Metal mediated routes to 5-membered rings

L. S. Liebeskind, Ramakrishnan Chidambaram, D. Mitchell, B. S. Foster
1988 Pure and Applied Chemistry  
New methods for the synthesis of functionalized alkylidene cyclopentenone and alkylidene indanone derivatives are described. The first, a method based on the reaction of cationic stoichiometric maleoylcobalt complexes with terminal alkynes, allows the synthesis of 5-alkylidene cyclopent-Z-ene-l,4-diones by reaction with terminal alkynes. The formation of the alkylidene cyclopentenedione ring system is presumed to arise via the intermediacy of a cationic vinylidene complex formed via
more » ... med via tautomerization of the terminal alkyne within the coordination sphere of the cobalt. A more practical process for the preparation of alkylidene cyclopentenediones and 2-alkylidene indan-lones was developed based on the palladium(I1) induced electrophilic ring expansion of 4-(l-alkynyl)-4-hydroxycyclobut-Z-en-l-one, 2-(Ialkynyl)-2-hydroxy benzocyclobutenone, and various derivatives. Some of the compounds prepared were assayed for in vitro antitumor activity. Natural products containing or derived from an alkylidene cyclopentenone substructure show significant biological activity. For example, there is a growing class of cyclopentanoid antibiotics2 such as methylenomycin A and B,3 1 and 2, the penten~mycins,~ 3 , ~anthocidin,~ -4 , and the known antitumor agent sarcomycin,6 5 . eicosanoids related to the prostaglandins, SUCK as the clavulones7 (claviridenones*) 6 , chloro9-bromo-and indovulones" 7, and the punaglandinsll 8, have been reported to possess remarkable cytotoxicity in both in vitro and in vivo studies.12 In fact, the non-naturally occurring arylidene cyclopentenediones 9 also show reasonable in vitro antitumor activity. l 3 The significant biological activity of the alkylidene cyclopentenone natural and non-natural products has prompted the development of numerous methods for the synthesis of this class of compounds. l4 We describe herein new methods for the preparation of functionalized alkylidene cyclopentenones and alkylidene indanones. More recently, a series of marine 4 Clavulone I: X=H; R=OAc; 5,6-Z; 7,8-E Clavulone 11: X = H R=OAc; 5.6-E; 7,8-E Clavulone 111: X=H; R=OAc; 5.6-E; 7.8-2 1
doi:10.1351/pac198860010027 fatcat:3mcbfggusrekfjkfl54seqa5ty