Mechanistic Investigation and Optimization of Photoredox Anti-Markovnikov Hydroamination

Abstract

The reaction mechanism and the origin of the selectivity for the photocatalytic intermolecular anti-Markovnikov hydroamination of unactivated alkenes with primary amines to furnish secondary amines have been revealed by time-resolved laser kinetics measurements of the key reaction intermediates. We show that backelectron transfer (BET) between the photogenerated aminium radical cation (ARC) and reduced photocatalyst complex (Ir(II)) is nearly absent due to rapid deprotonation of the ARC on the sub-100 ns time scale. The selectivity for primary amine alkylation is derived from the faster addition of the primary ARCs (as compared to secondary ARCs) to alkenes. The turnover of the photocatalyst occurs via the reaction between Ir(II) and a thiyl radical; the in situ formation of an offcycle disulfide from thiyl radicals suppresses this turnover, diminishing the efficiency of the reaction. With these detailed mechanistic insights, the turnover of the photocatalyst has been optimized, resulting in a >10-fold improvement in the quantum yield. These improvements enabled the development of a scalable flow protocol, demonstrating a potential strategy for practical applications with improved energy efficiency and cost-effectiveness.

Proton-Coupled Electron Transfer: The Engine of Energy Conversion and Storage

“…To date, most photoredox processes occur with high energy light and low quantum yields or, in the case of electroredox processes, high overpotentials and low faradaic efficiencies. The realization of higher efficiencies relies on averting nonproductive pathways of PCET intermediates, , providing an imperative for precisely defining reaction intermediates and mechanisms. Complementing traditional chemical synthesis, the powerful tool of synthetic biology allows the HIB approach to be generalized to a renewable chemical synthesis platform, depending on the biomachinery to which water-splitting is coupled .…”

Hydroalkylation of Unactivated Olefins via Visible-Light-Driven Dual Hydrogen Atom Transfer Catalysis

“…Further evaluation of substituent effect on the quinuclidinol scaffold led to the identification of borane QB5 as the optimal hydridic HAT catalyst and the yield of product 3 was increased to 89% (entry 6, see section 2 of the Supporting Information). Interestingly, replacing the thiol with 5 mol % of easy-to-handle and odorless bis­(2,4,6-triisopropylphenyl) disulfide [(TRIPS) 2 ] provided 3 in 91% yield upon isolation (entry 7) . Same efficiency was observed when benzene was used as the solvent (entry 8).…”

Insights into the Mechanism of an Allylic Arylation Reaction via Photoredox-Coupled Hydrogen Atom Transfer

“…In a more recent study, Knowles, Nocera, and coworkers examined a photoredox catalyzed anti-Markovnikov radical addition of aminium radical cations to alkenes, which yielded the tertiary amine product. 4 By studying the mechanism of the transformation, they were able to identify the source of the hydroamination selectivity, as well as which steps in the mechanism limited the overall reaction QY. With this knowledge they were able to tune the HAT catalyst and achieve a significant increase in QY.…”

“…A particularly successful class of tandem photoredox/organocatalytic reactions utilizes hydrogen atom transfer (HAT) catalysts as the co-catalyst. − In this context, HAT involves the simultaneous transfer of a proton and electron to generate a reactive radical species, which can then be captured via radical coupling. Thiol HAT catalysts are commonly utilized in tandem photoredox/HAT methods.…”