Piperidines trimer

Piperidine, 3-aryIoxymethyI-4-phenyI-as antidepressant, 1, 169 Piperidine, JV-bromo-photoelectron spectroscopy, 2, 142 Piperidine, cis-4- t-butyl-r- cyclohexyl-1 -phenyl-X-ray analysis, 2, 161 Piperidine, 3-chloro-pyrrolidines from, 4, 147 Piperidine, N-chloro-photoelectron spectroscopy, 2, 142 reactions, 2, 373 trimerization, 3, 510 Piperidine, 4-cycIopentyI-2,6-dioxo-synthesis... 

Nitrogen-containing heterocyclic compounds, including 1,2,3,4-tetrahydroqui-noline, piperidine, pyrrolidine and indoline, are also popular hydrogen donors for the reduction of aldehydes, alkenes, and alkynes [75, 76]. With piperidine as hydrogen donor, the highly reactive 1-piperidene intermediate undergoes trimer-ization or, in the presence of amines, an addition reaction [77]. Pyridine was not observed as a reaction product. 

The so-called trimerization of propynal in the presence of piperidine acetate provides a synthesis of 4-ethynyI-4//-pyran-3,5-dicarbaldehyde (149) (50LA(568)34> it should be noted that the structure proposed for the product in the original work has been corrected (64CB1959). In the absence of moisture, the reaction fails and it seems likely that the synthesis involves hydration of the alkyne to the divinyl ether. Finally, condensation with the third molecule of the aldehyde results in cyclization to the product (Scheme 20). 

Aryl-A3-iodane oxidation of amines to imines also involves a combination of ligand exchange and successive reductive -elimination. Oxidation of pyrrolidine with iodosylbenzene 18 affords quantitatively an equilibrium mixture of 1-pyrroline and its trimer [72]. When oxidation of piperidine with 18 (2 equiv) was carried out in water, 2-piperidone was produced [73]. In the latter reaction, a sequence of ligand exchange and reductive -elimination was repeated two times [Eq. (38)]. 

Trimeric phosphonitrile fluoride is much less susceptible to nucleophilic attack than the tetramer, as evidenced by the fact that the trimeric fluoride can be washed with water. It is believed that the P—N ring structure remains intact during aqueous hydrolysis, although a defined product has not been isolated. There is no indication of a reaction between (PNF2)s and anihne or piperidine, but while ammonia reacts, no well-defined product... 

The phosphonitrilic halides are weaker bases than are some related nonaromatic compounds, just as pyridine is a weaker base than piperidine. The bond type in the phosphonitrilic series is probably the same as in the phosphine-imines RaPrNR (80, 81) the stability of these compounds, too, increases with the electronegativity of the substituents on the phosphorus. Tetraphenylphosphine-imine is one of the most stable of these compounds, and forms a hydrochloride. Its base strength is therefore greater than those of the phosphonitrilic halides, presumably because the opportunities for electronic delocalization are less. The Af-ethyl ester of the trimeric phosphonitrilic acid, which has a cyclic structure, but in which resonance of the same type as in the phosphonitrilic halides cannot occur, also forms a hydrochloride ( 1). It is, therefore, a comparatively strong base, in spite of the inductive effect of the two oxygen atoms on the phosphorus. The extreme weakness of the phosphonitrilic halides as bases cannot therefore be wholly due to the inductive effect of the halogens. 

Cyclic imines, such as 1-pyrroline (6) and A -piperidine (32), which are prone to trimerization, can be prepared from iV-halopyirolidine and iV-halopiperidine respectively and treated in situ with organoli-thium reagents to provide 2-alkylated and 2-aiylated pyrrolidines and piperidines in modest yield. Corey et al. treated substituted piperidine (17) generated in this fashion with iV-pentyllithium to establish die stereochemistry of the remote pentyl side chain of perhydrohistrionicotoxin (33), as condensation occurred from the more accessible re-face of the imine ir-system of (17). 

Several amine adducts of j -isopropyltropolone complexes of nickel(ii) have been isolated NiL2(py)2, NiL2(y-pic)2, NiLjfa-pic), NiLjY (Y = piperidine, or diethyl-amine /I = 1 or 2). The complexes are octahedral and probably trimeric. The crystal structure of bis(diphenyldipyrazolylborato)nickel(ii), (Ph2B(C3H3N2)2 Ni has been determined. ... 

The trimer of 1-piperidine, best prepared by dehydrochlorination of N-chloropiperidine, has been known for some time. 1-Pyrroline also appears to exist largely as the trimer. Both undergo Mannich reactions with electron-rich heterocycles. Indole reacts with 1-piperidine in a citrate buffer to afford 3-(2-piperidyl)indole in 40-55% yield (equation 45). ° The iV-methylpiperidyl analog has also been... 

The principal reaction of chlorine dioxide with N-methylpiperidine (43) is methyl cleavage to produce piperidine the latter is further oxidized rather slow to piperideine, which rapidly trimerizes... 

Scheme 11. (i) one cycle 2 equiv. acid, 0-(7-azabenzotriazol-l-yl)-l,l,3,3-tetramethyluronium tetrafluoToborate (TATU), DIPEA, DMF, room temp., 45 min, quant., then 20% piperidine, DMF, 2x7 min (ii) TFA, CH2CI2, room temp., 2 x 2 h (Hi) one cycle 2x5 equiv. acid, 0-(7-azabenzotriazol-l-yl)-l,l,3,3-tetramethyluronium hexafluorophosphate (after structure revision N-[(dimethylamino)-17/-l,2,3-triazolo-[4,5- )]pyridin-l-ylmethylene]-A-methylmethanaminium hexafluorophosphate A-oxide [67], HATU), DIPEA, DMF, room temp, 20 min, 65-100% (iv) 3.6 equiv. 17, 0-(benzotriazol-l-yl)-l,l,3,3-tetramethyluronium hexafluorophosphate (HBTU), HOBt, PIPEA, DMF, room temp., 1 h, quant. (v) one cycle diisopropylcarbodiimide, HOBt, DMF di-thiothreitol, DIPEA, DMF, 50 °C, 30%, lower yield for trimer (vi) AC2O, Py 50% TFA-CH2CI2. 

A library of piperidine-based SPH trimers incorporating monomer 42 (Scheme 6) was tested for glycosidase activity. No inhibition was observed for yeast a-glucosi-dase and isomaltase, almond P-glucosidase, human placenta a-fucosidase, snail P-mannosidase, and E. coli P-galactosidase, possibly because of the small number of hydroxyl groups present. 

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