Structurally Stimulated Deprotonation/Alumination of the TMP Anion

Coerced conversion: Long utilized as a strong Brønsted base, the tetramethylpiperidine (TMP) anion is forced to convert to a Brønsted acid in the presence of a potassium–aluminate species. The new compound [(TMEDA)K(μ-TMP*)(μ-iBu)Al(iBu)] was obtained where TMP* represents a CH3- and NH-deprotonated dianionic variant of TMP (see scheme). Derived from the cyclic secondary amine 2,2,6,6-tetramethylpiperidine [TMP(H)] by removal of its nitrogen-attached hydrogen atom, the TMP anion 1 has had a 40 year career1 in the business of selective proton abstraction.2 Possessing attributes of high steric bulk and low nucleophilicity, without any β-hydrogen atoms (the presence of which often disadvantages its diisopropylamido analogue3 through β-hydride decomposition), 1 is usually employed as its lithium salt, LiTMP, which exists as a cyclotetramer in the crystal.4 NaTMP is a cyclotrimer,5 whereas KTMP remains still to be crystallographically characterized. Besides being strong Brønsted bases, these alkali metal TMP compounds are strong Lewis acids. Adding the Lewis base TMEDA (N,N,N′,N′-tetramethylethylenediamine) to them causes steric inflation of the alkali metal coordination sphere, concomitantly reducing the TMP complex aggregation state. Tetrameric LiTMP is reduced to the hemisolvated open dimer [(TMEDA)Li(μ-TMP)Li(TMP)];6 whereas the larger alkali metal complexes become fully solvated cyclodimers [{(TMEDA)M(μ-TMP)}2]7 (M=Na or K). Since such structural changes can modify the reactivity of the “TMP anion”, accommodating it within a more altered mixed-metal (and/or mixed-anion) environment can exert a strong influence on reactivity. This idea has stimulated much current research into TMP-based bimetallic reagents including TMP-magnesiates,8 TMP-zincates,9 TMP-cadmates,10 TMP-chromates,11 TMP-manganates,12 and TMP-ferrates,11 which can show significant improvements in, for example, functional group tolerance or kinetic stability compared to that of LiTMP. Of particular interest in this study are TMP-aluminates. Uchiyama and co-workers introduced the first TMP-aluminate “iBu3Al(TMP)Li” in 200413 showing its high chemo- and regioselectivity in proton abstraction reactions of functionalized aromatic substrates. In these and subsequent reactions of this type, the TMP anion is invariably the sole active (or most active) base ligand executing deprotonation upon the substrate and disembarking the assembly as TMP(H). The prospect of deprotonating this most powerful of bases to generate a TMP-based dianion would seem a challenge too far. However, here we present a rational structurally controlled approach that has met this challenge. Recent inorganic structurally focused studies14 have elaborated the design characteristics of a TMP-bimetallic complex that can render it a powerful metalating (magnesiating, zincating, aluminating etc.) agent. Commonly, the two distinct metals connect through a TMP bridge, with the di- or trivalent metal carrying two or three additional anions (alkyls and/or amides), while a neutral aggregation-blocking capping ligand (for example, multiple THF molecules or TMEDA) binds terminally to the alkali metal. With “iBu3Al(TMP)Li”, organic substrates such as benzamides can undergo ortho deprotonation/alumination with evolution of TMP(H) (Scheme 1).15 While such reactions are intermolecular, it is thought that the organic substrate coordinates to the bimetallic assembly (probably at the alkali metal site) prior to its deprotonation, so in effect the aluminum–hydrogen exchange reaction is intramolecular in origin.16 Building on this idea, we demonstrated that it was possible to effect deprotonation of the neutral cap by tuning the relative steric profiles of the cap, the alkali metal, and the anionic bridges.17 This was achieved by using a cap (TMEDA) that when bound to the smallest alkali metal (lithium) might encroach into