Collective Domino Approach toward the Core of Molecules Isolated from the Genus Schisandra

Abstract

A concise route to the ABC and ABCD core of molecules isolated from the genus Schisandra has been accomplished. The synthesis demonstrated high atom efficiency employing a new one-pot cascade which sequentially built three rings and a quaternary spirocenter.

First studies directed towards the diastereoselective synthesis of the BCD tricyclic core of brownin F

“…With cyclisation precursor 4a in hand, we were ready to explore the key intramolecular rhodium(II)-mediated [1,3]-dipolar cycloaddition reaction. In the event, we were pleased to observe the smooth formation of spirolactone 2c in the presence of a catalytic amount of Rh 2 (OAc) 4 in dichloromethane at room temperature, in good yield (78%) and as a single diastereomer (Scheme 10). The reaction is presumed to proceed via initial carbonyl ylide formation followed by a chemo-, regioand diastereoselective intramolecular cycloaddition reaction onto the exocyclic double bond of the dipolarophile.…”

“…were successively added. The Schlenk tube was sealed and then placed in a preheated oil bath at 55°C for 4 hours, following which the Schlenk tube was placed in an ice bath and a saturated aqueous solution of NH 4 Cl was added. Stirring at 0°C was allowed for 10 min and the reaction mixture was diluted in diethyl ether and filtered through a short pad of celite.…”

“…and propargyl bromide (80% w/w, 7.3 g, 34.4 mmol, 1.4 equiv.). Stirring at room temperature was allowed for 7 hours at which time a saturated aqueous solution of NH 4 Cl was poured into the reaction mixture. The aqueous layer was extracted with EtOAc and the combined organic layers were washed with brine, dried over anhydrous Na 2 SO 4 , filtered and concentrated in vacuo.…”

“…in anhydrous THF (13 mL) was added. The reaction mixture was stirred at this temperature for 2 hours at which time it was rapidly transferred to a saturated aqueous solution of NH 4 Cl. Then the aqueous layer was extracted with ethyl acetate and the combined organic layers were dried over anhydrous Na 2 SO 4 , filtered and concentrated in vacuo to afford a clear yellow oil which was used in the next step without further purification.…”

“…The γ-alkylidenebutenolide precursor has been used on several occasions within our group for the construction of complex structures presenting a spirocentre through the Diels-Alder 3 or domino reactions. 4 Herein we wish to describe a diastereoselective approach towards the synthesis of the tricyclic skeleton of brownin F 1 utilising an intramolecular [3 + 2] cycloaddition methodology 2,5 between a cyclic carbonyl ylide and a γ-alkylidenebutenolide.…”