PDF herunterladen
Synlett 2005(20): 3103-3106  
DOI: 10.1055/s-2005-922758
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Method for the Synthesis of 3a-Aryl-Substituted Cyclopenta[1,2-b]furan Derivatives

Hisao Nemoto*, Xian Peng, Weihui Zhong, Jun Xie, Tomoyuki Kawamura, Masaru Nishida
Division of Pharmaceutical Chemistry, Institute of Health Biosciences, Graduate School of the University of Tokushima, 1-78 Sho-machi, Tokushima 770-8505, Japan
Fax: +81(88)6337284; e-Mail: nem@ph.tokushima-u.ac.jp;
Weitere Informationen

Publikationsverlauf

Received 22 August 2005
Publikationsdatum:
28. November 2005 (online)

    Lizenzen und Reprints Alle Artikel dieser Rubrik

Abstract

An alternative method for the synthesis of cyclo­penta[1,2-b]furan (CPF) derivatives, which show promise as chiral resolving agents, was developed. Various CPF derivatives, aryl-substituted at the 3a-position, can be synthesized via Suzuki-Miyaura coupling reaction.

Key words

cyclopenta[1,2-b]furan - chiral resolution - divergent synthesis - secondary alcohols - acetals

    References

  • 1a Chirality in Industry: The Commercial Manufacture and Applications of Optically Active Compounds   Collins AD. Sheldrake GN. Crosby J. Wiley; Chichester: 1992. 
  • 1b Chirality in Industry II: Developments in the Commercial Manufacture and Applications of Optically Active Compounds   Collins AD. Sheldrake GN. Crosby J. Wiley; Chichester: 1997. 
  • 1c Sheldon RA. Chirotechnology: Industrial Synthesis of Optically Active Compounds   Dekker; New York: 1993. 
  • Previously reported acetal-type chiral reagents and the related one. See:
  • 2a Wuts PGM. Bigelow SS. J. Chem. Soc., Chem. Commun.  1984,  736 
    CrossrefPubMed
  • 2b Noe CR. Knollmüller M. Steinbauer G. Jangg E. Völlenkle H. Chem. Ber.  1988,  121:  1231 
    CrossrefPubMedSuche in Google Scholar
  • 2c Linderman RJ. Cusack KP. Jaber MR. Tetrahedron Lett.  1996,  37:  6649 
    CrossrefPubMedSuche in Google Scholar
  • 2d Lainé D. Fujita M. Lay SV. J. Chem. Soc., Perkin Trans. 1  1999,  1639 
    CrossrefPubMed
  • 2e Mori K. Uematsu T. Minobe M. Yanagi K. Tetrahedron Lett.  1982,  23:  1921 
    CrossrefPubMedSuche in Google Scholar
  • 2f Buchanan DJ. Dixon DJ. Hernandez-Juan FA. Org. Lett.  2004,  6:  1357 
    CrossrefPubMedSuche in Google Scholar
  • 3 Nemoto H. Tsutsumi H. Yuzawa S. Peng X. Zhong W. Xie J. Miyoshi N. Suzuki I. Shibuya M. Tetrahedron Lett.  2004,  45:  1667 
    CrossrefSuche in Google Scholar
  • 4 Nemoto H. Tetrahedron Lett.  1994,  35:  7855 
    Suche in Google Scholar
  • 5 Mazzocchiu PH. Kim CH. J. Med. Chem.  1982,  25:  1473 
    CrossrefSuche in Google Scholar
  • 6 Miyaura N. Suzuki A. Chem. Rev.  1995,  95:  2457 
    Suche in Google Scholar
7

We did not carry out the transformation reaction from 18 to the corresponding alkenyl ethers for the following reasons. 1) In a cooperative work with Zeon Corporation, exhaustive optimizations in industrial-scale were carried out for alcohol exchange reaction of acetal 6 and various dl-secondary alcohols. As a result, several dl-alcohols were converted to the corresponding diastereomers in excellent yields with high cost performance. Thus, priority of the optimization of acetal exchange reaction in laboratory scale is low. 2) We attempted the transformation reaction from 20 or 21 to the corresponding alkenyl ethers, and the carbon-carbon bond cleavage reactions were observed as shown in the following scheme. Conversely, we consider that possibility of such cleavage reactions for 18a-d is very low (Scheme [5] ).

8

In the case of 2 and 3 (CPF-Bzh derivatives of 2-alkanols), the absolute configuration of the 2-alkoxy position can be empirically determined by the chemical shift of benzylic position, which appears around at δ = 4.5-4.6 ppm as a clear singlet in 1H NMR and around at δ = 60-71 ppm in 13C NMR. In contrast, no such peak was observed in 1H NMR and 13C NMR of 19.

9

TLC used in all the experimental was obtained from Merck (1.05715.0009, silica gel 60F254).

