Synthesis of Enantiomerically Pure Cyclopropyl Trifluoroborates

Abstract

Enantiomerically pure cyclopropylboronic esters were converted to the corresponding trifluoroborates, versatile inter­mediates for a variety of transformations. The new deprotection conditions allowed the utilization of general building blocks for ­cyclopropyl amines.

boron - stereoselectivity - protecting groups - cyclo­propanes - cross-coupling

References and Notes

<A NAME="RD05306ST-1A">1a</A> Fontani P. Carboni B. Vaultier M. Carrié R. Tetrahedron Lett.  1989,  30:  4815 

<A NAME="RD05306ST-1B">1b</A> Fontani P. Carboni B. Vaultier M. Maas G. Synthesis  1991,  605 

<A NAME="RD05306ST-1C">1c</A> Imai T. Mineta H. Nishida S. J. Org. Chem.  1990,  55:  4986 

<A NAME="RD05306ST-1D">1d</A> Hildebrand JP. Marsden SP. Synlett  1996,  893 

<A NAME="RD05306ST-1E">1e</A> Charette AB. Giroux A. J. Org. Chem.  1996,  61:  8718 

<A NAME="RD05306ST-1F">1f</A> Pietruszka J. Widenmeyer M. Synlett  1997,  977 

<A NAME="RD05306ST-1G">1g</A> Zhou SM. Deng MZ. Xia LJ. Tang MH. Angew. Chem. Int. Ed.  1998,  37:  2845 

<A NAME="RD05306ST-1H">1h</A> Chen H. Deng M.-Z. J. Chem. Soc., Perkin Trans. 1  2000,  1609 

<A NAME="RD05306ST-1I">1i</A> Yao M.-L. Deng M.-Z. Synthesis  2000,  1095 

<A NAME="RD05306ST-2A">2a</A> Luithle JEA. Pietruszka J. Liebigs Ann./Recl.  1997,  2297 

<A NAME="RD05306ST-2B">2b</A> Luithle JEA. Pietruszka J. J. Org. Chem.  1999,  64:  8287 

<A NAME="RD05306ST-2C">2c</A> Pietruszka J. Witt A. J. Chem. Soc., Perkin Trans. 1  2000,  4293 

<A NAME="RD05306ST-2D">2d</A> Luithle JEA. Pietruszka J. J. Org. Chem.  2000,  65:  9194 

<A NAME="RD05306ST-2E">2e</A> Luithle JEA. Pietruszka J. Eur. J. Org. Chem.  2000,  2557 

<A NAME="RD05306ST-2F">2f</A> Markó IE. Kumamoto T. Giard T. Adv. Synth. Catal.  2002,  344:  1063 

<A NAME="RD05306ST-3A">3a</A> Garcia Garcia P. Hohn E. Pietruszka J. J. Organomet. Chem.  2003,  680:  281 

<A NAME="RD05306ST-3B">3b</A> Pietruszka J. Witt A. Frey W. Eur. J. Org. Chem.  2003,  3219 

<A NAME="RD05306ST-3C">3c</A> Hohn E. Pietruszka J. Adv. Synth. Catal.  2004,  346:  863 

Selected examples:

<A NAME="RD05306ST-4A">4a</A> Burgess K. Ho K.-K. Moye-Sherman D. Synlett  1994,  575 

<A NAME="RD05306ST-4B">4b</A> Vallgårda J. Appelberg U. Arvidsson L.-E. Hjorth S. Svensson BE. Hacksell U. J. Med. Chem.  1996,  39:  1485 

<A NAME="RD05306ST-4C">4c</A> Salaün J. Top. Curr. Chem.  2000,  207:  1 

<A NAME="RD05306ST-4D">4d</A> Aggarwal VK. de Vicente J. Bonnert RV. Org. Lett.  2001,  3:  2785 

<A NAME="RD05306ST-4E">4e</A> Ko SS, Delucca GV, Duncia JV, Kim UT, Wacker DA, and Zheng C. inventors; WO Patent  2001098270.  ; Chem. Abstr. 2001, 136, 69739

<A NAME="RD05306ST-4F">4f</A> Biftu T, Feng DD, Liang G.-B, Ponpipom MM, Qian X, Girotra N, Fisher MH, and Wyvratt MJ. inventors; WO Patent  2001034150.  ; Chem. Abstr. 2001, 134, 366803

<A NAME="RD05306ST-4G">4g</A> Goldstein S, Claude G, Charton Y, Lockhart B, and Lestage P. inventors; Eur. Pat. Appl.  1170281 A1.  ; Chem. Abstr. 2002, 136, 85625

<A NAME="RD05306ST-4H">4h</A> Gnad F. Reiser O. Chem. Rev.  2003,  103:  1603 

<A NAME="RD05306ST-4I">4i</A> de Meijere A. Kozhushkov SI. Savchenko AI. J. Organomet. Chem.  2004,  689:  2033 

Review:

<A NAME="RD05306ST-5A">5a</A> Darses S. Genêt J.-P. Eur. J. Org. Chem.  2003,  4313 

More recent examples:

<A NAME="RD05306ST-5B">5b</A> Kabalka GW. Meredy AR. Organometallics  2004,  23:  4519 

