RESUMO
The reactions of α,ß-unsaturated N-acyliminium ions, generated in situ from 4(S)-O-substitutedhydroxy-5-hydroxy-5-vinyl-N-alkylpyrrolidin-2-ones, with allylsilanes and indoles leading to the formation of spirocyclic heterocycles, are reported. Six single crystal X-ray structures and extensive 2D NMR experiments confirmed the structures and stereochemistries of these products. In addition, computational studies provided mechanistic insights and an understanding of the stereochemical outcomes of these reactions.
RESUMO
Novel tricyclic bridged heterocyclic systems can be readily prepared from sequential 1,4- and 1,2-addition reactions of allyl and 3-substituted allylsilanes to indolizidine and quinolizidine α,ß-unsaturated N-acyliminium ions. These reactions involve a novel N-assisted, transannular 1,5-hydride shift. Such a mechanism was supported by examining the reaction of a dideuterated indolizidine, α,ß-unsaturated N-acyliminium ion precursor, which provided specifically dideuterated tricyclic bridged heterocyclic products, and from computational studies. In contrast, the corresponding pyrrolo[1,2-a]azepine system did not provide the corresponding tricyclic bridged heterocyclic product and gave only a bis-allyl adduct, while more substituted versions gave novel furo[3,2-d]pyrrolo[1,2-a]azepine products. Such heterocyclic systems would be expected to be useful scaffolds for the preparation of libraries of novel compounds for new drug discovery programs.
RESUMO
Propargyl amines 4, where R(3) is aryl, undergo 5-exo-dig cyclization reactions under relatively mild conditions (AgNO(3), DMF, 60 °C, 1 h) to give 3-amino-2,3-dihydro-2-arylmethylidenebenzofurans 5 (R(3) = aryl). In contrast, substrates where R(3) is alkyl undergo competing 6-endo-dig and 5-exo-dig cyclization processes. The hydroxymethyl substrate 4 (R(3) = CH(2)OH), however, was smoothly converted to its corresponding 5-exo-dig cyclization product 5, likely due to the assistance of the primary hydroxyl group in the 5-exo-dig cyclization process by silver cation coordination. Under more enforcing conditions (AgNO(3), DMF, 100 °C, 18 h), the initially formed products 5 undergo a 1,3-allylic rearrangement to their corresponding 2-substituted benzofuran derivatives 6. This rearrangement can also be effected by treating 5 with AgNO(3) in DMF at 100 °C for 18 h or BF(3)·Et(2)O at rt. 2-(3-Butenyl)benzofurans 7 (Nu = allyl) can be prepared by treatment of 5 with BF(3)·Et(2)O and allyltributylstannane. Furan and MeOH could also be employed as external nucleophiles in these BF(3)·Et(2)O-promoted reactions.
Assuntos
Benzofuranos/química , Benzofuranos/síntese química , Cátions/química , Morfolinas/química , Ciclização , Espectroscopia de Ressonância Magnética , Estrutura MolecularRESUMO
The CuX (X = I, Br, Cl, CN)-mediated cyclization-halogenation and cyclization-cyanation reactions of beta-hydroxyalkynes and o-alkynylphenol and -aniline derivatives give rise to 3-halo- and 3-cyanofuro[3,2-b]pyrroles, 3-iodo-, 3-bromo-, and 3-cyanobenzofurans, and 3-cyanoindoles, respectively.
Assuntos
Alcinos/química , Compostos de Anilina/química , Cobre/química , Fenóis/química , Benzofuranos/síntese química , Benzofuranos/química , Ciclização , Indóis/síntese química , Indóis/química , Estrutura Molecular , Pirróis/síntese química , Pirróis/química , EstereoisomerismoRESUMO
Furo[3,2-b]pyrroles and furo[3,2-b]pyridines can be conveniently prepared in good yields from the cycloisomerization reactions of cis-4-hydroxy-5-alkynylpyrrolidinones and cis-5-hydroxy-6-alkynylpiperidinones, respectively, using Ag(I), Pd(II)/Cu(I), or Au(I) catalysis. In one case, the cycloisomerization product was unstable and produced a furan derivative by a ring-opening reaction.
Assuntos
Alcinos/síntese química , Metais Pesados/química , Piperidinas/síntese química , Piridinas/síntese química , Pirróis/síntese química , Pirrolidinas/síntese química , Alcinos/química , Catálise , Ciclização , Estrutura Molecular , Piperidinas/química , Piridinas/química , Pirróis/química , Pirrolidinas/química , EstereoisomerismoRESUMO
Novel bicyclic and tetracyclic spirocycles and tricyclic bridged heterocyclic systems can be readily prepared from sequential 1,4- and 1,2-addition reactions of latent bis-nucleophiles to α,ß-unsaturated N-acyliminium ions.
RESUMO
Pyrido- and pyrrolo[2,3-d]oxazoles can be conveniently prepared in high yield from the Ritter reaction of nitriles and in situ generated chiral cyclic N-acyliminium ions. cis-4-Hydroxy-5-acylaminopyrrolidines and cis-5-hydroxy-6-acylaminopiperidines can be readily obtained by acid hydrolysis of these bicyclic heterocyclic compounds, respectively.