Lithium, sodium and potassium enolate aggregates and monomers: syntheses and structures

Abstract

In this Article, we report the syntheses and comparative structural studies of lithium, sodium, and potassium anthracen-9-yl enolates, as their aggregates (Li, Na: hexamer; K: tetramer) and ligand-stabilized monomers (for Li and Na). The monomers add new members to the rare collection of group-1 metal monomeric enolates. Moreover, the series covers different group-1 metal cations (Li⁺, Na⁺ and K⁺) and aggregate sizes, allowing comparative structural studies to elucidate how the metal identity and aggregate size influence the enolate structure.

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Introduction

Enolates derive from α-deprotonation of organocarbonyls, such as ketones and aldehydes. They are widespread reaction intermediates in organic chemistry, and enable several textbook organic reactions, such as aldol addition.¹ The most commonly used approach to generate enolates is the deprotonation of organocarbonyls using organo-alkali metal reagents, such as organolithium. The resultant alkali metal enolates are subsequently subjected to further transformations. It is quite understandable that the alkali metal enolate structures play an underpinning role in their following reactions. But the structural studies of isolated alkali metal enolates are not as well-established as one may expect: the state-of-the-art is covered in the following paragraph. Given the diverse scope of organocarbonyls (e.g., ketones, aldehydes, esters, amides and so on), their derivative enolates feature a high level of structural diversity. Beyond the hydrocarbon enolates derived from ketones and aldehydes, heteroatom-substituted enolates, such as the ones derived from esters,² amides³ or α-hetero organocarbonyls (e.g., α-phosphino esters⁴), were also reported.

A key factor to influence the coordination complex structure is metal identity. For the enolate complexes, among the most common alkali metal cations Li⁺, Na⁺ and K⁺, lithium enolates are the most studied. Since the 1980s, the groups of Williard,⁵ Mulvey,⁶ Reich,⁷ Collum,⁸ and Hevia,⁹ among others,¹⁰ reported a number of isolated and structurally characterized lithium enolate complexes, most of which are aggregates. In comparison with the relatively well-documented lithium enolates, sodium^5e,11 and potassium^5e,12 enolates are far less studied. A comparative structural study of Li, Na and K enolates within the same system, i.e., the same enolate substitutions and the ligand, would help to unravel the metal identity's structural directing role. In 1986, Williard and Carpenter reported such a remarkable comparative study on a series of Li, Na and K enolates of pinacolone (tert-butyl methyl ketone).¹³ In these cases, the Li and K pinacolone enolates were found to be hexamers (Li: no solvent coordination; K: one coordinated THF per K), while the Na enolate is a tetramer (no solvent coordination). The aggregates remain in solution as proven by NMR studies.¹³ Despite clearly revealing “subtle structural differences” (according to the authors) induced by the metal identity, the work from Williard and Carpenter did not include another crucial comparison dimension: aggregate size.

Aggregate size is one of the most important structural factors in alkali metal chemistry, playing underpinning roles in the structure–reactivity relationship.¹⁴ In the enolate chemistry specifically, as early as in 1981, Seebach and co-workers examined the mechanistic implications of the tetrameric cubic structure of Li enolates in addition reactions.^15,16 In 2013, Cossío and co-workers conducted computational studies (DFT and molecular dynamics) on the relationship between alkali metal enolates aggregate sizes and their activity (reaction rate) in the aldol addition,¹⁷ where the monomers were found to be vastly superior to the dimers and tetramers. Out of the in silico chemical space, reported examples of crystallographically characterized alkali metal enolate monomers are rather limited. In 2009 and 2010, Reich and co-workers systematically studied the SCXRD and solution-state structures and the structural dynamics of several lithium enolates, with the presence of a series of ligands, including PMDTA, Me₃TACN (also known as TMTAN), HMPA, and cryptand [2.1.1].⁷ The tridentate cyclic Me₃TACN ligand was found to be able to stabilize a collection of lithium enolate monomers⁷ (Fig. 1A). Moving onto the heavier alkali metals, there is no sodium enolate monomer in literature, albeit a relevant sodium ethylacetoacetate monomer was reported as stabilized by 15-crown-5.¹⁸ A few monomers of potassium enolates and α-heteroatom substituted enolates were reported in 1993 ⁴ and 1994 ^12b,19 (Fig. 1B–F), including two separated ion pairs (Fig. 1C & E). Due to the scarcity of the alkali metal enolate monomers, an in-depth understanding of the structural differences between their aggregates and monomers remains an open question.

Fig. 1 The reported examples of Li and K enolate monomers.

Since the 2020s, our group has focused on unravelling the structural and reactivity directing roles of the two key factors in alkali metal chemistry: (1) aggregate size;^20,21 (2) metal identity.²² Herein, we bring the effort into Li, Na and K enolate chemistry by reporting the synthesis and characterisation of a series of Li, Na, K anthracen-9-yl enolates as their aggregates and ligand-stabilised monomers. We found that without external ligand, the Li and Na anthracen-9-yl enolates exist as hexamers but with different coordination geometries, while the K enolate exists as a tetramer. Employing the Me₆Tren ligand, we isolated and characterized two rare examples of Li and Na enolate monomers. Based on the complexes, the enolates structural trends are studied on two dimensions of comparison: (1) metal identity; (2) aggregate size. Our findings are elaborated in the following sections.

Results and discussion

Synthesis of the Li, Na and K enolates

As a part of our systematic studies of the Brønsted basicity and nucleophilicity of organo-alkali metal reagents,^20–22 9-acetylanthracene (1) was treated with lithium, sodium and potassium alkyl complexes [MCH₂SiMe₃]_n (M = Li, 2-Li;²³ M = Na, 2-Na;²⁴ M = K, 2-K²⁵) in d₆-benzene (for the NMR-scale reactions) or benzene (for the scale-up reactions) (Scheme 1). 9-Acetylanthracene was chosen as the substrate for its superior steric protection over the products, as well as the crystallinity induced by the anthracen-9-yl functional group. All the reactions occurred as deprotonation at the methyl position exclusively – we did not observe the possible nucleophilic addition side reaction towards the C=O bond. The corresponding Li, Na and K enolates, [M{OC(=CH₂)(C₁₄H₉)}]_n (3-Li/Na/K, n = 6 for Li and Na, n = 4 for K), were isolated in 73–97% crystalline yields. Among them, 3-Li and 3-Na crystallize into hexamers, while 3-K crystallizes as a tetramer. The ¹H and ⁷Li (for 3-Li) NMR spectra of 3-Li/Na/K are reported in the ESI,‡ from the in situ¹H NMR monitoring of the corresponding NMR-scale reaction. Upon formation, 3-Li/Na/K crystallise from the C₆D₆/C₆H₆ solutions rapidly, and can not be re-dissolved. For this reason, their ¹³C and ¹H DOSY NMR spectra are absent.

Scheme 1 Syntheses of Li, Na and K enolate clusters, 3-Li (hexamer), 3-Na (hexamer) and 3-K (tetramer).

Following the successful syntheses of the enolate clusters 3-Li/Na/K, reactions between 1 and the monomeric organo-alkali metal complexes, [M(CH₂SiMe₃)(Me₆Tren)] (M = Li, 4-Li;²⁶ M = Na, 4-Na^22,27) and [K(CH₂Ph)(Me₆Tren)] (5-K²⁸), were tested (Scheme 2). The 4-Li/Na reactions yielded corresponding Me₆Tren-coordinated Li/Na enolate monomers, 6-Li and 6-Na, respectively. In comparison, reaction between a benzyl potassium monomer 5-K²⁸ and 1 produced the potassium enolate tetramer 3-K, while the Me₆Tren ligand dissociated and was observed in the ¹H NMR spectroscopy as coordination-free. We attribute the Me₆Tren ligand dissociation in the potassium reaction to two factors: (1) the relatively low affinity between the Me₆Tren ligand and K⁺ (comparing with Li⁺/Na⁺): the low affinity between Me₆Tren and K⁺ allowed us to realize the first alkali metal cations selective reduction between K⁺ and Li⁺;²⁹ (2) The K enolate tetramer 3-K structure features much more significant cation–arene interactions (vide infra, Fig. 4) comparing with the structures of 3-Li (Fig. 2) and 3-Na (Fig. 3). The alkali metal cation–arene interaction is known to be more pronounced for heavier alkali metal cations.^21b,28,30

Fig. 2 The SCXRD structure of 3-Li. Hydrogen atoms, solvent benzene molecules in the lattice, and the two flanking phenyl rings of the anthracene are omitted for clarity. Only one third of the molecule is labelled, but the whole molecule is crystallographically independent. To facilitate readers, we labelled the atoms in a chemically intuitive way, instead of using the numeric atomic number system. The atomic numbers can be found in the Cambridge Structural Database archive. Key bond lengths are provided as ranges: Li_ap–O (1.95–1.97 Å), Li_eq–O (1.85–1.92 Å), O–C_C=CH2 (1.34–1.35 Å), C_C=CH2–C_C=CH2 (1.31–1.33 Å), C_C=CH2–C_ipso (1.49–1.51 Å).

Fig. 3 The SCXRD structure of 3-Na. Hydrogen atoms, solvent benzene molecules in the lattice, and the two flanking phenyl rings of the anthracene are omitted for clarity. Half of the whole molecule is crystallographically independent, while the key independent atoms are labelled. Key bond lengths are provided as ranges: Na–O (2.24–2.38 Å), O–C_C=CH2 (1.32–1.33 Å), C_C=CH2–C_C=CH2 (1.33–1.34 Å), C_C=CH2–C_ipso (1.49–1.51 Å).

Fig. 4 The SCXRD structure of 3-K. Hydrogen atoms, solvent benzene molecules in the lattice, and the two flanking phenyl rings of the anthracene are omitted for clarity. Both benzene and toluene molecules occupying the same positions throughout the crystal manifesting as disorder. The asymmetric unit also contains a solvent-accessible void in which there appear to be multiple orientations of both toluene and benzene. An unambiguous model for these solvent molecules in this site could not be achieved and hence the associated electron density was treated using the Olex2 solvent mask routine. To facilitate readers, we labelled the atoms in a chemically intuitive way, instead of using numeric numbers. Key bond lengths are provided as ranges: K–O (2.51–2.75 Å), O–C_C=CH2 (1.29–1.31 Å), C_C=CH2–C_C=CH2 (1.33–1.34 Å), C_C=CH2–C_ipso (1.50–1.52 Å).

Scheme 2 Syntheses of Li and Na enolate monomers 6-Li/Na.

Single-crystal X-ray diffraction (SCXRD) structures of the Li, Na and K enolates

The hexameric (3-Li, 3-Na), tetrameric (3-K) and monomeric (6-Li, 6-Na) structures were confirmed by the SCXRD studies: their solid-state molecular structures are presented in Fig. 2–6. In the following section, we will focus on the structural influences induced by two factors: (i) the metal identity; (ii) the aggregate size. In the aggregate clusters 3-Li/Na/K, we did not observe pronounced π–π stacking³¹ between the anthracenyl substitutes, or with the coordinated arene solvents. Hence, the π–π stacking is not a major structural contributor and therefore, we are confident that the trends summarized in the following section are not only limited to the anthracen-9-yl enolate, but also extrapolatable to other enolates.

Fig. 5 The SCXRD structure of 6-Li (left) and 6-Na (right). Hydrogen atoms and solvent molecules in the lattice are omitted for clarity. Key bond lengths: 6-Li: Li–O (1.827(2) Å), O–C13 (1.2836(13) Å), C13–C14 (1.3389(18) Å), C13–C15 (1.5148(14) Å); 6-Na: Na–O (2.1324(18) Å), O–C13 (1.279(3) Å), C13–C14 (1.343(3) Å), C13–C15 (1.521(3) Å).

Fig. 6 NBO charge per atom from natural population analyses of 6′-Li and 6′-Na.

