Combinatorial chemistry. Use of an intramolecular ruthenium catalyzed olefin/alkyne metathesis reaction in tandem with a Diels-Alder cycloaddition reaction to construct functionalized hexahydroisoindoles

Tetrahedron Letters

Volumn 39, Issue 38, 1998, Pages 6815-6818

  Heerding, Dirk A ^a   Takata, Dennis T ^a   Kwon, Chet ^a   Huffman, William F ^a   Samanen, James ^a  

^a GLAXOSMITHKLINE   (United Kingdom)

Author keywords

Combinatorial chemistry; Diels Alder reactions; Metathesis

Indexed keywords

ALKENE; ALKYNE; ISOINDOLE DERIVATIVE; RUTHENIUM;

ARTICLE; CATALYSIS; CHEMICAL ANALYSIS; CHEMICAL REACTION; DRUG SYNTHESIS; POLYMERIZATION;

BETULACEAE;

EID: 0032541701     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(98)01473-7     Document Type: Article

References (18)

1. 1. Marx, M.A.; Grillot, A. -L.; Louer, C.T.; Beaver, K.A.; Bartlett, P.A. J. Am. Chem. Soc. 1997, 119, 6135-6167.
2. 2. (a) An, H.; Haly, B.D.; Cook, P.D. J. Med. Chem. 1998, 41, 706-716.
3. (b) Ostrem, J.A.; Al-Obeidi, F.A.; Safar, P.; Safarova, A.; Stringer, S.K.; Patek, M.; Cross, M.T.; Spoonamore, J.; LoCascio, J.C.; Kasireddy, P.; Thorpe, D.; Sepetov, N.; Lebl, M.; Wildgoose, P.; Strop, P. Biochemistry 1998, 37, 1053-1059.
4. (c) Nicolaou, K. C.; Vourloumis, D.; Li, T.; Pastor, J.; Winssinger, N.; He, Y.; Ninkovic, S.; Sarabia, F.; Vallberg, H.; Roschangar, F.; King, N.P.; Finlay, M.R.V.; Giannakakou, P.; Verdier-Pinard, P.; Hamel, E. Angew. Chem. Int. Ed. Engl. 1997, 36, 2097-2103.
5. 3. (a) Yedidia, V.; Leznoff, C.C. Can J. Chem. 1980, 58, 1144-1150.
6. (b) Schlessinger, R.H.; Bergstrom, C.P. Tetrahedron Lett. 1996, 37, 2133-2136.
7. 4. (a) Kinoshita, A.; Mori, M. Synlett 1994, 1020-1022.
8. (b) Kinoshita, A.; Mori, M. J. Org. Chem. 1996, 61, 8356-8357.
9. (c) Kim, S.-H.; Zuercher, W.J.; Bowden, N.B.; Grubbs, R.H.J. Org. Chem. 1996, 61, 1073-1081.
10. 5. After the completion of this work, an example of an intermolecular ruthenium-catalyzed ene-yne cross metathesis on Merrifield resin was published. Schurer, S.C.; Blechert, S. Synlett 1998, 2, 166-168.
11. 6. 3-Amino-4-methylpent-1-ene (5b): Tamao, K.; Nakagawa, Y.; Ito, Y. J. Org. Chem. 1990, 55, 3438-3439.
12. 7. Kim, S.-H.; Bowden, N.; Grubbs, R.H. J. Am. Chem. Soc. 1994, 116, 10801-10802.
13. 8. Chloro-Wang resin was prepared from commercially available Wang resin (Polymer Labs; Lot No. Wang008; 250-300 μM mesh; 1.7 meq/g loading) according to Raju, B.; Kogan, T.P. Tetrahedron Lett. 1997, 38, 4965-4968
14. 1H NMR analysis. The material was also >98% pure by reverse phase HPLC analysis.
15. 10. Hamper, B.C.; Dukesherer, D.R.; South, M.S. Tetrahedron Lett. 1996, 37, 3671-3674.
16. 11. Apparently, the diethyl hydrazinedicarboxylate by-product of the Mitsunobu reaction effectively competed with the phenol as an alkylating agent for the resin. The side reaction could be suppressed by using a large excess of the allyl 4-hydroxybenzoate.
17. 12. Seitz, O.; Kunz, H. Angew. Chem. 1995, 107, 901-904.
18. 3 component consisted of hydrogen or alkyl groups. The dienophiles included cyclic, cis and trans disubstituted olefins containing at least one electron withdrawing group and alkynes containing at least one electron withdrawing group.