Formal total synthesis of (+/-)-gamma-lycorane and (+/-)-1-deoxylycorine using the [4+2]-cycloaddition/rearrangement cascade of furanyl carbamates

The total syntheses of gamma -lycorane and (+/-)-1-deoxylycorine were accom plished using an intramolecular Diels-Alder cycloaddition of a furanyl carb amate as the key step. The initially formed [4+2]-cycloadduct undergoes nit rogen assisted ring opening followed by deprotonatian/reprotonation of the resulting zwitterion to give a rearranged hexahydroindolinone. The stereoch emical outcome of the IMDAF cycloaddition has the side arm of the tethered alkenyl group oriented syn with respect to the oxygen bridge. The key inter mediate used in both syntheses corresponds to hexahydroindolinone 20. Remov al of the t-Boc group in 20 followed by reaction with 6-iodobenzo[1,3] diox ole-5-carbonyl chloride afforded enamide 22. Treatment of this compound wit h Pd(OAc)(2) employing the Jeffrey modification of the Heck reaction provid ed the galantfhan tetracycle 24 in good yield. Compound 24 was subsequently converted into (+/-)-gamma -lycorane using a four-step procedure to establ ish the cis-B, C-ring junction. A radical-based cyclization of the related enamide 33 was used for the synthesis of 1-deoxylycorine. Heating a benzene solution of 33 with AIBN and n-Bu3SnH at reflux gave the tetracyclic compo und 38 possessing the requisite trans fusion between rings B and C in good yield. After hydrolysis and oxidation of 38 to 40, an oxidative decarboxyla tion reaction was used to provide the C-2-C-3-C-12 allylic alcohol unit cha racteristic of the lycorine alkaloids The resulting enone was eventually tr ansformed into (+/-)-1-deoxylycorine via known synthetic intermediates.