Electrophilic boron carboxylate and phosphinate complexes †

The reactions of a series of carboxylic acids with H2B(C6F5)·SMe2 are shown to afford species of the form [RC(O)OB(C6F5)]2O, (R = Tol 1, Ph 2, C6F5 3, Me2BrC 4, Me 5) in 87–95% yields with the concurrent reduction of the carboxylic acid to the corresponding aldehyde. A mechanism for the formation of 1–5 is proposed to proceed via a cyclic eight-membered ring species. Analogues of these species were prepared via reactions of carboxylic and phosphinic acids with HB(C6F5)2 and H2B(C6F5)·SMe2, respectively, to give [TolC(O)OB(C6F5)2]2 6, [(C6F5)C(O)OB(C6F5)2]2 7, and [Ph2P(O)OBH(C6F5)]2 8. These products react subsequently to give TolC(O)OBH(C6F5)(NC5H4NMe2) 9 and Ph2P(O)OBH(C6F5)(NC5H4NMe2) 10. The acyloxyborate derivatives 1–4 were shown to be inactive in mediating the direct amidation of carboxylic acids, consistent with previous observations that infer the need for a sterically congested environment about the boron centres.


Introduction
The formulation of acyloxyboranes generated a lot of confusion in the early literature, specifically over the formulation of the product derived from the reaction of orthoboric acid and acetic anhydride.Originally thought to be boron acetate, this notion was revised in 1957 when Hayter et al. 1 correctly formulated the product as the acyloxyborate [RC(O)OBR′] 2 O (Scheme 1).Subsequently, a number of related studies have provided structural data or established new protocols to such species.These include reports by the groups of Lappert, 2 Perotti, 3 Sporzyński, 4 Köster, 5 and Wrackmeyer. 6Despite the relatively few studies of these compounds, acyloxyborates have found important applications in fire-proofing polymer compositions, as stabilisers for synthetic rubbers, and in the pharmaceutical industry. 7elated boron carboxylate species have also been proposed as intermediates in dehydrative condensations between a carboxylic acid and an amine using catalysts derived from borate esters [8][9][10] as well as boric, 11 boronic, [12][13][14][15][16][17][18][19][20][21] and borinic acids. 22ecently however, Whiting and coworkers 23 have suggested an alternative mechanism in which an oxo-bridged bis-boron species, i.e. an acyloxyborate, acts as the catalytically active species for direct amidation reactions (Scheme 1).In this catalysis, Whiting 23 showed that acyloxyborates are generated in situ by the reaction of boronic and carboxylic acids in the presence of molecular sieves, although these authors were able to prepare related species directly from the reaction of an arylboronic acid and phenylacetic acid.The intermediacy of these acyloxyborates was further supported by Ishihara and coworkers, 24 who showed that ortho-substituents on the boronbound aryl group prevented the coordination of amine to boron, thus accelerating the catalysis.
Our interest in boron-based species that incorporate electron withdrawing substituents has prompted us to probe related carboxylate derivatives.As is well established that borohydride reductions of carboxylic acids proceed via boron-carboxylate species, 25,26 we were interested in probing the reactions of carboxylic acids with the electrophilic boranes.In the initial effort, we previously reported the preparation of the salt [Cp* 2 Fe][PhCO 2 B(C 6 F 5 ) 3 ] via the one electron reduction of a peroxide in the presence of a borane. 27,28Herein, we describe the reactions of H 2 B(C 6 F 5 )•SMe 2 29 and HB(C 6 F 5 ) 2 with carboxylic and phosphinic acids.Generally, these reactions result in eight-membered cyclic products, while the reactions of H 2 B (C 6 F 5 )•SMe 2 and carboxylic acids provide a facile route to bicyclic acyloxyborate derivatives with concurrent acid-reduction to aldehyde.Experimental and computational data support a proposed mechanism for the formation of the latter products.The catalytic utility of these acyloxyborate species in the direct amidation reactions is also probed.

