A New Organocatalytic Process of Cyclotrimerization of Acetylenic Ketones Mediated by 2,4-Pentanedione

Abstract

A new organocatalytic process of cyclotrimerization of the aliphatic and aromatic acetylenic ketones was developed. The reaction catalyzed by DMAP in the presence of 2,4-pentanedione gave 1,3,5-trisubstituted benzenes in almost quantitative yields ­under very mild conditions. 2,4-Pentanedione was used as a co-­catalyst to promote the reaction efficiently, particularly for aliphatic acetylenic ketones.

acetylenic ketones - DMAP - cyclotrimerization - 2,4-pentanedione

References and Notes

<A NAME="RW19806ST-1A">1a</A> Shore NE. In Comprehensive Organic Synthesis   Vol. 5:  Trost BM. Fleming I. Paquette LA. Pergamon; Oxford: 1991.  p.1129-1162  

<A NAME="RW19806ST-1B">1b</A> Grotjahn DB. In Comprehensive Organometallic Chemistry II   Vol. 12:  Hegedus LS. Abel EW. Stone FGA. Wilkinson G. Pergamon; Oxford: 1995.  p.741-770  

<A NAME="RW19806ST-1C">1c</A> Lautens M. Klute W. Tam W. Chem. Rev.  1996,  96:  49 

<A NAME="RW19806ST-1D">1d</A> Frühauf H.-W. Chem. Rev.  1997,  97:  523 

<A NAME="RW19806ST-1E">1e</A> Yamamoto Y. Ishii J. Nishiyama H. Itoh K. J. Am. Chem. Soc.  2004,  126:  3712 

<A NAME="RW19806ST-1F">1f</A> Meriwether LS. Colthup EC. Kennerly GW. Reusch RN. J. Org. Chem.  1961,  26:  5155 

<A NAME="RW19806ST-2A">2a</A> Saito S. Yamamoto Y. Chem. Rev.  2000,  100:  2901 

<A NAME="RW19806ST-2B">2b</A> Ardizzoia GA. Brenna S. LaMonica G. Maspero A. Masciocchi N. J. Organomet. Chem.  2002,  649:  173 

<A NAME="RW19806ST-2C">2c</A> Kotha T. Brahmachary E. Lahiri K. Eur. J. Org. Chem.  2005,  4741 

<A NAME="RW19806ST-2D">2d</A> Xi C. Chen C. Lin J. Hong X. Org. Lett.  2005,  7:  347 

<A NAME="RW19806ST-2E">2e</A> Zhou L. Jiang H. Huang J. Tang J. Chin. J. Org. Chem.  2006,  26:  1 

<A NAME="RW19806ST-3A">3a</A> Pigge FC. Zheng Z. Tetrahedron Lett.  2001,  42:  8259 

<A NAME="RW19806ST-3B">3b</A> Pigge FC. Ghasedi F. Zheng Z. Rath NP. Nichols G. Chickos JS. J. Chem. Soc., Perkin Trans. 2  2000,  2458 

<A NAME="RW19806ST-3C">3c</A> Pigge FC. Ghasedi F. Rath NP. Tetrahedron Lett.  1999,  40:  8045 

<A NAME="RW19806ST-3D">3d</A> Matsuda K. Nakamura N. Iwamura H. Chem. Lett.  1994,  1765 

<A NAME="RW19806ST-3E">3e</A> Balasubramanian K. Selvaraj S. Venkataramani PS. Synthesis  1980,  29 

<A NAME="RW19806ST-3F">3f</A> Elghamry I. Synthesis  2003,  2301 

<A NAME="RW19806ST-3G">3g</A> Pena MA. Sestelo JP. Sarandeses LA. Synthesis  2005,  485 

<A NAME="RW19806ST-3H">3h</A> Abdel-Khalik MM. Elnagdi MH. Synth. Commun.  2002,  32:  159 

<A NAME="RW19806ST-3I">3i</A> Almazroa S. Elnagdi MH. El-Din AMS. J. Heterocycl. Chem.  2004,  41:  267 

<A NAME="RW19806ST-4">4</A> Yang J. Verkade G. J. Am. Chem. Soc.  1998,  120:  6834 

<A NAME="RW19806ST-5A">5a</A> Modern Arene Chemistry   Astruc D. Wiley-VCH; Weinheim: 2002. 

<A NAME="RW19806ST-5B">5b</A> The Chemistry of Phenols   Rappoport Z. Wiley-VCH; New York: 2003. 

