Tetrahydrofuran → HCID 75587249, compound

Participants

Reaction Conditions

Reaction Steps

A solution of tri-n-butyl-2-cyclohexenyltin (140 mg, 0.377 mmol) in THF (0.7 mL) was treated with n-BuLi (2.5 M in hexanes, 133 μL, 0.333 mmol) at −78° C. After 30 min, ZnCl2 (0.5 M in THF, 0.77 mL, 0.39 mmol) was added and following an additional 30 min, a solution of the crude aldehyde in THF (1.3 mL) was slowly added to the freshly prepared zinc reagent 46. The resulting mixture was stirred at −78° C. for 2.5 h, quenched with water and diluted with EtOAc (50 mL). The organic layer was washed with saturated NH4Cl and brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by flash chromatography (1:6 EtOAc/hexanes) to give a mixture of predominantly two diastereomers (12 mg, 33%, dr 3.5:1+trace minor diasts., 500 MHz 1H NMR) as a colorless oil which was carried directly to the next step without further characterization. The major diastereomer (±)-81 was confirmed to possess the correct relative stereochemistry following subsequent conversion to salinosporamide A (below): Rf=0.64 (40% EtOAc/Hexanes); IR (neat) 3467, 1828, 1692 cm−1; LRMS (ESI) Calcd. for C23H28ClNO5 [M+Li] 440, found 440.

Provenance & Evidence