Photocatalytic Spirocyclization of 2-Alk-ω-enyl-Substituted Cycloalkane-1,3-diones

Abstract

When irradiated with visible light, various cyclic 2-alk-4-enyl-substituted 1,3-diketones undergo an intramolecular endo-addition (m = 1) onto the double bond resulting in spirocyclic products (11 examples, 62–92% yield). Both an organic (TXT: thioxanthone, 20 mol%) and an organometallic Ir-based photocatalyst (5 mol%) promote the reaction. Addition of triisopropylthiophenol is required to secure high yields. The spirocyclization of a 2-alk-5-enyl-substituted substrate (m = 2) delivers a mixture of the seven-membered endo- and the six-membered exo-cyclization products.

Key words

catalysis - cyclization - electron transfer - iridium - photochemistry - radical reaction

Publikationsverlauf

Eingereicht: 28. November 2022

Angenommen nach Revision: 28. Dezember 2022

Accepted Manuscript online:
28. Dezember 2022

Artikel online veröffentlicht:
30. Januar 2023

• References and Notes

• 1 Challand BD, Hikino H, Kornis G, Lange G, De Mayo P. J. Org. Chem. 1969; 34: 794

Reviews:
• 2a De Mayo P. Acc. Chem. Res. 1971; 4: 41
• 2b Oppolzer W. Acc. Chem. Res. 1982; 15: 135
• 2c Winkler JD, Bowen CM, Liotta F. Chem. Rev. 1995; 95: 2003
• 2d Luque A, Paternoga J, Opatz T. Chem. Eur. J. 2021; 27: 4500

Reviews on the [2+2] photocycloaddition:
• 3a Baldwin SW. Org. Photochem. 1981; 5: 123
• 3b Crimmins MT, Reinhold TL. Org. React. 1993; 44: 297
• 3c Hoffmann N. Chem. Rev. 2008; 108: 1052
• 3d Poplata S, Tröster A, Zou Y.-Q, Bach T. Chem. Rev. 2016; 116: 9748
• 4 Begley MJ, Mellor M, Pattenden G. J. Chem. Soc., Perkin Trans. 1 1983; 1905
• 5 Intermolecular version: Pecho F, Zou Y.-Q, Gramüller J, Mori T, Huber SM, Bauer A, Gschwind RM, Bach T. Chem. Eur. J. 2020; 26: 5190
• 6 Review: Nikitas NF, Gkizis PL, Kokotos CG. Org. Biomol. Chem. 2021; 19: 5237

Recent examples from our group:
• 7a Rigotti T, Bach T. Org. Lett. 2022; 24: 8821
• 7b Xiong Y, Großkopf J, Jandl C, Bach T. Angew. Chem. Int. Ed. 2022; 61: e202200555

For 6-endo-cyclization reactions observed under typical radical conditions, see:
• 8a Julia M, Maumy M. Bull. Soc. Chim. Fr. 1969; 2415
• 8b Curran DP, Chang CT. J. Org. Chem. 1989; 54: 3140
• 8c Snider BB, Smith RB. Tetrahedron 2001; 58: 25
• 8d Jahn U, Hartmann P, Kaasalainen E. Org. Lett. 2004; 6: 257
• 8e Snider BB, Duvall JR. Org. Lett. 2004; 6: 1265
• 9 For a related recent study, see: Zhao Q.-Q, Rehbein J, Reiser O. Green Chem. 2022; 24: 2772

