Pyrroline Derivatives

Thermal rearrangement of 2-vinylaziridine 203, with an electron-withdrawing substituent on the nitrogen atom, at reflux in decalin predominantly yielded 2-pyr-roline 204 along with some 3-pyrroline derivatives 205 (Scheme 2.50) [79]. A similar reaction was also observed with l-alkyl-2-phenyl-3-vinylaziridines 206 [80]. From these observations, the nature of the products formed depends on the natures of the substituents on the aziridine ring if the ring carbon carries a phenyl substituent, the thermolysis in most cases preferentially yields 2-pyrrolines. 

The reaction of alkenylcarbene complexes and imines in the presence of a Lewis acid generates pyrroline derivatives as a result of a [3C+2S] cyclisation process [76]. This reaction has been extended to an asymmetric version by the use of chiral alkenylcarbene complexes derived from several chiral alcohols. However, the best results are found when (-)-8-phenylmenthol-derived complexes are used and catalytic amounts of Sn(OTf)2 are added to the reaction. In these conditions high levels of trans/cis selectivity are achieved and the hydrolysis of the major tram diastereoisomers allows the preparation of optically pure 2,5-disubstituted-3-pyrrolidinone derivatives (Scheme 29). 

Microwave irradiation in solvent-free conditions induces the cleavage of the 2,3-bond of 2-aroyl-aziridines 135 to give an azomethine ylide intermediate, which subsequently undergoes cycloadditions to a multiple bond and leads to oxazolidine, imidazoline, naphthooxazole and pyrroline derivatives 136 in good yields (Scheme 9.41) [32b], Reactions were performed at atmospheric pressure in an Erlenmeyer flask placed in a commercial domestic oven. The reactions were complete in 10-15 min while the conventional method requires 18-20 h. 

Akiyama developed a novel [3+2] cycloaddition reaction of alkenyl Fischer carbene complexes 11 with simple imines 12 in the presence of a catalytic amount of GaCb to produce 3-alkoxy-2,5-disubstituted-3-pyrroline derivatives 13 <00JA11741>. 

Addition of (4-methoxybenzyl)magnesium chloride to the pyrroline derivative (312) is a key step in the stereoselective synthesis of antibiotics (—)-anisomicine... 

Cycloadditions of pyrroline-derived nitrones (525) to 3-buten-l-ol (526) afford bicyclic isoxazolidines (527) which were transformed into indolizidines (528) (Scheme 2.249) (82, 111, 116, 750). 

Chromium carbene complexes have also been known to react with imine equivalents to afford /3-lactam derivatives234. Furthermore, [3 + 2]-cycloaddition of an alkenylchromium carbene 133 with imines proceeded to afford 3-pyrroline derivatives 134 in the presence of a Lewis acid catalyst (Equation (21)),235 where GaClj or Sn(OTf)2 were efficient promoters. Alkenylcarbenes bearing chiral auxiliaries afforded the desired cycloadduct in optically pure form. 

By starting from optically active 2,3-allenylamines 273 and 275, the Ag(I)-cata-lyzed cycloisomerization afforded trans- or cis-pyrroline derivatives 274 and 276, depending on the absolute configurations of the starting compounds [139]. 

The phosphine-phosphite BINAPHOS ligand was first used in the Rh-catalyzed asymmetric hydroformylation of heterocyclic olefins such as 2,5-dihydrofuran, 3-pyrroline derivatives, and 4,7-dihydro-1,3-dioxepin derivatives. It provided the optically active aldehydes as single products with enantioselectivity between 64-76% ee. In the hydroformylation of 2,5-di-... 

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. 

Further investigations on the acceptor-donor system arene-amine have been made by Sugimoto et al. They have reported that direct irradiation of 9-(cu-anilinoalkyl)phenanthrenes give spirocyclic pyrroline derivatives, invoked by... 

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. 

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... 

The recent synthesis of ( ) 8-coniceine (190) involved a pyrroline derivative (191) as a key intermediate as it was relatively stable. It was cyclized with methanolic hydrogen chloride, desulfurized with Raney... 

The same thioimidate can be reacted with unsymmetrical dipolarophiles to give mixtures of two regioisomeric pyrroline derivatives where the 2,3-disubstituted compound is predominant.453... 

A,-(Trimethylsilylmethyl)thioureas are readily accessible via the addition of an amine to the corresponding isothiocyanate. They are good starting materials for preparing 2-amino-A1-pyrroline derivatives via their corresponding azomethine ylids. This is illustrated by condensation with maleimide and different alkenes.245,469... 

Components 2 5 and 1 2 were first detected in wort, which was heated above 140 °C. Beer, produced by this process, possessed a bitter aftertaste. Compound 3. was recently identified as a reactive intermediate, which decomposed very soon even by storage at -20 °C. On heating L-proline and monosaccharides at 150 °C for 1.5 h all compounds increased ten to fiftyfold and 2,3-dihydro-1H-pyrrolizines and di- and tetrahydro-1H-azepines were characterized as major components. On roasting L-proline and monosaccharides (or sucrose) pyrrolidines and azepinones predominate among the Maillard products. These compounds were also formed by heating pyrrolidine and glucose at 100 "C. Azepinones and certain pyrrolin-derivatives possess extreme bitter taste and thresholds of 5 - 10 ppm ( 3, 5 ). ... 

For 78 and the 3-pyrroline derivative 75, deuterium exchange occurs at C-2 when the reaction is carried out in DzO solution. Hodges, L. M. Ph.D. dissertation, University of Virginia, 1995. 

An N-unsubstituted pyrroline derivative in which an exocyclic double bond has been established is compound 2. 

A situation analogous to that of the pyrroline derivatives also exists, according to spectroscopic data, with N-unsubstituted piperideine compounds. There is little experimental data because A 2-piperideines have not been studied as extensively as the analogous pyrrolines. The A structure has been established for some aliphatically substituted piperideines, e.g., J1(8)-hexahydropyrindene,12,13 J1(10)-octahydro-quinoline,13 and the alkaloid y-coniceine.14,15 According to conformational considerations, structures other than A piperideine could be expected more frequently in the piperideine series. The thia analog16 3 occurs in the amino form as shown by infrared spectral data and the estimation of active hydrogen. 

The effectiveness of various precursors of these compounds was investigated quantitatively by Ottinger and Hofmann.283 Hexose-derived cyclotene was the common precursor for both 33 and 35, as well as 34 and 36. The formation of each compound is very much determined by the nature of the N-containing precursor. Thus, for example, pyrrolidine (e.g., formed by thermal decarboxylation of proline) plus cyclotene produced 33 and 35 only, whereas 1-pyrroline (derived from proline... 

The photochemical rearrangement of azavinylcydopropane 125 also occurs [60] readily to produce 1-pyrroline derivatives 126 in high yield (50-85%) upon irradiation using Pyrex-filtered light, as shown in Scheme 8.36. 

Alkenyl aziridines are useful synthetic building blocks and can be converted to allylamines by conjugate addition of organocuprates [29], to pyrroline derivatives by rearrangement [30] and to P-lactams by Pd-catalyzed carbonylation [31]. 

---