A Dendralenic C–H Acid

Published as part of the 30 Years SYNLETT – Pearl Anniversary Issue

Abstract

The design and synthesis of a strong, dendralenic C–H acid is described. Crystal structure analyses confirm the proposed structure. Despite the moderate stability of our motif, an application to Brønsted acid catalysis has been explored.

Key words

dendralenic C–H acids - cross-conjugated acids - triflyl groups - strong acids - non-coordinating anions - Brønsted acids

• References and Notes

• 1a Kütt A, Rodima T, Saame J, Raamat E, Mäemets V, Kaljurand I, Koppel IA, Garlyauskayte RYu, Yagupolskii YL, Yagupolskii LM, Bernhardt E, Willner H, Leito I. J. Org. Chem. 2011; 76: 391
• 1b Koppel IA, Taft RW, Anvia F, Zhu S.-Z, Hu L.-Q, Sung K.-S, DesMarteau DD, Yagupolskii LM, Yagupolskii YL. J. Am. Chem. Soc. 1994; 116: 3047
• 1c Turowsky L, Seppelt K. Inorg. Chem. 1988; 27: 2135
• 1d Höfler D, van Gemmeren M, Wedemann P, Kaupmees K, Leito I, Leutzsch M, Lingnau JB, List B. Angew. Chem. Int. Ed. 2017; 56: 1411
• 1e Ishihara K, Hiraiwa Y, Yamamoto H. Synlett 2000; 80
• 1f For a description of pentacarboxycyclopentadiene-derived acids, see: Gheewala CD, Radtke MA, Hui J, Hon AB, Lambert TH. Org. Lett. 2017; 19: 4227 ; and references cited therein
• 2 Höfler D, Goddard R, Lingnau JB, Nöthling N, List B. Angew. Chem. Int. Ed. 2018; 57: 8326
• 3 Kuhn R, Rewicki D. Angew. Chem. 1967; 79: 648
• 4a Hansch C, Leo A, Taft RW. Chem. Rev. 1991; 91: 165
• 4b Hendrickson JB, Giga A, Wareing J. J. Am. Chem. Soc. 1974; 96: 2275
• 5a Yanai H, Egawa S, Taguchi T. Tetrahedron Lett. 2013; 54: 2160
• 5b Yanai H, Egawa S, Yamada K, Ono J, Aoki M, Matsumoto T, Taguchi T. Asian J. Org. Chem. 2014; 3: 556
• 6a Arnold Z, Budesinsky M. J. Org. Chem. 1988; 53: 5352
• 6b Krasnaya ZA, Smirnova YV, Krystal GV, Bogdanov VS. Mendeleev Commun. 1996; 6: 17
• 6c Buděšínský M, Fiedler P, Arnold Z. Synthesis 1989; 858
• 7 Triformylmethane was prepared in two steps from commercially available bromoacetic acid following our recently reported procedure, see Ref. 2.
• 8 HTMP·TBTA Schlenk flask was charged with bis(triflyl)methane (1.7 g, 6.0 mmol, 6.0 equiv) and dry CH₂Cl₂ (1 mL) was added under argon. The colorless, clear solution so obtained was cooled to –78 °C in an acetone/dry ice bath. Triformylmethane (0.10 g, 1.0 mmol) was added and a slurry was obtained. Trimethyl orthoacetate (0.47 g, 3.9 mmol, 0.50 mL, 3.9 equiv) and acetic anhydride (1.6 g, 16 mmol, 1.5 mL, 16 equiv) were added and the reaction mixture was allowed to reach RT overnight. A dark red solution was obtained. All volatiles were removed under reduced pressure and the solid mixture so obtained was dissolved in CH₂Cl₂ (5 mL). 2,2,6,6-Tetramethylpiperidine (0.85 g, 6.0 mmol, 1.0 mL, 6.0 equiv) was added and the reaction mixture was subsequently concentrated under reduced pressure. Almost complete removal of all volatiles was achieved by dissolving in CHCl₃ and evaporation to dryness. The solid mixture was transferred to a separation funnel with CHCl₃ (20 mL) and washed with sat. aq NaHCO₃ (20 mL). Both phases were separated and the aq phase was washed with CHCl₃ (20 mL), acidified with aq HCl (conc.) to a pH of 1, and extracted with CH₂Cl₂ (20 mL). The pooled CH₂Cl₂ phases were concentrated under reduced pressure to give the TMP salt of the title compound as an orange solid (0.35 g). As this compound still contained significant amounts of