bridging-anion territory. Thus we showed that merging together LiTMP, diisobutylaluminum(TMP), and TMEDA in hexane solution in the absence of an organic substrate, forced deprotonation/alumination of a terminal Me group on TMEDA to generate a methylenic CH2Al bond (Scheme 2). Two molecules of TMEDA (within the same bimetallic assembly) and its tridentate analogue PMDETA (N,N,N′,N′′,N′′-pentamethyldiethylenetriamine) can be similarly deprotonated α to nitrogen, which generally is a position challenging to metalate in tertiary amines.18 Example of an ortho-alumination using a TMP-aluminate. α-Methylalumination of TMEDA. Having successfully applied this intramolecular alumination trapping methodology to both added organic substrates and in their absence attached neutral caps, we pondered whether it could be extended to the considerably more taxing challenge of deprotonating an attached anion. This task proved surprisingly straightforward in practice. A simple plan was devised to combine a larger alkali metal (potassium) with a smaller fitting cap (TMEDA instead of tridentate PMDETA) in the hope of encouraging closer intramolecular contact between incipient anion bridges as two distinct metal compounds approach each other to generate a bimetallic assembly. Experimentally this meant reacting KTMP with iBu2Al(TMP) and TMEDA in a 1:1:1 stoichiometry in hexane solution. X-ray crystallographic studies19 supported by solution NMR spectroscopic studies established the crystalline product to be the new potassium aluminate [(TMEDA)K(μ-TMP*)(μ-iBu)Al(iBu)] (2) where TMP* represents a unique CH3-deprotonated as well as an NH-deprotonated dianionic variant of the bulky cyclic amine. Thus the planned “intramolecular” alumination strategy has been successful with the TMP anion undergoing a second deprotonation to form TMP* which has been trapped in the new bimetallic assembly. The molecular structure of 2 (Figure 1) varies from the common structure of TMP-bimetallic assemblies.14 Potassium connects to aluminum through an amido N bridge and an alkyl C bridge, with a bidentate TMEDA cap and an isobutyl ligand attached terminally to the respective metals. The new feature is an irregular, highly puckered four-atom (Al1-N3-C34-C37) ring, which closes through the making of the Al1C37 bond involving the methylenic CH2 unit that originates from deprotonation of one Me group on the α-C atom of TMP. Three other Me groups of TMP* retain their full complement of hydrogen atoms. Therefore TMP* functions in a new role as an N,C-bidentate, dianionic ligand towards Al. Consequently, both N3 and C34 become stereogenic centers. As the space group is centrosymmetric, these atoms exist as (S,R) and (R,S) enantiomeric pairs within the crystal. Selected dimensions in 2 are in the legend to Figure 1. TMP* makes an acute bite angle (N3-Al1-C37) of 73.55(9)°, which contributes to the marked distortion from tetrahedral of the Al center [widest bond angle: C37-Al1-C40 120.77(9)°; mean bond angle 108.87°]. There is little discrimination between the bond lengths of the three AlC bonds [largest difference 0.011 Å; mean value 2.016 Å], with the AlN bond being shorter at 1.897(2) Å. Potassium occupies a highly irregular four-coordinate CN3 geometry. All KN bond lengths are similar (mean value, 2.849 Å). The intramolecular K1C10 bond length is 3.184(3) Å, and there is also a moderately close intermolecular K1C37* contact [3.413(2) Å] with the methylenic CH2 of a neighboring molecule, giving a loose dimeric arrangement (see Supporting Information). Molecular structure of 2 with hydrogen atoms (except those of NCCH2Al) and the minor disordered component omitted for clarity. Thermal ellipsoids are drawn at 50 % probability. Selected bond lengths [Å] and angles [°]: K1–N1 2.897(2), K1–N2 2.825(2), K1–N3 2.825(1), K1–C10 3.184(3), Al1–C10 2.022(2), Al1–C37 2.011(3), Al1–N3 1.897(2); N1-K1-N2 64.29(6), N1-K1-N3 122.17(5), N2-K1-N3 146.26(6), C37-Al1-C40 