<A NAME="RW19806ST-6A">6a</A> Nefzi A. Ostresh JM. Houghten RA. Chem. Rev.  1997,  97:  449 

<A NAME="RW19806ST-6B">6b</A> Simon C. Constantieux T. Rodriguez J. Eur. J. Org. Chem.  2004,  4957 

<A NAME="RW19806ST-6C">6c</A> Li C. Chem. Rev.  2005,  105:  3095 

<A NAME="RW19806ST-7A">7a</A> Hanédanian M. Loreau O. Sawicki M. Taran F. Tetrahedron  2005,  61:  2287 

<A NAME="RW19806ST-7B">7b</A> Trost BM. Dake GR. J. Am. Chem. Soc.  1997,  119:  7595 

<A NAME="RW19806ST-7C">7c</A> Hanédanian M. Loreau O. Taran F. Mioskowski C. Tetrahedron Lett.  2004,  45:  7035 

<A NAME="RW19806ST-7D">7d</A> Xue S. Zhou Q. Zheng X. Synth. Commun.  2005,  35:  3027 

<A NAME="RW19806ST-8A">8a</A> Yamada YMA. Ikegami S. Tetrahedron Lett.  2000,  41:  2165 

<A NAME="RW19806ST-8B">8b</A> McDougal NT. Schaus SE. J. Am. Chem. Soc.  2003,  125:  12094 

<A NAME="RW19806ST-8C">8c</A> Shi M. Liu YH. Org. Biomol. Chem.  2006,  4:  1468 

For selected recent reactions catalyzed by amines, see:

<A NAME="RW19806ST-9A">9a</A> Wang Y. Cui S. Lin X. Org. Lett.  2006,  8:  1241 

<A NAME="RW19806ST-9B">9b</A> Sonye JP. Koide K. Org. Lett.  2006,  8:  199 

<A NAME="RW19806ST-9C">9c</A> Shi Y. Shi M. Org. Lett.  2005,  7:  3057 

<A NAME="RW19806ST-9D">9d</A> Tejedor D. Santos-Exposito A. Gonzalez-Cruz D. Marrero-Tellado JJ. Garcia-Tellado F. J. Org. Chem.  2005,  70:  1042 

<A NAME="RW19806ST-9E">9e</A> Bella M. Jørgensen KA. J. Am. Chem. Soc.  2004,  126:  5672 

<A NAME="RW19806ST-9F">9f</A> Li C. Shi M. Org. Lett.  2003,  5:  4273 

<A NAME="RW19806ST-10">10</A>

Typical Procedure.
A round-bottomed flask, equipped with a stirring bar, was charged with 2,4-pentanedione (0.15 mmol) and acetylenic ketone (0.3 mmol) dissolved in CH₂Cl₂ (2 mL) followed by DMAP (0.03 mmol). The reaction was run at r.t. for the indicated time (monitored by TLC). The reaction was concentrated under reduced pressure on a rotary evaporator and purified by silica gel chromatography using PE-EtOAc (10:1 to 3:1).
Compound 3a: ¹H NMR (300 MHz, CDCl₃): δ = 8.63 (s, 3 H), 2.64 (s, 9 H) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 196.7, 138.0, 131.8, 26.9 ppm. IR (KBr): ν = 1690, 1227 cm^-1. HRMS (EI): m/z calcd for C₁₂H₁₂O₃ [M]⁺: 204.0786; found: 204.0791.
Compound 3b: ¹H NMR (300 MHz, CDCl₃): δ = 8.56 (s, 3 H), 7.25-7.10 (m, 15 H), 3.31 (t, J = 7.5 Hz, 6 H), 3.03 (t, J = 7.5 Hz, 6 H) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 197.9, 140.8, 137.8, 131.3, 128.7, 128.6, 126.4, 40.8, 30.1 ppm. IR (KBr): ν = 1694, 1162 cm^-1. HRMS (EI): m/z calcd for C₃₃H₃₀O₃ [M]⁺: 474.2195; found: 474.2192.
Compound 6: ¹H NMR (300 MHz, CDCl₃): δ = 8.49 (d, J = 1.5 Hz, 2 H), 8.29 (d, J = 1.5 Hz, 1 H), 7.76 (d, J = 7.6 Hz, 4 H), 7.57-7.54 (m, 2 H), 7.47-7.42 (m, 4 H), 2.63 (s, 3 H) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 195.4, 193.9, 137.4, 136.4, 135.4, 133.8, 132.2, 131.5, 129.0, 127.6, 25.8 ppm. IR (KBr): ν = 1691, 1662, 1242 cm^-1. HRMS (EI): m/z calcd for C₂₂H₁₆O₃ [M]⁺: 328.1099; found: 328.1092.