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Synlett 2010(10): 1525-1527  
DOI: 10.1055/s-0029-1219950
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Regioselective Synthesis of Highly Functionalized Arylphosphonates by Cyclocondensation of 1,3-Bis(trimethylsilyloxy)buta-1,3-dienes with 3-Ethoxy-2-phosphonylalk-2-en-1-ones

Olumide Fatunsina, Mohanad Shkoora, Abdolmajid Riahia, Peter Langer*a,b
a Institut für Chemie, Universität Rostock, Albert Einstein Str. 3a, 18059 Rostock, Germany
b Leibniz-Institut für Katalyse an der Universität Rostock e.V., Albert Einstein Str. 29a, 18059 Rostock, Germany
Fax: +49(381)4986412; e-Mail: peter.langer@uni-rostock.de;
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Publikationsverlauf

Received 12 February 2010
Publikationsdatum:
25. Mai 2010 (online)

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Abstract

Highly functionalized arylphosphonates were prepared by TiCl4-mediated cyclocondensation of 3-ethoxy-2-phosphonyl­alk-2-en-1-ones with 1,3-bis(trimethylsilyloxy)buta-1,3-dienes.

Key words

cyclizations - regioselectivity - phosphonic acid derivatives - silyl enol ethers

    References and Notes

  • 1a Raboisson P. Baurand A. Cazenave J.-P. Gachet C. Schultz D. Spiess B. Bourguigon J.-J. J. Org. Chem.  2002,  67:  8063 
    Google Scholar
  • 1b Holstein SA. Cermak DM. Wiemer DF. Lewis K. Hohl R. J. Bioorg. Med. Chem.  1998,  6:  687 
    Google Scholar
  • 1c Lazrek HB. Rochdi A. Khaider H. Barascut JL. Imbach JL. Balzarini J. Witvrouw M. Pannecouque C. De Clercq E. Tetrahedron  1998,  54:  3807 
    Google Scholar
  • 1d Smith PW. Chamiec AJ. Cobley KN. Duncan K. Howes PD. Whittington AR. Wood MR. J. Antibiot.  1995,  4873 
    Google Scholar
  • 1e Dolman NP. More JCA. Alt A. Knauss JL. Troop HM. Bleakman D. Collingridge GL. Jane DE. J. Med. Chem.  2006,  49:  2579 
    Google Scholar
  • 1f Kim YC. Brown SG. Harden TK. Boyer JL. Dubyak G. King BF. Burnstock G. Jacobson KA. J. Med. Chem.  2001,  44:  340 
    Google Scholar
  • 1g Bigge CF. Johnson G. Ortwine DF. Drummond JT. Retz DM. Brahce LJ. Coughenour LL. Marcoux FW. Probert AW. J. Med. Chem.  1992,  35:  1371 
    Google Scholar
  • 1h Scapin G. Patel SB. Becker JW. Wang Q. Desponts C. Waddleton D. Skorey K. Cromlish W. Bayly C. Therien M. Gauthier JY. Li CS. Lau CK. Ramachandran C. Kennedy BP. Asante-Appiah E. Biochemistry  2003,  42:  11451 
    Google Scholar
  • 1i Nagarajan R. Pratt RF. Biochemistry  2004,  43:  9664 
    Google Scholar
  • 1j Petrakis KS. Nagabhushan TL. J. Am. Chem. Soc.  1987,  109:  2831 
    Google Scholar
  • 1k Sawa M. Kiyoi T. Kurokawa K. Kumihara H. Yamamoto M. Miyasaka T. Ito Y. Hirayama R. Inoue T. Kirii Y. Nishiwaki E. Ohmoto H. Maeda Y. Ishibushi E. Inoue Y. Yoshino K. Kondo H. J. Med. Chem.  2002,  45:  919 
    Google Scholar
  • 1l Ma D. Tian H. Zou G. J. Org. Chem.  1999,  64:  120 
    Google Scholar
  • 2 Welch CM. Gonzales EJ. Guthrie JD. J. Org. Chem.  1961,  26:  3270 
    CrossrefGoogle Scholar
  • 3a Jin JI. inventors; US  74-496233.  ; Chem. Abstr. 1979, 90, 153010m
  • 3b Onouchi H. Miyagawa T. Furuko A. Maeda K. Yashima E. J. Am. Chem. Soc.  2005,  127:  2960 
    Google Scholar
  • 3c Onouchi H. Maeda K. Yashima E. J. Am. Chem. Soc.  2001,  123:  7441 
    Google Scholar
  • 3d Allcock HR. Hofmann MA. Ambler CM. Morford RV. Macromolecules  2002,  35:  3484 
