Studies in duality : discovering a dual catalytic amination reaction and investigating the origin of biphilicity in phosphacycles

Abstract

First, the development of a novel C-H amination strategy using both a Cu(II) Lewis acid and an organic hydrogen atom transfer (HAT) catalyst to activate benzylic C-H bonds adjacent to aromatic azaheterocycles is described. This simple method demonstrates very high selectivity towards aromatic azaheterocycles without using exogenous directing groups and affords excellent site selectivity in substrates with more than one reactive position. A wide range of aromatic azaheterocyclic structures not compatible with previously reported catalytic systems have proven to be amenable to this approach. Mechanistic investigations indicate a possible radical-mediated H-atom abstraction for select substrates, which would stand in contrast to known closed-shell Lewis acid catalyzed processes. Second, the synthesis and analysis of a series of three homologous [alpha],[alpha],[alpha]',[alpha]'-tetramethyl-[subscript 1]-phenylphosphacycles in order to investigate the theory that 4-membered ring phosphacycles - phosphetanes - are maximally biphilic as a result of bond angle compression that minimizes the HOMO-LUMO gap is reported. Analysis of [superscript 31]P NMR principal components validates the decrease in HOMO-LUMO gap as the intra-ring bond angle is compressed in the synthesized series as predicted by TD-DFT computations; however, ¹J[subscript P-Se] coupling constants, cyclic voltammograms and UV-Vis measurements are less conclusive. Computational modeling of the (3+1) cheletropic addition of the phosphacycles to nitrobiphenyl as a measure of the biphilicity reveals relative activation barriers within computational error for all but the smallest ring, indicating that the effect of intra-ring bond angle compression on phosphorus biphilic reactivity is a generally subtle effect.