Azaborininones: Synthesis and Structural Analysis of a Carbonyl-Containing Class of Azaborines.

An approach to access azaborininones (carbonyl-containing, boron-based heterocyclic scaffolds) using simple reagents and conditions from both organotrifluoroborates and boronic acids is described. An inexpensive, common reagent, SiO2, was found to serve as both a fluorophile and desiccant to facilitate the annulation process across three different azaborininone platforms. Computational analysis of some of the cores synthesized in this study was undertaken to compare the azaborininones with the analogous carbon-based heterocyclic systems. Computationally derived pKa values, NICS aromaticity calculations, and electrostatic potential surfaces revealed a unique isoelectronic/isostructural relationship between these azaborines and their carbon isosteres that changed based on boron connectivity. Correlation to experimentally derived data supports the computational findings.

Introduction

The preparation of boron-based heteroaromatic species has long fascinated synthetic chemists. Such ring systems greatly expand the library of heterocyclic structures and redefine the reactivity profile of these conjugated systems.[1] Although historically studied as a means to understand aromaticity,[2] boron-based aromatic systems have been recognized as viable, emerging platforms for expanding molecular diversity.[3] Particularly privileged among these boron-based cores is the azaborine scaffold, in which a B–N bond is integrated into the aromatic system.[4] The B–N bond serves as a surrogate for a C=C bond in arenes or heteroarenes, providing structural mimicry with unique electronic properties (and hence chemical reactivity). The unique disconnections, wholly unavailable in the corresponding carbon analogues, provide opportunities for dissonant synthetic routes to bicyclic systems. Additionally, the interchange between B–N and C=C bonds is particularly attractive for drug discovery, as it greatly enhances available structural diversity, and the trivalent nature of boron provides alternative electrostatic contacts for enzymatic targets.[5] Taken together, not only could this enhance potency of existing scaffolds, but it could also lead to new pharmacons. Indeed, oxaboroles[6] and benzodiazaborines[7] have been shown to have unique modes of bioactivity, and recent studies on 2,1-borazaronaphthalenes indicate a strong correlation to known bioactive compounds.[4d,8] Thus, methods to construct new or unexplored boron heterocyclic species would dramatically improve the quality of drug discovery libraries.

Recently, our group has engaged in highly successful programs to access azaborinyl cores from potassium organotrifluoroborates (R-BF3Ks) via in situ generated dihaloboranes, resulting in rapid access to both the 2,1-borazaronaphthalene[9a] and 1,3,2-benzodiazaborole[9b] scaffolds. Although exploration of methods to functionalize these unique cores is being continued,[10] it is also of interest to expand into new polyheteroatom-based azaborinyl systems. Of particular interest was the azaborininone family (Figure ). These underexplored, carbonyl-bearing, boron-heterocyclic scaffolds chelate a boron atom between a carboxylate or an amide and a secondary point (either an aryl hydroxyl or amino group), thus establishing a 6,6-bicyclic ring system. The three resulting classes of azaborininones have been very sporadically explored[11] and have shown applications as boron protecting/directing groups for C–H activation,[11e−11g] as well as potential promise as therapeutics given their known abilities as insect chemosterilants.[11h] Development of a concise, robust synthetic method applicable to the entire family of azaborininones would be highly attractive. In addition to overcoming a synthetic challenge, the three core systems provide future opportunities to explore the reactivity of an entirely new library of boron-containing compounds. In parallel to these synthetic studies, a computational investigation of the azaborininone family would provide further understanding as to how the substitution of O–B and N–B affect the structural and electronic properties.

Figure 1

Azaborininones, their possible isosteric counterparts, and their requisite starting points.

Results and Discussion

Early synthetic efforts centered on accessing 1,3,2-benzodiazaborininones derived from anthranilamide 3a. Using the conditions established from the prior work with the similar 3,1,2-benzodiazaboroles,[9b] the defluorinative annulation with phenyltrifluoroborate was met with success (Scheme a). Unfortunately, the fluorophile used (BF3·NH2Et) to facilitate the cyclization proved unsuccessful in reactions with anthranilic acid, 3b, or salicylamide, 3c (Scheme b and 1c), likely because the strong Lewis acidity of BF3 diminished the already weak nucleophilicity of these systems. Thus, although the boron trifluoride based approach would grant access to one core, alternative conditions were required to access the remaining two cores reliably. Given the known affinity of SiO2 for fluoride in the context of organotrifluoroborates,[12] this reagent was considered as an alternative to BF3·NH2Et in enabling mild, defluorinative annulation. Not only would this mitigate the requirement of an excess of a harsh, boron trifluoride-based reagent, but it would also employ an extraordinarily inexpensive, readily available reagent already found in virtually any organic laboratory.

Scheme 1

Attempts at Preparing Various Azaborininones via Defluorinative Annulation: (a) Success with 1,3,2-Benzodiazaborininones; (b and c) Failed Attempts at Extension to the Mixed N,O-Azaborininone Classes

A brief screen of alternative additives in conjunction with 3a and potassium phenyltrifluoroborate revealed SiO2 to be the optimal fluorophile (Table ). Importantly, these same conditions could be extended to both anthranilic acid and salicylamide without modification. Upon further study of SiO2 as a fluorophile, oven-dried SiO2 was determined to be more effective and allowed the reaction temperature to be lowered to 60 °C. In addition to being a fluorophilic species, SiO2 can further convert organotrifluoroborates to their corresponding boronic acids,[12] suggesting a potential reaction intermediate. Exposure of phenylboronic acid in place of phenyltrifluoroborate (Scheme ) to the optimized conditions resulted in the near-identical yield of 4a (conditions b, Table ). This finding also explains the benefit observed with dried SiO2, as this improved the ability for the SiO2 to act as a desiccant in the annulation (whose byproduct is H2O). This indicates two viable mechanisms: one proceeding through a difluoro-organoborane and the other via a SiO2-mediated boronate species. Both may be operative under SiO2-mediated annulation, but only the former is possible when using the anhydrous BF3·NH2Et conditions.

Table 1

Fluorophilic Reagent Optimization

Conversion determined by 1H NMR spectroscopy.

Scheme 2

Successful Annulation Using a Boronic Acid Mediated by SiO2

Table 2

Synthesis of 1,3,2-Benzodiazaborininones via Defluorinative Annulation

Yield on 7 mmol scale (see Experimental Section for full reaction conditions).

Substrate Scope

With two complementary conditions in hand, the scope of each approach was assessed. In the case of the 1,3,2-benzodiazaborininones (Table ), derived from anthranilamide and the corresponding potassium organotrifluoroborates, a variety of annulated products could be accessed using either protocol. Typically, the BF3·NH2Et conditions outperformed SiO2-mediated cyclizations (compare yields for 4a, 4b, 4e, 4f, 4p–4r). Various functional groups were amenable to the annulation process, including ethers (4f, 4m), amines (4h), esters (4i), and cyano groups (4j). Furthermore, polycyclic (4l) and multiple heterocyclic (4n, 4o) species could be accessed, as well as nonaryl organotrifluoroborates (4p–4r). Finally, the BF3·NH2Et conditions were readily scalable to furnish gram quantities of 4b. Stability studies of 4a indicate that it is quite sensitive to an aqueous base, but is rather insensitive to aqueous acid or neutral pH solutions. Little to no hydrolysis was observed even after 18 h in aqueous DMSO (see Supporting Information for aqueous stability studies).

Utilization of the SiO2-based conditions enabled initial entry to the mixed N,O-azaborininone classes. Starting from anthranilic acid (3b), a variety of 1,3,2-benzoxazaborininones could be synthesized (Table ). A range of potassium organotrifluoroborates were quite competent in the synthesis of this class of oxazaborininone, and functional group tolerance remained high. In addition to retaining the functional group tolerance seen with 1,3,2-benzodiazaborininones, additional substrates containing ketones (5e) and indoles (5i) were demonstrated to be amenable to cyclization. Alkenyl- (5j) and alkyl-3,1,2-benzoxazaborinine substrates (5k, 5l) could also readily be prepared. One difficulty encountered was inconsistent conversion observed upon isolation of the products. Oftentimes, 3b would remain even after purification by silica plug, suggestive of a reversible process (via hydrolysis). Using 1H NMR spectroscopy, these compounds were determined to be very intolerant to water and rapidly hydrolyzed to the corresponding boronic acid and 3b in a quantifiable manner (see Supporting Information for stability studies).[11e,13] However, apart from hydrolysis, these systems were found to be stable in organic solutions even at elevated temperatures. With this in mind, supplementary conditions involving boronic acids were considered, capitalizing on azeotropic water removal to drive cyclization.[11e,14] These conditions (denoted conditions b) provide an alternative route that in many cases gives equal to superior yields, likely because of the now nonreversible annulation. Although not the focus of this study, considering the practical benefits of trifluoroborates,[15] this approach was useful for systems prone to hydrolysis (5a–5c, 5f–5i, 5l).

