Adam J. V. Marwitz

Recent Advances in Azaborine Chemistry

The chemistry of organoboron compounds has been primarily dominated by their use as powerful reagents in synthetic organic chemistry. Recently, the incorporation of boron as part of a functional target structure has emerged as a useful way to generate diversity in organic compounds. A commonly applied strategy is the replacement of a CC unit with its isoelectronic BN unit. In particular, the BN/CC isosterism of the ubiquitous arene motif has undergone a renaissance in the past decade. The parent molecule of the 1,2-dihydro-1,2-azaborine family has now been isolated. New mono- and polycyclic B,N heterocycles have been synthesized for potential use in biomedical and materials science applications. This review is a tribute to Dewars first synthesis of a monocyclic 1,2-dihydro-1,2-azaborine 50 years ago and discusses recent advances in the synthesis and characterization of heterocycles that contain carbon, boron, and nitrogen.

A Hybrid Organic/Inorganic Benzene

Benzene (c-C6H6) is arguably one of the most fundamentally significant small molecules in chemistry. First discovered by Faraday in 1825, the study of benzene introduced the basic concept of aromaticity and delocalization. In addition to its fundamental importance, benzene and its derivatives (arenes) are ubiquitous in chemical research with numerous applications ranging from biomedical research to materials science. The inorganic isoelectronic relative of benzene, borazine (cB3N3H6), [4] has also played a pivotal role in fundamental as well as applied chemistry. The isoelectronic and isostructural relationship between the B N and C=C bond and its consequence on the aromaticity of borazine has been a topic of discussion. From a more applied perspective, borazine serves as a precursor to BN-based ceramic materials. More recently, borazine has been implicated in chemical hydrogen storage applications because it is formed as an intermediate in the hydrogen release from ammonia– borane. Both benzene and borazine have been known for more than 80 years, and consequently, their chemical and physical properties have been thoroughly investigated. The corresponding organic/inorganic (or organometalloidal) hybrid structure containing carbon, boron, and nitrogen, that is, 1,2-dihydro-1,2-azaborine 1, has thus far eluded characterization. The development of boron–nitrogen heterocycles such as 1,2-dihydro-1,2-azaborines (from hereon in, abbreviated as 1,2-azaborines) has been a relatively unexplored area of research. Dewar and White pioneered the chemistry of monocyclic and ring-fused polycyclic 1,2-azaborine derivatives in the 1960s. Recently, contributions by the groups of Ashe, Piers, and Paetzold, as well as our group have further advanced the preparation of novel BN heterocycles and sparked a renewed interest in the chemistry and properties of these compounds. Despite the advances achieved to date, and given the powerful tools made available by modern chemical synthesis, it is surprising that a simple heterocycle such as the parent 1,2-dihydro-1,2-azaborine 1 has remained elusive. Dewar attempted its synthesis and isolation in 1967 but ultimately concluded that it “seems to be a very reactive and chemically unstable system, prone to polymerization and other reactions.” Herein, we describe the first isolation and characterization of 1,2-dihydro-1,2-azaborine. Its successful preparation allows a direct comparison of the physical and spectroscopic properties of the series of an organic, inorganic, and now, an organometalloidal benzene. The present study demonstrates that 1,2-dihydro-1,2-azaborine 1 is not only isolable but it actually exhibits remarkable stability, consistent with substantial aromatic character. Our experimentally determined structural and spectroscopic properties are consistent with values derived from high-level computations. Scheme 1 illustrates our synthetic route to compound 1. Coupling of the in situ-generated allylboron dichloride with tert-butyldimethylsilyl allyl amine (TBS allyl amine) furnished diene 2. Ring-closing metathesis of this intermediate with the first-generation Grubbs catalyst produced an isomeric mixture of 3 and 3’ (60:40 ratio) in 82 % yield. Dehydrogenation of this mixture was carried out in the presence of catalytic amounts of Pd/C to generate 4. Treatment of heterocycle 4 with LiBHEt3 installed the B H functionality to give 5 in quantitative yield. Complexation of 1,2-azaborine 5 to {Cr(CO)3} produced the piano-stool adduct 6. Subsequent removal of the N-protecting group gave 7 in 76% yield. Finally, decomplexation of 1 from {Cr(CO)3} was accomplished using triphenylphosphine. The use of {Cr(CO)3} as a temporary “protecting group” was necessary because efforts toward cleaving the N TBS bond directly from 5 were unsuccessful. Compound 1 proved to be difficult to isolate, owing to its high volatility. However, we ultimately accomplished its isolation (10 % yield) by fractional vacuum transfer in the presence of a low-boiling [*] M. H. Matus, Prof. Dr. D. A. Dixon Department of Chemistry, University of Alabama Tuscaloosa, AL 35487 (USA) E-mail: dadixon@as.ua.edu

