Synlett 2016; 27(14): 2117-2122
DOI: 10.1055/s-0035-1562845
cluster
© Georg Thieme Verlag Stuttgart · New York

Synthesis of a Five-Fold-Differentiated 1,3,5,7,9-Pentasubstituted Corannulene: A Maximal Labeling Problem in the Context of Corannulene

Roman Maag
a  Department of Chemistry, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland
,
Jay S. Siegel*
a  Department of Chemistry, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland
b  School of Pharmaceutical Science and Technology, Tianjin University, 92 Weijin Road, Nankai District, Tianjin, 300072, P. R. of China   Email: dean_spst@tju.edu.cn
› Author Affiliations
Further Information

Publication History

Received: 12 July 2016

Accepted after revision: 28 July 2016

Publication Date:
05 August 2016 (online)

Abstract

This work defines a maximally labeled isomer problem in the context of 1,3,5,7,9-pentasubstituted corannulenes and explores two new synthetic strategies for the construction of key C–C bonds in the corannulene nucleus: a) a Diels–Alder cycloaddition of thiophene dioxide and acenaphthene fragments; b) a manganese-mediated reductive coupling of benzylic halides, which tolerates carboxy ester functionality. It advances the area of curved aromatics based on corannulene by setting a new family of targets for chemical synthesis and providing additional general synthetic tools.