Table 3

Synthesis of 3,1,2-Benzoxazaborininones via Defluorinative Annulation

The isomeric 1,3,2-benzoxaborininones (Table ) could also be accessed from salicylamide (3c). These substrates were typically the lowest-yielding members of the azaborininone family. This can be attributed to the diminished nucleophilicity of the amidyl nitrogen relative to aniline, combined with the lability of O-borylated phenols. In this case, a significant difference in yield exists between the SiO2 conditions (a) and the Dean–Stark condensation (b). This likely relates to the unique electronics of this azaborininone class, which is more prone to degradation via hydrolysis. Similar to 5a, 6a underwent rapid hydrolysis in aqueous DMSO to give 3c and phenylboronic acid. Despite this sensitivity, many, if not all, of the boryl substitution patterns tolerated with other members of the azaborininone family could be accessed with this more sensitive core. Not surprisingly, the azeotropic protocol fared far better with these systems. Indeed, in some cases, such as the acetophenone derivative 6e, azeotropic condensation was the only way to effect annulation.

Table 4

Synthesis of 1,3,2-Benzoxazaborininones via Defluorinative Annulation

Computational Evaluation

In parallel to developing a user-friendly synthesis of this underexplored azaborine class, we sought to evaluate their electronic properties. More specifically, we hoped to discern what, if any, isostructural (or isoelectronic) character these systems possessed. Indeed, many possible isosteres were envisioned, such as isochromones for 3,1,2-benzoxazaborininones or isoquinolinones for 1,3,2-benzodiazaborole. The compounds compared were considered on an isostructural basis, focusing on the structural similarities, comparing B–N/C=C and the analogous B–O/C=N. Given the prior successes in analyzing the 1,3,2-benzodiazaborole core using quantum mechanical calculations,[9b] computational modeling was used to glean insight. All calculations were carried out using Gaussian 09,[16] and the structures were visualized via WebMO.[17] Geometry optimizations were performed in the gas phase at the B3LYP/6-311+G(2d,p) level of theory.[18] The method used for calculations involving thermochemical values (e.g., computed pKa) of the various systems involved (i) geometry optimization and vibrational frequency calculations in the gas phase at the B3LYP/6-311+G(2d,p) level of theory and (ii) geometry optimization and vibrational frequency calculations in implicit water (H2O) using PCM[19] at the B3LYP/6-311+G(2d,p) level of theory. Stationary points were characterized by frequency analysis at 298.15 K, with structures at energy minima showing no imaginary frequencies. To probe the ring current in these systems, nuclear independent chemical shift (NICS) values were determined at the GIAO-B3LYP/6-311+G(2d,p) level of theory at distances of 0.0 Å [A(0) and B(0)] and 1 Å [A(1) and B(1)] from each ring system as well as from the center of the bicyclic systems [Center(1)] in the perpendicular direction.[20]

Initial computational investigations focused on the truncated cores (i.e., without functionalization on boron) to explore the structural and electronic features in comparison to isostructural compounds (Table ). Looking at the 1,3,2-benzodiazaborininones, isoquinolinone 10 and quinolinone 11 were identified as likely isosteres. A pictorial comparison of the electrostatic potential maps of these isosteres with the truncated 1,3,2-benzodiazaborininone 7 seemed to indicate that this system was a hybrid of both structures, with 7 having comparable A ring electrostatic potential to 11 and B ring similarity to 10. This is not altogether surprising given that nitrogen is well-known to participate in electron donation to boron. Indeed, the B–N bond lengths in the 1,3,2-benzodiazaborininone are quite uniform despite the nitrogen atoms being in vastly different electronic environments. This is corroborated in the slight contraction seen in the C=O bond as compared to isoquinolinone (10), indicating diminished nitrogen participation in the carbonyl π system. NICS calculations, which provide a quantitative correlation for electron delocalization using “theoretical nuclei” at the center of a π-system to probe electron shielding, were used for further elucidations.[21] Specifically, NICS(1) values were highlighted based on their improved ability to observe a π-delocalized aromatic ring current. NICS studies indicated that, relative to its isosteres, 1,3,2-benzodiazaborininone 7 has less aromatic character in its B ring. This finding is in agreement with prior work by our group and others, wherein boryl-based aromatic systems display diminished aromatic character when compared to their indole counterparts.[9b,20a] This effect is less pronounced in the adjoined carbon ring but is still observed. NICS values between the two possible isosteres of this system are relatively similar, with 11 having slightly less aromatic character in its B ring and thus more similarity to 7. Because of the aforementioned inherent stability issues of these systems, experimentally derived pKa values were unobtainable, and thus theoretical values were pursued.[21] The computed pKa’s of 7 are quite uniform, indicative of a strong electron donation to boron by both nitrogen atoms. The pKa’s are notably higher than their isosteres, a consequence of the competitive donation by both nitrogen atoms into boron and the lack of complete resonance stabilization around the B ring to delocalize negative charge.

Table 5

Comparison of the Azaborininone Family with Their Probable Isosteresa

All distances given in angstroms (Å), and the electrostatic potentials range from +31.38 to −31.38 kcal mol–1. NICS(1) values are given in ppm where a more negative NICS value indicates greater electron shielding via a stronger ring current and more π-electron delocalization (thus greater aromatic character).

Moving to 3,1,2-benzoxazaborininone 8 and 1,3,2-benzoxazaborininones 9, similar trends were observed. As a whole these mixed N,O systems displayed less electron delocalization and were more acidic. This increased acidity can be attributed to diminished π-orbital overlap with boron by the secondary heteroatom (in this case oxygen). The lower participation of electron donation by oxygen likely also relates to the observed, less negative, NICS values for the B rings of these systems. However, the isosteric character of these two systems was not as uniform. Using electrostatic potentials, 8 more closely resembles isochromone 12, whereas 9 appears to be more of a hybrid of 14 and 15. These trends are also borne out in the NICS analysis of the B rings of 8 and 9, wherein 9 has slightly more aromatic character than 8, indicating more oxygen participation in the ring system and thus provides further plausibility to B–O/C=N mimicry.[22] Additionally, the C=N resonance contribution of amides renders the system more aromatic. The relatively longer B–N bond seen in 9 also is in line with enhanced oxygen participation. However, the NICS value for the B ring of 9 more closely aligns with the B ring of 15. The exact opposite is true for the A ring, thus supporting the notion that 9 is a hybrid of the two systems.

To probe the role of electronics in these systems further, substitution on boron was next explored (Table ). Four representative B-aryl groups were selected that not only provided a range of electronic environments but also were prepared during the synthetic studies to allow correlative studies. In general, adding a B-aryl group led to diminished aromatic character in both the A and B rings for all members of the azaborininone family, as the boron is in favorable π-orbital overlap with the external ring. In particular, the 1,3,2-benzoxazaborininones showed the most significant disparity in the NICS values of the B ring from its truncated system. Ultimately, this increase may relate to their observed experimental instability. Electronically, the 1,3,2-benzodiazaborininones were the least sensitive to electronic changes, suggesting the overriding participation of both nitrogen atoms in this core. The 3,1,2-benzoxazaborininones seemed to be most influenced by electronic changes and appeared to gain aromatic character in both the A and B rings with more electron-deficient B-arenes.

Table 6

NICS Analysis of Electronically Disparate Azaborininones Divided by Class

As a means of correlating some of the observed computational trends with experimental data, NICS calculations were compared with some possible values that could be experimentally derived. Although pKa’s would have been ideal, the instability of these systems to strongly basic environments prohibited such a correlative study. Instead, IR and NMR spectroscopy were used as a means of quantitatively comparing calculations to experiment. Initially, the computed IR values were compared against the NICS values for both rings, to determine if the double bond character of the carbonyl would be influenced by the aromatic character of the rings and the relative electron-donation propensity of the adjacent heteroatom with boron. It was observed that, whereas the amide-containing 1,3,2-benzoxazaborininones and 1,3,2-benzodiazaborininones were readily comparable, the 3,1,2-benzoxazaborininones did not trend with the other members of the azaborininone class (Figure ). This is not altogether that surprising given the pseudo-α,β-unsaturated character of the structures (via B–N/C=C isosterism) possible with the former two systems that are not possible in the latter. This trend is also in agreement with the findings of the truncated systems. Whereas the amide-based systems usually are hybrid structures and very much electronically related, the ester-like 3,1,2-benzoxazaborininones are more like their isochromenone isosteres. Comparison of the experimental values for these systems provided some level of correlation, but because of their complex IR spectrum, the correlations were less than ideal (see Supporting Information for details). For a more precise correlation, 13C NMR was used, which would be quite sensitive to electronic changes. Experimental NMR values correlated well with NICS(1) values in both rings, indicating the electronic shielding trends observed computationally may indeed occur in these systems experimentally (Figure ). In general, the distribution of these values was self-consistent within each structural class (i.e., bimodal for the two classes plotted). Moreover, although the B rings show aromatic character, the values observed for the A ring are more analogous to aromatic systems [NICS(1) value of benzene is −10.20].[20b] This is similarly reflected in these studies, with the A ring showing a stronger correlation than the B ring. Thus, this provides some level of experimental validation of the trends observed in the NICS studies.

