TANDEM BENZANNULATION-CYCLIZATION STRATEGIES FOR THE SYNTHESIS OF HIGHLY SUBSTITUTED INDOLES

Tandem benzannulation-cyclization strategies were developed for the synthesis of highly substituted indoles. The benzannulation strategies involved the reaction of vinylketenes (or aryl ketenes) with ynamides or with ynehydrazides to afford highly substituted phenols via a pericyclic cascade mechanism. The vinylketenes were generated via the Wolff rearrangement of diazo enones or via the 4π electrocyclic ring-opening of cyclobutenones. Two cyclization approaches were studied: (1) an intramolecular acid-promoted cyclization, and (2) a Fischer indole cyclization. The first approach required the development of a thermal benzannulation protocol and was applied in a concise total synthesis of (-)-herbindoles A-C and (+)-trans-herbindole A. The second approach required the development of a new benzannulation variant that employed ynehydrazides as the ketenophile.

Name thesis:degree_name

Doctoral

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Chemistry

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2023

Author dc:creator

• Faialaga, Nathan H.

Advisor dc:contributor.advisor

• Danheiser, Rick L.

Statement dc:rights

• In Copyright - Educational Use Permitted
• Copyright MIT

Licence dc:rights.uri

• http://rightsstatements.org/page/InC-EDU/1.0/

Handle dc:identifier.uri

https://hdl.handle.net/1721.1/150560

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/150560