Supporting Information

 
  • References and Notes

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  • 18 Cycloaddition To an oven-dried 50 mL round-bottom flask, equipped with stir bar and reflux condenser with N2 inlet, was added the acenaphthylene 6 (1.26 g, 3.83 mmol), thiophene-1,1-dioxide 10 (0.89 g, 3.86 mmol), and dry xylene (9 mL). The yellow solution was degassed three times by pulling vacuum and heated to reflux for 24 h. After cooling to r.t., the solvent was removed by rotary evaporation and the crude product was obtained as brown resin. In an oven-dried 100 mL round-bottom flask, equipped with stir bar and reflux condenser with N2 inlet, the crude dihydrofluoranthene (max. 3.83 mmol) was dissolved in dry benzene (65 mL). DDQ (1.3 g, 5.73 mmol) was added in one step, and the dark suspension was heated to reflux for 4 h. After cooling to r.t., the mixture was filtered through a plug of silica and thoroughly rinsed with CH2Cl2. The filtrate was evaporated giving a dark residue which was sonicated with n-hexane. The resulting suspension was filtered through Celite giving a yellow solution. The solution was washed with sat. aq NaHCO3, the organic phase was dried over MgSO4 and filtered. The solvent was evaporated, and the crude product was subjected to flash column chromatography on silica using n-hexane–EtOAc (50:1). The fluoranthenes 11-Br/12-Br (mixture of regioisomers) were obtained as yellow resins (1.05 g, 56%, two steps). Analytical separation of the two isomers was achieved by HPLC (Waters Spherisorb S5, Nitrile, 250 × 20mm, 25 mL/min) with n-hexane–EtOAc (200:1). The solvent mixture was recycled through rotary evaporation. Methyl 4-tert-Butyl-2-bromo-6-ethyl-1,7-dimethyl-10-propylfluoranthene-8-carboxylate (12-Br) Rf  = 0.3 (silica gel; n-hexane–EtOAc, 10:1). IR (film): 2958 (w), 2932 (w), 2872 (w), 1717 (s), 1585 (w), 1458 (m), 1433 (m), 1378 (w), 1364 (w), 1277 (m), 1255 (m), 1200 (s), 1168 (m), 1054 (m), 995 (w), 957 (w), 906 (m), 731 (s). 1H NMR (500 MHz, CDCl3): δ = 8.61 (s, 1 H), 7.81 (s, 1 H), 7.42 (s, 1 H), 3.95 (s, 3 H), 3.05 (q, 3 J = 7.5 Hz, 2 H), 2.96 (t-like, 3 J = 7.5 Hz, 2 H), 2.81 (s, 3 H), 2.73 (s, 3 H), 1.69 (sext, 3 J = 7.5 Hz, 2 H), 1.64 (s, 9 H), 1.35 (t, 3 J = 7.5 Hz, 3 H), 0.90 (t, 3 J = 7.5 Hz, 3 H). 13C{1H} NMR (125 MHz, CDCl3): δ = 168.67, 146.31, 142.11, 141.64, 138.96, 136.95, 134.38, 132.05, 131.40, 131.07, 130.81, 130.07, 130.06, 127.25, 125.86, 125.49, 51.95, 37.32, 36.12, 32.45, 32.43, 29.22, 24.54, 24.35, 21.96, 15.15, 14.16. ESI-HRMS: m/z [M + Na]+ calcd for C29H33BrNaO2 +: 515.1556; found: 515.1551. Methyl 3-tert-Butyl-5-bromo-1-ethyl-6,7-dimethyl-10-propylfluoranthene-8-carboxylate (11-Br) Rf  = 0.3 (silica gel; n-hexane–EtOAc, 10:1). 1H NMR (500 MHz, CDCl3): δ = 8.60 (s, 1 H), 7.85 (s, 1 H), 7.40 (s, 1 H), 3.95 (s, 3 H), 3.13–2.98 (m, 4 H), 2.74 (s, 3 H), 2.69 (s, 3 H), 1.71 (sext, 3 J = 7.5 Hz, 2 H), 1.65 (s, 9 H), 1.34 (t, 3 J = 7.5 Hz, 3 H), 0.96 (t, 3 J = 7.5 Hz, 3 H). 13C{1H} NMR (125 MHz, CDCl3): δ = 168.67, 147.17, 142.42, 141.83, 140.21, 137.89, 134.77, 134.59, 132.38, 131.79, 131.58, 131.06, 129.70, 129.54, 128.08, 126.13, 125.86, 52.13, 37.73, 36.34, 32.65, 31.96, 29.80, 25.15, 24.73, 22.59, 16.10, 14.21. Aryl Coupling The isomeric mixture of bromofluoranthenes 11-Br/12-Br (378 mg, 0.766 mmol), 4-methoxyphenylboronic acid (151.5 mg, 0.996 mmol), and K2CO3 were dissolved in a thoroughly degassed solvent mixture of toluene (13 mL), EtOH (13 mL), and H2O (3.3 mL). To the mixture was added Pd(PPh3)4, and the solution was heated to reflux for 5 h. After cooling to r.t., the mixture was washed with 10% aq HCl (3 × 50 mL) and brine (3 × 50 mL), and the organic phase was dried over MgSO4. Filtering and evaporating the solvent gave the crude product 11-Ar/12-Ar as a yellow solid which was purified by column chromatography on silica with n-hexane–EtOAc (100:1 to 50:1). The two isomers can be separated by normal gravity column chromatography, a first separation delivered the desired isomer as yellow solid (112 mg, 28%). Typically, collected mixed fractions were resubmitted. Methyl 4-tert-Butyl-2-(4-methoxyphenyl)-6-ethyl-1,7-dimethyl-10-propylfluoranthene-8-carboxylate (12-Ar) Rf  = 0.3 (silica gel; n-hexane–EtOAc, 10:1). IR (film): 2955 (m), 2932 (w), 2871 (w), 2835 (w), 1714 (s), 1608 (m), 1513 (m), 1462 (m), 1433 (m), 1390 (m), 1364 (m), 1281 (m), 1264 (s), 1245 (s), 1200 (s), 1174 (s), 1160 (m), 1055 (m), 1036 (m), 994 (w), 958 (w), 894 (m), 835 (m), 737 (s), 705 (m), 580 (m). 