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

• Published in: Chemistry : a European journal 2004-10, Vol.10 (21), p.5386-5397
• Main Authors: Fujioka, Hiromichi, Fujita, Tetsuya, Kotoku, Naoyuki, Ohba, Yusuke, Nagatomi, Yasushi, Hiramatsu, Atsushi, Kita, Yasuyuki
• Format: Article
• Language: English
• Subjects: asymmetric synthesis; chiral auxiliaries; desymmetrization; diols; Glycols - chemical synthesis; Glycols - chemistry; Isomerism; Molecular Structure; Norbornanes - chemical synthesis; Norbornanes - chemistry; norbornene; Stereoisomerism
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.200400444

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. Discriminating diols: Efficient desymmetrization of meso‐1,3‐ and meso‐1,4‐diols was achieved by using a 3‐endo‐phenylnorbornene aldehyde derivative (see scheme).