Thermal Dehydrogenation of Base-Stabilized B₂H₅⁺ Complexes and its Role in C–H Borylation

Abstract

Thermally induced dehydrogenation of the H-bridged cation L₂B₂H₅⁺ (L = Lewis base) is proposed to be the key step in the intramolecular C–H borylation of tertiary amine boranes activated with catalytic amounts of strong “hydridophiles”. Loss of H₂ from L₂B₂H₅⁺ generates the highly reactive cation L₂B₂H₃⁺, which in its sp²–sp³ diborane(4) form then undergoes either an intramolecular C–H insertion with B–B bond cleavage, or captures BH₃ producing L₂B₃H₆⁺. The effect of the counterion stability on the outcome of the reaction is illustrated by formation of LBH₂C₆F₅ complexes through disproportionation of L₂B₂H₅⁺ HB(C₆F₅)₃⁻.

Electrophilic activation of B–H bonds is the essential step in metal-free dehydrogenation of amine borane complexes,^[1] as well as in some electrophilic C–H borylations.^[2,3] While the majority of studies to date have focused on dehydrogenation of amine borane complexes possessing at least one hydrogen atom at the amine nitrogen (i.e. B–N dehydrocoupling), it appears that other dehydrogenative events can also occur in activated Lewis base borane complexes. This communication highlights the ability of activated amine and phosphine boranes to undergo thermal B–B dehydrocoupling,^[4] and the significance of this event in certain electrophilic C–H borylations.

The partial hydridic character of B–H bonds in tetracoordinate boron environment dictates their high reactivity towards electrophilic agents, and is central to the reducing properties of borane complexes.^[5] The outcome of the electrophilic activation of tertiary amine and phosphine borane complexes 1 depends on availability of Lewis bases in the reaction medium (Scheme 1).^[6] Thus, while neutral covalent adducts 2 and boronium ions 3 are preferentially formed under more basic conditions, tricoordinate borenium ions 5^[2,7] (or even their respective dicationic dimers^[8]) are accessible when the coordinating ability of the reaction medium is limited. Depending on the ratio of electrophile:1, borenium 5 can also form a 3-center-2-electron (3c2e) bonded adduct with 1, giving rise to the H-bridged L₂B₂H₅⁺ complex 4,^[1a,4a,9] which is the cationic analog of the well-known B₂H₇⁻ anion.

Scheme 1.

Lewis base borane complex activation by electrophiles, a few selected alternatives (L = tertiary amine or phosphine, E = “hydridophile”, X = counterion, Solv = Lewis basic solvent).

Tertiary amine boranes possessing suitably placed C–H bonds have been shown previously to undergo intramolecular borylation upon stoichiometric activation with strong electrophiles (Scheme 2).^[2a–c] In the reaction sequence involving 1 equiv of Ph₃C⁺ B(C₆F₅)₄⁻ in either PhBr or PhF, hydride abstraction from N,N-dimethylneopentylamine borane (6) leads to formation of unstabilized borenium 8 through the 3c2e bonded L₂B₂H₅⁺ intermediate 7. Availability of both an empty orbital and a partially hydridic H at the borenium center of 8 determines its high reactivity towards adjacent σ-bonds, resulting in a facile dehydrogenative borenium C–H insertion, leading to the cyclic cation 9. Quenching 9 with a suitable hydride source afforded the isolable cyclic amine borane 10.

Scheme 2.

The mechanism of dehydrogenative C–H borylation of N,Ndimethylneopentylamine borane 6 using stoichiometric Ph₃C⁺ activation.^[2a–c]

It is also possible to perform intramolecular borylations by using only a catalytic amount of a strong electrophile.^[2b,c] In this case only a small amount of 7 was produced by activation of the starting amine borane, and heating above 120 °C (typically in PhMe) was required to drive the process towards formation of the neutral cyclic product 10 and H₂. The initial mechanistic rationale assumed that the process involves intramolecular C–H insertion in borenium 8, which is generated by the thermal dissociative loss of 6 from the 3c2e-bonded cation 7. However, multiple discrepancies between this simple mechanism and experimental observations were soon identified and explicitly summarized in a previous communication,^[2c] outlining a clear need for a new mechanistic picture.

