Semester
Summer
Date of Graduation
2000
Document Type
Thesis
Degree Type
MS
College
Eberly College of Arts and Sciences
Department
Chemistry
Committee Chair
Bjorn C. Soderberg.
Abstract
A novel synthesis of indoles having electron withdrawing substituents in the 3-position has been developed. Various 2-nitrostyrenes were prepared via Stille coupling of 2-tributyl stannyl-2-propenoic acid ethyl ester with substituted 2-bromo-l-nitrobenzenes. Alternatively, sequential vicarious nucleophilic substitution of substituted nitrobenzenes and Knoevenagel condensation with formaldehyde was used to prepare 2-nitrostyrenes. Palladium catalyzed N-heteroannulation of 2-nitrostyrenes yielded indoles in 61--99%. For example, reaction of a 0.5 M solution of 1,1-dimethylethyl 2-(1-nitro-2-napthyl)propenoate (65) in N,N-dimethylformamide with carbon monoxide (4 atm), in the presence of a catalytic amount of bis(dibenzylideneacetone)palladium(0) (6 mol %), 1,3-bis(diphenylphosphino)propane (6 mol %), and 1,10-phenanthroline monohydrate (12 mol %), gave 1H-benzo[g]indole-3-carboxylic acid tert-butyl ester (83) in 99% isolated yield. Substituents on the benzene ring such as methoxy, ester, and halide groups were compatible with the reaction conditions all giving indoles. Additionally, a substituent in the 2-position of the indole can be introduced using aldehydes other than formaldehyde in the condensation step.;This methodology for the preparation of 3-substituted indoles is a key step in a proposed total synthesis of indolactam V. A retrosynthetic analysis of indolactam V affords 1-trifluoromethanesulfonyloxy-2-bromo-3-nitrobenzene, allyl glycine, and L-valine as the starting materials. Coupling of L-valine with 1-trifluoromethanesulfonyloxy-2-bromo-3-nitrobenzene in the presence of a palladium catalyst unexpectantly gave amination between the nitro and the triflate functionalty. This led to a study of the amination of various bromo-triflate and bromo-nitro-triflate substituted benzenes using cesium carbonate, palladium acetate, 2,2'bis(diphenylphosphino)-1,1 '-binapthyl, and morpholine. The purpose of this was to evaluate the site of amination, that is, bromo vs triflate, and examine if conditions can be developed to selectively substitute one.
Recommended Citation
Turner, Michael Robert, "Novel palladium-catalyzed synthesis of 3-substituted indoles and its application toward the total synthesis of indolactam V" (2000). Graduate Theses, Dissertations, and Problem Reports. 1148.
https://researchrepository.wvu.edu/etd/1148