Total Synthesis of (+)-Cladantholide and (−)-Estafiatin:  5-Exo,7-Endo Radical Cyclization Strategy for the Construction of Guaianolide Skeleton

The Renaissance of α‐Methylene‐γ‐butyrolactones: New Synthetic Approaches

“…[71] The Greene approach has been employed in many total syntheses. [71][72][73][74][75] For example, AubØ and co-workers utilized the Greene procedure in their synthesis of the stemona alkaloid (AE )-neostenine (95) published in 2008 (Scheme 16). [75] An elegant, tandem Diels-Alder/azido-Schmidt reaction between azido-silyl enol ether 91 and cyclohexenone afforded selectively the endo-adduct 92 in 43 % yield.…”

Synthesis of Biologically Active Guaianolides with a trans‐Annulated Lactone Moiety

“…A very elegant approach utilizing a radical cyclization cascade was reported by Lee and coworkers, [27] who sucwww.eurjoc.orgceeded in the total synthesis of (+)-cladantholide (3) isolated from Cladanthus arabicus. [28] and (-)-estafiatin (4).…”

“…Consequently, Ley and coworkers also started from (S)-carvone [(S)-72] and followed initially a similar route to that described above by Lee et al [27] Within 13 steps, aldehyde 87 was assembled with already one allyl side chain and five stereocenters installed (Scheme 16). Scheme …”

Access to Guaianolides: Highly Efficient Stereocontrolled Total Synthesis of (±)‐Geigerin

“…Over the past several decades, many strategies have been proposed to access guaian-6,12-and -8,12-olides, but they have involved numerous steps and lacked sufficient flexibility to reach both families. For example, Lee et al [10] reported in 1997 the total synthesis of (+)-cladantholide and (À)-estafiatin from (À)-carvone in 16 and 12 steps, respectively, which represented the shortest construction of naturally occurring guaianolides (Scheme 1). Our objective has been to develop a versatile, regio-and stereoselective synthetic approach to both guaianolide classes from inexpensive starting materials in fewer than 10 steps and without protecting-group chemistry.…”