Stereocontrolled conjugate additions to dihydroindolizinone systems. Synthesis of enantiopure polysubstituted tetrahydropyrrolo[2,1-a]isoquinolones

Camarero, Cristina; González-Temprano, Inés; Gómez-SanJuan, Asier; Arrasate, Sonia; Lete, Esther; Sotomayor, Nuria

doi:10.1016/j.tet.2009.05.011

Cited by 12 publications

(3 citation statements)

References 92 publications

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“…Due to the complex nature of the chiral starting material, structural changes that would enhance the diastereoselectivity are typically difficult to execute. Despite this disadvantage, this approach has been utilized in the synthesis of several natural products [ 7 – 8 25 , 65 – 70 ]. The following section highlights a couple examples.…”

Section: Reviewmentioning

confidence: 99%

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

Byrd¹

2015

Beilstein J. Org. Chem.

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SummaryThe conjugate addition reaction has been a useful tool in the formation of carbon–carbon bonds. The utility of this reaction has been demonstrated in the synthesis of many natural products, materials, and pharmacological agents. In the last three decades, there has been a significant increase in the development of asymmetric variants of this reaction. Unfortunately, conjugate addition reactions using α,β-unsaturated amides and lactams remain underdeveloped due to their inherently low reactivity. This review highlights the work that has been done on both diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams.

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Section: Reviewmentioning

confidence: 99%

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

Byrd¹

2015

Beilstein J. Org. Chem.

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“…These dihydropyrrolo-[2,1-a]isoquinolines 32 are also interesting substrates for further functionalization through conjugate addition reactions. [21] Scheme 9.…”

Section: Intramolecular α-Amidoalkylation and Parham Cyclization -Intmentioning

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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“…14 In contrast, the conjugate addition of stabilized anions does not require the presence of the activating ester substituent and can be a reversible process, depending on the nature of the nucleophile and lactam, as well as the reaction conditions. [15][16][17][18] In recent work, 19 in the context of model studies on the enantioselective synthesis of the indole alkaloid ervitsine we studied the stereochemical outcome of the conjugate addition of 2-acetylindole enolates to a variety of stereochemically diverse phenylglycinol-derived unsaturated oxazolopiperidone lactams 1, belonging to both the 3,8a-cis and -trans series (Scheme 1). The kinetic adducts 2a-c (7-H/8a-H trans) resulting from an exo attack were formed as the major products from the activated lactams 1a-c, whereas the alternative endo attack (7-H/8a-H cis) predominantly occurred from the non-activated lactam 1d, leading to the most stable 7-H/8-H trans isomer 2d.…”

Section: Introductionmentioning

confidence: 99%

Unsaturated oxazolopiperidone lactams: an unexpected domino-type double conjugate addition–cyclization process

Amat¹,

Llor²,

Checa³

et al. 2013

Arkivoc

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Stereocontrolled conjugate additions to dihydroindolizinone systems. Synthesis of enantiopure polysubstituted tetrahydropyrrolo[2,1-a]isoquinolones

Cited by 12 publications

References 92 publications

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

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

Unsaturated oxazolopiperidone lactams: an unexpected domino-type double conjugate addition–cyclization process

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