83622-41-7

Pinacol (dichloromethyl) boronate is a general reagent that was employed by Prof. Greg C. Fu and coworkers to achieve the iterative synthesis of asymmetric (secondary) alkyl boronate esters. These can be further derivatized through a growing suite of chemical transformations developed in the last decade (cross coupling, oxidation, amination, halogenation) that proceed with stereochemical fidelity.

A hexane solution (51.5 mmol, 20.6 mL) of 2.5 M n-butyllithium (n-BuLi) was added slowly and dropwise to a THF (110 mL) solution of dichloromethane (55 mmol, 3.53 mL) that had been cooled to -100 °C under 30 mm pressure. The resulting suspension was continued to be stirred at -100 °C for 30 min, followed by a one-time addition of trimethyl borate (55 mmol, 6.25 mL). After 30 min of reaction, the reaction was quenched with 5 M hydrochloric acid (10 mL) and the organic layer was separated. The aqueous layer was extracted with ether (2 x 25 mL) and the organic layers were combined and concentrated. The crude product was dissolved in benzene (110 mL) and pinacol (55 mmol, 6.5 g) was added all at once. The reaction mixture was refluxed at low temperature for 48 hours. Purification by fractional distillation afforded 4.64 g (40% yield) of the target compound pinacol (dichloromethyl) borate as a clear oil.1H NMR (400 MHz, CDCl3) δ 5.37 (s, 1H), 1.36 (s, 12H).

[1] Patent: WO2014/183221, 2014, A1. Location in patent: Paragraph 00221
[2] Organic Letters, 2017, vol. 19, # 22, p. 6104 - 6107