    Google Scholar
  • 4a Vedejs E. Daugulis O. Diver ST. Powell DR. J. Org. Chem.  1998,  63:  2338 
    Google Scholar
  • 4b Prim D. Campagne J. Joseph D. Andrioletti B. Tetrahedron  2002,  58:  2041 
    Google Scholar
  • 4c Inoue A. Shinokubo H. Oshima K. J. Am. Chem. Soc.  2003,  125:  1484 
    Google Scholar
  • 5a Kosolapoff GM. J. Am. Chem. Soc.  1952,  74:  4119 
    Google Scholar
  • 5b Doak GO. Freedman LD. J. Am. Chem. Soc.  1951,  73:  5658 
    Google Scholar
  • 5c Freedman LD. Doak GO. J. Am. Chem. Soc.  1955,  77:  173 
    Google Scholar
  • 5d Boumekouez A. About-Jaudet E. Savignac NCP. J. Organomet. Chem.  1992,  440:  297 
    Google Scholar
  • 5e Yuan C. Feng H. Synthesis  1990,  140 
    Google Scholar
  • 5f Tavas P. Chem. Ber.  1970,  103:  2428 
    Google Scholar
  • 5g Tavas P. Korte F. Tetrahedron  1967,  23:  4677 
    Google Scholar
  • 5h Gelman D. Jiang L. Buchwald SL. Org. Lett.  2003,  5:  2315 
    Google Scholar
  • 5i Osuka A. Ohmasa N. Yoshida Y. Suzuki H. Synthesis  1983,  69 
    Google Scholar
  • 5j Burger A. Dawson ND. J. Org. Chem.  1951,  16:  1250 
    Google Scholar
  • 5k Edmundson RS. Wrigley JOL. Tetrahedron  1967,  23:  283 
    Google Scholar
  • 5l Freeman S. Harger MJ. J. Chem. Soc., Perkin Trans. 1  1987,  1399 
    Google Scholar
  • 6a Hirao T. Masunga T. Ohshiro Y. Agawa T. Synthesis  1981,  56 
    Google Scholar
  • 6b Hirao T. Masunga T. Yamada N. Ohshiro Y. Agawa T. Bull. Chem. Soc. Jpn.  1982,  55:  909 
    Google Scholar
  • 6c Petrakis KS. Nagabhushan TL. J. Am. Chem. Soc.  1987,  109:  2831 
    Google Scholar
  • 6d Ngo HL. Lin W. J. Am. Chem. Soc.  2002,  124:  14298 
    Google Scholar
  • 6e Kabachnik MM. Solntseva MD. Izmer VV. Novikova ZS. Beletskaya IP. Russ. J. Org. Chem.  1998,  34:  93 
    Google Scholar
  • 6f Gooßen LJ. Dezfuli MK. Synlett  2005,  445 
    Google Scholar
  • For reviews of catalytic carbon-heteroatom bond formations, see:
  • 7a Beletskaya IP. Pure Appl. Chem.  1997,  69:  471 
    Google Scholar
  • 7b Hartwig JF. Palladium-Catalyzed Amination of Aryl Halides and Related Reactions, In Handbook of Organopalladium Chemistry for Organic Synthesis   Vol. 1:  Negishi E.-I. de Meijere A. Wiley-Interscience; New York: 2002.  p.1051 
    Google Scholar
  • 8a Kouno R. Okauchi T. Nakamura M. Ichikawa J. Minami T. J. Org. Chem.  1998,  63:  6239 
    Google Scholar
  • 8b Kouno R. Tsubota T. Okauchi T. Minami T. J. Org. Chem.  2000,  65:  4326 
    Google Scholar
  • 8c Arimori S. Kouno R. Okauchi T. Minami T. J. Org. Chem.  2002,  67:  7303 
    Google Scholar
  • 9 Yoffe ST. Petrovsky PV. Goryunov YI. Yershova TV. Kabachnik MI. Tetrahedron  1972,  28:  2783 
    CrossrefGoogle Scholar
  • 10 For a review of [3+3] cyclizations of 1,3-bis(silyl enol ethers), see: Feist H. Langer P. Synthesis  2007,  327 
    Artikel in Thieme ConnectGoogle Scholar
  • 11 For a review of the chemistry of 1,3-bis(silyl enol ethers), see: Langer P. Synthesis  2002,  441 
    Artikel in Thieme ConnectGoogle Scholar
  • 14 Chan T.-H. Brownbridge P. J. Am. Chem. Soc.  1980,  102:  3534 
    CrossrefGoogle Scholar
  • 15 Molander GA. Cameron KO. J. Am. Chem. Soc.  1993,  115:  830 
    Google Scholar
  • 16 Nguyen VTH. Bellur E. Appel B. Synthesis  2006,  2865 
    Artikel in Thieme ConnectGoogle Scholar
12

