Synthesis of Dictyopterene A

Abstract

The total synthesis of dictyopterene A was accomplished via an enantiomerically pure cyclopropylboronic ester building block. Crucial olefination steps were carried out employing the Julia-Kocienski as well as the Wittig reactions. The Matteson homologation was the final key step for the total synthesis.

boron - cyclopropanes - natural products - total synthesis - stereoselectivity

References and Notes

Reviews:

<A NAME="RD01008ST-1A">1a</A> Moore RE. Acc. Chem. Res.  1977,  10:  40 

<A NAME="RD01008ST-1B">1b</A> Jaenicke L. Müller DG. Fortschr. Chem. Org. Naurst.  1973,  30:  61 

<A NAME="RD01008ST-1C">1c</A> Moore RE. In Marine Natural Products   Scheuer PJ. Academic Press; New York: 1978.  Chap. 2.

<A NAME="RD01008ST-1D">1d</A> Jaenicke L. Boland W. Angew. Chem., Int. Ed. Engl.  1982,  21:  643 

<A NAME="RD01008ST-2A">2a</A> Moore RE. Pettus JA. Doty MS. Tetrahedron Lett.  1968,  9:  4787 

<A NAME="RD01008ST-2B">2b</A> Pettus JA. Moore RE. J. Chem. Soc., Chem. Commun.  1970,  1093 

<A NAME="RD01008ST-2C">2c</A> Pettus JA. Moore RE. J. Am. Chem. Soc.  1971,  93:  3087 

<A NAME="RD01008ST-2D">2d</A> Moore RE. Pettus JA. Mistysyn J. J. Org. Chem.  1974,  39:  2201 

<A NAME="RD01008ST-2E">2e</A> Moore RE. Lloydia  1976,  39:  181 

<A NAME="RD01008ST-2F">2f</A> Moore RE. Act. Chem. Res.  1977,  10:  40 

<A NAME="RD01008ST-2G">2g</A> Müller DG. Gassmann G. Boland W. Marnek F. Jaenicke L. Science  1981,  212:  1040 

<A NAME="RD01008ST-2H">2h</A> Müller DG. Clayton MN. Gassmann G. Boland W. Marner F.-J. Jaenicke L. Experientia  1984,  40:  211 

<A NAME="RD01008ST-2I">2i</A> Müller DG. Clayton MN. Gassmann G. Boland W. Marner F.-J. Schotten T. Jaenicke L. Naturwissenschaften  1985,  72:  97 

<A NAME="RD01008ST-2J">2j</A> Hombeck M. Pohnert G. Boland W. Chem. Commun.  1999,  243 

<A NAME="RD01008ST-2K">2k</A> Boland W. Müller DG. Tetrahedron Lett.  1987,  28:  307 

<A NAME="RD01008ST-2L">2l</A> Kajiwara T. Hatanaka A. Tahala Y. Kawai T. Ishihara M. Tsuneya T. Fujimura T. Phytochemistry  1989,  28:  636 

<A NAME="RD01008ST-2M">2m</A> Kajiwara T. Hatanaka A. Kodama K. Ochi S. Fujimura T. Phytochemistry  1991,  30:  1805 

<A NAME="RD01008ST-2N">2n</A> Wirth D. Fischer-Lui I. Boland W. Icheln D. Runge T. König WA. Philips J. Clayton M. Helv. Chim. Acta  1992,  75:  734 

<A NAME="RD01008ST-2O">2o</A> Pohnert G. Boland W. Tetrahedron  1996,  52:  10073 

<A NAME="RD01008ST-3">3</A>

Later, (1S,2S)-dictyopterene B enantiomer was discovered us a minor component in female gametes and essential oils of families Scytosiphonaceae, Chordariaceae, Dictyo-taceae, see ref. 2m.

