Synlett 2011(11): 1631-1637  
DOI: 10.1055/s-0030-1260793
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Constrained Tetramic Acids, Homostreptopyrrolidine, and their Analogues Based on Unusual Intramolecular Wittig Olefination with Phosphorus Ylides

Andrej Ïuriša, Adam Daïch*b, Dušan Berkeš*a
a Department of Organic Chemistry, Slovak University of Technology, Radlinského 9, 81237 Bratislava, Slovakia
Fax: +421(2)52968560; e-Mail: dusan.berkes@stuba.sk;
b Laboratoire de Chimie, URCOM, EA 3221, INC3M CNRS-FR 3038, UFR des Sciences et Techniques, Université du Havre, BP: 540, 25 Rue Philipe Lebon, 76058 Le Havre Cedex, France
Fax: +33(2)32744391; e-Mail: adam.daich@univ-lehavre.fr;
Further Information

Publication History

Received 21 March 2011
Publication Date:
15 June 2011 (online)

Abstract

The synthesis of bicyclic tetramic acids based on the ‘nonclassical’ intramolecular Wittig reaction catalyzed by the corresponding phosphonium salt was developed. We have found that such applications proceed smoothly with high yield with N-substituted aminobutanolides when catalyzed with hydrochloride salt of the starting aminolactones. In addition, a convenient multigram synthesis of optically pure 4-hydroxy-5-substituted pyrrolidinones, including homostreptopyrrolidine as methylene homologues of naturally occurring streptopyrrolidine, via two consecutive reduction is also developed.

