Here, we present a protocol for the synthesis of two carbonyl-decorated carbenes. The protocol makes these interesting compounds readily available to chemists of all skill levels. In addition to the synthesis of these two carbenes, their use in the activation of white phosphorus is also described.
Here we present a protocol for the synthesis of two distinct carbonyl-decorated carbenes. Both carbenes can be prepared using nearly identical procedures in multi-gram scale quantities. The goal of this manuscript is to clearly detail how to handle and prepare these unique carbenes such that a synthetic chemist of any skill level can work with them. The two carbenes described are a diamidocarbene (DAC, carbene 1) and a monoamidoaminocarbene (MAAC 2). These carbenes are highly electron-deficient and as such display reactivity profiles that are atypical of more traditional N-heterocyclic carbenes. Additionally, these two carbenes only differ in their electrophilic character and not their steric parameters, making them ideal for studying how carbene electronics influence reactivity. To demonstrate this phenomenon, we are also describing the activation of white phosphorus (P4) using these carbenes. Depending on the carbene used, two very different phosphorus-containing compounds can be isolated. When the DAC 1 is used, a tris(phosphaalkenyl)phosphane can be isolated as the exclusive product. Remarkably however, when MAAC 2 is added to P4 under identical reaction conditions, an unexpected carbene-supported P8 allotrope of phosphorus is isolated exclusively. Mechanistic studies demonstrate that this carbene-supported P8allotrope forms via a [2+2] cycloaddition dimerization of a transient diphosphene which has been trapped by treatment with 2,3-dimethyl-1,3-butadiene.
Stable carbenes have emerged as ubiquitous reagents in homogeneous catalysis1, organocatalysis2, materials science3,4, and more recently main group chemistry5-9. In the context of the latter, stable carbenes have recently been used in the activation and functionalization of white phosphorus (P4)5-9. The ability to directly convert P4 into organophosphorus compounds has become a topical research objective in an effort to develop “greener” methods that circumvent the use of chlorinated or oxychlorinated phosphorus precursors. Despite their widespread use, the preparation and handling of carbenes and reactive compounds such as P4 can be a daunting task. For this reason, we have written this manuscript to provide a clear and concise protocol that will allow synthetic chemists of all skill levels to synthesize and manipulate two very unique stable carbenes. Additionally, the activation of P4 using the described carbenes is detailed.
Herein we detail a protocol for the synthesis of two electron-deficient carbonyl decorated carbenes. We have chosen these carbenes because they differ only in their electrophilic properties, and not their steric parameters, making them ideal for studying the effects of carbene electronics on reactivity. The importance of carbene electronics with regard reactivity is exemplified by two similar compounds of the general formula carbene-P2-carbene that have been reported by Bertrand and Robinson5,8. Bertrand’s P2 derivative is supported by two cyclic alkyl amino carbene (CAAC) ligands, and is structurally, photophysically, and electrochemically different than Robinson’s compound which is a P2 fragment supported by two N-heterocyclic carbenes (NHCs)5,8. Indeed, Bertrand’s P2 complex is characterized as a yellow solid that features carbene-to-phosphorus double bonds in the solid state, whereas the derivative reported by Robinson is a dark red solid that contains NHC→P dative bonds. This structural difference also manifests itself electrochemically such that Robinson’s compound contains more electron-rich phosphorus centers that can undergo reversible 1- or 2-electron oxidations in contrast to Bertrand’s compound which can only undergo a single reversible oxidation10.
Based on the studies described above, we became interested in studying the activation of P4 using the highly electrophilic diamido- and monoamidoamino carbenes to determine if novel carbene-stabilized allotropes of phosphorus could be prepared. We focused on diamidocarbene (DAC) 1, and monoamidoamino carbene (MAAC) 2 which differ only in their respective electrophilicities to interrogate what role carbene electronics play in P4 activation. Interestingly when the more electrophilic DAC is used, a tris(phosphaalkenyl)phosphane (3) could be isolated as the exclusive product, whereas when a MAAC is used, a carbene-stabilized P8 allotrope (4) can be obtained11. We also interrogated the mechanism for the formation (4), and found that it is formed via a [2+2] cylcoaddition dimerization reaction of a transient diphosphene. The existence of this diphosphene was confirmed by trapping it with 2,3-dimethyl-1,3-butadiene to furnish the [4+2] cycloaddition adduct 5. The protocol for synthesizing these carbonyl-decorated carbenes and their corresponding P4 activated compounds is described herein.