Boron mimetics: 1,2-dihydro-1,2-azaborines bind inside a nonpolar cavity of T4 lysozyme.

The element boron has not received much attention in biomedical applications compared to its periodic table neighbors carbon, nitrogen and oxygen. Arguably, this might be due to the apparent “insignificance” of boron in Nature’s evolution of life.[1,2] Boron has however useful elemental and chemical features that include nuclear spin, large cross section for neutron capture, and Lewis acidity. If boron could be incorporated into biologically relevant molecules[3] it might benefit biomedical research by being used as a marker,[4] as a new pharmacophore,[5] or in cancer therapy.[6] We are interested in synthetic approaches that will allow the incorporation of boron into such molecules[7] with minimal perturbation of their structures. 1,2-Dihydro-1,2-azaborines (abbreviated as 1,2-azaborines) serve as a unique structural platform to accomplish this goal because of their isostructural relationship with arenes, a ubiquitous motif in living organisms and in pharmaceuticals. Furthermore, the bonding of arenes with cations and other arenes through cation-π[8] and π-π[9] interactions have been demonstrated to be vital in biological systems. Thus, the broad utility and fundamental importance of arenes in biomedical research combined with the unique elemental/chemical features of boron, and the potential of expanding the diversity of arene structures through CC/BN isosterism[10] make 1,2-azaborines attractive targets for biomedical investigation (Scheme 1).

Dihydrogen Activation with tBu3P/B(C6F5)3: A Chemically Competent Indirect Mechanism via in Situ-Generated p-tBu2P–C6F4–B(C6F5)2

A chemically competent indirect pathway for the activation of dihydrogen by the nonmetal Lewis acid/Lewis base pair (t)Bu(3)P/B(C(6)F(5))(3) is described. The reaction between (t)Bu(3)P and B(C(6)F(5))(3) produces [(t)Bu(3)PH](+)[FB(C(6)F(5))(3)](-) and the known phosphinoborane p-(t)Bu(2)P-C(6)F(4)-B(C(6)F(5))(2) (1-(t)Bu) with elimination of isobutylene. At 1:1 stoichiometry, 1-(t)Bu is produced rapidly in detectable quantities and can act as a catalyst for the formation of [(t)Bu(3)PH](+)[HB(C(6)F(5))(3)](-) from (t)Bu(3)P and B(C(6)F(5))(3) in the presence of H(2). The extent to which this indirect path competes with the direct path is explored.

BN-substituted diphenylacetylene: a basic model for conjugated π-systems containing the BN bond pair

We report the synthesis, structural characterization, and optoelectronic properties of BN-Tolan 1 and Bis-BN-Tolan 2, one of the simplest conjugated systems containing the BN bond pair. BN-tolans 1 and 2 display absorption and emission properties that are distinct from their carbonaceous analogue, tolan. In addition, Bis-BN-Tolan 2 exhibits unique N–H⋯π(C≡C) hydrogen bonding in the solid state.

