Synthetic Inorganic Chemistry Lab - 2023-bkcs-mechanochem

Mechanochemical Activation of NHC–CS2 Adducts for the Generation of N-Heterocyclic Carbenes

Subin Park, Youngsuk Kim*

Cite this article as: Bull. Korean Chem. Soc. 2023, 44, 1004.
DOI: https://doi.org/10.1002/bkcs.12782

Short Summary

This study introduces a novel, base-free mechanochemical method using ball milling at room temperature to successfully generate free N-heterocyclic carbenes (NHCs) from highly stable NHC–CS2 adducts, overcoming the high activation energy barriers that prevent traditional thermal activation.

Key Findings

Mechanochemical Success: Ball milling of stable NHC–CS2 adducts (such as IDipp–CS2 and IMes–CS2) with sulfur or selenium at 30 Hz for 2 hours at room temperature quantitatively yields free carbenes.
Thermal Activation Failure: Heating NHC–CS2 adducts in a solution phase fails to generate free carbenes and instead leads to decomposition, highlighting the necessity of mechanochemistry.
Computational Verification: Density functional theory (DFT, M06-2X/def2-SVP) calculations reveal that C–C bond cleavage in NHC–CS2 is energetically uphill with a high activation barrier (ΔG‡ = 32.0 kcal/mol for IDipp–CS2), which explains the failure of thermal activation.
Superior Precursor Stability: Unlike NHC–CO2 adducts that slowly decompose in air and moisture, NHC–CS2 adducts display excellent bench-top stability, making them highly practical carbene synthons.

Abstract

Stable N-heterocyclic carbenes (NHCs) have garnered significant attention in synthetic chemistry due to their versatile applications. In this study, we explored a novel mechanochemical method for the generation of free carbenes, which could be a good complement to traditional approaches that require strong bases or reductants. Ball milling of NHC–CS2 adducts at room temperature successfully resulted in the quantitative formation of free carbenes that can be subsequently trapped by sulfur or selenium. Importantly, heating NHC–CS2 adducts in solution phase did not lead to the successful generation of free carbenes, in agreement with the high activation energy required for NHC–CS2 dissociation. These findings underscore the potential of ball milling as a robust and versatile approach for generating NHCs from stable NHC-small molecule adducts, and opens new avenues for developing mechanochemical strategies for generating valuable NHC-derived compounds.

Keywords: N-Heterocyclic carbene, Mechanochemistry, Adduct, Bond activation, Small molecule activation

The Challenge of Generating Free NHCs

Stable N-heterocyclic carbenes (NHCs) are indispensable in modern synthetic chemistry, serving as powerful ligands for transition metals and main group elements. However, generating free NHCs typically requires azolium salts and strong bases, or the use of strong reducing agents like potassium metal to desulfurize thioureas. While masked carbenes (such as NHC–CO2 adducts) offer a base-free alternative through decarboxylation, they suffer from poor stability under ambient air and moisture. Conversely, NHC–CS2 adducts are easily synthesized and highly stable, but releasing the free carbene from them is notoriously difficult due to the exceptionally strong C–C bond.

Overcoming High Activation Barriers with Mechanochemistry

We hypothesized that the robust NHC–CS2 adduct could be activated without harsh chemical reagents if sufficient mechanical energy was applied. Our initial thermal experiments confirmed previous reports: simply heating the IDipp–CS2 adduct in an acetonitrile solution resulted in decomposition rather than a clean loss of CS2. However, when we transitioned to mechanochemical conditions using a stainless steel ball mill at room temperature, the reaction trajectory completely shifted. The mechanical force successfully bypassed the +32.0 kcal/mol activation barrier, smoothly cleaving the C–C bond and allowing the released free carbenes to be efficiently trapped by sulfur or selenium in up to 97% isolated yields.

Significance and Future Applications

This research establishes NHC–CS2 adducts as highly practical, bench-stable synthons for free NHCs. By utilizing mechanochemical activation, researchers can now generate valuable NHC-derived compounds without the need for strong bases, reductants, or complex inert-gas techniques. This opens new avenues for green and solid-state synthesis in organometallic chemistry.

Author's Manuscript (PDF)

2024-bkcs-mechanochem.pdf