Asymmetric desymmetrization based on an intramolecular haloetherification: a highly effective and recyclable chiral nonracemic auxiliary, 2-exo-methyl-3-endo-phenyl-5-norbornene-2-carboxaldehyde, for meso-1,3- and meso-1,4-diols.
A new chiral auxiliary, a 3-endo-phenyl norbornene aldehyde derivative, which is a crystalline, very stable, and easily handled, was developed for the desymmetrization of meso-1,3- and meso-1,4-diols. The key step of the method, an intramolecular bromoetherification, proceeded in a highly diastereoselective manner. A four-step sequence, 1) acetalization, 2) intramolecular bromoetherification followed by acid hydrolysis, 3) protection of the alcohol, and 4) retrobromoetherification, transformed the meso-diols into optically active derivatives. The 3-endo-phenyl norbornene aldehyde derivative was simultaneously reformed and could be used repeatedly. This is the first chemical example of a single auxiliary that is applicable for highly enantioselective desymmetrization of meso-1,3- and meso-1,4-diols; to the best of our knowledge, this is the best chemical method available for the desymmetrization of meso-1,4-diols.
Fujioka
Hiromichi
H
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6, Yamada-oka, Suita, Osaka, 565-0871, Japan. fujioka@phs.osaka-u.ac.jp
Fujita
Tetsuya
T
Kotoku
Naoyuki
N
Ohba
Yusuke
Y
Nagatomi
Yasushi
Y
Hiramatsu
Atsushi
A
Kita
Yasuyuki
Y
D006018:Glycols / Q000138:chemical synthesis* / Q000737:chemistry; D007536:Isomerism; D015394:Molecular Structure; D009636:Norbornanes / Q000138:chemical synthesis / Q000737:chemistry*; D013237:Stereoisomerism
D006018:Glycols; D009636:Norbornanes