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Synlett 2002(7): 1158-1160
DOI: 10.1055/s-2002-32588
LETTER
© Georg Thieme Verlag Stuttgart · New York

An Approach to New, Axially Chiral ζ-Amino Alcohols Using a Ring Opening Reaction

Markus Furegati, Andreas J. Rippert*
Organisch-Chemisches Institut, Universität Zürich, Winterthurerstr. 190, 8057 Zürich, Switzerland
Fax: +41(1)6356812; e-Mail: arippert@oci.unizh.ch;
Further Information

Publication History

Received 4 April 2002
Publication Date:
07 February 2007 (online)

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Abstract

The synthesis of axially chiral ζ-amino alcohols 5, carrying a biphenyl moiety, starting from C2 symmetric biphenyl derivatives 1 by a ring opening reaction as the key step is described. Although, evidence is given that enantiomerically pure (P)-1a can be transformed into (P)-5a without loss in enantiomeric purity.

Key words

axial chirality - amino alcohols - ring opening - biphenyl - dibenz[c,e]oxepines

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HPLC/GC analysis on a chiral stationary phase were not yet successful.

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Typical procedure and data on representative products: General procedure for the ring opening reaction: To a stirred solution of the dihydrooxepine (3 mmol) 1 and anhyd sodium iodide in dry acetonitrile (20 mL) at 0 °C was added boron trifluoride ethyl etherate (Fluka purum). The mixture was stirred at the temperature and for the period indicated in Table [1] . The iodine-coloured reaction mixture was poured into ice-cold water (50 mL) and extracted with dichloro-methane. For 2d no further purification was necessary. Protection of the alcohol: The dichloromethane phase (containing traces of iodine) was well dried over anhyd sodium sulfate and treated with hexamethyldisilazane (HMDS, Aldrich). After 2 min the reaction was completed. Filtration and evaporation of the solvent gave a residue, which was purified by a fast column chromatography over 6 g silica gel (eluant: hexane/MTBE 1:1). ( P )-2′-Iodomethyl-6,6′-dimethyl[1,1′-biphenyl]-2-methanol [( P )-2a]: 1H NMR (300 MHz, CDCl3): δ = 7.47 (ddd, 3 J = 7.6, 4 J = 1.3, 4 J = 0.6 Hz); 7.40 (dd, 3 J = 7.6, 4 J = 1.0 Hz ), 7.35 (t, 3 J = 7.6 Hz ); 7.25 (dd, 3 J = 7.5, 4 J = 0.5 Hz); 7.25 (t, 3 J = 7.5 Hz); 7.19 (ddd, 3 J = 7.5, 4 J = 1.4, 4 J = 0.6 Hz); 4.34, 4.27 (AB, 2 J AB = 13.2 Hz); 4.18, 4.05 (AB, 2 J AB = 9.3 Hz); 1.97 (s), 1.90 (s), 1.62 (s). 13C NMR (300 MHz, CDCl3): δ = 138.5; 137.7; 136.6; 136.1; 136.0; 135.7; 129.8; 129.5; 128.4; 128.0; 125.4; 62.8; 19.8; 4.9.
