The Ambivalent Chemistry of a Free Anionic N‐Heterocyclic Carbene Decorated with a Malonate Backbone: The Plus of a Negative Charge

Abstract

The anionic heterocycle "[maloNHC](-)", ([1](-)), is the archetype of a growing family of N-heterocyclic carbenes incorporating an anionic backbone; here, a malonate group. A comprehensive experimental exploration of its chemistry as a free entity (in the form of its lithium salt [1]·Li) is presented, and rationalized using DFT calculations at the B3LYP/6-31+G** level of theory. For the sake of comparison, similar computations were performed on other representative carbene types. Reactions of [1]·Li with a broad series of electrophilic reagents were used to ascertain its intrinsic nature as a nucleophilic carbene. Unexpectedly, [1]·Li was also seen to react with the nucleophilic tert-butylisocyanide, to give an anionic ketenimine, which could be subsequently derivatized, either into an imine by protonation of the ketenimine moiety, or into a neutral ketenimine by alkylation of the intracyclic malonate moiety. Further experiments on the electrophilic behavior of [1]·Li revealed its unexpected reactivity toward p-chlorobenzaldehyde, resulting in a formal C-H activation and the first structurally characterized keto-tautomer of the Breslow intermediate. Finally, [1]·Li remarkably activates polar E-H bonds, including N-H bonds from ammonia and amines, Si-H bonds, and B-H bonds. Importantly, DFT calculations indicate the importance of counterion effects. In particular, the key to the observed reactivity appears to be a modulation of energy levels associated with a dynamic variability of the Li-O distance between the remote malonate group and the counterion.

Experimental Assessment of the π‐Acidity of Anionic and Neutral Malonate‐Derived N‐Heterocyclic Carbenes

“…While the phosphorus atoms resonate at δ P = 37.8 and 38.3 ppm in the latter adducts, the signal of the phosphorus atom in compound 2 was found at δ P = 74.8 ppm. Such a lower‐field chemical shift was expected as we previously observed the same downfield shift for the diphenylphosphenium adduct of malo NHC 1· PPh 2 [ δ P = 16.1 ppm] compared to the more classical NHC · PPh 2 adducts [–5 ppm < δ P < –18 ppm] . The very high sensitivity of compound 2 towards moisture precluded its further characterization by mass spectrometry or elemental analysis.…”

“…It was fully characterized by spectroscopic and analytical techniques. Noteworthy, unlike the corresponding thiourea [ 1 =S] – that was protonated on the sulfur atom, it appeared that the protonation of [ 1 =Se]Li occurred exclusively at the central carbon atom of the malonate unit. Diagnostic signals for this regioselectivity are the quadruplet at δ = 3.78 ppm ascribed to the C 5 ‐ H proton, and the corresponding doublet at δ = 1.84 ppm for the apical methyl group in the 1 H NMR spectrum.…”

“…(a) Previously reported insertion of free anionic NHC [ 1 ]Li into various E–H bonds; (b) Calculated Kohn–Sham energy values of the σ and π* molecular orbitals of [ 1 ]M, along with their representation for [ 1 ]Li (calculations made at the B3LYP/6‐31+G** level of theory); (c) malo NHC‐derived carbenes considered in this study.…”

N‐Heterocyclic Carbenes as Key Intermediates in the Synthesis of Fused, Mesoionic, Tricyclic Heterocycles

“…[10] They are also highly efficient nucleophilic organocatalysts. [11] Conversely,a part from the use of NHCs as partners for the activationo fs mall molecules, [12] there are very few examples of synthetic protocols, which occur through the intermediacy of an NHCa so ne of the key reactive substrateso ri ntermediates. In as eminal contribution,C avell and co-workers reported on the decomposition of alkyl-and aryl-NHC-Pd II complexes through reductive elimination to form C2-substituted imidazolium salts and palladium black.…”

“…Molecular structure of 5a (ellipsoids are drawn at the 30 %p robability level).H ydrogen atoms and solvent molecule wereo mitted for clarity. Selectedbondlengths []: C12ÀN2 1.3565(14), C12ÀN1 1.3288(14), N2ÀC23 1.3853(14), C23ÀC241 .3909(16),C24ÀC25 1.4130(16), C25ÀC261 .3774(17), C26ÀC271.4255(17),C27ÀC10 1.3792(16),C3ÀC10 1.4321(15),C2ÀC3 1.4411(15), C2ÀC121 .4847(15), C2ÀO1 1.2519(12).…”