Indole Arynes in organic synthesis : discovery and applications for the total synthesis of complex natural products

Arynes and heteroarynes are very important and useful reactive intermediates with many applications in organic synthesis, including natural products total synthesis. Although benzyne, the parent and most famous aryne, has itself been known for over 50 years, arynes derived from the ubiquitous indole nucleus were virtually unknown before our work. The absence of these heteroarynes from the literature was surprising, given the potential utility of these reactive intermediates for an attractive entry into the indole alkaloid class of important and architecturally complex natural products. Some deceptively simple and other more unambiguously complex targets include such members as the trikentrins, herbindoles, teleocidins, nodulisporic acids, and penitrems to name just a few representative examples. We discovered the first indole arynes, namely the 5,6- and 6,7-indole arynes (aka indolynes), and provided a vastly superior preparation of the 4,5-indole aryne as well as the others by devising a facile metal-halogen exchange and elimination protocol with o-dihaloindoles. In addition to establishing the existence of these fascinating intermediates via trapping with their furan cycloadducts, we applied them to the successful total synthesis of several important, biologically active and challenging natural products including (±)-cis-trikentrin A, (±)-herbindole A, and (±)-herbindole B. These studies opened a successful strategy for the construction of natural products-inspired libraries based on this methodology. We also conducted experimental and computational studies on the indole arynes that revealed, among other things, their unique properties and reaction profiles. The versatility of the 6,7-indole aryne in particular was evident in the many regioselective cycloadditions, ring-opening reactions, and rearrangements it exhibited.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Chemistry (UMKC)

Grantor dc:publisher

University of Missouri -- Kansas City

Year dc:date.issued

2011

Author dc:creator

• Luo, Diheng, 1976-

Advisor dc:contributor.advisor

• Buszek, Keith R.

• Herbindole
• Trikentrin A
• Indole arynes

Language dc:language.iso

en_US

Handle dc:identifier.uri

http://hdl.handle.net/10355/10629

OAI identifier oai:identifier

oai:mospace.umsystem.edu:10355/10629