Selective copper(II) acetate and potassium iodide catalyzed oxidation of aminals to dihydroquinazoline and quinazolinone alkaloids

Richers, Matthew T.; Zhao, Chenfei; Seidel, Daniel

doi:10.3762/bjoc.9.135

Cited by 42 publications

(24 citation statements)

References 52 publications

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“…This compound was identified as 2-methyl-1-propylquinazolin-4(1 H )-one ( 6a ) ( Scheme 3 , (a), R 1 = Pr, R 2 = Me), arising from spontaneous benzylic oxidation of 2a . An analogous reaction had been previously reported for 3,4-dihydroquinazolines upon exposure to air ( Scheme 3 , (b)) [ 19 , 24 , 40 , 66 ].…”

Section: Resultssupporting

confidence: 65%

Syntheses of 3,4- and 1,4-dihydroquinazolines from 2-aminobenzylamine

Díaz¹,

Ranieri²,

Gruber³

et al. 2017

Beilstein J. Org. Chem.

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A straightforward strategy for the synthesis of dihydroquinazolines is presented, which allows for the preparation of 3,4- and 1,4-dihydroquinazolines with different substitution patterns from 2-aminobenzylamine (2-ABA) as common precursor. The required functionalization of both amino groups present in 2-ABA was achieved by different routes involving selective N-acylation and cesium carbonate-mediated N-alkylation reactions, avoiding protection/deprotection steps. The heterocycles were efficiently synthesized in short reaction times by microwave-assisted ring closure of the corresponding aminoamides promoted by ethyl polyphosphate (PPE).

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Section: Resultssupporting

confidence: 65%

Syntheses of 3,4- and 1,4-dihydroquinazolines from 2-aminobenzylamine

Díaz¹,

Ranieri²,

Gruber³

et al. 2017

Beilstein J. Org. Chem.

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“… 14 Using appropriate oxidation conditions, aminals can be directly converted to dihydroquinazoline and quinazolinone alkaloids. 13 , 15 , 17 , 18 …”

Section: Intramolecular Redox-transformationsmentioning

confidence: 99%

The Azomethine Ylide Route to Amine C–H Functionalization: Redox-Versions of Classic Reactions and a Pathway to New Transformations

Seidel

2015

Acc. Chem. Res.

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209

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ConspectusRedox-neutral methods for the functionalization of amine α-C–H bonds are inherently efficient because they avoid external oxidants and reductants and often do not generate unwanted byproducts. However, most of the current methods for amine α-C–H bond functionalization are oxidative in nature. While the most efficient variants utilize atmospheric oxygen as the terminal oxidant, many such transformations require the use of expensive or toxic oxidants, often coupled with the need for transition metal catalysts.Redox-neutral amine α-functionalizations that involve intramolecular hydride transfer steps provide viable alternatives to certain oxidative reactions. These processes have been known for some time and are particularly well suited for tertiary amine substrates. A mechanistically distinct strategy for secondary amines has emerged only recently, despite sharing common features with a range of classic organic transformations. Among those are such widely used reactions as the Strecker, Mannich, Pictet–Spengler, and Kabachnik–Fields reactions, Friedel–Crafts alkylations, and iminium alkynylations. In these classic processes, condensation of a secondary amine with an aldehyde (or a ketone) typically leads to the formation of an intermediate iminium ion, which is subsequently attacked by a nucleophile. The corresponding redox-versions of these transformations utilize identical starting materials but incorporate an isomerization step that enables α-C–H bond functionalization. Intramolecular versions of these reactions include redox-neutral amine α-amination, α-oxygenation, and α-sulfenylation. In all cases, a reductive N-alkylation is effectively combined with an oxidative α-functionalization, generating water as the only byproduct.Reactions are promoted by simple carboxylic acids and in some cases require no additives. Azomethine ylides, dipolar species whose usage is predominantly in [3 + 2] cycloadditions and other pericyclic processes, have been identified as common intermediates. Extension of this chemistry to amine α,β-difunctionalization has been shown to be possible by way of converting the intermediate azomethine ylides into transient enamines.This Account details the evolution of this general strategy and the progress made to date. Further included is a discussion of related decarboxylative reactions and transformations that result in the redox-neutral aromatization of (partially) saturated cyclic amines. These processes also involve azomethine ylides, reactive intermediates that appear to be far more prevalent in condensation chemistry of amines and carbonyl compounds than previously considered. In contrast, as exemplified by some redox transformations that have been studied in greater detail, iminium ions are not necessarily involved in all amine/aldehyde condensation reactions.

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“…Oxidation reactions with KMnO 4 or a mixture of potassium iodide and tert -butyl hydroperoxide (TBHP) give access to quinazolinones and have been reported for the synthesis of the naturally occurring alkaloids deoxyvasicinone, mackinazolinone or rutaecarpine [22,28] (Scheme 2). Besides total oxidation of the aminal core, also a partial oxidation towards 3,4-dihydroquinazolines is possible for the case that the oxidation is promoted either by Cu(AcO) 2 or by a mixture of elemental iodine and BuLi.…”

Section: Introductionmentioning

confidence: 99%

“…Besides total oxidation of the aminal core, also a partial oxidation towards 3,4-dihydroquinazolines is possible for the case that the oxidation is promoted either by Cu(AcO) 2 or by a mixture of elemental iodine and BuLi. These methods allow the synthesis of the partially unsaturated alkaloids vasicine or deoxyvasicine in good yields [22,28] (Scheme 2). Furthermore, copper-catalysed reactions or oxidation with sodium hypochlorite were also described to yield the aromatic quinazoline core [26,29–30] (Scheme 2).…”

Section: Introductionmentioning

confidence: 99%

Experimental and theoretical investigations into the stability of cyclic aminals

Sawatzky¹,

Drakopoulos²,

Rölz³

et al. 2016

Beilstein J. Org. Chem.

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Background: Cyclic aminals are core features of natural products, drug molecules and important synthetic intermediates. Despite their relevance, systematic investigations into their stability towards hydrolysis depending on the pH value are lacking. Results: A set of cyclic aminals was synthesized and their stability quantified by kinetic measurements. Steric and electronic effects were investigated by choosing appropriate groups. Both molecular mechanics (MM) and density functional theory (DFT) based studies were applied to support and explain the results obtained. Rapid decomposition is observed in acidic aqueous media for all cyclic aminals which occurs as a reversible reaction. Electronic effects do not seem relevant with regard to stability, but the magnitude of the conformational energy of the ring system and pK a values of the N-3 nitrogen atom. Conclusion: Cyclic aminals are stable compounds when not exposed to acidic media and their stability is mainly dependent on the conformational energy of the ring system. Therefore, for the preparation and work-up of these valuable synthetic intermediates and natural products, appropriate conditions have to be chosen and for application as drug molecules their sensitivity towards hydrolysis has to be taken into account.

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Selective copper(II) acetate and potassium iodide catalyzed oxidation of aminals to dihydroquinazoline and quinazolinone alkaloids

Cited by 42 publications

References 52 publications

Syntheses of 3,4- and 1,4-dihydroquinazolines from 2-aminobenzylamine

Syntheses of 3,4- and 1,4-dihydroquinazolines from 2-aminobenzylamine

The Azomethine Ylide Route to Amine C–H Functionalization: Redox-Versions of Classic Reactions and a Pathway to New Transformations

Experimental and theoretical investigations into the stability of cyclic aminals

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