Synthesis of 4-substituted cis,cis-1,6-cyclodecadienes via cycloalkylation

✍ Scribed by Mark S. Frazza; Bryan W. Roberts

• Publisher: Elsevier Science
• Year: 1981
• Tongue: French
• Weight: 243 KB
• Volume: 22
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(01)82101-8

✦ Synopsis

Cycloalkylation of dimethyl malonate and tosylmethylisocyanide with cis cis-1,9dibromonona-2,7-diene has demonstrated the feasibility of direct cyclization as a routeto functionalized cis cis-1,6-cyclodecadienes. _*-Eupacunin(&), an antileukemic sesquiterpene lactone isolated from Eupatorium cuneifolium, is one of a small number of germacranolides reported to contain the cis,cis-1,6-cyclodecadiene ring system. 1 This feature, together with the existence of the o-bromobenzoate lb in the less favored boat conformation 2 in the crystalla = led us to consider approaches to the total synthesis of this natural product. Construction of the medium ring diene by a method compatible with controlled incorporation of a number of substituents, especially allylic oxygen functionality, is essential to development of a rational strategy, and we have consequently turned our initial efforts toward this aspect of the problem. Known approaches to cis,cis-1,6-cyclodecadienes3 did not appear sufficiently flexible for this purpose. However, the efficient formation of 4,9dihetero analogues via double cycloalkylation with 1,4-dihalo-cis-2-butenes, 2a,4 together with the