The role of the bifunctional catalyst is decisive: The magnesium ion as Lewis acid and its nucleophilic iodide counterion contribute in synergy to the successful ring expansion of the cyclopropane 1 by aldimine 2 [Eq. (1)]. This reaction offers a novel route to spiro[pyrrolidin‐3,3′‐oxindoles] 3.

Dedicated to Prof. Dr. Jose Barluenga on the occasion of his 60th birthdayWe report a short synthetic route to (AE)-horsfiline that provides the racemate in five steps from commercially available, substituted isatin in 41% overall yield. Efficient entry into the spiro[oxindolepyrrolidine] ring system is possible through the application of the cyclopropane opening/ring expansion chemistry we have described with MgI 2 as a bifunctional catalyst.

Spirotryprostatin A (1) and B (2), two powerfully bioactive indole alkaloids, were isolated in 1996 by Osada et al. from the fermentation broth of Aspergillus fumigatus BM939. [1] Only miniscule amounts of 1 and 2 (11 and 1 mg, respectively) were isolated from 400 L of fermentation medium. Both compounds inhibit the cell cycle in the G2/M phase, and 2 shows cytotoxic activity on the growth of human leukemia cell lines. In this communication, we report a novel strategy towards the synthesis of spirotryprostatin B that is characterized by the MgI 2 -catalyzed annulation reaction of a spiro[oxindole-3,1'-vinylcyclopropane] and an alkynyl imine. It is notable that in the context of our investigations we have developed the functionalization of an advanced aldehyde intermediate which enables the generation of biologically active congeners. The synthetic chemistry of the spirotryprostatins has recently been the subject of intense investigations by several groups. The various creative, distinct strategies have been devised to provide access to the spiro[oxindole-3,3'-pyrrolidine] core. [2±6] We have recently developed a novel approach to spiro[oxindole-3,3'-pyrrolidines] by the MgI 2 -catalyzed ringexpansion reaction of spiro[cyclopropane-1,3'-oxindoles] and aldimines. [7] The methodological studies we have carried out to date have left unaddressed a pertinent issue, which impacts the general applicability of the method to provide access to a wide range of related alkaloids. In particular, in none of the earlier studies had we or others examined the use of 1,2disubstituted cyclopropanes, which would give access to 2,5substituted pyrrolidines. [8] At the outset, there were two key questions we wished to address: the use of vinyl cyclopropane 3 in the ring-expansion reaction to yield 7 and the relative stereochemical outcome of the annulation. With respect to the former, it was not at all clear whether the intermediate allylic iodide/enolate 5 would be stable, as it could collapse by intramolecular cyclization to form a dihydrofuroindole 6 (Scheme 1). [9] An additional problem we wished to explore was whether an aldehyde at C18 (spirotryprostatin B numbering) would serve as a useful precursor to the requisite prenyl side chain through an olefination reaction. Because earlier work in this area had concluded that olefination of a related aldehyde was unfeasible, revisting this strategic challenge was not without risk.Our synthesis commenced with known diazoketone 8, accessible in two steps and 79 % yield from isatin (Scheme 2). [10] Rhodium-catalyzed cyclopropanation of [*] Prof.

Spirotryprostatin A (1) and B (2), two powerfully bioactive indole alkaloids, were isolated in 1996 by Osada et al. from the fermentation broth of Aspergillus fumigatus BM939. [1] Only miniscule amounts of 1 and 2 (11 and 1 mg, respectively) were isolated from 400 L of fermentation medium. Both compounds inhibit the cell cycle in the G2/M phase, and 2 shows cytotoxic activity on the growth of human leukemia cell lines. In this communication, we report a novel strategy towards the synthesis of spirotryprostatin B that is characterized by the MgI 2 -catalyzed annulation reaction of a spiro[oxindole-3,1'-vinylcyclopropane] and an alkynyl imine. It is notable that in the context of our investigations we have developed the functionalization of an advanced aldehyde intermediate which enables the generation of biologically active congeners. The synthetic chemistry of the spirotryprostatins has recently been the subject of intense investigations by several groups. The various creative, distinct strategies have been devised to provide access to the spiro[oxindole-3,3'-pyrrolidine] core. [2±6] We have recently developed a novel approach to spiro[oxindole-3,3'-pyrrolidines] by the MgI 2 -catalyzed ringexpansion reaction of spiro[cyclopropane-1,3'-oxindoles] and aldimines. [7] The methodological studies we have carried out to date have left unaddressed a pertinent issue, which impacts the general applicability of the method to provide access to a wide range of related alkaloids. In particular, in none of the earlier studies had we or others examined the use of 1,2disubstituted cyclopropanes, which would give access to 2,5substituted pyrrolidines. [8] At the outset, there were two key questions we wished to address: the use of vinyl cyclopropane 3 in the ring-expansion reaction to yield 7 and the relative stereochemical outcome of the annulation. With respect to the former, it was not at all clear whether the intermediate allylic iodide/enolate 5 would be stable, as it could collapse by intramolecular cyclization to form a dihydrofuroindole 6 (Scheme 1). [9] An additional problem we wished to explore was whether an aldehyde at C18 (spirotryprostatin B numbering) would serve as a useful precursor to the requisite prenyl side chain through an olefination reaction. Because earlier work in this area had concluded that olefination of a related aldehyde was unfeasible, revisting this strategic challenge was not without risk.Our synthesis commenced with known diazoketone 8, accessible in two steps and 79 % yield from isatin (Scheme 2). [10] Rhodium-catalyzed cyclopropanation of [*] Prof.

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