1,2-Azaborine Cations†

1,2-Dihydro-1,2-azaborine is a six-membered aromatic heterocycle that is isoelectronic with benzene through the replacement of a C=C unit in benzene with an isoelectronic B–N unit.[1,2] Since the pioneering work by Dewar et al.,[3,4] significant advances have been made in the synthesis and reactivity studies of this family of heterocycles.[5–7] Our continued exploration of the 1,2-azaborine motif[8–15] has led us to consider the synthesis of cationic 1,2-azaborines, for which no examples have been reported. In particular, we envisioned that substitution of 1,2-azaborine on the boron atom with pyridine derivatives would furnish cationic biaryl-type structures[16] having the potential for use in materials applications (Scheme 1). Herein we report the synthesis, structural characterization, and optoelectronic properties of pyridine-substituted 1,2-azaborine cations, including a cationic heterocyclic analogue of para-terphenyl. Scheme 1 1,2-Azaborine cations. We have previously established nucleophilic substitution of the B–Cl bond in 1,2-azaborines by anionic nucleophiles (with Cl− serving as the leaving group).[8] Less reactive neutral nucleophiles did not displace the chloride from the boron atom. We hypothesized that a better leaving group on the boron atom (e.g., OTf) could render it susceptible to nucleophilic attack by weaker neutral nucleophiles. In the course of our studies, we discovered that silver reagents facilitate the ligand exchange at the boron position in 1,2-azaborines.[13] We were thus pleased to discover that treatment of 1,2-azaborine 1 with AgOTf produced the substituted 1,2-azaborine 2 in 59% yield as an extremely moisture-sensitive liquid (Scheme 2). The 1,2-azaborine 2 was characterized by 1H, 11B, and 13C NMR spectroscopy as well as IR spectroscopy. Scheme 2 Synthesis of 2. Tf = trifluoromethanesulfonyl. Heterocycle 2 readily reacts with para-substituted pyridines to form the desired cationic 1,2-azaborines 3. As can be seen from Scheme 3, the substitution reaction is independent of the electronic nature of the nucleophile. Excellent yields have been obtained with both electron-rich and electron-poor pyridines. Scheme 3 Synthesis of 1,2-azaborine cations 3. The 1,2-azaborine cations 3 are highly crystalline solids that fluoresce under UV light. We thus explored the solid-state fluorescence of the pyridine-substituted 1,2-azaborine cations 3. The solid-state fluorescence and quantum yields of aromatic hydrocarbons, including para-terphenyl, have been reported using an integrating sphere.[17] We have recorded the fluorescence spectra of crystalline samples of 3a–e (Figure 1), all of which were freshly recrystallized prior to making the fluorescence measurements. The solid-state fluorescence of 3a (R = Me) shows a peak at λem = 436 nm (ΦPL = 0.03) and is visibly less fluorescent than samples of 3b and 3c under a UV lamp (λ = 365 nm; see Figure 1, right). The solid-state emission spectrum of 3b (R = Ph) showed a relatively narrow band at λem = 448 nm (ΦPL = 0.86). The high quantum yield observed for 3b is quite similar to the values obtained for para-terphenyl, though the emission maximum of the cationic 3b is bathochromically shifted relative to the all-carbon para-terphenyl by approximately 75 nm.[17] We found that solid samples of 3c (R = H) were blue-green fluorescent (see Figure 1) with a relatively broad emission maximum at λem = 469 nm (ΦPL = 0.30). Compound 3d (R = CF3) exhibits yellow-green emission at λem = 527 nm (ΦPL = 0.11), which contrasts the blue emission observed for geometrically similar 3a. The data illustrated in Figure 1 suggest that the para substituent on pyridine has a substantial effect upon the emissive properties of 1,2-azaborine cations. DMAP-substituted 3e (R = NMe2;DMAP = 4-dimethylaminopyridine) does not fluoresce in the solid state (Figure 1, right), which is consistent with the reported fluorescence quenching by the presence of a nitrogen lone pair of electrons.[18] Figure 1 Normalized solid-state fluorescence spectra and images (under UV irradiation) of 1,2-azaborine cations 3. We also determined the absorption properties of 1,2-azaborine cations 3 in solution. The absorption maximum of 3a (R = Me) in CH2Cl2 was found at λ = 287 nm with an extinction coefficient of e = 12 713 m−1 cm−1. The absorption spectrum of 3b showed a broad, featureless peak at λ = 292 nm (e = 21 869 m−1 cm−1), which is close to that observed for 3a, but is slightly bathochromically shifted from the absorption maximum of para-terphenyl (observed at λ = 280 nm in CH2Cl2).