Pyrrolidine tetrahydrofuran

There are a number of fully saturated nonaromatic heterocycles. For example, pyrrolidine, tetrahydrofuran, isoxazolidine and piperidine are fully saturated derivatives of pyrrole, furan, isoxazole and pyridine, respectively. Partially saturated derivatives, e.g. 2-pyroline, 2-isoxazoline and 1,4-dihydropyridine, are also known. 

Catalytic reduction of pyrroles gives successively A3-pyrroles and pyrrolidines. Tetrahydrofurans are formed by the catalytic reduction of furans with Raney nickel and hydrogen ring cleavage products... 

In a somewhat similar synthesis (16) the lactam 46 which was prepared by two distinct routes was shown to undergo reductive cycliza-tion to give elaeocarpidine and dihydroelaeocarpidine. When this reduction step was carried out with lithium aluminum hydride in tetrahydrofuran a 1 2 mixtime of elaeocarpidine and dihydroelaeocarpidine was obtained but reduction with lithium aluminum hydride in pyrrolidine-tetrahydrofuran (1 1) at 0° gave a 52% yield of elaeocarpidine along with unchanged lactam (46). 

Miscellaneous. Lithium amides of chiral pyrrolidines, tetrahydrofurans, and tetrahydrothiophenes are evaluated as chiral ligands in the condensation of BuLi to o-tolualdehyde (eq 74). ... 

All these aromatic heterocycles have their counterparts in the corresponding saturated heterocycles. Among those, pyrrolidines, tetrahydrofurans, and oxazolidines are more frequently encountered in dmg discovery. 

The strain energies of these five-membered heterocycles are relatively small with values of 23.5, 24.8 and S.SkJmoF estimated for tetrahydrofuran, pyrrolidine and tetrahy-drothiophene respectively (74PMH(6)199). The closeness of the values for the two former compounds reflects the almost identical covalent radii of oxygen (0.66 A) and nitrogen (0.70 A) atoms. The sulfur atom with a much larger covalent radius of 1.04 A causes a... 

The present preparation illustrates a general and convenient irethod for ring contraction of cyclic ketones. The first step is the usual procedure for the preparation of enamines. The second step involves 1,3-dipolar cycloaddition of diphenyl phosphorazidate to an enamine followed by ring contraction with evolution of nitrogen. Ethyl acetate and tetrahydrofuran can be used as a solvent in place of toluene. Pyrrolidine enamines from various cyclic ketones smoothly undergo the reaction under similar reaction conditions. Diphenyl (cycloalkyl-1-pyrrolidinylmethylene)phosphoramidates with 5,6,7, and 15 members in the ring have been prepared in yields of 68-76%. 

Other advances include the construction of seven- and nine-membered rings via the analogous [4-1-3] and [6-1-3] cycloadditions with dienes and trienes respectively. Heterocycles, such as tetrahydrofurans and pyrrolidines, are accessible using carbonyl compounds and imines as substrates. The following discussion is organized around these recent discoveries. It serves to illustrate the versatility and the high degree of selectivity which are some of the distinctive features of the Pd-TMM chemistry. 

In 20%iger Schwefelsaure wird Methyl-(4-oxo-pentyl)-amin an Blei-Kathoden reduk-tiv zu 1,2-Dimethyl-pyrrolidin (65% d.Th.) cyclisiert3. In verdiinnter Schwefelsaure fiihrt die Coelektrolyse von Aceton mit Allylalkohol zu 2,2-Dimethyl-tetrahydrofuran (95% d.Th.)4. 

The electric dipole moments in units 1 X 10 18 e. s. u. of these molecules and their derivatives by hydrogenation measured19 in benzene solution are the following furan, 0.670 2,5-di-hydrofuran, 1.53 tetrahydrofuran, 1.68 pyrrole, 1.80 pyrroline, 1.42 pyrrolidine, 1.57 thiophene, 0.54 and tetrahydrothiophene, 1.87. We now give a very rough interpretation of these quantities based on the bond moments given... 

The monomer synthesis and cyclopolymerization were carried out following the procedure of Butler et al. (21). The resulting polyimide was shown to possess primarily pyrrolidine rings as indicated by infrared spectroscopy (21). Initially, the reduction was carried out with LiAlH in tetrahydrofuran. 

The catalytic preparation of substituted tetrahydrofurans and pyrrolidines with a number of N-protecting groups has been reported. The use of 1,2-... 

The extension of the cyclization from tetrahydrofurans and pyrrolidines to car-bocycles leads to a sharp decrease in the yield of cyclized product. This is due to the slower cyclization rate of 5-hexenyl radicals compared to 5-(3-oxahexenyl) radicals, which favors the competing bimolecular coupling to the acyclic product. Three measures help to increase the yield in these cyclizations. 

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.

The preparation of five-membered rings in solid-phase organic chemistry has been reported in several publications. Versatile syntheses of these heterocycles with different numbers and kinds of heteroatoms have been described. The synthesis of five-membered rings containing one nitrogen atom (Fig. 3.6) as pyrrolidines (231) [311-316] pyrroles (232) [317-320] pyrrolidinones (233) [321-323] pyr-rolinones (234) [324—326] 2,5-pyrrolidinediones (235) [327-329] 2,4-pyrrolidine-diones (236) [330-332] 2,5-pyrrolinediones (237) [333] or heterocycles with one oxygen or one sulfur atom like tetrahydrofurans (238) [334—336] 2,5-dihydrofurans (239) [337], furans (240) [338, 339], yS-lactones (241) [340-343], 2,5-dihydrofura-nones (242) [344] (Scheme 3.35) and thiophenes (243) [345, 346] can be accomplished on solid supports. 

Some of these heterocycles provide us with valuable laboratory solvents, e.g. the ethers tetrahydrofuran and dioxane (1,4-dioxane). Others are useful as organic bases, e.g. piperidine, pyrrolidine, and... 

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