A Convenient Synthesis of 1-[6-Fluoro-(2S)-3H,4H-dihydro-2H-2-chromenyl]-(1R)-1,2-ethanediol and 1-[6-Fluoro-(2R)-3H,4...

An-Guang Yu; Nai-Xing Wang; Ya-Lan Xing; Jun-Ping Zhang; Yun-Xu Yang; Wu-Wei Wang; Rui-long Sheng

doi:10.1055/s-2005-868508

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Synlett 2005(9): 1465-1467
DOI: 10.1055/s-2005-868508

LETTER

A Convenient Synthesis of 1-[6-Fluoro-(2S)-3H,4H-dihydro-2H-2-chromenyl]-(1R)-1,2-ethanediol and 1-[6-Fluoro-(2R)-3H,4H-dihydro- 2H-2-chromenyl]-(1R)-1,2-ethanediol

An-Guang Yu^a, Nai-Xing Wang*^a, Ya-Lan Xing^b, Jun-Ping Zhang^a, Yun-Xu Yang^a, Wu-Wei Wang^a, Rui-long Sheng^a
^a Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100101, P. R. China
Fax: +86(10)64879375; e-Mail: nxwang@mail.ipc.ac.cn;
^b Beijing University of Chemical Technology, Beijing 100029, P. R. China

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Publication History

Received 23 February 2005
Publication Date:
29 April 2005 (online)

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Abstract

1-[6-Fluoro-(2S)-3H,4H-dihydro-2H-2-chromenyl]-(1R)-1,2-ethanediol and 1-[6-fluoro-(2R)-3H,4H-dihydro-2H-2-chromenyl]-(1R)-1,2-ethanediol, important pharmaceutical intermediates, were synthesized from natural chiral pool d-mannitol.

Key words

chiral pool - reductions - ketones - aldol reactions

References

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11

Selected data for compound 2a: pale yellow solid: mp 94-95 °C; [α]_D +30.65 (c = 0.0802, MeOH); IR (KBr): 2997, 2916, 2900, 1687, 1621, 1487, 1371 cm^-1; ¹H NMR (300 MHz, CDCl₃): δ = 7.54 (dd, 1 H, J = 8.2 Hz, 3.1 Hz, C₆H₃F), 7.24-7.17 (m, 1 H, C₆H₃F), 6.96 (dd, 1 H, J = 9.0 Hz, 4.1Hz, C₆H₃F), 4.36-4.32 (m, 2 H, CH₂O), 4.23-4.18 (m, 1 H, FC₆H₃OCH), 4.06-4.02 (m, 1 H, CHCHCH₂), 2.93-2.75 (m, 2 H, O=CCH₂), 1.45 (s, 3 H, CH₃), 1.40 (s, 3 H, CH₃); ¹³C NMR (100 Hz,CDCl₃): δ = 25.0 (CH₃), 26.2 (CH₃), 39.0 (O=CCH₂), 66.4 (CH₂O), 76.3 (CH₂ CHO), 78.4 (CHOC), 110.3 (CH₃ CCH₃), 112.1 (FC₆H₃), 119.5 (FC₆H₃), 123.7 (FC₆H₃), 156.1 (FC ₆H₃), 157.1 (FC₆H₃), 158.5 (FC₆H₃), 190.8 (O=C); EIMS: m/z = 266, 101, 43; Anal. Calcd for C₁₄H₁₅FO₄: C, 63.15; H, 5.68; F, 7.14; O, 24.04. Found: C, 63.47; H, 5.92. Selected data for compound 2b: pale yellow solid: mp 84-86 °C; [α]_D 13.53 (c = 0.2142, CHCl₃); IR (KBr): 2997, 2916, 2900, 1687, 1622, 1487, 1371 cm^-1; ¹H NMR (300 MHz, CDCl₃): δ = 7.53 (dd, 1 H, J = 8.1 Hz, 3 Hz, C₆H₃F), 7.25-7.18 (m, 1 H, C₆H₃F), 7.04 (dd, 1 H, J = 9 Hz, 4.1 Hz, C₆H₃F), 4.51-4.46 (m, 1 H, C₆H₃OCH), 4.41-4.35 (m, 1 H, CHOC), 4.15 (dd, 1 H, J = 8.3 Hz, 6.3 Hz, OCCH₂), 4.03 (dd, 1 H, J = 8.3 Hz, 6.3 Hz, OCCH₂), 2.87 (dd, 1 H, J = 16.8 Hz, 12.9 Hz, O=CCH₂), 2.66 (dd, 1 H, J = 16.8 Hz,12.9 Hz, O=CCH₂), 1.43 (s, 3 H, CH ₃), 1.41 (s, 3 H, CH₃); ¹³C NMR (100 Hz,CDCl₃): δ = 25.2 (CH₃), 26.1 (CH₃), 38.6 (O=CCH₂), 64.9 (CH₂O), 76.4 (CH₂ CHO), 77.5 (CHOC), 110.3 (CH₃ CCH₃), 112.0 (FC₆H₃), 119.6 (FC₆H₃), 123.7 (FC₆H₃), 156.1 (FC₆H₃), 157.3 (FC₆H₃), 158.5 (FC₆H₃), 190.6 (O=C); EIMS: m/z = 266, 101, 43; Anal. Calcd for C₁₄H₁₅FO₄: C, 63.15; H, 5.68; F, 7.14; O, 24.04. Found: C, 63.48; H, 5.89.

