Facile and Highly Enantioselective Synthesis of Axially Chiral Biaryls by Enzymatic Desymmetrization

Takashi Matsumoto; Tadayoshi Konegawa; Takeshi Nakamura; Keisuke Suzuki

doi:10.1055/s-2002-19349

LETTER

Facile and Highly Enantioselective Synthesis of Axially Chiral Biaryls by Enzymatic Desymmetrization

Takashi Matsumoto*, Tadayoshi Konegawa, Takeshi Nakamura, Keisuke Suzuki
Department of Chemistry, Tokyo Institute of Technology, and CREST, Japan Science and Technology Corporation (JST), Tokyo 152-8551, Japan
Fax: +81(3)57343531; e-Mail: tmatsumo@chem.titech.ac.jp;

Abstract

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Abstract

The axially chiral biaryls 2 were obtained in high enantioselectivity by desymmetrization of the σ-symmetric biaryl diacetates 1 by lipase-catalyzed hydrolysis.

Key words

asymmetrization - hydrolysis - enzyme - axial chirality - biaryl

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Referenzen

References

For leading references, see:

<A NAME="RY19501ST-1A">1a</A> Bringmann G. Walter R. Weirich R. Angew. Chem., Int. Ed. Engl. 1990, 29: 977

<A NAME="RY19501ST-1B">1b</A> Gant TG. Meyers AI. Tetrahedron 1994, 50: 2297

For selected examples of the recent biaryl bond formation methods, see:

<A NAME="RY19501ST-2A">2a</A> Saito S. Kano T. Muto H. Nakadai M. Yamamoto H. J. Am. Chem. Soc. 1999, 121: 8943

<A NAME="RY19501ST-2B">2b</A> Bringmann G. Breuning M. Tasler S. Synthesis 1999, 525

<A NAME="RY19501ST-2C">2c</A> Kakiuchi F. Le Gendre P. Yamada A. Ohtaki H. Murai S. Tetrahedron: Asymmetry 2000, 11: 2647

<A NAME="RY19501ST-2D">2d</A> Kamikawa K. Uemura M. Synlett 2000, 938

<A NAME="RY19501ST-2E">2e</A> Cammidge AN. Crépy KVL. Chem. Commun. 2000, 1723

<A NAME="RY19501ST-2F">2f</A> Degnan AP. Meyers AI. J. Am. Chem. Soc. 1999, 121: 2762

<A NAME="RY19501ST-2G">2g</A> Lipshutz BH. Müller P. Leinweber D. Tetrahedron Lett. 1999, 40: 3677

<A NAME="RY19501ST-3A">3a</A> Hayashi T. Niizuma S. Kamikawa T. Suzuki N. Uozumi Y. J. Am. Chem. Soc. 1995, 117: 9101

<A NAME="RY19501ST-3B">3b</A> Harada T. Ueda S. Yoshida T. Inoue A. Takeuchi M. Ogawa N. Oku A. J. Org. Chem. 1994, 59: 7575

<A NAME="RY19501ST-4">4</A> For a review of the enzymatic asymmetric desymmetrization, see: Schoffers E. Golebiowski A. Johnson CR. Tetrahedron 1996, 52: 3769