1H NMR (500 MHz, CDCl3): δ = 8.25 (s, 1 H), 7.83 (s, 1 H), 7.46 (s, 1 H), 7.43 (d, 3 J = 8.5 Hz, 2 H), 7.04 (d, 3 J =  8.5 Hz, 2 H), 3.96 (s, 3 H), 3.91 (s, 3 H), 3.11 (q, 3 J = 7.5 Hz, 2 H), 3.04 (t-like, 3 J = 7.5 Hz, 2 H), 2.85 (s, 3 H), 2.52 (s, 3 H), 1.74 (sext, 3 J = 7.5 Hz, 2 H), 1.66 (s, 9 H), 1.37 (t, 3 J = 7.5 Hz, 3 H), 0.94 (t, 3 J = 7.5 Hz, 3 H). 13C{1H} NMR (125 MHz, CDCl3): δ = 169.07, 159.06, 147.23, 143.00, 142.24, 142.16, 138.67, 136.76, 135.54, 135.16, 134.43, 132.15, 131.31, 131.25, 131.16, 130.99, 129.80, 128.09, 126.95, 125.12, 113.98, 55.58, 52.06, 37.81, 36.44, 32.73, 29.52, 24.39, 23.27, 22.26, 15.53, 14.44. ESI-HRMS: m/z [M•+] calcd for C36H40NaO3 +: 543.2870; found: 543.2870. Methyl 3-tert-Butyl-5-(4-methoxyphenyl)-1-ethyl-6,7-dimethyl-10-propylfluoranthene-8-carboxylate (11-Ar) Rf  = 0.3 (silica gel; n-hexane–EtOAc, 10:1). IR (film): 2959 (m), 2873 (w), 1718 (m), 1608 (w), 1513 (m), 1461 (m), 1437 (m), 1391 (w), 1378 (w), 1365 (w), 1319 (s), 1219 (m), 1175 (m), 1108 (w), 1088 (w), 1058 (w), 1034 (m), 908 (m), 836 (m), 729 (m). 1H NMR (500 MHz, CDCl3): δ = 8.23 (s, 1 H), 7.85 (s, 1 H), 7.44 (d, 3 J = 8.5 Hz, 2 H), 7.04 (d, 3 J = 8.5 Hz, 2 H), 3.95 (s, 3 H), 3.90 (s, 3 H), 3.14 (q, 3 J = 7.5 Hz, 2 H), 3.05 (t-like, 3 J = 7.5 Hz, 2 H), 2.80 (s, 3 H), 2.46 (s, 3 H), 1.73 (sext, 3 J = 7.5 Hz, 2 H), 1.66 (s, 9 H), 1.35 (t, 3 J = 7.5 Hz, 3 H), 0.96 (t, 3 J = 7.5 Hz, 3 H). 13C{1H} NMR (125 MHz, CDCl3): δ = 168.80, 159.07, 147.92, 142.68, 142.40, 142.38, 139.75, 137.50, 135.46, 135.28, 134.44, 131.94, 131.64, 131.44, 131.20, 130.73, 129.30, 127.62, 127.45, 125.20, 113.97, 55.58, 52.04, 37.88, 36.45, 32.70, 29.90, 24.71, 23.72, 22.68, 16.27, 14.22.
  • 19 Maag R. PhD Thesis. University of Zurich; Switzerland: 2012
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  • 21 Bromination Fluoranthene 12-Ar (112 mg, 0.215 mmol) was dissolved in CCl4 (5 mL), and NBS (199 mg, 1.12 mmol) and BPO (2 mg) were added. The mixture was heated to reflux by irradiating with an incandescent light bulb (Osram, 100 W). After 7 h the suspension was cooled in an ice bath, and the succinimide was filtered with a frit. The filtrate was evaporated (recycling of CCl4) and dissolved in CH2Cl2. The CH2Cl2 solution was thoroughly washed with H2O, dried over MgSO4, filtered, and evaporated to deliver a crude bromide mixture (185 mg). Ring Closure To an oven-dried two-necked 50 mL round-bottom flask, equipped with stir bar, was added the crude mixture of bromofluoranthenes (185 mg) in THF (16 mL), and H2O (10 mL) was added. The solution was thoroughly degassed and CuCl2 was added and the now yellow-greenish mixture was stirred at r.t. for 3 min, prior to the addition of Mn powder in one step. The reaction mixture was stirred at r.t. for 24 h, and was then quenched with 10% aq HCl and extracted with MTBE (3 × 60 mL). The organic phase was washed with brine (3 × 50 mL), dried over MgSO4, filtered, and evaporated to give a crude cyclized product as an orange-brownish resin (83 mg). Dehydrogenation The crude cyclized product (42 mg) was dissolved in dry benzene (4 mL), and DDQ (55.6 mg, 0.245 mmol) was added. The dark mixture was refluxed for 5 h and was diluted with n-hexane after cooling to r.t. The suspension was filtered through a plug of Al2O3, which was thoroughly rinsed with n-hexane–EtOAc (20:1). The filtrate was washed with sat. aq NaHCO3, dried over MgSO4, filtered, and evaporated to give the crude corannulene 15 as a yellow-brownish resin (18 mg). Preparative TLC with n-hexane–EtOAc (50:1) followed by n-hexane–EtOAc–toluene (50:1:1) afforded the pentasubstituted corannulene 15 as a yellowish resin (5.2 mg, 11%, 3 steps). Rf  = 0.3 (silica gel; n-hexane–EtOAc, 10:1). IR (film): 2955 (w), 2930 (w), 2871 (w), 1715 (m), 1607 (w), 1514 (m), 1463 (m), 1438 (w), 1394 (w), 1365 (w), 1247s, 1207 (w), 1175 (m), 1137 (w), 1121 (w), 1094 (w), 1069 (w), 1035 (w), 988 (w), 882 (w), 835 (w). 1H NMR (500 MHz, CDCl3): δ = 8.79 (s, 1 H), 8.30 (q, 4 J = 1.1 Hz, 1 H), 8.25 (s, 1 H), 7.84 (s, 1 H), 7.69 (d, 3 J = 8.7 Hz), 7.55 (t, 4 J = 0.9 Hz), 7.12 (d, 3 J = 8.7 Hz), 4.09 (s, 3 H), 3.93 (s, 3 H), 3.15 (dq, 3 J = 7.5 Hz, 4 J = 0.9 Hz, 2 H), 2.85 (d, 4 J = 1.1 Hz, 3 H), 1.74 (s, 9 H), 1.46 (t, 3 J = 7.5 Hz). 13C{1H} NMR (125 MHz, CDCl3): δ = 167.83, 159.44, 150.54, 144.25, 140.07, 138.26, 137.99, 135.70, 134.36, 134.32, 133.54, 132.57, 131.00, 130.35, 130.32, 130.21, 128.60, 128.57, 127.70, 127.63, 127.56, 126.19, 123.98, 119.74, 114.28, 55.44, 22.24, 37.29, 32.61, 26.43, 19.03, 16.90. ESI-HRMS: m/z [M•+] calcd for C36H32NaO3 +: 535.2249; found: 535.2241.