120.77(9), N3-Al1-C37 73.55(9), Al1-N3-C34 92.9(1), Al1-C37-C34 87.1(1), N3-C40-C37 100.4(1). Recorded in [D12]cyclohexane solution, 1H and 13C NMR spectral data of 2 support the structure observed in the crystal. Most informatively, the methylenic CH2 unit is diastereotopic giving rise to two inequivalent 1H resonances (one doublet at δ=0.38 ppm; the other obscured by an overlapping iBu CH2 resonance spanning δ=−0.17 to −0.28 ppm), coupled to the same 13C resonance (at δ=32.9 ppm). Formally the reaction leading to 2 can be regarded as a self-deprotonation, with one TMP anion reacting with another (Scheme 3). This unusual reactivity emphasizes the greater scope of mixed-metal chemistry as TMP self-deprotonation/metalation is unlikely to be reproduced (in a controlled manner) in a homometallic system. While this reaction is unprecedented, TMP dispensed as Mg(TMP)2 has been reported20 to deprotonate LiHMDS (HMDS is 1,1,1,3,3,3-hexamethyldisilazide) at a Si(CH3) site, though this is a much less challenging task as several examples of Si(CH3) deprotonation have appeared.21 In general, CH activation of CH3 groups is a well-known, somewhat random phenomenon across organometallic chemistry.22 The reaction reported herein represents a special and surprising case of CH bond activation which introduces a novel modified form of TMP. As a bonus, the structurally well-defined bimetallic approach that made it possible could offer model systems with which to study systematically special intramolecular deprotonations, especially in cases where CH bonds have exorbitantly high pKa values, and are normally resistant to conventional bases. Self-deprotonation of the TMP anion. The reaction was carried out under a protective argon atmosphere using standard Schlenk techniques. Full details are given in the Supporting Information. Synthesis of 2: Hexane (10 mL) was added to an oven-dried Schlenk tube. Next, 1.6 M nBuLi (1.25 mL, 2 mmol) was added, followed by TMP(H) (0.34 mL, 2 mmol) at room temperature. The reaction mixture was left to stir for 30 min and then iBu2AlCl (0.38 mL, 2 mmol) was injected into the Schlenk tube, producing a white suspension almost immediately. The reaction was left to stir for 45 min and was then filtered through Celite and glass wool, which was then washed with more hexane (10 mL). To a separate Schlenk tube containing a suspension of freshly prepared KTMP in hexane (10 mL) [from a mixture of KCH2SiMe3 (0.24 g, 2 mmol) of and TMP(H) (0.34 mL, 2 mmol)], the solution was added through a cannula to give a tan-colored suspension. Finally, TMEDA (0.30 mL, 2 mmol) was injected, and the reaction mixture quickly turned into a homogeneous solution which was left to stir for 30 min before the Schlenk tube was left in the refrigerator at −4 °C. A crop (0.43 g, 49 %) of colorless crystals formed in solution that were suitable for X-ray crystallographic analysis. 1H NMR (400.13 MHz, 298 K, C6D12): δ=2.34 [4 H, s, 2×CH2 of TMEDA], 2.24 [12 H, s, 4×CH3 of TMEDA], 1.98–1.82 [2 H, m, 2×CH of iBu], 1.75–1.60 [1 H, m, 1×γC(H)2 of TMP], 1.58–1.24 [5 H, m, 1×γC(H)2 of TMP and 2×βCH2 of TMP], 1.23 [3 H, s, 1×CH3 of TMP], 1.01–0.91 [18 H, m, 2×CH3 of TMP and 4×CH3 of iBu], 0.38 [1 H, d, 2J(H,H)=12.5 Hz, 1×metal-C(H)2 of metalated TMP-Me], 0.11–(−0.04) [2 H, m, CH2 of iBu], −0.17–(−0.28) [2 H, m, 1×metal-C(H)2 of metalated TMP-Me, 2J(H,H)=11.8 Hz, and 1×C(H)2 of iBu], −0.42–(−0.49) ppm [1 H, m, 1×C(H)2 of iBu]. 13C{1H} (100.62 MHz, 298 K, C6D12): δ=58.1 [2×CH2 of TMEDA], 57.2 [1×quaternary C of TMP], 50.6 [1×quaternary C of TMP], 46.1 [4×CH3 of TMEDA], 40.6 [1×βCH2 of TMP], 39.6 [1×βCH2 of TMP], 36.9 [1×CH3 of TMP], 36.6 [1×CH3 of TMP], 32.9 [1×metal-CH2 of TMP], 31.8 [1×CH2 of iBu], 31.5 [1×CH3 of TMP], 30.2 [1×CH3 of iBu], 29.5 [1×CH3 of iBu], 29.3 [1×CH3 of iBu], 28.8 [1×CH3 of iBu], 28.5 [1×CH of iBu], 28.4 [1×CH of iBu], 27.3 [1×CH2 of iBu], 20.9 ppm [1×γCH2 of TMP]. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.