An Ugi Reaction Incorporating a Redox-Neutral Amine C–H Functionalization Step

Zhu, Zhengbo; Seidel, Daniel

doi:10.1021/acs.orglett.5b03529

Cited by 39 publications

(17 citation statements)

References 87 publications

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“…In an interesting work, Seidel and Zhu demonstrated a simple and efficient method for α-amidation with concurrent N -alkylation of pyrrolidine and THIQ 174 (Scheme ). , In this reaction, C−H functionalization was afforded via an isomerization step in which azomethine ylides act as cyclic imines 175 . It is worth noting that water is provided by the external addition or is generated in the condensation step for the nucleophilic attack to the isocyanide.…”

Section: Cyclic Imines In Joulliè−ugi Reactionmentioning

confidence: 99%

Cyclic Imines in Ugi and Ugi-Type Reactions

et al. 2020

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Ugi four-component reactions (U-4CRs) are widely recognized as being highly efficient for the synthesis of pseudopeptides. However, the products of these reactions are not so interesting as drug candidates because they are not conformationally restricted enough for a potent interaction with biological targets. One possible way to overcome this problem is to replace amine and oxo components in the U-4CRs with cyclic imines in so-called Joullié−Ugi three-component reactions (JU-3CRs). This approach provides a robust single-step route to peptide moieties connected to N-heterocyclic motifs that are found as core skeletons in many natural products and pharmaceutical compounds. JU-3CRs also provide much better diastereoselectivity than their four-component analogues. We survey here the redesign of many synthetic routes for the efficient preparation of a wide variety of three-, five-, six-, and seven-membered heterocyclic compounds connected to the peptide backbone. Additionally, in the Ugi reactions based on the cyclic imines, α-acidic isocyanides, or azides can be replaced with normal isocyanides or acids, respectively, leading to the synthesis of N-heterocycles attached to oxazoles or tetrazoles, which are of great pharmaceutical significance. This Review includes all research articles related to Ugi reactions based on the cyclic imines to the year 2020 and will be useful to chemists in designing novel synthetic routes for the synthesis of individual and combinatorial libraries of natural products and drug-like compounds.

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Section: Cyclic Imines In Joulliè−ugi Reactionmentioning

confidence: 99%

Cyclic Imines in Ugi and Ugi-Type Reactions

et al. 2020

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“…A new variant of the classic Ugi reaction involving the -C-H bond functionalization of cyclic amines was reported by our group (Scheme 51). 98 Amines readily react with aromatic aldehydes/ketones and isocyanides under reflux in toluene. These redox-Ugi reactions are promoted by acetic acid and lack the prototypical Mumm rearrangement.…”

Section: Redox-ugi Reactionsmentioning

confidence: 99%

Condensation-Based Methods for the C–H Bond Functionalization of Amines

Chen

Seidel

2021

Synthesis

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This review aims to provide a comprehensive overview of condensation-based methods for the C–H bond functionalization of amines that feature azomethine ylides as key intermediates. These transformations are typically redox-neutral and share common attributes with classic name reactions such as the Strecker, Mannich, Friedel−Crafts, Pictet−Spengler, and Kabachnik−Fields reaction, while incorporating a redox-isomerization step. This approach provides an ideal platform to rapidly transform simple starting materials into complex amines.

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“…25,26 The incorporation of fluorene derivatives by MCRs to give adducts with many points of diversification is of high importance, but is quite underexplored and limited in scope. [27][28][29][30][31][32] Structural diversity and complexity in such libraries are critical to the elucidation of structure-activity relationships that drive the development of new products and technologies. Orru and co-workers, 33 in their pioneering work, took advantage of the -acidic nature of 9-isocyano-1H-fluorene (1; pK a = 12.3 in DMSO), which becomes aromatic after deprotonation, [34][35][36] and were able to synthesize the druglike spiro-2-imidazolines 2 through a threecomponent reaction, now known as the Orru reaction (Orru-3CR; Scheme 1).…”

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confidence: 99%

Fluorene-Based Multicomponent Reactions

Lei

Thomaidi

Angeli

et al. 2021

Synlett

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Fluorene and fluorenone are privileged structures with extensive utility both in material science and drug discovery. Here, we demonstrate the implementation of those moieties via the isocyanide-based multicomponent reactions and their incorporation in diverse and complex derivatives that can be further utilized. We performed six different IMCRs, based on the dual functionality of the 9-isocyanofluorene and describe 23 unprecedented adducts.

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An Ugi Reaction Incorporating a Redox-Neutral Amine C–H Functionalization Step

Abstract: Pyrrolidine and 1,2,3,4-tetrahydroisoquinoline (THIQ) undergo redox-neutral α-amidation with concurrent N-alkylation upon reaction with aromatic aldehydes and isocyanides. Reactions are promoted by acetic acid and represent a new variant of the Ugi-reaction.

Cited by 39 publications

References 87 publications

Cyclic Imines in Ugi and Ugi-Type Reactions

Cyclic Imines in Ugi and Ugi-Type Reactions

Condensation-Based Methods for the C–H Bond Functionalization of Amines

Fluorene-Based Multicomponent Reactions

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