Pyridines, acylation from piperidines

The C2-symmetrical chiral amine tran.v-(2/ ,6y )-2,6-bis(benzyloxymethyl)piperidine (1), prepared15 from commercially available (S)-2-(benzyloxymethyl)oxirane, has been used in diastereoselective amide alkylations. Thus, the chiral amine of 76% ee is acylated [anhydride or mixed trimethylacetic acid anhydride, 1.2 equivalents of triethylamine and 0.05 equivalents of 4-(dimethylamino)pyridine] and the resulting amide 2 treated with 2.1 equivalents of lithium diisopropylamide at —78 CC to give the enolate. This is then alkylated to give high diastereo-meric ratios (>94 6) of alkylation products 3 in 60-93% yield16. 

Gutman,50 in his process route, which did not report any yields, hydrogenated the pyridine ring first to access the piperidine moiety and constructed the indanone ring system via an intramolecular Friedel-Crafts acylation (Scheme 5). Hydrogenation of diester 31, obtained from condensation of 4-pyridine carboxaldehyde and dimethyl malonate, followed by benzylation of the piperidine intermediate afforded A-benzylated piperidine 32. Alkylation of 32 with 3,4-dimethoxybenzyl chloride (33) and subsequent hydrolysis gave dicarboxylic acid 34. Subjection of 34 to strong acid resulted in intramolecular Friedel-Crafts acylation and in situ decarboxylation to provide 3. 

In pyridine/water solution, the system making use of [Mn VMe(piperidine) Br] % sodium borohydride, and O2 produced a very small amount of cyclohexene oxide from cyclohexene. Similar systems involving different solvents, substrates and reducing agents failed to give evidence for autoxidation. The addition of acyl halides and acetic anhydride to these solutions in an effort to facilitate 0-0 bond cleavage by acylation also failed to produce detectable concentrations of products. ... 

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