4- Piperidinols formation

We now turn to the remaining two hydroxylamines that are N-hydroxylated derivatives of 2,2,6,6-tetramethyl-4-piperidone and -4-piperidinol. The enthalpies of formation of some simple 4-piperidones and their corresponding 4-piperidinols have recently been determined. The values of gaseous N-methyl-4-piperidone and Af-methyl-4-piperidinol are —160.7 1.7 and —226.8 1.8 kJmol (also see Reference 18). The difference between these contemporary values is — 66.1 2.5 kJmol while for the hydroxylated and methylated counterpart species the difference is —47.0 4.8 kJmoH. For comparison, the formal enthalpy of reduction of 3-hexanone to 3-hexanol is ca —54 kJmoH. As has been discussed earlier, reduction enthalpies are not necessarily constant . Relatedly, reaction 8 that exchanges N-methyl and N-hydroxy and parent and tetramethylpiperidines is endothermic by 19.1 5.4 kJmol . The deviation from thermoneutrality is more... 

An Sn2 reaction with anchimeric assistance (via formation of a bicyclic aziridinium ion intermediate) has been proposed for the nucleophilic substitution of trans-2-substituted 3-piperidinol mesylates by nitrogen nucleophiles with retention of trans... 

The metabolism of the prodines must be assumed to be hydrolysis of the ester, formation of the corresponding piperidinol derivatives, and N-dealkylation, which is the most important step. Possible hydroxylation products analogous to those formed in the metabolism of phencyclidine may also be produced. 

The aldehyde could readily be converted to the desired y-amidoallylboronate 50 by the standard enamide formation method (Schiff-bavSe formation, followed by acetylation, followed by deprotonation of the acylirnmonium ion to the enamide). Treatment of 50 with either Yb(OTf>3or LiBp4 in moist dichloromethane or acetonitrile did liberate the desired aldehyde 47 which indeed cyclized as anticipated to the desired trans-2-vinyl-3-piperidinol 46. Yet the yields remained unsatisfactory (40 - 45%). The main reaction was the acid-catalyzed hydrolysis of the enamide function, which eventually gave rise to the formation of the undesired pyrrolidine derivative 51. (25)... 

We subjected this compound to rhodium catalyzed hydroformylation using the BIPHEPHOS ligand, which guarantees the predominant formation of the unbranched aldehyde. (28, 29) Hydroformylation, allylboration and the second hydroformylation proceeded cleanly to furnish the piperidinol derivative 57 in 73% yield. The latter compound was found to exist as a mixture of the lactoi and the aldehyde form. (25)... 

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