Solvent Effects in Thermal (2+2) Cycloaddition Reactions. Intramolecular Capture of 1,4-Dipolar Intermediates vs. (2+2) Cycloaddition in Reactions of 3-(1-Pyrrolidinyl)thiophenes with Electron-Deficient Acetylenes

Article abstract of DOI:10.1021/jo00315a038

3-(1-Pyrrolidinyl)thiophenes (1) react as "pseudo" enamines with electron-deficient acetylenes, such as dimethyl acetylenedicarboxylate (DMAD), dicyanoacetylene, and methyl propiolate.In apolar solvents with DMAD (2+2) cycloadducts are formed.These cycloadducts (2) isomerize under the reaction conditions to yield thiepins (3), which are also thermally unstable and eliminate sulfur via the isomeric norcaradienes (4) to give the benzene derivates (5), the isolated products.In protic polar solvents with DMAD, 6,7,7a,8-tetrahydro-5H-thieno<2,3-b>pirrolizines (6) are formed by intramolecular abstraction of hydrogen, or deuterium in specifically labeled 1d, in the initially formed 1,4-dipolar intermediate.In aprotic polar solvents the two modes of reaction compete and in these solvents and with excess of DMAD present, thiophenol derivatives (12) and a 4H-1-benzothia-pyran-4-one (13) were also isolated.Compounds 12 and 13 arise from S-alkylation of the thianorcaradienes (4), the valence isomers of the thiepins (3), by DMAD.The structures of the 5H-thieno<2,3-b>pyrrolizine 6e and the thiophenol derivatives 12d (E isomer) were proven by single-crystal X-ray analyses.A 1,4-dipolar intermediate formed from 1d and DMAD in acetonitrile has been intercepted by phenyl isocyanate; the 1:1:1 reaction product was obtained in 15percent yield.Dicyanoacetylene reacts with 1f in apolar solvent (CH2Cl2) to give a 6,7,7a,8-tetrahydro-5H-thieno<2,3-b>pyrrolizine (17).Methyl propiolate and 1d and DMAD and 4-(4-morpholinyl)-2-phenylthiophene afford linear Michael adducts (19 and 20, respectively) in methanol.