Pyrrolidine from pyrrole

Mono-, bis-, and tris-substituted A-pyrrolyl or /V-pyrrolidine phosphines have recently been described and prepared in excellent yields from pyrrole (or pyrrolidine), a phosphorus halide and base (NEt3, pyrrolidine, or DBU), as illustrated by the syntheses of (206) (Equation (49)) and (207) (Equation (50)) 451-453... 

Fig. 18. Comparison of far-infrared spectra of zeolites Na-Y and K-Y before and after adsorption of pyrrole [371] and pyrrolidine (from [372] with permission)...

Pyrrole derivatives are quite rare in plants, except for the chlorophylls present in plants, pigments in the blood (heme), and the bile pigments derived from heme. Therefore, one may initially regard chlorophyll and heme as alkaloids containing a pyrrolidine or pyrrole ring that might possibly be derived from proline in their chemical strucmres. 

A domino Mannich/aza-Michael reaction was applied to the synthesis of 2,5-cis-configured polysubstituted pyrrolidines from y-malonate-substituted a,P-unsaturated esters with N-protected arylaldimines [117]. In this report, bifunctional thioureas were trialed with the Takemoto catalyst, being the most efficient with respect to yield as well as enantiomeric and diastereomeric excess. In a separate approach, the Garcia-Tellado group approached the pyrrole ring system 234, beginning with a tertiary skipped diyne 233 and a primary amine (Scheme 7.50). 

H. Okada, T. Akaki, Y. Oderaotoshi, S. Minakata, M. Komatsu, Generation and cycloaddition of polymer-supported azomethine yhde by utilizing the characteristics of silicon a facile route to pyrrolidines and pyrroles from a-silylimines bound to resin. Tetrahedron 2003, 59, 197 205. 

Kathiravan and Raghxmathan reported the synthesis of pyrrole-fused polycyclic heterocycles via intramolecular 1,3-dipolar cycloaddition reaction of azomethine ylides derived from pyrrole-2-carbaldehyde 28 and secondary amino acids in IL [BM1M][BF4]. The methodology involved the synthesis of N-alkenyl carboxaldehyde from 28 followed by freafment with sarcosine in [BM1M][BF4] as reaction medium at 85-95 C for about 3h to afford pyrrolo-pyrrolidines 29 in good yield (Scheme 3). The same reaction when carried out in organic solvents such as toluene, methanol, and acetonitrile, the reactions observed were slow, giving product in low yield [80]. 

As discussed in Chapter 6, nitro compounds are converted into amines, oximes, or carbonyl compounds. They serve as usefid starting materials for the preparation of various heterocyclic compounds. Especially, five-membered nitrogen heterocycles, such as pyrroles, indoles, ind pyrrolidines, are frequently prepared from nitro compounds. Syntheses of heterocyclic compounds using nitro compounds are described partially in Chapters 4, 6 and 9. This chapter focuses on synthesis of hetero-aromadcs fmainly pyrroles ind indolesi ind saturated nitrogen heterocycles such as pyrrolidines ind their derivadves. 

In addition to cydocondensation reactions of the Paal-Knorr type, cycloaddition processes play a prominent role in the construction of pyrrole rings. Thus, 1,3-dipo-lar cycloadditions of azomethine ylides with alkene dipolarophiles are very important in the preparation of pyrroles. The group of de la Hoz has studied the micro-wave-induced thermal isomerization of imines, derived from a-aminoesters, to azomethine ylides (Scheme 6.185) [346]. In the presence of equimolar amounts of /i-nitrostyrenes, three isomeric pyrrolidines (nitroproline esters) were obtained under solvent-free conditions in 81-86% yield within 10-15 min at 110-120 °C through a [3+2] cycloaddition process. Interestingly, using classical heating in an oil bath (toluene reflux, 24 h), only two of the three isomers were observed. 

Pyrrole itself is an obvious precursor of pyrrolidine by catalytic hydrogenation. One example of construction of an ant pyrrolidine analog from a pyrrole has been published (Scheme 24) (169). 

Pyrrolines and pyrroles can be readily prepared from the rearrangement of a-aminoallenes. Optically enriched a-aminoallene 137 is rearranged to pyrroline 138 by catalytic silver nitrate (Eq. 13.45) [53], The yield of the reaction is high and the cyclization occurs with high levels of asymmetry transfer. Annulated 3-pyrroline 140 is the product of rearrangement of allenyl pyrrolidine 139 (Eq. 13.46) [53]. 

Diethyl aminomalonate reacts with 1,3-diketones in boiling acetic acid to the corresponding pyrrolecarboxylates 11 (87JOC3986). From N-ac t-amidomalonate and acroleins, pyrrolidines were prepared and they were further transformed into functionalized pyrroles, which are a part of the antibiotic lyncomycin and an antimalarial agent (67JA2459 72JMC1255). 

In connection with the synthesis of cytohalasin B, a pyrrole derivative 13 was prepared from methyl (5)-3-aminophenylbutyrate (78JA7775). In connection with the synthesis of l,2,4-triazolo[4,3-a]pyrazine derivatives with human Renin inhibitor activity, a /3,y-diamino acid derivative was transformed into a pyrrolidin-2-one (91JMC151). 

Better reagents than lithium aluminum hydride alone are its alkoxy derivatives, especially di- and triethoxyaluminohydrides prepared in situ from lithium aluminum hydride and ethanol in ethereal solutions. The best of all, lithium triethoxyaluminohydride, gave higher yields than its trimethoxy and tris(/er/-butoxy) analogs. When an equimolar quantity of this reagent was added to an ethereal solution of a tertiary amide derived from dimethylamine, diethylamine, W-methylaniline, piperidine, pyrrolidine, aziridine or pyrrole, and the mixture was allowed to react at 0° for 1-1.5 hours aldehydes were isolated in 46-92% yields [95,1107], The reaction proved unsuccessful for the preparation of crotonaldehyde and cinnamaldehyde from the corresponding dimethyl amides [95]. 

Tables I through VIII summarize the occurrences of alkaloids from ants and other insects. Each table presents chemical structures as well as specific sources of particular types of alkaloids e.g.. Table I covers piperidines and pyridines. Table II, pyrrolidines, pyrroles, and indolizidines.

Many synthetic methods have been reported for the pyrrolidine alkaloids, including procedures based on the Hofmann-Loffler reaction 132,412), the metal hydride reduction of pyrrolines 413,414), the a-alkylation of N-nitro-sopyrrolidine 412,415), the catalytic hydrogenation of pyrroles 133), the reductive amination of 1,4-diketones 25,138), the direct alkylation of 1-methoxy-carbonyl-3-pyrroline 416), the versatile synthesis from the Lukes-Sorm dilac-... 

B1 NH3 and aldehydes were also obtained when the peroxidic solutions were reduced with sodium sulfite, except that pyrrol (442) was formed from pyrrolidine (439). The results obtained so far suggest that... 

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