bis(triflyl)methane, the solid mixture was dissolved in CHCl₃, washed with aq HCl (conc.), dried over MgSO₄, filtered, and concentrated under reduced pressure. The red solid so obtained was dissolved in CHCl₃ and all volatiles were removed under reduced pressure. This procedure was repeated once more with CHCl₃ and then with 1,2-dichloroethane. A red solid was obtained, which was triturated with CHCl₃ to give the TMP salt of the title compound as a yellow solid (60 mg, 0.058 mmol, 5.8% yield). ¹H NMR (500 MHz, CDCl₃): δ = 8.31 (s, 3 H), 5.61 (s, 2 H), 1.86–1.81 (m, 2 H), 1.75–1.72 (m, 4 H), 1.49 (s, 12 H). (¹⁴N couplings can be observed in the ¹H NMR spectrum. However, the signals of NH₂ group was not sharp enough for an accurate determination of ¹ J _1H14N.) ¹³C NMR (126 MHz, CDCl₃): δ = 165.51, 119.82 (q, ¹ J _CF = 328 Hz), 114.79, 108.53, 59.94, 35.23, 27.87, 15.95; ¹⁹F NMR (471 MHz, CDCl₃): δ = –73.96; HRMS (ESIneg): m/z [M – H⁺] calcd for C₁₃H₃O₁₂F₁₈S₆ ^–: 884.7667; found: 884.7667. Single crystals suitable for structural analysis were obtained after dissolving the initially obtained orange solid [containing bis(triflyl)methane impurities] in CHCl₃ or 1,2-dichloroethane and slowly evaporating the solvent.
• 9 Synthesis of HTBT as the Free Acid HTMP·TBT (17 mg, 0.017 mmol) was dissolved in CH₂Cl₂ (10 mL) and conc. H₂SO₄ (10 mL) was added. The mixture was stirred at RT for 30 min and the sulfuric acid phase was removed using a Pasteur pipet. BaCl₂ (dry) was added and after stirring for 30 min, the solution was filtered and all volatiles were removed under reduced pressure. A yellowish solid was obtained. NMR spectra (¹H and ¹⁹F) in CDCl₃ were acquired. After 3 d, ¹H and ¹⁹F NMR spectra were acquired once again, but after this time period, all product signals had vanished due to deprotonation and decomposition. ¹H NMR (501 MHz, CDCl₃): δ = 8.80 (t, J = 1.7 Hz, 1 H), 8.59 (t, J = 1.7 Hz, 1 H), 6.52 (d, J = 10.9 Hz, 1 H), 5.36 (d, J = 10.9 Hz, 1 H); ¹³C NMR (126 MHz, CD₂Cl₂): δ = 162.66, 158.32, 136.73, 123.98, 119.52 (q, J = 331 Hz), 76.06. (Due to the fast decomposition of the desired product and the observed ¹³C to ¹⁹F coupling, not all signals in the ¹³C NMR spectrum were obtained.) ¹⁹F NMR (471 MHz, CDCl₃): δ = –71.48, –72.25, –72.52, –72.87, –73.00. The HTMP·TBT salt (0.017 g, 0.017 mmol) was dissolved in CH₂Cl₂ (10 mL) and conc. H₂SO₄ (10 mL) was added. The mixture was stirred at RT for 30 min and the sulfuric acid phase was removed. Treatment with BaCl₂ was omitted. After three months, single crystals of the title compound were obtained which were suitable for structure analysis.
• 10 Höfler D. Ph.D. thesis. Universität zu Köln: Germany 2018
• 11 Conversion of HTBT into the Etherate SaltHTMP·TBT (43 mg, 0.042 mmol) was dissolved in CH₂Cl₂ (10 mL) and conc. H₂SO₄ (10 mL) was added. The mixture was stirred at RT for 30 min and the sulfuric acid phase was removed. All volatiles were removed under reduced pressure and a colorless solid was obtained. Et₂O was added, which afforded a clear, yellow solution. All volatiles were removed under reduced pressure and a yellow solid was obtained. CH₂Cl₂ (10 mL) was added and the formation of a biphasic mixture was noticed. Slow evaporation over 14 d led to the formation of single crystals of the etherate salt, which were suitable for structure analysis.
• 12 Jutzi P, Müller C, Stammler A, Stammler H.-G. Organometallics 2000; 19: 1442