179945-86-9Relevant academic research and scientific papers
A triple cascade sequence as a strategy for the construction of the erythrinane skeleton
Padwa, Albert,Hennig, Rudiger,Oliver Kappe,Reger, Thomas S.
, p. 1144 - 1155 (2007/10/03)
α-Thiocarbocations generated from Pummerer reactions of several o- imido sulfoxides were intercepted by adjacent carbonyl groups to produce α- amido-substituted isobenzofurans as transient intermediates. When an olefinic tether was present, intramolecular Diels-Alder cycloaddition occurred followed by a ring-opening-elimination sequence that produced an N- acyliminium ion. Deprotonation of the iminium ion led to oxindole derivatives in good yields. When the iminium ion contained both a blocking substituent, such as a carbomethoxy group, as well as an activated aromatic π-tether, the N-acyliminium ion intermediate underwent stereoselective spirocyclization to afford cis-3,4-benzoerythrinane or homerythrinane derivatives in good yield. The overall triple cascade sequence represents an efficient one-pot approach toward the erythrina skeleton in which the spirocyclic ABC skeleton is assembled in a single operation. The scope and limitations of the triple cascade were explored by varying both the olefinic and nucleophilic tethers. The required sulfoxide precursors for these Pummerer-induced transformations were easily synthesized starting from 2-[(ethylthio)methyl]benzoic acid. The tandem Pummerer/Diels-Alder/N-acyliminium ion cyclization was used for the synthesis of indoloisoquinoline 38. Since compound 38 was converted to 47 which, in turn, was transformed into erysotramidine (2), its preparation represents an extraordinarily facile, formal synthesis of this member of the Erythrina alkaloid family.
Studies dealing with the cycloaddition/ring opening/elimination sequence of 2-amino-substituted isobenzofurans
Padwa, Albert,Kappe, C.Oliver,Cochran, John E.,Snyder, James P.
, p. 2786 - 2797 (2007/10/03)
The α-thiocarbocation generated from the Pummerer reaction of an o-amido-substituted sulfoxide is intercepted by the adjacent amido carbonyl group to produce a 2-amino-substituted isobenzofuran as a transient intermediate. In the presence of an electron-deficient dienophile, the reactive isobenzofuran undergoes a Diels-Alder cycloaddition followed by ring opening to furnish a vinylogous C-acyliminium ion that readily aromatizes. The one-pot intramolecular cascade process only occurs either if the olefinic tether is activated by an ester or if a carbonyl group is located adjacent to the nitrogen atom of the 2-amino-substituted isobenzofuran. To examine the amine vs amide influence on the course of intramolecular cycloaddition, density functional theory (DFT) calculations have been carried out for both ground and transition states. The results strongly suggest that the amide-substituted isobenzofurans are destabilized by steric effects between the aromatic ring and the nitrogen-containing side chain. Raising of the ground-state amide energies thereby reduces the activation energy for internal cycloaddition and leads to Diels-Alder adducts more rapidly than for the corresponding amines. Amide tethers emerge as remote-site promoters of intramolecular cycloaddition for tandem processes yielding products with multiple fused rings.