Diethyl (1-Ethoxy-3-oxobut-1-en-2-yl)phosphonate (2a)
A mixture of 1a (1.10 g, 1.0 mL, 5.55 mmol), triethyl orthoformiate (1.1 mL, 6.62 mmol) and Ac2O (1.5 mL, 16.0 mol) was stirred for 2 h at 120 ˚C and subsequently for 2 h at 140 ˚C. The resulting mixture was distilled to give 2a as a brownish oil (1.20 g, 86%). ¹H NMR (300 MHz, CDCl3): δ = 1.21-1.24 (m, 6 H, 2 × OCH2CH 3), 1.36 (t, ³ J = 6.9 Hz, 3 H, OCH2CH 3), 2.25 (s, 3 H, CH3), 4.04-4.08 (m, 4 H, 2 × OCH 2CH3), 4.23 (q, ³ J = 7.2 Hz, 2 H, OCH 2CH3), 7.70 (d, ³ J P,H = 11.4 Hz, 1 H, CH). ¹³C NMR (CDCl3, 75 MHz): δ = 15.0, 15.9, 16.0, 20.6 (CH3), 62.2, 62.4, 73.0 (OCH2), 107.3 (d, J C,P = 191 Hz,Cq), 169.9 (d, J CH,P = 25.5 Hz, CH), 195.0 (CO). ³¹P NMR (250 MHz, CDCl3): δ = 19.64. GC-MS (EI, 70 eV): m/z (%) = 250 (5) [M+], 235 (47), 221 (12), 207 (43), 205 (13), 179 (42), 177 (11), 151 (100), 123 (23), 121 (15), 105 (11), 81 (11), 53 (13), 43 (13), 29 (10). HRMS (EI): m/z calcd for C10H19O5P [M]+: 250.09646; found: 250.09666.

13

Diethyl (1-Ethoxy-3-oxo-3-phenylprop-1-en-2-yl)phosphonate (2b)
A mixture of 1b (1.50 g, 1.27 mL, 5.85 mmol), triethyl orthoformiate (1.70 mL, 10.24 mmol), and Ac2O (1.56 mL, 16.61 mmol) was stirred for 36 h at 140 ˚C. The mixture was cooled to 20 ˚C and purified by column chromatography to give 2b as a brownish oil (1.350 g, 74%). ¹H NMR (300 MHz, CDCl3): δ = 1.08 (t, ³ J = 7.1 Hz, 3 H, OCH2CH 3), 1.21 (t, ³ J = 7.0 Hz, 6 H, 2 × OCH2CH 3), 3.94 (q, ³ J = 7.1 Hz, 2 H, OCH 2CH3), 4.01-4.10 (m, 4 H, 2 × OCH 2CH3), 7.34-7.48 (m, 5 H, CHAr), 7.80-7.82 (m, 1 H, CH). ³¹P NMR (250 MHz, CDCl3): δ = 16.25 Hz. ¹³C NMR (75 MHz, CDCl3): δ = 15.1, 16.1, 16.2 (CH3), 62.3, 62.4, 71.4 (OCH2), 106.4 (d, J P,C = 189.3 Hz), 128.2 (2 × CHAr), 129.3 (2 × CHAr), 133.0 (CHAr), 137.6 (d, J P,C = 4.3 Hz), 163.5 (d, J P,C = 21.0 Hz, CH), 192.2 (d, J P,C = 4.8 Hz, CO). IR (neat): 3060 (w), 2982 (w), 2932 (w), 2905 (w), 1716 (w), 1660 (m), 1597 (m), 1448 (m), 1391 (m), 1305 (w), 1244 (s), 1204 (m), 1145 (m), 1050 (m), 1016 (s), 959 (s), 853 (m), 790 (s), 723 (m), 690 (m), 659 (m), 564 (m), 534 (m) cm-¹. GC-MS (EI, 70 eV): m/z (%) = 312 (4) [M+], 297 (3), 283 (11), 267 (53), 239 (25), 211 (17), 183 (21), 159 (14), 151 (34), 129 (45), 105 (100), 77 (54). ESI-HRMS: m/z calcd for C15H22O5P [M + H]+: 313.1199; found: 313.1198.

