Total Synthesis of Grossularines-1 and -2

Article abstract of DOI:10.1021/jo00123a028

The first total syntheses of grossularines-1 (1a) and -2 (1b) have been completed.The cross-coupling reaction between ethyl 3-iodoindole-2-carboxylate (6) and the directed metalation-derived imidazole 9b gave the ethyl 3-(5-imidazolyl)indole-2-carboxylate 11b.Hydrolysis of the ester group of 11b, followed by Curtius rearrangement, yielded the 2-isocyanatoindole 13b.The thermal electrocyclic reaction of 13b was carried out to provide the desired tetracyclic pyrido<2,3-b>indole ring system 14b, which was converted into the triflate 15b.The three-component cross-coupling reaction of the triflate 15b, carbon monoxide, and p-(OMOM)phenylboronic acid (17) followed by hydrolysis gave glossularine-2 (1b) in low yield.In addition, the palladium-catalyzed carbonylation of the triflate 15b afforded the N-deprotected methyl ester 19a or the methyl ester 19b depending on the amounts of triethylamine used.Compound 19a was treated with either p-(OMOM)phenyllithium or 3-(N-TIPS)indolyllithium to obtain grossularine-2 (1b) and grossularine-1 (1a) (37percent), respectively.By contrast, when 19b was treated with the same aryllithium reagents, grossularine-2 (1b) (51percent) and grossularine-1 (1a) (63percent) were produced, respectively.