Total Synthesis Highlights

This synthesis illustrates the power of the elegant enantioselective seven-membered ring
construction developed by the Davies group. The Williams phosphonium salt will also have
general applicability. In a simpler manifestation, conversion of an aldehyde to, e.g., the enol
benzoate, followed by exposure to dilute methoxide, will allow the conversion of an aldehyde to
the aldehyde one carbon longer, without the acidic hydrolysis usually required for such a
transformation.
D. F. Taber, Org. Chem. Highlights 2009, December 7.
URL: http://www.organic-chemistry.org/Highlights/2009/07December.shtm
18.The Kobayashi Synthesis of (-)-Norzoanthamine
The Zoanthus alkaloids, exemplified by (-)-norzoanthamine (3a) and zoanthamine (3b), show
promising activity against osteoporosis. Susumu Kobayashi of the Tokyo University of Science
assembled (Angew. Chem. Int. Ed. 2009, 48, 1400, ; Angew. Chem. Int. Ed. 2009, 48, 1404, ) the
challenging tricyclic core of 3a employing the intramolecular Diels-Alder cyclization of 1 to 2.
The cyclopentane of 1 served as useful scaffolding, even though it was cleaved en route to 3a.
The cyclohexane ring of 1 has five of its six positions substituted, including three that are
alkylated quaternary centers. The starting point for the preparation of 1 was the
enantiomerically-pure Hajos-Parrish ketone 4, containing the first of the those quaternary centers.
Conjugate addition of MeLi established the second quaternary center. The less stable endo alkyl
branch of 1 was installed by conjugate addition to the more reactive α-methylene ketone of the
cross-conjugated 5, followed by kinetic quench. Addition of vinyl cuprate across the open face of
the enone 7 then established the final quaternary center, setting the stage for the intramolecular
Diels-Alder reaction. The silyl enol ether from the cyclization of 1 was not stable, so it was
directly oxidized to the enone 2.