Results and discussion
The reaction of p-toluic acid with Lancaster's reagent, H 2 B (C 6 F 5 )•SMe 2 , 29 was performed in DCM at room temperature prompting the evolution of H 2 .Repeated reactions showed that all the reagents were consumed when combined in an acid to borane ratio of 3 : 2. The 11 B NMR spectrum revealed the complete conversion of H 2 B(C 6 F 5 )•SMe 2 into a new fourcoordinate boron species that exhibited a broad resonance at 5.1 ppm.The 19 F{ 1 H} NMR spectrum showed a gap between the resonances attributed to the meta-and para-fluorine atoms of the perfluorinated arene rings (Δδ = 8.3 ppm), consistent with the presence of a four-coordinate boron centre.After work-up, a white solid 1 was isolated in 95% yield (Scheme 2).Single crystals for X-ray diffraction analysis were obtained through diffusion of pentane into a benzene solution at ambient temperature (Fig. 1).The solid-state structure showed that 1 was [TolC(O)OB(C 6 F 5 )] 2 O, a [3,3,1] bicycle in which two boron centres are linked by a bridging oxygen atom and two carboxylate ligands.In a similar fashion, benzoic acid, pentafluorobenzoic acid, 2-bromo-2-methylpropionic acid, and acetic acid reacted with H 2 B(C 6 F 5 )•SMe 2 to give the products formulated as [RC(O)OB (C 6 F 5 )] 2 O (R = Ph 2, C 6 F 5 3, Me 2 BrC 4, Me 5) in 87-90% yields (Scheme 1).The spectroscopic data for these compounds were similar to those described for 1. Crystallographic studies also confirmed the formulations of 2 and 3 (Fig. 1).
The structural data for 1-3 confirmed a pseudo-tetrahedral geometry about the two boron centres linked by an oxygen atom and bridged by two carboxylate units.In addition to H 2 , the second by-product in the formation of 1-5 was identified as the aldehyde derived from the reduction of the starting carboxylic acid.Examination of the reaction mixture by DART-MS confirmed the formation of the corresponding aldehyde (for details see the ESI †).In addition, the 1 H NMR spectrum of the reaction mixture of compound 1 showed a broad resonance ca. 12 ppm, supporting the presence of the corresponding aldehyde.
The mechanism of the formation of 1-5 is thought to be initiated by protonolysis generating boryl-ester.Dimerization of this species is consistent with the electrophilic nature of the boron centre.In the subsequent reaction with a third equivalent of acid, its carbonyl fragment is in close proximity to a boron hydride, which presumably results in the liberation of aldehyde and the formation of the oxo-bridge between the two boron centres (Scheme 3).
In support of the proposed initial dimerization in this mechanism, a related product was derived from the reaction of p-toluic acid with Piers' borane, HB(C 6 F 5 ) 2 . 30This reaction afforded the near quantitative formation of a product formulated as [TolC(O)OB(C 6 F 5 ) 2 ] 2 6 (Scheme 4).The 19 F NMR spectrum showed resonances at −135.1, −154.0, and −162.1 ppm, while the 11 B NMR signal was observed at 5.2 ppm.These data are consistent with four-coordinate boron centres and this was confirmed crystallographically (Fig. 2).The structure demonstrates the eight-membered ring in which the carboxylic units bridge the two boron centres.This species is structurally similar to dialkyl-group 13 carboxylates reported by Justyniak et al. 31 as well as the species [Ph 2 PO 2 B(C 6 F 5 ) 2 ] 2 . 32Overall, this ring adopts a pseudo-boat conformation in which the C 6 F 5 rings on each of the boron atoms are oriented so as to permit π-stacking.This observation appears to be a solid-state packing effect as this inequivalence of the fluoroarene rings is not reflected in the 19 F NMR spectral data.
In a similar fashion, the corresponding reaction of pentafluorobenzoic acid with Piers' borane, HB(C 6 F 5 ) 2 , afforded the product formulated as [(C 6 F 5 )C(O)OB(C 6 F 5 ) 2 ] 2 7 in 83% isolated yield (Scheme 4).While the 19 F and 11 B NMR data were consistent with the formulation of 7, its poor solubility precluded the acquisition of 13 C data.
