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

Emma K. Edelstein; Andrea C. Grote; Maximilian D. Palkowitz; James P. Morken

doi:10.1055/s-0037-1610172

Synlett, Table of Contents

Synlett 2018; 29(13): 1749-1752
DOI: 10.1055/s-0037-1610172

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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

Abstract

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^◊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.

Key words

organoboron - asymmetric synthesis - amination - chiral amines - stereochemistry

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References

References and Notes

For reviews, see:

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For a recent copper-catalyzed amination of primary 9-BBN boranes, see:

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7 Mlynarski SN. Karns AS. Morken JP. J. Am. Chem. Soc. 2012; 134: 16449
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): ν_max = 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): ν_max = 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

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