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Synlett 2004(10): 1808-1810  
DOI: 10.1055/s-2004-829575
LETTER
© Georg Thieme Verlag Stuttgart · New York

Enantiopure Oxygen-Functionalized Bipyridine Derivatives: Synthesis and Characterization

Marco Lama, Olimpia Mamula*, Rosario Scopelliti
Institute of Chemical Sciences and Engineering, Swiss Federal Institute of Technology, BCH, 1015 Lausanne, Switzerland
Fax: +41(21)6939825; e-Mail: olimpia.mamula@epfl.ch;
Further Information

Publication History

Received 5 May 2004
Publication Date:
15 July 2004 (online)

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Abstract

A new class of chiral pinene 2,2′-bipyridine compounds containing carboxylic or alcoholic groups have been synthesized using the Kröhnke procedure followed by haloform or lithium mediated substitution reactions.

Key words

pyridine - chiral ligands - carboxylic acids - alcohols - diastereoselectivity

    References

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Spectroscopic Data for Compounds 3-5. Compound 3: 1H NMR (400 MHz, DMSO-d 6): δ = 9.02 [d, 2 H, H(10), H(14), 3 J 10,11 = 7.5 Hz], 8.73 [m, 1 H, H(12)], 8.26 [dd, 2 H, H(11), H(13), 3 J 4,3 = 7.8 Hz, 3 J 4,5 = 7.8 Hz], 8.18 [dd, 1 H, H(4), 3 J 4,3 = 7.8 Hz, 3 J 4,5 = 7.8 Hz], 8.02 [d, 1 H, H(3), 3 J 3,4 = 7.8 Hz], 7.91 [d, 1 H, H(5), 3 J 5,4 = 7.8 Hz], 6.50 [s, 2 H, CH2 (8)], 3.55 [AB, 4 H, H(17), H(19), 2 J = 10.3 Hz], 1.60 (s, 3 H, Me), 1.48 (s, 3 H, Me), 0.71 (s, 3 H, Me) ppm.
Compound 4: 1H NMR (400 MHz, CDCl3): δ = 8.61 [dd, 1 H, H(2), 3 J 2,3 = 7.8 Hz, 4 J 2,4 = 1.2 Hz], 8.22 [d, 1 H, H(7), 3 J 7,8 = 7.7 Hz], 8.02 [dd, 1 H, H(4), 3 J 4,3 = 7.6 Hz, 4 J 4,2 = 1.1 Hz], 7.93 [dd, 1 H, H(3), 3 J 3,4 = 7.5 Hz, 3 J 3,2 = 7.5 Hz], 7.38 [d, 1 H, H(8), 3 J 8,7 = 7.8 Hz], 3.21 [d, 2 H, H(13a), H(13b), 3 J 13b,12 = 2.7 Hz], 2.86 [dd, 1 H, H(10), 3 J 10,15a = 5.6 Hz, 3 J 10,15b = 5.6 Hz], 2.84 [s, 3 H, Me(18)], 2.74 [ddd, 1 H, H(15b), 2 J 15b,15a = 9.6 Hz, 3 J 15b,10 = 5.81 Hz, 3 J 15b,12 = 5.81 Hz], 2.44 [ddt, 1 H, H(12), 3 J 12,15b = 5.8 Hz, 4 J 12,10 = 5.8 Hz, 3 J 12,15b = 2.8 Hz], 1.45 [s, 3 H, Me(17)], 1.34 [d, 1 H, H(15a), 2 J 15a,15b = 9.6 Hz], 0.71 [s, 3 H, Me(16)] ppm. MS (CI): m/z (%) = 293 (46) [M + H]+, 278 (29), 264 (25), 250 (100) [M - C2H3O]+. IR: ν = 2929 (m), 1695 (s), 1575 (m), 1440 (m), 1355 (s), 810 (s) cm-1.
Compound 5: 1H NMR (400 MHz, DMSO-d 6): δ = 8.57 [dd, 1 H, H(2), 3 J 2,3 = 7.8 Hz, 4 J 2,4 = 1.2 Hz], 8.36 [d, 1 H, H(7), 3 J 7,8 = 7.7 Hz], 8.18 [dd, 1 H, H(3), 3 J 3,4 = 7.6 Hz, 3 J 3,2 = 7.6 Hz], 8.12 [d, 1 H, H(4), 3 J 4,3 = 7.6 Hz], 7.80 [d, 1 H, H(8), 3 J 8,7 = 7.8 Hz], 3.23 [AB, 2 H, H(13a), H(13b), 2 J 13a,13b = 17.7 Hz], 2.98 [dd, 1 H, H(10), 3 J 10,15a = 5.6 Hz, 3 J 10,15b = 5.6 Hz], 2.75 [ddd, 1 H, H(15b), 2 J 15b,15a = 9.6 Hz, 3 J 15b,10 = 5.81 Hz, 3 J 15b,12 = 5.81 Hz], 2.41 [ddt, 1 H, H(12), 3 J 12,15b = 5.8 Hz, 4 J 12,10 = 5.8 Hz, 3 J 12,15b = 2.8 Hz], 1.43 [s, 3 H, Me(17)], 1.28 [d, 1 H, H(15a), 2 J 15a,15b = 9.6 Hz], 0.64 [s, 3 H, Me(16)] ppm. 13C NMR (100 MHz, DMSO-d 6): δ = 167.8, 157.1, 156.7, 153.3, 152.1, 141.8, 137.6, 133.9, 123.0, 120.3, 118.1, 45.4, 40.2, 38.3, 35.9, 32.2, 25.6, 21.0 ppm. HRMS: m/z calcd for C18H19N2O2: 295.1442; found: 295.1441. IR: ν = 3414 (m), 3306 (m), 2934 (m), 2741 (b), 2567 (m), 2083 (b), 1709 (s), 1609 (m), 1373 (s), 1210 (s) cm-1. [α]D = -90 deg·mL·g-1·dm-1 (MeCN, 20 °C).

