Studies toward the synthesis of EFGH ring system diazonamide A Pummerer chemistry applied toward the synthesis of 3,3-spirocyclic oxindoles
Abstract (Summary)iii Synthetic approaches to 3,3-spirocyclic oxindoles, moieties commonly encountered in many natural products, has been described. Initial efforts were focused on the construction of the EFGH core of the marine alkaloid diazonamide A. This substructure, characterized by a 3,3-disubstituted oxindole unit, was designed to be synthesized via a photoinduced electrocyclic reaction of the corresponding 2-(ptolyloxy)indole. However, no such cyclization was observed under the reaction conditions but a mixture of rearrangement products was isolated. A single electron transfer-initiated radical cleavage in the starting diaryl ether was proposed to rationalize the origination of the products. A new oxidative cyclization approach to the 3,3-spirocyclic oxindole problem was proposed. The methodology employed a variant of the Pummerer reaction of an indole precursor. 3-Substituted 2-(phenylsulfinyl)indole derivatives were tested under conditions typical for the classical rearrangement. The corresponding products, 3,3spirocyclic 2-(phenylthio)indolenines, were isolated in excellent yields and hydrolyzed to uncover the oxindole functionality. The Pummerer reaction was performed on enantioenriched sulfinyl compounds and the products were obtained with good enantiomeric excess, suggesting additive mechanism of the rearrangement. The corresponding 3-substituted 2-(phenylsulfenyl)indoles were studied in a Pummerer-like transformation induced by Stang's reagent, PhI(CN)OTf. The resultant 3,3-spirocyclic 2- (phenylthio)indolenines were obtained in very good yields directly from the thioether compounds, thus shortening the route to the desired 3,3-spirocyclic oxindoles.
School Location:USA - Pennsylvania
Source Type:Master's Thesis
Date of Publication: