Ruthenium-Catalyzed Hydrovinylation of Dienoates: Model Studies Directed Toward the C10-C18 Segment of Ambruticin

Abstract

The ruthenium-catalyzed hydrovinylation of 2,4-dienoates 3 proceeds in a regioselective fashion to give 4-alkyl-2,5-dienoates 4 in good yields. Olefin cross-metathesis of a vinylcyclopropane with 4e demonstrates a synthetic route to the C10-C18 ­segment of ambruticin.

Key words

ruthenium catalysis - hydrovinylation - cross-metathesis

References

• 1a RajanBabu TV. Chem. Rev.  2003,  103:  2845 
• 1b Goossen LJ. Angew. Chem. Int. Ed.  2002,  41:  3775 
• 1c Jolly PW. Wilke G. In Applied Homogeneous Catalysis with Organometallic Compounds   Cornils B. Herrmann WA. Wiley-VCH; New York NY: 2000.  p.1024-1072  
• 2a Trost BM. Science  1991,  254:  1471 
• 2b Trost BM. Angew. Chem., Int. Ed. Engl.  1995,  34:  259 
• 3a Nomura N. Jin J. Park H. RajanBabu TV. J. Am. Chem. Soc.  1998,  120:  459 
• 3b Nandi M. Jin J. RajanBabu TV. J. Am. Chem. Soc.  1999,  121:  9899 
• 3c Park H. RajanBabu TV. J. Am. Chem. Soc.  2002,  124:  734 
• 3d Kumarsewaran R. Nanti M. RajanBabu TV. Org. Lett.  2003,  5:  4345 
• 3e RajanBabu TV. Nomura N. Jin J. Nandi M. Park H. Sun X. J. Org. Chem.  2003,  68:  8431 
• 3f Wegner A. Leitner W. Chem. Commun.  1999,  1583: 
• 3g Bosmann A. Francio G. Jenssen E. Solinas M. Leitner W. Wasserscheid P. Angew. Chem. Int. Ed.  2001,  40:  2697 
• 3h Francio G. Faraone F. Leitner W. J. Am. Chem. Soc.  2002,  124:  736 
• 4 He Z. Yi CS. Donaldson WA. Org. Lett.  2003,  5:  1567 
• 6 Trost BM. Keinan E. J. Am. Chem. Soc.  1978,  100:  7779 
• 7 Notably, the Ru-H species 8 has been proposed as an intermediate in the coupling of alkynes with ethylene using catalyst 1: Yi CS. Lee DW. Chen Y. Organometallics  1999,  18:  2043 
• For isolation see:
• 8a Connor DT. Greenough RC. von Strandtmann M. J. Org. Chem.  1977,  42:  3664 
• 8b For total syntheses see the following: Kende AS. Mendoza JS. Fujii Y. J. Am. Chem. Soc.  1990,  112:  9645 
• 8c Kirkland TA. Colucci J. Geraci LS. Marx MA. Schneider M. Kaelin DE. Martin SF. J. Am. Chem. Soc.  2001,  123:  12432 
• 8d Lee E. Choi SJ. Kim H. Han HO. Kim YK. Min SJ. Son SH. Lim SM. Jang WS. Angew. Chem. Int. Ed.  2002,  41:  176 
• 8e Liu P. Jacobsen EN. J. Am. Chem. Soc.  2001,  123:  10772 
• 9 Chatterjee AK. Choi T.-L. Sanders DP. Grubbs RH. J. Am. Chem. Soc.  2003,  125:  10103 
• For other examples of olefin cross-metathesis of vinylcyclopropanes see:
• 10a Verbicky C. Zercher CK. Tetrahedron Lett.  2000,  41:  8723 
• 10b Itoh T. Mitsukuru K. Ishida N. Uneyama K. Org. Lett.  2000,  2:  1431 
• 11a Muller P. Baud C. Jacquier Y. Can. J. Chem.  1998,  76:  738 
• 11b Castellino AJ. Bruice TC. J. Am. Chem. Soc.  1988,  110:  7512 

5

General Procedure: A 25 mL medium walled vacuum Schlenk tube equipped with stirring bar and Teflon stopcock was charged with degassed dienoate 3a (386 mg, 3.45 mmol), catalyst 1 (16.0 mg, 1.82 × 10^-4 mmol), and CH₂Cl₂ (4.0 mL) in a nitrogen-filled glove box. The tube was removed from the glove box, cooled in a liquid N₂ bath, and excess ethylene (ca. 13 mmol) was condensed into the tube. The tube was stoppered, removed from the liquid N₂ bath, warmed to r.t., and immersed in a 75 °C oil bath. (CAUTION: These conditions result in an increase in pressure in the medium wall reaction vessel. Heating of the reaction flask should be conducted in a fume hood behind a closed safety sash). After 10 h, the reaction tube was cooled to r.t., and the tube opened to the air. The reaction mixture was concentrated and the residue was purified by column chromatography (hexanes-Et₂O, 10:1) to give 4a as a colorless oil (290 mg, 61%). ¹H NMR (CDCl₃) δ = 6.95 (dd, J = 6.8, 15.8 Hz, 1 H), 5.82-5.72 (m, 2 H), 5.09-5.03 (m, 2 H), 3.74 (s, 3 H), 3.08-3.01 (m, 1 H), 1.18 (d, J = 6.9 Hz, 3 H). ¹³C NMR (CDCl₃): δ = 167.0, 152.0, 139.9, 119.6, 114.7, 51.5, 40.1, 18.9. Anal. Calcd for C₈H₁₂O₂: C, 68.54; H, 8.63. Found: C, 68.39; H, 8.59.

12

14: ¹H NMR (CDCl₃): δ = 7.15-7.05 (m, 6 H), 6.94-6.91 (m, 4 H), 5.74 (dd, J = 0.9, 9.9 Hz, 1 H), 5.66 (dd, J = 6.6, 15.3 Hz, 1 H), 5.41 (dd, J = 7.6, 15.3 Hz, 1 H), 4.23 (q, J = 7.2 Hz, 2 H), 3.93 (m, 1 H), 2.51 (d, J = 5.7 Hz, 2 H), 2.31 (m, 1 H), 1.95 (s, 3 H), 1.35 (t, J = 7.2 Hz, 3 H), 1.15 (d, J = 6.6 Hz, 3 H). ¹³C NMR (CDCl₃): δ = 167.2, 145.1, 137.1, 132.4, 130.1, 128.3, 127.2, 125.2, 60.3, 36.4, 33.1, 29.4, 21.3, 21.0, 14.9. FAB-HRMS: m/z [M + Li⁺] calcd for C₂₅H₂₈O₂Li: 367.2249; found: 367.2263.