ORGN 815 |
| Isoxazolidine 1 is a key intermediate, whose stereochemistry is established through a chiral auxiliary controlled diastereoselective [1,3]-dipolar cycloaddition reaction. Due to the presence of the competing dechlorination side reaction, the widely-used H2/Pd debenzylation reaction is not applicable. A three-step transformation via mesylate was initially employed to effect the removal of chiral auxiliary, giving ~86% overall assay yield. An undesired elimination pathway leading to byproduct 3 accounted for ~10% product loss. The newly developed triflate process afforded the desired product 1 exclusively, likely via formation of an aziridinium ion, remarkably different from the b-elimination mechanism believed to be involved for the mesylate. Recently, we discovered that oxidation of alcohol 2 to aldehyde 4, followed by basic treatment not only facilely removed the chiral auxiliary, but also directly led to amino alcohol 5, eliminating the need for a subsequent Ra-Ni hydrogenation.
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Combinatorial, Parallel and Process Chemistry, Heterocycles, Aromatics, New Reactions and Methodology
8:00 PM-10:00 PM, Wednesday, August 22, 2007 BCEC -- Exhibit Hall - B2, Poster
Sci-Mix
Division of Organic Chemistry |