In an analogous reaction, the combination of stoichiometric amounts of H 2 B(C 6 F 5 )•SMe 2 and Ph 2 P(O)OH was performed.This led to the release of H 2 and the formation of a clear and colourless solution after 12 h (Scheme 4).A colourless crystalline solid 8 was isolated in 68% yield after workup.Dissolution of 8 in CDCl 3 gives rise to two 31   37.6 ppm was altered slightly to 1 : 0.56.These data suggest a dynamic equilibrium in which a dimer formulated as [Ph 2 P(O)OBH(C 6 F 5 )] 2 dissociates to a monomeric species.Subsequently, single crystals of 8 suitable for X-ray diffraction analysis were obtained by cooling a saturated dichloromethane solution of 8 at −35 °C.The solid-state structure revealed a dimeric structure with the expected eight-membered ring, adopting a pseudo-chair conformation (Fig. 3).The B-O and P-O bond distances were found to be on average 1.438(6) and 1.525(3) Å, respectively.
The nature of 8 is analogous to the proposed intermediate Int, in the above reactions with carboxylic acids.However, in contrast to the carboxylic acid analogues, efforts to react 8 with an excess amount of diphenylphosphinic acid or with carboxylic acids failed.In addition, 8 did not react with 1,4-pentadiene in toluene even on heating to 110 °C for 12 h.The latter result is consistent with the strong basicity of the phosphinic acid fragment that binds to boron, precluding the generation of a transient boron centre necessary for hydroboration.
While the NMR data for 8 suggests a monomer/dimer equilibrium, the corresponding data for 6 indicate a robust eightmembered ring.Nonetheless, the reaction of 6 and 8 with DMAP resulted in the formation of new species 9 and 10, respectively.In the case of 9, the 19  , respectively (Scheme 5).These formulations were confirmed crystallographically (Fig. 4).The B-O distances in 9 and 10 were found to be 1.484(3) and 1.485(3) Å, while the B-N distances were 1.605(3) and 1.595(4) Å, respectively.
To probe the stability of 8 further, DFT computations were performed at the M062X/def2-TZVPP level of theory with GD3 dispersion and PCM modelling of dichloromethane solvation.Given that 8 is the phosphinic acid analogue of the proposed intermediate, Int1 (Scheme 2), in the formation of 1-5, the optimized structures of 8 and Int1 were computed.Interestingly, the lowest energy conformation of 8 is one in which the hydride atoms on boron adopt a transoid conformation.In contrast, for Int1 the orientation in which the hydride atoms are cisoid is lower in energy.This difference is attributed to the minimization of steric conflict in 8.The HOMO for 8 is located on the fluoroarene rings, whereas the hydride atoms on boron in Int1 contributed to the HOMO (Fig. 5).Finally, as Whiting has proposed that the active catalysts in their direct amidation reactions are structurally analogous to 1-5, the utility of the present compounds was probed.Addition of two equivalents of aniline to the species 1-4 generated insoluble products that could not be characterised.However, the corresponding reaction of 5 gave soluble products and showed the generation of a trace amount of amide after 12 h as evidenced by the 1 H NMR spectrum (see the ESI †).The corresponding 11 B NMR spectrum revealed the consumption of 5 and the appearance of two signals at 3 and 18 ppm.These results were reminiscent of data presented by Whiting 23 and Ishihara 24 for analogous species with sterically unencumbered boron centres.Although these products could not be isolated from the present reaction, the inability of 5 to catalyse amide formation is consistent with the need for steric hindrance about the boron atom to prompt nucleophilic attack at the carbon of a bridging carboxylic group, thereby prompting the amidation pathway as proposed by Whiting and Ishihara.This notion is also supported by the formation of 9 and 10 which illustrates the ready access of a donor to the respective boron sites in 6 and 8.

