Iodocyclisation of Electronically Resistant Alkynes: Synthesis of 2-Carboxy (and sulfoxy)-3-iodobenzo[b]thiophenes*

Shuqi Chen; Bernard L. Flynn

doi:10.1071/CH20218

RESEARCH ARTICLE

Previous Contents Vol 74(1)

Iodocyclisation of Electronically Resistant Alkynes: Synthesis of 2-Carboxy (and sulfoxy)-3-iodobenzo[b]thiophenes*

Shuqi Chen

^A and Bernard L. Flynn

^A ^B

+ Author Affiliations

- Author Affiliations

^A Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Vic. 3052, Australia.

^B Corresponding author. Email: bernard.flynn@monash.edu

Australian Journal of Chemistry 74(1) 65-76 https://doi.org/10.1071/CH20218
Submitted: 13 July 2020 Accepted: 23 September 2020 Published: 23 October 2020

Abstract

The iodocyclisation of alkynes bearing tethered nucleophiles is a highly effective method for the construction and diversification of heterocycles. A key limitation to this methodology is the 5-endo-dig iodocyclisation of alkynes that have an unfavourable electronic bias for electrophilic cyclisation. These tend to direct electrophilic attack of the iodonium atom to the wrong carbon for cyclisation, thus favouring competing addition reactions. Using our previously determined reaction conditions for the 5-endo-dig iodocyclisations of electronically resistant alkynes, we have achieved efficient synthetic access to 2-carboxy (and sulfoxy)-3-iodobenzo[b]thiophenes. The corresponding benzo[b]furans and indoles were not accessible under these conditions. This difference may arise due to the availability of a radical mechanism in the case of iodobenzo[b]thiophenes. The 2-carboxy functionality of the iodocyclised products can be further employed in iterative alkyne-coupling iodocyclisation reactions, where the carboxy group or an imine (Schiff base) partakes in a second iodocyclisation to generate a lactone or pyridine ring.

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