probe the HAT species by Zuo , and Walsh/Schelter, as a standard hydrocarbon substrate for the evaluation of site selectivity.…”

“…Photoinduced ligand-to-metal charge transfer (LMCT) instead of traditional redox processes has recently proved to be an effective synthetic tool for the construction of organic molecules . The direct excitation of high-valent metal–ligand complexes allowed the generation of reactive radical species, which could undergo an intermolecular HAT process with hydrocarbons and trigger a series of C­(sp 3 )–H functionalization reactions (Scheme b) . In particular, photoinduced chlorine radical species have been identified as key intermediates in these developed LMCT methods for the C­(sp 3 )–H arylation, alkylation, amination, and alkynylation.…”

Photo-Triggered, Copper(II) Chloride-Catalyzed Radical Hydroalkylation and Hydrosilylation of Vinylboronic Esters To Access Alkylboronic Esters

“…Based on our experimental observations and relevant literature, , we propose the mechanism as depicted in Scheme E. First, the excitation of CuCl 2 with 365 nm light induces the generation of a chlorine radical through the LMCT process.…”

Iron Photoredox Catalysis–Past, Present, and Future

“…The activated substrate can oxidize the iron species, regenerate the catalyst, and form a substrate anion that reacts further. Although this reaction mode is of use in the catalysis of a wide variety of organic transformations, − the exact photoreactive species are in many cases not unambiguously assigned by thorough mechanistic investigations. The traditional reaction systems utilizing visible light (Scheme A–D) − suffer from impaired reactivity in solvents other than acetonitrile and show a general necessity for irradiation with higher-energy light (390 nm).…”

“…Although this reaction mode is of use in the catalysis of a wide variety of organic transformations, − the exact photoreactive species are in many cases not unambiguously assigned by thorough mechanistic investigations. The traditional reaction systems utilizing visible light (Scheme A–D) − suffer from impaired reactivity in solvents other than acetonitrile and show a general necessity for irradiation with higher-energy light (390 nm). However, the adaption of the reaction system through the addition of additives, such as TRIP 2 S 2 (1,2-bis­(2,4,6-triisopropylphenyl) disulfane) and 2,4,6-collidine (Scheme A) or the introduction of pyridine-diimine (PDI)-based ligands (Scheme E) increases the absorption wavelength to 440–450 nm, resulting in more benign reaction conditions, thereby potentially diminishing undesirable side-reactions.…”