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STUDIES IN AZIRIDINE-ALLYLSILANE CHEMISTRY: EXTENSION OF SCOPE

Lapinsky, David J
http://rave.ohiolink.edu/etdc/view?acc_num=osu1038954949

Abstract Details

2002, Doctor of Philosophy, Ohio State University, Pharmacy.
We have been interested in developing methodology for the synthesis of alkaloids and other heterocycles that could serve as potential drug candidates. In this regard, we have discovered a method that could serve as a useful procedure for the synthesis of these molecules. Specifically, we can convert an aziridine-allylsilane to either the g-amino olefin, the silylated azabicycle, or the desilylated azabicycle. In order to extend the scope of our methodology, the synthesis and intramolecular cyclizations of C-2 aziridine-allylsilanes were examined. Due to an initial failure in our traditional allylsilane-organocuprate / N-Ts-aziridine methanol approach, a new converse strategy for the synthesis of C-2 aziridine-allylsilanes was developed. The Suzuki cross-coupling reaction of olefinic aziridines proved to be an effective route for the synthesis of C-2 aziridine-allylsilanes and substituted aziridines. We observed that connection of C-2 of an allylsilane to a tethered aziridine ring yields exocyclic g-amino olefins and desilylated azabicyclo[x.2.1]-systems upon cyclization with BF3.OEt2. Furthermore, manipulation of a specific exocyclic g-amino olefin provided access to an azabicyclo[3.3.1]nonane. This methodology should be useful for the preparation of natural products and pharmacologically active agents containing these bicyclic heterocyclic systems. With intentions of applying our methodology to the synthesis of natural products and studying the effect of a substituted tether on the diastereoselectivity of intramolecular C-3 aziridine-allylsilane cyclizations, a C-3 aziridine-allylsilane containing a methyl substituent on the tether was envisioned based on a proposed retrosynthesis of (+)-a-skytanthine. The target aziridine-allylsilane was synthesized via Suzuki cross-coupling of a known allylsilane-vinyl iodide with a chiral aziridine-olefin containing the key methyl substituent. Unfortunately, the diastereoselectivity of products resulting from the cyclization of a tether-substituted C-3 aziridine-allylsilane did not improve. In fact, the tether-substituted aziridine-allylsilane offered an additional mode of cyclization that was not seen in our previous cyclizations of C-3 aziridine-allylsilanes. A hydroboration-oxidation / Mitsunobu reaction sequence was performed on select g-amino olefin cyclization products to form 3-azabicyclo[4.3.0]nonane and 2-azabicyclo[3.3.1]nonane frameworks. One of the 3-azabicyclo[4.3.0]nonanes synthesized represents the tosylated analog of a known natural product, nor-a-skytanthine.
Robert Brueggemeier (Advisor)
256 p.
Chemistry, Pharmaceutical
aziridines; allylsilanes; nitrogen heterocycles; bicyclic heterocyclic compounds

Recommended Citations

Citations

  • Lapinsky, D. J. (2002). STUDIES IN AZIRIDINE-ALLYLSILANE CHEMISTRY: EXTENSION OF SCOPE [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1038954949

    APA Style (7th edition)

  • Lapinsky, David. STUDIES IN AZIRIDINE-ALLYLSILANE CHEMISTRY: EXTENSION OF SCOPE. 2002. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1038954949.

    MLA Style (8th edition)

  • Lapinsky, David. "STUDIES IN AZIRIDINE-ALLYLSILANE CHEMISTRY: EXTENSION OF SCOPE." Doctoral dissertation, Ohio State University, 2002. http://rave.ohiolink.edu/etdc/view?acc_num=osu1038954949

    Chicago Manual of Style (17th edition)

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