1. Synthesis of Diamidocarbene (Compound 1)
2. Synthesis of Monoamidocarbene (Compound 2)
3. Synthesis of a Tris(phosphaalkenyl)phosphane (Compound 3)
Caution Statement: White phosphorus is extremely pyrophoric as well as toxic and should be handled cautiously in a glovebox whenever possible.
4. Synthesis of a Carbene-stabilized P8 Allotrope (Compound 4)
5. Trapping a Transient E-1,2-bis(phosphaalkenyl)diphosphene via [4+2] Cycloaddition: Synthesis of Compound 5
The ability to isolate a tris(phosphaalkenyl)phosphane such as 3 or the P8-allotrope (4) from white phosphorus relies on the use of an electrophilic carbene to activate the P4 tetrahedron11,16. Therefore, it is critical to prepare carbenes with enhanced π-acidity, and by extension electrophilicity. Figure 2 illustrates the synthesis of carbene precursor 1-HCl and its subsequent deprotonation to afford the diamidocarbene 113. The synthesis of diamidocarbene 1 can be accomplished in a single day (approximately 6 hr from start to finish), and the carbene can be isolated as a white powder in 72% overall yield.
Figure 2. Synthesis of diamidocarbene 1 by coupling N,N′-dimesitylformamidine to dimethylmalonyl dichloride. Please click here to view a larger version of this figure.
By removing one of the carbonyl moieties from carbene 1, the π-acidity of the diamidocarbene can be attenuated. To accomplish this task, monoamidocarbene 2 can be prepared in a similar manner to carbene 1 using 3-chloropivaloyl chloride and N,N′-dimesitylformamidine15. Figure 3 describes the synthesis of 2 which can be carried out in approximately two days. The free monoamidocarbene can be isolated as a white powder in 56% overall yield.
Figure 3. Synthesis of monoamidocarbene 2 by coupling N,N′-dimesitylformamidine to 3-chloropivaloyl chloride. To date there have been several reports that detail the activation of white phosphorus using stable carbenes. In these studies, it has been well-demonstrated that the electronic properties of the carbenes directly govern the identity of the activated phosphorus product5. To demonstrate this phenomenon, carbenes 1 and 2, which differ only in their respective electrophilicities, can be used to activate P4 to afford very different products. When the more electrophilic diamidocarbene 1 is used, the tris(phosphaalkenyl)phosphane (3) can be prepared as a red solid in 82% yield (Figure 4). However, when the less electrophilic monoamidocarbene 2 is used, the P8-allotrope (4) can be isolated as an orange solid in yields ranging from 51-75% yield depending on the conditions used (Figure 4). Please click here to view a larger version of this figure.
Figure 4. Synthesis of tris(phosphaalkenyl)phosphane 3 and carbene-stabilized P8 allotrope 4 starting from carbenes 1 and 2, respectively (Mes = 2,4,6(CH3)3C6H2).
A mechanism has been proposed for the formation of compounds 3 and 4 (Figure 5) which describes how the differing electrophilicities of carbenes 1 and 2 influences the reaction with P4. For both carbenes, zwitterionic intermediate A, which features two coordinated carbene ligands has been suggested as forming initially upon activation of the P4 tetrahedron. When the more electrophilic diamidocarbene 1 is used, intermediate A is sufficiently nucleophilic to add to the empty p-orbital of a third molecule of 1, eventually resulting in the formation of tris(phosphaalkenyl)phosphane 3 through intermediate B. However, when the less electrophilic carbene 2 is used, A is not sufficiently nucleophilic to add a third molecule of 2, and subsequently rearranges to afford the linear diphosphene intermediate C. Intermediate C then rapidly undergoes a [2+2] cycloaddition-dimerization to afford the P8-allotrope 4. It is proposed that intermediate C is the source of the dark green color observed in the synthesis of the 4. Please click here to view a larger version of this figure.
