Organic synthesis
SET/HAT flips benzylamine C–H arylation site
Open access · cc by · source: Europe PMC
PhC(O)SH plus Ir(ppy)3 switches photoredox arylation from N-methyl C–H to the benzylic position, giving 1,1-diarylmethylamines in hours.
Key findings
SET-only: 12 h, 95% mass balance but major product from the 1° N-methyl radical. With 1 mol% PhC(O)SH, benzylic arylation is 91% in 1 h (r.r. >20:1). Down to 0.5 mol% Ir and 1 mol% thiol still gives 90%. Yields 56–98%. BDE: PhC(O)S–H 87.4 vs benzylic C–H 84.9 kcal mol–1. PhC(O)SK Epox = +0.80 V vs SCE, below the amine.
Methodology
They coupled N,N-dimethylbenzylamines with terephthalonitrile using Ir(ppy)3. Without a HAT catalyst, the N-methyl product dominated. Adding thiobenzoic acid (or PhC(O)SK) inverted selectivity. CV compared oxidation potentials; scope included cyclic amines and late-stage drugs.
Limitations
The aryl partner is an electron-poor arene (terephthalonitrile class), not a generic aryl halide. Full kinetic isotope effects and computed BDEs for every substrate are not given. Scale-up beyond millimole flasks is not the focus.
How this study connects
Role on claims
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PhC(O)SH plus Ir(ppy)3 switches photoredox arylation from N-methyl C–H to the benzylic position, giving 1,1-diarylmethylamines in hours.
Evidence for the claim as stated.
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