Vinyl heterocycles, cycloaddition reactions with

Veda-Arques J. S., Abarca-Gonzalez B., Medio-Simon M. Cycloaddition Reactions With Vinyl Heterocycles Adv. Heterocycl. Chem. 1995 63 339-401 Keywords azadienophiles, intramoiecuiar Dieis-Aider reactions... 

J. Sepulveda-Arques, B. Abarca-Gonzalez, and M. Medio-Simon (Valencia, Spain) contributed the last chapter, Cycloaddition Reactions with Vinyl Heterocycles which centers on their Diels-Alder and competing reactions. 

Sepulveda-Arques, J., Abarca-Gonzalez, B., Medio-Simon, M., Cycloaddition Reactions with Vinyl Heterocycles, 63, 339. 

Heterocyclic systems with one heteroatom. Condensed heteroaromatic cations are reactive in [2 + 4] cycloaddition reactions with inverse electron demand. For instance, 2-benzopyrylium salts 403 react with vinyl ethyl ether to afford naphthalene derivatives 405 in good yields via initial adducts 404 <1990KGS315>. Similar transformations (Bradsher reaction) are also known for isoquinolinium salts <1984CC761>. 

Cycloaddition, ring-opening, and other novel reactions of thiophenes, Iddon, B., Heterocycles, 1983, 20, 1127 Cycloaddition reactions with vinyl heterocycles , Sepiilveda-Arques, J., Abarca-Gonzalez, B., and Medio-Simon, Adv. Heterocycl. Chem., 1995, 63, 339. 

Several vinyl isocyanates undergo a [4+2] cycloaddition reaction with benzyne. For example, from benzyne and the vinyl isocyanate 498, the heterocycle 499 is obtained in 58 % yield 529. 

Benzo[Z)]furans and indoles do not take part in Diels-Alder reactions but 2-vinyl-benzo[Z)]furan and 2- and 3-vinylindoles give adducts involving the exocyclic double bond. In contrast, the benzo[c]-fused heterocycles function as highly reactive dienes in [4 + 2] cycloaddition reactions. Thus benzo[c]furan, isoindole (benzo[c]pyrrole) and benzo[c]thiophene all yield Diels-Alder adducts (137) with maleic anhydride. Adducts of this type are used to characterize these unstable molecules and in a similar way benzo[c]selenophene, which polymerizes on attempted isolation, was characterized by formation of an adduct with tetracyanoethylene (76JA867). 

It was shown <1998CCC681> that [l]benzothieno[3,2-3]furan 60, due to its low furan aromaticity, possesses dienophilic behavior and reacts with electron-rich dienes with the formation of a new heterocyclic system [l]ben-zothieno[3,2-3][l]benzofuran 93. Furthermore, it was reported <1999CCC389> that introduction of a vinyl moiety at C-2 of 57 created a reactive diene 94, which reacted with various dienophiles. Thus, both cycloaddition reactions led to new derivatives of heterocycle 93 substituted in the benzofuran part of the heterocyclic system (Scheme 10). 

From the synthetic viewpoint, a particularly interesting trifluoroacetylation reaction of simple vinyl ethers was reported first by Hojo et al in 1976 [73] The scope and limitation of this particular reaction were elaborated intensively, the reaction proved to be of general applicability with practically no restrictions on substituents of the vinyl ether moiety 9] (equation 34) This general validity is particularly beneficial because a trifluoroacetylated vinyl ether is the synthetic equivalent of a specifically protected tnfluoromethyl-substituted 1,3-dicarbonyl compound 19], thus the reaction provides access to a broad spectrum of variously substituted synthetic building blocks with selective reactivities on each carbon acceptor (a) and donor (d) center (equation 35) Obviously, such building blocks can react as heterodiene systems m cycloaddition reactions [< 74] or can be treated with a wide variety ot 1,2 or 1 3-dinucleophihc species to give any desired tnfluoromethyl-substituted carbocychc or heterocyclic system [8 75] Treatment of simple vinyl ethers with an excess of trifluoroacetic anhydride at elevated temperature leads to doubly acylated products [76] Comparable acylation reactions occur with vinyl thioethers [73], and the mesoiomc l,3-oxathiol-4-ones show, at least in a formal sense, similar behavior [77] (equation 36)... 

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. 

The reaction of 2- and 3-vinylindoles with dienophile 214 constitutes the first example of an asymmetric Diels-Alder reaction of vinyl heterocycles. From 3-vinylindoles, enantiomerically pure carbazoles 215a-c were obtained, whereas from the vinylindole 197 together with 215d, diastereomer 216 was obtained as a minor product. Conversely, 2-vinylindoles provided inseparable mixtures of diasteromeric carbazoles. On the other hand, the cycloaddition reactions of 3-vinylindoles with 217 furnish the tetrahy-drocarbazoles 218 with endo-diastereoselectivity (93T2863). 

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