Figure 2

Plots of computed C=O IR stretch vs NICS values for both the A and B rings of various azaborininones.

Figure 3

Plots of experimental 13C NMR values vs computed NICS values for both the A and B rings of various 1,3,2-benzoxazaborininones and 1,3,2-benzodiazaborininones.

Conclusions

In summary, a modular approach to the synthesis of the underexplored azaborininone family of azaborines is presented. A set of simple conditions enables various organotrifluoroborates to undergo facile defluorinative annulation facilitated by two inexpensive fluorophiles. Alternatively, boronic acids also succumb to annulation via a more classical condensation route. Three classes, 1,3,2-benzodiazaborininones, 1,3,2-benzoxazaborininones, and 3,1,2-benzoxazaborininones, can be prepared using these varying approaches. These classes were further studied using computational methods, revealing some similarities to possible carbon isosteres. Whereas 1,3,2-benzodiazaborininones and 3,1,2-benzoxazaborininones appear to represent a hybrid between their plausible isosteres, the 1,3,2-benzoxazaborininones seem to align closely with isochromenones. Correlations between computed NICS values and experimentally derived trends provide support for these computed trends.

Experimental Section

General Considerations

All reactions were carried out under an inert atmosphere of nitrogen or argon in oven-dried glassware, unless otherwise noted. Toluene and cyclopentyl methyl ether (CPME) were dried using a J. C. Meyer solvent system. SiO2 was dried in a laboratory oven at 160 °C. All reagents were purchased commercially and used as received, unless otherwise noted. Melting points (°C) are uncorrected. Mass spectra (ESI- or EI-TOF) were recorded using CH2Cl2 or MeCN as the solvent. IR spectra were recorded using FTIR-ATR of the neat oil or solid products. NMR spectra (1H, 13C {1H}, 11B, 19F {1H}) were performed at 298 K. 1H (500.4 MHz) and 13C {1H} (125.8 MHz) NMR chemical shifts are reported relative to internal TMS (δ = 0.00 ppm) or to residual protonated solvent. Any observed splitting in the 13C {1H} NMR spectra is due to 13C–19F coupling. 11B (128.4 MHz) chemical shifts were referenced to external BF3·Et2O (0.0 ppm). Data are presented as follows: chemical shift (ppm), multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, sept = septet, m = multiplet, br = broad), coupling constant J (Hz), and integration.

Procedure A: Cyclization of Potassium Organotrifluoroborates Activated with BF3·EtNH2 To Form 1,3,2-Benzodiazaborininones

To a microwave vial with a stir bar were added anthranilamide (1.0 equiv) and the appropriate potassium organotrifluoroborate (1.05 equiv) along with BF3·EtNH2 (3.0 equiv). The reaction vessel was capped and purged with argon, upon which CPME and toluene were added in a 1:1 mixture (3 mL/mmol). The reaction was then heated at 80 °C for 16 h. Upon cooling to rt, the reaction mixture was washed with an aqueous solution of NaHCO3, extracted with EtOAc, and dried (MgSO4), before being concentrated to afford the azaborininone product. If needed, the product was further purified by passage of the crude matter through a short pad of silica, using a 9:1 mixture of hexane/EtOAc as eluent.

Procedure B-1: Cyclization of Potassium Organotrifluoroborates Activated with SiO2 To Form Azaborininones

To a microwave vial with a stir bar were added anthranilamide, anthranilic acid, or salicylamide (1.0 equiv) and potassium organotrifluoroborates (1.05 equiv) along with oven-dried SiO2 (100 mg/mmol). The reaction vessel was capped and purged with argon, upon which CPME and toluene were added in a 1:1 mixture (3 mL/mmol). The reaction was then heated at 60 °C for 16 h. Upon cooling to rt, the reaction mixture was filtered through a short pad of Celite and flushed with MeOH, before being concentrated. If needed, the solid was further washed with EtOAc for purification to afford the azaborininone product.

2-Phenyl-1,3,2-benzodiazaborininone (4a)

Obtained as a white solid by procedure A (195 mg, 88%, 1.0 mmol scale) and procedure B-1 (113 mg, 51%, 1.0 mmol scale); mp: 206–208 °C; 1H NMR (CDCl3, 500.4 MHz): δ 8.27 (d, J = 7.9 Hz, 1H), 7.70 (d, J = 7.5 Hz, 2H), 7.61–7.44 (m, 5H), 7.18 (t, J = 7.6 Hz, 1H), 7.12 (d, J = 8.1 Hz, 1H), 6.81 (s, 1H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 166.9, 144.4, 134.1, 132.0, 131.2, 129.4, 128.7, 122.1, 119.1, 117.8 ppm; 11B NMR (CDCl3, 128.4 MHz): δ 29.4 ppm; IR: ν = 3347, 3245, 1635, 1612, 1526, 1484, 1270, 747, 686 cm–1; HRMS (CI) m/z calcd for C13H12BN2O [M + H]+ 223.1043, found 223.1043.

2-(o-Tolyl)-1,3,2-benzodiazaborininone (4b)

Obtained as a white solid by procedure A after recrystallization from EtOAc (1.43 g, 87%, 7.0 mmol scale) and procedure B-1 (132 mg, 56%, 1.0 mmol scale); mp: 168–169 °C; 1H NMR (CDCl3, 500.4 MHz): δ 8.25 (d, J = 7.9 Hz, 1H), 7.55 (t, J = 7.6 Hz, 1H), 7.45 (d, J = 7.2 Hz, 1H), 7.34 (t, J = 7.5 Hz, 1H), 7.30 (s, 1H), 7.23 (d, J = 6.1 Hz, 2H), 7.18 (t, J = 7.6 Hz, 1H), 7.07 (d, J = 8.1 Hz, 1H), 6.72 (s, 1H), 2.48 (s, 3H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 166.5, 144.4, 140.9, 134.0, 132.7, 130.1, 130.1, 129.3, 125.6, 122.1, 119.0, 117.7, 22.6 ppm; 11B NMR (CDCl3, 128.4 MHz): δ 30.7 ppm; IR: ν = 3385, 3210, 1614, 1516, 1484, 1455, 745, 723 cm–1; HRMS (ES+) m/z calcd for C14H14BN2O [M + H]+ 237.1199, found 237.1193.

2-(2,6-Fluorophenyl)-1,3,2-benzodiazaborininone (4c)

Obtained as a beige solid by procedure A after recrystallization from EtOAc (150 mg, 58%, 1.0 mmol scale); mp: 164–165 °C; 1H NMR (acetone-d6, 500.4 MHz): δ 8.59 (s, 1H), 8.55 (s, 1H), 8.15 (d, J = 7.9 Hz, 1H), 7.64–7.50 (m, 2H), 7.42 (d, J = 8.1 Hz, 1H), 7.18 (t, J = 7.5 Hz, 1H), 7.05 (t, J = 7.8 Hz, 2H) ppm; 13C {1H} NMR (DMSO-d6, 125.8 MHz): δ 165.9, 164.8 (dd, J = 244.6, 13.7 Hz), 145.4, 133.9, 133.1 (t, J = 10.1 Hz), 128.4, 121.8, 119.4, 118.5, 111.6 (dd, J = 22.7, 5.3 Hz) ppm; 19F {1H} NMR (acetone-d6, 470.8 MHz): δ −103.6 ppm; 11B NMR (acetone-d6, 128.4 MHz): δ 28.0 ppm; IR: ν = 3438, 3362, 1666, 1616, 1454, 982, 762, 750, 720 cm–1; HRMS (ES+) m/z calcd for C13H10BN2OF2 [M + H]+ 259.0854, found 259.0862.

2-(p-Tolyl)-1,3,2-benzodiazaborininone (4d)

Obtained as a white solid by procedure A (177 mg, 75%, 1.0 mmol scale); mp: 255–256 °C; 1H NMR (CDCl3, 500.4 MHz): δ 8.26 (d, J = 7.8 Hz, 1H), 7.61 (d, J = 7.8 Hz, 2H), 7.56 (t, J = 7.7 Hz, 1H), 7.51 (s, 1H), 7.31 (d, J = 7.6 Hz, 2H), 7.18 (t, J = 7.6 Hz, 1H), 7.11 (d, J = 8.1 Hz, 1H), 6.76 (s, 1H), 2.43 (s, 3H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 166.7, 144.5, 141.6, 134.0, 132.0, 129.6, 129.4, 122.0, 119.1, 117.7, 21.8 ppm; 11B NMR (CDCl3, 128.4 MHz): δ 29.5 ppm; IR: ν = 3321, 3247, 1635, 1615, 1486, 1364, 1342, 1272, 752, 719, 477 cm–1; HRMS (EI) m/z calcd for C14H13BN2O [M]+ 236.1121, found 236.1136.

