Intermolecular Nucleophilic Additions to Thermally-generated Benzynes and Mechanistic Studies

Abstract

ortho-Benzynes compose a highly versatile class of reactive intermediate in organic chemistry. They can be trapped in situ by a variety of nucleophile-electrophile pairs or enter into pericyclic reactions to generate multi-substituted arene moieties that can be further functionalized to different target molecules. Compare to traditionally generated benzynes (through elimination of arene derivatives), the thermally generated benzynes [through the hexadehydro-Diels–Alder (HDDA) reaction] provide both a synthetic approach to functionalized arene derivatives and unusual modes of reactivity. In this Thesis, I will emphasize some of the more recent aspects of HDDA reactions as a tool for synthesizing multi-functionalized arene derivatives, along with divergent reaction pathways and mechanistic insight. Details of this Thesis include (i) the phenol-ene reaction to construct biaryl moieties (Chapter 2), (ii) reaction of HDDA-generated benzynes with N-heterocycles (Chapter 3), (iii) an atypical mode of “1,3-dipolar” cycloaddition reaction between benzynes and electron-deficient thioamides (Chapter 4), (iv) divergent reactivity by glycidol analogs: ring cleavage via pinacol-like rearrangements vs. oxirane fragmentations (Chapter 5), and (v) total synthesis of isohericerin using the HDDA reaction (Chapter 6).