Dynamic covalent self-assembled macrocycles prepared from 2-formyl-aryl-boronic acids and 1,2-amino alcohols

Abstract

Reaction of 2-formyl-aryl-boronic acids with 1,2-amino alcohols results in dynamic covalent self assembly to quantitatively afford tetracyclic macrocyclic Schiff base boracycles containing bridging boron–oxygen–boron functionality.

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Introduction

The development of boronic acid based saccharide sensors that rely on the dynamic covalent interaction of boronic acids with diols has been widely investigated.^1–9Boronic ester formation with diols has also been used for the construction of discrete macrocycles and cages.¹⁰ The reversible nature of boronic acid complexation with diols makes this type of interaction highly suitable for the reversible self-assembly of multicomponent systems. With these types of reversible systems any errors that occur during the assembly process may be corrected because equilibration of the reactive species results in formation of a thermodynamically favoured product. A number of boracycles have been prepared that employ a combination of facile imine formation and boronic acid esterification to afford multicomponent macrocycles.^11–24 For example, Severin has prepared a series of self assembled macrocycles/cages by combining 3- or 4-formyl-phenyl-boronic acids with bis or tris primary amines and pentaerythritol (tetraol).^25,26 Nitschke has also prepared a macrocycle derived from pentaerythritol, 2-formyl-phenyl-boronic acid and para-diaminobenzene, as well as a cage compound arising from self assembly of cyclotricatechylene, meta-xylylenediamine and 2-formyl-phenyl-boronic acid.²⁷ Farfan has prepared boracycles from boric acid, 4-diethylamino salicylaldehyde and (R)-phenylglycinol 6d. This complex was formed in two steps involving reaction of 4-diethylamino salicylaldehyde and (R)-6d to produce an imine, followed by reflux with boric acid in toluene under Dean–Stark conditions for 18 h to produce the observed complex.²⁸

We now report herein that simple room temperature mixing of 2-formyl-aryl-boronic acids with 1,2-amino alcohols results in dynamic covalent self assembly to afford stable tetracyclic macrocyclic Schiff base complexes that contain a rigid bridging boron–oxygen–boron functionality.

Results and discussion

We have recently reported the development of versatile three-component derivatization protocols for determining the enantiomeric excess of chiral primary amines, diols or diamines.^29–35 For the case of amines, this approach involves derivatization of a chiral amine 1 with 2-formyl-phenyl-boronic acid 2 and enantiopure BINOL (S)-3 in CDCl₃ to quantitatively afford a mixture of diastereoisomeric imino-boronate esters (S,S)-4 and (S,R)-5. The diastereoisomeric ratio of (S,S)-4:(S,R)-5 is then determined by ¹H NMR spectroscopic analysis, and since no kinetic resolution occurs this value is an accurate reflection of the enantiomeric excess of the parent amine (Scheme 1).

Scheme 1 Three-component protocol for determining the enantiomeric purity of chiral amines by ¹H NMR spectroscopic analysis.

We reasoned that this type of three-component derivatization protocol might also be useful for analyzing the enantiopurity of chiral 1,2-amino alcohols. Therefore, (S)-leucinol 6b was treated with 2-formyl-phenyl-boronic acid 2 and (S)-BINOL 3 in CDCl₃ and its ¹H NMR spectrum acquired after ten minutes. The resultant ¹H NMR spectra revealed the presence of a complicated mixture of interconverting products that was clearly unsuited for carrying out ee determination. However, on standing overnight, the crude reaction product fractionally crystallised to afford the expected oxazolidine-boronate ester (S,2R,4S)-7, whose structure was subsequently confirmed by X-ray crystallographic analysis (Scheme 2).

Scheme 2 Formation and X-ray crystal structure of boronic ester (S,2R,4S)-7.