2′-Iodomethyl-6,6′-dinitro[1,1′-biphenyl]-2-methanol (2d): 1H NMR (300 MHz, CDCl3): δ = 8.18 (d, 3 J = 8.2 Hz); 8.08 (dd, 3 J = 8.2, 4 J = 1.2 Hz); 7.96 (dd, 3 J = 7.8, 4 J = 0.5 Hz); 7.82 (dd, 3 J = 7.8, 4 J = 1.1 Hz); 7.68 (t, 3 J = 8.0 Hz); 7.57 (t, 3 J = 8.0 Hz); 4.38, 4.32 (AB, 2 J AB = 13.5 Hz); 4.13, 3.95 (AB, 2 J AB = 10.1 Hz); 1.89 (br. s). 13C NMR (300 MHz, CDCl3): δ = 148.9; 147.6; 141.2; 138.9; 135.7; 133.6; 129.9; 129.9; 129.4; 128.3; 124.4; 124.3; 62.3; 0.7.
{( P )-2′-Azidomethyl-6,6′-dimethyl[1,1′-biphenyl]-2-methyl}trimethylsilylether [( P )-4a(TMS)]: IR (neat,
cm-1): 2099 (s). 1H NMR (300 MHz, CDCl3): δ =7.42 - 7.22 (m); 4.16 (A2, J = 13.6 Hz); 3.99, 3.94 (AB, 2 J AB = 13.9 Hz), 1.92 (s); 1.90 (s); 0.00 (s). 13C NMR (300 MHz, CDCl3): δ = 138.9; 138.9; 137.3; 137.2; 136.4; 134.4; 130.7; 129.9; 128.6; 128.5; 126.9; 126.1; 63.5; 53.8; 20.6; 20.3; 0.0. GC/MS (EI): m/z (%) = 310(100)[M - N2]+.
2′-Azidomethyl-6,6′-dinitro[1,1′-biphenyl]-2-methanol (4d): IR (neat, cm-1): 2102 (s), 1H NMR (300 MHz, CDCl3): δ = 8.13 (dd, 3 J = 7.1, 4 J = 1.1 Hz); 7.91 (d, 3 J = 7.6 Hz); 7.77 (d, 3 J = 7.7 Hz); 7.66 (t, 3 J = 7.9 Hz); 7.65 (t, 3 J = 7.9 Hz); 4.26, 4.23 (AB, J AB = 13.2 Hz); 4.06, 4.02 (AB, J AB = 14.2 Hz); 1.98 (br. s). 13C NMR (300 MHz, CDCl3): δ = 148.8; 148.2; 141.0; 136.3; 133.9; 133.6; 130.0; 129.9; 129.7; 128.5; 124.6; 124.2; 62.4; 52. MS (CI, NH3): m/z (%) = 347(100)[M + NH4]+, 302(20) [M - N2 + H]+.
( P )-2′-Aminomethyl-6,6′-dimethyl[1,1′-biphenyl]-2-methanol [( P )-5a]: [α]D 20 -111.43 (c 1.21, CHCl3). UV (MeOH): λmax 288 (2.71, sh), 274 (3.03), 266 (3.09), 253 (3.10); λmin 273 (3.03), 260 (3.08), 250 (3.10). CD (MeOH): 335.5 (0.12), 322.5 (0.02), 296.0 (0.13), 289.0 (0.03), 280.0 (0.08), 259.0 (-0.48), 236.5 (0.27, sh), 223.0 (3.93), 217.5 (3.06), 207.0 (6.32). IR (neat, cm-1): 3353 (s), 3280 (s), 3063 (s), 2918 (s), 2862 (s), 1935 (w), 1868 (w), 1662 (w), 1591 (m), 1460 (s), 1381 (s), 1236 (m), 1208 (w), 1164 (m), 1074 (s), 1033 (s), 1005 (s). 1H NMR (300 MHz, CDCl3): δ =7.42 (dd, 3 J = 7.0, 4 J = 1.0 Hz, 1 H); 7.33 -7.17 (m, 5 H); 4.18, 4.08 (AB, 2 J AB = 11.3 Hz, CH2OH); 3.66 (d, 2 J = 11.4 Hz, CHHNH2); 3.16 (d, 2 J = 11.4 Hz, CHH NH2); 1.86 (s, CH3); 1.84 (s, CH3). 13C NMR (300 MHz, CDCl3): δ =140.3; 138.9; 138.7; 137.9; 136.6; 135.4; 129.2; 129.1; 128.1; 127.8; 127.6; 126.8; 62.1; 43.1; 20.3; 20.1. MS (CI, NH3):
