EuFOD-Catalyzed Hetero-Diels-Alder (HDA) Reaction under Microwave Heating

Panunzio, Mauro; Bandini, Elisa; D'Aurizio, Antonio; Millemaggi, Alessia; Xia, Zhining

doi:10.1055/s-2007-965985

Cited by 11 publications

(2 citation statements)

References 16 publications

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“…All of these effects are easily illustrated in some recent examples: the reaction of 1-phenyl-2-aza-1,3-diene with aldehydes, performed under microwave irradiation and acid catalysis, yields only the HDA product. 13 On the other hand, reaction of cyclohexanone and 1-phenyl-4-p-methoxyphenyl-3-trimethylsilyloxy-2-aza-1,3-diene furnishes the HDA product only at low temperatures (À781) and in the presence of BF 3 as catalyst, meanwhile it yields the 2+2EC product under reflux generated by convective or microwave irradiation. 2c The results so far reported clearly show a general pattern: (a) reactions using aldehyde or ketones as dienophile in the presence of a catalyst at À78 1C furnished only HDA adduct.…”

Section: Resultsmentioning

confidence: 99%

Silyloxyazadienes: one intermediate and two competitive pericyclic reactions

Bongini

Panunzio²,

Venturini³

2010

Phys. Chem. Chem. Phys.

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The two competing mechanisms in the reaction of 3-trialkylsilyloxy-2-aza-1,3 dienes to form beta-lactams through a [2+2] electrocyclic ring closure or tetrahydrooxazinan-4-ones via a [4+2] hetero-Diels-Alder reaction were studied using Density Functional computations. Although the [2+2] and [4+2] mechanisms are typical of dienes, their competition, starting from the same diene intermediate, has not yet been observed and analyzed. This competition is governed by a delicate interplay between temperature and substituents at the diene and dienophile, respectively. Clearly, entropy tends to favor the [4+2] hetero-Diels-Alder at low temperatures and the [2+2] electrocyclic ring closure at high temperatures, but simple substituent modifications at the diene and dienophile, can make the [4+2] competitive at high temperatures and sometimes even transform the [4+2] concerted mechanism into a two-step Mukaiyama-type process. Moreover, a study of the global electrophilicity values showed that charge transfer in the hetero-Diels-Alder transition states is driven by chemical hardness rather than by chemical potential.

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Section: Resultsmentioning

confidence: 99%

Silyloxyazadienes: one intermediate and two competitive pericyclic reactions

Bongini

Panunzio²,

Venturini³

2010

Phys. Chem. Chem. Phys.

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“…The necessary [4+2] HDA reaction was next attempted taking advantage of our recent procedure for the preparation of 1,3-perhydrooxazin-4-ones by EuFod [europium(III) tris(1,1,2,2,3,3-heptafluoro-7,7-dimethyl-4,6octanedionate]-catalyzed microwave-assisted organic synthesis (MAOS). 8 Accordingly, reaction of the azadiene 4 with dienophile cyclohexanone (5) was performed, using EuFod (0.05%) as catalyst and chlorobenzene as solvent under microwave irradiation (Scheme 2). Workup of the reaction mixture showed the formation of traces of the desired 1,3-perhydrooxazin-4-one 6 ( whereas the major product was constituted by the trans-blactam ring 7, arising from a [2+2] electrocyclization (for the sake of easy reading only one enantiomer of the racemic mixtures has been depicted in Scheme 2) irrespective of the presence or not of the Lewis acid (Table 1, entry 2).…”

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Synthesis of Venlafaxine from Azadiene via a Hetero-Diels-Alder Approach: New Microwave-Assisted Transketalization and Hydroxymethylation Reactions