Figure 5. Proposed mechanism for the formation of compounds 3 and 4. The formation of the putative diphosphene intermediate C was verified by trapping with 2,3-dimethyl-1,3-butadiene to afford compound 5 (Figure 6). In a typical experiment, when the activation of P4 using carbene 2 is carried out in a large excess of 2,3-dimethyl-1,3-butadiene, compound 5 can be isolated as a bright yellow solid in 71% yield. Please click here to view a larger version of this figure.
Figure 6. Synthesis of compound 5 by trapping intermediate C with 2,3-dimethyl-1,3-butadiene (Mes = 2,4,6(CH3)3C6H2). To demonstrate the effectiveness of these synthetic methods, we have provided 1H NMR spectra for carbenes 1 and 2 as well as 31P NMR spectra for compounds 3, 4, and 5 (see Figures 7-11, respectively). Please click here to view a larger version of this figure.
Figure 7. 1H NMR (C6D6) of DAC 1 prepared using the described protocol.
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Figure 8. 1H NMR (C6D6) of MAAC 2 prepared using the described protocol. Please click here to view a larger version of this figure.
Figure 9. 31P NMR (C6D6) of 3 prepared using the described protocol.
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Figure 10. 31P NMR (THF-D8) of 4 prepared using the described protocol. Please click here to view a larger version of this figure.
Figure 11. 31P NMR (C6D6) of 5 prepared using the described protocol. Please click here to view a larger version of this figure.
A straightforward procedure for generating carbonyl-decorated carbenes and their application in the activation of white phosphorus is presented here. The critical steps in the protocol for synthesizing the carbenes are: (a) make sure all solvents are properly dried before use, (b) make sure the addition of acid chlorides to the formamidine is done very slowly, (c) if the Celite is not oven-dried for a minimum of 12 hr at 180 °C, hydrolysis of the 1-HCl as well as carbenes 1 and 2 occur. In some cases, the white phosphorous will convert to red phosphorous. For the P4 activation reactions, it is imperative that the reactions be conducted in the dark or in foil-wrapped reaction vessels to ensure that the white phosphorus does not convert into red phosphorus.
There are no major limitations of the techniques described herein, and indeed these methods may be applied to the future synthesis of other carbenes. One significant advantage to our method of preparing the described carbenes is the utilization of NaHMDS as the base for the deprotonation of compounds 1-HCl and 2-HCl. NaHMDS is well-suited to the generation of carbenes as it is soluble in aromatic hydrocarbons in which the vast majority of carbenes are stable.
The authors have nothing to disclose.
We are grateful to the Research Corporation for Science Advancement (20092), the National Science Foundation (CHE-1362140), and Texas State University for their generous support.
2,4,6-trimethylaniline | Alfa Aesar | AAA13049-0E | 98% |
Triethylorthoformate | Alfa Aesar | AAA13587 | 98% |
Dimethylmalonyl dichloride | TCI | D2723 | >98% |
3-chloro-pivaloyl chloride | Aldrich | 225703-25G | 98% |
Triethylamine | Alfa Aesar | AAA12646 | Stored over dried, activated 3 Å molecular sieves |
Celite™ 545 | EMD | CX0574-3D | Oven-dried at 180 °C for a minimum of 12 hrs |
Sodium hexamethyldisilazide | Across | 200014-462 | 95+% |
2,3-dimethyl-1,3-butadiene | Alfa Aesar | AAAL04207-09 | 98% |
dichloromethane | EMD | DX0835-5 | Purified through solvent purification system, or standard methods |
tetrahydrofuran | Mallinckrodt | 8498-09 | Purified through solvent purification system, or standard methods |
Hexanes | EMD | HX0299-3 | Purified through solvent purification system, or standard methods |
Benzene | EMD | BX0220-5 | Purified through solvent purification system, or standard methods |
Toluene | BDH | 1151-19L | Purified through solvent purification system, or standard methods |
white phosphorus | Generously donated from the Texas A&M chemistry store room. | NA | Purified through sublimation and transferred directly into a glovebox while under vacuum in the sublimator |