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Enantiomeric purities of the biaryls 2a-2d were determined by chiral HPLC analyses. Enantiomerically pure samples of 2a-2c could be obtained by recrystallization. Data for the compounds 2a-2d follow; (+)-2a (>99% e.e.): Mp 97-98 °C (hexane-EtOAc); [α]¹⁸ _D +101 (c 1.03, CHCl₃); ¹H NMR (CDCl₃) δ 1.69 (s, 3 H), 4.77 (s, 1 H), 6.83 (dd, 1 H, J = 8.3, 1.0 Hz), 7.00 (dd, 1 H, J = 8.3, 1.0 Hz), 7.3-7.6 (m, 6 H), 7.94 (dd, 2 H, J = 8.1, 8.1 Hz); ¹³C NMR (CDCl₃) δ 20.3, 113.2, 114.6, 119.8, 125.3, 125.6, 126.4, 126.9, 128.3, 128.5, 128.8, 129.3, 129.5, 131.8, 133.8, 149.4, 154.4, 169.3; IR (KBr) 3419, 1740 cm^-1. Anal. Calcd for C₁₈H₁₄O₃: C, 77.68; H, 5.07. Found: C, 77.62; H, 5.37. HPLC (Daicel CHIRACEL OJ, 250 × 4.6 mm, hexane-i-PrOH = 9:1,
0.5 mL/min) retention time: 34.6 min for (+)-2a [43.1 min for (-)-2a].
(-)-2b (>99% e.e.): Mp 87-88 °C (hexane-EtOAc); [α]²⁴ _D
-17.6 (c 1.06, CHCl₃); ¹H NMR (CDCl₃) δ 1.86 (s, 3 H), 2.13 (s, 3 H), 4.84 (s, 1 H), 6.73 (dd, 1 H, J = 8.3, 1.0 Hz), 6.90 (dd, 1 H, J = 8.3, 1.0 Hz), 7.1-7.4 (m, 5 H); ¹³C NMR (CDCl₃) δ 19.4, 20.4, 113.1, 114.3, 121.3, 126.3, 129.0, 129.1, 130.3, 130.6, 130.9, 138.3, 148.9, 153.8, 169.2; IR (KBr) 3422, 1761 cm^-1. Anal. Calcd for C₁₅H₁₄O₃: C, 74.36; H, 5.82. Found: C, 74.59; H, 5.82. HPLC (Daisel CHIRACEL OD-H, 250 × 4.6 mm, hexane-ⁱPrOH = 9:1, 0.7 mL/min) retention time: 8.13 min for (-)-2b [7.68 min for (+)-2b].
(-)-2c (>99% e.e.): Mp 56-57 °C (hexane-EtOAc); [α]²³ _D
-41.5 (c 1.06, CHCl₃); ¹H NMR (CDCl₃) δ 1.09 (t, 3 H, J = 7.6 Hz), 1.85 (s, 3 H), 2.43 (q, 2 H, J = 7.6 Hz), 4.74 (s, 1 H), 6.74 (dd, 1 H, J = 8.3, 1.3 Hz), 6.91 (dd, 1 H, J = 8.3, 1.3 Hz), 7.1-7.4 (m, 5 H); ¹³C NMR (CDCl₃) δ 14.8, 20.4, 25.9, 113.0, 114.3, 121.1, 126.4, 128.8, 129.1, 129.2, 129.5, 131.0, 144.2, 148.9, 153.9, 169.2; IR (KBr) 3438, 1744
cm^-1. Anal. Calcd for C₁₆H₁₆O₃: C, 74.98; H, 6.29. Found: C, 74.86; H, 6.35. HPLC (Daisel CHIRACEL OD-H, 250 × 4.6 mm, hexane-i-PrOH = 9:1, 0.7 mL/min) retention time: 8.40 min for (-)-2c [7.83 min for (+)-2c].
(-)-2d (99% e.e.): Colorless oil; [α]_D ²³ -18.4 (c 1.23, CHCl₃); ¹H NMR (CDCl₃) δ 1.79 (s, 3 H), 4.34 (s, 2 H), 4.45 (d, 1 H, J = 11.6 Hz), 4.53 (d, 1 H, J = 11.6 Hz), 6.22 (s, 1 H), 6.74 (dd, 1 H, J = 8.2, 1.0 Hz), 6.97 (dd, 1 H, J = 8.2, 1.0 Hz), 7.1-7.5 (m, 9 H), 7.5-7.6 (m, 1 H); ¹³C NMR (CDCl₃) δ 20.3, 71.4, 73.1, 114.6, 115.2, 122.3, 127.8, 128.0, 128.4, 128.5, 128.8, 129.3, 130.1, 131.4, 131.7, 137.1, 137.3, 149.0, 154.8, 169.2; IR (KBr) 3422, 1758 cm^-1. Anal. Calcd for C₂₂H₂₀O₄: C, 75.84; H, 5.79. Found: C, 75.72; H, 5.96. HPLC (Daisel CHIRACEL OD-H, 250 × 4.6 mm, hexane-i-PrOH = 9:1, 0.5 mL/min) retention time: 12.9 min for (+)-2d and 14.5 min for (-)-2d.

Upon heating in toluene at 60 °C, (+)-2a racemized 1% after 12 h, and 80 °C, 7% after 12 h.