Fused indoles Diels-Alder cycloaddition

The furo[3,4-h]indole analogs serve as fused indolo-2,3-qumodimethanes and have been widely used in Diels-Alder cycloaddition reactions. Recent publications have reviewed the various methods developed for the synthesis of furo[3,4-b]indoles [126], as well as the pioneering work on the utility of these precursors in cycloaddition reactions to produce various heterocychc derivatives [127]. The early application of [4-1-2] cycloaddition reactions with furo[3,4-b]indoles to the synthesis of natural products was highlighted by the first regioselective Diels-Alder synthesis of ellipticine (385), which involved a cycloaddition reaction of the furoindole 382 with a dihydropyridone derivative 381 as the key step (Scheme 86) [128]. 

The chiral holmium(III)-complex-catalysed Diels-Alder cycloaddition of siloxyvinylindoles (70) with e-deficient olefins (71) formed exo-substituted hydro-carbazoles (72) in up to 99% yield and 94% ee. Alkylation of these cycloadducts gave tricyclic compounds (73) with four continuous chiral centres (Scheme 20). The thermal 4-i-2-cycloaddition reaction of 7-substituted 4-styrylcoumarins with A-phenylmaleimide and tetracyanoethylene in nitrobenzene yielded 3,4-annulated coumarins. The thermal Diels-Alder cycloaddition of ( )-l,3-dihydro-3-phenacylidene-2//-indol-2-ones (74) with l,2-dihydro-2-oxospiro[3//-indole-3,2 -[2H,9a//-pyrido[2,l-fe][l,3]oxazines]] (75) produced complex dispirooxindoline fused [l,3]oxazines (76) with high regio- and stereo-selectivity (Scheme 21). " ... 

A set of Diels-Alder reactions of fused pyran-2-ones with ethyl vinyl ether (an appropriate synthetic equivalent of acetylene) gave fused carbocyclic systems. DABCO was used as a catalyst for the elimination of ethanol under microwave irradiation (Juranovic et al., 2012). The Diels-Alder cycloaddition reaction in 3-nitro-l-(p-toluenesulfonyl)indole with dienes under microwave irradiation in solvent-free conditions gave carbazole derivatives after elimination of the nitro group and in situ aromatization (Victoria et al., 2009). 

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). 

Utilizing an alternate mode of Diels-Alder reactivity, Harman has examined the cycloaddition reactions of 4,5-T -Os(II)pentaammine-3-vinylpyrrole complexes with suitably activated dienophiles <96JA7117>. For instance, cycloaddition of the p-vinylpyrrole complex 58 with 4-cyclopentene-l,3-dione, followed by DDQ oxidation affords 59, possessing the fused-ring indole skeleton of the marine cytotoxic agent, herbindole B. 

Easily prepared from glycols, enones have been investigated as dienophiles. They react with butadiene under Lewis acid catalysis to form chiral cyclohexenes used in the synthesis of compactin analogs [353]. Levoglucosenone has been used in a Diels-Alder reaction with acetoxy-butadiene to construct a part of the indole alkaloid reserpine [354], and in synthetic studies toward tetrodotoxin [355]. Analogs of the anthracycline rhodomycinone have been similarly prepared [356]. [4 + 2]-Cycloaddition of the same enone with silyloxydiene allowed the creation of the fused ring system present in actinobolin [357]. 

A formal [4h-2] cycloaddition between arylidenoxin-doles and ethyl allenoate afforded dihydropyran-fused indoles, as shown by Wang and colleagues (Scheme 10, equation 1) [67]. Density functional theory (DFT) implicates a stepwise mechanism. A not-unrelated synthesis of indole-annulated dihydropyrano[3,4-c]chromenes via a hetero-Diels-Alder reaction was discovered by Jha and colleagues (equation 2) [68]. The requisite precursors 26... 

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