2-(4-Methoxyphenyl)-1,3,2-benzodiazaborininone (4e)

Obtained as a white solid by procedure A (82 mg, 65%, 0.5 mmol scale) and procedure B-1 (58 mg, 68%, 0.5 mmol scale); mp: 215–217 °C; 1H NMR (CDCl3, 500.4 MHz): δ 8.26 (d, J = 7.9 Hz, 1H), 7.65 (d, J = 8.5 Hz, 2H), 7.56 (dt, J = 7.8, 1.5 Hz, 1H), 7.52 (s, 1H), 7.17 (t, J = 7.6 Hz, 1H), 7.10 (d, J = 8.1 Hz, 1H), 7.02 (d, J = 8.5 Hz, 2H), 6.73 (s, 1H), 3.88 (s, 3H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 166.8, 162.2, 144.6, 134.0, 133.7, 129.4, 121.9, 119.0, 117.6, 114.4, 55.4 ppm; 11B NMR (CDCl3, 128.4 MHz): δ 29.2 ppm; IR: ν = 3352, 3290, 1640, 1602, 1507, 1487, 1242, 1179, 753 cm–1; HRMS (ES+) m/z calcd for C14H1410BN2O2 [M + H]+ 252.1185, found 252.1187.

2-(4-(Trifluoromethyl)phenyl)-1,3,2-benzodiazaborininone (4f)

Obtained as a white solid by procedure A (270 mg, 93%, 1.0 mmol scale) and procedure B-1 (197 mg, 68%, 1.0 mmol scale); mp: >260 °C; 1H NMR (DMSO-d6, 500.4 MHz): δ 9.80 (s, 1H), 9.45 (s, 1H), 8.23 (d, J = 7.5 Hz, 2H), 8.04 (d, J = 7.7 Hz, 1H), 7.77 (d, J = 7.6 Hz, 2H), 7.57 (t, J = 7.4 Hz, 1H), 7.43 (d, J = 7.9 Hz, 1H), 7.11 (t, J = 7.7 Hz, 1H) ppm; 13C {1H} NMR (DMSO-d6, 125.8 MHz): δ 166.7, 145.6, 134.3, 133.8, 130.9 (q, J = 31.7 Hz), 128.3, 124.6 (q, J = 272.2 Hz), 124.6 (q, J = 3.4 Hz), 121.5, 119.3, 118.6 ppm; 19F {1H} NMR (DMSO-d6, 470.8 MHz): δ −63.1 ppm; 11B NMR (CDCl3, 128.4 MHz): δ 28.5 ppm; IR: ν = 3333, 3245, 1630, 1616, 1316, 1110, 1066, 763, 526 cm–1; HRMS (ES+) m/z calcd for C14H11BN2OF3 [M + H]+ 291.0917, found 291.0916.

2-(4-Bromophenyl)-1,3,2-benzodiazaborininone (4g)

Obtained as a white solid by modification to procedure A, as 4g was not particularly soluble in EtOAc. As a result, some product could be collected as a precipitate from the aqueous workup (273 mg, 91%, 1.0 mmol scale); mp: >260 °C; 1H NMR (DMSO-d6, 500.4 MHz): δ 9.73 (s, 1H), 9.36 (s, 1H), 8.04–7.95 (m, 3H), 7.65 (d, J = 8.3 Hz, 2H), 7.60–7.53 (m, 1H), 7.40 (d, J = 8.0 Hz, 1H), 7.10 (t, J = 7.3 Hz, 1H) ppm; 13C {1H} NMR (DMSO-d6, 125.8 MHz): δ 166.6, 145.7, 135.8, 133.8, 131.1, 128.3, 125.0, 121.3, 119.2, 118.5 ppm; 11B NMR (THF, 128.4 MHz): δ 29.4 ppm; IR: ν = 3331, 3240, 1615, 1486, 1269, 753, 717, 528 cm–1; HRMS (ES+) m/z calcd for C13H11BN2OBr [M + H]+ 301.0148, found 301.0157.

2-(3-Aminophenyl)-1,3,2-benzodiazaborininone (4h)

Obtained as a tan solid by modification to procedure A, as 4h was minimally soluble in EtOAc. As a result, the product could be collected directly as a precipitate from the aqueous workup (173 mg, 73%, 1.0 mmol scale); mp: 210–213 °C; 1H NMR (DMSO-d6, 500.4 MHz): δ 9.38 (s, 1H), 9.17 (s, 1H), 7.99 (d, J = 7.9 Hz, 1H), 7.61–7.50 (m, 1H), 7.42 (d, J = 8.2 Hz, 1H), 7.19–7.12 (m, 2H), 7.12–7.04 (m, 2H), 6.70 (d, J = 7.7 Hz, 1H), 4.92 (s, 2H) ppm; 13C {1H} NMR (DMSO-d6, 125.8 MHz): δ 166.6, 148.3, 146.0, 133.6, 128.7, 128.2, 121.5, 121.0, 119.1, 118.5, 116.6, 99.9 ppm; 11B NMR (MeCN, 128.4 MHz): δ 30.1 ppm; IR: ν = 3395, 3292, 3211, 1657, 1608, 1526, 1484, 757, 509 cm–1; HRMS (ES+) m/z calcd for C13H12BN3ONa [M + Na]+ 260.0971, found 260.0984.

2-(3-(Methoxycarbonyl)phenyl)-1,3,2-benzodiazaborininone (4i)

Obtained as a white solid by modification to procedure A, as 4i was not particularly soluble in EtOAc. As a result some product was also collected as a precipitate from the aqueous workup (258 mg, 92%, 1.0 mmol scale); mp: 234–235 °C; 1H NMR (DMSO-d6, 500.4 MHz): δ 9.82 (s, 1H), 9.48 (s, 1H), 8.63 (s, 1H), 8.27 (d, J = 7.4 Hz, 1H), 8.05 (d, J = 7.8 Hz, 1H), 8.01 (d, J = 7.8 Hz, 1H), 7.63–7.54 (m, 2H), 7.44 (d, J = 8.1 Hz, 1H), 7.10 (t, J = 7.5 Hz, 1H), 3.89 (s, 3H) ppm; 13C {1H} NMR (DMSO-d6, 125.8 MHz): δ 166.9, 166.6, 145.8, 138.5, 134.5, 133.8, 131.4, 129.7, 128.6, 128.3, 121.3, 119.3, 118.6, 52.5 ppm; 11B NMR (THF, 128.4 MHz): δ 29.5 ppm; IR: ν = 3320, 3226, 2951, 1716, 1623, 1487, 1289, 749, 690 cm–1; HRMS (ES+) m/z calcd for C15H14BN2O3 [M + H]+ 281.1097, found 281.1092.

2-(3-Cyanophenyl)-1,3,2-benzodiazaborininone (4j)

Obtained as a white solid by procedure A after purifying via plug of silica gel with EtOAc/hexane (1:1) as eluent (138 mg, 56%, 1.0 mmol scale); mp: >260 °C; 1H NMR (DMSO-d6, 500.4 MHz): δ 9.84 (s, 1H), 9.47 (s, 1H), 8.48 (s, 1H), 8.35 (t, J = 6.6 Hz, 1H), 8.01 (d, J = 7.5 Hz, 1H), 7.93 (d, J = 6.9 Hz, 1H), 7.66 (t, J = 7.5 Hz, 1H), 7.58 (d, J = 7.1 Hz, 1H), 7.40 (d, J = 7.1 Hz, 1H), 7.16–7.03 (m, 1H) ppm; 13C {1H} NMR (DMSO-d6, 125.8 MHz): δ 166.6, 145.6, 138.2, 137.3, 134.1, 133.9, 129.2, 128.3, 121.5, 119.4, 119.3, 118.6, 111.6 ppm; 11B NMR (THF, 128.4 MHz): δ 29.3 ppm; IR: ν = 3365, 3197, 2230, 1651, 1619, 1485, 760, 699, 687 cm–1; HRMS (ES+) m/z calcd for C14H11BN3O [M + H]+ 248.0995, found 248.0991.

2-(3-Nitrophenyl)-1,3,2-benzodiazaborininone (4k)

Obtained as a beige solid by procedure A (123 mg, 92%, 0.5 mmol scale); mp: >260 °C; 1H NMR (DMSO-d6, 500.4 MHz): δ 9.97 (s, 1H), 9.62 (s, 1H), 8.92 (s, 1H), 8.46 (d, J = 7.4 Hz, 1H), 8.31 (dd, J = 8.2, 1.4 Hz, 1H), 8.02 (d, J = 7.9 Hz, 1H), 7.74 (t, J = 7.8 Hz, 1H), 7.63–7.55 (m, 1H), 7.44 (d, J = 8.1 Hz, 1H), 7.13 (t, J = 7.5 Hz, 1H) ppm; 13C {1H} NMR (DMSO-d6, 125.8 MHz): δ 166.6, 148.1, 145.6, 140.3, 140.3, 133.9, 129.7, 128.3, 125.4, 121.6, 119.3, 118.6 ppm; 11B NMR (THF, 128.4 MHz): δ 29.1 ppm; IR: ν = 3325, 1614, 1515, 1484, 1345, 1269, 763, 679 cm–1; HRMS (ES-) m/z calcd for C13H9BN3O3 [M – H]− 266.0737, found 266.0747.