[19] The absorption spectrum of 3c (R = H) also showed a broad peak at λ = 286 nm (e = 8624 m−1 cm−1). The observed absorption peaks of 3d at λ = 285 nm (e = 8126 m−1 cm−1) and 3e at λ = 283 nm (e = 21 303 m−1 cm−1) are relatively unchanged from the other derivatives of 3. Interestingly, of the prepared cationic derivatives, only terphenyl analogue 3b was found to be fluorescent in solution. The fluorescence spectrum of 3b in CH2Cl2 showed an emission peak at λem = 360 nm (ΦPL = 0.06), and the absorption maximum was found at λ = 292 nm in CH2Cl2 (Figure 2). The large Stokes shift of 68 nm for 3b is indicative of considerable reorganization between the ground and the excited state. We also observed a bathochromic shift in the emission peak when MeCN was used as the solvent (λem = 382 nm, ΦPL = 0.17) instead of CH2Cl2. Furthermore, the fluorescence of 3b in MeCN was quenched upon the addition of NaI,[20] highlighting the potential of these materials in sensing applications. Figure 2 Normalized absorption (dashed line) and emission (solid line) spectra of 3b in CH2Cl2. Table 1 summarizes the photophysical properties of pyridine-substituted 1,2-azaborine cations 3a–e. To assess whether the extended conjugation provided by the 1,2-azaborine ring is critical for the observed optoelectronic properties of the 1,2-azaborine cations 3, we prepared the corresponding protonated pyridinium species 4a–e (Scheme 4). We determined that under the same conditions for 3, pyridinium triflate salts 4a–e do not exhibit solid-state fluorescence emission in the visible region. This is consistent with a critical role of the 1,2-azaborine moiety in the observed emission properties of 1,2-azaborine cations 3. Scheme 4 Table 1 Photophysical data for 3a–3e. We have obtained the X-ray crystal structures of 1,2-azaborine cations 3 (except for 3c), thus unambiguously establishing their structural identity. As a representative example, the solid-state structure of 3b is illustrated in Figure 3 and reveals that the pyridine nitrogen atom is bound to the boron atom with the triflate group serving as a noncoordinating anion.[21] As expected, the dative exocyclic B–N bond (B-N(2) = 1.531(2) A) in 3b is significantly longer than the covalent exocyclic B–NPh2 bond in a 1,2-azaborine recently reported in our group (B-N(2) = 1.486(2) A).[9] The exocyclic B–N bond in cationic 3b is slightly shorter than the B–N bond in the charge-neutral borabenzene-4-phenylpyridine adduct (B-N = 1.551(3) A) reported by Fu and coworkers.[22] The 1,2-azaborine ring in 3b is completely planar and is twisted by approximately 50° relative to the pyridine ring. In contrast, the phenyl ring of 3b is only slightly twisted relative to the pyridine ring (18°). Figure 3 ORTEP illustration of 3b, with thermal ellipsoids drawn at the 35% probability level (hydrogen atoms have been omitted for clarity). Bond distances (in A): B-N(1) 1.413(2), B-N(2) 1.531(2), B-C(3) 1.496(2), C(3)-C(4) 1.369(2), C(4)-C(5) 1.408(3), ... We were also interested in examining the structural features of the 1,2-azaborine ring in 3b. The intra-ring B–N bond is short (B-N(1) = 1.413(2) A), as is the intra-ring B–C bond (B-C(3) = 1.496(2) A), which is consistent with bond distances observed for electron-deficient 1,2-azaborines.[13] Selected bond parameters for 1,2-azaborine cations 3 are given in Table 2. The para substituent in the pyridine ring has little influence on the observed bond lengths, which are virtually identical for all derivatives. The torsion angles between the pyridine and 1,2-azaborine ring are similar for derivatives 3a, 3b, and 3d, although in 3e (R = NMe2) the 1,2-azaborine ring is nearly perpendicular to the pyridine ring. It noteworthy that the 1,2-azaborine cations 3 represent a new family of borenium cations for which only a few members have been structurally characterized by single-crystal diffraction.[23] Table 2 Selected bond distances [in A] and angles [°] for 1,2-azaborine cations 3. In summary, we prepared the first examples of 1,2-azaborine cations through a nucleophilic substitution reaction between pyridine nucleophiles and the highly Lewis acidic 1,2-azaborine 2. 1,2-Azaborine cations 3a–3d exhibit solid-state fluorescence that is distinct from the neutral all-carbon analogues. Furthermore, 4-phenylpyridine-substituted 1,2- azaborine cation 3b, an analogue of terphenyl, displays solution-phase fluorescence in addition to solid-state emission. Control experiments establish the 1,2-azaborine ring as an essential component for the observed optoelectronic properties. This study highlights the unique properties of 1,2-azaborine cations and underscores the potential utility of these complexes in materials applications.

