Pyridinones cycloaddition

In another paper, the same authors investigated the 1,3-dipolar cycloaddition on 2-(lH)-pyrazine scaffolds 72 and electron-rich azides, using Cu(0) and CUSO4 as pre-catalysts. To demonstrate the versatility of this approach, they reported the generation of different templates (73 in Scheme 25) as an application of cUck chemistry . They also investigated the Diels-Alder reaction of the so obtained triazoles with dimethyl acetylenedicarboxylate (DMAD), under microwave irradiation. The latter reaction allowed obtaining various pyridinones in good yields (74 and 75 in Scheme 25) [57]. 

Van der Eycken and coworkers have presented a study describing the microwave-assisted solid-phase Diels-Alder cycloaddition reaction of 2(lH)-pyrazinones with dienophiles [69]. After fragmentation of the resin-bound primary cydoadduct formed by Diels-Alder reaction of the 2(lH)-pyrazinone with an acetylenic dieno-phile, separation of the resulting pyridines from the pyridinone by-products was achieved by applying a traceless linking concept, whereby the pyridinones remained on the solid support with concomitant release of the pyridine products into solution (Scheme 7.58). 

Intermolecular cycloadditions involving pyridinones are well known (80H(14)1793). 4-Cyano-l-methylpyridin-2-one undergoes Diels-Alder reaction with a suitable diene (equation 195) (79H(12)l). The pyridinone (307) forms 1 1 and 1 3 adducts on reaction with DMAD under pressure (Scheme 225) (82H(19)499). 2-Azabarrelenone (308) may be prepared by a sequence (Scheme 225), the first step of which is the addition of maleic anhydride to l-benzylpyridin-2-one (80AG(E)463). 

Cycloadditions of Enones and Pyridinones. When the carbonyl group is conjugated to a C=C double bond, cycloaddition takes place at that double bond and a new ketone is formed. These reactions are fairly general with enones and their derivatives, as illustrated in Figure 4.54. The cyclobutane products are often useful synthetic intermediates. 

Figure 4.54 Cycloaddition of olefins to enones and pyridinones. Z=CH (enone) or NR (pyridinone)...

Mesoionic compounds may undergo 1,3-dipolar cycloaddition reactions. Thus anhydro-1 -hydroxythiazolo[3,2-a]guinolinium hydroxide (396) is a substrate for the reaction with DMAD. The formation of the pyrrolo[l,2-a]quinoline (397) from this reaction involves COS elimination from the initial adduct. Ethyl propiolate also reacts in the same fashion. The orientation in the cycloadduct can be arrived at from the ylide form (396a). With fumaronitrile, however, the fused pyridinone (398) is formed by loss of sulfur from the primary cycloadduct (78JOC2700). 

Numerous structures containing the thiocarbonyl ylide dipole are conceivable. Incorporation of the thiocarbonyl ylide dipole into a bicyclic heterocyclic system is possible by the conversion of the cyclic thione (203) into the ring-fused mesoionic system (204). The thiocarbonyl ylide dipole (205) undergoes cycloaddition with both alkenic and alkynic electron-poor dipolarophiles in refluxing benzene or xylene so that, after extrusion of hydrogen sulfide or sulfur, respectively, from the initial 1 1 cycloadducts (206) and (207), a ring-fused pyridinone is formed. The method has been used for the annelation of pyridinones to the imidazole, 1,2,4-triazole, thiazole and 1,3,4-thiadiazole systems... 

Pyridinones have been obtained by reaction of malononitrile with some enamines of 1-tetralone178, and 2-pyridinones 313 were obtained by 1,4-dipolar cycloaddition... 

The photoaddition of methyl acrylate to pyridones (49) gave the three [2 + 2] cycloaddition products (50), (51), and (52).Similar observations have been reported previously.A patent has been lodged which deals with the photoad-dition of alkenes (RCH=CH2 R = H, CN, or MeC02CH2) to the pyridones (53) to yield the adducts (54) and (55). The photocycloaddition of vinyl acetate to the pyridinones (56) affords the head-to-tail adducts (57) preferentially. ... 

