Radicals Derived from S-4-Pentynyl Carbamothioates. under Tin-Free Conditions

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1 Generation and Cyclization of Unsaturated Carbamoyl Radicals Derived from S-4-Pentynyl Carbamothioates under Tin-Free Conditions Luisa Benati,* Giorgio Bencivenni, Rino Leardini, Matteo Minozzi, Daniele Nanni, Rosanna Scialpi,* Piero Spagnolo,* and Giuseppe Zanardi Dipartimento di Chimica Organica "A. Mangini", Università di Bologna, Viale Risorgimento 4, I Bologna, Italy Supporting Information Table of contents: Pages S2-S3. Experimental procedures. Page S4. Table with the complete results of the reactions of carbamothioates 1a-k. Page S5. References. S1

2 General remarks. All melting points (Kofler melting point apparatus) are uncorrected. 1 H and 13 C NMR spectra were normally carried out in CDCl 3 solutions, using tetramethylsilane as the internal standard. Mass spectra were determined by the electron impact method (70 ev) or electron spray ionization (ESI). IR spectra were recorded in CHCl 3 solutions. Column chromatography was performed on ICN silica gel ( Å) by gradual elution with light petroleum (bp C)/diethyl ether and final elution with ethyl acetate/diethyl ether/methanol mixtures. The alkenylamines and 2-alkenylanilines used in this work were commercially available or prepared according to literature procedures. The primary amines were converted into the requisite N-benzyl/N-tosyl/N-Boc derivatives, which were all known compounds, by standard reactions with benzyl bromide, tosyl chloride, or di-tertbutyl carbonate. Preparation of the Pentynyl Carbamothioates 1a-k and 11. General Procedure. To a stirred solution of triphosgene (1.7 mmol) and pyridine (5 mmol) in benzene (5 ml) was slowly added, at room temperature and under a stream of nitrogen, a solution of appropriate N-benzyl-/N-tosyl-substituted alkenylamine or 2-alkenylaniline, N-Boc-allylamine, or N-tosyl-4-chloroaniline (5 mmol) in benzene (30 ml). The resulting mixture was stirred at room temperature until virtual disappearance of the starting substrate as monitored by TLC. After removal of excess benzene under reduced pressure, the crude carbamoyl chloride was dissolved in dichloromethane (3 ml) and directly added to DMAP (6.5 mmol) in dicloromethane (3 ml). This mixture was slowly treated, under a stream of nitrogen, with freshly prepared 4-pentyn-1-thiol 1 (7 mmol) in dichloromethane (4 ml) and then stirred at room temperature for 1-17 h, until TLC monitored reaction completion. The resulting crude mixture was treated with diethyl ether (ca 70 ml) to give a white precipitate, which was filtered off. The filtered organic layer was concentrated and the residue eventually subjected to column chromatography. The preparation of the N-tosyl-N-(2-vinylphenyl)carbamothioate 1f was similarly performed, except that the crude carbamoyl chloride was first treated with the pentynthiol in anhydrous dichloromethane at 0 C for 5 min and then additionally treated with DMAP at room temperature for 5 h. Overall yields of the produced carbamothioates 1a-k,11 amounted to 45-85%. S2

3 Reactions of Carbamothioates 1a-k,11 with Benzenethiol. General Procedure. A toluene (20 ml) solution of benzenethiol (1.1 mmol) was added by a syringe pump over ca 4 h to a refluxing solution of the appropriate carbamothioate (1 mmol) in toluene (40 ml) under a nitrogen atmosphere. ACCN (0.30 mmol) was also added in two equal portions within 1 h. The resulting reaction mixture was refluxed for a further 3-6 h, until the virtual disappearance of the starting substrate (TLC). After cooling to room temperature, the excess solvent was removed in vacuo and the crude eventually subjected to column chromatography. Yields of the separated reaction products are collected in Table 1. Structural assignments to known reaction products such as the (E)- and (Z)-dihydrothiophene 3, 1 the pyrrolidinones 4a, 2 4e, 3 and 4h, 4 the formamides 5a, 2a 5h, 5 5i, 2a and 5j, 2a the indolinones 6b, 6 6c, 7 and 6d, 8 the quinolinone 7, 9 and the azetidinones 13h, 2b 13i, 2a and 13j 2a were performed on the basis of reported physical and/or spectral data. The quinolinones 9f and 9g were consistent with commercial samples. S- Phenyl N-(4-chlorophenyl)carbamothioate 10 was characterized by comparison with a sample prepared by reacting 4-chlorophenyl isocyanate with benzenethiol. N-(2-isopropenylphenyl)-4- methylbenzenesulfonamide was characterized by comparison with an authentic sample. 11 S3

4 Table. Radical Reactions of Pentynyl Carbamothioates 1a-k with Benzenethiol. entry substrate Products (%) a 1 1a 4a(63), 5a(25), 3(88) b 2 1b 6b(67), 3(71) b 3 1c 6c(65), 7(16), 3(85) b 4 1d 6d(70), 3(77) b 5 1e 4e(57), 3(17), b 8(30) b 6 1f 9f(45), 3(15), b 8(29) b 7 1g 9g(50), 3(29), b 8(30), b c 8 1h 4h(21), 5h(55), 13h(12), 3(88) b 9 1i 5i(42), 13i(25), 3(81) b 10 1j 5j(30), 13j(32), 3(70) b 11 1k 13k(42), 3(70), b d a Yields isolated by column chromatography. b Mixture of (E)- and (Z)-isomer. c N-(2-isopropenylphenyl)- 4-methylbenzenesulfonamide (25%). d Minor amounts of a mixture of unidentified products. S4

5 References 1. Benati, L.; Calestani, G.; Leardini, R.; Minozzi, M.; Nanni, D.; Spagnolo, P.; Strazzari, S. Org. Lett. 2003, 5, (a) Bella, A. F.; Jackson, L. V.; Walton, J. C. Org. Biomol. Chem. 2004, 2, 421. (b) Scanlan, E. M.; Slawin, A. M. Z.; Walton, J. C. Org. Biomol. Chem. 2004, 2, Mizutani, T.; Ukaji, Y.; Inomata, K. Bull. Chem. Soc. Jpn. 2003, 76, Yang, Y. H.; Shi, M. J. Org. Chem. 2005, 70, Ciganek, E.; Schubert, E. M. J. Org. Chem. 1995, 60, Tagigawa, Y.; Ito, H.; Omodera, K. M.; Ito, T. Tetrahedron 2004, 60, Lee, S.; Hartwig, J. F. J. Org. Chem. 2001, 66, Tacconi, G.; Invernizzi, A. G.; Desimoni, G. J. Chem. Soc., Perkin Trans , Clark, A. J.; Jones, K.; McCarthy, C.; Storey, J. M. D. Tetrahedron Lett. 1991, 32, Crosby, D. G.; Niemann, C. J. Am. Chem. Soc. 1954, 76, Capozzi, G.; Ottana, R.; Romeo, G. Heterocycles 1986, 24, 583. S5