Pyrrolidine synthesis

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

Simple examples shown above are the base-catalysed formation of oxygen- and nitrogen-containing ring systems. We have shown base-initiated ionization of the alcohol to an alkoxide anion in epoxide formation the anion is a better nucleophile than the alcohol. For pyrrolidine synthesis, the amino group is sufficiently nucleophilic for reaction to occur, but base is required to remove a proton from the first-formed intermediate. 

Some A -enecarboxylic acids undergo a rapid intramolecular cyclization reaction of the 5-exo-trig type prior to the radical coupling step. Substituted tetrahydro-furans [95] and pyrrolidines [96] can be prepared by this Kolbe route. It is preferable to protect the amine function in the pyrrolidine synthesis by N-formy ation in... 

RING REARRANGEMENT METATHESIS (RRM) - A NEW CONCEPT IN PIPERIDINE AND PYRROLIDINE SYNTHESIS... 

Much more successful in a pyrrolidine synthesis was the use of a stereochemically defined organolithium 362 formed by tin-lithium exchange from an almost enantiomerically pure stannane 361, itself a product of Beak s sparteine lithiation chemistry. Despite the high temperature (20 °C) required for tin-lithium exchange in hexane-ether, it is nonetheless possible to carry out a stereospecific cyclisation via an organolithium which is configurationally stable, even at 20 °C, on the timescale of the cyclisation.169 The cyclisation proceeds with retention and gives the alkaloid pseudoheliotridane 363 in 87% yield and with no loss of enantiomeric excess. 

Hong CY, et al. Novel fluoroquinolone antibacterial agents containing oxime-substituted (aminomethyl)pyrrolidines synthesis and antibacterial activity of 7-(4-(aminomethyl)-3-(methoxyimino)-pyrrolidin-l-yl)-l-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro[l,8]naphthyridine-3-car-boxylic acid (LB 20 304). J. Med. Chem., 1997, 40, 3584-3593. 

Pyrrolidine Synthesis. The lithium (Z)-enolate of methyl iV-benzylideneglycinate undergoes a cycloaddition rapidly at —78°C with methyl (4J ,5R)-( )-3-( 1,3-dimethyl-4,5-diphenyl-2-imidazolidinyl)propenoate (1) to give pyrrolidine-2,4-dicarboxylate in quantitative yield and as a single stereoisomer (eq 1). Removal of the chiral auxiliary from the cycloadduct can be readily performed by treatment with cone Sulfuric Acid in MeOH at rt to produce the optically pure pyrrolidine-2,4-dicarboxylate bearing an acetal substituent at the 3-position. 

ORTON Haloaniline rearrangement 282 OSTROMISLENSKY Butadiene synthesis 282 OVERMAN Pyrrolidine synthesis 263... 

As mentioned above, cyanocyclopropanes are frequently used precursors for imines (see equation 30). A recent pyrrolidine synthesis which involves an in situ reduction of the intermediate dihydropyrrole by formic acid follows these lines (equation 33). ... 

The history of C-H amination can be traced to the earliest work of Hofmann involving the reactivity of /V-bi omoamines. chemistry later recognized by Loffler and Freytag for its potential to facilitate pyrrolidine synthesis from simple acyclic precursors [11]. The intermediacy of both haloamine and aminyl radical in this stepwise oxidation reaction is now generally accepted, as is the hyper-reactivity of... 

HOFMANN Amide degradation 173 HOFMANN IsonitrHe synthesis 173 HOFMANN Elimination 174 HOFMANN LOEFFLER - FREYTaG Pyrrolidine synthesis 175... 

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