Umpolung of Enamines: An Overview on Strategies and Synthons

Sukhorukov, Alexey Yu.

doi:10.1055/s-0037-1610741

Cited by 8 publications

(2 citation statements)

References 42 publications

(40 reference statements)

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“…Differently from Shi’s work, in our case the same C-C bond formation is realized exploiting the reversal of polarity of the azoalkene ( B ) system (“umpoled” of carbonyl compounds) [ 44 , 45 , 46 , 47 ]. Taking advantage of the intrinsic reactivity of the pertinent substrates, a new and complementary synthetic approach toward these unusual N -polyheterocyclic structures can be successfully achieved ( Scheme 4 ).…”

Section: Resultsmentioning

confidence: 97%

Construction of Unusual Indole-Based Heterocycles from Tetrahydro-1H-pyridazino[3,4-b]indoles

et al. 2020

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Herein, we report the successful syntheses of scarcely represented indole-based heterocycles which have a structural connection with biologically active natural-like molecules. The selective oxidation of indoline nucleus to indole, hydrolysis of ester and carbamoyl residues followed by decarboxylation with concomitant aromatization of the pyridazine ring starting from tetrahydro-1H-pyridazino[3,4-b]indole derivatives lead to fused indole-pyridazine compounds. On the other hand, non-fused indole-pyrazol-5-one scaffolds are easily prepared by subjecting the same C2,C3-fused indoline tetrahydropyridazines to treatment with trifluoroacetic acid (TFA). These methods feature mild conditions, easy operation, high yields in most cases avoiding the chromatographic purification, and broad substrate scope. Interestingly, the formation of indole linked pyrazol-5-one system serves as a good example of the application of the umpolung strategy in the synthesis of C3-alkylated indoles.

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Section: Resultsmentioning

confidence: 97%

Construction of Unusual Indole-Based Heterocycles from Tetrahydro-1H-pyridazino[3,4-b]indoles

et al. 2020

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“…Among the most iconic examples is the polarity reversal of the aldehyde ipso carbon in the Corey–Seebach reaction, benzoin condensation, and Stetter reaction, − allowing functionalization of an otherwise electrophilic site with electrophilic reagents (Scheme a). These and numerous other examples have manifested umpolung as a routine operation in synthesis planning. − …”

Section: Introductionmentioning

confidence: 99%

Organocatalyzed Cross-Nucleophile Couplings: Umpolung of Catalytic Enamines

2022

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Conspectus The concept of umpolung, or polarity reversal, introduced by Seebach and Corey nearly half a century ago, ushered a new paradigm into synthetic chemistry. Novel connections were able to be forged among functional groups that were typically inaccessible. Conceptually, an umpolung reaction is identified only upon retrosynthetic analysis. Stoichiometric examples have served as a platform to develop and refine elegant methodologies into catalytic processes. The advent of these unconventional arrangements of canonical synthons into new points of diversity has expanded the repertoire of the synthetic toolbox. Within this context, asymmetric organocatalyzed methodologies remain rare, and there are even fewer aminocatalyzed variants. Recent years have witnessed a renaissance in α-functionalizations of aldehydes, specifically in the context of oxidative umpolung strategies. Unlike previous open-shell approaches, application of a quinone-based oxidant in conjunction with an aminocatalyst leads to a discrete, substitutionally labile quinone adduct. These have proven to be valuable building blocks toward polar reactivityauguring the advent of new avenues to construct tetrasubstituted tertiary stereocenters through the application of conventional nucleophiles to form C–C, C–N, C–O, and C–S bonds through an organocatalyzed cross-nucleophile coupling (organo-CNC) reaction. The resulting nonepimerizable stereocenter demonstrates high optical fidelity and provides a significant advancement in many applications that suffer from racemization, such as in vivo studies. This strategy harnesses a trifunctional aminocatalyst to promote an unusual SN2 reaction at a highly congested center. The selection of the quinone oxidant and nucleophile converges to a continuum of reactivity ranging from enantioselective oxidation to stereoselective substitution. A remarkable aspect of these developments is the identification of an asymmetric SN2 dynamic kinetic resolution (SN2-DKR) manifold. These organo-CNC reactions are highly modular and demonstrate complete stereocontrol from the catalyst with minimal influence from incoming chiral nucleophiles. Leveraging this facet, these technologies have been extended to peptidic bioconjugations bearing bio-orthogonoal linker molecules. This Account aims to highlight the progress, from an internal perspective, toward directing the initial result into established methodologies. Within this construct, the underlying principles of each reaction will be disseminated with specific content on inherent challenges and opportunity. Combined, these will serve as an instructive tool to stimulate applications in cross-disciplinary interfaces.

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1,2‐Diaza‐1,3‐Dienes as a Multifaceted Synthons for the Synthesis of Heterocycles: A Fifteen‐Years Update

De Crescentini,

Mari,

Santeusanio

et al. 2024

Eur J Org Chem

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The discovery of structurally unique scaffolds entities with increased complexity and balanced physicochemical properties has the potential to allow synthetic chemists to exploit areas of chemical space that were previously inaccessible. Among the different strategies employed for generating N‐heterocycles, cyclization and cycloaddition reactions represent a valuable synthetic tool. The purpose of this minireview is to summarize the recent advances (2009‐present) from our laboratory on the generation of intriguing five‐, six‐ and seven‐membered mono‐ or poly‐heterocyclic architectures (linear, fused and spiro) employing 1,2‐diaza‐1,3‐dienes (DDs) as key synthons.

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Umpolung of Enamines: An Overview on Strategies and Synthons

Cited by 8 publications

References 42 publications

Construction of Unusual Indole-Based Heterocycles from Tetrahydro-1H-pyridazino[3,4-b]indoles

Construction of Unusual Indole-Based Heterocycles from Tetrahydro-1H-pyridazino[3,4-b]indoles

Organocatalyzed Cross-Nucleophile Couplings: Umpolung of Catalytic Enamines

1,2‐Diaza‐1,3‐Dienes as a Multifaceted Synthons for the Synthesis of Heterocycles: A Fifteen‐Years Update

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