Piperidine tetrahydropyran

These methods parallel the synthesis just described for the five-membered rings. As indicated in structures (42)—(49), standard reactions of aliphatic chemistry can be extended to the preparation of piperidines, tetrahydropyrans and pentamethylene sulfides (44 Z = N, O, S) glutarimides, glutaric anhydrides and glutaric thioanhydrides (46 Z = N, O, S) and 8-lactams, 8-lactones and 8-thiolactones (49 Z = N, O, S). 

Loss of formaldehyde is not only among the low critical energy processes of oxi-rane and oxetane molecular ions, but also of larger cyclic ethers such as tetrahy-drofurane and tetrahydropyran. [219] Again, imine loss from/V-heterocycles [220] behaves analogously. The mass spectra of tetrahydrofuran, pyrrolidine, tetrahydropyran, and piperidine are compared below (Fig. 6.52). The strong [M-H] peaks in all of those four spectra are due to a-cleavage. 

Fig. 6.52. El mass spectra of tetrahydrofuran (a), pyrrolidine (b), tetrahydropyran (c), and piperidine (d). Spectra used by permission of NIST. NIST 2002.

As six-membered heterocycles are present in a number of natural products and biologically important molecules, solid-phase synthesis of these has been reported very often (Fig. 3.9). Solid-phase synthesis for nearly every six-membered ring including one nitrogen atom are known piperidines (272) [376], tetrahydropyridines (273) [377, 378], dihydropyridines (274) [219, 379, 380], pyridines (275) [349, 381-386], (Scheme 3.37), piperidinones (276) [387], dihydropyridones (277-279) [313, 378, 388-390], pyridinones (280-281) [328, 329] and piperidindiones (282) [391] derivatives. In contrast, the synthesis of six-membered rings with one single oxygen is rarely described. Nevertheless, solid-phase synthesis of dihydropyrans (283-284) [392-394] and tetrahydropyrans (285) [335, 336] has been reported. 

It was reported that Pd(0)-catalyzed coupling reactions of allenic alcohols, amines and acids with hypervalent iodonium salts afforded cyclized heterocyclic tetrahydrofurans, tetrahydropyrans, pyrrolidines, piperidines, or lactones under mild conditions <99SL324>. Intramolecular 1,5-hydrogen atom transfer radical cyclization reaction of pyrrolidine derivatives was examined. Reaction of 3,4-dialiyloxy-JV-(0-bromobenzyl)pyrtolidine gave hexahydro-... 

The cosolvents chosen for this study were urea (U), acetone (ACT), di-methylsulfoxide (DMSO), p-dioxane (D), piperidine (PD), morpholine (M), terf-butanol (TBA), and to a lesser extent acetamide (ACM). The study of the binary system was also extended to piperazine (PZ) and tetrahydropyran (THP). This choice of cosolvents is sufficiently varied to allow an examination of the various factors which influence the transfer functions. 

Carbon-13 shift values of parent heterocycloalkanes [408] collected in Table 4.61 are essentally determined by the heteroatom electronegativity, in analogy to the behavior of open-chain ethers, acetals, thioethers, thioacetals, secondary and tertiary amines. Similarly to cyclopropanes, three-membered heterocycloalkanes (oxirane, thiirane, and azirane derivatives) display outstandingly small carbon-13 shift values due to their particular bonding state. Empirical increment systems based on eq. (4.1) permit shift predictions of alkyl- and phenyl-substituted oxiranes [409] and of methyl-substituted tetrahydropyrans, tetrahydrothiapyrans, piperidines, 1,3-dithianes, and 1,3-oxathianes [408], respectively. Methyl increments of these heterocycloalkanes are closely related to those derived for cyclohexane (Table 4.7) due to common structural features of six-membered rings. 

Piperidine derivatives and acyclic substances such as trihalogeno-alkanes and dihalogenoalkylamines may be used as starting materials. The piperidine derivatives are obtained mainly from pyridine compounds. Dihalogenoalkylamines and trihalogenoalkanes are prepared from tetrahydropyran derivatives, dialkoxy-substituted malonic esters, or alkane-tetracarboxylic esters. 

Intramolecular examples of iron-catalyzed formal Alder-ene reactions, which are also denoted cycloisomerization reactions, were described in the late 1980s by the groups of Tietze and Takacs in reactions directed towards cyclopentane [6, 7], cyclohexane [8], piperidine [9] and tetrahydropyran derivatives [10]. 

Tetrahydrofuran, tetrahydropyran, pyrrolidine, and piperidine skeletons can be constructed by these reactions. 

Chemistry and biology of immunosuppressant (-)-FK-506 (containing piperidine and tetrahydropyran fragments) 92YGK522. 

A series of 16 molecules, which include different monofunctional compounds, were chosen to determine the enthalpy of solvation in water. Besides four hydrocarbons (hexane, heptane, octane and cyclohexane) and water, the series of molecules include alcohols (2-methylpropan-2-ol, 1-butanol and 2-butanol), ethers (diethylether, tetrahydrofuran and tetrahydropyran), amines (propylamine, butylamine, diethy-lamine and dibutylamine) and piperidine. This choice allows us to examine the differences between different functional groups, as well as the influence of the molecular size on the enthalpic contributions for a given series of monofunctional compounds. Free energies of hydration as well as the corresponding enthalpies taken from the data compiled by Cabani and coworkers [26] are shown in Table 4-1. 

Heterocyle assembly. The allylation of aldehydes using functionalized ( )-allylsilanes is followed by cyclization to give frans-2,3-disubstituted tetrahydropyrans and piperidines. Using a (Z)-allylsilane of shorter chain length cii-2,3-disubstituted tetrahydrofurans are obtained. ... 

Wahrend 4-(2-Nitro-phenylthiocarbonyl)-3-oxo-tetrahydropyran (konz. Ammoniak/Ethanol) analog zu 2-(2-Carboxymethoxy-ethyl)-l,3-benzothiazol-3-oxid reagiert (68% Schmp. 126-128°), erhalt man aus (l-Methyl-3-(2-nitro-phenylthio)-4-oxo-piperidin (Natronlauge/Te-trahydrofuran) unter zusatzlichcr Spaltung dcr C ,N-Bindung des Piperidin-Ringes 2-Formyl-1,3-benzothiazol (47% Schmp. 72-74°)81. 

Tetrahydropyran derivatives 37, 38, 41 and 42 as well as the piperidine derivatives 44, 45, 55 and 56 can be prepared with high enantiomeric purity. Bi- and tricyclic... 

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