m/z (%) = 242(100), [M + H]+, 224(6)[M + H - H2O]+. Anal. Calcd for C16H19NO: C, 79.63; H, 7.94; N, 5.80. Found: C, 79.45; H, 7.77; N, 5.61.
2′-Aminomethyl-6,6′-dinitro[1,1′-biphenyl]-2-methanol (5d): 1H NMR (300 MHz, CDCl3): δ = 8.07 (d, 3 J = 8.1 Hz, 2 H); 7.89 (d, 3 J = 7.7 Hz, 1 H); 7.72-7.58 (m, 3 H); 4.30, 4.04 (AB, 2 J AB = 12.3 Hz, CH2OH); 3.81 (d, 2 J = 12.6 Hz, 1 H); 3.23 (d, 2 J = 12.6 Hz, 1 H); 2.92 (br., NH2). 13C NMR (300 MHz, CDCl3): δ = 143.1; 141.3; 135.5; 134.2; 130.3; 129.7; 128.7; 123.9; 61.3; 42.9. ( P )- N -Methyl-2′-aminomethyl-6,6′-dimethyl[1,1′-biphenyl]-2-methanol [( P )-6a]: [α]D 20 -101.32 (c 1.09, CHCl3). UV (MeOH): λmax 274 (2.90), 267 (2.96), 205 (4.56); λmin 272 (2.87), 247 (2.64). CD (MeOH): 324.5
(-0.12), 316.0 (0.10), 308.0 (-0.09), 290.5 (0.10), 278.0 (0.04), 264.5 (-0.27), 253.5 (-0.10), 238.5 (0.22, sh), 223.5 (3.94), 216.5 (2.93), 207.0 (5.46). IR (neat, cm-1): 3281 (s), 3064 (s), 3020 (s), 2919 (s), 2854 (s), 2796(s), 2688(m), 1935(m), 1582(s), 1462(s), 1380(s), 1355(s), 1235(s), 1164(s), 1130(s), 1086(s), 1034(s), 1006(s). 1H NMR (300 MHz, CDCl3): δ = 7.41 (d, J = 7.1 Hz, 1 H); 7.32-7.15 (m, 5 H); 4.17, 4.04 (AB, 2 J AB = 11.1 Hz, CH2OH); 3.37, 3.09 (AB, 2 J AB = 11.1 Hz, CH2NHCH3); 2.25 (s, NCH3); 1.86 (s, CH3); 1.84 (s, CH3). 13C NMR (300 MHz, CDCl3): δ = 140.3; 139.3; 138.0; 136.6; 135.7; 129.4; 129.1; 128.3; 127.7; 127.5; 127.3; 62.2; 53.0; 35.6; 20.3; 20.1. MS (EI):
m/z (%) = 255(68)[M]+, 237(39) [M - H2O]+, 224(34) [M - NH2CH3]+, 222(100). Anal. Calcd for C17H21NO: C, 79.96; H, 8.29; N, 5.49. Found: C, 79.74; H, 8.20; N, 5.25.
( P )- N , N -Dimethyl-2′-aminomethyl-6,6′-dimethyl[1,1′-biphenyl]-2-methanol [( P )-7a]: [α]D 20 -103.66 (c 1.98, CHCl3). UV (MeOH): λmax 274 (2.81), 267 (2.87), 201 (4.72); λmin 272 (2.78), 247 (2.33). IR (neat, cm-1): 3362(br), 3064(br), 2947(s), 2861(s), 2824(s), 2780(s), 1935(w), 1869(w), 1580(m), 1456(s), 1381 (s), 1364 (s), 1303(m), 1240(s), 1174(s), 1148(m), 1098(m), 1075(s), 1040(s), 1006(s). 1H NMR (300 MHz, CDCl3): δ = 7.41 (d, 3 J = 7.42 Hz, 1 H); 7.38-7.21 (m, 4 H); 7.11 (dd, 3 J = 6.10, 4 J = 2.7 Hz, 1 H); 4.18, 4.08 (AB, 2 J AB = 10.7 Hz, CH2OH); 3.16 [d, 2 J = 11.9 Hz, CHHN(CH3)2]; 2.74 [d, 2 J = 11.9, CHHN(CH3)2]; 2.02 [s, N(CH3)2]; 1.87 (s, CH3), 1.82 (s, CH3). 13C NMR (300 MHz, CDCl3): δ = 140.1; 140.0; 138.2; 136.5; 135.1; 134.9; 129.6; 129.3; 129.0; 128.3; 127.7; 126.7; 62.7; 61.3; 44.6; 20.4; 20.1. MS (CI, NH3): m/z (%) = 270(100)[M + H]+. Anal. Calcd for C18H23NO: C, 80.25; H, 8.61; N, 5.20. Found: C, 80.12; H, 8.72; N, 5.18.