Photocatalytic 1,4-Addition of Aromatic Aldehydes or Ketones via Umpoled Carbinol Anions

Abstract

A 1,4-addition reaction of aromatic aldehydes or ketones to electron-deficient olefins was achieved under photocatalytic conditions. In the reaction, an umpoled carbinol anion generated in situ through two successive one-electron reductions of the carbonyl compound reacted nucleophilically with the electron-deficient olefin. Various electron-deficient aromatic aldehydes and ketones successfully underwent the reaction to afford the corresponding γ-functionalized alcohols.

Key words

1,4-addition reaction - carbinol anions - umpolung - photocatalysis - iridium catalysis - alcohols

• References and Notes


For selected examples of nucleophilic addition reactions of carbonyls via carbinol anion equivalents, see:
• 1a Hou Z, Takamine K, Aoki O, Shiraishi H, Fujiwara Y, Taniguchi H. J. Org. Chem. 1988; 53: 6077
• 1b Kise N, Sakurai T. J. Org. Chem. 2015; 80: 3496
• 1c Takeda M, Mitsui A, Nagao K, Ohmiya H. J. Am. Chem. Soc. 2019; 141: 3664
• 1d Liu X.-F, Zhang K, Tao L, Lu X.-B, Zhang W.-Z. Green Chem. Eng. 2022; 3: 125
• 1e Cao G.-M, Hu X.-L, Liao L.-L, Yan S.-S, Song L, Chruma JJ, Gong L, Yu D.-G. Nat. Commun. 2021; 12: 3306
• 2 Okumura S, Uozumi Y. Org. Lett. 2021; 23: 7194
• 3 Okumura S, Takahashi T, Torii K, Uozumi Y. Chem. Eur. J. 2023; e202300840
• 4a Giese B. Angew. Chem. Int. Ed. 1983; 22: 753
• 4b Srikanth GS. C, Castle SL. Tetrahedron 2005; 61: 10377
• 4c Gant Kanegusuku AL, Roizen JL. Angew. Chem. Int. Ed. 2021; 60: 21116

For selected examples of conventional ketyl Giese addition using stoichiometric amount of metal reductants, see:
• 5a Corey EJ, Pyne SG. Tetrahedron Lett. 1983; 24: 2821
• 5b Fukuzawa S, Nakanishi A, Fujinami T, Sakai S. J. Chem. Soc., Chem. Commun. 1986; 624
• 5c Enholm EJ, Prasad G. Tetrahedron Lett. 1989; 30: 4939
• 5d Yeh C.-H, Korivi RP, Cheng C.-H. Adv. Synth. Catal. 2013; 355: 1338

For selected reviews and examples of photocatalytic and photoinduced reactions of ketyl radicals
• 6a Lee KN, Ngai M.-Y. Chem. Commun. 2017; 53: 13093
• 6b Xia Q, Dong J, Song H, Wang Q. Chem. Eur. J. 2019; 25: 2949
• 6c Péter Á, Agasti S, Knowles O, Pye E, Procter DJ. Chem. Soc. Rev. 2021; 50: 5349
• 6d Qu Z, Tian T, Tan Y, Ji X, Deng G.-J, Huang H. Green Chem. 2022; 24: 7403
• 6e Yan Y, Li G, Ma J, Wang C, Xiao J, Xue D. Green Chem. 2023; 25: 4129

For selected examples on photocatalytic pinacol coupling, see:
• 7a Shibata T, Kabumoto A, Shiragami T, Ishitani O, Pac C, Yanagida S. J. Phys. Chem. 1990; 94: 2068
• 7b Nakajima M, Fava E, Loescher S, Jiang Z, Rueping M. Angew. Chem. Int. Ed. 2015; 54: 8828
• 7c Xi Z.-W, Yang L, Wang D.-Y, Feng C.-W, Qin Y, Shen Y.-M, Pu C, Peng X. J. Org. Chem. 2021; 86: 2474
• 7d Wang H, Qu J.-P, Kang Y.-B. Org. Lett. 2021; 23: 2900
• 7e Calogero F, Magagnano G, Potenti S, Pasca F, Fermi A, Gualandi A, Ceroni P, Bergamini G, Cozzi PG. Chem. Sci. 2022; 13: 5973

