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

Markus Furegati; Andreas J. Rippert

doi:10.1055/s-2002-32588

LETTER

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;

Abstract

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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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References

<A NAME="RG08602ST-1A">1a</A> Ager DJ. Prakash I. Schaad DR. Chem. Rev. 1996, 96: 835

<A NAME="RG08602ST-1B">1b</A> Bergmeier SC. Tetrahedron 2000, 56: 2561

<A NAME="RG08602ST-2A">2a</A> Abiko A. Masamune S. Tetrahedron Lett. 1992, 33: 5517

<A NAME="RG08602ST-2B">2b</A> McKennon MJ. Meyers AI. J. Org. Chem. 1993, 58: 3568

<A NAME="RG08602ST-3A">3a</A> Rippert AJ. Helv. Chim. Acta 1998, 81: 676

<A NAME="RG08602ST-3B">3b</A> Keller F. Rippert AJ. Helv. Chim. Acta 1999, 82: 125

<A NAME="RG08602ST-4A">4a</A> Wittig G. Zimmermann H. Chem. Ber. 1953, 86: 629

<A NAME="RG08602ST-4B">4b</A> Insole JM. J. Chem. Res., Synop. 1988, 74

<A NAME="RG08602ST-5">5</A> Vankar YD. Trinadha Rao C. J. Chem. Res., Synop. 1985, 232

<A NAME="RG08602ST-6">6</A> Mandal AK. Soni NR. Ratnam KR. Synthesis 1985, 274

<A NAME="RG08602ST-7">7</A> Karimi B. Golshani B. J. Org. Chem. 2000, 65: 7228

<A NAME="RG08602ST-8">8</A> (P)-3b was derived from the corresponding enantiomerically pure diphenic acid, which was resolved using brucine: Kanoh S. Muramoto H. Kobayashi N. Motoi M. Suda H. Bull. Chem. Soc. Jpn. 1987, 60: 3659

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

<A NAME="RG08602ST-10">10</A> Gololobov YG. Kasukhin LF. Tetrahedron 1992, 48: 1353

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): λ_max 288 (2.71, sh), 274 (3.03), 266 (3.09), 253 (3.10); λ_min 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): λ_max 274 (2.90), 267 (2.96), 205 (4.56); λ_min 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): λ_max 274 (2.81), 267 (2.87), 201 (4.72); λ_min 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.