Intramolecular pyrroline

Amines undergo aminopalladation to alkynes. The intramolecular addition of amines to alkynes yields cyclic imines. The 3-alkynylamine 273 was cyclized to the 1-pyrroline 274, and the 5-alkynylamine 275 was converted into the 2,3,4,5-tetrahydropyridine 276[137]. Cyclization of o-(l-hexynyl)aniline (277)... 

Whereas the cycloaddition of arylazirines with simple alkenes produces A -pyrrolines, a rearranged isomer can be formed when the alkene and the azirine moieties are suitably arranged in the same molecule. This type of intramolecular photocycloaddition was first detected using 2-vinyl-substituted azirines (75JA4682). Irradiation of azirine (54) in benzene afforded a 2,3-disubstituted pyrrole (55), while thermolysis gave a 2,5-disubstituted pyrrole (56). Photolysis of azirine (57) proceeded similarly and gave 1,2-diphenylimidazole (58) as the exclusive photoproduct. This stands in marked contrast to the thermal reaction of (57) which afforded 1,3-diphenylpyrazole (59) as the only product. 

When the chain between the azirine ring and the alkene end is extended to three carbon atoms, the normal mode of 1,3-intramolecular dipolar cycloaddition occurs. For example, irradiation of azirine (73) gives A -pyrroline (74) in quantitative yield 77JA1871). In this case the methylene chain is sufficiently long to allow the dipole and alkenic portions to approach each other in parallel planes. 

Addition to 1,2-dimethyl- -piperideine or 1,2-dimethyl- -pyrroline is followed by intramolecular alkylation by the ester group as a side reaction to give 140 and 141 ( = 1, 2), respectively. Cyclization products 142 and... 

The Rh and Ir complexes 85-88 (Fig. 2.14) have been tested for the intramolecular hydroamination/cyclisation of 4-pentyn-l-amine to 2-methyl-1-pyrroline (n = 1). The reactions were carried out at 60°C (1-1.5 mol%) in THF or CDCI3 The analogous rhodium systems were more active. Furthermore, the activity of 87 is higher than 85 under the same conditions, which was attributed to the hemilabihty of the P donor in the former complex, or to differences in the trans-eSects of the phosphine and NHC ligands, which may increase the lability of the coordinated CO in the pre-catalyst [75,76]. 

Katritzky developed a facile synthesis of l,2-diaryl(heteroaryl)pyrroles in a two-step procedure from A-allylbenzotriazoles via intramolecular oxidative cyclization in the presence of a Pd(II) catalyst <00JOC8074>. Thus, treating A-allylbenzotriazole (21) with n-butyllithium followed by addition of a diarylimine yielded the (2-benzotriazolyl-l-arylbut-3-en)anilines 22 which were subsequently heated in the presence of the system Pd(OAc)2-PPh3-CUCI2-K2CO3 to undergo intermolecular amination with simultaneous oxidation of the intermediate 3-pyrroline to the pyrroles 23. 

Substituted 3-hydroxy-2-pyrrolidinones were synthesised via 1,3-DC reactions of furfuryl nitrones with acrylates and subsequent intramolecular cyclisation after N-0 bond reduction. Addition of iV-acryloyl-(2/()-bomane-10,2-sultam to Z-nitrone 83 gave the endo/exo cycloadducts in 85 15 ratio with complete stereoface discrimination <00JOC1590>. The 1,3-DC of pyrroline A-oxide to chiral pentenoates using (-)-/rans-2-phenylcyclohexanol and (-)-8-phenylmenthol as chiral auxiliaries occurred with moderate stereocontrol (39% de and 57% de, respectively) and opposite sense of diastereoselectivity <00EJO3595>. The... 

Intramolecular variations of a series of bifunctional derivatives lead to the formation of cyclic nitrones. Many pyrroline /V-oxide derivatives were obtained in the course of intramolecular interaction in situ between carbonyl and hydrox-ylamine groups, resulting from the reduction of a y-nitro group (Scheme 2.31) (Fig. 2.8) (238-253). 

A trihydroxyindolizidine lactone is obtained by elaboration of an isoxazolidine synthesized by a domino stereoselective retrocycloaddition/intramolecular cycloaddition process of an enantiopure pyrroline-iV-oxide <2006TA292>. 

The intramolecular photochemistry of 9-[2-(7V-substituted aminomethyl)-l-naph-thyl]phenanthrenes has also been studied101 (equation 40). The pyrroline derivatives are obtained by the addition of the N—H to the C-9 carbon atom of phenanthrene ring. Reasonable yields for the highly regioselective products are obtained by irradiation in benzene solution. 