    References and Notes

  • For a review on synthesis and use of tetramic acid derivatives, see:
  • 1a Schobert R. Schlenk A. Bioorg. Med. Chem.  2008,  16:  4203 
  • 1b Athanasellis G. Igglessi-Markopoulou O. Markopoulos J. Bioinorg. Chem. Appl.  2010,  315056 
  • 1c Andrews MD. Brewster A. Moloney MG. Tetrahedron: Asymmetry  1994,  5:  1477 
  • 1d Andrews MD. Brewster AG. Moloney MG. Owen KL. J. Chem. Soc., Perkin Trans. 1  1996,  227 
  • 1e Andrews MD. Brewster A. Moloney MG. Synlett  1996,  612 
  • 1f Andrews MD. Brewster AG. Crapnell KM. Ibbett AJ. Jones T. Moloney MG. Prout K. Watkin D. J. Chem. Soc., Perkin Trans. 1  1998,  223 
  • 1g Jeong Y.-C. Moloney MG. Synlett  2009,  2487 
  • 2a Pifferi G, and Pinza M. inventors; US  4118396.  1978
  • 2b Aschwanden W, and Kyburz E. inventors; US  4,476,308.  1984
  • 2c Miyamoto S. Mori A. Neurosciences  1985,  11:  1 
  • 2d Iriuchijima S, Kobayashi H, Aoki K, Oda T, Shinoyama M, and Nosaka Y. inventors; US  4,686,296.  1987
  • 2e Pinza M, and Pfeiffer UC. inventors; US  4,797,496.  1989
  • 2f Jeong Y.-C. Hwang SK. Ahn K.-H. Bull. Korean Chem. Soc.  2005,  26:  826 
  • 3 Courcambeck J. Bihel F. De Michelis C. Quéléver G. Kraus JL. J. Chem. Soc., Perkin Trans. 1  2001,  1421 
  • 4 Schobert R. Wicklein A. Synthesis  2007,  1499 
  • 5 Wittenberger SJ. Baker WR. Donner BG. Tetrahedron  1993,  49:  1547 
  • 6a Gennari C. Moresca D. Vulpetti A. Pain G. Tetrahedron  1997,  53:  5593 
  • 6b Reddy GV. Rao GV. Iyengar DS. Tetrahedron Lett.  1999,  40:  775 
  • 7 Shioiri T. Hayshi K. Hamada Y. Tetrahedron  1993,  49:  1913 
  • 8 Mattern R.-H. Tetrahedron Lett.  1996,  37:  291 
  • 9a Huang PQ. Zheng X. Wang SL. Ye JL. Jin LR. Chen Z. Tetrahedron: Asymmetry  1999,  10:  3309 
  • 9b Park TH. Paik S. Lee SH. Bull. Korean Chem. Soc.  2003,  24:  1227 
  • 10 Coleman RS. Walczak MC. Campbell EL. J. Am. Chem. Soc.  2005,  127:  16038 
  • 11a Agatsuma T. Akama T. Nara S. Matsumiya S. Nakai R. Ogawa H. Otaki S. Ikeda S.-i. Saitoh Y. Kanda Y. Org. Lett.  2002,  4:  4387 
  • 11b Hoye TR. Dvornikovs V. J. Am. Chem. Soc.  2006,  128:  2550 
  • 12 Du J.-X. Huang H.-Y. Huang PQ. Tetrahedron: Asymmetry  2004,  15:  3461 
  • 13 Oba M. Ito C. Hayashi T. Nishiyama K. Tetrahedron Lett.  2009,  50:  25053 
  • 14a Poncet J. Jouin P. Castro B. Nicolas L. Boutar M. Gaudemer A. J. Chem. Soc., Perkin Trans. 1  1990,  611 
  • 14b Kondekar NB. Kandula SRV. Kumar P. Tetrahedron Lett.  2004,  45:  5477 
  • 15 Shin HJ. Kim TS. Lee HS. Park JY. Choi IK. Kwon HJ. Phytochemistry  2008,  69:  2363 
  • 16a Xiang S.-H. Yuan H.-Q. Huang P.-Q. Tetrahedron: Asymmetry  2009,  20:  2021 
  • 16b Ye ZB. Chen J. Meng WH. Huang PQ. Tetrahedron: Asymmetry  2010,  21:  895 
  • 17a Schobert R. Gordon GJ. Curr. Org. Chem.  2002,  6:  1181 
  • 17b Schobert R. Org. Synth.  2005,  82:  140 
  • 17c Schobert R. Dietrich M. Mullen G. Urbina-Gonzalez J.-M. Synthesis  2006,  3902 
  • 18a Schobert R. Jagusch C. Melanophy C. Mullen G. Org. Biomol. Chem.  2004,  2:  3524 
  • 18b Schobert R. Jagusch C. Tetrahedron  2005,  61:  2301 
  • 18c Biersack B. Diestel R. Jagusch C. Rapp G. Sasse F. Schobert R. Chem. Biodiversity  2008,  5:  2423 
  • 19 Schobert R. Naturwissenschaften  2007,  94: 
  • 20 Murphy PJ. Lee SE. J. Chem. Soc., Perkin Trans. 1  1999,  3049 
  • 21 Taillefumier C. Chapleur Y. Chem. Rev.  2004,  104:  263 
  • 22a Murphy PJ. Dennison ST. Tetrahedron  1993,  49:  6695 
  • 22b Cagnolini C. Ferri M. Jones PR. Murphy PJ. Ayres B. Cox B. Tetrahedron  1997,  53:  4815 
  • 22c Bittner C. Burgo A. Murphy PJ. Sung CH. Thornhill AJ. Tetrahedron Lett.  1999,  40:  3455 
  • 22d Heys L. Murphy PJ. Coles SJ. Gelbrich T. Hursthouse MB. Tetrahedron Lett.  1999,  40:  7151 
  • 22e Evans LA. Griffiths KE. Guthmann H. Murphy PJ. Tetrahedron Lett.  2002,  43:  299 
  • 23a Brennan J. Murphy PJ. Tetrahedron Lett.  1988,  29:  2063 
  • 23b Reddy GV. Rao GV. Iyengar DS. Tetrahedron Lett.  1999,  40:  775 
  • 24a Comesse S. Sanselme M. Daïch A. J. Org. Chem.  2008,  73:  5566 
  • 24b Oukli N. Comesse S. Chafi N. Oulyadi H. Daïch A. Tetrahedron Lett.  2009,  50:  1459 
  • 24c Allous I. Comesse S. Berkeš D. Alkyat A. Daïch A. Tetrahedron Lett.  2009,  50:  4411 
  • 24d Saber M. Comesse S. Dalla V. Daïch A. Sanselme M. Netchitaïlo P. Synlett  2010,  2197 
  • 25a Kolarovič A. Berkeš D. Baran P. Pova˛anec F. Tetrahedron Lett.  2005,  46:  975 
  • 25b Berkeš D. Kolarovič A. Manduch R. Baran P. Pova˛anec F. Tetrahedron: Asymmetry  2005,  16:  1927 
  • 25c Berkeš D. Jakubec P. Winklerová D. Pova˛anec F. Daïch A. Org. Biomol. Chem.  2007,  5:  121 
  • 26a Ohtsuki K. Matsuo K. Yoshikawa T. Moriya C. Yokotani-Tomita K. Shishido K. Shindo M. Org. Lett.  2008,  10:  1247 
  • 26b Matsuo K. Ohtsuki K. Yoshikawa T. Yokotani-Tomita K. Shindo M. Tetrahedron  2010,  66:  8407 
  • 26c Matsuo K. Shindo M. Org. Lett.  2010,  12:  5346 
  • 27 For an example, see: Schobert R. Siegfried S. Gordon GJ. J. Chem. Soc., Perkin Trans. 1  2001,  2393 
  • 30 Niwa H. Okamoto O. Miyachi Y. Uosaki Y. Yamada K. J. Org. Chem.  1987,  52:  2941 
  • 32 For a recent paper stating on this equilibrium, see: Storgaard M. Dörwald FZ. Peschke B. Tanner D. J. Org. Chem.  2009,  74:  5032 ; and the references cited therein
28

