Study of the hydroxylation of N-substituted 1,2,5,6-tetrahydropyridines

Synthesis of Functionalized Nitrogen Heterocycles by Radical Decarboxylation of β‐ and γ‐Amino Acids

“…For example, treatment of 29 with DBU gives the alkene 37 28 (Scheme ) in good yields. This product reacts with OsO 4 to afford the dihydroxylated piperidine (±)‐ 38 28c in satisfactory yields.…”

“…The residue was purified by chromatography on silica gel (hexanes/EtOAc, 50:50) to yield the diol 38 (28 mg, 57%) as a colourless oil. An alternative synthesis of diol 38 has been reported previously 28c…”

Cascade and stepwise oxidation of 4-phenyl- and 4-(γ-pyridyl)tetrahydropyridines

“…The ability of 1,2,3,6-tetrahydropyridines (THP) to react with aqueous KMnO 4 was reported 1 to depend considerably on the nature of the substituent present at the 4-position of the pyridine ring. For example, the 4-methyl-substituted THPs are easily hydroxylated under the classical conditions of the Vagner reaction (cooling, water-alcohol solution), whereas their 4-phenyl analogues appeared to be completely inert.…”

“…For example, the 4-methyl-substituted THPs are easily hydroxylated under the classical conditions of the Vagner reaction (cooling, water-alcohol solution), whereas their 4-phenyl analogues appeared to be completely inert. 1 This latter fact appears to be connected with the coplanarity of the phenyl and tetrahydropyridine moities which increases steric hindrance to permanganate anion attack on the double bond. Nevertheless, we have recently found 2,3 that 4-phenylTHP 1a and 4-(γ-pyridyl)THP 1b can be readily polyfunctionalised by a one-pot oxidation protocol, making available a high-yield synthetic method for the preparation of 3,4-dihydroxypiperidin-2-ones 3a,b under slightly modified conditions (20-35 °C, water-acetonitrile solution).…”

“…It was therefore established that oxidation of 4-pyridyl-THP 1b into 2b and 4b proceeded well, though with lower yields (27% and 58%, respectively) in comparison with the analogous reactions of 4-phenylTHP. 2,4 The lactams 2a,b were readily hydroxylated at < 0 °C (in contrast to the inert 4-aryl THP 1 1 ) into the cis-diol lactams 3a,b with yields 54% and 45%, respectively. However, at room temperature the yield of 3a was increased to 76%.…”