Application of furanyl carbamate cycloadditions toward the synthesis of hexahydroindolinone alkaloids.
A convenient synthesis of various substituted hexahydroindolinones has been 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 deprotonation of the resulting zwitterion to give the rearranged ketone. The stereochemical outcome of the IMDAF cycloaddition has the sidearm of the tethered alkenyl group oriented syn with respect to the oxygen bridge. A synthetic route to (+/-)-mesembrane and (+/-)-crinane was accomplished using this methodology. It was possible to carry out a stereoselective reduction of the initially formed hexahydroindolinone ring to produce the cis-3a-aryl-hydroindole skeleton. A related [4 + 2]-cycloaddition/rearrangement sequence was also used for a formal synthesis of the Chinese ornamental orchid (+/-)-dendrobine. The tricyclic alkaloid core was formed stereoselectivity from the thermolysis of N-[(2-methyl-2-cyclopentenyl)methyl]-N-(4-isopropyl-furan-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.
Padwa
A
A
Department of Chemistry, Emory University, Atlanta, Georgia 30322, USA. chemap@emory.edu
Brodney
M A
MA
Dimitroff
M
M
Liu
B
B
Wu
T
T
D000470:Alkaloids / Q000138:chemical synthesis*; D002219:Carbamates / Q000138:chemical synthesis*; D003500:Cyclization; D007211:Indoles / Q000737:chemistry*; D008567:Membranes, Artificial; D010946:Plants, Medicinal / Q000737:chemistry*
D000470:Alkaloids; D002219:Carbamates; D007211:Indoles; D008567:Membranes, Artificial; C429964:hexahydroindolinone; C002077:dendrobine