Piperidines, acyl, conformations

Anodic methoxylation of conformation-ally biased 2-substituted At-acyl piperidines leads regioselectively to 6-methoxy products owing to the steric constraints... 

Spiroacylal 2 was designed under the rationale that the constraint of the carbonyl groups into a conformation in which overlap of their 7r-orbitals with the bent bonds of the cyclopropane is assured should dramatically increase the vulnerability of the cyclopropane toward nucleophilic attack.8 Experimental support for this notion is abundant.8 Spiroacylal 2 is considerably more reactive than 1,1-dicarbethoxycyclopropane in such reactions. For instance, reaction of 2 with piperidine occurs at room temperature. The corresponding reaction in the case of the diester is conducted at 110°C.5 Reactions with enolates also occur under mild conditions.8 Compound 2 reacts with the weak nucleophile pyridine at room temperature to give a betaine.8 An illustrative mechanism for the reaction of the acylal 2 with aniline to afford 2-oxo-l-phenyl-3-pyrrolidinecarboxylic acid (3) is... 

The reaction indeed worked well. Thus, heating to reflux a methanolic solution of piperazine, formaldehyde, acetic acid, and cyclohexyl isocyanide afforded the split-Ugi adduct 79 in 75% yield. Note that in this reaction, the symmetric diamine has been effectively desymmetrized since one nitrogen atom was alkylated while the other was acylated. The piperidine ring in intermediate 77 has to adopt a boat conformation in order for the transacylation to take place smoothly [Scheme 5.23, reaction (a)]. 

A -Piperideine — see Pyridine, 2,3,4,5-tetrahydro-A2-Piperideine — see Pyridine, 1,2,3,4-tetrahydro-A3-Piperideine — see Pyridine, 1,2,3,6-tetrahydro-Piperideines — see Pyridines, tetrahydro-Piperidine, 1-acryloyl-polymers, I, 284 Piperidine, N-acyl-IJC chemical shifts, 2, 15 Piperidine, 2-alkyl- N-nitro-conformation, 2, 160 Piperidine, 4-amino-synthesis... 

A series of papers has appeared from Casy s laboratory dealing with the synthesis, stereochemistry, and conformations of some piperidin -ols. - Three diastereoisomeric l,2,5-trimethyl-4-phenylpiperidin-4-ols were isolated. Making the questionable assumptions (i) that the phenyl group will be equatorial in any chair conformation and (ii) that first-order spectral analysis is applicable, they arrive at configurational and conformational assignments different from those proposed earlier by a Russian group. Subsequent papers deal with acyl derivatives of the above compounds and the n.m.r. spectra of compounds in this series. Similar work has also been reported for ciS and tra 5-l,3-dimethylpiperidin-4-ols and their derivatives. ... 

Lipases can also perform the KR of conformational isomers, processes that have been useful in the synthesis of a key intermediate of the famesyl protein transferase inhibitor, SCH 6636 [218]. The use of the lipase Toyobo LIP-300 and 3 equivalents of trifluoroethyl isobutyrate for a 2.3 g of substrate N-acylation reaction allowed the separation of the piperidine enantiomers, which exist due to atropisomerism about an exocyclic double bond, obtaining after 26 h at room temperature the substrate and product in around 97% ee after 50% conversion. 

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