Wolff/Cope Approach to the AB Ring of the Sesterterpenoid Variecolin

Abstract

Image AbstractA stereoselective synthesis of the AB ring of the complex sesterterpenoid variecolin is presented. Our strategy features the development of a tandem Wolff/Cope rearrangement of α-diazo cyclobutyl ketones for the construction of fused, eight-membered carbocycles. Preliminary studies revealed a facile Wolff rearrangement but a difficult vinyl ketene cyclobutane Cope rearrangement. We have leveraged an efficient microwave-promoted tandem rearrangement to prepare the desired functionalized cyclooctadienones that we envision as potential key intermediates in the convergent synthesis of variecolin.

Recent Advances in the Total Synthesis of Natural Products Containing Eight-Membered Carbocycles (2009–2019)

“…Because of their fascinating structures and biological importance, natural products containing eight-membered rings have attracted considerable attention from the synthetic community. Nowadays, numerous methodologies have been developed to construct eight-membered ring systems, some of which were reported very recently, − and many of which have also been applied to total synthesis of cyclooctanoids. Nevertheless, more practical, flexible, and efficient strategies to synthesize eight-membered rings are still required.…”

Zn(OAc)2-Catalyzed C3-Carbonylacetylation of Indoles with α-Diazoketones Involving Wolff Rearrangement

“…Considering that the previous mechanism studies have disclosed that both a cobalt-catalyzed Wolff rearrangement and a thermal Wolff rearrangement could lead to the formation of active ketenes, the cross-coupling between N -methylindole ( 1a ) and α-benzoyl-α-diazoester ( 2a ) was first performed in the presence of Co­(acac) 2 (50 mol %) in toluene at 120 °C under an Ar atmosphere for 12 h (Table ). Gratifyingly, we soon found Co­(acac) 2 gave the desired product 3a in 31% yield (entry 1), in which the carbonylacetylation regioselectively occurred at the C3-position of the indole 1a .…”

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

“…7 Rearrangement: synthesis of variecolin (3) with tandem Wolff/Cope rearrangement Stoltz reported a stereoselective access to the bicyclo[3.6.0]undecane core through a tandem Wolff/Cope rearrangement approach [88]. The strategy was first designed in a racemic version and further developed in an asymmetric fashion.…”

“…trans-Hydrindanone 87 was isolated as a single diastereomer and possesses 5 out of the 10 stereogenic centers of nitidasin (93). In parallel, (−)-citronellene (88) was converted into derivative 89 possessing a terminal alkene and a vinyl iodide moiety in 9 steps. This compound can be considered as a difunctionalized compound.…”