In order to investigate this complexation reaction further, it was decided to determine what products would be formed when 2-formyl-phenyl-boronic acid 2 was individually reacted with either (S)-BINOL 3 or (R)-valinol 6a. Two-component mixing of 2-formyl-phenyl-boronic acid 2 with (S)-BINOL 3 in CDCl₃ resulted in no reaction occurring. However, reaction of 2 with (R)-valinol 6a at room temperature in chloroform resulted in exclusive formation of a new boracycle (R,R)-8a in quantitative yield (Scheme 3). The structure of symmetrical boracycle (R,R)-8a was confirmed by X-ray crystallographic analysis (Fig. 1), which revealed it to be the condensation product of two equivalents of 2-formyl-phenyl-boronic acid 2 with two equivalents of (R)-valinol 6a, with concomitant elimination of five molecules of water. This complexation reaction results in formation of the densely packed central core of boracycle (R,R)-8a which comprises two fused seven membered rings formed from two tetrahedral sp³-boron atoms, two imino alcohol fragments, and a central oxygen atom that bridges both boron atoms. This architecture results in its central fused bicyclic ring structure being further appended by two five-membered rings formed from two imino-boronate ester linkages that confer sp³ character on the boron atoms. The scope and limitation of this four-component condensation reaction was then investigated via treatment of a series of five chiral amino alcohols 6b–f with 2-formyl-phenyl-boronic acid 2, which resulted in clean formation of their respective boracycles 8b–f in 84–96% isolated yield (Scheme 3).

Scheme 3 Condensation of 2-formyl-phenylboronic acid 2 with chiral amino alcohols 6a–f and achiral amino alcohols 6g, h affords four-component boracycles 8a–h.

Fig. 1 Crystal structure of macrocycle 8a. (a) Viewed along the boron–boron axis. (b) Viewed perpendicular to the boron–boron axis.

The reversible nature of macrocycle formation of these boracycles 8a–f was confirmed by adding one equivalent of amino alcohol (S)-6a to macrocycle (S,S)-8b in chloroform. Mass spectrometry indicated that this solution now contained a mixture of three macrocycles, (S,S)-8a (M + H 431 m/z), (S,S)-8b (M + H 445 m/z) and a mixed macrocycle derived from (S)-6a and (S)-6b (M + H 417 m/z) in a statistical 1:1:2 ratio.

Norman and coworkers have previously reported the synthesis of achiral boracycle 8g derived from condensation of 2-aminophenol with 2-formyl-phenyl-boronic acid 2 in ethanol at reflux.³⁶ Attempts to repeat this condensation reaction using our mild complexation conditions at room temperature resulted in no reaction occurring. However, heating 2-aminophenol 6g (or 4-methyl-2-aminophenol 6h) with 2-formyl-phenyl-boronic acid 2 at reflux in 95:5 ethanol:benzene under Dean–Stark conditions did result in quantitative formation of the boracycles 8g (or 8h). Comparison of the X-ray crystal structures of boracycle (S)-8a with that of boracycle 8h (Fig. 2) revealed that whilst they belong to the same class of bridging boracycle, their three dimensional architectures are very different. In the case of boracycle 8a, the central bridging oxygen atom lies on the opposite side to the other two oxygen atoms about the plane bisected by the two boron atoms. This results in the alkyl side-chains of their amino alcohol fragments adopting a conformation that creates the walls of a potential binding cavity centred around its bridging oxygen atom, with its aryl rings acting as buttressing elements to contribute structural rigidity. Conversely, for the case of macrocycle 8h, the presence of the more rigid aminophenol fragments results in the three oxygen atoms now being presented on the same face of the plane bisected by the boron atoms. This, in turn, results in the aryl rings of the boronic acid fragment forming the walls of a cavity centred around the bridging oxygen atom, with its aminophenol derived fragments now adopting the role of buttressing substituents to confer structural rigidity.

Fig. 2 Crystal structure of macrocycle 8h. (a) Viewed along the boron–boron axis. (b) Viewed perpendicular to the boron–boron axis.

