Alkene Amination Reactions Enabled by Organoselenium Catalysis

Abstract

The discovery of new modes of catalytic reactivity represents the forefront of organic methodology. Many important transformations are catalyzed by expensive transition metal catalysts. Replacing these with cheaper, more abundant alternatives is an important goal. This dissertation explores the development of new catalytic oxidative transformations enabled by organoselenium catalysts. The focus of this work is on using these organoselenium catalysts to enable a variety of amination reactions.Herein, the development of three oxidative allylic C-H amination reactions enabled by novel organoselenium catalysis is presented: the allylic C-H amination of alkenes using sulfonamides, the expansion of this transformation to utilize carbamates and trifluoroacetamide as nucleophiles, and the direct formation of conjugated sulfonyl imines from alkenes. The development of a 1,2-diamination of alkenes using these same organoselenium catalysts is also discussed. A novel selenium-catalyzed C-H amination reaction was achieved using either phosphine or imidazolium-based ligands on selenium with diacetoxyiodobenzene as an oxidant and sulfonamides serving as the amine sources. This transformation enabled amination for all alkene substitution patterns with a highly predictable regiochemical outcome. An extensive number of functional groups were tolerated by these reaction conditions and numerous synthetically valuable sulfonamide and sulfamate nucleophiles were found to be suitable coupling partners for this reaction. Pharmaceutical drugs, natural products, and terpenoids were derivatized using this method demonstrating its power for late-stage functionalization. A direct protocol for the synthesis of conjugated sulfonyl imines from highly substituted alkenes was also developed. This reaction was realized by increasing the oxidizing power of the amination reaction conditions and through the careful optimization of the catalyst and sulfonamide coupling partner. The use of the triarylphosphine selenide catalysts were critical in the development of this reaction by suppressing a competitive diamination reaction. The use of electron rich sulfonamides was found to be important for high yields of the desired imine products. Various novel derivatizations of the imine products were developed including a transimination protocol. An expansion of the selenium-catalyzed C-H amination reaction described above to incorporate carbamate nucleophiles was also realized. The use of N-tert-butyl imidazolium ligand on selenium proved critical in enabling good yields for this transformation. Numerous synthetically valuable carbamate nucleophiles including benzyl, allyl, and trimethylsilyl ethyl carbamates were found to be competent coupling partners in this reaction. The transformation was successful for a variety of 1,1-di- and tri-substituted olefins offering unprecedented direct access to allylic carbamates through catalytic C-H activation. Trifluoroacetamide was also shown to be a suitable coupling partner for this reaction. The late stage C-H amination of natural products and terpene derivatives was demonstrated. A novel selenium catalyzed 1,2-diaddition of alkenes was also demonstrated. Unlike the previous three reports, this transformation proceeds via formation of a seleniranium intermediate. The use of TMSOTf as a fluoride scavenger was critical to prevent the addition/elimination pathway typically observed for oxidative selenium alkene reactions. High yields were enabled for this transformation using phosphoramide ligands on selenium. The diamination reaction was demonstrated on an extensive variety of terminal and 1,2-disubstituted alkenes in high yields.