A rapid, efficient route to 3,3-disubstituted oxindoles from o-iodo anilines has been developed. It involves the cyclisation of the corresponding fumarate amides 4 and 15 with butyllithium at -1 00 "C in the presence of an excess of trimethylchlorosilane. An X-ray crystal structure of 4 suggests that the speed and efficiency of this intramolecular Michael addition is dependent on the conformation adopted by 4 which is particularly suitable for the reaction. This method has been applied to the synthesis of the alkaloids physovenine, physostigmine and esermethole in very high overall yields.The pyrrolo[2,3-h]indole alkaloid physostigmine 1 isolated from the Calabar bean of West Africa is well known for its inhibition of acetylcholine esterase. Many syntheses of both 1 and its oxygen analogue physovenine 2 have been reported.' We now describe a novel, simple route to 3,3-disubstituted oxindoles. a structural feature of many oxindole alkaloids, and its application to the synthesis of 1 and 2 in high yield. mixture with aqueous ammonium chloride at this temperature revealed that much polymeric and ill-defined material was formed together with only a 432) yield of the desired product 5. We attributed the low yield to anionic polymerisations initiated by the ester enolate that results from the cyclisation. To forestall such processes 5 equiv. of trimethylchlorosilane were added to the reaction mixture before the addition of butyllithium at Me 1 X=NMe 2 x = o R3 3
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