Powdered KOH in DMSO: An efficient base for asymmetric Cyclization via memory of chirality at ambient temperature

Enolate chemistry has been extensively used for stereoselective C-C bond formation, in which metal amide bases are frequently employed in strictly anhydrous solvents at low temperatures. However, we found that asymmetric intramolecular C-C bond formation via axially chiral enolate intermediates proceeded in up to 99% ee at 20 degrees C using powdered KOH in dry or wet DMSO as a base. The enantioselectivity was even higher than that of the corresponding reactions with potassium hexamethyldisilazide in DIVIF at -60 degrees C. The racemization barrier of the axially chiral enolate intermediate was estimated to be similar to 15.5 kcal/mol. On the basis of the barrier, the chiral enolate intermediate was supposed to undergo cyclization within similar to 10(-3) sec at 20 degrees C after it is generated to give the product in 2 >= 99% ee. Thus, enolates generated with powdered KOH in DMSO were expected to be extremely reactive.