Panunzio¹,

Bandini²,

D'Aurizio³

et al. 2008

Synthesis

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Hetero-Diels-Alder (HDA) methodology has been applied to the synthesis of Venlafaxine taking advantage of a novel MW-assisted transketalization and hydroxymethylation reaction.2-Azadienes 1 have been demonstrated to be versatile intermediates in hetero-Diels-Alder (HDA) reactions 2 with aldehydes to furnish perhydroxazin-4-ones. The latter have been utilized for the production of the 1,3-hydroxyamino moiety, or skeleton, of different biologically active compounds and of important chiral auxiliaries/ ligands in asymmetric organic synthesis. 3 In the course of our studies on these interesting intermediates, we have reported on the preparation of biologically active CNSdrugs, Prozac and Duloxetine, in racemic and optically pure form as well, presenting a scaffold of an 1,3-aminol unsubstituted in the 2-position and a secondary hydroxy functionality. 4 In this paper we report our attempts to apply this strategy to the synthesis of (±)-Venlafaxine (1) 5 characterized by the presence of a substituent (4-methoxyphenyl group) in the 2-position of the 1,3-aminol skeleton ( Figure 1) and a tertiary hydroxy functionality. The importance of 1 resides in the fact that, among a large number of chemical structures found to exhibit antidepressant activity with diminished cardiovascular and anticholinergic liability, this compound has been proven to be the most potent antidepressant agent and has been approved by the drug agencies of many countries for the treatment of depression thanks to its faster onset of action and increased efficiency. From synthetic point of view, the choice of this particular target was dictated by our attempts of rendering the HDA protocol, developed in our laboratories, suitable for the preparation of a library of variably functionalized compounds presenting the 1-hydroxy-3-amino functionalities with or without further substitutions in the backbone chain identified by 1,3-aminol moiety and using as carbonyl-dienophile a ketone. Previous results showed that perhydroxazin-2-ones may be prepared from an 2-aza-1,3-diene variably substituted in the position 1 but unsubstituted in position 4, and a ketone as dienophile, including hindered ones such as menthone. 6 These results were very interesting since the poor reactivity of ketones compared to aldehydes in heteroDiels-Alder reactions is well known, owing to both steric and electronic reasons. As a matter of fact, until recently, only a very few examples of HDA reactions of ketones have been reported. 7 Having in hand this information, we started our studies by preparing the intermediate azadiene 4 from (4-methoxyphenyl)acetyl chloride (2) and the trimethylsilylbenzaldimine 3 according to an existing protocol 1a,8 (Scheme 1).

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Formation of Alkenes by Diels–Alder Reactions

Larock

2018

Comprehensive Organic Transformations

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General Reviews Regioselectivity Exo / Endo Selectivity Asymmetric Diels–Alder Reaction Mechanism Use of High Pressure Microwave Irradiation Infrared Irradiation Mechanical Ball Milling Ultracentrifugation Use of Ultrasound Catalysis Solvent Effects Cavity Effects Retro‐Diels–Alder Reaction Intramolecular Diels–Alder Reaction Inverse Electron‐Demand Diels–Alder Reaction Radical Cation Diels–Alder Reaction Ionic Diels–Alder Reaction Use of Heterodienophiles Use of Heteroatom‐Containing “Dienes” Use of Substituted 1,3‐Dienes o ‐Quinodimethanes and Heterocyclic Analogues Arynes and Hetarynes Some Other Dienophiles Dienophile Equivalents Transition Metal Carbenes as Dienophiles

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EuFOD-Catalyzed Hetero-Diels-Alder (HDA) Reaction under Microwave Heating

Abstract: An efficient EuFOD-catalyzed hetero-Diels-Alder reaction between azadienes and aldehydes under microwave irradiation is reported. The reaction proceeds under microwave heating with 5 mol% of EuFOD in 45-83% yields.

Cited by 11 publications

References 16 publications

Silyloxyazadienes: one intermediate and two competitive pericyclic reactions

Silyloxyazadienes: one intermediate and two competitive pericyclic reactions

Synthesis of Venlafaxine from Azadiene via a Hetero-Diels-Alder Approach: New Microwave-Assisted Transketalization and Hydroxymethylation Reactions

Formation of Alkenes by Diels–Alder Reactions

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