10

Data of four CPF derivatives synthesized by Suzuki-Miyaura coupling reaction and their synthetic intermediates are as following.
Compound 14: colorless crystals; mp 94-95 °C (hexane). FT-IR (KBr): 3053, 2953, 2843, 1902, 1619, 1585, 1486 cm-1. 1H NMR (400 MHz, CDCl3): δ = 7.41 (d, J = 8.4 Hz, 2 H), 7.27 (d, J = 8.4 Hz, 2 H), 6.17 (s, 1 H), 2.68-2.63 (m, 2 H), 2.53-2.48 (m, 2 H), 2.01 (td, J = 14.8, 7.6 Hz, 2 H). 13C NMR (100 MHz, CDCl3): δ = 141.3 (C), 135.7 (C), 131.2 (2 × CH), 127.1 (2 × CH), 127.0 (CH), 120.5 (C), 33.5 (CH2), 33.2 (CH2), 23.4 (CH2). HRMS (EI): m/z calcd for C11H11Br [M+]: 222.0044; found: 222.0060. Anal. Calcd for C11H11Br: C, 59.22; H, 4.97. Found: C, 58.91; H, 4.94.
Compound 15: colorless oil. FT-IR (KBr): 3029, 2966, 2876, 1899, 1741, 1589, 1488, 1402 cm-1. 1H NMR (400 MHz, CDCl3): δ = 7.44 (d, J = 8.4 Hz, 2 H), 7.06 (d, J = 8.4 Hz, 2 H), 3.26 (dd, J = 11.4, 8.0 Hz, 1 H), 2.51-2.42 (m, 2 H), 2.31-2.21 (m, 1 H), 2.18-2.10 (m, 1 H), 2.08-2.00 (m, 1 H), 1.95-1.85 (m, 1 H). 13C NMR (100 MHz, CDCl3): δ = 217.0 (C), 137.1 (C), 131.5 (2 × CH), 129.7 (2 × CH), 120.7 (C), 54.6 (CH), 38.2 (CH2), 31.4 (CH2), 20.8 (CH2). HRMS (EI): m/z calcd for C11H11BrO [M+]: 237.9993; found: 237.9996.
Compound 16: colorless crystals; mp 48-49 °C (hexane). FTIR (KBr, CHCl3): 2955, 2829, 1489, 1316 cm-1. 1H NMR (400 MHz, CDCl3): δ = 7.41 (d, J = 8.8 Hz, 2 H), 7.25 (d, J = 8.8 Hz, 2 H), 4.05 (t, J = 7.2 Hz, 2 H), 3.20 (s, 3 H), 2.49-2.42 (m, 1 H), 2.29-2.22 (m, 2 H), 1.98-1.89 (m, 3 H), 1.83-1.76 (m, 2 H). 13C NMR (100 MHz, CDCl3): δ = 143.4 (C), 130.8 (2 × CH), 129.1 (2 × CH), 119.8 (C), 118.1 (C), 66.2 (CH2), 58.6 (C), 50.9 (CH3), 40.3 (CH2), 38.1 (CH2), 34.3 (CH2), 21.4 (CH2). HRMS (EI): m/z calcd for C14H17BrO2 [M+]: 296.0412; found: 296.0402. Anal. Calcd for C14H17BrO2: C, 56.58; H, 5.77. Found: C, 56.43; H, 5.67.
Compound 18a: colorless solid; mp 155-156 °C (EtOAc-hexane). FT-IR (KBr): 3027, 2948, 2880, 2829, 1605, 1515, 1495, 1447, 1426, 1366 cm-1. 1H NMR (400 MHz, CDCl3): δ = 7.76 (d, J = 8.0 Hz, 1 H), 7.52-7.47 (m, 4 H), 7.41 (d, J = 7.2 Hz, 1 H), 7.40 (t, J = 8.0 Hz, 2 H), 7.31 (d, J = 12.4 Hz, 1 H), 7.29 (d, J = 12.4 Hz, 1 H), 4.15-4.06 (m, 2 H), 3.41 (s, 4 H), 3.27 (s, 3 H), 2.62-2.55 (m, 1 H), 2.37-2.27 (m, 2 H), 2.13-1.98 (m, 3 H), 1.94-1.80 (m, 2 H). 13C NMR (100 MHz, CDCl3): δ = 146.0 (C), 145.3 (C), 143.1 (C), 139.5 (C), 137.4 (C), 135.4 (C), 129.7 (C), 129.1 (2 × CH), 128.5 (CH), 127.8 (CH), 127.2 (2 × CH), 121.0 (C), 119.1 (CH), 118.4 (CH), 66.2 (CH2), 58.8 (C), 50.9 (CH3), 40.7 (CH2), 38.1 (CH2), 34.4 (CH2), 30.6 (CH2), 30.1 (CH2), 21.5 (CH2). HRMS (EI): m/z calcd for C26H26O2 [M+]: 370.1933; found: 370.1953. Anal. Calcd for C26H26O2: C, 84.29; H, 7.07. Found: C, 84.56; H, 7.21.
