Synthesis of Heteroaromatic Compounds with "Enamine" Reactivity

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

“…The necessary 5-substituted 3-(lpyrrolidinyl)thiophenes were prepared via the tetrahydrothiophen-3-ones by methods described previously. 39 The reactivity of la-d with dimethyl acetylenedicarboxylate (DMAD) at room temperature in apolar solvents such as diethyl ether and tetrachloromethane was shown to be similar to that of the parent 3-(l-pyrrolidinylHhiophene.30 Complete conversion at 25 °C of starting materials (la-d) took less than 1 h and the corresponding benzene derivatives (5a-d) were isolated in yields of 35-77%. However, the reaction of lc with DMAD in tetrachloromethane at room temperature was sufficiently retarded to allow permanent monitoring of the characteristic singlet absorptions of lc ( -2 5.51), 2c ( -4.28), 3c ( _2 6.34), and 5c (5H-arom 6.86 and 7,12) in the NMR spectrum of the reaction mixture (Figure 1).…”

“…Preparation of 3-(l-PyrrolidinyI)thiophenes 1. Compounds la, Id, and lf-h were prepared as described previously. 39 2-(l-Methylethyl)-4-(l-pyrrolidinyl)thiophene (lb) (1-[5-(l-methylethyl)-3-thienyl]pyrrolidine) was prepared in a multistep synthesis starting from 4-methyl-2-pentenoic acid.68,69 Addition of mercaptoacetic acid to 4-methyl-2-pentenoic acid in a manner as described before39 afforded 3-[(carboxymethyl)thio]-4-methylpentanoic acid (65%) as a yellow oil, bp 190-195 °C (0.4 torr), and ring closure yielded 4,5-dihydro-5-(l-methylethyl)-3(2R)-thiophenone (70%), bp 94-98 °C (15 torr). The corresponding oxime was prepared by refluxing the ketone with an excess of hydroxylamine hydrochloride and barium carbonate in methanol during 4 h (95%), mp 30-35 °C.…”

ChemInform Abstract: SYNTHESIS OF HETEROCYCLES BY THERMAL (2+2)‐CYCLOADDITION REACTIONS OF ACETYLENES

“…When we carried out the same reactions in the presence of equimolar amounts of a l m inun chloride the major product was a (2+2)-cycloadduct (1-3, scheme 5). 14 14 15 13 16 17 18…”

l-Proline-Catalyzed Three-Component Domino [3+2+1] Annulation for the Regio- and Diastereoselective Synthesis of Highly Substituted Thienothiopyrans Containing Three or Four Stereocenters

“…Supporting Information Available: Experimental procedures, analytical data, structural study of compounds 4a, 4b, and 14 by NMR, X-ray crystallographic determination of compounds 4a and 9a, copies of chiral chromatogram of 4a, and 1 H, 13 C, and 2D NMR spectra of new compounds. This material is available free of charge via the Internet at http:// pubs.acs.org.…”

“…Stirring at room temperature for 24 h a solution of ethyl 2-[(2-oxo-2-arylethyl)sulfonyl]acetate or ethyl 2-[(2-ethoxy- 2-oxoethyl)sulfonyl]acetate 1 , a 5-aryltetrahydro-3-thiophenone derivative 2 (R 2 = Ar), and an aromatic aldehyde 3 in an equimolar ratio in the presence of l -proline (50 mol %) in methanol furnished the thieno[3,2- c ]thiopyran derivatives 4 − 13 , bearing four stereocenters, in 49−79% yields as mixtures of two diastereomers in ca . 7/3 ratio (Scheme , Table ).…”