No abstract

The direct β-activation of saturated aldehydes and ketones has long been an elusive transformation. We found that photoredox catalysis in combination with organocatalysis can lead to the transient generation of 5π-electron β-enaminyl radicals from ketones and aldehydes that rapidly couple with cyano-substituted aryl rings at the carbonyl β-position. This mode of activation is suitable for a broad range of carbonyl β-functionalization reactions and is amenable to enantioselective catalysis.

The direct C–H functionalization and arylation of benzyl ethers has been accomplished via photoredox organocatalysis. The productive merger of a thiol catalyst and a commercially available iridium photoredox catalyst in the presence of household light directly affords benzylic arylation products in good to excellent yield. The utility of this methodology was further demonstrated in the direct arylation of 2,5-dihydrofuran to form a single regioisomer.

2a MeI 85 95:5 (R) 2a Me2SO4 67 92:8 (R) 2a BrCH2CO2Bn 46 94:6 (R) 2a ClCH2OBn 74 92:9 (R) 2a allyl iodide 86 90:10 (R) 2a BnBr 70 84:16 (R) 2b MeI not reported 98:2 (R) 2b BnBr not reported 97:3 (R) 3a MeI 96 83:17 (S) 3a BnBr 96 55:45 (S)Scheme 2 a a Reagents and conditions: (a) nBuLi, Et2O, -78 °C; (b) trisylN3, -78 °C; (c) Ac2O, warm to rt, 8 h; (d) Al-Hg, EtOH; (e) 4 N HCl, dioxane, reflux; (f) KHMDS, THF, -78 °C; (g) AcOH; (h) H2, 5% Pd/C, EtOH. a BnBr (2′S)-14 60 >99:1 (S)-17 b MeI (2′R)-14 81 >99:1 (R)-17 a allyl iodide (2′S)-15 61 >99:1 (S)-18 c MeI (2′R)-15 49 >99:1 (R)-18 b allyl iodide (2′R)-16 79 >99:1 (R)-19 c BnBr (2′S)-16 43 >99:1 (S)-19 Scheme 3 a a Reagents and conditions: (a) cyclohexanone, PhH, reflux, 8 h; (b) LDS, THF, -78 °C; (c) RX, THF, 0 or -10 °C; (d) citric acid, H2O.