Optically pure dictyopterene A:

<A NAME="RD01008ST-4A">4a</A> Kajiwara T. Nakatomi T. Sasaki Y. Hatanaka A. Agric. Biol. Chem.  1980,  44:  2099 

<A NAME="RD01008ST-4B">4b</A> Schotten T. Boland W. Jaenicke L. Helv. Chim. Acta  1985,  68:  1186 

<A NAME="RD01008ST-4C">4c</A> Grandjean D. Pale P. Chuche J. Tetrahedron  1991,  47:  1215 

<A NAME="RD01008ST-4D">4d</A> Colobert F. Genet JP. Tetrahedron Lett.  1985,  26:  2779 

<A NAME="RD01008ST-4E">4e</A> Narjes F. Bolte O. Icheln D. König WA. Schaumann E. J. Org. Chem.  1993,  58:  626 

<A NAME="RD01008ST-4F">4f</A> Itoh T. Inoue H. Emoto S. Bull. Chem. Soc. Jpn.  2000,  73:  409 

<A NAME="RD01008ST-5">5</A> Optically pure dictyopterene B: Dorch D. Kunz E. Helmchen G. Tetrahedron Lett.  1985,  26:  3319 ; and ref. 4a,b

Selected examples:

<A NAME="RD01008ST-6A">6a</A> Yamada K. Tan H. Hirota K. Tetrahedron Lett.  1980,  21:  4873 

<A NAME="RD01008ST-6B">6b</A> Ohloff G. Pickenhagen W. Helv. Chem. Acta  1969,  52:  880 

<A NAME="RD01008ST-6C">6c</A> Billups WE. Chow WY. Gross JH. J. Chem. Soc., Chem. Commun.  1974,  252 

<A NAME="RD01008ST-6D">6d</A> Das KC. Weinstein B. Tetrahedron Lett.  1969,  40:  3459 

<A NAME="RD01008ST-6E">6e</A> Abraham WD. Cohen T. J. Am. Chem. Soc.  1991,  113:  2313 

<A NAME="RD01008ST-6F">6f</A> Schneider MP. Goldbach M. J. Am. Chem. Soc.  1980,  102:  6114 

<A NAME="RD01008ST-7">7</A> Hohn E. Pietruszka J. Solguda G. Synlett  2006,  1531 

<A NAME="RD01008ST-8A">8a</A> Luithle JEA. Pietruszka J. J. Org. Chem.  1999,  64:  8287 

<A NAME="RD01008ST-8B">8b</A> Luithle JEA. Pietruszka J. Eur. J. Org. Chem.  2000,  2557 

<A NAME="RD01008ST-8C">8c</A> Hohn E. Pietruszka J. Adv. Synth. Catal.  2004,  346:  863 

<A NAME="RD01008ST-9">9</A>

Thematic issue on cyclopropane chemistry (guest editor: A. de Meijere): Chem. Rev. 2002, 103, 931-1647.

<A NAME="RD01008ST-10A">10a</A> Dess DB. Martin JC. J. Org. Chem.  1983,  48:  4155 

<A NAME="RD01008ST-10B">10b</A> Ireland RE. Liu L. J. Org. Chem.  1993,  58:  2899 

<A NAME="RD01008ST-10C">10c</A> Wavrin L. Viala J. Synthesis  2002,  326 

<A NAME="RD01008ST-11A">11a</A> Luithle JEA. Pietruszka J. J. Org. Chem.  2000,  65:  9194 

<A NAME="RD01008ST-11B">11b</A> Garcia PG. Hohn E. Pietruszka J. J. Organomet. Chem.  2003,  680:  281 

<A NAME="RD01008ST-12">12</A> Review: Maryanoff BE. Reitz AB. Chem. Rev.  1989,  89:  863 

<A NAME="RD01008ST-13A">13a</A> Chatterjee AK. Choi T.-L. Sanders DP. Grubbs RH. J. Am. Chem. Soc.  2003,  125:  11360 

<A NAME="RD01008ST-13B">13b</A> Blackwell HE. O’Leary DJ. Chatterjee AK. Washenfelder RA. Bussmann DA. Grubbs RH. J. Am. Chem. Soc.  2000,  122:  58 

<A NAME="RD01008ST-14A">14a</A> Schlosser M. Christmann KF. Angew. Chem., Int. Ed. Engl.  1966,  5:  126 

<A NAME="RD01008ST-14B">14b</A> Schlosser M. Tuong HB. Schaub B. Tetrahedron Lett.  1985,  26:  311 

<A NAME="RD01008ST-15A">15a</A> Reviews: Blakemore PR. J. Chem. Soc., Perkin Trans. 1  2002,  2563 

