N-C bond formation

Within the aim to directly form nitrogen-element bonds from N2, N-C bond formation has a lot of attention to generate amines or N-heterocycles. So far, catalytic systems have not been shown but many stoichiometric examples are realised, both with a retained N-N bond or after full cleavage of the triple bond.^126,127 Within this subchapter, some historical, or promising, or for this work especially relevant examples are discussed.

In 1969, Volpin showed N-C bond formation via reacting N2 with [TiCl2(Cp)2] in presence of excess phenyllithium. Besides ammonia, aniline and ortho-aminodiphenyl are formed showcasing C-N bond formation. The fate of the Ti-fragment remains unclear and the N-incorporated products are only obtained in low yields.¹³² Directly after, quantitative acylation of coordinated N2 was shown upon reaction of trans-[W(N2)2(dppe)2] (dppe = 1,2-bisiphenylphosphinoethane) with acetyl- and benzoyl chlorides, Scheme 24. Unexpectedly, the hydrazido complex was formed attributed to traces of water and deprotonation can yield the diazenido compound.¹³³ For related Mo systems, N-fragment release was established as highlighted by means of electrochemistry in Scheme 26 (vide infra).

Scheme 24. Left: First example of coordinated N2 acylation by Chatt.¹³³ Left: Stoichiometric silylated aniline release from N2 by Holland.¹³⁴

Very recently, an impressive example was reported by Holland for the release of N2-derived silylated aniline. Upon reduction of [Fe(η⁶-C6H6)(HC(CCH3N(2,6-(iPr)2C6H3))2)], using an excess of Na in presence of a crownether, the Fe-(η¹-C6H5) adduct is formed, see Scheme 24. This occurs via reductive induced oxidative addition of benzene and subsequent hydride abstraction.

This adduct coordinates N2 when cooling to –100 ˚C, and reduction in presence of Me3SiX (X = Br, I) leads to a surprising structure: besides silylation of the terminal nitrogen (Nβ) to form a hydrazido moiety, migration of the aryl group to the Nα occurred. Via control experiments, they propose that these reaction steps follow the same order: first silylation and then migration.

Further reduction in presence of silylhalides and benzene provides silylated aniline and amine and the regeneration of the starting complex. This reaction is very impressive, yet unfortunately, no catalysis is realised so far: the C-H activation of the benzene ligand and subsequent hydride loss require at least RT as reaction condition, at which temperature sodium and trimethylsilylhalide are unfortunately incompatible. Larger scale one-pot reactions with repeating temperature cycles and additions of the silyl reagent allowed for formation of aniline up to 85 % yield. Concomitantly, a catalytic yield of silyl amine was found: Fe-degradation products that appear over time apparently catalyse the silylation of N2.¹³⁴

Scheme 25. Stoichiometric tetra substituted hydrazido release from N2 by Xi.⁶²

Xi and co-workers recently established N-C bond functionalisation from the side-on N2-bridging Sc complex [{Sc(Cp*)(C(Bu)(NiPr)2}2(μ-η²:η²-N2)]]⁻ (Scheme 25). This species was formed upon reduction of a corresponding bridging halide-precursor under a N2-atmosphere.

Functionalisation using MeOTf forms the doubly methylated hydrazido compound, yet in low yields and accompanied by the oxidised, neutral N2-bridged compound. Likely, the Me-reagent gets reduced, reflecting the strong reducing ability of the anionic compound. Subsequent additions of MeOTf and potassium fortunately increases the yield. Starting from this hydrazido species, several transformations are possible, such as protonation, oxidation and further reaction with electrophiles. The latter allowed for regeneration of the starting precursor by

simple addition of electrophilic halides to regenerate [{Sc(Cp*)(C(Bu)(NiPr)2}2(μ-η²:η²-X)2]] (X

= Cl, Br). Via this route, tetra substituted hydrazido compounds were formed and a one-pot reaction with subsequent reduction, methylation and further reaction with benzoyl chloride yielded the product and starting precursor in circa 50 % yield. No catalytic activity is yet possible due to the incompatibility of MeOTf and the strong reductant potassium.⁶²

Both examples by Holland and Xi emphasise a mismatch of redox-potentials between the redox reagent (reductant) to re-generate the metal-N2 or metal-nitride precursor and the carbon-based reagent for C-N bond functionalisation. Substituting these redox-reagents by means of electrochemistry would at least diminish the over-potential that is now often applied (as only certain redox-potentials are available depending on the chemical reductants).

