Synlett 2024; 35(08): 899-902
DOI: 10.1055/s-0043-1763674
cluster
Special Issue dedicated to Keith Fagnou

An Exploration of Regioselectivity During Formation of Aminoboronates from Epoxides

Alina Trofimova
,
Chelsey Brien
,
Joanne Tan
,
Vincent Trudel
,
Andrei K. Yudin
Natural Sciences and Engineering Research Council of Canada


Abstract

α-Aminoboronic acids and their derivatives are important synthetic targets. Our research interest has been focused on the synthesis and applications of MIDA (N-methyliminodiacetic acid) protected aminoboronates. Herein we report syntheses of regioisomeric β-borylated azidoalcohols. The geminal azidoboronate represents a rare example of an α-azidoalcohol and is produced through trapping of oxonium ions that develop during the rearrangement of α-boryl aldehydes. The vicinal azidoboronate can be obtained from α-bromoacetyl MIDA boronate and enables the preparation of aziridine MIDA boronate through the Staudinger reaction.

Supporting Information



Publication History

Received: 08 November 2023

Accepted after revision: 29 November 2023

Article published online:
11 January 2024

© 2024. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References and Notes

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  • 16 Boryl 1,1-Azidoalcohol (7) To a flame-dried flask equipped with a magnetic stirring bar and a rubber septum was added oxiranyl MIDA boronate (4a, 0.3 mmol, 1.0 equiv., 83 mg) in 3 mL anhydrous DCM. The solution was cooled to –30 °C. TMSN3 (0.6 mmol, 2.0 equiv., 0.079 mL) was added dropwise with stirring. After that, BF3·Et2O (0.3 mmol, 1.0 equiv., 0.037 mL) was added dropwise with stirring at –30 °C. The mixture was then stirred at –30 °C to 0 °C over 30 min. The reaction was quenched by saturated aqueous NaHCO3. The organic layer was then separated using DCM for washing the flask; the aqueous layer was extracted with EtOAc (2 × 5 mL). The combined organic layer was dried over anhydrous Na2SO4 and concentrated to dryness. The crude residue was purified using flash column chromatography on silica gel (hexanes/EtOAc, 1:1 → EtOAc → EtOAc/MeCN, 9:1) to afford pure products 5a (77% isolated yield, 63 mg) and 7 (10% isolated yield, 9 mg). The NMR spectra matched the reported spectra of 5a. 1H NMR (600 MHz, CD3CN): δ = 7.35–7.29 (m, 4 H), 7.28–7.23 (m, 1 H), 5.40 (d, J = 8.7 Hz, 1 H), 4.13–3.87 (m, 3 H), 3.49 (d, J = 17.2 Hz, 1 H), 2.94 (s, 3 H), 2.64 (d, J = 8.7 Hz, 1 H) ppm. 13C NMR (101 MHz, CD3CN): δ = 168.8, 168.7, 140.2, 130.8, 129.4, 127.5, 81.4, 64.3, 63.8, 47.7 ppm. 11B NMR (128 MHz, CD3CN): δ = 11.5 ppm. As the carbon directly attached to the boron atom exhibited significant line broadening due to quadrupolar relaxation, its chemical shift was deduced from HMBC spectra and was 42.1 ppm.
  • 17 Boryl 1,2-Azidoalcohol (2b) To a flask equipped with a magnetic stirring bar and a rubber septum was added α-bromoacetyl MIDA boronate (3b, 2.82 mmol, 1.0 equiv., 790 mg) in 5.6 mL DMSO (0.5 M) at room temperature under air. To a solution was added sodium azide (8.47 mmol, 3.0 equiv., 550 mg). The mixture was then heated to 60 °C, and the reaction was stirred at 60 °C for 18 h or as indicated by TLC. Upon completion, the reaction mixture was diluted with water and EtOAc and transferred to a separatory funnel. The organic layer was then separated. The aqueous layer was extracted with EtOAc. The combined organic layer was washed with brine, dried over anhydrous Na2SO4, and concentrated to dryness. The crude residue was purified using flash column chromatography on silica gel (EtOAc → EtOAc/MeCN, 9:1) to afford pure product 2b (42% isolated yield, 287 mg). 1H NMR (400 MHz, CD3CN): δ = 3.96 (dd, J = 16.8, 2.0 Hz, 2 H), 3.83 (dd, J = 16.8, 2.8 Hz, 2 H), 3.53–3.42 (m, 2 H), 3.33 (dd, J = 12.9, 10.0 Hz, 1 H), 3.04 (s, 3 H) ppm. 13C NMR (126 MHz, CD3CN): δ = 169.5, 168.8, 63.1, 62.9, 56.2, 46.4 ppm. 11B NMR (128 MHz, CD3CN): δ = 10.3 ppm. HRMS (DART-AccuTOF 4G) [M + NH4 +]: m/z calcd for C7H15BN5O5: 260.1161; found: 260.1164.
  • 18 Boryl Aziridine (1) To a flame-dried flask equipped with a magnetic stirring bar and a rubber septum was added 1,2-azidoalcohol 2b (0.48 mmol, 1.0 equiv., 116 mg) in 5 mL anhydrous MeCN at room temperature. Triphenylphosphine (0.96 mmol, 2.0 equiv., 251 mg) was then added to the solution. The mixture was allowed to stir at room temperature for 1 h. The mixture was then heated to 60 °C, and the reaction was stirred at 60 °C for 2 h or as indicated by TLC. Upon completion, the reaction mixture was concentrated in vacuo to dryness. Et2O was added to a crude reaction and sonicated under air. Et2O was decanted, and the washing was repeated 2 times. The white solid was then dried in vacuo to afford pure product 1 (88% isolated yield, 83 mg). 1H NMR (400 MHz, CD3CN): δ = 3.97–3.77 (m, 4 H), 3.03 (s, 3 H), 1.72 (d, J = 6.9 Hz, 1 H), 1.36 (d, J = 4.2 Hz, 1 H), 0.99 (dd, J = 6.9, 4.4 Hz, 1 H) ppm. 13C NMR (126 MHz, CD3CN): δ = 168.9, 63.1, 62.7, 46.8, 22.5 ppm. 11B NMR (128 MHz, CD3CN): δ = 11.3 ppm. HRMS (ESI-MS) [M + H+]: m/z calcd for C7H12BN2O4: 198.0921; found: 198.0921.