Studies on a catalytic cadogan cyclization by PI̳I̳I̳/PV̳=O redox cycling

Thesis: S.M., Massachusetts Institute of Technology, Department of Chemistry, 2018.Cataloged from PDF version of thesis. The double underlined I̳I̳I̳ and V̳ in title on title page appear as superscript capital letters.Includes bibliographical references.Organophosphorus reagents offer potential for developing catalytic protocols by inclusion of a reductant such as hydrosilanes to (re)generate the chemically active phosphine in situ. In our research, we have successfully adapted this concept to the Cadogan reductive cyclization by using a strained 4-membered phosphetane precatalyst, which proved to be more competent than acyclic and 5-membered analogs for P(III)/P(V)=O redox cycling. A variety of substrates were found to successfully undergo catalytic Cadogan indazole cyclization. The mechanism of the cyclization has been expanded. The resting state of phosphorus was determined to be the P" phosphetane, and this phosphetane proved to be 8 times faster than the acyclic n-Bu₃P at driving the reductive cyclization of N-phenyl o-nitrobenzaldimine to 2-phenylindazole. A nitrosoarene, presumed an intermediate in the overall cyclization, was found to undergo cyclization under reaction conditions. In addition, a new unique oxazaphosphetane was observed as an intermediate during the course of cyclization, which may lead to a more complete understanding of other-phosphorus mediated deoxygenations, including nitro reduction. Initial studies in nitro reduction have been undertaken, though further work is necessary to fully develop a phosphorus-mediated catalytic protocol.by Tyler S. Harrison.S.M