The examples of electrochemical assisted N-fragment release from defined molecular complexes are limited and this field is dominated by the work of Pickett. A first example is from 1981, starting from trans-[Mo(N2)2(dppe)2], Scheme 26. It was shown before that the Nβ of a coordinated dinitrogen can be doubly functionalised by alkyl halides, and Br(CH2)5Br forms a cyclic piperazine compound.¹³⁵ Reductive CPE of this compound at Eappl. = −2.35 V (vs. Fc^+/0) in THF under a N2-atmosphere is slow, but reveals the liberation of N-aminopiperidine in 60 % yield accompanied by the transfer of 4 electrons per Mo. No external acid is added to this reaction, and traces of water likely provide the required proton equivalents. The N2 precursor is re-formed in circa 45 % yield, allowing to formulate a synthetic cycle (see Scheme 26).¹³⁶

From the same group comes the electrochemical release of amines in 1995 and 1997.^137,138 The nitride [MoN(dppe)2], which is likely to be derived from N2 in a complex pathway (vide infra), reacts readily with electrophilic alkyl halides, of various chain lengths and functional groups.^137,139 For instance, an ester functional group containing Mo(IV) imido [Mo(NCH2C(O)OMe)Cl(dppe)2]I is formed. Upon reduction at Eappl. = −2.3 V vs. Fc^+/0 in THF in presence of phenol and N2, glycine methyl ester is released. On the Mo-side, both a bis N2- and an azavinilydene complex are formed, the latter being the result of the starting material acting as sacrificial proton donor, see Scheme 26, bottom. To prevent this and to increase the amide yield, acetic acid was examined as alternative acid. This indeed raises the amide yield up to 80 %, but the acetate coordinates the Mo-centre, which promotes the formation of hydrides and subsequently the formation of H2. Similar reactivity was also extended to only hydrocarbon substituted imides, as shown by the release of methylamine in Scheme 26, top right.¹³⁸

Scheme 26. Electrochemical C-N bond containing fragment release by Pickett. Top left: N-aminopiperidine release from [Mo(N2)2(dppe)2].¹³⁶ Top right: methylamine release from [Mo(NMe)Cl(dppe)2] in presence of phenol. Bottom:

amine release from [Mo(NCH2C(O)OMe)Cl(dppe)2]I in presence of phenol.¹³⁷

Regarding N-C bond formation, especially the generation of double or triple bonds in for instance N-heterocycles, heterocummules or nitriles are an appealing target. Focusing on reactions where the N-N bond is retained, Caulton calculated a large series of possible reactions partners for N2 (i.e. with alkynes) and identified which reactions are exothermic. For instance, the reaction of two equivalents of acetylene with N2 to pyridazine is strongly exothermic (ΔH⁰ =

−40.9 kcal mol^-1). The double or triple bonds in the products can offset the high energy required for activation of N2. Hydrazido products with a single N-N bond can be unfavourable due to electronic repulsion of the nitrogen lone pairs in close proximity.¹⁴⁰ Regarding splitting of N2, the full bond energy can be offset for instance by formation of nitriles: the bond energy of HC≡N (224 kcal mol^-1) is the same of N2 (226 kcal mol^-1)³, as will be discussed in the next Section. Here, examples of isocyanate and isonitrile are highlighted.

Kawaguchi published the reductive splitting of N2 starting from [V(ONO)(THF)] (ONO = 2,6-(3-tBu-5-Me-2-OC6H2CH2)-4-tBu-(p-tolyl)NC6H4) (Scheme 27). In the initial step, a V(IV) dimeric structure is obtained bridged by nitrides and a potassium moiety has inserted in one of the V-O arms of the ligands. Subsequent oxidation using benzoquinone restores the tridentate ligand coordination and yields terminal nitrides linked via potassium moieties in the solid state.

This nitride reacts both with CO and isonitrile XyNC, upon formation of formal V(III) adducts.