2-(4-(Naphthalen-1-yl)phenyl)-1,3,2-benzodiazaborininone (4l)

Obtained as a beige solid by procedure A (247 mg, 71%, 1.0 mmol scale); mp: 255–256 °C; 1H NMR (DMSO-d6, 500.4 MHz): δ 9.76 (s, 1H), 9.42 (s, 1H), 8.20 (d, J = 7.8 Hz, 2H), 8.01 (t, J = 8.7 Hz, 2H), 7.96 (d, J = 8.2 Hz, 1H), 7.82 (d, J = 8.3 Hz, 1H), 7.61–7.52 (m, 5H), 7.52–7.43 (m, 3H), 7.10 (t, J = 7.4 Hz, 1H) ppm; 13C {1H} NMR (DMSO-d6, 125.8 MHz): δ 166.8, 146.0, 142.5, 139.7, 133.9, 133.8, 133.8, 131.1, 129.6, 128.8, 128.3, 128.2, 127.3, 126.8, 126.3, 125.9, 125.5, 121.2, 119.2, 118.6 ppm; 11B NMR (THF, 128.4 MHz): δ 29.9 ppm; IR: ν = 3320, 1657, 1316, 1533, 1511, 1485, 1358, 798, 774, 760, 716 cm–1; HRMS (ES-) m/z calcd for C23H16BN2O [M – H]− 347.1356, found 347.1357.

2-(4-(Benzyloxy)phenyl)-1,3,2-benzodiazaborininone (4m)

Obtained as a white solid by procedure A (265 mg, 81%, 1.0 mmol scale); mp: 249–251 °C; 1H NMR (DMSO-d6, 500.4 MHz): δ 9.57 (s, 1H), 9.20 (s, 1H), 8.07–7.94 (m, 3H), 7.54 (t, J = 7.6 Hz, 1H), 7.46 (d, J = 7.7 Hz, 2H), 7.43–7.37 (m, 3H), 7.33 (t, J = 7.3 Hz, 1H), 7.11–7.03 (m, 3H), 5.17 (s, 2H) ppm; 13C {1H} NMR (DMSO-d6, 125.8 MHz): δ 166.7, 160.8, 146.0, 137.3, 135.5, 133.7, 128.8, 128.3, 128.2, 128.0, 120.9, 118.9, 118.4, 114.7, 69.4 ppm; 11B NMR (THF, 128.4 MHz): δ 29.6 ppm; IR: ν = 3404, 3302, 1645, 1622, 1604, 1486, 1214, 996, 759, 721 cm–1; HRMS (ES+) m/z calcd for C20H18BN2O2 [M + H]+ 329.1461, found 329.1458.

2-(Furan-3-yl)-1,3,2-benzodiazaborininone (4m)

Obtained as a light brown solid by procedure A (172 mg, 81%, 1.0 mmol scale); mp: 190–192 °C; 1H NMR (CDCl3, 500.4 MHz): δ 8.25 (d, J = 7.9 Hz, 1H), 8.00 (s, 1H), 7.90 (s, 1H), 7.60 (s, 1H), 7.55 (t, J = 8.2 Hz, 1H), 7.27 (s, 1H), 7.17 (t, J = 7.5 Hz, 1H), 7.09 (d, J = 8.1 Hz, 1H), 6.68 (s, 1H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 167.0, 148.6, 144.5, 144.1, 134.0, 129.3, 121.9, 119.1, 117.5, 111.7 ppm; 11B NMR (EtOAc, 128.4 MHz): δ 28.2 ppm; IR: ν = 3347, 3250, 1636, 1610, 1516, 1487, 1150, 754, 732, 668, 527 cm–1; HRMS (ES+) m/z calcd for C11H10BN2O2 [M + H]+ 213.0835, found 213.0836

2-(Thiophen-2-yl)-1,3,2-benzodiazaborininone (4n)

Obtained as a white solid by procedure A (169 mg, 74%, 1.0 mmol scale); mp: 211–213 °C; 1H NMR (DMSO-d6, 500.4 MHz): δ 9.71 (s, 1H), 9.26 (s, 1H), 7.99 (dd, J = 11.2, 2.5 Hz, 2H), 7.92 (d, J = 4.6 Hz, 1H), 7.55 (td, J = 7.8, 1.5 Hz, 1H), 7.41 (d, J = 8.1 Hz, 1H), 7.29 (dd, J = 4.6, 3.5 Hz, 1H), 7.09 (t, J = 7.5 Hz, 1H) ppm; 13C {1H} NMR (DMSO-d6, 125.8 MHz): δ 166.4, 145.8, 136.7, 133.8, 132.8, 129.0, 128.3, 121.2, 119.2, 118.5 ppm; 11B NMR (EtOAc, 128.4 MHz): δ 27.7 ppm; IR: ν = 3315, 3240, 1614, 1530, 1486, 1264, 1025, 753, 698, 687, 474 cm–1; HRMS (ES+) m/z calcd for C11H10BN2OS [M + H]+ 229.0607, found 229.0618.

(E)-2-(Prop-1-en-1-yl)-1,3,2-benzodiazaborininone (4o)

Obtained as an off-white solid by procedure A (166 mg, 89%, 1.0 mmol scale) and procedure B-1 (156 mg, 84%, 1.0 mmol scale); mp: 142–143 °C; 1H NMR (DMSO-d6, 500.4 MHz): δ 9.25 (s, 1H), 8.91 (s, 1H), 7.93 (d, J = 7.8 Hz, 1H), 7.55–7.45 (m, 1H), 7.22 (d, J = 8.2 Hz, 1H), 7.02 (t, J = 7.5 Hz, 1H), 6.77 (dq, J = 18.7, 6.3 Hz, 1H), 5.69 (dd, J = 17.9, 1.7 Hz, 1H), 1.86 (d, J = 6.3 Hz, 3H) ppm; 13C {1H} NMR (DMSO-d6, 125.8 MHz): δ 166.4, 145.9, 145.7, 133.5, 128.3, 120.7, 119.1, 118.1, 22.1 ppm; 11B NMR (EtOAc, 128.4 MHz,): δ 28.4 ppm; IR: ν = 3315, 3201, 1608, 1517, 1485, 1362, 986, 754 cm–1; HRMS (ES+) m/z calcd for C10H12BN2O [M + H]+ 187.1043, found 187.1048.

2-Methyl-1,3,2-benzodiazaborininone (4p)

Obtained as a white solid by procedure A after purifying via a plug of silica gel with EtOAc/hexane (1:1) as eluent (86 mg, 54%, 1.0 mmol scale) and procedure B-1 (86 mg, 62%, 1.0 mmol scale); mp: 181–182 °C; 1H NMR (CDCl3, 500.4 MHz): δ 8.20 (d, J = 6.8 Hz, 1H), 7.50 (t, J = 6.8 Hz, 1H), 7.12 (t, J = 7.2 Hz, 2H), 6.98 (d, J = 7.3 Hz, 1H), 6.40 (s, 1H), 0.59 (s, 3H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 166.5, 144.4, 133.8, 129.2, 121.6, 118.7, 117.2 ppm; 11B NMR (CDCl3, 128.4 MHz): δ 32.3 ppm; IR: ν = 3267, 3190, 1609, 1519, 1486, 1364, 909, 749 cm–1; HRMS (CI) m/z calcd for C8H9BN2O [M]+ 160.0808, found 160.0808.

2-Cyclopropyl-1,3,2-benzodiazaborininone (4q)

Obtained as a white solid by procedure A (121 mg, 65%, 1.0 mmol scale) and procedure B-1 (108 mg, 58%, 1.0 mmol scale); mp: 186–188 °C; 1H NMR (DMSO-d6, 500.4 MHz): δ 8.98 (s, 1H), 8.50 (s, 1H), 7.90 (dd, J = 7.9, 1.4 Hz, 1H), 7.47 (td, J = 7.8, 1.6 Hz, 1H), 7.17 (d, J = 8.0 Hz, 1H), 6.99 (t, J = 7.5 Hz, 1H), 0.68 (dt, J = 9.2, 2.5 Hz, 2H), 0.65–0.59 (m, 2H), 0.05 (ddd, J = 9.2, 6.5, 2.9 Hz, 1H) ppm; 13C {1H} NMR (DMSO-d6, 125.8 MHz): δ 166.2, 145.8, 133.4, 128.2, 120.4, 118.7, 117.8, 5.4 ppm; 11B NMR (EtOAc, 128.4 MHz): δ 30.4 ppm; IR: ν = 3380, 3308, 3189, 1615, 1557, 1488, 1393, 1254, 752 cm–1; HRMS (ES+) m/z calcd for C10H12BN2O [M + H]+ 187.1043, found 187.1048.

Procedure C: Condensation of Boronic Acids To Form Oxazaborininones

To a round-bottomed flask with a stir bar were added the appropriate boronic acid (1 equiv) and either anthranilic acid or salicylamide (1 equiv) followed by toluene (4 mL/mmol). The flask was equipped with a Dean–Stark trap, and the reaction was heated to reflux. The reaction was stirred at this temperature overnight. After this time, the solvent was removed in vacuo by rotary evaporation, giving a crude solid. The resulting solid was further purified by washing with hexane/EtOAc (1:1), affording the desired, pure oxazaborininone.

