Hetero-Diels-Alder reaction cycloaddition

The first microwave-assisted hetero-Diels-Alder cycloaddition reaction was described by Diaz-Ortiz and co-workers in 1998 between 2-azadiene 198 and the same electron-poor dienophiles as for the preparation of pyrazolo[3,4-b]pyridines 200 (Scheme 72) [127]. These dienes reacted with... 

Shao reported the microwave-assisted hetero-Diels-Alder cycloaddition reaction of a series of acetylenic pyrimidines to introduce a fused lactone/lactam ring, with no degradation of either reactants or products typical for the harsh thermal conditions (150-190°C, 15-144h) [131]. In contrast to the results reported when conventional heating was applied, the Diels-Alder cycloaddition under microwave irradiation gave a high yield of the desired fused lactones or lactams [132]. This reaction provided a practical and general method for the preparation of fused bicyclic pyridines 205 (Scheme 74). 

Ab initio Hartree-Fock and density functional theory (DFT) calculations were performed to study transition geometries in the intramolecular hetero-Diels-Alder cycloaddition reactions of azoalkenes 20 (LJ = CH2, NFI, O) (Equation 1). The order of the reactivities was predicted from frontier orbital energies. DFT calculations of the activation energies at the B3LYP level were in full agreement with the experimental results described in the literature <2001JST(535)165>. 

Inter- and intramolecular hetero-Diels-Alder cycloaddition reactions in a series of functionalized 2-(lH)-pyrazinones have been studied in detail by the groups of Van der Eycken and Kappe (Scheme 6.95) [195-197]. In the intramolecular series, cycloaddition of alkenyl-tethered 2-(lH)-pyrazinones required 1-2 days under conventional thermal conditions involving chlorobenzene as solvent under reflux conditions (132 °C). Switching to 1,2-dichloroethane doped with the ionic liquid l-butyl-3-methylimidazolium hexafluorophosphate (bmimPF6) and sealed-vessel microwave technology, the same transformations were completed within 8-18 min at a reaction temperature of 190 °C (Scheme 6.95 a) [195]. Without isolating the primary imidoyl chloride cycloadducts, rapid hydrolysis was achieved by the addition of small amounts of water and subjecting the reaction mixture to further microwave irradia-... 

Scheme 6.95 Hetero-Diels-Alder cycloaddition reactions of 2(1 H)-pyrazinones.

The Lewis acid-mediated reactions of 2-aza-l,3-dienes and aldehydes, resulting in tetrahydro-l,3-oxazin-4-one derivatives, were explained in terms of the competitive existence of two reaction pathways a [4+2] hetero-Diels-Alder cycloaddition reaction and a Mukaiyama aldol reaction <2001TA439>. 

Oxamborolidenes. There are noteworthy advances in the design, synthesis, and study of amino acid-derived oxazaborolidene complexes as catalysts for the Mukaiyama aldol addition. Corey has documented the use of complex 1 prepared from A-tosyl (S)-tryptophan in enantioselective Mukaiyama aldol addition reactions [5]. The addition of aryl or alkyl methyl ketones 2a-b proceeded with aromatic as well as aliphatic aldehydes, giving adducts in 56-100% yields and up to 93% ee (Scheme 8B2.1, Table 8B2.1). The use of 1-trimethylsilyloxycyclopentene 3 as well as dienolsilane 4 has been examined. Thus, for example, the cyclopentanone adduct with benzaldehyde 5 (R = Ph) was isolated as a 94 6 mixture of diastereomers favoring the syn diastereomer, which was formed with 92% ee, Dienolate adducts 6 were isolated with up to 82% ee it is important that these were shown to afford the corresponding dihydropyrones upon treatment with trifuoroacetic acid. Thus this process not only allows access to aldol addition adducts, but also the products of hetero Diels-Alder cycloaddition reactions. 

A further means of access to unsaturated carbohydrates from nonsugars is by application of the hetero-Diels Alder cycloaddition reaction between substituted-1,3-dienes (167) and aldehydes to give dihydropyrans (168). This... 

Kametani, T., Hibino, S., The Synthesis of Natural Heterocyclic Products by Hetero Diels-Alder Cycloaddition Reactions,... 

Heterocyclic iminium salts, oxidative transformation, 41, 275 Heterocyclic mesomeric betaines and analogs in natural product chemistry, 85, 67 Heterocyclic oligomers, 15, 1 Heterocyclic products, natural, synthesis of by hetero Diels-Alder cycloaddition reactions, 42, 245... 

Hetero Diels-Alder cycloaddition reactions, synthesis of natural heterocyclic products by, 42, 245... 

Hetero Diels-Alder cycloaddition reactions, synthesis of natural heterocyclic products by, 42, 245 Heterodienophiles, new, heterocyclic synthesis using, 55, 1 Hilbert-Johnson reaction of 2,4-... 

Hetero-Diels-Alder Cycloaddition Reactions. Copper-bis-(oxazoline) complex (2) facilitates a variety of asymmetric hetero-Diels-Alder reactions between a diverse range of substrates. A... 

This article summarizes recent advances in the synthesis of natural products by hetero Diels-Alder cycloaddition reactions up to 1985. These recent disclosures have had a great impact on heterocyclic natural product syntheses. 

Alves, C. N., Romero, O. A. S., Da Silva, A. B. F. Theoretical study on the stereochemistry of intramolecular hetero Diels-Alder cycloaddition reactions of azoalkenes. Int. J. Quantum Chem. 2003, 95, 133-136. 

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