Catalytic C–H Alumination of Thiophenes: DFT Predictions and Experimental Verification

08 November 2022, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

A computational model for the palladium-catalysed C–H functionalisation of thiophenes with aluminium hydride reagents has been developed. This model predicts metalation should occur exclusively at the 2-position of the heterocycle. While related 2-metallated furans are known to undergo a ring-expansion reactions, further calculations suggest that the thiophene-derived organoaluminium compounds should be both kinetically and thermodynamically stable with respect to ring-opening. This model is supported by experimental data. Selective C–H alumination of thiophene, 2-methylthiophene, 2-methoxythiophene, and benzothiophene was achieved using [Pd(PCy3)2] as a catalyst with loadings as low as 0.02 mol%. Even under extremely forcing conditions (200 ºC) there was no evidence for a ring-opening event. The differences in selectivity between furan and thiophene systems are rationalised in terms of the stabilisation of a key intermediate (and transition state) in the pathway for furan ring opening by a strong dative O–Al interaction.

Keywords

C-H functionalisation
alumination
C-H borylation
palladium catalysis
mechanism

Supplementary materials

Title
Description
Actions
Title
Supporting Information
Description
Experimental and computational details
Actions
Title
crystallographic data
Description
cif file
Actions

Comments

Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.