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.

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 

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.

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 

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.