ABSTRACT
Readily accessible 3-alkoxycarbonyl-6-hydroxy-5-halocoumarins can be converted into 4-halo-5-hydroxyindoles by a sequence whose essential steps are conjugate reduction or conjugate addition, decarboxylation, lactone opening with ammonia, phenolic oxygen protection, Hofmann rearrangement to an N-Boc ethylamine, oxidation to a quinone and deprotection of the nitrogen. The resulting beta-aminoethyl quinone cyclizes to a mixture of quinone imine and indole, and the imine tautomerizes to the indole spontaneously or on treatment with rhodium on alumina.
Subject(s)
Coumarins/chemistry , Indoles/chemical synthesis , Cyclization , Indoles/chemistry , Molecular Structure , StereoisomerismABSTRACT
Two independent routes for the total synthesis of the bioactive neolignan (-)-conocarpan are described. The first (98% ee) is based on formal radical cyclization onto a benzene ring, and involves a 5-exo-trigonal closure onto a double bond restrained within a 6-membered ring. The second route (88% ee), which is shorter, is based on 5-exo-trigonal cyclization of an aryl radical onto a pendant terminal double bond. The two routes differ in their degree of stereoselectivity. The absolute configuration originally assigned to (+)-conocarpan had previously been called into question on the basis of empirical chiroptical rules; the present chemical work confirms the need for revision, and the assigned absolute configurations of several compounds correlated with (+)-conocarpan must also be changed.
Subject(s)
Benzofurans/chemical synthesis , Benzofurans/chemistry , Cyclization , Free Radicals/chemistry , Molecular StructureABSTRACT
(-)-Conocarpan (1) was synthesized by a method based on radical cyclization, and the absolute configuration was established by chemical degradation; the original 2R,3R-assignment to (+)-conocarpan should be reversed, as suggested by a later chiroptical study of model 2,3-dihydrobenzofurans.
