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An approach to dihydroindoles and tetrahydroquinolines from N-alkenylated 2-acylamino-3-furancarbonitriles via a [4 + 2] cycloaddition reaction is described. Thermal treatment of N-alkenylated 2-acylamino-3-furancarbonitriles 5a-d, 6a-d, 9a-d, and 10a-d, which were prepared from 2-acylamino-3-furancarbonitriles 3a-d and/or 4a-d and 4-bromo-1-butene and/or 5-bromo-1-pentene, caused an intramolecular Diels-Alder reaction to give the corresponding dihydroindole and tetrahydroquinoline derivatives 7a-d, 8a-d, 11a-d, and 12a-d. This method has the advantage of easier work-up procedure.

The title compounds were prepared from 4,5-dihydro-3-furan- and -3-thiophene-carbonitriles having an active methylene group at C-2 position 1, 2, 7, and 8 as key starting materials. Compounds 1 and 2 condensed with N,N-dimethylformamide dimethyl acetal to give the corresponding enamines 3 and 4. This condensation was followed by exchange reaction of amines and subsequent intramolecular cyclization reaction in the presence of ammonium acetate to lead the corresponding furo- and thieno-[3,2-c]pyridines 5 and 6. On the other hand, the reactions of compounds 7 and 8 with amines such as aqueous ammonium hydroxide and benzylamine afforded the intermediate acetamide derivatives A, without isolation of them, which underwent intramolecular cyclization reaction in the presence of sodium methoxide to yield the corresponding furo- and thieno-[3,2-c]pyridin-6(2H)-ones 9-12.

A versatile strategy is described for the synthesis of new fused thiopyranthione and thiophene derivatives. The reaction of heterocyclic α,β-unsaturated nitriles 3a-c, 4a-d, 5a-c, and 6a-d, which were prepared from tetrahydro-2-oxo-3-thiophene- and -3-furan-carbonitriles 1a-c and/or 2a-d and alkylidene phosphoranes such as (triphenylphosphoranylidene)acetonitrile and methyl (triphenylphosphoranylidene)acetate through Wittig reaction, with carbon disulfide in the presence of sodium hydride in THF gave the corresponding 6-thioxothieno[3,2-c]thiopyran and 6-thioxothiopyrano[4,3-b]furan derivatives 7a-c, 8a-d, 9a-c, and 10a-d. On the other hand, treatment of compounds 3a-c, 5a-c, and 6a-d with sulfur powder in the presence of triethylamine in methanol caused Gewald reaction to provide the corresponding thieno[3,4-b]thiophene and - furan derivatives 11a-c,12a-c, and 13a-d.

A new and easy synthetic route to furo[2,3-b]furans 7a-d and furo[2,3-b]pyrroles 8a-d has been achieved by the C-phenacylation/cyclization reactions of 2-amino-4,5-dihydro-3-furancarbonitrile (5). Thermal treatment of the key intermediate 3-phenacylated tetrahydro-2-imino-3-furancarbonitriles 6a-d, which were prepared from compound 5 and phenacyl bromides, e.g. phenacyl bromide, 4-chlorophenacyl bromide, 4-methylphenacyl bromide and 4-methoxyphenacyl bromide, with acetic anhydride caused intramolecular cyclization to yield the corresponding furo[2,3-b]furans 7a-d. On the other hand, methanolic sodium methoxide-assisted cyclocondensation of compounds 6a-d gave the corresponding furo[2,3-b]pyrroles 8a-d.

An efficient Diels-Alder reaction is described in the furan series, leading to phthalimides in high yields. Thermal treatment of 2-(4-morpholinyl, 1-piperidinyl, and 1-pyrrolidinyl)-3-furancarbonitriles with maleimide derivatives, e.g. maleimide, N-methylmaleimide, N-benzylmaleimide, N-phenylmaleimide and N-(4-nitrophenyl)maleimide, in boiling acetic acid caused a [4 + 2] cycloaddition reaction to give the corresponding phthalimide derivatives.

A novel and efficient approach to 2-pyrrolidinones and dihydropyrans via the ring transformation of 3-phenacylated tetrahydro-2-imino-3-furancarbonitriles in the presence of sodium iodide is described. The key feature in the ring transformation is that C-phenacylation of 2-amino-4,5-dihydro-3-furancarbonitriles using phenacyl bromides, e.g. phenacyl bromide, 4-chlorophenacyl bromide and 4-methoxyphenacyl bromide, proceeds smoothly and the ring-opening intermediate having leaving group such as iodide ion is produced.

The ring opening of 2-acylamino-4,5-dihydro-3-furancarbonitriles with titanium (IV) chloride gave the corresponding N-acyl-4-chloro-2-cyanobutanamides (I). On treatment with potassium carbonate, compounds I were converted to the corresponding N-acyl-1-cyanocyclopropanecarboxamides . On the other hand, the reaction of 2-benzamido-4,5-dihydro-3-thiophenecarbonitriles with titanium (IV) chloride gave the corresponding 2-benzamido-4,5-dihydro-3-thiophenecarboxamides.