Improved Synthesis of the Pheromone of the Longtailed Mealybug

Abstract

A short and efficient synthesis of the longtailed mealybug pheromone featuring an Ireland-Claisen rearrangement as the key step is described.

Key words

pheromone - monoterpenoid - allylic cyclopentenol - ­Ireland-Claisen rearrangement

References and Notes

• 1 Millar JG. Moreira JA. McElfresh JS. Daane KM. Freund AS. Org. Lett.  2009,  11:  2683 
• 2a Golino DA. Sim ST. Gill R. Rowhani A. California Agric.  2002,  56:  196 
• 2b Golino DA. Weber E. Sim S. Rowhani A. California Agric.  2008,  62:  156 
• 3 Charles JG. Cohen D. Walker JTS. Forgie SA. Bell VA. Breen KC. New Zealand Plant Protec.  2006,  59:  330 
• 4 Zou Y. Millar JG. J. Org. Chem.  2009,  74:  7207 
• 5a Imanishi T. Matsui M. Yamashita M. Iwata C. Tetrahedron Lett.  1986,  27:  3161 
• 5b Kobayashi Y. Murugesh MG. Nakano M. Takahisa E. Usmani SB. Ainai T. J. Org. Chem.  2002,  67:  7110 
• 5c Sumi S. Matsumoto K. Tokuyama H. Fukuyama T. Org. Lett.  2003,  5:  1891 
• 5d Sumi S. Matsumoto K. Tokuyama H. Fukuyama T. Tetrahedron  2003,  59:  8571 
• 5e Yoshikawa N. Tan L. Yasuda N. Volante RP. Tillyer RD. Tetrahedron Lett.  2004,  45:  7261 
• 5f Kondo K. Matsumoto M. Mori F. Angew. Chem., Int. Ed. Engl.  1975,  14:  103 
• 6a Nakashima H. Sato M. Taniguchi T. Ogasawara K. Synlett  1999,  1754 
• 6b Nakashima H. Sato M. Taniguchi T. Ogasawara K. Synthesis  2000,  817 
• 6c Nonaka H. Wang Y. Kobayashi Y. Tetrahedron Lett.  2007,  48:  1745 
• 7a Pearson AJ. Chen Y. Han G. Hsu S. Ray T.
  J. Chem. Soc., Perkin Trans. 1  1985,  267 
• 7b Srikrishna A. Reddy TJ. Palani N. Balasubramanian KK. Synth. Commun.  2003,  33:  1537 
• 7c Hu Q. Rege PD. Corey EJ. J. Am. Chem. Soc.  2004,  126:  5984 
• 8a Conia JM. Leriverend ML. Bull. Soc. Chim. Fr.  1970,  2981 
• 8b Gowda G. McMurry TBH. J. Chem. Soc., Perkin Trans. 1  1979,  274 
• 8c Mori K. Sasaki M. Tetrahedron  1980,  36:  2197 
• 8d Schwartz KD. White JD. Org. Synth.  2006,  83:  49 

9

In ref. 8c and 8d, the α,β-unsaturated ester was reacted with hot polyphosphoric acid for 10 min and 3 min, respectively, before the reaction was stopped. However, in our hands, only starting material was recovered with such short reaction times. We found the reaction to be complete after ca. 5 h, which is more consistent with ref. 8a and 8b.

10

When AcCl was used instead of Ac₂O, the yield was lower (65%).

11

Data for Acetic Acid 3,4,4-Trimethyl-cyclopent-2-enyl Ester (6) ^¹H NMR (400 MHz, CDCl₃): δ = 5.50 (m, 1 H), 5.33 (m, 1 H), 2.13 (dd, J = 14.0, 7.2 Hz, 1 H), 1.99 (s, 3 H), 1.69 (dd, J = 14.0, 2.8 Hz, 1 H), 1.66 (t, J = 1.6 Hz, 3 H), 1.08 (s, 3 H), 1.01 (s, 3 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 171.3, 155.8, 122.1, 78.4, 46.9, 45.4, 27.9, 27.4, 21.6, 12.4. IR (film): 3055, 2959, 2869, 1734, 1654, 1438, 1373, 1242, 1019, 970 cm^-¹. MS: m/z (rel. abundance) = 41 (34), 43 (85), 55 (18), 67 (21), 77 (22), 91 (24), 93 (100), 108 (15), 109 (36), 111 (24), 126 (17), 153 (2), 168 (7) [M⁺]. HRMS (CI/CH₄ on GC-MS): m/z calcd for [C₁₀H₁₆O₂]⁺: 168.1150; found: 168.1151.

12

When 1.3 equiv of tert-butyldimethylsilyl chloride was used, a silicon-containing acidic byproduct was formed, which was difficult to separate from 3c. With 1.05 equiv, this byproduct was not observed.