The influence of the metal's identity is obvious for enolate clusters 3-Li/Na/K, especially in their aggregate sizes and geometries. For the smallest Li⁺, the enolate hexamer 3-Li features a Li₆O₆ hexagonal prismatic core (Fig. 2), which is similar to a Li pinacolone enolate hexamer reported by Williard and co-workers.^5h In 3-Li, each Li center coordinates with three O sites and features a coordination number of three. Upon moving from Li⁺ to Na⁺, one may expect the metal's coordination number to increase with the increase of metal's ionic radius. Indeed, 3-Na features a three-deck square prismatic structure (Fig. 3), with the inner deck Na⁺ centers featuring a coordination number of four, while the outer decks Na⁺ centers’ coordination number is three. While 3-Li and 3-Na can also be considered as two stacked layers of M₃O₃ motif, it is interesting to compare the M₃O₃ layer structures (Scheme 3). The larger Na⁺ cation leads to longer Na–O bond, which “tethers” the M and O in the middle of the M₃O₃ unit (Scheme 3). From another perspective, 3-Li is a “ring-laddering” loop, while 3-Na features a “ring-stacking” structure (Scheme 3). It worth mentioning that the ring-laddering and ring-stacking are ubiquitous structural features in group-1 metal coordination chemistry and have been well documented.³² Reviewing the literature³³ suggests that the determining factor is metal identity, or more specifically, the metal ionic radius, as we observed herein; though influences from ligand atom (e.g., C vs. N vs. O) and ligand steric profile should also be considered.

Scheme 3 The M₃O₃ unit in 3-Li and 3-Na, and the ring-laddering (3-Li) and ring-stacking (3-Na) representation of the complexes.

A further increase in the ionic radius going from Na⁺ to K⁺ leads into a distorted cubic K₄O₄ core in 3-K (Fig. 4), which features significant cation–π interactions with the arene solvent molecules. It is interesting to note that both benzene and toluene solvent molecules coordinate to the K centers (albeit disordered), and only three out of the four K centers are coordinated by the arene solvent molecules. This solvent molecule coordination discrimination, i.e., not all the K centres are coordinated, results in an asymmetric K₄O₄ core, and could likely be a result of steric crowding. The cation–π interaction is much more pronounced in 3-K than in 3-Li/Na (not at all for 3-Li, very little Na-anthracenyl interactions in 3-Na), which can be attributed to the stronger π-affinity of K⁺.^21b,28 Compared with the pronounced metal identity structural influence in the aggregate size and geometry, the anionic enolate ligand structure, [OC(=CH₂)(C₁₄H₉)]⁻, in 3-Li/Na/K, is largely unaffected by changes of the metal identity and the resultant changes of aggregate size. But we did observe non-negligible differences of the anionic enolate ligand structure between the clusters 3-Li/Na and the monomers 6-Li/Na, which will be elaborated in the following paragraphs.

The enolate monomers 6-Li/Na share a similar five-coordinate core structure (Fig. 5), where the Me₆Tren ligand's four nitrogen atoms and the oxygen atom of the enolate ligand furnish the inner coordination sphere. The Na–N/O bonds in 6-Na are longer than the corresponding Li–N/O bonds in 6-Li, reflecting sodium's larger ionic radius. The geometries of enolate ligand in 6-Li/Na are very similar, which is also reflected by the density functional theory (DFT) charge distribution studies. Examining the natural bonding orbital (NBO) atomic charges for the modelled monomers 6′-Li/Na indicates little differences between the Li and Na complexes (Fig. 6). For both 6′-Li and 6′-Na, a positive charge of approximately 0.9 is located on the metal cation, and a countering negative charge is located on the oxygen atom.

However, despite being largely immune to the change of metal identity, the enolate ligand structure can be influenced by the aggregate size. By comparing the enolate units in the hexamers (3-Li/Na) and monomers (6-Li/Na), we noted that the C–O bonds are significantly shorter in the monomers (monomers 1.27–1.28 Å vs. hexamers 1.32–1.35 Å) (Scheme 4). While the C=C and C–Ar bonds appear as slightly longer in the monomers, these elongation (0.01–0.02 Å) are too small to be considered as pronounced. The shortening of C–O bond in the monomers could be attributed to a weaker stabilization of the negative charge on the oxygen cf. the hexamers: In the hexamers, each anionic oxygen is coordinated by three (3-Li) or four (3-Na) metal cations, but the number is one in the monomers.