12

Selected data for compound 1a: mp 87-89 °C; [α]_D +70.30 (c = 0.1, MeOH); IR (KBr): 3590, 3518, 2967, 2937, 2849, 1607, 1493, 1217, 511 cm^-1; ¹H NMR (400 MHz, CDCl₃): δ = 6.96-6.84 (m, 3 H, C₆H₃F), 4.18-4.05 (m, 1 H, FC₆H₃OCH), 4.05-3.99 (m, 3 H, CHOH, CH ₂OH), 3.01-2.94 (m, 2H, FC₆H₃CH ₂), 2.32-2.27 (m, 1H, FC₆H₃CH₂CH ₂), 2.03-2.01 (m, 1 H, FC₆H₃CH₂CH ₂); ¹³C NMR (100 Hz, CDCl₃): δ = 23.0 (FC₆H₃CH₂ CH₂), 24.5 (FC₆H₃ CH₂CH₂), 63.3 (CH₂OH), 73.5 (CHOH), 76.5 (OCHCH), 113.9 (C₆H₃F), 115.5 (C₆H₃F), 117.5 (C₆H₃F), 123.1 (C₆H₃F), 150.1 (C₆H₃F), 158.1 (C₆H₃F); EIMS: m/z = 212, 150; Anal. Calcd for C₁₁H₁₃FO₃: C, 62.26; H, 6.17; F, 8.95; O, 22.62. Found: C, 61.97; H, 6.12. Selected data for compound 1b: mp 92-94 °C; [α]_D +63.08 (c = 0.1, MeOH); IR (KBr): 3406, 3281, 2960, 2924, 2885, 1496, 1217, 1081, 1052 cm^-1; ¹H NMR (400 MHz, CDCl₃): δ = 6.82-6.73 (m, 3 H, C₆H₃F), 4.07-4.04 (m, 1 H, FC₆H₃OCH), 3.84-3.78 (m, 3 H, CHOH, CH ₂OH), 2.88-2.78 (m, 2 H, FC₆H₃CH ₂), 2.40 (s, 2 H, OH), 2.00-1.93 (m, 2 H, FC₆H₃CH₂CH ₂); ¹³C NMR (100 Hz, CDCl₃): δ = 23.5 (FC₆H₃CH₂ CH₂), 24.6 (FC₆H₃ CH₂CH₂), 63.6 (CH₂OH), 73.6 (CHOH), 76.7 (OCHCH), 113.9 (C₆H₃F), 115.3 (C₆H₃F), 117.6 (C₆H₃F), 123.1 (C₆H₃F), 150.1 (C₆H₃F), 158.1 (C₆H₃F); EIMS: m/z = 212, 151, 57; Anal. Calcd for C₁₁H₁₃FO₃: C, 62.26; H, 6.17; F, 8.95; O, 22.62. Found: C, 62.13; H, 6.08.