<A NAME="RD01008ST-15B">15b</A> Blakemore PR. Kocienski PJ. Morley A. Muir K. J. Chem. Soc., Perkin Trans. 1  1999,  955 

<A NAME="RD01008ST-15C">15c</A> Blakemore PR. Cole WJ. Kocienski PJ. Morley A. Synlett  1998,  26 

<A NAME="RD01008ST-15D">15d</A> Bellingham R. Jarowicki K. Kocienski P. Martin V. Synthesis  1996,  285 

<A NAME="RD01008ST-16">16</A>

Representative Procedure - Synthesis of E -olefin 6 To a stirred solution of the sulfone 7 (0.08 g, 0.28 mmol, 1.5 equiv) in anhyd DME (4 mL) at -60 °C under N₂ was added dropwise via cannula a solution of KHMDS (0.07 g, 0.34 mmol, 1.8 equiv) in anhyd DME (2 mL) over 5 min. The yellow-orange solution was stirred for 5 min and the aldehyde 3 (0.1 g, 0.19 mmol, 1 equiv) in anhyd DME (2 mL) was added dropwise via cannula over 5 min. The reaction mixture was stirred additional 10 min at -60 °C and was then quenched with H₂O (1 mL). The mixture was stirred vigorously whilst warming to r.t., diluted with Et₂O (4 mL) and H₂O (4 mL), and finally extracted with Et₂O (3 × 4 mL). The combined organic layers were dried (MgSO₄), filtered, and concentrated under reduced pressure. The crude product 6 was purified by flash column chromatography (SiO₂, petroleum ether-EtOAc, 95:5) to afford the E-olefin 6 (0.10 g, 93%) as colorless crystals; E/Z > 99:1. The minor Z-isomer 6 was only detected by 600 MHz ¹H NMR and was removed by a single recrystallization from pentane.
E-Olefin 6: [α]_D ²⁰ -79.7 (c 1.0, CHCl₃); mp 113 °C. Anal. Calcd for C₃₉H₄₃BO₄ (586.57): C, 79.86; H, 7.39. Found: C, 79.91; H, 7.31. MS-FAB (NBA + NaI): m/z (%) = 609 (<5) [M + Na⁺], 197 (100) [Ph₂COCH₃ ⁺], 167 (12) [Ph₂C⁺], 105 (10) [C₇H₅O⁺], 77 (6) [C₆H₅ ⁺]. IR (film): 3060, 3024, 2956, 2932, 2833, 1493, 1446, 1421, 1366, 1239, 1184, 1075, 1032, 1019, 965, 921, 857 cm^-1. ¹H NMR (600 MHz, CDCl₃): δ = -0.53 (ddd, ³ J _{1 ′,3 ′b} = 9.8 Hz, ³ J _{1 ′,3 ′a} = 6.5 Hz, ³ J _{1 ′,2 ′} = 5.3 Hz, 1 H, 1′-H), 0.24 (ddd, ³ J _{2 ′,3a ′}= 7.8 Hz, ³ J _{1 ′,3 ′a} = 6.4 Hz, ³ J _{3 ′a,3 ′b} = 3.4 Hz, 1 H, 3′-H_a), 0.34 (ddd, ³ J _{1 ′,3 ′b} = 9.8 Hz, ³ J _{2 ′,3 ′b} = 6.5 Hz, ³ J _{3 ′a, 3 ′b} = 3.4 Hz, 1 H, 3′-H_b), 0.91 (t, ³ J _{5 ′′,6 ′′} = 7.2 Hz, 3 H, 6′′-H), 1.17-1.27 (m, 1 H, 2′-H), 1.28-1.36 (m, 4 H, 4′′-H, 5′′-H), 1.95 (m, 2 H, 3′′-H), 2.99 (s, 6 H, OCH₃), 4.79 (dd, ³ J _{1 ′′,2 ′′} = 15.1 Hz, ³ J _{1 ′′,2 ′} = 8.5 Hz, 1 H, 1′′-H), 5.25 (s, 2 H, 4-H, 5-H), 5.51 (dt, ³ J _{1 ′′,2 ′′} = 15.1 Hz, ³ J _{2 ′′,3 ′′} = 6.9 Hz, 1 H, 2′′-H), 7.27-7.34 (m, 20 H, arom. H). ¹³C NMR (125 MHz, CDCl₃): δ = 1.8 (C-1′), 12.4 (C-6′′), 13.8 (C-3′), 21.0 (C-5′′), 22.1 (C-4′′), 27.2 (C-2′), 31.8 (C-3′′), 51.7 (CPh₂OCH₃), 77.7 (C-4 and C-5), 83.3 (CPh₂OCH₃), 127.1, 127.2, 127.4, 127.7, 128.1, 128.3 (arom. CH), 129.6 (C-1′′), 133.5 (C-2′′), 141.1, 141.3 (arom. C_ipso).

