<scp>Aza‐Michael</scp> addition of 1,<scp>2‐diazoles</scp> to structurally diverse enones: Efficient methods toward <scp>β‐amino</scp> ketones

Polina, Saibabu; Putta, V. P. Rama Kishore; Gujjarappa, Raghuram; Pujar, Prasad Pralhad; Malakar, Chandi C.

doi:10.1002/jhet.4221

Cited by 4 publications

(5 citation statements)

References 38 publications

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“…[20] The successful addition of pyrazoles to five-, sixor seven-membered cyclic and acyclic enones is realized in the presence of 1.1 equivalent of 2,4,6tripropyl-1,3,5,2,4,6-trioxatriphosphorinane-2,4,6-trioxide (T3P) under mild reaction conditions. [21] The aza-Michael reaction proceeds smoothly in good to high yields even for 4-nitro-lH-pyrazole: the corresponding adduct 16 is isolated in 65% yield (Scheme 5). This approach shows an excellent func- tional group tolerance and can be applied to tri-and tetrazoles.…”

Section: Pyrazoles Imidazoles Triazoles and Tetrazolesmentioning

confidence: 99%

Weak Nucleophiles in the Aza‐Michael Reaction

Rulev

2023

Adv Synth Catal

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The 1,4‐conjugated addition of nitrogen centered nucleophiles to electron‐deficient alkenes is one of the most significant and widely used reactions in modern synthetic organic chemistry. To date, various protocols for the aza‐Michael reaction have been developed. However, these reports mainly focus on the use of strong Michael donors. In recent years, the conjugate addition of weak nitrogen nucleophiles to various Michael acceptors gained increasing popularity. Impressive progress in this area has been achieved by the use of more efficient catalyst systems. This review aims to provide a critical analysis of the results obtained in reactions of weak nucleophiles (azoles, pyrroles, indoles, carbamates, purines, amides, hydrazides, uraciles etc) with electron‐deficient alkenes which were reported over the past twelve years.

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Section: Pyrazoles Imidazoles Triazoles and Tetrazolesmentioning

confidence: 99%

Weak Nucleophiles in the Aza‐Michael Reaction

Rulev

2023

Adv Synth Catal

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“…After establishing the optimized conditions for the envisaged transformation, we focused on proposing a plausible mechanistic pathway under the HMPT-mediated conditions for the synthesis of desired products (Scheme 2). 12,14 The electron pair situated on oxygen atom of enone 1a may participate in nucleophilic attack towards the phosphorus atom of P(NMe2)3 (A), which leading to the formation of expected intermediate B and that may be assumed in the existence of resonance form B′. The reaction between intermediate B′ and azole 2 could deliver the intermediate C, which finally produces the expected molecule 3 followed by consequent hydrolysis of P-O bond and tautomerization process.…”

Section: Conditions A)mentioning

confidence: 99%

“…Recently, a T3P-mediated approach has been described for the reaction of enone-molecules with diverse azoles employing aza-Michael addition protocol at room temperature with good yields and selectivity. 12 Additionally, during the past decades, the greener approaches of Michael-addition reaction have accumulated increasing interest and found enormous application in organic synthesis. [3][4][5]7,11 In this regard, we have designed a new process by utilizing a mild and robust HMPT as reagent for the reaction between enones and azoles at room temperature.…”

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confidence: 99%

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N-Alkylation of Azoles with Enones Assisted by P(III) or Fe2O3-Nanoparticles as Recyclable Catalyst

Malakar¹,

Devi²,

Polina³

et al. 2023

HETEROCYCLES

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Hexamethylphosphorous triamide (HMPT)-assisted and Fe2O3nanoparticles (NPs) catalysed approaches towards the formation of C-N bond is described by the reaction between azoles and enone-compounds. The transformations were accomplished under mild conditions at temperatures 25 °C and 50 °C respectively. The efficacy and robustness of the reaction conditions can be envisioned by regioselective construction of N-heterocyclic scaffolds embedded with cycloalkyl residue. The established reaction conditions were found competent over a series of enones and azole derivatives to furnish the desired molecules in high yields ranging from 52-86% under P(III)-mediated conditions and 67-86% under the influences of Fe2O3-NPs as recyclable catalyst.It was observed that the catalyst can be recycled up to six times with good yields of the product.The recognition of cycloalkyl-substituted N-heterocyclic moieties can be realized by their ubiquitous appearances in diversity of bioactive molecules. 1 Importance of these moieties was further witnessed by their occurrences in modern drugs such as phosphoinositide 3-kinase (PI3K) inhibitors, 1a epidermal growth factor receptor (EGFR) inhibitors, 1b cilostazol (to treat peripheral vascular disease), 1c cytochrome P450 (CYP) 17 inhibitors anti-androgens, 1d interleukin-1 receptor-associated kinases (IRAKs) inhibitors 1e (Figure 1). These heterocyclic skeletons were prepared by C-N bond formation approach. In the area of C-N bond formation, the traditionally employed strategy such as aza-Michael protocol holds an important position owing to its advantage over other methodologies. Nevertheless, the preferences of adding azoles to cyclic enones were hindered by the structural complexities of cyclic enones and due to the low nucleophilicity of azoles. 2 According to earlier reported methods, a series of reagents such as metals, 3 bases, 4 organocatalysts, 5 inorganic supports, 6 lanthanides, 7 fluorides, 8 and enzymes 9 have been widely explored to accomplish aza-Michael addition reactions. These transformations were also described under catalyst-free conditions and Brønsted acid-induced conditions, which are operated under harsh conditions at high pressure to deliver unselective product formation. 10,11 Nonetheless, it is noteworthy to mention that the reactions of cyclic enone derivatives with azole molecules using aza-Michael addition approach are rarely explored. 2a,6b,11

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“…Despite significant advances in the aza-Michael addition of various heterocycles, most transformations have been limited to acyclic α , β -unsaturated substrates, and only a few studies have reported the synthesis of N -cycloalkyl-substituted β -amino carbonyls from cyclic substrates. 4 Furthermore, the aza-Michael addition of heterocycles to β , β -disubstituted enones for the construction of quaternary carbon centers bearing a nitrogen substituent has been rarely explored. To the best of our knowledge, Kotsuki et al have been the only to report the synthesis of a single product of β -amino ketones bearing heterocyclic-substituted quaternary centers via the addition of a triazole to a 3-methylcyclohex-2-enone under high-pressure and high-temperature conditions (Scheme 1a).…”

Section: Introductionmentioning

confidence: 99%