Lithium diisopropylamide

The Uses of Lithium diisopropylamide

Lithium diisopropylamide is a sterically hindered nonnucleophilic strong base used for selective deprotonations, especially for the production of kinetic enolates (i.e., the thermodynamically less favored isomer) and (hetero-)aromatic carbanions. In the production of the serum lipid regulating agent Gemfibrozil one key intermediate is formed by quenching an ester enolate with 1-bromo-3-chloropropane.

The Uses of Lithium diisopropylamide

To a solution of the SM (4.0 g, 14.6 mmol) in THF (30 mL) at -78 C was added dropwise LDA (2.0M in THF/heptane/ethylbenzene, 9.6 mL, 16.9 mmol). The mixture was stirred at -78 C for 1 h. A solution of DMF (1.7 mL, 22.0 mmol) in THF (5 mL) was added slowly at - 78 C, and the reaction mixture was stirred for 3 h. The mixture was quenched with sat aq NH4Cl (50 mL) and extracted with EtOAc (2 x 30 mL). The combined organics were washed with H2O (50 mL), brine (50 mL), dried (Na2SO4), and concentrated. The resulting material was purified by silica gel column chromatography (20% EtOAc/hexane) to provide the product as a colorless oil. [1.4 g, 32%]