Download PDF
Synlett 2005(20): 3099-3102  
DOI: 10.1055/s-2005-921934
LETTER
© Georg Thieme Verlag Stuttgart · New York

Microwave-Assisted Rearrangement of Vinylaziridines to 3-Pyrrolines: Formal Synthesis of (-)-Anisomycin

Sebastian Hirner, Peter Somfai*
KTH Chemical Science and Engineering, Organic Chemistry, 100 44 Stockholm, Sweden
Fax: +46(8)7912333; e-Mail: somfai@kth.se;
Further Information

Publication History

Received 14 October 2005
Publication Date:
28 November 2005 (online)

    Permissions and Reprints All articles of this category

Abstract

An efficient microwave-assisted rearrangement of activated vinylaziridines to 3-pyrrolines is described. The rearrangement proceeds in good to excellent yields and is mediated by NaI or LiI in MeCN at elevated temperatures. The synthetic utility of this reaction is shown in an efficient formal total synthesis of the antibiotic (-)-anisomycin.

Key words

vinylaziridines - pyrrolines - rearrangement - ring expansion - total synthesis

    References

  • For recent examples of 3-pyrrolines as intermediates in organic synthesis, see:
  • 1a Green MP. Prodger JC. Hayes CJ. Tetrahedron Lett.  2002,  43:  6609 
    CrossrefSearch in Google Scholar
  • 1b Huwe CM. Blechert S. Tetrahedron Lett.  1995,  36:  1621 
    CrossrefSearch in Google Scholar
  • 1c Burley I. Hewson AT. Tetrahedron Lett.  1994,  35:  7099 
    CrossrefSearch in Google Scholar
  • 1d As MAO inhibitors, see: Lee Y. Huang H. Sayre LM. J. Am. Chem. Soc.  1996,  118:  7241 
    CrossrefSearch in Google Scholar
  • 1e As NMDA receptor agonists, see: Rondeau D. Gill P. Chan M. Curry K. Lubell WD. Bioorg. Med. Chem. Lett.  2000,  10:  771 
    CrossrefSearch in Google Scholar
  • 1f As κ-agonists, see: Mou Q.-Y. Chen J. Zhu Y.-C. Zhou D.-H. Chi Z.-Q. Long Y.-Q. Bioorg. Med. Chem. Lett.  2002,  12:  2287 
    CrossrefSearch in Google Scholar
  • 1g As tumor inhibitors, see: Anderson WK. Milowsky AS. J. Med. Chem.  1987,  30:  2144 
    CrossrefSearch in Google Scholar
  • For recent examples, see:
  • 2a Dieter RK. Chen N. Yu H. Nice LE. Gore VK. J. Org. Chem.  2005,  70:  2109 
    CrossrefSearch in Google Scholar
  • 2b Morita N. Krause N. Org. Lett.  2004,  6:  4121 
    CrossrefSearch in Google Scholar
  • 2c Dieter RK. Yu H. Org. Lett.  2001,  3:  3855 
    CrossrefSearch in Google Scholar
  • 2d Green MP. Prodger JC. Sherlock AE. Hayes CJ. Org. Lett.  2001,  3:  3377 
    CrossrefSearch in Google Scholar
  • 3a Atkinson RS. Rees CW. J. Chem. Soc. C  1969,  778 
    Crossref
  • 3b Scheiner P. J. Org. Chem.  1967,  32:  2628 
    CrossrefSearch in Google Scholar
  • 3c Fugami K. Miura K. Morizawa Y. Oshima K. Utimoto K. Nozaki H. Tetrahedron  1989,  45:  3089 
    CrossrefSearch in Google Scholar