Scheme 4 Comparing the bond lengths in the enolate units of the hexamers and the monomers. The most pronounced structural changes are observed in the C–O bond length and the M–O–C bond angle (highlighted in red).

To further understand whether there is a thermodynamic preference between the liner and the bent M–O–C angles, or if it is largely kinetic-driven (i.e., depends on the steric congestion), we conducted potential energy surface scans. The methodology has been well-established to probe the energetic preference for cis or trans conformations in coordination chemistry.³⁴ The calculations are based on the hypothetical model of the monomeric M–O–C(=CH₂)Ar (Ar: anthracenyl), which removes all the ligand and secondary bridging units, minimizing the steric influence. The M–O–C angle was initially set to 90° leaving the remainder of the M–O–C(=CH₂)Ar moiety unchanged from the optimized structure and was then sequentially increased by 5° until equal to 270°. All geometric parameters were relaxed to loose convergence criteria at each angle step except the M–O–C angle itself which was fixed. It was found that the minimum energy of M–O–C(=CH₂)Ar was at 205° regardless of the metal identity, with the near linear structures being favored over the more bent structures. The resulting plots are shown in Fig. 7. We also observed that the 90° angle (metal cation pointing towards the C=CH₂ unit) is preferred over the 270° angle (metal cation pointing towards the aryl), which could be a result of steric repulsion between the bulky anthracenyl and the metal cation.

Fig. 7 Potential energy surface scans of the M–O–C angle M–O–C(=CH₂)Ar (M = Li – left and M = Na – right).

Conclusion

Herein, we report the syntheses and structures of a series of Li, Na and K enolates. Without any external ligand, the enolates aggregate into hexamers (Li and Na) and tetramer (K), and their geometries are heavily influenced by the metal identity, as well as the particularly pronounced metal cation–arene interactions in the potassium case. With the presence of the Me₆Tren ligand, the Li and Na enolates exist as monomers with similar structures. The coordination of the Me₆Tren ligand to Li⁺ or Na⁺ is the key to form the monomeric structures. In comparison, the Me₆Tren ligand failed to coordinate to K⁺, hence the corresponding K enolate monomer is not available.

This work adds five new members to the alkali metal enolate family. In particular, the two monomers 6-Li and 6-Na are the newest examples of the scarce collection of alkali metal enolate monomers. The aggregates, 3-Li/Na/K, exhibit a clear structural trend dictated by the metal identity, specifically, the metal ionic radius. Comparisons between the monomers 6-Li/Na and their corresponding hexamers 3-Li/Na unveils an interesting influence of the aggregate size towards the carbon–oxygen bond length in the enolate ligand. It would be interesting to see how the structural observations in this work would be translated into the enolate reactivity – more investigations are underway and will be reported in due course.

Author contributions

E. L. and N. D. conceived and conceptualised the studies. N. D. conducted the syntheses and experimental characterisations under E. L.'s supervision. J. M. H. designed and conducted the computational studies under the guidance of E. L. P. G. W. collected and refined and the single-crystal X-ray diffraction data. E. L. wrote the manuscript with input from all the authors.

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

The authors thank the Chemistry Technical Support Team (Drs Laura McCorkindale and Amy Roberts, Mr Niall Straughan) at Newcastle University for supporting our research. E. L., N. D. and J. M. H. thank the Newcastle University Academic Track (NUAcT) Fellowship (E. L. and N. D.) and the Leverhulme Trust (RPG-2022-231) for financial support.

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Footnotes

† This article is dedicated to Professor Chang-Tao Qian, Shanghai Institute of Organic Chemistry, on the occasion of his 90^th birthday.

‡ Electronic supplementary information (ESI) available. CCDC CCDC 2307285 (3-Li), 2307287 (3-Na), 2307288 (3-K), 2307289 (6-Li) and 2307290 (6-Na). For ESI and crystallographic data in CIF or other electronic format see DOI: https://doi.org/10.1039/d4dt00211c

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