The reactivity of 2-sulfonamidoindoles with acetoxy allenoates under phosphine catalysis depends on the disposition of the acetoxy (OAc) group on the allenoate. In the temperature-controlled [3 + 3] annulations, δ-acetoxy allenoates afforded dihydrocarboline and carboline scaffolds with carbon−nitrogen nucleophilic 2-sulfonamidoindoles, in which allenoate serves as a β-, γ-, and δ-carbon donor. At room temperature (25 °C), dihydro-α-carboline motifs were obtained exclusively through Michael addition, 1,4-proton shift, isomerization, 1,2-proton transfer, phosphine elimination, and aza-Michael addition. The higher temperature (80 °C) cascade protocol using Ph 3 P−Cs 2 CO 3 combination involves addition−elimination, aza-Claisen rearrangement, tosyl migration, and aromatization as key steps to give α-carbolines containing tosyl functionality at the γ-carbon. In contrast, with β′acetoxy allenoate, 2-sulfonamidoindole acts only as a carbo-nucleophile in (p-tolyl) 3 P-directed [4 + 1] spiro-annulation, leading to five-membered spiro-carbocyclic motifs essentially as single diastereomers (dr >20:1) via chemoselective carbo-annulation.
1-Methylindole-3-carboxamides react with substituted propargyl alcohols to afford lactams by [4 + 3]-annulation and carboxamide group migration to the indole-2-position. In contrast, indole-2-carboxylic acids/amides form fused sevenmembered lactones/lactams (oxepinoindolones/azepinoindolones) upon treatment with substituted propargyl alcohols using catalytic Cu(OTf) 2 . Decarboxylative cyclization of 1-methylindole-2-or indole-3-carboxylic acids with substituted propargyl alcohols under Lewis (for 1-methylindole-2-carboxylic acid) or Brønsted (for 1-methylindole-3-carboxylic acid) acid catalysis gives the same 3,4-dihydrocyclopentaindoles, demonstrating 3-to 2-carboxylate migration in the latter case.I ndole-fused seven-membered ε-lactams are often found as core structural motifs in natural products and biologically active compounds (Figure 1), but reported methods for their
Lewis base dependent (3 + 3) annulations of β'/δ-acetoxy allenoates with iminoindolines offer αcarbolines with varying substituents depending on the base used as well as subtle changes in the reaction conditions. The phosphine-catalyzed annulation of δ-acetoxy allenoates with iminoindolines involves 6-exotrig cyclization, tosyl anion elimination/trapping, and ethyl acetate elimination as key steps in delivering β-H and γ-tosyl containing α-carbolines. An unobvious elimination (by C α -C β bond cleavage) of the À CH 2 CO 2 Et moiety is observed here. The same reactants under DBU catalysis offer α-carbolines that retain À CH 2 CO 2 Et moiety but are devoid of À Ts group via 6-exo-dig cyclization. The reaction of β'-acetoxy allenoate with iminoindolines is completely tertiary amine dependent; the use of DABCO affords tetrahydro-α-carbolines exclusively with excellent stereoselectivity while DBU offers substituted α-carbolines that are distinct from those using DABCO. Several control experiments and HRMS studies have been done in support of a plausible reaction mechanism.
Lewis base-controlled (3 + 3) annulation of δ-acetoxy allenoates with N-Boc-oxindole, benzofuranone, or pyrazolone affords fused pyrans; the base DBU gives pyrans, while DMAP affords dihydropyrans.
In this paper, we highlight some addition/cycloaddition reactions of allenylphosphonates and allenylphosphine oxides, mostly based on the work done in our laboratory. Thus the electrophilic addition of iodine monochloride (ICl) with allenylphosphine oxides affords cyclic phosphonium salts rather than γ-chloro-β-iodovinylphosphine oxides (NMR, HRMS, X-ray) that exhibit rather unusual downfield shifts in the 31P NMR spectra. These compounds undergo hydrolysis to afford γ-hydroxy-β-iodovinylphosphine oxides; the hydroxymethyl group in these compounds can be oxidized by Dess-Martin periodinane to afford the corresponding aldehyde-substituted vinylphosphine oxides. A [2+2] cycloaddition product of an allenylphosphonate has also been structurally characterized. Other reactions that are highlighted include those leading to (Z)/(E)-β-aminovinylphosphonates, β-ketophosphonates (and their utility in Horner-Wadsworth-Emmons reaction), indolyl/furanyl/isocoumaranyl/naphthyl phosphine oxides, thiophosphorylated phosphonates and azo-substituted coumarin phosphonates.
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