We have also varied the nature of the boronic acid template used for supramolecular assembly, demonstrating that complexation of 2-formyl-furanyl-boronic acid 9 with chiral aminoalcohols 6a–e in chloroform quantitatively affords their corresponding four-component boracycles 10a–e in 85–92% isolated yield (Scheme 4). ¹¹B NMR spectroscopic analysis of these macrocycles reveals that the boron atoms of the furan derived boracycles 10a–e (δ 4.6–5.4 ppm) have more tetrahedral character than their corresponding phenyl derived boracycles 8a–f (δ 10.5–11.5 ppm). This increased tetrahedral character may be a consequence of the need to incorporate a more geometrically constrained five-membered furan ring into these complexes. It may also explain why reaction of achiral amino alcohols 6g–h with 2-formyl-furanyl-boronic acid 9 did not result in clean formation of their corresponding four component boracycles, which may be precluded by the opposing steric demands of incorporating tetrahedral sp³boron atoms and vicinal sp² aryl carbon atoms into the central boracyclic core of the macrocyclic ring system.

Scheme 4 Preparation of boracycles 10a–e.

Conclusions

In conclusion, a range of covalent self-assembled macrocycles 8 and 10 containing bridging O–B–O–B–O have been prepared and fully characterised. Their ease of preparation suggests that this class of boracycle is well suited for the reversible self-assembly of multicomponent systems, and we are currently investigating the recognition properties of this structurally diverse class of macrocycle.

Experimental

General synthetic methods

The solvents and reagents were reagent grade unless otherwise stated and were purchased from Acros Organics, Alfa Aesar, Fisher Scientific UK, Frontier Scientific Europe Ltd., TCI Europe or Sigma-Aldrich Company Ltd., and were used without further purification. Infra-red spectra were recorded on a Perkin Elmer Spectrum RX spectrometer between 4400 cm⁻¹ and 450 cm⁻¹. Samples were evaporated from CHCl₃ on to a NaCl disc (film). Nuclear magnetic resonance spectra were run in either chloroform-d. A Bruker AVANCE 300 was used to acquire ¹H-NMR spectra and recorded at 300 MHz, ¹¹B-NMR spectra at 100 MHz and ¹³C{¹H} NMR spectra at 75 MHz. Chemical shifts (δ) are expressed in parts per million and are reported relative to the residual solvent peak or to tetramethylsilane as an internal standard in ¹H and ¹³C{¹H} NMR spectra. Boron trifluoride diethyl etherate was used as an external standard in ¹¹B NMR spectra. Mass spectra were acquired with a micrOTOFQ electrospray time-of-flight (ESI-TOF) mass spectrometer (Bruker Daltonik GmbH).

General procedure for the preparation of boracycles 8a-f and 10a–e

2-Formyl-phenyl-boronic acid 2 (60 mg, 0.4 mmol) or 3-formyl-furanyl-2-boronic acid 9 (56 mg, 0.4 mmol) was stirred with a chiral 1,2-amino alcohol 6a–f or 6a–e (0.4 mmol) in chloroform (5 mL) for 10 min. The solvent was then removed under reduced pressure to afford boracycles 8a–f or 10a–e in 84–96% yield.

(R,R)-8a. Yellow oil (70 mg, 84%); [α]²⁰_D +22.0 (c 1.0, CH₂Cl₂); v_max (film) 1628 (C=N); δ_H (300 MHz; CDCl₃) 8.08 (2H, s, CH=N), 7.51 (2H, d, J 7.4, ArH), 7.35–7.27 (4H, m, ArH), 7.11 (2H, dt, J 7.4 and 1.1, ArH), 4.26 (2H, dd, J 12.2 and 1.3, CH_AH_B(O)), 3.98 (2H, dd, J 12.2 and 1.3, CH_AH_B(O)), 3.13 (2H, m, CH(ⁱPr)–N), 2.96–2.83 (2H, m, CH(CH₃)₂), 1.02 (6H, d, J 6.8, C(CH₃)(CH₃)) and 0.88 (6H, d, J 6.8, C(CH₃)(CH₃)); δ_C (75 MHz; CDCl₃) 167.3 (C=N), 136.8, 133.6, 129.4, 127.2, 127.0, 126.2, 76.0, 60.9, 27.0, 21.1 and 19.4; δ_B (100 MHz; CDCl₃) 10.7; m/z LRMS (ESI⁺) 418 [(M + H)⁺, 13%], 283.2 (100), 200.1 (2); HRMS (ESI⁺) found 417.2531 ([M + H]⁺ C₂₄H₃₀B₂N₂O₃ requires 417.2515).

