Diels-Alder reaction, with azadienes

Cycloadditions The Diels-Alder and the Alder ene reactions [3,3] and [2,3[Sigmatropic rearrangements the aza Cope rearrangement Other pericyclic processes giving nitrogen heterocycles Part II- Cycloadditions to Make Nitrogen Heterocycles Diels-Alder Reactions with Azadienes... 

Problems with the Diels-Alder reactions with azadienes Stable 1-azadienes... 

Intramolecular Diels-Alder Reactions with Azadienes... 

Tungsten alkynyl Fischer carbene complexes are excellent dienophile partners in the classical Diels-Alder reaction with 1-azadienes (see Sect. 2.9.2.1). On the contrary, the chromium-derived complexes exhibit a different behaviour and they react through a [4S+3C] heterocyclisation reaction to furnish azepine derivatives [116] (Scheme 68). The reaction is initiated by a 1,2-addition of the nitrogen lone pair to the carbene carbon followed by a [l,2]-Cr(CO)5 shift-pro-... 

An interesting parallel was found while the microwave-enhanced Heck reaction was explored on the C-3 position of the pyrazinone system [29]. The additional problem here was caused by the capability of the alkene to undergo Diels-Alder reaction with the 2-azadiene system of the pyrazinone. An interesting competition between the Heck reaction and the Diels-Alder reaction has been noticed, while the outcome solely depended on the substrates and the catalyst system. Microwave irradiation of a mixture of pyrazinone (Re = H), ethyl acrylate (Y = COOEt) and Pd(dppf)Cl2 resulted in the formation of a mixture of the starting material together with the cycloaddition product in a 3 1 ratio (Scheme 15). On the contrary, when Pd(OAc)2 was used in combination with the bulky phosphine ligand 2-(di-t-butylphosphino)biphenyl [41-44], the Heck reaction product was obtained as the sole product. When a mixture of the pyrazinone (Re = Ar) with ethyl acrylate or styrene and Pd(dppf)Cl2 was irradiated at 150 °C for 15 min, both catalytic systems favored the Heck reaction product with no trace of Diels-Alder adduct. 

Azadienes undergo Diels-Alder reactions to form pyridine, dihydro- and tetrahydropyridine derivatives. N-Vinyl lactim ethers undergo Diels-Alder reactions with a limited set of dienophiles. " Thioketones react with dienes to give Diels-Alder cycloadducts. The carbonyl group of lactams have also been shown to be a dienophile. Certain heterocyclic aromatic rings (among them furans) can also behave as dienes in the Diels-Alder reaction. Some hetero dienes that give the reaction are -C=C-C=0, 0=C-C=0, and N=C-C=N. ... 

Microwave irradiation at solvent-free conditions induces pyrazoyl 2-azadienes to undergo Diels-Alder reactions with nitroalkenes, within 5-10 min good yields of pyrazolo[ 3,4-b pyridine s are obtained (see Eq. 8.25).39 Without irradiation the reaction produces only traces of products on classical heating. 

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. 

This procedure describes the preparation of an electron-deficient heterocyclic azadiene suitable for use in inverse electron demand (LUMOd gpg controlled) Diels-Alder reactions with electron-rich dienophiles. 

The benzoxazoles 59 and 60 can act as azadienes in Diels-Alder reactions with nucleophilic alkenes such as vinyl ethers <98JCS(P1)3389>. ... 

Bis-silyloxy-3,4-dihydropyridines are stable dienes easily synthesized from glutarimide. The Diels-Alder reaction of azadiene 47 with iV-methylmaleimide in benzene at 60 °C gives predominantly the endo-adduct 48, whereas the selectivity is reversed in reaction with lithium trifluoromethanesulfonimide in ether giving predominantly the < vo-adduct 49 (Scheme 12) <1995SL565>. When methyl acrylate is used as the dienophile, the reaction... 

Diels-Alder reactions pyrrolesThis azadiene undergoes [4 + 2] cycloaddi-non with unactivated dienophiles to form dimethyl l,2-diazine-3,6-dicarboxylates, hich are reduced by zinc in acetic acid with ring contraction to dimethyl pyrrole-1.5-dicarboxylates. 

Employment of pyrido[3,4-d]pyridazine derivatives (18) as azadienes in inverse electron-demand Diels-Alder reactions with 1-pyrrolidino-l-cyclopentene, or its six-membered homologue, provides a good route to the isoquinolines (19) after aromatization of the dihydroisoquinoline intermediates (Equation (2)) <92TL7173>. 

Five-membered heteroaromatic systems that possess an electron-deficient azadiene substructure, e.g., oxazoles and thiazoles, are suitable for participation in Diels-Alder reactions with inverse electron-demand [49JA3062 59JA4342 62AG(E)329]. The introduction of strongly electron-donating substituents in many cases is sufficient to overcome the electron-deficient nature of the azadiene moiety and permits normal HOMO diene/ LUMO dienophile controlled Diels-Alder reactions (87MI6). 

Diels-Alder reactions 1,2,4-triazines. The electron-deficient azadiene system present in 1 can undergo Diels-Alder reactions with electron-rich dienophiles to give an adduct that loses nitrogen to provide 1,2-diazines. Reactions with imidates (>C=NH) substituted with an active leaving group such as SCH, proceed at moderate temperatures to afford 1,2,4-triazines in high yield (equation I). 

A synthesis of streptonigrin (5), an antitumor antibiotic, depends on two sequential Diels-Alder reactions of azadienes, reaction of 1 with an S-methyl thioimidate to give the 1,2,4-triazine 2, and reaction of 2 with a morpholinoenamine (3) to afford 4 (Chart I). ... 

Oxazoles represent the most widely recognized heteroaromatic azadiene capable of [4 + 2] cycloaddition reactions. The course of the oxazole Diels-Alder reaction and the facility with which it proceeds are dependent upon the dienophile structure (alkene, alkyne), the oxazole and dienophile substitution, and the reaction conditions. Alkene dienophiles provide pyridine products derived from fragmentation of the [4 + 2] cycloadducts which subsequently aromatize through a variety of reaction pathways to provide the substituted pyridines (Scheme 14). In comparison, alkyne dienophiles provide substituted fiirans that arise from the retro Diels-Alder reaction with loss of R CN from the initial [4 + 2] cycloadduct (Scheme 15,206 Representative applications of the [4 + 2] cycloaddition reactions of oxazoles are summarized in Table 14. Selected examples of additional five-membered heteroaromatic azadienes participatiitg in [4 + 2] cycloaddition reactions have been detailed and include the Diels-Alder reactions of thiazoles, - 1,3,4-oxadiazoles, isoxazoles, pyrroles and imidazoles. ... 

Pyridine annelation.1 1,2,4-Triazine can function as a reactive azadiene in Diels-Alder reactions with enamines, particularly pyrrolidine enamines, to form substituted pyridines. 

Diels-Alder reactions with A-methyl anilines as azadienes 02H(57)1525. 

The preparation or in situ generation of azabutadienes bearing a formal positive charge, i.e. an im-monium cation, provides a substantial enhancement of the electron-deficient character of the azadiene and in many instances such systems have proven to be effective 41 components in Diels-Alder reactions with electron-rich or neutral dienophiles. The most widely recognized class of cationic azadienes shown... 

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