17

General Procedure for the Synthesis of Arylphosphonates 4a-l To a CH2Cl2 solution (2 mL/1.0 mmol of 2a,b) of 2a,b was added 3a-k (1.1 mmol) and, subsequently, TiCl4 (1.1 mmol) at -78 ˚C. The temperature of the solution was allowed to warm to 20 ˚C over 12 h with stirring. To the solution was added HCl (10%, 20 mL), and the organic and the aqueous layer were separated. The latter was extracted with CH2Cl2 (3 × 20 mL). The combined organic layers were dried (Na2SO4), filtered, and the filtrate was concentrated in vacuo. The residue was purified by chromatography (silica gel, n-heptane-EtOAc) to give 4a-l.

18

Methyl 3-(Diethoxyphosphoryl)-6-hydroxy-2-methyl-benzoate (4a)
Starting with 2a (0.375 g, 1.5 mmol) and 3a (0.429 g, 1.65 mmol), 4a was isolated after chromatography (silica gel, heptanes-EtOAc) as a yellowish oil (0.217 g, 48%). ¹H NMR (300 MHz, CDCl3): δ = 1.24 (m, 6 H, 2 × OCH2CH 3), 2.65 (s, 3 H, CH3), 3.91 (s, 3 H, OCH3), 3.99-4.07 (m, 4 H, 2 × OCH 2CH3), 6.83 (dd, ³ J H,H = 8.6 Hz, 4 J P,H = 3.3 Hz, 1 H, CHAr), 7.90 (dd, ³ J H,H = 9.0 Hz, ³ J P,H = 14.0 Hz, 1 H, CHAr), 11.0 (s, 1 H, OH). ¹³C NMR (75 MHz, CDCl3): δ = 16.2, 16.2, 20.6 (CH3), 52.5 (OCH3), 62.0, 62.0 (OCH2), 114.9 (d, J P,CH = 15.2 Hz, CHAr), 115.9 (d, J P,C = 16.1 Hz), 119.0 (d, J P,C = 193.0 Hz), 139.3 (d, J P,CH = 11.0 Hz, CHAr), 145.8 (d, J P,C = 13.5 Hz), 164.0 (d, J P,C = 3.4 Hz, COH), 171.2 (d, J P,C = 2.4 Hz, CO). ³¹P NMR (250 MHz, CDCl3): δ = 19.56. IR (neat): 2920 (m), 2851 (m), 1733 (m), 1660 (w), 1636 (w), 1580 (m), 1456 (m), 1437 (m), 1376 (w), 1308 (m), 1285 (m), 1199 (m), 1161 (m), 1158 (m), 1016 (s), 961 (m), 906 (m), 844 (m), 793 (m), 741 (m), 678 (w), 614 (w), 535 (m) cm-¹. GC-MS (EI, 70 eV): m/z (%) = 302 (65) [M]+, 287 (50), 274 (20), 270 (48), 259 (17), 242 (100), 229 (18), 227 (13), 214 (84), 197 (43), 186 (21), 167 (17), 161 (31), 158 (23), 134 (15), 105 (19), 77 (27), 65 (10), 51 (12), 29 (14). HRMS (EI): m/z calcd for C13H19O6P [M]+: 302.09138; found: 302.09139.