Isolating Free Carbenes, their Mixed Dimers and Organic Radicals

Summary

We present protocols for the isolation of stable heterocyclic carbenes. The synthesis of a cyclic (alkyl)(amino) carbene (CAAC) and an N-heterocyclic carbene (NHC) is demonstrated using filter cannulas and Schlenk technique. We furthermore present the synthesis of the related oxygen-sensitive, electron-rich mixed “Wanzlick dimer” and the reduced stable organic radical.

Abstract

Protocols for the isolation of the commonly employed cyclic (alkyl)(amino) carbene (CAAC) and N-heterocyclic carbene (NHC) are reported. Furthermore, the synthesis of their mixed CAAC–NHC “Wanzlick” dimer and the synthesis of the related stable organic “olefin” radical are presented. The main goal of this manuscript is to give a detailed and general protocol for the synthetic chemist of any skill level on how to prepare free heterocyclic carbenes by deprotonation using filter cannulas. Due to the air-sensitivity of the synthesized compounds, all experiments are performed under inert atmosphere using either Schlenk technique or a dinitrogen filled glovebox. Controlling Wanzlick’s equilibrium (i.e., the dimerization of free carbenes), is a crucial requirement for the application of free carbenes in coordination chemistry or organic synthesis. Thus, we elaborate on the specific electronic and steric requirements favoring the formation of dimers, heterodimers, or monomers. We will show how proton catalysis allows for the formation of dimers, and how the electronic structure of carbenes and their dimers affects the reactivity with either moisture or air. The structural identity of the reported compounds is discussed based on their NMR spectra.

Introduction

More than half a century ago, Wanzlick reported arguably the first attempts to synthesize N-heterocyclic carbenes^1,2,3. However, instead of isolating the free carbenes, he succeeded only in characterizing their dimers. This observation prompted him to suggest an equilibrium between the olefin dimer and the respective free carbenes, which is now commonly referred to as “Wanzlick’s equilibrium” (Figure 1, I.)^4,5,6. Later on, it w....

Protocol

CAUTION: Carry out all syntheses in a well-ventilated fume hood. Wear appropriate personal protective equipment (PPE) including a lab coat and safety goggles.

NOTE: The starting materials were synthesized according to the literature: 1-(2,6-diisopropylphenyl)-2,2,4,4-tetramethyl-3,4-dihydro-2H-pyrrol-1-ium tetrafluoroborate (1^prot) (For the synthesis of CAACs, see:^{18,30,.......}

Discussion

Herein, we present a general and adaptable protocol for the synthesis of stable carbenes (NHC, CAAC) and their electron rich dimer. All steps can readily be upscaled to at least a 25 g scale. Crucial for a successful synthesis are the strict exclusions of moisture (air, respectively) for the synthesis of the carbenes, and of oxygen (air, respectively) for the electron rich olefin. The herein applied filtration cannula technique in combination with a Schlenk line is a very convenient method to separate solutions from.......

Materials

Name	Company	Catalog Number	Comments
Equipment
Glass micro fiber filter, 691, 24 mm. Particle retention 1.6 mm	VWR	516-0859
magnetic stir bar	FengTecEx	various
PTFE tape	Sigma-Aldrich	Z148814-1PAK	PTFE tape used in this manuscript was obtained from a local supplier. Tape from Sigma Aldrich should show comparable performance.
rubber septum	FengTecEx	RS112440	Joint size: 24/29
rubber septum	FengTecEx	RS111420	Joint size: 14/23
rubber septum	FengTecEx	RS111922	Joint size: 19/26
schlenk flasks	FengTecEx	various	100 mL
steel cannula	FengtecEx	C702024	Attachment of a steel joint by a machine shop not required, but facilitates preparation of filter cannula
syringe cannula	FengtecEx	S380221
Name	Company	Catalog Number	Comments
Reactants
1-(2,6-diisopropylphenyl)-2,2,4,4-tetramethyl-3,4-dihydro-2H-pyrrol-1-ium tetrafluoroborate			Synthesized according to: Jazzar, R., Dewhurst, R. D., Bourg, J. B., Donnadieu, B., Canac, Y., Bertrand, G. Intramolecular “Hydroiminiumation” of alkenes: Application to the synthesis of conjugate acids of cyclic alkyl amino carbenes (CAACs). Angewandte Chemie International Edition 46 (16), 2899-2902, (2007).
1,3-dimethyl-4,5-dihydro-1H-imidazol-3-ium iodide			Synthesized according to: Benac, B. L., Burgess, E. M., Arduengo, A. J. 1,3-Dimethylimidazole-2-Thione. Organic Synthesis 64, 92, (1986).
potassium hexamethyldisilazide	Sigma-Aldrich	324671-100G	CAS 40949-94-8
silver trifluoromethanesulfonate	Sigma-Aldrich	85325-25G	CAS 2923-28-6
Name	Company	Catalog Number	Comments
Solvents
acetonitrile-D3	Deutero	00202-10m	distilled from CaH2, stored over activated molecular sieves
benzene-D6	Deutero	00303-100ml	dried over activated molecular sieves, stored over potassium
diethylether	-	-	dried by two-column, solid-state purification system and degassed by three freeze-pump-thaw cycles, stored over activated molecular sieves
hexanes	-	-	dried by two-column, solid-state purification system and degassed by three freeze-pump-thaw cycles, stored over activated molecular sieves
tetrahydrofuran	-	-	dried by two-column, solid-state purification system and degassed by three freeze-pump-thaw cycles, stored over activated molecular sieves
toluene	-	-	dried by two-column, solid-state purification system and degassed by three freeze-pump-thaw cycles, stored over activated molecular sieves