Iminophosphoranes (also known as phosphine imides, phosphinimide, phosphinimines, λ5-phosphazenes, acyclic phosphazenes) are a class of organophosphorus compounds and an acyclic subclass of phosphazenes with the general formula R3P=NR′. First reported by Staudinger and Meyer in 1919, these isoelectronic analogues of phosphine oxides and phosphonium ylides (also known as Wittig reagents) are most commonly synthesized via the Staudinger reaction or Kirsanov reaction, though alternative synthetic routes have also been developed. The P=N bond is best described as a highly polarized single bond consistent with ylidic resonance structure R3P+=N−R′, and the steric and electronic character may be tuned by varying the substituents on either the phosphorus or nitrogen. These properties allowing for interesting reactivity of iminophosphoranes as a Brønsted superbase or coordinating ligand at the nitrogen, or for [2+2] cycloadditions with the P=N bond. Iminophosphoranes have found diverse applications as ligands for homogeneous catalysis (i.e. cross coupling, polymerization, etc.), superbasic or bifunctional organocatalysts, and probes for chemical biology.
Synthesis
Staudinger Reaction The earliest synthesis of an iminophosphorane was reported by Staudinger and Meyer in 1919 from the reaction of an azide and a phosphine with nitrogen extrusion. This reaction proceeds via nucleophilic attack of the phosphine on the azide through a cis-transition state to form a phosphazide intermediate which undergoes a four-membered ring closure to expel N2 (Figure 1). Over 100 years later, the Staudinger reaction remains one of the most general and widely used methods. A variation of the Staudinger reaction, Staudinger ligation, is a highly selective bioorthogonal reaction that is prominent in chemical biology in labeling or modifying cellular environments, proteins, DNA, etc.
Kirsanov Reaction
A second notable method to synthesize iminophosphoranes is the Kirsanov reaction first reported in 1950 in which P-halogenated iminophosphoranes are accessed from phosphorus pentachloride and amine starting materials (Figure 2). In 1959 a modified Kirsanov reaction in which halogenation of a tertiary phosphine produces a phosphonium salt, which is treated in situ with a primary amine to yield the iminophosphorane (Figure 3) was published.
Other Synthetic Routes Staudinger and Kirsanov reactions are considered the two most common synthetic routes, but many other potential synthetic strategies to access iminophosphoranes have also been developed to address potential limitations. For instance, the Staudinger reaction involves high energy and potentially explosive azides, and there are some instances when azide may not be readily available. The phosphorus pentachloride and bromine reagents involved in the Kirsanov and modified Kirsanov reaction are also toxic. Examples of alternative routes include the synthesis of N-acyliminophosphoranes via iron-catalyzed imidization of phosphines with N-acyloxyamides (Figure 4, bottom) or by an iron-photocatalyzed nitrene transfer reaction with dioxazolones (Figure 4, top). Another example is the electrochemical nickel-catalyzed synthesis of N-cyanoiminophosphoranes from treating phosphines with bis(trimethylsilyl)carbodiimide (Figure 5).
Structure The precise nature of the iminophosphorane P=N bond (and more generally, P=E bonds, where E = C, N, O) has historically been the subject of much discussion. Initially, from around 1950 to 1970, the P=N bond was thought to have significant contribution from a π-type interaction between low lying d orbitals on phosphorus and the p orbitals on nitrogen due to a shortened P=N bond length relative to a single P−N bond indicated by spectroscopic studies, dipole measurements, and X-ray analyses. However, further computations in the 1980s would clearly demonstrate that d-orbitals are not significantly involved in such bonds. This model was also inconsistent with observed reactivity (i.e. cleavage of the P−N bond by metal organyls in polar solvents or susceptibility to hydrolysis, which would be difficult with a true P=N double bond).
Over time, the accepted bond model was revised to be that there is no true P−C π bond and the interaction is instead best described as a strongly polarized P+−N− bond. The shortened strengthened bond and stabilization of the phosphorus can be justified by negative hyperconjugation, in which electron density on the nitrogen p-orbital delocalizes into the 𝜎* (P−C) orbital. This was supported by theoretical studies. In 2004 experimental evidence of this model with charge-density studies and topological analysis of alkali-metal coordinated iminophosphoranes showed a polar P+−N− "augmented by electrostatic contributions." Therefore, although the iminophosphorane P=N bond is typically drawn as a double bond, it is highly polarized and is most accurately described as a hybrid of resonance contributors between the ylene and ylidic forms (Figure 6). The P=N bond of iminophosphoranes is isoelectronic with the P=C bond of phosphonium ylides, also known as Wittig reagents, and comparisons between their structure and reactivity can be made. For instance, the P=C bond of the phosphonium ylide is similar to the P=N bond of iminophosphoranes in that both are best described with the ylidic resonance form with no true π bond and a short P=C bond due to negative hyperconjugation. Because of these structural similarities, both the iminophosphoranes and phosphinium ylides show strong 𝜎- donor and little to no π-acceptor capabilities (see below). There are some structural differences, with computational studies demonstrating a slightly higher P=N bond order in the iminophosphorane compared to the P=C bond of the phosphonium ylide. A 2023 study comparing the two ylidic species demonstrated that electronic properties of both ylidic species are strongly influenced by the substituent, but between the unsubstituted ylides (P=CH2 vs. P=NH), the phosphonium ylide donates more electron density to a metal center. Furthermore, the Wittig reaction with the phosphonium ylide for the formation of C=C bonds is comparable to the aza-Wittig reaction see below with iminophosphoranes for the formation of C=N bonds, with both mechanisms proceeding through similar four-membered intermediates and generating phosphine oxide byproduct.
Reactivity
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