<A NAME="RD05306ST-5C">5c</A> Kim BJ. Matteson DS. Angew. Chem.  2004,  116:  3118 

<A NAME="RD05306ST-5D">5d</A> De S. Welker ME. Org. Lett.  2005,  7:  2481 

<A NAME="RD05306ST-5E">5e</A> Yuen AKL. Hutton CA. Tetrahedron Lett.  2005,  46:  7899 

<A NAME="RD05306ST-6A">6a</A> Fang G.-H. Yan Z.-J. Deng M.-Z. Org. Lett.  2004,  6:  357 

<A NAME="RD05306ST-6B">6b</A> Charette A. Mathieu S. Fournier J.-F. Synlett  2005,  1779 

<A NAME="RD05306ST-7A">7a</A> Vaultier M. Truchet F. Carboni B. Hoffmann RW. Denne I. Tetrahedron Lett.  1987,  28:  4169 

<A NAME="RD05306ST-7B">7b</A> Hoffmann RW. Dresely S. Synthesis  1988,  103 

<A NAME="RD05306ST-8">8</A> Denmark SE. O’Connor SP. J. Org. Chem.  1997,  62:  584 

<A NAME="RD05306ST-9">9</A>

Using (S,S)-8 or (R,R)-8 as enantiomerically pure ligands did not furnish the product in high selectivity.

<A NAME="RD05306ST-10">10</A> Vedejs E. Chapman RW. Fields SC. Lin S. Schrimpf MR. J. Org. Chem.  1995,  60:  3020 

<A NAME="RD05306ST-11">11</A> Darses S. Michaud G. Genêt J.-P. Eur. J. Org. Chem.  1999,  1875 

<A NAME="RD05306ST-12">12</A>

Representative Procedure - Synthesis of ent -15.
KHF₂ (5.50 g, 70.5 mmol) was placed in a round-bottom flask (caution: use Teflon vessel) and dissolved in MeOH (150 mL). The boronic ester 10 (880 mg, 1.41 mmol), dissolved in a minimum amount of CH₂Cl₂, was added and the mixture heated at 80 °C for 2 d. The solvents were removed under reduced pressure, the remaining colorless solids transferred on a Büchner funnel and washed with Et₂O. The product was dissolved in MeCN, the solvent removed under reduced pressure, and the remaining solid recrystallized from MeCN (10 mL). Yield: 92% (345 mg, 1.29 mmol); [α]_D ²⁰ -16.4 (c 0.5, DMSO); mp 197 °C. Anal. Calcd for C₁₁H₁₃BF₃KO (268.12): C, 49.27; H, 4.89. Found: C, 48.82; H, 4.87. ¹H NMR (400 MHz, DMSO-d ₆): δ = -0.87 (ddd, ³ J _1,3a = 9.8 Hz, ³ J _1,3b = 6.7 Hz, ³ J _1,2 = 3.4 Hz, 1 H, 1-H), -0.16 (ddd, ³ J _3a,1 = 9.8 Hz, ³ J _3a,2 = 3.3 Hz, ² J _3a,3b = 2.9 Hz, 1 H, 3-H_a), 0.09 (ddd, ³ J _3b,2 = 6.8 Hz, ³ J _3b,1 = 6.7 Hz, ² J _3b,3a = 2.9 Hz, 1 H, 3-H_a), 0.79 (m_c, 1 H, 2-H), 3.07 (dd, ² J _4a,4b = 10.2 Hz, ³ J _4a,2 = 7.3 Hz, 1 H, 4-H_a), 3.30 (dd, ² J _4b,4a = 10.2 Hz, ³ J _4b,2 = 6.1 Hz, 1 H, 4-H_b), 4.61 (d, ² J = 12.2 Hz, 1 H, Bn-H_a), 4.68 (d, ² J = 12.2 Hz, 1 H, Bn-H_b), 7.25-7.34 (m, 5 H, arom.-H) ppm. ¹³C NMR (100 MHz, DMSO-d ₆): δ = 6.9 (C-3), 13.6 (C-2), 70.6 (Bn-CH₂), 76.4 (C-4), 126.9, 127.2, 128.0 (CH_arom), 139.1 (C _arom) ppm. ¹⁹F NMR (400 MHz, DMSO-d ₆): δ = -140.06 (s, 3 F, BF ₃) ppm.

<A NAME="RD05306ST-13">13</A> Matteson DS. Kim GY. Org. Lett.  2002,  4:  2153 

Related examples:

<A NAME="RD05306ST-14A">14a</A> Armstrong A. Scutt JN. Chem. Commun.  2004,  510 

<A NAME="RD05306ST-14B">14b</A> Martín-Vilà M. Muray E. Aguado GP. Alvarez-Larena A. Branchadell V. Minguillón C. Giralt E. Ortuño RM. Tetrahedron: Asymmetry  2000,  11:  3569 

<A NAME="RD05306ST-14C">14c</A> Csuk R. Schabel MJ. von Scholz Y. Tetrahedron: Asymmetry  1996,  7:  3505 

<A NAME="RD05306ST-15">15</A>

CCDC-297716 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge at www.ccdc.cam.ac.uk/conts/retrieving.html [or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: [phone]; email: [e-mail]].