Reviews:
• 10a Hiesinger K, Dar’in D, Proschak E, Krasavin M. J. Med. Chem. 2021; 64: 150
• 10b Westphal R, Venturini Filho E, Medici F, Benaglia M, Greco SJ. Synthesis 2022; 54: 2927
• 11 Li X, Kutta RJ, Jandl C, Bauer A, Nuernberger P, Bach T. Angew. Chem. Int. Ed. 2020; 59: 21640
• 12a Romero NA, Nicewicz DA. J. Am. Chem. Soc. 2014; 136: 17024
• 12b Zhu Q, Graff DE, Knowles RR. J. Am. Chem. Soc. 2018; 140: 741
• 12c Capacci AG, Malinowski JT, McAlpine NJ, Kuhne J, MacMillan DW. C. Nat. Chem. 2017; 9: 1073
• 13 Schneider LM, Schmiedel VM, Pecchioli T, Lenz D, Merten C, Christmann M. Org. Lett. 2017; 19: 2310
• 14 TXT-Catalyzed Cyclization; General Procedure A solution of substrate (1.00 equiv.), TXT (20 mol%) and 2,4,6-triisopropylthiophenol (50 mol%) in degassed dichloromethane (20 mL per 200 μmol of substrate) was irradiated (λ = 420 nm) for four hours in a flame-dried phototube²⁸ under an argon atmosphere at room temperature. Subsequently, the solvent was removed under reduced pressure and the residue was purified by flash chromatography (Et₂O/pentane as eluent). Exemplarily, product 7a (152 mg, 910 μmol, 91%) was obtained as a colorless solid from substrate 6a (166 mg, 1.00 mmol) after purification by flash chromatography (Et₂O/pentane = 10:90). ¹H NMR (500 MHz, CDCl₃): δ = 1.44–1.51 (m, 2 H, C-8-H₂), 1.53–1.58 (m, 4 H, C-7-H₂, C-9-H₂), 1.63–1.70 (m, 4 H, C-6-H₂, C-10-H₂), 2.72 (s, 4 H, C-2-H₂, C-3-H₂). ¹³C NMR (101 MHz, CDCl₃): δ = 20.7 (t, C-7, C-9), 25.1 (t, C-8), 29.5 (t, C-6, C-10), 34.5 (t, C-2, C-3), 56.1 (s, C-5), 216.0 (s, C-1, C-4). The data match the reported values.²⁹ For atom numbering, see Figure 1.
• 15 Lowry MS, Goldsmith JI, Slinker JD, Rohl R, Pascal RA, Malliaras GG, Bernhard S. Chem. Mater. 2005; 17: 5712
• 16 Review: Wu Y, Kim D, Teets TS. Synlett 2022; 33: 1154
• 17 Ir-Catalyzed Cyclization; General Procedure A solution of substrate (1.00 equiv.), Ir(dFCF₃ppy)₂(dtbbpy)PF₆ (5 mol%) and 2,4,6-triisopropylthiophenol (30 mol%) in degassed dichloromethane (20 mL per 200 μmol of substrate) was irradiated (λ = 420 nm) for 16–22 hours in a flame dried-phototube²⁸ under an argon atmosphere at room temperature. Subsequently, the solvent was removed under reduced pressure and the residue was purified by flash chromatography (Et₂O/pentane as eluent). Exemplarily, product 7i (231 mg, 900 μmol, 90%) was obtained as a colorless solid (irradiation time 22 h) from substrate 6i (256 mg, 1.00 mmol) after purification by flash chromatography (Et₂O/pentane = 10:90). ¹H NMR (500 MHz, CDCl₃): δ = 1.44–1.52 (m, 2 H, C-9-H₂), 1.54–1.60 (m, 2 H, C-10-H₂*), 1.71–1.78 (m, 2 H, C-8-H₂*), 1.90–1.94 (m, 2 H, C-7-H₂**), 2.07–2.11 (m, 2 H, C-11 -H₂**), 2.78–2.88 (m, 2 H, C-2-HH, C-4-HH), 3.09–3.19 (m, 3 H, C-3-H, C-2-HH, C-4-HH), 7.23–7.27 (m, 2 H, 2 × C-H _ortho ), 7.28–7.33 (m, 1 H, C-H _para ), 7.37–7.41 (m, 2 H, 2 × C-H _meta ). ¹³C NMR (101 MHz, CDCl₃): δ = 22.1 (t, C-8*), 23.0 (t, C-10*), 25.7 (t, C-9), 27.5 (t, C-7**), 35.1 (t, C-11**), 36.7 (d, C-3), 45.1 (t, C-2, C-4), 66.8 (s, C-6), 126.6 (d, 2 × C _ortho ), 127.5 (d, C _para ), 129.2 (d, 2 × C _meta ), 141.9 (C_ipso), 208.7 (s, C-1, C-5). **An unambiguous assignment of the indicated signals was not possible. For atom numbering, see Figure 2.
• 18 Pavlishchuk VV, Adison AW. Inorg. Chim. Acta 2000; 298: 97
• 19 Yoshida J, Nakatani S, Sakaguchi K, Isoe S. J. Org. Chem. 1989; 54: 3383
• 20 Arias-Rotondo DM, McCusker JK. Chem. Soc. Rev. 2016; 45: 5803
• 21 Herkstroeter WG, Lamola AA, Hammond GS. J. Am. Chem. Soc. 1964; 86: 4537
• 22 Timpe HJ, Kronfeld KP. J. Photochem. Photobiol. A, Chem. 1989; 46: 253
• 23 Our own measurements produced a half-peak potential for compound 6a of E _p/2 = E _ox = +1.36 V (MeCN). The reported values for E _1/2(TXT/TXT^•–) and E _1/2(Ir^III/Ir^II) of Ir(dFCF₃ppy)₂(dtbbpy)PF₆ could be reproduced. See the Supporting Information for further details.
• 24 Luo Y.-R. Handbook of Bond Dissociation Energies in Organic Compounds. CRC Press; Boca Raton: 2003
• 25 Larsen AG, Holm AH, Roberson M, Daasbjerg K. J. Am. Chem. Soc. 2001; 123: 1723
• 26 Shibuya M, Pichierri F, Tomizawa M, Nagasawa S, Suzuki I, Iwabuchi Y. Tetrahedron Lett. 2012; 53: 2070
• 27a Julia M. Acc. Chem. Res. 1971; 4: 386
• 27b Beckwith AL. J, Schiesser CH. Org. Biomol. Chem. 2011; 9: 1736
• 28 For the set-up, see: Poplata S, Bach T. J. Am. Chem. Soc. 2018; 140: 3228
• 29 Burnell DJ, Wu Y.-I. Can. J. Chem. 1990; 68: 804