CC BY-NC-ND 4.0 · Synlett 2022; 33(01): 38-39
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Editorial Board Cluster
A Chiral, Dendralenic C–H Acid
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Generous support from European Research Council (Advanced Grant ‘C–H Acids for Organic Synthesis, CHAOS’), the Horizon 2020 Framework Programme, and the Deutsche Forschungsgemeinschaft (Leibniz Award to B.L. and Cluster of Excellence RESOLV, EXC 1069) is gratefully acknowledged.
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
Supporting Information
Supporting information for this article is available online at https://doi.org/10.1055/a-1705-9786.
Supporting Information
Publikationsverlauf
Eingereicht: 17. September 2021
© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
Georg Thieme Verlag KG
References and Notes
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General Procedure for Achiral Acid 1 A 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 CH2 Cl2 ) afforded the title compound as an orange solid (60 mg, 0.064 mmol, 7.7% yield).1 H 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 C43 H33 O12 S6
– : 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.1 H 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). 13 C 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 2 A 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 CH2 Cl2 ) and acidification with aq. HCl (6 M) afforded the title compound as an orange solid (12 mg, 0.05 mmol, 19% yield).1 H 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 C67 H39 O12 S6
– : 1227.0771; found 1227.0771.
6
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