Microwave spectrum, structural parameters, and quadrupole coupling for 1,2-dihydro-1,2-azaborine

The first microwave spectrum for 1,2-dihydro-1,2-azaborine has been measured in the frequency range 7-18 GHz, providing accurate rotational constants and nitrogen and boron quadrupole coupling strengths for three isotopomers, H(6)C(4)(11)B(14)N, H(6)C(4)(10)B(14)N, and H(5)DC(4)(11)B(14)N. The measured rotational constants were used to accurately determine coordinates for the substituted atoms and provide sufficient data to determine most of the important structural parameters for this molecule. The spectra were obtained using a pulsed beam Fourier transform microwave spectrometer, with sufficient resolution to allow accurate measurements of (14)N, (11)B, and (10)B nuclear quadrupole hyperfine interactions. High-level ab initio calculations provided structural parameters and quadrupole coupling strengths that are in very good agreement with measured values. The rotational constants for the parent compound are A = 5657.335(1), B = 5349.2807(5), and C = 2749.1281(4) MHz, yielding the inertial defect Delta(0) = 0.02 amu x A(2) for the ground-state structure. The observed near-zero and positive inertial defect clearly indicates that the molecular structure of 1,2-dihydro-1,2-azaborine is planar. The least-squares fit analysis to determine the azaborine ring structure yielded the experimental bond lengths and 2sigma errors R(B-N) = 1.45(3) A, R(B-C) = 1.51(1) A, and R(N-C) = 1.37(3) A for the ground-state structure. Interbond angles for the ring were also determined. An extended Townes-Dailey population analysis of the boron and nitrogen quadrupole coupling constants provided the valence p-electron occupancy p(c) = 0.3e for boron and p(c) = 1.3e for nitrogen.

Microwave measurements and ab initio calculations of structural and electronic properties of N-Et-1,2-azaborine.

Rotational transitions for N-Et-1,2-azaborine were measured in the 5-13 GHz range using a Flygare-Balle type Fourier transform spectrometer system. Twelve distinct rotational transitions with over 130 resolved hyperfine components, which included a-dipole and b-dipole transitions, were measured and analyzed to obtain rotational constants and (11)B and (14)N nuclear quadrupole coupling constants in the principal rotational axis system. Rotational constants obtained are A=4477.987(4), B=1490.5083(7), and C=1230.6728(6) MHz. The quadrupole coupling constants for (11)B are eQq(aa)=-1.82(1), (eQq(bb)-eQq(cc))=-3.398(4) MHz, and for (14)N, eQq(aa)=1.25(1), (eQq(bb)-eQq(cc))=0.662(4) MHz. Quantum electronic structure calculations predict a ground-state structure with the ethyl group perpendicular to the azaborine plane and rotational constants in very good agreement with the measured structure and rotational constants. The theoretical conformational analysis of the ethyl group rotation around the N[Single Bond]C bond in relation to the heterocyclic ring yielded an asymmetric torsional potential energy surface with barrier heights of about 900 and 1350 cm(-1) for the N-Et-1,2-azaborine. Results of the measurements and calculations indicate that the basic molecular structure of N-Et-1,2-azaborine is similar to ethylbenzene. Electrostatic potential calculations qualitatively show that pi-electron density is somewhat delocalized around the 1,2-azaborine ring.

Photo Lewis Acid Generators: Photorelease of B(C6F5)3 and Applications to Catalysis.

A series of molecules capable of releasing of the strong organometallic Lewis acid B(C6F5)3 upon exposure to 254 nm light have been developed. These photo Lewis acid generators (PhLAGs) can now serve as photoinitiators for several important B(C6F5)3-catalyzed reactions. Herein is described the synthesis of the triphenylsulfonium and diphenyliodonium salts of carbamato- and hydridoborates, their establishment as PhLAGs, and studies aimed at defining the mechanism of borane release. Factors affecting these photolytic reactions and the application of this concept to photoinduced hydrosilylation reactions and construction of siloxane scaffolds are also discussed.