Diels-Alder cycloadditions heterocycle

Triazine (38) is ideal for inverse electron-demand Diels-Alder cycloadditions, for example, with azulene to give a l,4-bis(CF3)phthalazine (89CB711). A rare example of the synthesis of a five-membered heterocycle originating from [4 + 1] cycloaddition followed by [4 + 2] cycloreversion was reported using (38). The intermediate tetraazanorbomadienimine (39) is highly strained and eliminates N2 [82AG(E)284]. 

Padwa A. Application of Diels-Alder Cycloaddition Chemistry for Heterocyclic Synthesis Prog. Heterocycl. Chem. 1995 7 21-42... 

Microwave-assisted Diels-Alder cycloaddition reactions using water-soluble aquo-cobaloxime complexes have been reported by Welker and coworkers [198]. Many more examples of microwave-assisted cycloaddition processes leading to heterocycles are described in Section 6.24. 

Cycloaddition reactions of furans are still widely used as key steps in the construction of complex molecules including natural products. As an example, the intramolecular Diels-Alder cycloaddition of 2-amido substituted furans provides a useful tool for the synthesis of fused, nitrogen-containing poly-heterocycles. Thus, thermolysis of 3-substituted amidofuran produces tricyclic indolinone 39 as a 2 1 mixture of diastereomers via amidofuran cycloaddition-rearrangement methodology, which serves as a key intermediate in the total synthesis of ( )-dendrobine, a major component of the Chinese ornamental orchid Dendrobium nobile . 

A rapid access to carbocyclic nucleosides, containing a fused isoxazoline ring has been proposed, starting from cyclopentadiene. The route involves a het-ero Diels-Alder cycloaddition reaction of nitrosocarbonylbenzene followed by a 1,3-dipolar cycloaddition of nitrile oxides, cleavage of the N-0 tether and transformation of the heterocyclic aminols into nucleosides via construction of purine and pyrimidine heterocycles (457). 

Keywords Absolute configuration, Amines, Amino acids, Carbenes, Cascade reactions, 2-chloro-2-cyclopropylideneacetates. Combinatorial libraries. Cycloadditions, Cyclobutenes, Cyclopropanes, Diels-Alder reactions. Heterocycles, Michael additions. Nitrones, Nucleophilic substitutions, Peptidomimetics, Palladium catalysis. Polycycles, Solid phase synthesis, Spiro compounds. Thiols... 

Resin-bound 4/7-1,3-oxazines 115 were synthetized by the stepwise condensation of an amide resin 489, an aldehyde, and an alkyne. Formation of the oxazine ring took place in the presence of the catalyst BF3-Et20 via a hetero-Diels-Alder cycloaddition of the alkyne and the acyliminium 491 arising from the condensation of the amide and the aldehyde (Scheme 92). The quantitative efficacy of the process was determined by elemental analysis of a model system bearing a bromine atom on the aldehyde moiety (R =C6H4Br(p)), which indicated a 78% conversion for the heterocyclization <2001CEJ2318, 2004JC0846>. 

Although the number of Diels-Alder cycloadditions with open-chain and alicyclic dienes is very large, the number of examples with aromatic heterocyclic compounds is relatively small. The introduction of a vinyl group as a substituent onto a heterocycle increases the number of possibilities of reaction. This new possibility, however attractive for synthetic purposes, is successful, with a few exceptions, only with 7r-excessive five-membered heterocyclic derivatives. As is usual in this kind of reaction, Michael additions, ene reactions, [2 + 2]-cycloadditions, and polymerization compete with the Diels-Alder cycloaddition. 

The reaction of 2-vinylthiophene 59 with DMAD in benzene at reflux afforded four compounds 60-63. (85T2435). Compound 60 was the result of a Diels-Alder cycloaddition followed by aromatization. The adducts 61 and 62 are obtained by an ene reaction. The structure of compound 63 was unique for cycloadditions of vinyl heterocycles. 

The very reactive arynes have also been used as dienophiles in Diels-Alder cycloadditions with vinyl heterocycles and are included here, after the acetylenic esters, because of the similarity of their reactive functions. This reaction is of considerable importance because of its application in the synthesis of polycyclic compounds. 

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... 

Heterocyclic azadienes like di- and triazines have been used in the synthesis of pyridine rings. In general terms the reaction involves a regiospecific inverse electron demand Diels-Alder cycloaddition between the heterocycle and the enamine 280 followed by elimination of HCN (diazines) or N2 (triazines) and an amine from the primary cycloadduct 281 or 283, respectively, to give pyridines 282 and 284 (equation 61). At least in one case the latter type of intermediate has been isolated and fully characterized148. 

A multi-gram enantioselective synthesis of (+)-37, a key precursor to the tetracycline antibiotics, has been performed from simple heterocyclic compounds. Key steps in the route involve enantioselective addition of divinylzinc to 3-benzyloxy-5-isoxazolecarboxaldehyde (with 93% ee) for the preparation of 36 and, after its nucleophilic addition to 35, an intramolecular furan Diels-Alder cycloaddition <07OL3523>. 

The various heterocyclic ligands just described are easily cleaved from the respective molybdenum centers either by reaction with sulfur or through ligand exchange with l,2-bis(diphenylphosphino)ethane (Scheme 17).44a The Diels-Alder cycloaddition is successfully expanded to transient 1-phospha-1,3-diene complexes such as 25 and suitable dienophiles. As illustrated in Scheme 12, the isomeric 1,2-dihydrophosphetes (e.g., 26) are their masked stable precursors. Reaction of 26 with dimethyl acetylenedicarboxy-late or with benzaldehyde furnishes the Diels-Alder adducts of transient 25, compound 71, as a mixture of two isomers, and isomerically pure 72.44b (See Scheme 18.)... 

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-... 

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