General Procedure for ‘Nonclassical’ Wittig Reaction - Method B
To a mixture of lactone 9a (2.19 g, 7.78 mmol) in dry toluene (120 mL) were added subsequently the catalyst 9a˙HCl (0.124 g, 0.39 mmol) and the ylide 10 (4.608 g, 13.23 mmol). The reaction mixture was refluxed under argon atmosphere for 1 h. The solvent was then evaporated under reduced pressure, and the residue was purified by chroma-tography on silica gel column (hexane-EtOAc = 3:1) to provide the constrained tetramic acid 7a (2.33 g, 7.63 mmol, 93%) as a white solid; mp 111-113 ˚C (Et2O-heptane), [α]D ²0 205.7 (c 0.32, CHCl3). IR (KBr): νmax = 3105, 2983 (CH), 1668 (C=O), 1644 (C=C), 1185 (COC) cm. ¹H NMR (300 MHz, CDCl3): δ = 7.26-7.41 (m, 10 H, ArH), 5.55-5.65 (m, 1 H, H-1′, 1 H, H-2), 5.06 (s, 1 H, H-6), 4.02 (ddd, 1 H, J = 1.0, 6.6, 11.7 Hz, H-3a), 2.66 (ddd, 1 H, J = 4.4, 6.5, 10.9 Hz, H-3A), 1.93 (q, 1 H, J = 22.9 Hz, H-3B), 1.56 (d, 3 H, J = 7.3 Hz, H-2′). ¹³C NMR (75 MHz, CDCl3): δ = 178.7 (C-6a), 175.6 (C-5), 140.9, 137.7, 129.2, 128.9, 128.8, 127.6, 127.1, 126.2 (ArC), 91.4 (C-6), 90.8 (C-2), 59.6 (C-1′), 48.7 (C-3a), 41.3 (C-3), 18.7 (C-2′). Anal. Calcd for C20H19NO2 (305.14): C, 78.66; H, 6.27; N, 4.59. Found: C, 80.00; H, 6.51; N, 4.66.
Method C
To a mixture of lactone 9a (0.391 g, 1.39 mmol) in dry toluene (15 mL) were added subsequently the additive 11 (0.718 g, 1.67 mmol) and Et3N (0.141 g, 1.39 mmol). The reaction mixture was refluxed under argon atmosphere for 2 h. The white precipitate deposited was filtered off and washed with toluene. Filtrates were then evaporated under reduced pressure, and the residue was purified by chroma-tography on silica gel column (hexane-EtOAc = 3:1) to provide the constrained tetramic acid 7a (0.401 g, 1.31 mmol, 94%) as a white solid.

