@article{THESIS,
      recid = {1682},
      author = {Elkin, Pavel Konstantinovich},
      title = {Advances In Pericyclic Reactions: I. Novel Highly Reactive  Aminodienes For Diels-Alder Reactions II. Dearomative  Indolo-Claisen Rearrangements III. Synthetic Studies  Towards Hinckdentine A And Melonine},
      publisher = {University of Chicago},
      school = {Ph.D.},
      address = {2018-06},
      number = {THESIS},
      pages = {384},
      abstract = {Pericyclic reactions are, arguably, one of the most  important classes of reactions in organic synthesis. Their  ability to provide access to complex and sterically  hindered structures in a regio- and stereo-controlled  manner in a highly atom economical fashion has played a  crucial role in the total synthesis of innumerable complex  natural products over the past several decades. Despite the  significant interest from the synthetic community, multiple  aspects of pericyclic reactions still remain unexplored. In  this dissertation, we focused our research efforts on two  different classes of pericyclic reactions, the Diels-Alder  reaction and Claisen rearrangement, and their application  towards the total synthesis of the natural products  Hinckdentine and Melonine.

The first part of this  dissertation (Chapter 2) describes the development of a  novel class of doubly activated dienes –  oxazolidinebutadienes – for the Diels-Alder reactions.  Previously, doubly-activated dienes, specifically  Danishefsky’s diene, Rawal’s diene and Brassard’s diene,  have found enormous popularity in the synthetic community  due to their high reactivity towards a range of  dienophiles, including heterodienophiles. Another reason  for their popularity is the ability to easily convert the  resulting Diels-Alder cycloadducts into substituted  cyclohexenones, dihydropyranones and phenols, thus  significantly expanding the scope and application of the  Diels-Alder reaction. While these dienes provide direct  access to key building blocks of many complex molecules, it  produces only 4,4-disubstituted cyclohexenones, limiting  the applications of these useful 4 components. We  envisioned that the development of other activation  patterns on dienes could expand the utility of the  Diels-Alder reaction in organic synthesis and provide a  useful tool to construct the core fragments of multiple  natural products. In this vein, we developed a novel class  of doubly activated 1-amino-1-oxo-1,3-butadienes, which  proved to be highly reactive dienes in the Diels-Alder  reaction with a variety of common dienophiles, giving rise  to corresponding cyclohexenes in high yields and with high  endo-selectivity. Hydrolysis of the resulting cyclohexenes  gave rise to 6,6-disubstituted cyclohexenones, a valuable  intermediate for the total synthesis of various natural  products. Brief kinetic studies revealed that our newly  developed diene is ~100 times more reactive than  Danishefsky’s diene.

The second part of this dissertation  (Chapter 3) is focused on the development of a  3,3-sigmatropic rearrangement as an efficient tool to  access 2,2-disubstituted indolines, the core motive of  multiple bioactive natural products. The downside of the  approaches to the 2,2-disubstituted indolines, that have  been demonstrated to date, is a limited substrate scope -  in many cases minor modifications in the structures of the  compounds dramatically change the reaction outcome. We  envisioned that the Claisen rearrangement of the indole  alcohols, which can be easily accessed from the  corresponding ketones and aldehydes, can provide a general  route to access various substituted indolines. Our research  indicated that, among other sigmatropic rearrangements,  only the Meerwein-Eschenmoser-Claisen rearrangement was  able to provide access to the desired indolines in a nearly  quantitative yield, starting from the corresponding indole  alcohols. Use of enantioenriched alcohols, which can be  accessed from the corresponding ketones utilizing the  Corey-Bakshi-Shibata asymmetric reduction protocol, as  substrates for rearrangement resulted in a complete  transfer of chirality, providing the corresponding  2,2-disubstituted indolines in an enantioenriched  fashion.

The third part of this dissertation (Chapters  4-5) describes the application of our newly developed  indolic Claisen rearrangement towards the total synthesis  of two distinctive indoline-based alkaloids, Hinckdentine A  and Melonine. Successful application of our methodology  provided an efficient access to the core structures of  these natural products, which were further elaborated to  complete the formal synthesis of these complex molecules.},
      url = {http://knowledge.uchicago.edu/record/1682},
      doi = {https://doi.org/10.6082/uchicago.1682},
}