选择性保护醛酮让酯参与反应

A new reagent, the dimethylaluminum N,O-dimethylhydroxylamine complex, is effective at masking reactive carbonyl groups in situ from nucleophilic addition. This reagent allows chemoselective addition of reducing reagents, Grignard reagents, organolithiums, Wittig reagents, and enolates into substrates with multiple carbonyl groups. Moreover, the trapped carbonyl group, a stable aminal, can be unmasked in situ for additional synthetic manipulations.

4-(2-hydroxypropan-2-yl)cyclohexanone

To a 0 °C mixture of MeONHMe·HCl (42.9 mg, 0.44 mmol) in THF (2 mL) was added a solution of n-BuLi (180 μL, 2.5 M in hexanes). The mixture was stirred at 0 °C until the solution became homogeneous, and then, Me₃Al (220 μL, 2.0 M in hexanes) was added. The reaction mixture was warmed to rt and stirred for 30 min. Next, the reaction mixture was added to a 0 °C solution of ethyl 4-oxocyclohexanecarboxylate 4 (63 μL, 0.40 mmol) in THF (10 mL), and the resultant mixture was stirred for 2 h at rt. The reaction was cooled to 0 °C, MeMgBr (530 μL, 3.0 M in Et₂O) was added, and the mixture was stirred for 1 h at rt. The reaction was quenched with saturated aqueous NH₄Cl (10 mL) and extracted with EtOAc (3 × 15 mL). The organics were dried over Na₂SO₄ and concentrated under reduced pressure. SiO₂ flash chromatography (3:1 hexanes/acetone) afforded product as a colorless oil (49.2 mg, 79% yield).

Ref: Org. Lett. 2013, 15, 3082–3085