Solid phase ring-closing metathesis: Cyclization/cleavage approach towards a seven membered cycloolefin

Tetrahedron Letters

Volumn 37, Issue 45, 1996, Pages 8249-8252

  Van Maarseveen, Jan H ^a   Den Hartog, Jack A J ^a   Engelen, Victor ^a   Finner, Emil ^b   Visser, Geb ^a   Kruse, Chris G ^a  

^a Solvay Pharmaceuticals Inc   (Netherlands)

^b Solvay Pharmaceuticals GmbH   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

AZEPINE DERIVATIVE;

ARTICLE; CYCLIZATION; DRUG SYNTHESIS; NUCLEAR MAGNETIC RESONANCE; REACTION ANALYSIS;

EID: 0030569374     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/0040-4039(96)01881-3     Document Type: Article

References (24)

1. 1 a) Thompson, L.A.; Ellman, J.A. Chem.Rev. 1996, 96, 555-600.
2. b) Hermkens, P.H.H.; Ottenheijm, H.C.J.; Rees, D. Tetrahedron 1996, 52, 4527-4554.
3. 2 a) Plunkett, M.J.; Ellman, J.A. J.Org.Chem. 1995, 60, 6006-6007.
4. b) Chenera, B.; Finkelstein, J.A.; Veber, D.F. J.Am.Chem.Soc. 1995, 117, 11999-12000.
5. 3 Smith, A.L.; Thomson, C.G.; Leeson, P.D. Bioorg.Med.Chem.Lett. 1996, 6, 1483-1486, and references cited therein.
6. 4 The following paper, which has been published after completion of our manuscript, describes solid phase RCM and cross metathesis yielding immobilized cycloolefins and asymmetric vic-disubstituted olefins, respectively; Schuster, M.; Pernerstorfer, J.; Blechert, S. Angew.Chem. 1996, 108, 2111-2112.
7. 5 a) Schwab, P.; France, M.B.; Ziller, J.W.; Grubbs, R.H. Angew.Chem.Int.Ed.Engl. 1995, 34, 2039-2041.
8. b) Schwab, P.; Grubbs, R.H.; Ziller, J.W. J.Am.Chem.Soc. 1996, 118, 100-110.
9. 6 For excellent reviews, see: a) Grubbs, R.H.; Miller, S.J.; Fu, G.C. Acc.Chem.Res. 1995, 28, 446-452.
10. b) Schmalz, H.G. Angew.Chem.Int.Ed.Engl. 1995, 34, 1833-1836. See also: Fürstner, A.; Langemann, K. J.Org.Chem. 1996, 61, 3942-3943.
11. b) Schmalz, H.G. Angew.Chem.Int.Ed.Engl. 1995, 34, 1833-1836. See also: Fürstner, A.; Langemann, K. J.Org.Chem. 1996, 61, 3942-3943.
12. 7 Miller, S.J.; Grubbs, R.H. J.Am.Chem.Soc. 1995, 117, 5855-5856.
13. 8 The additional resorcinol unit introduces the synthetically versatile phenol moiety which allows etherification by the mild Mitsunobu reaction. This method was initially chosen for attachment of 8 at alcohol type resins (see ref. 12).
14. 3), 1705 (C=O, carbamate), 1640 (C=O, 3° amide), 1180(C-O).
15. +, 100).
16. 11 Grubbs et al. (see ref. 7) described RCM of a bis terminal diolefin to give a similar seven membered lactam in only 50% yield. The lower yield obtained by Grubbs et al. (50% vs. 97%) might be explained by the fact that in our approach only one terminal olefin is present at which initial metallation occurs preferably. Probably, efficient product formation is only possible by initial reaction at the allyl glycine double bond.
17. 12 Mitsunobu type etherification of resorcinol monoether 8 with 1% DVB hydroxyethyl polystyrene or TentaGel® S-OH using several conditions failed. MicroIR analysis on both resin types revealed the presence of urethane carbonyls, presumably originating from 1,2-diethoxycarbonyl hydrazide fragments.
18. 13 Schwarz, M.; Oliver, J.E.; Sonnet, P.E. J.Org.Chem. 1975, 40, 2410-2411. Synthesis of the allylic chloride via the allyl alcohol, as performed in solution, failed. Removal of the THP group proceeded quantitatively, but transformation into the allylic chloride, using the same conditions as for the synthesis of 9, could not be accomplished.
19. 3), 1710 (C=O, carbamate), 1650 (C=O, 3° amide), 1175 (C-O); polystyrene at 3060, 3025, 2850 and 700.
20. 15 With FTIR microspectroscopy only one 90μm bead is analyzed. One analysis only takes 10 min. (including sample preparation). Due to the high loading it was even necessary to flatten the beads (with a diamond anvil cell) to avoid too intensive absorptions. See: Yan, B.; Kumaravel, G. Tetrahedron 1996, 52, 843-848.
21. 16 a) Anderson, R.C.; Jarema, M.A.; Shapiro, M.J.; Stokes, J.P.; Ziliox, M. J.Org.Chem. 1995, 60, 2650-2651.
22. b) Anderson, R.C.; Stokes, J.P.; Shapiro, M.J. Tetrahedron Lett. 1995, 36, 5311-5314.
23. 2. The resin was allowed to swell/shrink for 5 min. before each filtration. The combined filtrates were concentrated in vacito followed by passing the residue through a short path of silica (hexanes/EtOAc=4/1), to remove the catalyst remainings. In entries 3 and 4 also 7-tetradecene was isolated in yields of 40% and 62%, respectively, resulting from metathetical dimerization of 1-octene.
24. 18 It was ruled out that the formed product gave ring-opening metathesis with ethylene. Stirring of 4 with catalyst 1 in an ethylene atmosphere in toluene at room temperature for 2 days did not show any conversion.