2-Phenyl-3,1,2-benzoxazaborininone (5a)

Obtained as a white solid by procedure B-1 (367 mg, 83%, 2.0 mmol scale) and procedure C (650 mg, 93%, 3.0 mmol scale); mp: 211–212 °C; 1H NMR (CDCl3, 500.4 MHz): δ 8.21 (d, J = 7.8 Hz, 1H), 7.95 (d, J = 6.9 Hz, 2H), 7.64–7.59 (m, 1H), 7.58–7.53 (m, 1H), 7.48 (t, J = 7.4 Hz, 2H), 7.20 (t, J = 7.5 Hz, 1H), 7.09 (d, J = 8.1 Hz, 1H), 6.89 (s, 1H) ppm; 13C {1H} NMR (DMSO-d6, 125.8 MHz): δ 161.8, 146.1, 135.8, 133.8, 131.8, 130.1, 128.3, 122.2, 118.1, 114.9 ppm; 11B NMR (CDCl3, 128.4 MHz): δ 28.9 ppm; IR: ν = 3315, 1685, 1613, 1484, 1431, 1271, 1227, 750, 692 cm–1; HRMS (ES+) m/z calcd for C13H11BNO2 [M + H]+ 224.0883, found 224.0904.

2-(p-Tolyl)-3,1,2-benzoxazaborininone (5b)

Obtained as an off-white solid by procedure B-1 (408 mg, 86%, 2.0 mmol scale) and procedure C (230 mg, 97%, 2.0 mmol scale); mp: 220–221 °C; 1H NMR (DMSO-d6, 500.4 MHz): δ 9.66 (s, 1H), 7.94 (d, J = 7.9 Hz, 1H), 7.88 (d, J = 7.8 Hz, 2H), 7.67–7.62 (m, 1H), 7.33 (d, J = 8.1 Hz, 1H), 7.29 (d, J = 7.6 Hz, 2H), 7.13 (t, J = 7.6 Hz, 1H), 2.35 (s, 3H) ppm; 13C {1H} NMR (DMSO-d6, 125.8 MHz): δ 161.4, 145.7, 141.3, 135.5, 133.6, 129.7, 128.7, 121.8, 117.7, 114.4, 21.3 ppm; 11B NMR (MeCN, 128.4 MHz): δ 29.2 ppm; IR: ν = 3307, 1701, 1613, 1485, 1280, 756, 695, 626 cm–1; HRMS (ES+) m/z calcd for C14H13BNO2 [M + H]+ 238.1039, found 238.1033.

2-(4-Methoxyphenyl)-3,1,2-benzoxazaborininone (5c)

Obtained as a white solid by procedure B-1 (154 mg, 61%, 1.0 mmol scale) and procedure C after an additional wash with t-BuOH (364 mg, 72%, 2.0 mmol scale); mp: 205–206 °C; 1H NMR (CDCl3, 500.4 MHz): δ 8.18 (d, J = 7.8 Hz, 1H), 7.88 (d, J = 8.5 Hz, 2H), 7.61–7.54 (m, 1H), 7.16 (t, J = 7.5 Hz, 1H), 7.04 (d, J = 8.1 Hz, 1H), 6.99 (d, J = 8.6 Hz, 2H), 6.75 (s, 1H), 3.87 (s, 3H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 162.5, 161.8, 146.2, 135.9, 135.8, 130.1, 122.1, 118.0, 114.7, 114.1, 55.5 ppm; 11B NMR (CDCl3, 128.4 MHz): δ 28.6 ppm; IR: ν = 3340, 1698, 1599, 1428, 1281, 1251, 1224, 1180, 753, 693 cm–1; HRMS (ES+) m/z calcd for C14H13BNO3 [M + H]+ 254.0988, found 254.0984.

2-(4-(Trifluoromethyl)phenyl)-3,1,2-benzoxazaborininone (5d)

Obtained as a white solid by procedure B-1 (226 mg, 78%, 1.0 mmol scale); mp: >260 °C; 1H NMR (DMSO-d6, 500.4 MHz): δ 9.50 (s, 1H), 8.12 (d, J = 7.8 Hz, 2H), 7.93 (d, J = 7.7 Hz, 1H), 7.81 (d, J = 7.9 Hz, 2H), 7.62 (t, J = 7.4 Hz, 1H), 7.28 (d, J = 8.1 Hz, 1H), 7.09 (t, J = 7.5 Hz, 1H) ppm; 13C NMR (DMSO-d6, 126 MHz): δ 162.1, 146.7, 136.0, 134.5, 131.4 (q, J = 31.4 Hz), 130.4, 124.9 (q, J = 272 Hz), 125.0 (q, J = 3.5 Hz), 122.0, 118.2, 115.0 ppm; 19F {1H} NMR (DMSO-d6, 470.8 MHz): δ −61.3 ppm; 11B NMR (EtOAc, 128.4 MHz): δ 28.8 ppm; IR: ν = 3307, 1686, 1615, 1326, 1265, 1149, 1108, 1071, 759, 635 cm–1; HRMS (ES+) m/z calcd for C14H10BNO2F3 [M + H]+ 292.0757, found 292.0753.

2-(4-Acetylphenyl)-3,1,2-benzoxazaborininone (5e)

Obtained as a white solid by procedure B-1 (313 mg, 59%, 2.0 mmol scale); mp: 252–253 °C; 1H NMR (DMSO-d6, 500.4 MHz): δ 9.64 (s, 1H), 8.09 (d, J = 7.9 Hz, 2H), 8.03 (d, J = 7.9 Hz, 2H), 7.96 (d, J = 7.8 Hz, 1H), 7.65 (t, J = 7.5 Hz, 1H), 7.32 (d, J = 8.1 Hz, 1H), 7.13 (t, J = 7.5 Hz, 1H), 2.62 (s, 3H) ppm; 13C {1H} NMR (DMSO-d6, 125.8 MHz): δ 198.7, 162.0, 146.5, 139.2, 136.1, 134.1, 130.3, 128.0, 122.3, 118.3, 115.1, 27.5 ppm; 11B NMR (acetone-d6, 128 MHz): δ 27.6 ppm; IR: ν = 3308, 1668, 1614, 1484, 1399, 1261, 1233, 760, 628 cm–1; HRMS (ES+) m/z calcd for C15H13BNO3 [M + H]+ 266.0988, found 266.0983.

2-(3-Cyanophenyl)-3,1,2-benzoxazaborininone (5f)

Obtained as an off-white solid by procedure B-1 (136 mg, 55%, 1.0 mmol scale) and procedure C (677 mg, 91%, 3.0 mmol scale); mp: >260 °C; 1H NMR (DMSO-d6, 500.4 MHz): δ 9.33 (s, 1H), 8.26 (s, 1H), 8.15 (d, J = 7.5 Hz, 1H), 7.90 (d, J = 7.6 Hz, 2H), 7.64 (t, J = 7.6 Hz, 1H), 7.59 (t, J = 7.5 Hz, 1H), 7.21 (d, J = 8.1 Hz, 1H), 7.06 (t, J = 7.5 Hz, 1H) ppm; 13C {1H} NMR (DMSO-d6, 125.8 MHz): δ 162.1, 146.8, 138.1, 137.2, 136.0, 134.5, 130.4, 129.6, 121.8, 119.5, 118.1, 114.8, 111.8 ppm; 11B NMR (acetone-d6, 128 MHz): δ 27.1 ppm; IR: ν = 3313, 2235, 1694, 1621, 1526, 1483, 1279, 753, 688, 524 cm–1; HRMS (ES+) m/z calcd for C14H10BN2O2 [M + H]+ 249.0835, found 249.0836.

2-(2-Nitrophenyl)-3,1,2-benzoxazaborininone (5g)

Obtained as a light yellow solid by procedure B-1 (81 mg, 30%, 1.0 mmol scale) and procedure C (498 mg, 93%, 2.0 mmol scale); mp: 210–211 °C; 1H NMR (DMSO-d6, 500.4 MHz): δ 9.43 (s, 1H), 8.25 (d, J = 8.2 Hz, 1H), 7.98 (d, J = 7.8 Hz, 1H), 7.92–7.85 (m, 2H), 7.76 (t, J = 7.3 Hz, 1H), 7.65 (t, J = 7.5 Hz, 1H), 7.19–7.13 (m, 2H) ppm; 13C {1H} NMR (DMSO-d6, 125.8 MHz): δ 161.8, 151.3, 146.5, 136.3, 135.1, 134.3, 131.6, 130.4, 123.8, 122.5, 118.2, 114.8 ppm; 11B NMR (methanol-d4, 128 MHz): δ 27.0 ppm; IR: ν = 3348, 1698, 1510, 1484, 1342, 1266, 756, 724, 695 cm–1; HRMS (ES+) m/z calcd for C13H10BN2O4 [M + H]+ 269.0734, found 269.0741.

