Synlett, Table of Contents Synlett 2014; 25(12): 1697-1700DOI: 10.1055/s-0034-1378203 letter © Georg Thieme Verlag Stuttgart · New YorkConvenient Access to Cycloalk-2-enone-Derived N-Sulfonyl Imines Sebastian Hirner Fachbereich Chemie, Philipps-Universität Marburg, Hans-Meerwein-Straße, 35032 Marburg, Germany Fax: +49(6421)2825362 Email: zezschwitz@chemie.uni-marburg.de , Johannes Westmeier Fachbereich Chemie, Philipps-Universität Marburg, Hans-Meerwein-Straße, 35032 Marburg, Germany Fax: +49(6421)2825362 Email: zezschwitz@chemie.uni-marburg.de , Sandra Gebhardt Fachbereich Chemie, Philipps-Universität Marburg, Hans-Meerwein-Straße, 35032 Marburg, Germany Fax: +49(6421)2825362 Email: zezschwitz@chemie.uni-marburg.de , Christian H. Müller Fachbereich Chemie, Philipps-Universität Marburg, Hans-Meerwein-Straße, 35032 Marburg, Germany Fax: +49(6421)2825362 Email: zezschwitz@chemie.uni-marburg.de , Paultheo von Zezschwitz* Fachbereich Chemie, Philipps-Universität Marburg, Hans-Meerwein-Straße, 35032 Marburg, Germany Fax: +49(6421)2825362 Email: zezschwitz@chemie.uni-marburg.de› Author AffiliationsRecommend Article Abstract Buy Article All articles of this category Abstract The first synthesis of N-tosyl imines from various cyclopent-2-enones and cyclohex-2-enones was achieved by direct condensation with tosyl amide in the presence of TiCl(OEt)3 and Et3N. In addition, N-tert-butylsulfonyl imines from five- to seven-membered cycloalk-2-enones were obtained through formation of the respective oximes and subsequent Hudson reaction. These compounds are easy to handle solids and they are interesting starting materials for a variety of transformations. Key words Key wordscondensation - enones - imines - titanium - sulfonamides Full Text References References and Notes 1a Weinreb SM. Top. Curr. Chem. 1997; 190: 131 1b Shukla DK. Synlett 2009; 1859 1c Kobayashi S, Mori Y, Fossey JS, Salter MM. Chem. Rev. 2011; 111: 2626 1d Monbaliu J.-CM, Masschelein KG. R, Stevens CV. Chem. Soc. Rev. 2011; 40: 4708 2 For a calculation of the LUMO energies of benzaldehyde and various derived imines, see: Charette A. In Chiral Amine Synthesis . Nugent TC. