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Asymmetric Synthesis of 1,1-Diarylalkanes via Friedel–Crafts Alkylation of Donor–Acceptor Cyclopropanes with Electron-Rich Benzene
Asymmetric Synthesis of 1,1-Diarylalkanes via Friedel–Crafts Alkylation of Donor–Acceptor Cyclopropanes with Electron-Rich Benzene
Journal of the Korean Chemical Society. 2016. Oct, 60(5): 374-377
Copyright © 2016, Korean Chemical Society
  • Received : June 04, 2016
  • Accepted : July 06, 2016
  • Published : October 20, 2016
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Jong-Tack Sim
Sung-Gon Kim

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EXPERIMENTAL
General procedure for indane-bis(oxazoline)/Mg(ClO4)2-catalyzed asymmetric Friedel−Crafts alkylation reaction: To a flame-dried flask charged with Mg(ClO 4 ) 2 (0.010 mmol, 0.10 equiv), indane-bis(oxazoline) L6 (0.012 mmol, 0.12 equiv), and 4 Å molecular sieve (20 mg, 3.0% w/v) in an inert atmosphere, was added CH 2 Cl 2 (0.75 mL) and the resulting mixture was stirred vigorously for q h under an inert atmosphere. A solution of N , N -methylaniline 1 (0.10 mmol, 1.0 equiv) and cyclopropane (0.12 mmol, 1.2 equiv) in CH 2 Cl 2 (0.25 mL) was then added via syringe. The resulting mixture was stirred at rt until complete consumption of N , N -methylaniline 1 was observed as determined by TLC. The resulting mixture was directly purified on silica gel column chromatography using ethyl acetate and hexane as eluents to afford the desired 1,1-diarylalkane compound 3 .
Dimethyl 2-(2-(4-(dimethylamino)phenyl)-2-phenylethyl) malonate (3a). colorless gum;
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= −74.5 ( c = 0.066, CHCl 3 ); 1 H NMR (400 MHz, CDCl 3 ) δ 7.30–7.20 (m, 4H), 7.16 (t, J =7.0 Hz, 1H), 7.09 (d, J = 8.6 Hz, 2H), 6.67 (d, J =8.6 Hz, 2H), 3.84 (t, J =8.0 Hz, 1H), 3.70 (d, J =2.0 Hz, 6H), 3.30 (t, J =7.4 Hz, 1H), 2.90 (s, 6H), 2.62 (t, J =7.7 Hz, 2H); 13 C NMR (100 MHz, CDCl 3 ) δ 169.93, 169.90, 149.33, 144.26, 131.12, 128.52, 127.79, 126.30, 112.83, 52.54, 52.53, 50.12, 47.73, 40.68, 34.72; IR (film) 2951, 2708, 1751, 1613, 1513, 1434, 1310, 1223, 1148, 1047 cm −1 ; HRMS (EI) m/z calcd for [M] + C 21 H 25 NO 4 : 355.1784 Found: 355.1782: 84:16 er; Chiralpak IA column and IA guard column (5% EtOH:hexanes, 1.0 mL/min flow, λ = 254 nm); minor -isomer t r = 8.4 min and major -isomer t r = 9.4 min.
Dimethyl 2-(2-(4-(dimethylamino)phenyl)-2-(4-methoxyphenyl)ethyl)-malonate (3b). colorless gum;
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= 6.7 ( c = 0.17, CHCl 3 ); 1 H NMR (400 MHz, CDCl 3 ) δ 7.13 (d, J = 8.6 Hz, 2H), 7.07 (d, J = 8.7 Hz, 2H), 6.81 (d, J = 8.7 Hz, 2H), 6.66 (d, J = 8.7 Hz, 2H), 3.79 (t, J = 8.0 Hz, 1H), 3.76 (s, 3H), 3.70 (d, J = 1.3 Hz, 6H), 3.29 (t, J = 7.4 Hz, 1H), 2.90 (s, 6H), 2.59 (t, J = 7.7 Hz, 2H); 13 C NMR (100 MHz, CDCl 3 ) δ 169.95, 158.02, 149.29, 136.38, 131.58, 128.74, 128.41, 113.89, 112.85, 55.25, 52.52, 50.14, 46.88, 40.71, 34.93; IR (film) 2951, 1732, 1610, 1509, 1435, 1341, 1246, 1225, 1153, 1034 cm −1 ; HRMS (EI) m/z calcd for [M] + C 22 H 27 NO 5 : 385.1889 Found: 385.1867; 78:22 er; Chiralpak IA column and IA guard column (5% EtOH: hexanes, 1.0 mL/min flow, λ = 254 nm); minor -isomer t r = 11.4 min and major -isomer t r = 13.3 min.
Dimethyl 2-(2-(4-(dimethylamino)phenyl)-2-(4-methoxyphenyl)ethyl)-malonate (3b). colorless gum;
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= 6.7 ( c = 0.17, CHCl 3 ); 1 H NMR (400 MHz, CDCl 3 ) δ 7.13 (d, J = 8.6 Hz, 2H), 7.07 (d, J = 8.7 Hz, 2H), 6.81 (d, J = 8.7 Hz, 2H), 6.66 (d, J = 8.7 Hz, 2H), 3.79 (t, J = 8.0 Hz, 1H), 3.76 (s, 3H), 3.70 (d, J = 1.3 Hz, 6H), 3.29 (t, J = 7.4 Hz, 1H), 2.90 (s, 6H), 2.59 (t, J = 7.7 Hz, 2H); 13 C NMR (100 MHz, CDCl 3 ) δ 169.95, 158.02, 149.29, 136.38, 131.58, 128.74, 128.41, 113.89, 112.85, 55.25, 52.52, 50.14, 46.88, 40.71, 34.93; IR (film) 2951, 1732, 1610, 1509, 1435, 1341, 1246, 1225, 1153, 1034 cm −1 ; HRMS (EI) m/z calcd for [M] + C 22 H 27 NO 5 : 385.1889 Found: 385.1867; 78:22 er; Chiralpak IA column and IA guard column (5% EtOH: hexanes, 1.0 mL/min flow, λ = 254 nm); minor -isomer tr = 11.4 min and major -isomer tr = 13.3 min.
Dimethyl 2-(2-(4-(dimethylamino)phenyl)-2-(3,4-dimethoxyphenyl)-ethyl)malonate (3c). colorless gum;
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= −7.8 ( c = 0.16, CHCl 3 ); 1 H NMR (400 MHz, CDCl 3 ) δ 7.08 (d, J = 8.6 Hz, 2H), 6.78 (s, 2H), 6.72 (s, 1H), 6.67 (d, J = 8.7 Hz, 2H), 3.83 (s, 6H), 3.79 (t, J = 8.1 Hz, 1H), 3.70 (d, J = 0.7 Hz, 6H), 3.31 (t, J = 7.3 Hz, 1H), 2.90 (s, 6H), 2.59 (t, J = 7.7 Hz, 2H); 13 C NMR (100 MHz, CDCl 3 ) δ 169.95, 149.32, 148.88, 147.47, 136.82, 131.39, 128.36, 119.59, 112.84, 111.25, 111.15, 55.88, 55.84, 52.52, 50.11, 47.32, 40.69, 34.93; IR (film) 2951, 2836, 1731, 1612, 1514, 1437, 1342, 1234, 1142, 1028 cm −1 ; HRMS (EI) m/z calcd for [M] + C 23 H 29 NO 6 : 415.1995 Found: 415.1992; 85:15 er; Chiralpak IA column and IA guard column (5% i -PrOH:hexanes, 1.0 mL/min flow, λ = 254 nm); major -isomer t r = 26.6 min and minor -isomer t r = 29.2 min.
Dimethyl 2-(2-(4-(dimethylamino)phenyl)-2-p-tolylethyl) malonate (3d). colorless gum;
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= 8.6 ( c = 0.41, CHCl 3 ); 1 H NMR (400 MHz, CDCl 3 ) δ 7.09 (dd, J = 13.4, 7.6 Hz, 6H), 6.66 (d, J = 8.7 Hz, 2H), 3.80 (t, J = 8.1 Hz, 1H), 3.69 (d, J = 1.6 Hz, 6H), 3.30 (t, J = 7.4 Hz, 1H), 2.89 (s, 6H), 2.60 (t, J = 7.7 Hz, 2H), 2.28 (s, 3H); 13 C NMR (100MHz, CDCl 3 ) δ 170.04, 149.41, 141.33, 135.86, 131.57, 129.31, 128.55, 127.76, 112.98, 52.61, 50.25, 47.41, 40.81, 34.89, 21.09; IR (film) 2950, 1732, 1612, 1519, 1434, 1342, 1273, 1224, 1152 cm −1 ; HRMS (EI) m/z calcd for [M] + C 22 H 27 NO 4 : 369.1940 Found: 369.1954; 71:29 er; Chiralpak IA column and IA guard column (2% EtOH: hexanes, 1.0 mL/min flow, λ = 254 nm); minor -isomer t r = 10.4 min and major -isomer t r = 13.6 min.
Dimethyl 2-(2-(4-(dimethylamino)phenyl)-2-(4-fluorophenyl) ethyl)-malonate (3e). colorless gum;
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= 3.3 ( c = 0.16, CHCl 3 ); 1 H NMR (400 MHz, CDCl 3 ) δ 7.17 (dd, J = 8.5, 5.5 Hz, 2H), 7.06 (d, J = 8.7 Hz, 2H), 6.95 (t, J = 8.7 Hz, 2H), 6.67 (d, J = 8.7 Hz, 2H), 3.83 (t, J = 8.1 Hz, 1H), 3.70 (d, J = 4.4 Hz, 6H), 3.28 (t, J = 7.4 Hz, 1H), 2.90 (s, 6H), 2.59 (t, J = 7.7 Hz, 2H); 13 C NMR (100 MHz, CDCl 3 ) δ 169.91, 169.90, 162.70, 160.27, 149.49, 140.18, 140.15, 130.84, 129.32, 129.24, 128.52, 115.45, 115.24, 112.91, 52.66, 52.64, 50.14, 47.08, 40.72, 34.94; IR (film) 2952, 1732, 1613, 1520, 1507, 1434, 1344, 1275, 1220, 1157 cm −1 ; HRMS (EI) m/z calcd for [M] + C 21 H 24 FNO 4 : 373.1689 Found: 373.1674; 80:20 er; Chiralpak IA column and IA guard column (2% i-PrOH:hexanes, 1.0 mL/min flow, λ = 254 nm); minor-isomer t r = 17.5 min and major-isomer t r = 18.7 min.
Dimethyl 2-(2-(4-(dimethylamino)phenyl)-2-(furan-2-yl)ethyl)malonate (3f). colorless gum;
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= −25.6 ( c = 0.13, CHCl 3 ); 1 H NMR (400 MHz, CDCl 3 ) δ 7.30 (d, J = 0.9 Hz, 1H), 7.08 (d, J = 8.6 Hz, 2H), 6.68 (d, J = 8.7 Hz, 2H), 6.27 (dd, J = 2.9, 1.9 Hz, 1H), 6.06 (d, J = 3.1 Hz, 1H), 3.93–3.84 (m, 1H), 3.71 (d, J = 22.5 Hz, 6H), 3.31 (dd, J = 8.0, 6.8 Hz, 1H), 2.91 (s, 6H), 2.67 (dt, J = 15.2, 7.6 Hz, 1H), 2.45 (ddd, J = 13.9, 8.9, 6.7 Hz, 1H); 13 C NMR (100 MHz, CDCl 3 ) δ 169.85, 169.82, 157.25, 149.80, 141.63, 128.75, 128.64, 112.92, 110.10, 105.62, 52.69, 52.66, 49.85, 42.10, 40.76, 33.86; IR (film) 2952, 1732, 1613, 1520, 1435, 1345, 1222, 1153 cm −1 ; HRMS (EI) m/z calcd for [M] + C 19 H 23 NO 5 : 345.1576 Found: 345.1543; 68:32 er; Chiralpak IA column and IA guard column (2% EtOH: hexanes, 1.0 mL/min flow, λ = 254 nm); major -isomer t r = 11.4 min and mino -isomer t r = 13.1 min.
Dimethyl 2-(2-(4-(dimethylamino)phenyl)-2-(thiophen-2-yl)ethyl)malonate (3g). colorless gum;
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= 2.8 ( c = 0.31, CHCl 3 ); 1 H NMR (400 MHz, CDCl 3 ) δ 7.12 (dd, J = 8.5, 4.8 Hz, 3H), 6.90 (dd, J = 5.0, 3.5 Hz, 1H), 6.84 (d, J = 3.4 Hz, 1H), 6.68 (d, J = 8.7 Hz, 2H), 4.12– 4.04 (m, 1H), 3.70 (d, J = 19.0 Hz, 6H), 3.33 (dd, J = 8.1, 6.7 Hz, 1H), 2.91 (s, 6H), 2.70 (ddd, J = 15.2, 8.1, 7.1 Hz, 1H), 2.58 (ddd, J = 13.8, 9.1, 6.6 Hz, 1H); 13 C NMR (100 MHz, CDCl 3 ) δ 169.75, 169.72, 149.65, 148.92, 130.55, 128.40, 126.59, 123.85, 123.80, 112.75, 52.58, 49.94, 43.47, 40.62, 36.19; IR (film) 2951, 1732, 1612, 1520, 1434, 1346, 1221, 1155 cm −1 ; HRMS (EI) m/z calcd for [M] + C 19 H 23 O 4 S: 361.1348 Found: 361.1313; 53:47 er; Chiralpak IA column and IA guard column (2% EtOH:hexanes, 1.0 mL/min flow, λ = 254 nm); major -isomer t r = 12.8 min and mino- isomer t r = 15.5 min.
Acknowledgements
This work was supported by Kyonggi University Research Grant 2015.
References
Kim A. , Kim S.-G. 2015 Eur. J. Org. Chem. 6419 -