Routes for the Synthesis of (2S)-2-Methyltetrahydropyran-4-one from Simple Optically Pure Building Blocks
Citations Over TimeTop 20% of 2009 papers
Abstract
Routes to (2S)-2-methyltetrahydropyran-4-one of high optical purity starting from readily available chiral pool precursors and suitable for large-scale manufacture are described. In one approach, the key step is cyclisation of (S)-5-hydroxyhex-1-en-3-one, derived either from an alkyl (S)-3-hydroxybutyrate or (S)-propylene oxide. Formation of the tetrahydropyran ring directly via an intramolecular oxy-Michael reaction under acid-catalysed conditions resulted in loss of optical purity, whereas proceeding through the intermediate (2S)-2-methyl-2,3-dihydropyran-4-one, via an oxidative Pd-catalysed ring closure, followed by hydrogenation of the alkenyl bond, preserved the optical purity. An alternative approach to (2S)-2-methyl-2,3-dihydropyran-4-one is also reported, again starting from an alkyl (S)-3-hydroxybutyrate by elaboration to a carbonyl-protected (6S)-6-methyl-5,6-dihydropyran-2,4-dione derivative, followed by partial reduction and dehydration. Alternatively, the carbonyl group can be reduced out completely in one step to furnish (2S)-2-methyltetrahydropyran-4-one directly after deprotection.
Related Papers
- → Synthetic studies on the phorboxazoles: a short synthesis of an epi-C23 tetrahydropyran core(2010)7 cited
- → Synthetic Studies of Ambruticin: Preparation of the C1-C8 Tetrahydropyran and the C17-C24 Dihydropyran Segments(2015)
- → ChemInform Abstract: Regioselective Dihydropyran Formation from 4‐Iodo‐2,6‐disubstituted Tetrahydropyran Derivatives Using In(OAc)3/LiI System as the Promoter.(2016)
- → ChemInform Abstract: Synthesis of 2,6‐trans‐ and 3,3,6‐Trisubstituted Tetrahydropyran‐4‐ones from Maitland—Japp Derived 2H‐Dihydropyran‐4‐ones: A Total Synthesis of Diospongin B.(2016)
- → Synthetic Studies of Ambruticin: Preparation of the C1-C8 Tetrahydropyran and the C17-C24 Dihydropyran Segments(2015)