(S,S)-8b. Yellow solid (79 mg, 89%); m.p. 206–210 °C (dec); [α]²⁰_D−26.1 (c 1.0, CH₂Cl₂); v_max (film) 1628 (C=N); δ_H (300 MHz; CDCl₃) 8.16 (2H, s, CH=N), 7.51 (2H, d, J 7.4, ArH), 7.36–7.27 (4H, m, ArH), 7.11 (2H, dt, J 7.4 and 1.1, ArH), 4.35 (2H, dd, J 11.9 and 1.7, CH_AH_B(O)), 3.81–3.73 (4H, m, CH_AH_B(O) and CH–N), 2.16–2.06 (2H, m, CH_AH_BC(N)), 2.02–1.92 (2H, m, CH_AH_BC(N)), 1.72–1.63 (2H, m, CH(CH₃)₂) and 0.90 (12H, app t, J 6.8, C(CH₃)₂); δ_C (75 MHz; CDCl₃) 166.9 (C=N), 136.9, 133.5, 133.1, 129.4, 127.2, 126.1, 66.7, 62.5, 40.4, 24.8, 23.0 and 22.9; δ_B (100 MHz; CDCl₃) 11.5; m/z LRMS (ESI⁺) 445 [(M + H)⁺, 14%], 412.4 (100), 292.2 (66), 227.2 (15); HRMS (ESI⁺) found 445.2873 ([M+H]⁺ C₂₆H₃₄B₂N₂O₃ requires 445.2828).

(R,R)-8c. Yellow oil (69 mg, 88%); [α]²⁰_D +14.7 (c 1.0, CH₂Cl₂); v_max (film) 1628 (C=N); δ_H (300 MHz; CDCl₃) 8.13 (2H, s, CH=N), 7.50 (2H, t, J 7.4, ArH), 7.3–7.26 (4H, m, ArH), 7.12–7.07 (2H, m, ArH), 4.33 (2H, dd, J 12.0 and 1.7, CH_AH_B(O)), 3.78 (2H, dd, J 12.0 and 1.7, CH_AH_B(O)), 3.51 (2H, m, CH(Et)–N), 2.20–2.09 (4H, m, CH_AH_BMe) and 0.93 (6H, t, J 7.6, CH₃); δ_C (75 MHz; CDCl₃) 167.3 (C=N), 136.9, 133.5, 133.3, 129.3, 127.2, 126.2, 70.7, 62.4, 24.8 and 11.5; δ_B (100 MHz; CDCl₃) 11.2; m/z LRMS (CI⁺) 389 [(M + H)⁺, 6%], 188.2 (50), 106.0 (46), 72.0 (100); HRMS (EI⁺) found 388.2126 (2 ×¹¹B) (M⁺˙ C₂₂H₂₆B₂N₂O₃ requires 388.2124).

(R,R)-8d. Yellow oil (88 mg, 91%); [α]²⁰_D +21.1 (c 1.0, CH₂Cl₂); v_max (film) 1627 (C=N); δ_H (300 MHz; CDCl₃) 7.66–7.63 (4H, m, CH=N and ArH), 7.43–7.30 (12H, m, ArH), 7.20 (2H, br t, J 7.4, ArH), 7.09 (2H, dt, J 7.4 and 0.8, ArH), 5.25 (2H, m, CH_AH_B(O)), 4.65 (2H, dd, J 11.9 and 10.4, CH(Ph)-N), 3.95 (2H, m, CH_AH_B(O)); δ_C (75 MHz; CDCl₃) 166.1 (C=N), 137.0, 135.7, 133.9, 133.5, 132.3, 130.0, 129.9, 129.7, 129.5, 127.2, 126.8, 126.7, 71.4, and 69.1; δ_B (100 MHz; CDCl₃) 11.3; m/z LRMS (ESI⁺) 485 [(M + H)⁺, 9%], 368.2 (10), 312.1 (100), 278.2 (16); HRMS (ESI⁺) found 485.2230 ([M + H]⁺ C₃₀H₂₆B₂N₂O₃ requires 485.2202).