Conclusions
In summary, synthetic methods to new acyloxyborates of the formula [RC(O)OB(C 6 F 5 )] 2 O (1-5) are derived from the reactions of H 2 B(C 6 F 5 )•SMe 2 with carboxylic acids.These species are formed via reactions involving protonolysis of the B-H bonds and reduction of carboxylic acid to generate the corresponding aldehyde.The mechanism is proposed to proceed via a cyclic intermediate that dissociates and allows the B-H bonds to react with an additional equivalent of carboxylic acid.This proposed intermediate is analogous to the cyclic species 6-8.For the latter species, the lack of steric effects of the orthosubstituent on the boron atoms results in dimer cleavage and facile binding of donors to the boron centres affording 9 and 10.These observations together with the ineffective catalytic activity of 1-5 in direct amidation reactions are consistent with the previous inference of the need for steric congestion to generate a catalytically active acyloxyborate. 23,24Efforts to use boron carboxylate derivatives as catalysts in a variety of reactions are the subject of ongoing study.

X-ray diffraction studies
Single crystals were coated with paratone oil, mounted on a cryoloop and frozen under a stream of cold nitrogen.Data were collected on a Bruker Apex2 X-ray diffractometer at 150(2) K for all crystals using graphite monochromated Mo-Kα radiation (0.71073 Å).Data were collected using Bruker APEX-2 software and processed using SHELX and an absorption correction applied using multi-scan within the APEX-2 program.All structures were solved and refined by direct methods within the SHELXTL package.

Scheme 4
Scheme 3 Proposed mechanism for the formation of 1-5.

Fig. 2
Fig. 2 POV-ray depiction of 6. C: black, O: red, B: yellow-green, and F: pink.All hydrogen atoms have been omitted for clarity.
F NMR spectrum showed signals at −133.5, −157.3, and −163.6 ppm while the 11 B resonance was seen at 1.6 ppm, consistent with a four-coordinate boron centre.A similar conclusion was drawn for 10 based on the 19 F NMR signals at −134.9, −158.1, and −164.0 ppm, with the 11 B signal at 0.8 ppm.The 31 P NMR resonance for 10 was seen at 25.3 ppm.These data suggest the coordination of DMAP to the boron centres of 9 and 10, resulting in products TolCO 2 BH(C 6 F 5 )(NC 5 H 4 NMe 2 ) and Ph 2 PO 2 BH(C 6 F 5 ) (NC 5 H 4 NMe 2 )

Fig. 3 Scheme 5
Fig. 3 POV-ray depiction of 8. C: black, O: red, B: yellow-green, F: pink, P: orange, and H: white.All hydrogen atoms except those on boron have been omitted for clarity.

Fig. 4
Fig. 4 POV-ray depictions of (a) 9 and (b) 10.C: black, O: red, B: yellow-green, F: pink, P: orange, O: red, N: blue, and H: white.All hydrogen atoms except those on boron have been omitted for clarity.
General remarksAll reactions and work-up procedures were performed under an inert atmosphere of dry, oxygen-free N 2 by means of standard Schlenk techniques or glovebox techniques (MBRAUN glovebox equipped with a −35 °C freezer) unless otherwise specified.All glassware was oven-dried and cooled under vacuum before use.Dichloromethane (DCM) was distilled over CaH 2 .Pentane was collected from a Grubbs-type column system manufactured by Innovative Technology and degassed.Solvents were stored over activated 4 Å molecular sieves.Molecular sieves, type 4 Å ( pellets, 3.2 mm diameter), purchased from Sigma Aldrich were activated prior to usage by iteratively heating under vacuum for 24 hours.CDCl 3 purchased from Cambridge Isotope Laboratories was vacuum distilled, further degassed, and stored over activated 4 Å molecular sieves in a glovebox for at least 8 hours prior to use.Unless otherwise mentioned, chemicals were purchased from Sigma Aldrich or TCI.Lancaster's reagent H 2 B(C 6 F 5 )•SMe 2 29 and Piers' borane HB(C 6 F 5 ) 2 30 were prepared using literature methods.NMR spectra were recorded at room temperature (298 K) unless otherwise mentioned on a Bruker Avance III 400 MHz, an Agilent DD2 400, and an Agilent DD2 500.Spectra were referenced to the residual solvent signals (CDCl 3 : 1 H = 7.26; 13 C = 77.2ppm; toluene-d 8 : 1 H = 7.09, 7.01, 6.97, and 2.08 ppm and 13 C = 137.48,128.87, 17.96, 125.13, and 20.43 ppm).Chemical shifts (δ) are reported in ppm and coupling constants ( J) are listed as absolute values in Hz.Multiplicities are reported as singlet (s), doublet (d), triplet (t), multiplet (m), overlapping (ov), and broad (br).High-resolution mass spectra (HRMS) were obtained on a JMS-T100LC JOEL DART mass spectrometer.Elemental analyses for C, H, and N were performed by ANALEST (University of Toronto) employing a PerkinElmer 2400 Series II CHNS Analyser.