Dichloroketene-Induced Cyclizations of Vinyl Sulfilimines:  Application of the Method in the Synthesis of (±)-Desoxyeseroline

Abstract

The reactions of several aryl-, furanyl-, and vinyl-substituted sulfilimines with dichloroketene proceeded at 25 degrees C to yield thioalkyl-substituted gamma-lactams. The overall process involves nucleophilic addition of the nitrogen atom of the sulfilimine onto the highly electrophilic dichloroketene to first generate a zwitterionic intermediate. A subsequent [3,3]-sigmatropic rearrangement is followed by intramolecular trapping of the Pummerer cation by the amido anion to furnish the observed gamma-lactam product. Incorporation of donor groups on the aromatic ring of the sulfonyl functionality had little effect when aryl-substituted sulfilimines were used but exhibited a major effect on the efficiency of the reaction with furanyl-substituted systems. The placement of an electron donor group (i.e., OMe) on the sulfonyl aryl group enhances the nucleophilicity of the amido anion contained within the sulfonium ion intermediate and facilitates the rate of the 3,3-sigmatropic rearrangement. Styryl-substituted sulfilimines cyclize in a stereospecific manner and produce a 3:2-mixture of gamma-lactams and the isomeric imino-lactone system. The heavily functionalized gamma-lactams are easily converted to a variety of nitrogen containing substrates. The vinyl sulfilimine cyclization method was applied to the total synthesis of the Calabar alkaloid (+/-)-desoxyeseroline.

Structure, Bioactivity and Synthesis of Natural Products with Hexahydropyrrolo[2,3‐b]indole

“…[183] www.chemeurj.org (Scheme 34). [191] This route comprised reaction of the indolyl sulfylimine 167 with the highly electrophilic dichloroketene to generate a zwitterionic intermediate. Subsequent [3.3]-sigmatropic rearrangement, followed by intramolecular trapping of the Pummerer cation by the amido anion, furnished the g-lactam product 169 in good yield.…”

“…Synthesis of (AE )-desoxyeseroline (108). [191] a) Zn/Cu, THF, Cl 3 CCOCl, 78 %; b) Zn, AcOH, TMEDA, EtOH, then HCO 2 H, 72 %; c) Na, naphthalene, THF, 81 %; d) MeI, NaH, THF, 87 %; e) BH 3 ·THF, THF, 80 %. TMEDA = tetramethylethylenediamine.…”

Facile synthesis of heteroaryl substituted $\gamma$-lactams from nitrovinyl arenes

“…18 Reactions of 2a with nitrovinyl arenes 1a-d gave addition products 3a-d in 65%-80% yields (Table 1, entries 1-4). Reactions of ethyl acetoacetate (2b) among the active methylene compounds with 1a-d gave 3e-h in high yields (86-99%) ( Table 1, entries [5][6][7][8]. Moreover, addition of methyl cyanoacetate (2c) to nitrovinyl arenes 1a-c produced 3i-k in moderate yields (50%-71%) while no product was formed from the addition reaction to nitrovinyl indole 1d (Table 1, entries 9-12).…”

“…1 For this reason, different methodologies have been developed for their synthesis. These methods include ring expansion of β -lactams, 2 domino ring opening-cyclization of aziridines, 3 intramolecular cyclization, 4,5 [3 + 3] cycloaddition, 6,7 or radical cyclization reactions.…”

Convergent Assembly of Enantioenriched Tetrahydrobenzofuro[2,3‐b]pyrrole Scaffolds by AgI‐Catalyzed Asymmetric Domino Reaction of Isocyanoacetates

“…Chiral tetrahydrobenzofuro[2, 3-b]pyrroles, especiallyt hose bearing characteristic quaternary carbon stereogenic centers at the ring junctions, are core scaffolds embedded in al arge array of biologically active substances ( Figure 1). [1] However,a ssembly strategiesf or these tricyclics caffolds currently are very limited.E xisting methodss uch as the stepwise C3-arylation/C2oxygenation of indoles, [2] skeletal rearrangement of benzoxazines [3] and chromen-2-ones, [4] cyclization of nitrones, [5] cycloaddition of dichloroketenes with sulfilimines, [6] radical annulation of N-chlorosulfonamides with benzofurans, [7] and also the recently developed radical-initiated cyclativer earrangemento f conjugated aryl oxime ether, [8] always suffer from multiple synthetic steps,u navailabilityo fs tarting materials, and/or lack of enantioselectivity.H ence, the development of novel, efficient, and particularly asymmetrica ccesses from readily available startingm aterials is undoubtedly of significance and deserves investigation.…”