The simplest available derivatives of pyrrole in this sense are pyrrolines (97) which are accessible by simple intramolecular aza-Wittig reaction of iminophosphorane 96, the latter being formed by a Staudinger reaction from -y-azidoketones (95), as shown in Scheme 44. The process occurs under neutral conditions, so that once the double bond is formed, it cannot isomerize (86TL1031 87NKK1250). 

A recent adaptation of this type of approach involves the spontaneous intramolecular cyclization of imino ketones, formed by the reduction of nitro ketones through the action of tributylphosphine/diphenyl sulfide (Scheme 6.14). When the corresponding esters (R = OR) are used, pyrrolin-2-ones are formed (Scheme 6.15). 

The cyano-substituted nitrile ylides 123 have been generated via 1,1-elimination reactions. For example, the benzyhdene derivative 122 (R=Ph) eliminated benzene on vapor phase pyrolysis to give 123 (R=Ph), which reacted via 1,5-electrocycli-zation [see also (66)] to give the isoindole 124 (41%) (67). In a similar way, 122 [R=(CH2)3CH=CH2] gave the corresponding nitrile yhde that reacted via intramolecular cycloaddition to give the pyrroline derivative 126. 

Pearson et al. (64) developed an approach to the fused bicyclic 3-pyrrolines 328 based on an intramolecular azide-alkene cycloaddition (Scheme 9.64). Azides (327) were heated at various temperamres between 70 and 110°C to afford the... 

The palladium catalysed substitution reaction of allylic systems has also been utilised in the formation of five membered rings. Intramolecular nucleophilic attack of the amide nitrogen atom on the allylpalladium complex formed in the oxidative addition of the allyl acetate moiety on the catalyst led to the formation of the five membered ring (3.63.). In the presence of a copper(II) salt the intermediate pyrroline derivative oxidized to pyrrole.80... 

Alike olefins, allenes also undergo palladium mediated addition in the presence of N-H or O-H bonds. Although these reactions show some similarity to Wacker-type processes, from the mechanistic point of view they are quite different. Allenes, such as the cr-aminoallene in 3.69., usually undergo addition with palladium complexes (e.g. carbopalladation in 3.69. and 3.70., or hydropalladation in 3.71.), which leads to the formation of a functionalized allylpalladium complex. Subsequent intramolecular nucleophilic attack by the amino group leads to the closure of the pyrroline ring.87... 

A new synthesis of pyrrolizidine, which is based on the reaction of bis-tertiary glycols with co-chloronitriles, was reported by Meyers and Libano.28 The method involves three steps (a) condensation of 2,5-dimethyl-2,5-hexanediol (48) with 4-chlorobutyronitrile in the presence of sulfuric acid to give a derivative of A 1-pyrroline (49), (6) reduction of 49 with sodium borohydride to give the corresponding pyrrolidine (50), and (c) intramolecular cyclization of the pyrrolidine in the presence of alkali to give the pyrrolizidine derivative 51. The three-step synthesis was performed without isolation of the intermediate products. 

Vinyl azide intramolecular cycloaddition is further illustrated by the formation of azidotriazoline 32 as a minor product in the thermolysis of the bisvinyl azide 31 (Scheme 41).200 An analogy is provided by the formation of 2,5-diphenylpyrrole from the slow decomposition of a-azidostyrene.202 Pyrrole formation is interpreted in terms of cycloaddition of the azide onto the electron-rich double bond of a second molecule to give a triazoline that loses nitrogen and rearranges to a pyrroline followed by hydrogen azide elimination (Section IV,D).203... 

The seco-phenanthroindolizidine alkaloid septicine has been synthesized by a nitrone route. A cycloaddition of 1-pyrroline 1-oxide with 2,3-bis-(3,4-dimethoxyphenyl)butadiene gives two stereoisomeric isoxazolidines, one of which is converted into ( ) septicine.10 ( )-Tylophorine and 5-coniceine have been prepared by a new route that makes use of an intramolecular imino-Diels-Alder reaction.11 A stereoselective synthesis of 3,5-dialkyl-indolizidines has been applied to the synthesis of a stereoisomer of the trail pheromone of the Pharaoh ant and to a stereoisomer of gephyrotoxin 223.12 A stereoselective total synthesis of ( )-perhydrogephyrotoxin (21)13 and a simple synthesis of ( )-gephyran14 have been reported. 

We have shown that the ylids 3 react with a number of nucleophiles (3). In particular 3a and 3b react quantitatively with the alkylidene phosphoranes 5 to give 3-pyrrolines 6a and 6b as a mixture of diastereoisomers. The cyclisation occurs via an intramolecular Wittig reaction on the carbonyl of an ester group (M. In the same conditions, 2c reacts with 5 to give quantitatively the pyrrolines 7c (two diastereoisomers) as a result of a Wittig reaction on the carbonyl of the keto group in 3c. 

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