Enantioselective Synthesis, Structure, and Application of an ortho-Sulfinyl Arylboronic Acid

Abstract

Despite their potential use as catalysts and reagents, few chiral arylboronic acids are known, especially those with a proximal stereogenic ortho-substituent. Herein, the design, synthesis, structural study, and preliminary application of optically enriched ortho-sulfinyl arylboronic acids is described. These compounds were prepared in 90% enantiomeric excess by way of electrophilic trapping of lithiobenzene with the optically enriched reagent, tert-butyl tert-butanethiosulfinate, followed by a sulfoxide-directed ortho-lithiation/borylation. The resulting products were found to exist in the open boronic acid form, and they show promise as direct amidation catalysts and as resolving agents for the analysis of enantiomeric purity of chiral diols.

Keywords

amidation - boronic acid catalysis - chiral boronic acid - diol resolution - enantiomeric excess - kinetic resolution

Publication History

Received: 22 January 2026

Accepted after revision: 18 March 2026

Article published online:
02 April 2026

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Experimental procedure for the synthesis of (±)-9a: A flame-dried 50 mL round-bottom flask was charged with (±)-(tert-butylsulfinyl)benzene 10a (499 mg, 2.74 mmol, 1.00 equiv) under N₂. Anhydrous THF (13.7 mL) was added, and the solution was cooled to −78 °C. n-BuLi (2.50 M in hexanes, 1.21 mL, 3.02 mmol, 1.10 equiv) was added dropwise, and the mixture was stirred at −78 °C for 2 h. B(OMe)₃ (0.340 mL, 3.02 mmol, 1.10 equiv) was then added dropwise, and stirring was continued at −78 °C for 2 h before warming to room temperature and stirring for 16 h. The reaction was cooled to 0 °C and quenched with 1 M HCl in Et₂O to pH ≈ 2, then stirred at room temperature for 2 h. After concentration, the residue was extracted with EtOAc and water, washed with brine, dried over Na₂SO₄, filtered, and concentrated. The crude product was precipitated from EtOAc/hexanes to afford the product as a white solid (564 mg, 91.0% yield). ¹H NMR (498 MHz, acetone-d₆ )*: 8.02–7.96 (m, 1H), 7.66 (m, 1H), 7.60–7.53 (m, 2H), 1.15 (s, 9H). ¹³C NMR (125 MHz, acetone-d₆ )*: δ 144.1, 137.3, 131.4, 130.1, 128.4, 57.6, 23.4. ¹¹B-NMR (160 MHz, acetone-d ₆)*: δ 28.4. FTIR (KBr, cm⁻¹): 3403 (br, m), 3124 (w), 3053 (s), 2961 (s), 2925 (s), 2867 (m), 1633 (w), 1586 (s), 1558 (m), 1429 (s), 1123 (m), 1076 (w), 1042 (s). HRMS (ESI) for C₁₀H₁₄BO₃S [M−H]^–: calcd: 225.0762; found: 225.0764. *2 drops of D₂O were added.