Azadiene synthesis

Boger D. L. Heterocyclic and Acyclic Azadiene Diels-Alder Reactions Total Synthesis of Nothapodytine B. J. Heterocycl. Chem. 1998 35 1003-1011 Keywords inverse electron-demand Diels-Alder reactions, acyclic azadienes, synthesis of natural products... 

Azabicyclo[3.1.0]hexanes and analogs with further heteroatom substitution, 27, 1 Azadienes, synthesis of heterocycles from, 57, 1... 

Azadienes, synthesis of heterocycles from (review), 57, I I-Aza-1,3-dienes cheletropic addition to... 

Gilchrist et al. used the reaction of inverse azadiene synthesis to obtain 1 -phthaloylaminopyrazoles (14) from tetrazole (13) and activated acetylene compounds [73CC8I9 75JCS(P1)1747]. Heating l-c>-nitrophenylpyrazoles with triethylphosphite leads to pyrazolo[l,2-a]benzotriazoles [Eq. (2)]... 

Amino-l-azadiene synthesis. A direct approach to this class of compounds consists of reaction of the zincoenamines derived from (V-arylketimines with nitriles. 

Heterocyclic and acyclic azadiene Diels-Alder reaction in total synthesis of nothapodyine B, alkaloid with antiviral activity 98JHC1003. 

For examples of Diels-Alder reactions involving 2-azadienes, see (a) Boger, D.L. Weinreb, S.M. In Hetero Diels-Alder Methodology in Organic Synthesis, Academic Press San Diego, 1987, p. 255 (b) Boger, D. L. Tetrahedron 1983, 39, 2869. 

The 2-azadiene system of the pyrazinone scaffold undergoes inter- and intramolecular cycloaddition reactions with a variety of (functionalized) alkenes forming bicyclic adducts, leading to the stereoselective generation of a variety of natural product analogues as well as peptidomimetics [58]. These bicyclic compounds could serve as key intermediates in the synthesis... 

A one-pot, four-component process involving the in situ formation of an azadiene followed by an intermolecular or intramolecular Diels-Alder reaction for the synthesis of highly functionalized piperidone scaffolds has been reported [81]. The compounds were obtained in good yields and diastereoselectivities (Figure 5). 

Other multicomponent reactions are exemplified in the following two schemes. A new highly diastereoselective four-component reaction was developed for the synthesis of dihydropyridones 191 substituted with an isocyanide functionality <06OL5369>, thereby generating a synthetically useful complex isocyanide for use in further reactions. In this strategy, a phosphonate, a nitrile, and an aldehyde are used to generate an azadiene intermediate 192, which is trapped by an isocyanoacetate in the same pot. 

Moody and coworkers have employed a biomimetic hetero-Diels-Alder-aroma-tization sequence for the construction of the 2,3-dithiazolepyridine core unit in amythiamicin D and related thiopeptide antibiotics (Scheme 6.243 a) [426]. The key cycloaddition reaction between the azadiene and enamine components was carried out by microwave irradiation at 120 °C for 12 h and gave the required 2,3,6-tris(thi-azolyl)pyridine intermediate in a moderate 33% yield. Coupling of the remaining building blocks then completed the first total synthesis of the thiopeptide antibiotic... 

The Boger pyrrole synthesis based on a heterocyclic azadiene Diels-Alder strategy (1,2,4,5-tetrazine to 2,2-diazine to pyrrole) was employed by the author for the total synthesis of ningalin B . Thus a Diels-Alder reaction of the electron-rich acetylene 52 with the electron deficient 1,2,4,5-tetrazine 53 proceeded to give the desired diazine 54 which underwent subsequent ring contraction to afford the core pyrrole structure 55. 

Few examples of the preparation of six-membered heteroaromatic compounds using Fischer-type carbene complexes have been reported [224,251,381]. One intriguing pyridine synthesis, reported by de Meijere, is sketched in Figure 2.35. In this sequence a (2-aminovinyl)carbene complex first rearranges to yield a complexed 1 -azadiene, which undergoes intermolecular Diels-Alder reaction with phenylacetylene. Elimination of ethanol from the initially formed adduct leads to the final pyridine. 

Boger et al. reported the first total synthesis of ningaline D (282) starting from the diphenylacetylene 1092 and dimethyl l,2,3,4-tetrazine-3,6-dicarboxylate (1093) (687). In this synthesis, the key step is the formation of the fully substituted pyrrole core using an inverse electron demand heterocyclic azadiene Diels-Alder reaction followed by a reductive ring contraction of the resultant 1,2-diazine. 

In recent years heterodienes, in particular azadienes, have become a useful tool for construction of heterocyclic compounds. In fact, their application toward natural product synthesis through pericyclic processes has been reviewed and their great potential in the field of the alkaloid... 

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