tBuOLi-Promoted Hydroboration of Esters and Epoxides

Commercially available and inexpensive lithium tert-butoxide (tBuOLi) acts as a good precatalyst for the hydroboration of esters, lactones, and epoxides using pinacolborane as a borylation agent. Functional groups such as cyano-, nitro-, amino-, vinyl, and alkynyl are unaffected under the presented hydroboration process, representing high chemoselectivity. This transformation has also been effectively applied to the synthesis of key intermediates of Erlotinib and Cinacalcet. Preliminary investigations of the mechanism show that the hydroboration proceeds through the in situ formed BH3 species.

In a nitrogen-filled glovebox, to a 10 mL Schlenk reaction tube equipped with a magnetic stirrer, t BuOLi (8.0 mg, 5 mol%), THF (1.0 mL), HBpin (2.5 mmol) and the corresponding lactones (1 mmol) were added in sequence. The reaction mixture was then heated at 100 °C (oil bath) with vigorous stirring for 24 hours. Thereafter, the reaction mixture was cooled down to room temperature and NaOH/MeOH (2 mL, 10 % aq.) solution was added. The resulting mixture was stirred overnight for complete hydrolysis. Organic compounds were extracted from the mixture with CH2Cl2 (3 x 12 mL). The organic fraction was dried over Na2SO4 and all volatiles were removed using rotary evaporator. The crude mixture was monitored by 1 H NMR analysis using biphenyl or hexamethylbenzene as internal standard. The crude mixture was purified by flash column chromatography using PE/EtOAc (2/1) as the eluent to give the corresponding products.

Procedure for the epoxides
In a nitrogen-filled glovebox, to a 10 mL Schlenk reaction tube equipped with a magnetic stirrer, t BuOLi (4.0 mg, 5 mol%), THF (1.0 mL), HBpin (2.5 mmol) and the corresponding epoxides (1 mmol) were added in sequence. The reaction mixture was then heated at 100 °C (oil bath) with vigorous stirring for 24 hours. Thereafter, the reaction mixture was cooled down to room temperature and S3 NaOH/MeOH (2 mL, 10 % aq.) solution was added. The resulting mixture was stirred overnight for complete hydrolysis. Organic compounds were extracted from the mixture with CH2Cl2 (3 x 12 mL).
The organic fraction was dried over Na2SO4 and all volatiles were removed using rotary evaporator.
The crude mixture was monitored by 1 H NMR analysis using hexamethylbenzene as internal standard.
The crude mixture was purified by flash column chromatography using PE/EtOAc (3/1) as the eluent to give the corresponding products.