A Chiral, Dendralenic C–H Acid

Abstract

We report the synthesis of a chiral dendralenic C–H acid, which contains three unsubstituted binaphthyl moieties. This motif and an achiral variant can be made from their corresponding bis(sulfone) precursors in one step. Despite the presence of the enantiopure binaphthyl backbone, the newly designed chiral C–H acid showed only poor enantioselectivity in a Mukaiyama aldol reaction. First attempts toward the synthesis of 3,3′-hexasubstituted binaphthyl-based dendralenic acids are also reported.

Key words

dendralenic C–H acids - C ₃ symmetry - Brønsted and Lewis acid catalysis - binaphthyl backbone - conjugated anion

• References and Notes

• 1a Mitschke B, Turberg M, List B. Chem 2020; 6: 2515
• 1b Schreyer L, Properzi R, List B. Angew. Chem. Int. Ed. 2019; 58: 12761
• 2a Höfler D, Goddard R, Nöthling N, List B. Synlett 2019; 30: 433
• 2b Gatzenmeier T, van Gemmeren M, Xie Y, Höfler D, Leutzsch M, List B. Science 2016; 351: 949
• 2c Gheewala CD, Collins BE, Lambert TH. Science 2016; 351: 961
• 3a Okamoto K, Kitagawa T, Takeuchi K, Komatsu K, Kinoshita T, Aonuma S, Nagai M, Miyabo A. J. Org. Chem. 1990; 55: 996
• 3b Jutz C, Amschler H. Chem. Ber. 1964; 97: 3331
• 3c Kuhn R, Rewicki D. Angew. Chem. 1967; 79: 648
• 4 General Procedure for Achiral Acid 1A Schlenk flask was charged with commercially available bis(phenylsulfonyl)methane (0.77 g, 2.5 mmol, 3.0 equiv) and perchlorate salt 3 (0.32 g, 0.83 mmol, 1.0 equiv). The solid mixture was partially dissolved in pyridine (5.4 mL) and a solution of NaOMe (0.42 g, 2.9 mmol, 3.5 equiv) in MeOH (0.53 mL, 5.4 M) was added. A clear, orange solution was obtained, and the reaction mixture was heated to 120 °C for 3 h which provided a dark red solution. All volatiles were removed under reduced pressure. Purification via flash column chromatography (silica, 0.5–10% gradient of MeOH in CH₂Cl₂) afforded the title compound as an orange solid (60 mg, 0.064 mmol, 7.7% yield).¹H NMR (501 MHz, CDCl₃): δ = 8.50 (t, J = 1.9 Hz, 1 H), 8.40 (t, J = 1.7 Hz, 1 H), 7.98–7.92 (m, 4 H), 7.91–7.86 (m, 2 H), 7.84–7.76 (m, 6 H), 7.76–7.71 (m, 2 H), 7.62–7.57 (m, 4 H), 7.57–7.52 (m, 2 H), 7.52–7.44 (m, 2 H), 7.44–7.38 (m, 2 H), 7.34 (dddd, J = 9.9, 8.2, 6.5, 2.0 Hz, 6 H), 6.01 (dt, J = 11.1, 2.0 Hz, 1 H), 5.22 (d, J = 11.1 Hz, 1 H). MS (ESIneg): m/z = 933 [M – H⁺]. HRMS (ESIneg): m/z [M – H⁺] calcd for C₄₃H₃₃O₁₂S₆ ^–: 933.0302; found: 933.0302. Owing to the expected high symmetry of the anion, triethylamine was added and NMR spectra of this species in CDCl₃ were acquired.¹H NMR (500 MHz, CDCl₃): δ = 8.36 (s, 3 H), 7.70 (d, J = 7.8 Hz, 12 H), 7.33 (t, J = 7.4 Hz, 6 H), 7.19 (t, J = 7.7 Hz, 12 H). ¹³C NMR (126 MHz, CDCl₃): δ = 156.81, 142.11, 132.43, 128.47, 128.15, 125.14, 107.38. MS (ESIneg): m/z = 933 [M – H⁺].
• 5 General Procedure for Chiral Acid 2A Schlenk flask was charged with solid (S)-4H-dinaphtho[2,1-d:1′,2′-f][1,3]dithiepine 3,3,5,5-tetraoxide (S3, 0.06 g, 0.15 mmol, 3.0 equiv) and perchlorate salt 3 (0.02 g, 0.05 mmol, 1.0 equiv). The solid mixture was partially dissolved in pyridine (2.0 mL) and a solution of NaOMe (0.26 g, 0.18 mmol, 3.5 equiv) in MeOH (0.033 mL, 5.4 M) was added.^3a A clear, red solution was obtained and the reaction mixture was heated to 100 °C for 3 h. A dark red solution was obtained. All volatiles were removed under reduced pressure. Purification via flash column chromatography (silica, 0.25–10% gradient of MeOH in CH₂Cl₂) and acidification with aq. HCl (6 M) afforded the title compound as an orange solid (12 mg, 0.05 mmol, 19% yield).¹H NMR (501 MHz, CDCl₃): δ = 8.27 (d, J = 4.9 Hz, 1 H), 8.25 (dd, J = 3.9, 1.1 Hz, 3 H), 8.23 (s, 1 H), 8.21 (d, J = 3.5 Hz, 1 H), 8.19 (d, J = 3.6 Hz, 1 H), 8.08–7.94 (m, 9 H), 7.92 (d, J = 8.2 Hz, 1 H), 7.87 (d, J = 8.2 Hz, 1 H), 7.77–7.62 (m, 7 H), 7.59 (d, J = 8.8 Hz, 1 H), 7.48–7.31 (m, 6 H), 7.28 (d, J = 8.7 Hz, 1 H), 7.22 (dd, J = 8.9, 5.1 Hz, 3 H), 7.17 (t, J = 8.2 Hz, 2 H), 6.05 (dt, J = 10.5, 1.9 Hz, 1 H), 5.55 (d, J = 10.5 Hz, 1 H). MS (ESIneg): m/z = 1227 [M – H⁺].HRMS (ESIneg): m/z [M – H⁺] calcd for C₆₇H₃₉O₁₂S₆ ^–: 1227.0771; found 1227.0771.
• 6 García-García P, Lay F, García-García P, Rabalakos C, List B. Angew. Chem. Int. Ed. 2009; 48: 4363
• 7a Akiyama T. Chem. Rev. 2007; 107: 5744
• 7b Seayad J, Seayad AM, List B. J. Am. Chem. Soc. 2006; 128: 1086