In proposing an alternative mechanism for the catalytic borylation, the following experimental observations must be accounted for:^[2c] (1) The role of H-bridged cations such as 7 is clearly significant, since the catalytic reaction was only shown to proceed efficiently with those electrophiles that led to generation of the L₂B₂H₅⁺ species. (2) The catalytic and stoichiometric processes display different regiochemical trends. (3) The rate-limiting step of the catalytic process appears to be a C–H insertion, and is primarily dominated by steric factors.

For C–H borylation to occur in a concerted insertion step, the key intermediate must be a coordinatively unsaturated boron species possessing both a sufficiently empty p-orbital, and a perpendicular “filled” orbital, such as an unshared electron pair in borylenes,^[10] or a hydridic B–H in boranes or borenium ions. The search for an alternative mechanism for the catalytic borylation began by noting that the L₂B₂H₅⁺ species are unstable with respect to loss of H₂ at 90 °C in d₅-PhBr solutions, even when no intramolecular borylation is possible. This observation suggested that the key borylating intermediate may be generated by the thermally induced loss of H₂ from L₂B₂H₅⁺, and computational studies (M06-2X/6-311++G(3df,2p)//MP2/cc-pVDZ, SMD solvation) were performed to outline a plausible mechanism for the cyclization of 6 in PhMe (Figure 1).

Figure 1.

The major features of the reaction profile calculated at M06-2X/6-311++G(3df,2p)//MP2/cc-pVDZ level of theory in PhMe solvent (SMD solvation). Path A represents the B–B dehydrocoupling mechanism proposed in this article, while Path B shows the previously considered mechanism inspired by the stoichiometric reaction. See the Supporting Information for details.

Since 7 can be viewed as the σ-complex of 8 and 6, it follows that the 3c2e-bonded cation 7 preorganizes the components for a dehydrogenative insertion of borenium 8 into the B–H bond of amine borane 6, in a fashion similar to the C–H insertion in the stoichiometric borylation process. Indeed, a sufficiently low-lying transition state (TS) 13 (G^‡ = 27.8 kcal/mol) was identified for the process leading from 7 to the B–B bonded L₂B₂H₃⁺ cation 14 and H₂ (Figure 1, Path A). In the most stable conformation of cation 14, the tricoordinate boron atom enjoys some stabilization from a C–H bond in the proximal neopentyl group, much like the borenium center in the lowest energy conformation of cation 8. Because of this stabilizing interaction, cation 14 preferentially exists in the open borenium form, although the isomeric C₂ symmetric H-bridged form is higher in energy by only 1.4 kcal/mol (gas phase, see the Supporting Information).

Natural bond orbital (NBO) analysis of the lowest energy structure of 14 reveals that natural charges of the two interconnected boron atoms are distinctly different, +0.80 and −0.42 for the tri- and tetracoordinate B centers, respectively. Additionally, LUMO of 14 has a substantial contribution from the unoccupied p-orbital of the tricoordinate B center, while the B–B σ-bonding orbital is contributing to HOMO of the cation.^[11] Therefore, since the tricoordinate B atom of 14 possesses an empty p-orbital (“acid”) orthogonal to the strongly polarized B–B σ-bond (“base”), it satisfies the requirements for a species capable of inserting into adjacent C–H σ-bonds. Indeed, the ability of diborane(4) 14 to react with proximal C–H bonds was confirmed by locating the appropriate TS 15 (G^‡ = 29.4 kcal/mol), leading directly to a new H-bridged product 16 containing the cyclized amine borane subunit. Hydride exchange between 16 and 6 delivers the final product 10, and regenerates the crucial intermediate 7, completing the catalytic cycle.^[12] The new mechanism is in good agreement with the requirements defined by the previous experimental work (vide supra), as H₂ loss from 7 indeed precedes the C–B bond formation, and the steric demands in 15 are more prominent than in 11, which is consistent with the higher selectivity of the catalytic process for less hindered borylation products.^[2c] The open form of 14 can also be viewed as a sp²–sp³ diborane(4), and the synthetic potential of this structural motif has recently been recognized in anionic and neutral, but not cationic setting.^[13] It should also be noted that this appears to be the first example of a cationic sp²–sp³ diborane(4) being formed in situ from L–BH₃ complexes, and functioning as the key species in the catalytic cycle.

In contrast, the borylation pathway proceeding via the same primary borenium 8 as in the stoichiometric transformation is characterized by a higher activation barrier (Figure 1, Path B). Dissociation of the H-bridged cation 7 to the starting amine borane 6 and borenium 8 is endergonic by 16.4 kcal/mol, and the C–H insertion transition state 11 is located even higher on the free energy profile (G^‡ = 35.9 kcal/mol).^[14] The chain of events leading from transition state 11 to the cyclized product via the thermodynamically unstable borenium H₂ complex 12 follows that of the stoichiometric borylation.^[2a]

Seeking experimental support for the reaction mechanism outlined in the computational studies, controlled thermal decomposition of L₂B₂H₅⁺ salts was performed.^[15] Hydride abstraction from Me₃P–BH₃ by 0.5 equiv of Ph₃C⁺ B(C₆F₅)₄⁻ in d₅-PhBr resulted in formation of the H-bridged cation 18a (δ ¹¹B −25.6 ppm, J_P–B = 90 Hz) (Figure 2). Heating to 90 °C led to disappearance of 18a, and formation of H₂ was detected by ¹H NMR (δ ¹H 4.51 ppm). Three new signals (δ ¹¹B −9.8, −33.4 and −38.9 ppm in ca. 1:1:2 ratio) attributable to cationic boron species were observed by ¹¹B NMR at this point, while stability of the counterion and Ph₃CH byproduct under the reaction conditions was confirmed by ¹⁹F and ¹H NMR spectroscopy, respectively. The multiplet at δ ¹¹B −33.4 ppm upon proton decoupling transformed into a triplet with J_P–B = 90 Hz, and was thus identified as originating from the unremarkable boronium cation 19a. The H-coupled broad signal at δ ¹¹B −9.8 ppm did not show any detectable coupling to ³¹P, while the complex multiplet at δ ¹¹B −38.9 ppm was transformed into a doublet with J_P–B = 110 Hz upon proton decoupling. Both signals were shown to originate from non-equivalent B atoms in the same boron cation, which was ultimately identified as the base-stabilized B₃H₆⁺ species 20a.^[16] Several triboron cations of this type have been prepared previously by either basic cleavage of tetraborane(10),^[17] or by reacting diborane(4) derivatives with boron Lewis acids,^[18,19] although formation of L₂B₃H₆⁺ cations from L₂B₂H₅⁺ has not been reported previously. Cation 20a can be viewed as an adduct of L₂B₂H₃⁺ (fragment highlighted in Figure 2) and “BH₃”, thus explaining formation of boronium salt 19a.^[20] Electrospray ionization mass spectra (ESI MS+) of the reaction mixture showed signals with m/z 165, 177 and 191, and the isotope peaks of the latter two signals were consistent with the presence of two and three B atoms, respectively. While the signals with m/z 165 and 191 are due to boronium 19a and triboron cation 20a, respectively, the intense m/z 177 signal is due to L₂B₂H₃⁺ cation, apparently arising from fragmentation of 20a, emphasizing close relationship of the two species.

Figure 2.

Formation of triboron cations 20 (L₂B₂H₃⁺ fragment highlighted) in the thermal decomposition of the H-bridged complexes 18. Below: ¹¹B NMR spectra (L = Me₃P, X = B(C₆F₅)₄) (i) immediately following generation of 18a in d₅-PhBr, and (ii) after 18 h at 90 °C. Other signals: B(C₆F₅)₄⁻, −16.2 ppm; Me₃P–BH₃, −36.4 ppm.

Similar observations were made when the activated trimethylamine borane derivative 18b (L = Me₃N, X = B(C₆F₅)₄⁻) was heated at 90 °C in d₅-PhBr. In this case disappearance of the L₂B₂H₅⁺ signal at δ ¹¹B −0.3 ppm was accompanied by appearance of new H-coupled peaks at δ ¹¹B −10.2 ppm and −15.8 ppm, although the latter partially overlapped with the B(C₆F₅)₄⁻ peak at −16.1 ppm. The signals were identified as the BH₂ (−10.2 ppm) and LBH (−15.8 ppm) subunits of 20b,^[18a] and formation of L₂BH₂⁺ boronium cation 19b (δ ¹¹B 3.6 ppm) was also observed. In this case ESI MS+ pattern (m/z 131 (19b), 143 (L₂B₂H₃⁺), 157 (20b)) paralleled that observed in Me₃P derivatives, supporting the general similarity of events in activated amine and phosphine boranes.^[21]

