Pyrrolidine derivatives reaction

When allene derivatives are treated with aryl halides in the presence of Pd(0), the aryl group is introduced to the central carbon by insertion of one of the allenic bonds to form the 7r-allylpalladium intermediate 271, which is attacked further by amine to give the allylic amine 272. A good ligand for the reaction is dppe[182]. Intramolecular reaction of the 7-aminoallene 273 affords the pyrrolidine derivative 274[183]. 

Aldehydes take part in the cycloaddition to give the methylenetetrahydrofuran 178 by the co-catalysis of Pd and Sn compounds[115]. A similar product 180 is obtained by the reaction of the allyl acetate 179, which has a tributyltin group instead of a TMS group, with aldehydesfl 16]. The pyrrolidine derivative 182 is formed by the addition of the tosylimine 181 to 154[117]. 

The enamines derived from cyclic ketones give the normal alkylated products, although there is some evidence that unstable cycloadducts are initially formed (55b). Thus the enamine (28) derived from cyclohexanone and pyrrolidine on reaction with acrylonitrile, acrylate esters, or phenyl vinyl sulfone gave the 2-alkylated cyclohexanones (63) on hydrolysis of the intermediates (31,32,55,56). These additions are sensitive to the polarity of the solvent. Thus (28) in benzene or dioxane gave an 80% yield of the... 

Reaction of the chloro-substituted propargyl acetate 132 with aniline gave the pyrrolidine derivative 133 that was cyclized through treatment with... 

Cyclization of the thiazolidine methylidinemalonate 684 with PPA gave thiazoloquinoline 3-carboxylate which upon hydrolysis afforded 685 and reaction with A-methylpiperazine or a pyrrolidine derivative gave 686 as antibacterial agent (82EP58392, 85USP4550104) (Scheme 116). 

Alkylation of these as their sodium salts with the ubiquitous N-C2-chloroethyl)dimethylamine affords the desired antihistamines. There are thus obtained, respectively, mephenhydramine (23a) chlorphenoxamine (23b), and mebrophenhydramine (23c)Alkylation of the tertiary alcohol, 22b, with the pyrrolidine derivative, 24, affords meclastine (25). In much the same vein, reaction of 2-acetylpyridine with phenyImagnesium bromide gives the tertiary alcohol, 27. Alkylation in the usual way leads to the potent antihistamine, doxylamine (28). " ... 

Benzodiazepin-2-ones are converted efficiently into the 3-amino derivatives by reaction with triisopropylbenzenesulfonyl (trisyl) azide followed by reduction <96TL6685>. Imines from these amines undergo thermal or lithium catalysed cycloaddition to dipolarophiles to yield 3-spiro-pyrrolidine derivatives <96T13455>. Thus, treatment of the imine 50 (R = naphthyl) with LiBr/DBU in the presence of methyl acrylate affords 51 in high yield. 

Parker, Raphael, and Wilkinson have investigated a synthetic approach to tropinone (124), which they call the acetylenic route (78). Reaction of hexa-1,5-diyne-l,6-dicarboxylate (145) with methylamine yields the pyrrolidine derivative (146), which by catalytic hydrogenation affords the diester 147 (79,50). 

Under similar conditions, reactions between pyrrolidine derivatives 632 and MTAD proceed much more slowly and less cleanly with formation of a polymeric material. When the reaction is stopped before 50% conversion is reached, starting compound 632 is isolated as the main component (c. 40%) and compound 637 as a minor product (10-14%). Mechanistically, the most difficult problem lies in the fact that a reduction step has to be involved and no particular reduction agent is present. A proposed mechanism is shown in Scheme 103. The pathway includes a Cannizzaro-type hydride transfer between dipole 633 and product 634 (keto tautomer), resulting in the formation of the iminium derivative 635, which might be responsible for the polymeric material, and hydroxy derivative 636, the direct precursor of the final products 637. The low experimental yield of 637 could be explained by this mechanism <2003EJ01438>. 

Figure 15.5 A trityl-protected pyrrolidine derivative of Cgg can be prepared by the reaction of N-trityl-oxazolidinone with a fullerene. Deprotection of the trityl group using methanesulfonic acid gives the secondary amine, which can be used in further conjugation reactions.

Figure 15.7 The reaction of aziridine derivatives with fullerenes also can give pyrrolidine derivatives useful for...