Subsequent stoichiometric release of potassium isocyanate in 80 % was established with concomitant reformation of the precursor in a multi-step procedure closing a synthetic cycle. It is not specially mentioned if large-scale one-pot reactions are tried, but it assumed that the N2 -splitting and the CO coordination reaction step are incompatible, as coordination of the latter would block all available coordination sides for N2-activation.¹⁴¹

Scheme27. Isonitrile and isocyanate formation from a vanadium nitride by Kawaguchi.¹⁴¹

A similar example is from our group by Dr. B. Schluschaβ, who reacted the nitride [WN(PNP)(CO)] as established from N2-splitting (vide supra) with CO (Scheme 28). The corresponding isocyanate species is formed via an intramolecular mechanism as was concluded from NMR spectroscopy upon labelling: reaction under ¹³CO leads to the formation of the N¹²CO⁻ analogue. Quantitative release of isocyanate was established upon reaction with TMSCl, and via a two step procedure of oxidation and irradiation, the precursor [WCl3(PNP)] is formed, which represents the entry for N2-fixation to close the synthetic cycle.⁶⁷

Scheme 28. Isocyanate formation and release from a tungsten nitride by Schneider.⁶⁷

For N-C bond formation (or N-E in general) from terminal nitrides, it is important to know whether the nitride reacts with incoming nucleophiles or electrophiles. This reactivity depends partly on the energy levels of the metal d- and nitrogen p-orbitals that form the (anti)-binding M-N π-bonds. A very schematic representation of two extreme cases is shown in Scheme 29.

When the nitrogen orbitals are lower in energy, the π-orbital will be mainly nitrogen-based: the

nitride reacts with incoming electrophiles. In the opposite case, when the metal d-orbitals are lower in energy, the π*-orbital will be mainly nitrogen based inducing reactivity with incoming nucleophiles. For early transition metals, the d-orbitals are high in energy, resulting in nitrides that react with incoming electrophiles. Moving to the right in the periodic table slowly shows a transition to nitrides that prefer reactivity with incoming nucleophiles,¹⁴² yet nitride reactions with electrophiles is more established in general.

Scheme 29. Schematic MO scheme showing one π orbital set of a metal-nitride fragment to rationalise if the nitride preferentially reacts with an incoming electrophile (left) or nucleophile (right).¹⁴²

The nitride reactivity also depends on the formal metal oxidation state, as is shown for the nitride [ReNCl(PNP)] (3^Cl), as obtained from N2-splitting (vide supra). As Re(V) nitride, it was shown to only react with strong electrophiles such as alkyl triflates. Nucleophiles as MeLi result in halide to methyl exchange on the Re-centre, without nitride involvement. Scheme 30 shows its reaction with EtOTf to [Re(NCH2CH3)Cl(PNP)]OTf, that was further reacted to liberate acetonitrile (vide infra).⁷⁹

Scheme 30. Formal metal oxidation state influence on reactivity with incoming electrophiles (left) or incoming nucleophiles (right) on N2-derived [ReNCl(PNP)].^79,143

However, oxidation of the nitride leads to different reactivity, as shown by Holland and co-workers. As predicted from its CV, [ReNCl(PNP)] is readily oxidised at mild potentials to the cationic Re(VI) species. In an attempt to form a Nnitride-O bond, its reaction with 3-chlorobenzoic acid (mCPBA) was explored, surprisingly showing Namide-O bond formation to the formal nitroxide Re(VI) compound. The weak O-Re interaction results in some donation of the lone pair

of the oxygen into the Re-Nnitride antibonding π-orbital, slightly weakening this bond. Addition of phosphines show reactivity at the Nnitride, although the resulting adduct species decompose over time. Phosphines are mainly considered nucleophilic reagents, yet can react ambiguous.¹⁴⁴ Therefore reactions kinetics for P(p-F-Ph)3, PPh3, and P(o-tolyl)3 were measured in the order of increasing electron density. As the latter phosphine reacts the fastest, their nucleophilic in this reaction is substantiated.¹⁴³ This represents an Umpolung of the reactivity character compared to the neutral Re(V) nitride. This reactivity with a nucleophile is an exemption: in the following Section N2 to nitrile transformation is discussed, for which C-N bond formation is almost exclusively based on nitrides reacting with electrophiles.