<A NAME="RD01008ST-17A">17a</A> Vedejs E. Chapman RW. Fields SC. Lin S. Schrimpf MR. J. Org. Chem.  1995,  60:  3020 

<A NAME="RD01008ST-17B">17b</A> Matteson DS. Kim GY. Org. Lett.  2002,  4:  2153 

<A NAME="RD01008ST-17C">17c</A> Kim BJ. Matteson DS. Angew. Chem. Int. Ed.  2004,  43:  3056 

<A NAME="RD01008ST-18">18</A> Yuen AKL. Hutton CA. Tetrahedron Lett.  2005,  46:  7899 

<A NAME="RD01008ST-19">19</A> Published racemate of oxaborinane 9: Markó IE. Giard T. Sumida S. Gies A.-E. Tetrahedron Lett.  2002,  43:  2317 

<A NAME="RD01008ST-20A">20a</A> Sadhu KM. Matteson DS. Organometallics  1985,  4:  1687 

<A NAME="RD01008ST-20B">20b</A> Matteson DS. Tetrahedron  1998,  54:  10555 

<A NAME="RD01008ST-20C">20c</A> Pietruszka J. Witt A. J. Chem. Soc., Perkin Trans. 1  2000,  4293 

<A NAME="RD01008ST-21">21</A>

(-)-(1S,2S)-Dictyopterene A (1): [α]_D ²⁰ -69.3 (c 0.40, CHCl₃); ref. 2d: [α]_D ²² +72 (c 6.74, CHCl₃) for the 1R,2R-enantiomer. GC-MS (EI, 70 eV): m/z (%) = 150 (100) [M⁺], 135 (15) [M⁺ - CH₃], 122 (24) [M - C₂H₄ ⁺], 121 (60) [M - C₂H₅ ⁺]. ¹H NMR (600 MHz, CDCl₃): δ = 0.75-0.84 (m, 2 H, 3′-H), 0.87 (t, ³ J _{5 ′′,6 ′′} = 7.0 Hz, 3 H, 6′′-H), 1.25-1.35 (m, 4 H, 4′′ and 5′′-H), 1.36-1.41 (m, 2 H, 1′-H and 2′-H), 1.95-2.05 (m, 2 H, 3′′-H), 4.84 (dd, ³ J _1,2 = 10.2 Hz, ² J _2a,2b = 2.3 Hz, 1 H, 2-H_a), 4.98 (dd, ³ J _1,2 = 17.2 Hz, ² J _2a,2b = 2.3 Hz, 1 H, 2-H_b), 5.03 (dd, ³ J _{1 ′′,2 ′′} = 15.1 Hz, ³ J _{1 ′′,2 ′} = 6.1 Hz, 1 H, 1′′-H), 5.36 (ddd, ³ J _1,2 = 10.2 Hz, ³ J _1,2 = 17.2 Hz, ³ J _{1,1 ′} = 6.7 Hz, 1 H, 1-H), 5.46 (dt, ³ J _{1 ′′,2 ′′} = 15.1 Hz, ³ J _{2 ′′,3 ′′} = 6.9 Hz, 1 H, 2′′-H). ¹³C NMR (150 MHz, CDCl₃): δ = 14.1 (C-6′′), 14.8 (C-3′), 22.3 (C-5′′), 23.6 (C-2′), 24.3 (C-1′), 31.8 (C-4′′), 32.2 (C-3′′), 111.8 (C-2), 129.2 (C-2′′), 131.6 (C-1′′), 140.9 (C-1).