For selected examples of photocatalytic intramolecular ketyl Giese reactions, see:
• 8a Pandey G, Hajra S, Ghorai MK, Kumar KR. J. Org. Chem. 1997; 62: 5966
• 8b Tarantino KT, Liu P, Knowles RR. J. Am. Chem. Soc. 2013; 135: 10022
• 8c Foy NJ, Forbes KC, Crooke AM, Gruber MD, Cannon JS. Org. Lett. 2018; 20: 5727
• 8d Venditto NJ, Liang YS, El Mokadem RK, Nicewicz DA. J. Am. Chem. Soc. 2022; 144: 11888
• 9 For a photocatalytic intermolecular Giese-type allylation of carbonyl compounds with vinyl sulfones via carbinol radicals, see: Qi L, Chen Y. Angew. Chem. Int. Ed. 2016; 55: 13312
• 10 Gu J.-Y, Zhang W, Jackson SR, He Y.-H, Guan Z. Chem. Commun. 2020; 56: 13441
• 11 For an example of a metal–organic layer (MOL)-mediated ketyl Giese addition in which the MOL suppressed the undesired pinacol dimerization, see: Fan Y, You E, Xu Z, Lin W. J. Am. Chem. Soc. 2021; 143: 18871
• 12 For a report on an ionic 1,4-addition of diaryl ketones using an excess of TiCl₄–Mg, see: Pons J.-M, Santelli M. Tetrahedron 1990; 46: 513
• 13 The amount of CO₂ that dissolved in the DMA (5 mL) was up to 0.04 M (see the Supplementary Information, Section 2–1).
• 14 Methyl 4-(3-Cyano-1-hydroxy-1-methylpropyl)benzoate (3aA); Typical Procedure Ir(ppy)₂(dtbbpy)PF₆ (1.88 mg, 0.0021 mmol, 1 mol%) and DMBI (134.2 mg, 0.60 mmol, 3 equiv) were placed in a 20 mL Schlenk tube equipped with a stirrer bar. The Schlenk tube was filled with N₂ by vacuum–refill cycles (×3). DMA (4 mL) was added, and CO₂ (5 mL) was bubbled into the solution over 30 s using a syringe pump. A N₂ balloon was attached to the Schlenk tube, and acrylonitrile (2A; 52.7 mg, 1.0 mmol, 5 equiv) was added. By using a syringe pump, a solution methyl 4-acetylbenzoate (1a; 35.9 mg, 0.20 mmol) in DMA (1 mL) was added dropwise over 80 min to the reaction mixture under blue-light irradiation (λ = 448 nm) at 20 °C, and the mixture was stirred for a further 70 min. 2 M aq HCl was added and the resulting mixture was extracted with EtOAc (×3). The combined organic phase was washed with water (×2) and brine, then dried (MgSO₄) and concentrated under reduced pressure. The crude residue was purified by flash column chromatography [silica gel, 20–35% EtOAc–hexane (gradient)] to give a white solid; yield: 35.6 mg (0.15 mmol, 76%). IR (ATR): 3454 (m), 2257 (m), 1719 (s), 1279 (s) cm^–1. ¹H NMR (396 MHz, CDCl₃): δ = 8.03 (d, J = 8.6 Hz, 2 H), 7.49 (d, J = 8.6 Hz, 2 H), 3.92 (s, 3 H), 2.46–2.38 (m, 1 H), 2.18 (t, J = 7.7 Hz, 2 H), 2.10–2.02 (m, 1 H), 1.99 (s, 1 H), 1.64 (s, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 166.9, 150.7, 130.0, 129.3, 124.9, 120.0, 73.7, 52.3, 39.5, 30.7, 12.2. HRMS (ESI⁺): m/z [M + Na]⁺ calcd for C₁₃H₁₅NNaO₃: 256.0944; found: 256.0951.

For selected examples on CO₂-mediated reactions, see:
• 15a Sahoo PK, Zhang Y, Das S. ACS Catal. 2021; 11: 3414
• 15b Zhang K, Liu X.-F, Ren W.-M, Lu X.-B, Zhang W.-Z. Chem. Eur. J. 2023; 29: e202204073