Pyrrolidine reactions

These useful hetcrocyclcs were prepared originally by reaction of amino alcohols with BHi TIIF or boronic acids, but these methods can require lengthy reaction times in the case of hindered pyrrolidines such as 1, (S)-2-(diphcnylhydroxymcthyl)pyrrolidine. Reaction of 1 with a bis(trifluorocthyl)alkylboronatc 2 at 110° for 30 minutes, generates the desired oxazaborolidinc 3 in situ, which can be isolated if desired in 95% yield.1... 

Pyrrolidines. Reaction of the dianions derived from 3-ketoesters with A-tosylaziridine gives e-tosylamino-P-ketoesters, which cyclize on treatment with an ff-form ion exchange resin. 

In the presence of an imine, a three-component cyclization occurred to produce pyrrolidine. Reaction of the allene 443, the imine 447, and iodobenzene catalyzed by Pd(PPh3)4 in the presence of Bu4NBr gave the m-pyrrolidine 448 in 92 % yield. The pyrrolidine 448 was formed by the reaction of the intermediate 444 with the imine before the cyclization. The product 449, obtained by the two-component reaction, was the minor product [170]. 

In spite of the diverse nature of alkaloid structures, two structural units, i.e. fused pyrrolidine and piperidine rings in different oxidation states, appear as rather common denominators. We therefore chose to give several examples for four types of synthetic reactions which have frequently been used in alkaloid total synthesis and which provide generally useful routes to polycyclic compounds with five- or six-membered rings containing one nitrogen atom. These are ... 

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]. 

Enamines as nucleophiles react with butadiene, and a-octadienyl ketones or aldehydes are obtained after hydrolysis[57]. This is a good way of introducing an octadienyl group at the o-position of ketones or aldehydes, because butadiene does not react with ketones or aldehydes directly. The reaction of the pyrrolidine enamine of cyclohexanone gives, after hydrolysis, 2-(2,7-octadie-nyOcyclohe.xanone (58) as the main product, accompanied by a small amount of 2,6-di(2,7-octadienyl)cyclohexanone. The reaction of the optically active enamine 59 with butadiene gave 2-(2,7-octadienyl)cyclohexanone (60) in 72% ce[58]. 

The converse situation in which ring closure is initiated by the attack of a carbon-based radical on the heteroatom has been employed only infrequently (Scheme 18c) (66JA4096). The example in Scheme 18d begins with an intramolecular carbene attack on sulfur followed by rearrangement (75BCJ1490). The formation of pyrrolidines by intramolecular attack of an amino radical on a carbon-carbon double bond is exemplified in Scheme 19. In the third example, where cyclization is catalyzed by a metal ion (Ti, Cu, Fe, Co " ), the stereospecificity of the reaction depends upon the choice of metal ion. 

Benzo[b]furan, 3-(pyrrolidin-1 -yl)-cycloaddition reactions, 4, 636 synthesis, 4, 648 Benzo[b]furan, tetrahydro-synthesis, 4, 671... 

Piperidine, 3-aryIoxymethyI-4-phenyI-as antidepressant, 1, 169 Piperidine, JV-bromo-photoelectron spectroscopy, 2, 142 Piperidine, cis-4- t-butyl-r- cyclohexyl-1 -phenyl-X-ray analysis, 2, 161 Piperidine, 3-chloro-pyrrolidines from, 4, 147 Piperidine, N-chloro-photoelectron spectroscopy, 2, 142 reactions, 2, 373 trimerization, 3, 510 Piperidine, 4-cycIopentyI-2,6-dioxo-synthesis... 

HOFMANN - LOEFFLER FREYTAG Pyrrolidine Synthesis Synthesis of pyrrolidines or piperidines from N-haloamlnes (free radical reaction). 

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%. 

There are several reaction sequences which involve such intramolecular hydrogen abstraction steps. One example is the photolytically intitiated decomposition of N-haloamines in acidic solution, which is known as the Hofinann-Loffier reactionThe reaction leads initially to y-haloamines, but these are usually converted to pyrrolidines by intramolecular nucleophilic substitution ... 

The objection that Formula (A) for nicotine does not provide for the benzoyl derivative of nicotine obtained by fitard was overcome when Pinner 35 showed that in this reaction the pyrrolidine ring is opened, giving rise to metonicotine (isonieotine), and that the supposed benzoylnieotine is benzoylwietanieotine,... 

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