29

General Procedure for the Reduction of Tetramic Acids 7a-h into Corresponding Compounds 12a-h
To the bicyclic tetramate 7a (2.33 g, 7.63 mmol) dissolved in EtOAc (190 mL) was added catalyst (0.47 g, 10 mol% Pd/C), and the resultant suspension was then vigorously stirred under an hydrogen atmosphere for 2 h. After the reaction was complete, the catalyst was filtered off and the product purified by flash chromatography on silica gel column (hexane-EtOAc = 4:1) to provide the sat. bicyclic lactam 12a (1.82 g, 77%); mp 52-54 ˚C (Et2O-heptane); [α]D ²0
-69.3 (c 0.23, CHCl3). IR (KBr): νmax = 3064, 2929 (CH), 1661 (C=O), 1056 (COC) cm. ¹H NMR (300 MHz, CDCl3): δ = 7.15-7.32 (m, 10 H, ArH), 5.53 (q, 1 H, J = 7.3 Hz, H-1′), 4.74 (dd, 1 H, J = 5.2, 10.5 Hz, H-2), 4.50 (td, 1 H, J = 5.5, 7.5 Hz, H-7), 3.86 (dd, 1 H, J = 7.4, 14.2 Hz, H-3a), 2.78 (d, 2 H, J = 5.4 Hz, H-6), 2.51 (ddd, 1 H, J = 5.3, 7.5, 12.6 Hz, H-3A), 1.84 (ddd, 1 H, J = 6.6, 10.6, 12.4 Hz, H-3B), 1.53 (d, 3 H, J = 7.3 Hz, H-2′). ¹³C NMR (75 MHz, CDCl3): δ = 172.6 (C-5), 140.0, 139.4, 128.7, 128.6, 128.0, 127.9, 127.5, 125.8 (ArC), 81.7 (C-2), 74.9 (C-7), 61.2 (C-1′), 50.4 (C-3a), 43.8 (C-6), 38.3 (C-3), 17.7 (C-2′). Anal. Calcd for C20H21NO2 (307.16): C, 78.15; H, 6.89; N, 4.56. Found: C, 78.23; H, 7.04; N, 4.54.

31

General Procedure for the Reduction of Bicycles 7a-h into Corresponding Tetramic Acids 13a-h
To the bicyclic tetramate 7a (1.013 g, 3.3 mmol) dissolved in MeOH (50 mL) was added catalyst (0.203 g, 10 mol% Pd/C), and the resultant suspension was then vigorously stirred under an hydrogen atmosphere for 4 h. After the reaction was complete, the catalyst was filtered off and the product purified by flash chromatography on silica gel column (hexane-EtOAc = 4:1) to provide the 5-arylalkyltetramic acid 13a (0.648 g, 64%) as colorless oil; [α]D ²0 11 (c 0.42, CHCl3). ¹H NMR (300 MHz, CDCl3): δ = 7.01-7.35 (m, 10 H, ArH), 5.70 (q, 1 H, J = 7.3 Hz, H-1′′), 3.58 (dd, 1 H, J = 2.9, 6.7 Hz, H-5), 3.05 (s, 1 H, H-3), 2.68 (ddd, 2 H, J = 4.1, 11.4, 13.7 Hz, H-2′A), 2.38 (ddd, 1 H, J = 6.6, 11.3, 13.4 Hz, H-2′B), 2.13 (dddd, 2 H, J = 3.1, 6.6, 11.2, 14.3 Hz, H-1′A), 1.80-1.92 (m, 1 H, H-1′B), 1.73 (d, 3 H, J = 7.3 Hz, H-2′′). ¹³C NMR (75 MHz, CDCl3): δ = 207.0 (C-4), 169.2 (C-2), 140.0, 138.0, 128.9, 128.6, 128.3, 128.2, 127.6, 126.4 (ArC); 65.6 (C-5), 50.9 (C-1′′), 41.8 (C-3), 33.3 (C-2′), 29.5 (C-1′), 18.4 (C-2′′).

