DFT-Assisted Design and Evaluation of Bifunctional copper(I) Catalysts for the Direct Intermolecular Addition of Aldehydes and Ketones to Alkynes

20 April 2018, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

Bifunctional catalysts containing discrete metal pi-acid and amine sites were designed and investigated for the direct intermolecular addition of aldehydes and ketones to unactivated alkynes. Despite prior reports of intramolecular (Conia-ene-type) reactions and confirmation here that Cu(I)-based catalysts are effective, NMR studies indicated that a dual catalytic approach using separate amine and pi-acid catalysts may not be feasible for intermolecular reactions due to undesirable enamine competition with alkynes for metal complexation. Bifunctional precatalysts were designed with tridentate ligands and potentially hemilabile heterocyclic spacers, expected to be suitable for the binding of pi-acidic metals such as copper (I) and silver (I). The structures of the designed catalysts were computed using density functional theory (DFT), and the relative energies of putative catalytic intermediates were estimated. The calculated free energy changes upon carbon–carbon bond formation were used to prioritize catalyst designs, and several modular precatalysts were selected and prepared, with a focus on thiazole-containing systems synthesized via a 9-step sequence. Catalysts were screened for the direct addition of aldehydes and ketones to several internal and terminal alkynes. The precatalysts were combined with several different transition metal salts, and their structures studied with 1H NMR and x-ray crystallography. Despite the lack of observed intermolecular reactions, DFT calculations of putative catalyst intermediates appears to be a promising strategy for the design and prioritization of bifunctional catalysts for C–C bond formation, and the combined results suggest that more rigid complexes may be necessary to catalyze direct intermolecular additions of aldehydes/ketones to alkynes.

Keywords

alkenylation
copper(I)
alkynes
Hybrid catalysts
Organocatalysis
aldehyde
ketone
DFT
catalyst design

Supplementary materials

Title
Description
Actions
Title
2018 04 19 Additions to alkynes SI
Description
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.