(R,R)-8e. Yellow solid (140 mg, 95%); m.p. 125–129 °C (dec); [α]²⁰_D +19.4 (c 1.0, CH₂Cl₂); v_max (film) 1635 (C=N); δ_H (300 MHz; CDCl₃) 8.25 (2H, s, CH=N), 7.64 (2H, d, J 7.0, ArH), 7.48–7.14 (16H, m, ArH), 5.46 (2H, br d, J 9.8, CH_AH_B(N)), 4.50–4.42 (2H, m, CH(Ph)(O)) and 4.03 (2H, br d, J 9.8, CH_AH_B(N)); δ_C (75 MHz; CDCl₃) 166.0, 137.0, 135.6, 133.9, 133.5, 132.3, 130.0, 129.9, 129.7, 129.4, 128.0, 127.3, 126.8, 71.3 and 65.8; δ_B (100 MHz; CDCl₃) 10.5; m/z LRMS (ESI⁺) 485 [(M + H)⁺, 100%], 312.1 (99); HRMS (ESI⁺) found 485.2219 ([M + H]⁺C₃₀H₂₆B₂N₂O₃ requires 485.2202).

(rac)-8f. Yellow solid (85 mg, 96%); m.p. 142–144 °C (dec); v_max (film) 1625 (C=N); δ_H (300 MHz; CDCl₃) 8.20 (2H, d, J 3.0, CH=N), 7.47 (2H, d, J 6.8, ArH), 7.35 (2H, d, J 7.4, ArH), 7.28 (2H, app dt, J 7.5 and 1.1, ArH), 7.10 (2H, app dt, J 7.5 and 1.1, ArH), 3.96–3.88 (2H, m, CH(N)), 3.79–3.70 (2H, m, CH(O)), 2.26 (2H, br d, J 12.0, CH_AH_BC–O), 1.88–1.81 (4H, m, CH_AH_BC–O and CH_AH_BC–N), 1.71–1.66 (2H, m, CH_AH_BC–N) and 1.50–1.12 (8H, m, 2×(CH₂)₂); δ_C (75 MHz; CDCl₃) 164.0 (C=N), 137.2, 133.2, 129.9, 129.1, 126.9, 126.3, 65.6, 36.3, 29.8, 27.3, 24.9 and 24.8; δ_B (100 MHz; CDCl₃) 10.8; m/z LRMS (ESI⁺) 440 [(M + H)⁺, 100%], 290.2 (15); HRMS (ESI⁺) found 441.2549 ([M + H]⁺ C₂₆H₃₀B₂N₂O₃ requires 441.2515).

8g . 2-Aminophenol 6g (200 mg, 1.83 mmol) and 2-formylphenylboronic acid 2 (275 mg, 1.83 mmol) were dissolved in 95:5 ethanol–benzene (25 mL) in a round bottom flask fitted with a Dean–Stark condenser and stirred at reflux for 4 h. The reaction mixture was cooled and the solvent removed under reduced pressure. Washing with a little cold methanol afforded 8g as a yellow powder (709 mg, 90%): m.p. 182–183 °C (dec.) (Lit. 180 °C (dec.)³⁶); δ_H (300 MHz, CDCl₃) 8.65 (s, 2H), 7.49 (2H, d, J = 7.5 Hz), 7.40–7.37 (2H, m, Ar), 7.29–7.12 (8H, m), 6.92 (4H, m); δ_C (75 MHz, CDCl₃) δ = 160.9, 155.5, 135.1, 134.2, 134.13, 133.1, 132.9, 131.5, 127.9, 118.7, 115.8, 113.7; δ_B (96.3 MHz, CDCl₃) 9.6; m/z HRMS (ESI⁺) found 429.1571. ([M + H]⁺ C₂₆H₁₉B₂N₂O₃ (M + H⁺) requires 429.1582).

