Synthesis of N-Substituted 1,6-Dihydro-3(2H)-pyridinones and 1-Acyl-3-piperidines

Synthesis of the N-substituted 1,6-dihydro-3(2H)pyridinones (3, 5 , and 9) and 1-acyl-3-piperidones (l and 10) is described.1-Benzylpiperidine-3,5-dione (1) was converted into N-substituted 1,6-dihydro-3(2H)-pyridinones (3, 6 , and 9) via the methyl en01 ethers (2, 5, and 8).Selective reduction of -6 and 9 with Et3SiH in the presence of TiC14 produced the 1acyl-3-piperidones (? and 10).Recently, 1,6-dibydro-3(2H)-pyridinone system has been reported by M. Hanaoka and his co-workers1 to be a potential synthon to many kinds of alkaloid syntheses, and 1-acyl-3-piperidone derivatives have proved to be useful intermediates for syntheses analogues of nipecotic acid and guvacine.'Hence, we have investigated the chemistry of 1,6-dihydro-3(2H)-pyridinones and wish to report herein a convenient route to the N-substituted 1,6-dihydro-3(2H)-pyridinones and l-acyl-3piperidones.The synthesis of the title compounds in the Scheme 1 was achieved from the known 1-benzylpiperidine-3.5-dione (L), which was subsequently converted into l-benzyl-3-methoxy-5-0~0-3,4-dehydropiperidine (2) [ mp 111-112°C (lit.3 109.5-11O0C)] by treatment with dry MeOH and HC1 gas in yield of 67%.Reduction of 2 using NaBH4 in EtOH gave a 71% yield of 1-benzyl-1,6-dihydro-3(2H)-pyridinone ( 3 ) [ syrup, 3 max 1685 cm-l, mle 187 (M+) 1. Dehenzylation of 1 hydrochloride by catalytic hydrogenation on 5% Pd-C in MeOH at room temperature gave a 80% yield of 3-methoxy-5-0x0-3.4-dehydropiperidine(4) [ oil, $ max 1650 and 1610 cm-l, mle 127 ( M ' ) 4