  • For reviews, see:
  • 3d Somfai P. Åhman J. In Targets in Heterocyclic Systems   Italian Society of Chemistry; Rome: 1999.  p.341 
    Crossref
  • 3e Hudlicky T. Reed JW. In Comprehensive Organic Synthesis   Vol. 4:  Trost BM. Fleming I. Pergamon; Oxford: 1991.  p.899 
    CrossrefSearch in Google Scholar
  • 4 For a definition of the term-activated aziridine, see: Ham GE. J. Org. Chem.  1964,  29:  3052 
    Search in Google Scholar
  • A similar isomerization of vinylaziridines, catalyzed by Pd(0), has been published:
  • 7a Mimura N. Ibuka T. Akaji M. Miwa Y. Taga T. Nakai K. Tamamura H. Fujii N. Yamamoto Y. Chem. Commun.  1996,  351 
  • 7b Ibuka T. Mimura N. Aoyama H. Akaji M. Ohno H. Miwa Y. Taga T. Nakai K. Tamamura H. Fujii N. Yamamoto Y. J. Org. Chem.  1997,  62:  999 
    Search in Google Scholar
  • 8 For ab initio calculations of the energy difference between different conformations of vinylaziridines, see: Toda A. Aoyama H. Mimura N. Ohno H. Fujii N. Ibuka T. J. Org. Chem.  1998,  63:  7053 
    CrossrefSearch in Google Scholar
  • 9 Basavaiah D. Rao AJ. Satyanarayana T. Chem. Rev.  2003,  103:  811 
    CrossrefPubMedSearch in Google Scholar
  • 10a Kappe CO. Angew. Chem. Int. Ed.  2004,  43:  6250 
    CrossrefSearch in Google Scholar
  • 10b Lindström UM. Olofsson B. Somfai P. Tetrahedron Lett.  1999,  40:  9273 
    CrossrefSearch in Google Scholar
  • 11 The microwave heating was performed with a Smith Creator single mode cavity from Personal Chemistry AB, Uppsala, Sweden, equipped with a magnetic stirrer and automatic temperature control.
  • 12 General Procedure for the Preparation of 3-Pyrrolines.2- Tert -butyl-1-tosyl-3-pyrroline ( 2e). A solution of 2-tert-butyl-1-tosyl-vinylaziridine (1e, 27.9 mg, 0.1 mmol, cis:trans = 18:82) and LiI (26.8 mg, 0.2 mmol) in dry MeCN (3 mL) was heated in the microwave cavity for 30 min at 200 °C. After the reaction, the solvent was removed in vacuo and the residue purified by flash chromatography (pentane-Et2O, 10:1) to yield 2e as a white solid (26.4 mg, 95%); mp 149-152 °C (dec). IR (neat): 2964, 1335, 1160 cm-1. 1H NMR (400.1 MHz, CDCl3): δ = 7.67 (d, 2 H, J = 8.2 Hz), 7.25 (d, 2 H, J = 8.2 Hz), 5.64-5.56 (m, 2 H), 4.30 (m, 1 H), 4.12 (m, 1 H), 3.93 (m, 1 H), 2.40 (s, 3 H), 0.97 (s, 9 H). 13C NMR (100.6 MHz, CDCl3): δ = 143.2, 134.8, 129.4, 128.8, 127.8, 126.5, 56.5, 36.8, 26.4, 21.5. MS (ESI): m/z = 280 [M + H]+. 2-Phenethyl-1-tosyl-3-pyrroline ( 2d). Colorless oil. IR (neat): 2924, 2864, 1342, 1163. 1H NMR (400.1 MHz, CDCl3): δ = 7.66 (d, 2 H, J = 8.3Hz), 7.34-7.16 (m, 7 H), 5.62 (m, 2 H), 4.50 (m, 1 H), 4.20-4.08 (m, 2 H), 2.75 (ddd, 1 H, J = 13.8, 9.6, 6.4 Hz), 2.59 (ddd, 1 H, J = 13.8, 9.9, 6.9 Hz), 2.41 (s, 3H), 2.17-2.03 (m, 2H). 13C NMR (125.8 MHz, CDCl3): δ = 143.3, 141.6, 134.6, 129.6, 129.4, 128.4, 128.3, 127.4, 125.7, 125.0, 66.7, 55.7, 37.3, 30.7, 21.4. MS (ESI): m/z = 350 [M + Na]+.The analytical data of compounds 2b and 2g were in accordance to literature data. See: Evans PA. Robinson JE. Org. Lett.  1999,  1:  1929 
