Asymmetric Synthesis of Tetracyclic Benzo[<i>a</i>]quinolizidine Targets

Allin, Steven M.; Gaskell, Sean N.; Elsegood, Mark R. J.; Martin, Wayne

doi:10.1021/jo801019h

Cited by 12 publications

(2 citation statements)

References 28 publications

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“…[68] An analogous procedure has been applied for the synthesis of tetracyclic benzo[a]quinolizidines such as 142 (Scheme 43). [69] In these examples the intramolecular α-amidoalkylation cyclizations took place through bicyclic tertiary N-acyliminium ions, as in the case of 136. The stereochemical outcomes are also explained by the same conformational models as discussed above.…”

Section: Stereochemical Aspects -Diastereoselective α-Amidoalkylationmentioning

confidence: 99%

Strategies Based on Aryllithium and N‐Acyliminium Ion Cyclizations for the Stereocontrolled Synthesis of Alkaloids and Related Systems

et al. 2011

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The intramolecular α-amidoalkylation reactions of aromatic and heteroaromatic ring systems constitute a versatile approach for the synthesis of nitrogen heterocyles in a diastereoselective or enantioselective fashion. On the other hand, the intramolecular reactions of aryllithium compounds have also been extensively used in the synthesis of carbocycles and heterocycles. The use of imides as internal electrophiles is particularly attractive because of the potential to introduce diverse functionality into the cyclized products by subjecting the resulting α-hydroxylactams to intermolecular IntroductionAryllithium compounds and N-acyliminium ions are extremely versatile intermediates for the formation of carboncarbon bonds in organic synthesis. Cyclization of aryllithium compounds generated by halogen/lithium exchange with internal electrophiles (Parham cyclization) has become a valuable protocol for the stereoselective construction of carbocyclic and heterocyclic systems.[1] Many electrophiles remain inert during halogen/metal exchange reaction at low temperature, but are reactive enough to participate in a subsequent cyclization reaction. Halides, epoxides, or alkenes [2] are thus among the different types of internal electrophiles used in the Parham cyclization. When the internal electrophile is a carboxylate derivative, this anionic cyclization could be considered an anionic Friedel-Crafts equivalent, with the advantage that it lacks the electronic requirements of the classical reaction. Although it is possible to use carboxylic acids [3] or esters, [4] carbamates have proven to be much more effective internal electrophiles in Parham cycliacylations.[5] Amides are also useful electrophiles in Parham cyclizations, and it has been reported that in some cases there is an influence of the natures of the substituents at the nitrogen atom on the course of the cyclization reaction. [6,7] [a] Departamento In connection with our interest in aromatic lithiation, we have developed an anionic cyclization approach directed towards the construction of the pyrrolo[1,2-b]isoquinolone core based on N-(o-halobenzyl)pyrrole-2-carboxamides, showing that Weinreb amides and morpholine amides function as excellent internal electrophiles.[8] This observation could be explained by assuming that halogen/lithium exchange could be favored by a complex-induced proximity effect (CIPE).[9] This concept has been invoked to explain other metal/metal, hydrogen/metal, or halogen/metal [10] exchange reactions. Lithium/halogen exchange would thus be favored first by coordination of the inducing organolithium compound with amide or carbamate groups, and then by stabilization of the resulting aryllithium compound. The better behavior of Weinreb and morpholine amides relative to N,N-diethyl amides could be attributed to the extra stabilization of the intermediate generated after cyclization through the formation of an internal chelate. The scope of these Parham-type cyclizations has been extended to the formation of seven-and eight-membered rings [8b] ...

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Section: Stereochemical Aspects -Diastereoselective α-Amidoalkylationmentioning

confidence: 99%

Strategies Based on Aryllithium and N‐Acyliminium Ion Cyclizations for the Stereocontrolled Synthesis of Alkaloids and Related Systems

et al. 2011

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“…Chiral tetracyclic nitrogen heterocycles can be found among biologically active molecules, including alkaloids (e.g., sparteine, asperlicin, benzo[a]quinolizidine derivatives 7 ), azasteroids 8 (e.g., finasteride, chandonium), and various drugs (e.g., antidepressants mianserin and mirtazapine). Compounds from this class, sparteine and Troger's base, are also widely used in organic synthesis and as chiral discrimination compounds.…”

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confidence: 99%