Compound 18b: colorless solid; mp 144-145 °C (EtOAc-hexane). FT-IR (KBr): 2950, 2881, 2828, 2244, 1610, 1510, 1492, 1450, 1317 cm-1. 1H NMR (400 MHz, CDCl3): δ = 8.76 (d, J = 8.0 Hz, 1 H), 8.70 (d, J = 8.0 Hz, 1 H), 8.00 (d, J = 8.0 Hz, 1 H), 7.87 (d, J = 8.0 Hz, 1 H), 7.68-7.57 (m, 4 H), 7.54-7.47 (m, 5 H), 4.16-4.07 (m, 2 H), 3.29 (s, 3 H), 2.64-2.57 (m, 1 H), 2.39-2.28 (m, 2 H), 2.15-2.00 (m, 3 H), 1.92-1.82 (m, 2 H). 13C NMR (100 MHz, CDCl3): δ = 143.5 (C), 138.6 (C), 138.1 (C), 131.6 (C), 131.1 (C), 130.6 (C), 129.8 (C), 129.5 (2 × CH), 128.6 (CH), 127.5 (CH), 127.2 (2 × CH), 127.0 (CH), 126.7 (CH), 126.43 (CH), 126.36 (2 × CH), 122.8 (CH), 122.5 (CH), 118.4 (C), 66.3 (CH2), 58.9 (C), 51.0 (CH3), 40.7 (CH2), 38.2 (CH2), 34.4 (CH2), 21.5 (CH2). HRMS (EI): m/z calcd for C28H26O2 [M+]: 394.1933; found: 394.1954. Anal. Calcd for C28H26O2: C, 85.25; H, 6.64. Found: C, 85.60; H, 6.85.
Compound 18c: colorless solid; mp 225-226 °C (EtOAc-hexane). FT-IR (KBr): 3048, 2971, 2886, 2830, 1815, 1621, 1514, 1441, 1412, 1362, 1319 cm-1. 1H NMR (400 MHz, CDCl3): δ = 8.48 (s, 1 H), 8.03 (d, J = 8.4 Hz, 2 H), 7.73 (d, J = 8.4 Hz, 2 H), 7.58 (d, J = 8.0 Hz, 2 H), 7.45 (t, J = 7.6 Hz, 2 H), 7.37 (d, J = 8.0 Hz, 2 H), 7.34 (t, J = 7.6 Hz, 2 H), 4.21-4.11 (m, 2 H), 3.32 (s, 3 H), 2.71-2.63 (m, 1 H), 2.46-2.40 (m, 1 H), 2.38-2.31 (m, 1 H), 2.22-2.04 (m, 3 H), 2.00-1.85 (m, 2 H). 13C NMR (100 MHz, CDCl3): δ = 143.7 (C), 137.0 (C), 135.9 (C), 131.4 (2 × C), 130.7 (2 × CH), 130.3 (2 × C), 128.2 (2 × CH), 127.2 (2 × CH), 127.0 (2 × CH), 126.4 (CH), 125.1 (2 × CH), 125.0 (2 × CH), 118.5 (C), 66.4 (CH2), 59.0 (C), 51.0 (CH3), 41.1 (CH2), 38.2 (CH2), 34.7 (CH2), 21.6 (CH2). HRMS (EI): m/z calcd for C28H26O2 [M+]: 394.1933; found: 394.1954. Anal. Calcd for C28H26O2: C, 85.25; H, 6.64. Found: C, 85.20; H, 6.77.
Compound 18d: light yellow crystals; mp 196-197 °C (EtOAc-hexane). FT-IR (KBr): 2955, 2828, 1917, 1796, 1601, 1584, 1520, 1499, 1402 cm-1. 1H NMR (400 MHz, CDCl3): δ = 8.24 (d, J = 9.2 Hz, 1 H), 8.18 (d, J = 8.0 Hz, 1 H), 8.14 (t, J = 8.0 Hz, 2 H), 8.05 (s, 2 H), 8.00-7.95 (m, 3 H), 7.57-7.52 (m, 4 H), 4.16-4.06 (m, 2 H), 3.30 (s, 3 H), 2.64-2.57 (m, 1 H), 2.38-2.28 (m, 2 H), 2.15-2.00 (m, 3 H), 1.93-1.81 (m, 2 H). 13C NMR (100 MHz, CDCl3): δ = 143.4 (C), 138.5 (C), 137.8 (C), 131.4 (C), 131.0 (C), 130.4 (C), 130.0 (2 × CH), 128.4 (C), 127.6 (CH), 127.4 (CH), 127.28 (3 × CH), 127.26 (CH), 127.24 (C), 125.9 (CH), 125.5 (CH), 124.95 (CH), 124.9 (C), 124.7 (CH), 124.6 (CH), 118.4 (C), 66.3 (CH2), 58.9 (C), 51.0 (CH3), 40.7 (CH2), 38.2 (CH2), 34.4 (CH2), 21.5 (CH2). HRMS (EI): m/z calcd for C30H26O2 [M+]: 418.1933; found: 418.1941. Anal. Calcd for C30H26O2: C, 86.09; H, 6.26. Found: C, 85.93; H, 6.37.