Mercuric Triflate·3TMU Catalyzed Cyclization of ω-Alkynoic Acids and ­Synthesis of a Naturally Occurring γ-Methylene-γ-lactone

Abstract

Hg(OTf)₂·3TMU showed efficient catalytic activity for the cyclization of ω-alkynoic acid to give ω-methylene-ω-lactone in excellent yield, and the procedure was efficiently applied for the synthesis of naturally occurring γ-methylene-γ-lactone. The absolute structure of the natural product was established by this synthesis.

Key words

catalytic cyclizations - carboxylic acids - alkynes - lactones - mercury

References and Notes

• 1a Nishizawa M. Takenaka H. Nishide H. Hayashi Y. Tetrahedron Lett.  1983,  24:  2581 
• 1b Nishizawa M. Morikuni E. Asoh K. Kan Y. Uenoyama K. Imagawa H. Synlett  1995,  169 
• 2 Nishizawa M. Skwarczynski M. Imagawa H. Sugihara T. Chem. Lett.  2002,  31:  12 
• 3 Nishizawa M. Yadav VK. Skwarczynski M. Takao H. Imagawa H. Sugihara T. Org. Lett.  2003,  5:  1609 
• 4 Nishizawa M. Takao H. Yadav VK. Imagawa H. Sugihara T. Org. Lett.  2003,  5:  4563 
• 5 Imagawa H. Kurisaki T. Nishizawa M. Org. Lett.  2004,  6:  3679 
• 6 Imagawa H. Iyenaga T. Nishizawa M. Org. Lett.  2005,  7:  451 
• 7 Imagawa H. Iyenaga T. Nishizawa M. Synlett  2005,  703 
• Silver salt catalyzed reaction, see:
• 8a Castaner J. Pascual J. J. Chem. Soc.  1958,  3962 
• 8b Jong TT. Williard PG. J. Org. Chem.  1984,  49:  735 
• 8c Ogawa Y. Maruno M. Wakamatsu T. Heterocycles  1995,  2587 
• Mercuric salt catalyzed reaction, see:
• 9a Amos RA. Katzenellenbogen JA. J. Org. Chem.  1978,  43:  560 
• 9b Krafft GA. Katzenellenbogen JA. J. Am. Chem. Soc.  1981,  103:  5459 
• Transition metal-catalyzed reaction, see:
• 10a Lambert C. Uchimoto K. Nozaki H. Tetrahedron Lett.  1984,  46:  5323 
• 10b Yanagihara N. Lambert C. Iritani K. Utimoto K. Nozaki H. J. Am. Chem. Soc.  1986,  108:  2753 
• 10c Chan DMT. Marder TB. Milstein D. Taylor NJ. J. Am. Chem. Soc.  1987,  109:  6385 
• 10d Wakabayashi T. Ishii Y. Ishikawa K. Hidai M. Angew. Chem., Int. Ed. Engl.  1996,  35:  2123 
• 11a Ravi BN. Wells RJ. Aust. J. Chem.  1982,  35:  105 
• 11b Synthesis of racemic 8 was reported. See: Dalla V. Pale P. New J. Chem.  1999,  23:  803 
• 12 Wasserman HH. Frechette R. Oida T. von Duzer JH. J. Org. Chem.  1989,  54:  6012 
• 13 Midland MM. McDowell DC. Hatch RL. Tramontano A. J. Am. Chem. Soc.  1980,  102:  867 
• 14a Ohtani I. Kusumi T. Kashman Y. Kakisawa H. J. Am. Chem. Soc.  1991,  113:  4092 
• 14b

  The absolute configuration of β-hydroxyester 10 was established after conversion to the desilylation product by the reaction with TBAF in THF. The resulting desilylated compound was acylated by (R)- and (S)-MTPA using EDCI and 4-DMAP in CH₂Cl₂. The Δδ (δ_S-δ_R) values of (R)- and (S)-MTPA esters were shown below (Figure [1] ).

• 15 Cossy J. Schmitt A. Cinquin C. Buisson D. Belotti D. Bioorg. Med. Chem. Lett.  1997,  7:  1699 
• 16 Corey EJ. Bakshi RK. Shibata S. J. Am. Chem. Soc.  1987,  109:  5551 
• 17 Frater G. Helv. Chim. Acta  1979,  62:  2825 

18

We could obtain neither the natural product nor NMR spectra and could not check the purity of the natural product.

19

General Experimental Procedure.
To a solution of alkynoic acid (0.30 mmol) in CD₃CN (3 mL, 0.1 M) was added tetramethylurea (0.1 M in CD₃CN, 90 µL, 9.0 µmol) and then a 0.1 M CD₃CN solution of Hg(OTf)₂ (30 µL, 3.0 µmol) at r.t. After stirring for 15 min at r.t., Et₃N (100 µL, 0.14 mmol) and naphthalene (internal standard, 0.3 M CD₃CN solution, 0.25 mL, 0.075 mmol) were added. The solution was directly subjected to ¹H NMR analysis, and the yield was calculated from the integral value.