Application of furanyl carbamate cycloadditions toward the synthesis of hexahydroindolinone alkaloids

A convenient. synthesis of various substituted hexahydroindolinones has bee n achieved by an intramolecular Diels-Alder cycloaddition reaction (IMDAF) of furanyl carbamates bearing tethered alkenyl,groups. The initially formed [4 + 2]-cycloadduct undergoes nitrogen-assisted ring opening followed by d eprotonation of the resulting zwitterion to give the rearranged ketone. The stereochemical outcome of the IMDAF cycloaddition has the sidearm of the t ethered alkenyl group oriented syn with respect to the oxygen bridge. A syn thetic route to (+/-)-mesembrane and (+/-)-crinane was accomplished using t his methodology. It was possible to carry out a stereoselective reduction o f the initially formed hexahydroindolinone ring to produce the cis-3a-aryl- hydroindole skeleton. A related [4 + 2] -cycloaddition/rearrangement sequen ce was also used for a formal synthesis of the Chinese ornamental orchid (/-)-dendrobine. The tricylic alkaloid core was formed stereoselectivity fr om the thermolysis of N-[(2-methyl-2-cyclopentenyl)methyl]-N-(4-isopropyl-f uran-2-yl)carbamic acid tert-butyl ester. Kende's advanced intermediate 33 was prepared in seven additional steps by standard transformations, thereby completing a formal synthesis of (+/-)-dendrobine.