8h . 2-Hydroxy-5-methylaniline 6h (123 mg, 1.0 mmol) and 2-formyl-phenyl-boronic acid 1 (150 mg, 1.0 mmol) were dissolved in 95:5 ethanol–benzene (20 mL) in a round bottom flask fitted with a Dean–Stark condenser and stirred at reflux for 4 h. The reaction mixture was cooled and the solvent removed under reduced pressure. Washing with a little cold methanol afforded 8h as a orange powder (374 mg, 82%): m.p. 231–232 °C (dec.); δ_H (300 MHz, CDCl₃) 8.64 (2H, s, CH=N), 7.42 (2H, m, ArH), 7.36 (2H, s, ArH), 7.29–7.16 (6H, m, ArH), 7.11 (2H, d, J 8.4 ArH), 6.85 (2H, d, J 8.4), 2.35 (6H, s, CH₃); δ_C (75 MHz, CDCl₃) 158.24, 154.9, 148.8, 134.9, 134.1, 133.9, 132.9, 131.2, 128.2, 127.8, 115.3, 113.8, 21.5; δ_B (100 MHz, CDCl₃) 8.9; m/z HRMS (ESI⁺) found 457.2011. ([M + H]⁺ C₂₈H₂₃B₂N₂O₃ (M + H⁺) requires 457.1889).

(S,S)-10a. Dark brown solid (74 mg, 93%); m.p. 131–140 °C (dec); [α]²⁰_D−36.8 (c 1.0, CH₂Cl₂); v_max (film) 1649 (C=N); δ_H (300 MHz; CDCl₃) 8.13 (2H, d, J 3.0 CH=N), 7.35 (2H, d, J 1.9, ArH), 6.33 (2H, d, J 1.9, ArH), 4.39 (2H, dd, J 9.4 and 6.2, CH_AH_B(O)), 4.15 (2H, dd, J 9.4 and 4.0, CH_AH_B(O)), 3.90–3.84 (2H, m, CH=N), 2.28–2.17 (2H, m, CH(CH₃)₂) and 1.06 (12H, app dd, J 6.8 and 7.2, C(CH₃)₂); δ_C (75 MHz; CDCl₃) 157.2, 144.5, 132.6, 123.3, 110.2, 69.3, 63.5, 32.6, 20.0 and 17.4; δ_B (100 MHz; CDCl₃) 4.7; m/z LRMS (ESI⁺) 397 [(M + H)⁺, 9%], 345.2 (100), 283.2 (36); HRMS (ESI⁺) found 397.2122 ([M + H]⁺C₂₀H₂₆B₂N₂O₅ requires 397.2100).

(S,S)-10b. Red oil (76 mg, 90%); [α]²⁰_D−34.0 (c 1.0, CH₂Cl₂); v_max (film) 1649 (C=N); δ_H (300 MHz; CDCl₃) 8.13 (2H, d, J 3.0, CH=N), 7.36 (2H, d, J 1.9, ArH), 6.32 (2H, d, J 1.9, ArH), 4.39 (2H, dd, J 8.9 and 6.0, CH_AH_B(O)), 4.24–4.15 (2H, m, CH–N), 3.99 (2H, dd, J 8.9 and 7.4, CH_AH_B(O)), 1.77–1.65 (6H, m, CH_AH_BCH(CH₃)₂) and 1.00 (12H, app t, J 5.5, C(CH₃)₂); δ_C (75 MHz; CDCl₃) 157.2, 144.7, 132.7, 122.8, 110.0, 71.9, 52.2, 32.6, 20.5, 8.9 and 8.1; δ_B (100 MHz; CDCl₃) 4.6; m/z LRMS (ESI⁺) 425 [(M + H)⁺, 32%], 412.4 (27), 389.3 (35), 375.2 (100); HRMS (ESI⁺) found 425.2452 ([M + H]⁺ C₂₂H₃₀B₂N₂O₅ requires 425.2419).