Ring-fused mesoionic anhydro triazolium hydroxide systems 131 (84M11) that incorporate the thiocarbonyl ylide dipole undergo cycloaddition with both olefinic and acetylenic dipolarophiles the unstable 1 1 cycloadducts 132 and 133 yield ring-fused a-pyridinones 134 by elimination of hydrogen sulfide or sulfur, respectively (Scheme 42) (79JOC3803). 

Similarly, the planar chiral tricarbonylchromium complexes of ortho substituted benzaldimines are useful for a variety of stereoselective cycloaddition reactions. For example, the benzaldimine chromium complexes gave aza-Diels-Alder product, 2,3-dihydro-4-pyridinone chromium complexes with high diastereoselectivity by reaction with Danishefsky s diene (Eq. 18) [11,17,18]. The high diastereoselectivity of the cycloadducts is also based on the preferred antz-conformation of the starting benzaldimine chromium complexes as well as the planar chiral benzaldehyde chromium complexes. The cycloaddition of imines having arene chromium complex at the remote position with Danishefsky s diene underwent smoothly in good yields, but the diastereoselectivity was low (Eq. 19) [17]. 

The synthesis of optically active thiazolo[3,2-fl]pyridinones has been described. Chiral thiazolines 27, prepared from the condensation of imino ethers 25 with (R)-cysteine methyl ester 26, undergo a ketene-imine cycloaddition reaction with Meldrum s acid derivatives 28 to give thiazolo[3,2-a]pyridinones 29 in good yields <01JOC6756>. 

In 2000, a selective cycloaddition of cyclopropyl imines, derived from cyclopropyl phenyl ketone and tert-butylamine and CO (2 bar), was developed by the same group (Scheme 1.5) [16]. The reaction was allowed to proceed in toluene (3 ml) in presence of a catalytic amount of Ru3(CO)j2 (0.02 mmol) at 160°C for 60 h, giving the pyridinone derivative in 76% isolated yield. 

Danishefsky s diene and imines to produce l,2-dialkyl-2,3-dihydro-4-pyridinones in high yields. Chiral non-racemic 2,5-diketopiperazine diene undergoes intermolecular hetero-Diels-Alder cycloaddition reactions with both c-rich and e-deficient alkene dienophiles, leading to bicyclo[2.2.2]diazaoctane structures. The regiochemical, stereoelectronic, and reactivity preferences of the diketopiperazine cycloadditions were investigated. ... 

The reaction of (chlorocarbonyl)phenylketene 126 with enaminones takes place effectively in refluxing toluene, furnishing a facile and rapid synthesis of 4-hydroxy-3,4,6-trisubstituted-2(lfJ)-pyridinone 346 in high yield via ring closure of intermediates 344—345 (Scheme 107) (2009JHC96). On the other hand, the cycloaddition of 4-[(2-aminoethyl) amino]-3-penten-2-one 347 with 126 led to the generation of ethyl... 

While the replacement of an alkyne against an olefin unit in the transition-metal-mediated [2 -I- 2 -I- 2] cycloaddition widens the scope of its applicability to more complex carbo- and/or heterocyclic structures, the same accounts for the formal replacement of an alkyne against a heterocumulene moiety [60]. However, as such a strategy led to the development of new concepts for the construction of heterocyclic compounds (i.e., the formation of 2-pyridinones via the [2- -2-1-2] cycloaddition reaction of alkynes with isocyanates [61]), the application in the field of total synthesis is still at its infancy and so is limited to a few examples. 

Although in principle the thermal [2-I-2-I-2] cycloaddition process is allowed by orbital symmetry rules, there are problems with the entropy component, which may be overcome by using transition metal catalysis. This approach (Scheme 2.35) is one of the most convenient for the synthesis of pyridines 2.100. Metal-induced cycloaddition of two alkyne and one nitrile molecules has been described in general reviews of cycloaddition reactions [3,4]. However in some reviews on heterocycles the nitriles are considered as equivalent to alkyne in the [2+2+2] cyclotrimerization reaction [76], in particular, for the synthesis of pyridines and pyridinones in the reactions catalyzed by cobalt, ruthenium, titanium, and zirconium. 

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