The 1,3-dipolar cycloaddition reactions to unsaturated carbon-carbon bonds have been known for quite some time and have become an important part of strategies for organic synthesis of many compounds (Smith and March, 2007). The 1,3-dipolar compounds that participate in this reaction include many of those that can be drawn having charged resonance hybrid structures, such as azides, diazoalkanes, nitriles, azomethine ylides, and aziridines, among others. The heterocyclic ring structures formed as the result of this reaction typically are triazoline, triazole, or pyrrolidine derivatives. In all cases, the product is a 5-membered heterocycle that contains components of both reactants and occurs with a reduction in the total bond unsaturation. In addition, this type of cycloaddition reaction can be done using carbon-carbon double bonds or triple bonds (alkynes). 

An interesting modification of such a reaction, wherein the reactivity of the excited chromophore is increased by protonation is outlined in the following example whereby a pyrrolenine derivative is photocyclized to a pyrrolidine derivative (4.75) 488). 

The ring-closing metathesis (RCM) approach is useful for the synthesis of indolizidinone derivatives. The procedures published are based on the use of compound 103, an amide of a pyrrolidine derivative bearing on C-l the second unsaturated branch ready for the cyclization. The reaction proceeded smoothly with high yields in both examples (Scheme 27) <2001JOC9056, 2004JOC3968>. 

Organoelement groups like the phenylthio- or diphenylarsanyl group can be removed reductively from alkyl residues very well by Raney-Nickel (Scheme 8). But the transfer of this splitting reaction to our products of anionic cycloadditions - pyrrolidine derivatives - led to difficulties because, as demonstrated in Scheme 8, in addition to the splitting of the element carbon bond ring opening or aromatization occured. 

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-... 

Cyclopentene-ynes 54a and 54b having as- or /ra r-substituents on the cyclopentene are reacted with Ic under ethylene gas to give pyrrolidine derivatives 55a and 55b, respectively, in high yields. The reaction proceeds in a highly stereoselective manner. However, under similar reaction conditions, cyclohexene-yne 54c having cis-substituents on the cyclohexene ring gives selectively triene 56, which is a CM product of an alkyne part and... 

Blechert carried out a tandem reaction of enynes in the presence of olefins instead of ethylene (Scheme 21). Treatment of cyclopentenol derivative 58a with Ic in the presence of an alkene affords 59a. The five-membered ring in estrone 58b is cleaved by Ic to give 59 and an alkene part is introduced on the six-membered C ring. However, cycloalkenyl amine derivative 60 is treated in a similar manner in the presence of an allyl alcohol derivative to give pyrrolidine derivative 61, and in this case, an alkene part is introduced on the diene moiety. Presumably, ruthenium carbene complex XVI reacts with an alkyne part to produce the pyrrolidine ring with a regioselectivity opposite to the other cases. 

Ojima has reported a rhodium-catalyzed protocol for the disilylative cyclization of diynes with hydrosilanes to form alkylidene cyclopentanes and/or cyclopentenes. As an example, reaction of dipropargylhexylamine with triethyl-silane catalyzed by Rh(acac)(GO)2 under an atmosphere of CO at 65 °G for 10 h gave an 83 17 mixture of the disilylated alkylidene pyrrolidine derivative 92b (X = N-//-hexyl) and the disilylated dihydro-1/ -pyrrole 92c (X = N-//-hexyl) in 76% combined yield (Equation (60)). Compounds 92b and 92c were presumably formed via hydrosilyla-tion and hydrosilylation/isomerization, respectively, of the initially formed silylated dialkylidene cyclopentane 92a (Equation (60)). The 92b 92c ratio was substrate dependent. Rhodium-catalyzed disilylative cyclization of dipro-pargyl ether formed the disilylated alkylidene tetrahydrofuran 92b (X = O) as the exclusive product in low yield, whereas the reaction of dimethyl dipropargylmalonate formed cyclopentene 92c [X = C(C02Et)2] as the exclusive product in 74% isolated yield (Equation (60)). 

Rydberg et al. (1996) investigated the reaction of diepoxybutane with valinamide in vitro (40°C, pH >9, 100 h) as a model for the N-terminal valine in haemoglobin. The main products at the lowest diepoxybutane concentration (1 mmol/L) were Al-(2,3,4-trihydroxybutyl)valinamide and erythritol, formed with similar yields. The amount of a ring-closed pyrrolidine derivative (2,2-Al,Al-(2,3-dihydroxybuta-l,4-diyl)valinamide) was three-fold lower. A cross-linked 2,2 -AW-(2,3-dihydroxybuta-l,4-diyl)bis-valina-mide was detectable at 100 mmol diepoxybutane/L. 

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