    CrossrefSearch in Google Scholar
  • 13a Arini LG. Sinclair A. Szeto P. Stockman RA. Tetrahedron Lett.  2004,  45:  1589 
    CrossrefSearch in Google Scholar
  • 13b Li A.-H. Dai L.-X. Hou X.-L. Chen M.-B. J. Org. Chem.  1996,  61:  4641 
    CrossrefSearch in Google Scholar
  • 14a Sobin BA. Tanner FW. J. Am. Chem. Soc.  1954,  76:  4053 
    Search in Google Scholar
  • 14b The Merck Index   12th ed.:  Windholz M. Merck; Whitehouse Station, NJ: 1996.  p.710 
  • 14c Hosoya Y. Kameyama T. Naganawa H. Okami Y. Takeuchi T. J. Antibiot.  1993,  46:  1300 
    Search in Google Scholar
  • 14d Nader K. Schafe GE. Le Doux JE. Nature (London)  2000,  406:  722 
    Search in Google Scholar
  • For examples, see:
  • 15a Kaden S. Brockmann M. Reissig HU. Helv. Chim. Acta  2005,  88:  1826 
    CrossrefSearch in Google Scholar
  • 15b Kim JH. Curtis-Long MJ. Seo WD. Ryu YB. Yang MS. Park KH. J. Org. Chem.  2005,  70:  4082 
    CrossrefSearch in Google Scholar
  • 15c Takahata H. Banba Y. Tajima M. Momose T. J. Org. Chem.  1991,  56:  240 
    CrossrefSearch in Google Scholar
  • 15d Takano S. Iwabuchi Y. Ogasawara K. Heterocycles  1989,  29:  1861 
    CrossrefSearch in Google Scholar
  • 15e Jegham S. Das BC. Tetrahedron Lett.  1988,  29:  4419 
    CrossrefSearch in Google Scholar
  • 15f Meyers AI. Dupre B. Heterocycles  1987,  25:  113 
    CrossrefSearch in Google Scholar
  • 15g Buchanan JG. MacLean KA. Wightman RH. Paulsen H. J. Chem. Soc., Perkin Trans. 1  1985,  1463 
    Crossref
  • 15h Schumacher DP. Hall SS. J. Am. Chem. Soc.  1982,  104:  6076 
    CrossrefSearch in Google Scholar
  • 16a Hu S. Jayaraman S. Oehlschlager AC. J. Org. Chem.  1996,  61:  7513 
    Search in Google Scholar
  • 16b Hertweck C. Boland W. J. Org. Chem.  1999,  64:  4462 
    Search in Google Scholar
5

Vinylaziridines 1a,b were synthesized from the corresponding vinylepoxides. [10b]

6

The cis- and trans-vinylaziridines can be distinguished by the 3 J HH coupling constant of the ring protons (cis ca. 6.8-8.4 Hz; trans ca. 4.1-4.4 Hz).

17

For ee determination, the chlorohydrine was converted to the corresponding vinylepoxide by treatment with 5 equiv DBU in CH2Cl2 (r.t., 12 h, 96%). [16b] The ee was shown to be >95% by chiral HPLC analysis (Chiracel OD, hexane-i-PrOH, 99.5:0.5, 0.5 mL/min).

18

[α]D 25 -99.9 (c 1.20, THF) {lit: [α]D 25 -93.8 (c 0.485, THF); [15c] [α]D 25 -101.2 (c 1.44, THF); [15d] [α]D 25 -89.3 (c 1.26, THF) [15e] }.

19

[α]D 25 -48.4 (c 0.37, CH2Cl2).