Aza-Nazarov Cyclization Reactions via Anion Exchange Catalysis

Dönmez, Selin Ezgi; Soydaş, Emine; Aydin, G.; Şahın, Onur; Bozkaya, Uğur; Türkmen, Yunus E.

doi:10.1021/acs.orglett.8b03886

Cited by 11 publications

(14 citation statements)

References 73 publications

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“…Mechanistically, this novel cyclization could be explained through one of the two plausible pathways: anti-Baldwin intramolecular aza-Michael reaction (5- endo - trig ) or thermally allowed pericyclic aza-Nazarov cyclization, both potentially benefiting from a general acid promotion. A previous study conducted by Klumpp on aza-Nazarov cyclizations of N -acyliminium salts under superacid catalysis suggests that the cyclization proceeds through a dicationic species, which is consistent with the reports by Olah and Shudo for reactions with TfOH under the conditions of superelectrophilic solvation. On the other hand, Würthwein disclosed an aza-Nazarov cyclization of 1-azapenta-1,4-dien-3-ones via monoprotonated reactive intermediates.…”

supporting

confidence: 85%

Synthesis of C-Ring-Substituted Vasicinones and Luotonins via Regioselective Aza-Nazarov Cyclization of Quinazolinonyl Enones

et al. 2019

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supporting

confidence: 85%

Synthesis of C-Ring-Substituted Vasicinones and Luotonins via Regioselective Aza-Nazarov Cyclization of Quinazolinonyl Enones

et al. 2019

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“…Substitution of the phenylthio group of 3b with a hydroxy group was readily achieved by treatment with CuBr in aqueous media (THF/H 2 O) to afford the corresponding hydroxylactam in 90% yield (Scheme 2). However, the subsequent spirolactonization with p-toluenesulfonic acid (p-TsOH) was unsuccessful, leading to predominant production of bislactam derivative 4a (97%) [23][24][25]. Although acidic spirolactamization was contrary to our initial expectations, a new type of N-phenyl spirobislactam, which could not be obtained by our previous method, became accessible through this reaction.…”

Section: Reactions Of 3-(phenylthio)isoindolinone Derivatives Bearing Anmentioning

confidence: 71%

Bifurcated synthesis of methylene-lactone- and methylene-lactam-fused spirolactams via electrophilic amide allylation of γ-phenylthio-functionalized γ-lactams

Sengoku

Makino

Iijima

et al. 2020

Beilstein J. Org. Chem.

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New synthetic methods for spirolactams bearing an α-methylene-γ-butyrolactone or its analogous methylene-lactam have been developed. The allylation of γ-phenylthio-functionalized γ-lactams with 2-(acetoxy)methyl acrylamides was accomplished by using 2.5 equivalents of NaH to give the corresponding adducts in excellent yields. The remaining phenylthio group was substituted with a hydroxy group by treatment with CuBr, and the resulting γ-hydroxyamides were cyclized under acidic conditions to afford the corresponding methylene-lactam-fused spirolactams in high yields. On the other hand, methylene-lactone-fused spirolactams could be delivered from the allyl adducts in high yields through a sequential N-Boc protection/desulfinative lactonization.

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“…dihydroisoquinoline substrates as cyclic imines was investigated under these conditions [35]. In the current work, we first opted to examine the activities of other Lewis acids in the aza-Nazarov cyclization of imine 5a with acyl chloride 6b.…”

Section: Resultsmentioning

confidence: 99%

Catalytic aza-Nazarov cyclization reactions to access α-methylene-γ-lactam heterocycles

Yagci¹,

Dönmez²,

Şahın³

et al. 2023

Beilstein J. Org. Chem.

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We have developed a catalytic aza-Nazarov reaction of N-acyliminium salts generated in situ from the reaction of a variety of cyclic and acyclic imines with α,β-unsaturated acyl chlorides to afford substituted α-methylene-γ-lactam heterocycles. The reactions proceed effectively in the presence of catalytic (20 mol %) amounts of AgOTf as an anion exchange agent or hydrogen-bond donors such as squaramides and thioureas as anion-binding organocatalysts. The aza-Nazarov cyclization of 3,4-dihydroisoquinolines with α,β-unsaturated acyl chlorides gives tricyclic lactam products 7 in up to 79% yield with full diastereocontrol (dr = >99:1). The use of acyclic imines in a similar catalytic aza-Nazarov reaction with 20 mol % of AgOTf results in the formation of α-methylene-γ-lactam heterocycles 19 in up to 76% yield and with good to high diastereoselectivities (4.3:1 to 16:1). We have demonstrated the scalability of the reaction with a gram-scale example. The relative stereochemistry of the α-methylene-γ-lactam products 19 has been determined via the single-crystal X-ray analysis of lactam 19l. In order to shed light on the details of the reaction mechanism, we have performed carefully designed mechanistic studies which consist of experiments on the effect of β-silicon stabilization, the alkene geometry of the α,β-unsaturated acyl chloride reactants, and adventitious water on the success of the catalytic aza-Nazarov reaction.

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Aza-Nazarov Cyclization Reactions via Anion Exchange Catalysis

Cited by 11 publications

References 73 publications

Synthesis of C-Ring-Substituted Vasicinones and Luotonins via Regioselective Aza-Nazarov Cyclization of Quinazolinonyl Enones

Synthesis of C-Ring-Substituted Vasicinones and Luotonins via Regioselective Aza-Nazarov Cyclization of Quinazolinonyl Enones

Bifurcated synthesis of methylene-lactone- and methylene-lactam-fused spirolactams via electrophilic amide allylation of γ-phenylthio-functionalized γ-lactams

Catalytic aza-Nazarov cyclization reactions to access α-methylene-γ-lactam heterocycles

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