2-(Thiophen-3-yl)-3,1,2-benzoxazaborininone (5h)

Obtained as an off-white solid by procedure B-1 (147 mg, 64%, 1.0 mmol scale) and procedure C after washing with t-BuOH (400 mg, 87%, 3.0 mmol scale); mp: 227–229 °C; 1H NMR (CDCl3, 500.4 MHz): δ 8.19 (d, J = 7.9 Hz, 1H), 8.13 (s, 1H), 7.60 (t, J = 7.7 Hz, 1H), 7.53 (d, J = 4.8 Hz, 1H), 7.49–7.43 (m, 1H), 7.19 (t, J = 7.6 Hz, 1H), 7.07 (d, J = 8.1 Hz, 1H), 6.77 (s, 1H) ppm; 13C {1H} NMR (DMSO-d6, 125.8 MHz): δ 161.7, 146.1, 136.7, 135.9, 131.6, 130.1, 127.0, 122.2, 118.0, 114.9 ppm; 11B NMR (CDCl3, 128.4 MHz): δ 27.0 ppm; IR: ν = 3295, 1694, 1619, 1524, 1483, 1273, 1096, 695, 658, 521 cm–1; HRMS (ES+) m/z calcd for C11H9BNO2S [M + H]+ 230.0447, found 230.0445.

2-(1-Methyl-1H-indol-5-yl)-3,1,2-benzoxazaborininone (5i)

Obtained as a white solid by procedure B-1 (138 mg, 50%, 1.0 mmol scale) and procedure C (524 mg, 95%, 2.0 mmol scale); mp: >260 °C; 1H NMR (DMSO-d6, 500.4 MHz): δ 9.65 (s, 1H), 8.28 (s, 1H), 7.95 (d, J = 7.8 Hz, 1H), 7.79 (d, J = 8.3 Hz, 1H), 7.64 (t, J = 8.3 Hz, 1H), 7.53 (d, J = 8.3 Hz, 1H), 7.38–7.34 (m, 2H), 7.12 (t, J = 7.5 Hz, 1H), 6.53 (d, J = 2.8 Hz, 1H), 3.81 (s, 3H) ppm; 13C {1H} NMR (DMSO-d6, 125.8 MHz): δ 161.9, 146.4, 138.8, 135.8, 130.6, 130.1, 128.3, 127.6, 126.4, 122.0, 118.0, 114.7, 109.8, 101.5, 32.9 ppm; 11B NMR (acetone-d6, 128 MHz): δ 28.7 ppm; IR: ν = 3285, 1693, 1612, 1520, 1485, 1293, 1268, 1175, 753, 717, 697 cm–1; HRMS (ES+) m/z calcd for C16H14BN2O2 [M + H]+ 277.1148, found 277.1147.

2-Vinyl-3,1,2-benzoxazaborininone (5j)

Obtained as an off-white solid by procedure B-1 (142 mg, 41%, 2.0 mmol scale); mp: 140–141 °C; 1H NMR (CDCl3, 500.4 MHz): 8.14 (d, J = 8.6 Hz, 1H), 7.55 (td, J = 7.7, 1.5 Hz, 1H), 7.15 (t, J = 7.6 Hz, 1H), 6.98 (d, J = 8.1 Hz, 1H), 6.51 (s, 1H), 6.41 (dd, J = 19.1, 3.6 Hz, 1H), 6.16 (dd, J = 13.6, 3.4 Hz, 1H), 6.07 (dd, J = 19.1, 13.6 Hz, 1H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 161.8, 144.2, 137.2, 135.5, 131.1, 122.9, 117.1, 115.6 ppm; 11B NMR (CDCl3, 128.4 MHz): δ 27.6 ppm; IR: ν = 3265, 1706, 1618, 1516, 1486, 1351, 1283, 1175. 755, 694 cm–1; HRMS (ES+) m/z calcd for C9H9BNO2 [M + H]+ 174.0726, found 174.0730.

2-Phenethyl-3,1,2-benzoxazaborininone (5k)

Obtained as a yellow solid by procedure B-1 (377 mg, 75%, 2.0 mmol scale); mp: 100–102 °C; 1H NMR (CDCl3, 500.4 MHz): δ 8.12 (d, J = 7.9 Hz, 1H), 7.52 (td, J = 8.2, 1.5 Hz, 1H), 7.30 (t, J = 7.5 Hz, 2H), 7.26–7.23 (m, 2H), 7.22–7.17 (m, 1H), 7.13 (t, J = 7.6 Hz, 1H), 6.84 (d, J = 8.0 Hz, 1H), 6.23 (s, 1H), 2.91 (t, J = 8.0 Hz, 2H), 1.50 (t, J = 8.0 Hz, 2H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 161.9, 144.1, 143.6, 135.5, 131.0, 128.7, 128.1, 126.1, 122.8, 116.8, 115.2, 29.8 ppm; 11B NMR (CDCl3, 128.4 MHz): δ 32.7 ppm; IR: ν = 3118, 1689, 1619, 1520, 1489, 1276, 1131, 757, 693 cm–1; HRMS (ES+) m/z calcd for C15H15BNO2 [M + H]+ 252.1196, found 252.1196.

2-Cyclopropyl-3,1,2-benzoxazaborininone (5l)

Obtained as a beige solid by procedure B-1 after washing with 5:1 hexane/EtOAc instead of straight EtOAc (137 mg, 73%, 1.0 mmol scale) and procedure C (516 mg, 92%, 3.0 mmol scale); mp: 155–156 °C; 1H NMR (CDCl3, 500.4 MHz): δ 8.07 (d, J = 7.8 Hz, 1H), 7.52 (t, J = 7.7 Hz, 1H), 7.08 (t, J = 7.6 Hz, 1H), 6.94 (d, J = 8.1 Hz, 1H), 6.58 (s, 1H), 0.82–0.71 (m, 4H), 0.02 (tt, J = 8.7, 6.6 Hz, 1H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 162.1, 144.4, 135.3, 130.7, 122.0, 116.5, 114.8, 5.0 ppm; 11B NMR (CDCl3, 128.4 MHz): δ 32.3 ppm; IR: ν = 3270, 1699, 1615, 1515, 1486, 1442, 1163, 755 cm–1; HRMS (ES+) m/z calcd for C10H1110BNO2 [M + H]+ 187.0919, found 187.0925.

Procedure B-2: Cyclization of Potassium Trifluoroborates Activated with Silica Gel To Form 1,3,2-Benzoxazaborininones

To a microwave vial with a stir bar were added salicylamide (1.0 equiv) and the appropriate potassium organotrifluoroborates (1.05 equiv) along with oven-dried silica gel (100 mg/mmol). The reaction vessel was capped and purged with argon, and subsequently dry MeOH was added (3 mL/mmol). The reaction was then heated at 60 °C for 16 h. Upon cooling to rt, the reaction mixture was filtered through a short pad Celite and flushed with additional MeOH. Removal of the solvent in vacuo afforded the desired 1,3,2-benzoxazaborininone product.

2-Phenyl-1,3,2-benzoxazaborininone (6a)

Obtained as a white solid by procedure B-2 after recrystallization from CHCl3 (123 mg, 55%, 1.0 mmol scale) and procedure C (2.75 g, 81%, 10.0 mmol scale); mp: 195–196 °C; 1H NMR (CDCl3, 500.4 MHz): δ 8.25 (s, 1H), 8.22 (dd, J = 7.8, 1.6 Hz, 1H), 8.01 (d, J = 6.8 Hz, 2H), 7.70–7.64 (m, 1H), 7.61–7.56 (m, 1H), 7.52 (t, J = 7.3 Hz, 2H), 7.41 (d, J = 8.2 Hz, 1H), 7.32 (t, J = 7.5 Hz, 1H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 165.3, 155.8, 134.8, 133.3, 132.1, 128.4, 128.3, 123.7, 119.5, 119.1 ppm; 11B NMR (128.4 MHz, CDCl3): δ 32.2 ppm; IR: ν = 3202, 3101, 1688, 1471, 11373, 1276, 1245, 758, 629 cm–1; HRMS (ES+) m/z calcd for C13H11BNO2 [M + H]+ 224.0883, found 224.0880.

2-(p-Tolyl)-1,3,2-benzoxazaborininone (6b)

Obtained as a white solid by procedure B-2 after recrystallization from CHCl3 (156 mg, 66%, 1.0 mmol scale) and procedure C (1.32 g, 90%, 5.0 mmol scale); mp: 200–202 °C; 1H NMR (CDCl3, 500.4 MHz): δ 8.20 (dd, J = 7.8, 1.7 Hz, 1H), 7.97 (s, 1H), 7.87 (d, J = 7.9 Hz, 2H), 7.66 (td, J = 7.8, 1.7 Hz, 1H), 7.39 (d, J = 8.3 Hz, 1H), 7.34–7.28 (m, 3H), 2.44 (s, 3H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 165.1, 155.9, 142.6, 134.8, 133.3, 129.1, 128.3, 123.6, 119.4, 119.1, 21.7 ppm; 11B NMR (CDCl3, 128.4 MHz): δ 30.7 ppm; IR: ν = 3210, 3098, 1667, 1609, 1454, 1372, 1276, 860, 760 cm–1; HRMS (ES+) m/z calcd for C14H13BNO2 [M + H]+ 238.1039, found 238.1031.

