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 DMF at -60 degrees C. The racemization barrier of the axially chiral enolate intermediate was estimated to be approximately 15.5 kcal/mol. On the basis of the barrier, the chiral enolate intermediate was supposed to undergo cyclization within approximately 10(-3) sec at 20 degrees C after it is generated to give the product in >or=99% ee. Thus, enolates generated with powdered KOH in DMSO were expected to be extremely reactive.
Kawabata
Takeo
T
Institute for Chemical Research, Kyoto University Uji, Kyoto 611- 0011, Japan. kawabata@scl.kyoto-u.ac.jp
Moriyama
Katsuhiko
K
Kawakami
Shimpei
S
Tsubaki
Kazunori
K
D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D004121:Dimethyl Sulfoxide / Q000737:chemistry*; D006878:Hydroxides / Q000737:chemistry*; D008968:Molecular Conformation; D017680:Potassium Compounds / Q000737:chemistry*; D011208:Powders; D013237:Stereoisomerism; D013696:Temperature
D000596:Amino Acids; D006878:Hydroxides; D017680:Potassium Compounds; D011208:Powders; C029943:potassium hydroxide; D004121:Dimethyl Sulfoxide