7-endo radical cyclizations catalyzed by titanocene(III). Straightforward synthesis of terpenoids with seven-membered carbocycles.
We describe a novel procedure for the straightforward synthesis of seven-membered carbocycles via free-radical chemistry, based on titanocene(III)-catalyzed 7-endo-dig and 7-endo-trig cyclizations. This procedure has proved to be useful for the chemical preparation of terpenoids with different skeletons containing cycloheptane rings, including the first total syntheses of dauca-4(11),8-diene (2), barekoxide (3), authentic laukarlaol (81), and a valparane diterpenoid (72), as well as a substantially improved synthesis of karahanaenone (1). We also provide theoretical and experimental evidence in support of a plausible mechanism, which may rationalize the preference for the unusual 7-endo cyclization mode shown by radicals with substitution patterns characteristic of the linalyl, nerolidyl, and geranyl linalyl systems. In light of these chemical findings, we discuss the potential involvement of radical cyclizations in the biosynthesis of some terpenoids containing seven-membered carbocycles.
Justicia
José
J
Department of Organic Chemistry, University of Granada, Faculty of Sciences, Campus Fuentenueva s/n, E-18071 Granada, Spain.
Oller-López
Juan L
JL
Campaña
Araceli G
AG
Oltra
J Enrique
JE
Cuerva
Juan M
JM
Buñuel
Elena
E
Cárdenas
Diego J
DJ
D002384:Catalysis; D003500:Cyclization; D005609:Free Radicals / Q000737:chemistry; D008956:Models, Chemical; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*; D013237:Stereoisomerism; D013729:Terpenes / Q000138:chemical synthesis* / Q000737:chemistry
D005609:Free Radicals; D009942:Organometallic Compounds; D013729:Terpenes; C406884:titanocene