2-(4-Methoxyphenyl)-1,3,2-benzoxazaborininone (6c)

Obtained as a white solid by procedure B-2 after recrystallization from CHCl3 (106 mg, 42%, 1.0 mmol scale) and procedure C (466 mg, 92%, 2.0 mmol scale); mp: 231–233 °C; 1H NMR (CDCl3, 500.4 MHz): δ 8.19 (d, J = 8.2 Hz, 1H), 7.89 (d, J = 8.3 Hz, 2H), 7.66 (t, J = 7.7 Hz, 1H), 7.58 (s, 1H), 7.38 (d, J = 8.3 Hz, 1H), 7.30 (t, J = 7.3 Hz, 1H), 7.03 (d, J = 8.3 Hz, 2H), 3.90 (s, 3H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 164.8, 162.9, 155.9, 135.1, 134.8, 128.4, 123.5, 119.3, 119.0, 113.9, 55.1 ppm; 11B NMR (THF, 128.4 MHz): δ 31.2 ppm; IR: ν = 3203, 1680, 1471, 1454, 1373, 1334, 1247, 756, 708 cm–1; HRMS (ES+) m/z calcd for C14H13BNO3 [M + H]+ 254.0991, found 254.0991.

2-(4-(Trifluoromethyl)phenyl)-1,3,2-benzoxazaborininone (6d)

Obtained as a white solid by procedure B-2 after recrystallization from CHCl3 (167 mg, 57%, 1.0 mmol scale); mp: 245–246 °C; 1H NMR (CDCl3, 500.4 MHz): δ 8.21 (dd, J = 7.8, 1.6 Hz, 1H), 8.08 (d, J = 8.0 Hz, 2H), 7.97 (s, 1H), 7.76 (d, J = 8.2 Hz, 2H), 7.69 (td, J = 7.6, 1.5 Hz, 1H), 7.42 (d, J = 8.3 Hz, 1H), 7.34 (t, J = 7.6 Hz, 1H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 165.0, 155.8, 135.4, 134.0 (q, J = 32.5 Hz), 133.8, 128.7, 125.2 (q, J = 3.7 Hz), 124.3, 124.0 (d, J = 272.5 Hz), 119.7, 119.4 ppm; 19F {1H} NMR (CDCl3, 470.8 MHz): δ −63.2 ppm; 11B NMR (MeCN, 128.4 MHz): δ 31.6 ppm; IR: ν = 3172, 3100, 1683, 1614, 1323, 1108, 1097, 1069, 865, 835, 755, 636 cm–1; HRMS (ES+) m/z calcd for C14H10BNO2F3 [M + H]+ 292.0757, found 292.0750.

2-(4-Acetylphenyl)-1,3,2-benzoxazaborininone (6e)

Obtained as a white solid by procedure C (398 mg, 75%, 2.0 mmol scale); mp: 236–238 °C; 1H NMR (CDCl3, 500.4 MHz): δ 8.21 (dd, J = 7.8, 1.7 Hz, 1H), 8.06 (dd, J = 10.3, 8.5 Hz, 4H), 7.91 (s, 1H), 7.69 (td, J = 7.8, 1.7 Hz, 1H), 7.42 (d, J = 8.2 Hz, 1H), 7.34 (t, J = 7.5 Hz, 1H), 2.67 (s, 3H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 197.9, 164.7, 155.6, 139.7, 135.1, 133.5, 128.5, 127.8, 124.0, 119.4, 119.1, 26.7 ppm; 11B NMR (THF, 128.4 MHz): δ 31.4 ppm; IR: ν = 3158, 3100, 2985, 1687, 1673, 1402, 1258, 864, 753, 619 cm–1; HRMS (ES+) m/z calcd for C15H13BNO3 [M + H]+ 266.0988 found 266.0990.

2-(2-Methoxyphenyl)-1,3,2-benzoxazaborininone (6f)

Obtained as a white solid by procedure B-2 after further washing with acetone (89 mg, 35%, 1.0 mmol scale) and procedure C (454 mg, 90%, 2.0 mmol scale); mp: 169–171 °C; 1H NMR (THF-d8, 500.4 MHz): δ 8.59 (s, 1H), 8.12 (dd, J = 7.8, 1.6 Hz, 1H), 8.06 (dd, J = 7.4, 1.6 Hz, 1H), 7.67–7.62 (m, 1H), 7.56–7.46 (m, 1H), 7.38 (dd, J = 8.3, 0.6 Hz, 1H), 7.27 (t, J = 7.5 Hz, 1H), 7.06 (t, J = 7.4 Hz, 2H), 3.97 (s, 3H) ppm; 13C {1H} NMR (THF-d8, 125.8 MHz): δ 165.2, 163.0, 155.9, 135.6, 134.0, 133.4, 127.9, 123.0, 120.2, 118.6, 110.2, 54.6 ppm; 11B NMR (THF-d8, 128.4 MHz): δ 31.4 ppm; IR: ν = 3397, 1694, 1598, 1468, 1420, 1365, 1243, 767, 752 cm–1; HRMS (ES+) m/z calcd for C14H13BNO3 [M + H]+ 254.0988, found 254.0981.

2-(Thiophen-3-yl)-1,3,2-benzoxazaborininone (6g)

Obtained as a white solid by procedure B-2 after further washing with acetone (44 mg, 19%, 1.0 mmol scale) and procedure C (408 mg, 89%, 2.0 mmol scale); mp: 215–217 °C; 1H NMR (CDCl3, 500.4 MHz): δ 8.24–8.18 (m, 2H), 8.11 (s, 1H), 7.70–7.63 (m, 1H), 7.60 (dd, J = 4.8, 0.9 Hz, 1H), 7.50 (dd, J = 4.8, 2.7 Hz, 1H), 7.38 (d, J = 8.3 Hz, 1H), 7.31 (t, J = 7.5 Hz, 1H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 165.3, 155.9, 136.5, 134.9, 130.7, 128.4, 126.4, 123.6, 119.4, 119.0 ppm; 11B NMR (CDCl3, 128.4 MHz): δ 29.7 ppm; IR: ν = 3163, 3102, 1679, 1469, 1385, 1263, 1244, 760, 662 cm–1; HRMS (ES+) m/z calcd for C11H9BNO2S [M + H]+ 230.0447, found 230.0463.

2-(1-Methyl-1H-indol-5-yl)-1,3,2-benzoxazaborininone (6h)

Obtained as a beige solid by procedure B-2 after recrystallization from CHCl3 (41 mg, 15%, 1.0 mmol scale) and procedure C (528 mg, 95%, 2.0 mmol scale); mp: 244–246 °C; 1H NMR (CDCl3, 500.4 MHz): δ 8.27 (s, 1H), 8.19 (dd, J = 7.8, 1.7 Hz, 1H), 7.75 (d, J = 8.3 Hz, 1H), 7.70–7.62 (m, 2H), 7.43 (dd, J = 12.4, 8.3 Hz, 2H), 7.28 (t, J = 7.5 Hz, 1H), 7.12 (d, J = 3.1 Hz, 1H), 6.61 (s, 1H), 3.85 (s, 3H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 165.0, 156.1, 139.0, 134.7, 129.5, 128.5, 128.3, 127.4, 125.8, 123.3, 119.4, 119.0, 109.2, 101.9, 32.8 ppm; 11B NMR (CDCl3, 128.4 MHz): δ 29.9 ppm; IR: ν = 3210, 2185, 3097, 1680, 1601, 1372, 1242, 1184, 1177, 759, 622, 598 cm–1; HRMS (ES+) m/z calcd for C16H14BN2O2 [M + H]+ 277.1148, found 277.1157.

2-Phenethyl-1,3,2-benzoxazaborininone (6i)

Obtained as a white solid by procedure B-2 after further washing with acetone (75 mg, 30%, 1.0 mmol scale); mp: 115–116 °C; 1H NMR (CDCl3, 500.4 MHz): δ 8.13 (dd, J = 7.8, 1.6 Hz, 1H), 7.65–7.59 (m, 1H), 7.40 (s, 1H), 7.33–7.25 (m, 6H), 7.21 (t, J = 7.2 Hz, 1H), 2.93 (t, J = 8.1 Hz, 2H), 1.53 (t, J = 8.1 Hz, 2H) ppm; 13C {1H} NMR (CDCl3, 125.8 MHz): δ 164.6, 155.7, 143.2, 134.7, 128.4, 128.3, 127.8, 125.9, 123.5, 119.3, 118.8, 29.4 ppm; 11B NMR (acetonitrile, 128.4 MHz): δ 32.7 ppm; IR: ν = 3105, 2928, 1688, 1468, 1373, 1348, 752, 731, 699 cm–1; HRMS (CI) m/z calcd for C15H15BNO2 [M + H]+ 252.1196, found 252.1194.