13

Crystal data for 5·H2O·HCl: C18H21ClN2O3 were deposited at the Cambridge Crystallography Data Centre, CCDC 235123.

15

Spectroscopic Data for Compounds 7 and 8. Compound 7: 1H NMR (400 MHz, DMSO-d 6): δ = 13.6 (br s, 1 H, COOH), 8.71 [m, 2 H, H(2), H(7)], 8.56 [s, 1 H, H(8)], 8.31 [dd, H(3), 3 J 3,4 = 7.8 Hz, 3 J 3,2 = 7.8 Hz], 8.23 [d, 1 H, H(4), 3 J 4,3 = 7.8 Hz], 3.26 [ABq, 2 H, H(13), 2 J 13a,13b = 19.3 Hz], 3.17 [dd, 1 H, H(10), 3 J 10,15b = 5.5 Hz, 4 J 10,12 = 5.5 Hz], 2.78 [ddd, 1 H, H(15b), 2 J 15a,15b = 10.3 Hz, 3 J 15b,10 = 5.5 Hz, 3 J 15b,12 = 5.5 Hz], 2.36 [ddt, 1 H, H(12), 3 J 12 ,15b = 5.5 Hz, 4 J 12,10 = 5.5 Hz, 3 J 12,13 = 2.6 Hz], 1.42 [s, 3 H, H(17)], 1.21 [d, 1 H, H(15a), 2 J 15a,15b = 10.3 Hz], 0.63 [s, 3 H, H(16)] ppm. 13C NMR (100 MHz, DMSO-d 6): δ = 165.0, 154.7, 148.9, 147.7, 146.8, 146.1, 140.0, 139.1, 126.0, 125.0, 123.1, 43.5, 40.1, 38.3, 33.5, 30.5, 25.3, 21.1 ppm. HRMS: m/z calcd for C18H19N2O2: 295.1441; found: 295.1441. IR: ν = 2931 (m), 1694 (s), 1583 (s), 1245 (s), 1233 (s). [α]D = -94 deg·mL·g-1·dm-1 (MeCN, 20 °C).
Compound 8: 1H NMR (400 MHz, CDCl3): δ = 8.20 [d, 1 H, H(2), 3 J 2,3 = 7.8 Hz], 8.17 [s, 1 H, H(8)], 8.06 [s, 1 H, H(7)], 7.70 [dd, 1 H, H(3), 3 J 3,2 = 7.8 Hz, 3 J 3,4 = 7.8 Hz], 7.12 [d, 1 H, H(4), 3 J 4,3 = 7.6 Hz], 4.70 (br, 1 H, OH), 4.09 [t, 2 H, H(β), 3 J α , β = 5.5 Hz], 3.07 [t, 2 H, H(α), 3 J β , α = 5.5 Hz], 3.02 [d, 2 H, H(13), 3 J 13,12 = 2.8 Hz], 2.83 [dd, 1 H, H(10), 3 J 10,15b = 5.6 Hz, 4 J 10,12 = 5.6 Hz], 2.68 [ddd, 1 H, H(15b), 3 J 15b,15a = 9.6 Hz, 3 J 15b,10 = 5.6 Hz, 3 J 15b,12 = 5.6 Hz, 2 J 15b,15a = 9.6 Hz], 2.29 [ddt, 1 H, H(12), 3 J 12,15b = 5.6 Hz, 4 J 12,10 = 5.6 Hz, 3 J 12,13 = 2.8 Hz], 1.39 [s, 3 H, H(17)], 1.21 [d, 1 H, H(15a), 2 J 15a,15b = 9.6 Hz], 0.63 [s, 3 H, H(16)]. 13C NMR (100 MHz, CDCl3): δ = 159.9, 156.0, 154.2, 145.7, 145.6, 143.2, 137.7, 123.0, 120.3, 118.9, 61.9, 44.6, 40.2, 39.3, 38.9, 33.1, 31.9, 26.1, 21.5 ppm. HRMS: m/z calcd for C19H23N2O: 295.1805; found: 295.1805. MS (CI): m/z (%) = 294 (20)[M+], 265 (100) [M - CH2OH]+. IR: ν = 3337 (b), 2922 (s), 1588 (m), 1573 (m), 1553 (m), 1456 (s), 1049 (s) cm-1. [α]D = -91 deg·mL·g-1·dm-1 (MeCN, 20 °C).