Synlett 2018; 29(13): 1749-1752
DOI: 10.1055/s-0037-1610172
letter
© Georg Thieme Verlag Stuttgart · New York

A Protocol for Direct Stereospecific Amination of Primary, Secondary, and Tertiary Alkylboronic Esters

Emma K. Edelstein
Department of Chemistry, Boston College, Chestnut Hill, MA 02467, USA   Email: morken@bc.edu
,
Andrea C. Grote ◊
Department of Chemistry, Boston College, Chestnut Hill, MA 02467, USA   Email: morken@bc.edu
,
Maximilian D. Palkowitz ◊
Department of Chemistry, Boston College, Chestnut Hill, MA 02467, USA   Email: morken@bc.edu
,
James P. Morken*
Department of Chemistry, Boston College, Chestnut Hill, MA 02467, USA   Email: morken@bc.edu
› Author Affiliations
This work was supported by the NIH (NIGMS 59417).
Further Information

Publication History

Received: 03 April 2018

Accepted after revision: 11 May 2018

Publication Date:
20 June 2018 (online)


These authors contributed equally this work

Abstract

The direct, stereospecific amination of alkylboronic and borinic esters can be conducted by treatment of the organoboron compound with methoxyamine and potassium tert-butoxide. In addition to being stereospecific, this process also enables the direct amination of tertiary boronic esters in an efficient fashion.

Supporting Information

 
  • References and Notes


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  • 8 Aggarwal has accomplished the stereospecific amination of tertiary boronic esters employing multistep route that involves conversion of the boronic ester into a trifluoroborate, chlorination to provide the dichloroborane, and then reaction with benzylazide.6b
  • 9 General Procedure In a glove box, a 2-dram vial equipped with magnetic stir bar was charged with t-BuOK (5.0 equiv). The vial was sealed with a septum cap and was removed from the glove box. Toluene and methoxyamine (1.96 M in THF, 3.0 equiv) were added via syringe. Subsequently, the alkyl boronic ester (1.0 equiv) was added as a solution in toluene to achieve a final substrate concentration of 0.2 M. The vial was sealed with tape and left to stir for 16 h at 80 °C behind a blast shield. The reaction mixture was then cooled to room temperature before Boc2O (5.0 equiv) and saturated NaHCO3 were added. After stirring under N2 at 80 °C for 5 h, the mixture was cooled to room temperature, water was added, and the mixture and extracted three times with ethyl acetate. Drying (Na2SO4), filtration, and purification on silica gel delivered the final product. Product from 10 1H NMR (600 MHz, CDCl3): δ = 7.32–7.26 (m, 2 H), 7.24–7.14 (m, 3 H), 4.29 (br s, 1 H), 3.82 (br s, 1 H), 2.76 (br m, 2 H), 1.52–1.91 (m, 15 H), 0.87 (t, J = 6.7 Hz, 3 H). 13C NMR (150 MHz, CDCl3): δ = 155.6, 138.5, 129.7, 128.4, 126.3, 79.1, 51.7, 41.5, 34.0, 28.5, 28.3, 22.7, 14.2. IR (neat): νmax = 3339.4 (m), 2958.1 (m), 2928.4 (m), 2857.0 (w), 1699.6 (m), 1683.0 (s), 1524.6 (s), 1454.7 (w), 1363.5 (m), 1251.4 (s), 1169.2 (s), 1045.4 (m), 1014.2 (m), 743.3 (w), 699.0 (m) cm–1. HRMS (DART+) for C17H28NO2 [M + H]+ calcd: 278.2120; found: 278.2107. [α]D 20 –15.953 (c = 0.890, CHCl3, l = 50 mm). Product from 19 1H NMR (600 MHz, CDCl3): δ = 7.36–7.30 (m, 4 H), 7.30–7.26 (m, 1 H), 4.50 (s, 2 H), 3.48 (t, J = 6.5 Hz, 2 H), 1.62 (p, J = 6.5 Hz, 2 H), 1.47 (br s, 2 H), 1.43–1.33 (m, 4 H), 1.08 (s, 6 H). 13C NMR (150 MHz, CDCl3): δ = 138.7, 128.5, 127.8, 127.6, 73.0, 70.4, 49.7, 44.9, 30.5, 30.3, 21.3. IR (neat): νmax = 2935.3 (br), 2860.1 (w), 1453.9 (w), 1362.9 (m), 1100.0 (s), 841.9 (br), 733.0 (s), 696.4 (s) cm–1. HRMS (DART+) for C14H23NO [M + H]+ calcd: 222.1858; found: 222.1852.
  • 10 Voth S. Hollett JW. McCubbin JA. J. Org. Chem. 2015; 80: 2545