Conversion of L₂B₂H₅⁺ (18) to L₂B₃H₆⁺ (20) is reminiscent of the processes observed in isostructural boron anions, such as formation of the stable σ-aromatic B₃H₈⁻ anion by thermolysis of B₂H₇⁻,^[22] which is believed to proceed via the poorly known B₂H₅^−.[23,24] Thermal dehydrogenation of H-bridged cations 7 and 18 is thus expected to generate cationic analogs of B₂H₅⁻ (i.e. 14), which subsequently stabilize either by intramolecular C–H insertion (formation of 16), or BH₃ incorporation leading to L₂B₃H₆⁺ cations such as 20. Since 20 was shown previously to produce diborane(4) derivatives upon treatment with Lewis bases,^[17,18] thermolysis of 18, followed by basic cleavage of the resulting triboron cation 20 can be viewed as a method for building electron-precise B–B bonds from mononuclear L–BH₃ complexes.^[4c,25] While instability of the corresponding neutral L₂B₂H₄ complex prevented independent generation of 14 by hydride abstraction,^[26] it should be noted that the ability of L₂B₂H₃⁺ to insert into σ-bonds is not without precedent.^[27]

It was also of interest to explore the thermal behavior of H-bridged cations paired with anions that are less stable to electrophilic attack, and the reactivity of amine and phosphine boranes with B(C₆F₅)₃ was thus explored. Addition of Et₃N–BH₃ to 0.5 equiv of B(C₆F₅)₃ in CD₂Cl₂ at rt resulted in a rapid hydride abstraction and formation of the H-bridged cation 21 (B–H–B, ¹H δ −2.0–−3.3 ppm; ¹¹B δ −3.0 ppm, unres. t.) (Scheme 3). Unlike in the trityl activation experiments described above, the other product of the hydride abstraction was the HB(C₆F₅)₃⁻ counterion (δ ¹¹B −25.4 ppm, d, J_{B –H} = 80 Hz), and the difference in the counterion structure and stability was found to have a prominent effect on the subsequent events. Thus, even at rt degradation of the H-bridged cation 21 was evident, and heating the solution to 40 °C resulted in formation of B₂H₆, and another compound identified as 22 (δ ¹¹B −14.2 ppm) upon isolation. Formation of 22 is the result of disproportionation involving some HB(C₆F₅)₃⁻ derivative, and despite the 1:1.5 “R₃N–BH₃”:“C₆F₅” reaction stoichiometry, only C₆F₅BH₂ complexes were formed.^[28]

Scheme 3.

Formation of 22 by disproportionation of 21.

The reaction was further developed to a preparative protocol, optimized with respect to decreasing the amount of B(C₆F₅)₃ used (0.36 equiv vs. theoretical 0.33 equiv), and simplified product isolation, which in most cases was accomplished by filtering the reaction mixture through a plug of silica gel, followed by removal of the solvent. The results listed in Table 1 suggest that this method can be conveniently used to access C₆F₅BH₂ complexes of simple tertiary amines and phosphines.^[29]

Table 1.

Synthesis of C₆F₅BH₂ complexes^[a]

Entry	Substrate	Solvent	Product	Yield
1[b]	Et3N–BH3	PhF	Et3N–BH2C6F5 (22)	>99%
2	Me3N–BH3	CH2Cl2	Me3N–BH2C6F5 (23)	97%
3	BnMe2N–BH3	PhF	BnMe2N–BH2C6F5 (24)	>99%
4[c]	Ph3P–BH3	CH2Cl2	Ph3P–BH2C6F5 (25)	71%

^[a]0.36:1 B(C₆F₅)₃:L–BH₃; 50 °C; 1 h; the reaction performed in sealed vials.

^[b]3 h.

^[c]40 °C.

To summarize, involvement of highly electrophilic L₂B₂H₃⁺ complexes in the high-temperature intramolecular C–H borylation of amine boranes activated with catalytic amounts of strong “hydridophiles” is postulated based on experimental and theoretical studies. Such sp²–sp³ diborane(4) cations are formally isoelectronic to B₂H₅⁻, and appear to arise from the thermally induced dehydrogenative borenium B–H insertion within the isolable H-bridged cations L₂B₂H₅⁺. High reactivity of the cation L₂B₂H₃⁺ manifests itself either in high-yielding intramolecular C–H insertions proceeding with the cleavage of the B–B bond, or in BH₃ incorporation resulting in formation of the more stabilized L₂B₃H₆⁺ cation. In view of these findings, it appears plausible that new borylating reagents can be identified among electrophilically activated diborane(4) derivatives, particularly those of the sp²–sp³ type.