33

General Procedure for the Debenzylation Process
A solution of 12a (1.591 g, 5.16 mmol) in dry THF (30 mL) was added to liquid NH3 (40 mL) at -78 ˚C. Small pieces of Na (15-20 equiv) were added until the reaction mixture remained blue, and the mixture was stirred at -78 ˚C. After 30 min of the reaction, the solution was then quenched with aq NH4Cl. The residual ammonia was evaporated, and the mixture was extracted three times with Et2O. The combined organic layers were dried over Na2SO4, filtered, and evaporated in vacuo. The residue was purified by column chromatography on silica gel column (MeOH-EtOAc = 1:10) to provide ultimately (4S,5S)-4-hydroxy-5-phenyl-ethylpyrrolidin-2-one (8a) in yield 80% (0.85 g); mp 104-106 ˚C (Et2O); [α]D ²0 -18.4 (c 0.114, MeOH). ¹H NMR (300 MHz, CDCl3): δ = 7.14-7.30 (m, 5 H, H-Ar), 4.25 (t,
1 H, J = 4.3 Hz, H-4), 3.52 (dd, 1 H, J = 7.0, 11.7 Hz, H-5), 2.67 (t, 2 H, J = 7.2 Hz, H-2′), 2.53 (dd, 1 H, J = 5.8, 17.2 Hz, H-3A), 2.28 (dd, 1 H, J = 1.4, 17.2 Hz, H-3B), 1.91-2.05 (m, 1 H, H-1′A), 1.80-1.90 (m, 1 H, H-1′B). ¹³C NMR (75 MHz, CDCl3): δ = 176.8 (C-2), 141.1, 128.5, 128.3, 126.1 (ArC), 68.6 (C-4), 59.2 (C-5), 41.0 (C-3), 32.3 (C-2′), 30.4 (C-1′).

34

Synthesis of Products 14
By using same procedure such as from the substrate 12g as starting material, the expected (2R,3aS,7S)-2-tert-butyl-hexahydrofuro[3,2b]-pyrrol-5-one (14g) was isolated in 73% yield; mp 145-147 ˚C (Et2O); [α]D ²0 13.5 (c 0.1, MeOH). ¹H NMR (300 MHz, CDCl3): δ = 4.74 (t, 1 H, J = 5.6 Hz, H-7), 4.31 (t, 1 H, J = 5.5 Hz, H-3a), 3.78 (dd, 1 H, J = 4.8, 10.9 Hz, H-2), 2.40-2.68 (m, 2 H, H-6), 1.86 (dd, 1 H, J = 4.8, 13.2 Hz, H-3A), 1.40-1.49 (m, 1 H, H-3B), 0.88 (s, 9 H, H-2′′). ¹³C NMR (75 MHz, CDCl3): δ = 177.7 (C-5), 85.5 (C-2), 59.6 (C-7), 51.1 (C-3a), 38.9 (C-6), 34.1 (C-3), 32.9 (C-1′′), 25.9 (C-2′′).