(R,R)-10c. Red oil (134 mg, 91%); [α]²⁰_D +33.0 (c 1.0, CH₂Cl₂); v_max (film) 1656 (C=N); δ_H (300 MHz; CDCl₃) 8.13 (2H, s, CH=N), 7.34 (2H, d, J 1.9, ArH), 6.31 (2H, d, J 1.9, ArH), 4.42–4.39 (2H, m, CH_AH_B(O)), 4.09–3.99 (4H, m, CH_AH_B(O) and CH–N), 2.05–1.90 (4H, m, CH₂Me) and 1.07 (6H, t, J 7.0, CH₃); δ_C (75 MHz; CDCl₃) 156.3, 144.5, 132.6, 123.3 110.2, 67.7, 65.7, 26.4 and 10.4; δ_B (100 MHz; CDCl₃) 4.8; m/z LRMS (ESI⁺) 369 [(M+H)⁺, 65%], 288.2 (100), 201.1 (34); HRMS (ESI⁺) found 369.1791 ([M+H]⁺ C₁₈H₂₂B₂N₂O₅ requires 369.1785).

(R,R)-10d. Red solid (79 mg, 85%); m.p. 115–118 °C (dec); [α]²⁰_D +39.6 (c 1.0, CH₂Cl₂); v_max (film) 1657 (C=N); δ_H (300 MHz; CDCl₃) 7.83 (2H, d, J 3.0, CH=N), 7.53–7.44 (10H, m, ArH), 7.42 (2H, d, J 1.9, ArH), 6.24 (2H, d, J 1.9, ArH), 5.35–5.28 (2H, m, CH(Ph)–N) and 4.57–4.45 (4H, m, CH_AH_B(O)); δ_C (75 MHz; CDCl₃) 158.3, 144.9, 136.6, 131.4, 129.8, 129.60, 129.59, 129.55, 129.50, 124.6, 110.3, 71.3 and 70.4; δ_B (100 MHz; CDCl₃) 5.4; m/z LRMS (ESI⁺) 465 [(M + H)⁺, 100%], 415.2 (33), 335.2 (36), 292.1 (32), 215.1 (10); HRMS (ESI⁺) found 465.1833 ([M + H]⁺C₂₆H₂₂B₂N₂O₅ requires 465.1787).

(R,R)-10e. Dark brown solid (85 mg, 92%); m.p. 124–126 °C (dec); [α]²⁰_D +18.5 (c 1.0, CH₂Cl₂); v_max (film) 1662 (C=N); δ_H (300 MHz; CDCl₃) 8.26 (2H, br s, CH=N), 7.56 (4H, br d, ArH), 7.45 (2H, d, J 1.9, ArH), 7.39–7.26 (6H, m, ArH), 6.34 (2H, d, J 1.9, ArH), 5.56–5.51 (2H, m, CH_AH_B(N)) and 4.11–4.08 (4H, m, CH_AH_B(N)) and CH(Ph)(O)); δ_C (75 MHz; CDCl₃) 157.7, 145.1, 142.1, 129.7, 128.8, 128.6, 128.1, 126.7, 124.5, 110.4, 76.2 and 63.7; δ_B (100 MHz; CDCl₃) 5.0; m/z LRMS (ESI⁺) 465 [(M + H)⁺, 65%], 415.2 (100), 323.2 (83); HRMS (ESI⁺) found 465.1841 ([M + H]⁺ C₂₆H₂₂B₂N₂O₅ requires 465.1787).

Acknowledgements

We would like to acknowledge the EPSRC, Royal Society, the Leverhulme Trust, Beckman-Coulter and University of Bath for funding.

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Footnote

† CCDC reference numbers 694358–694361 [(S,2R,4S)-7, 8a, 8f and 8h]. For crystallographic data in CIF or other electronic format see DOI: 10.1039/b815138e

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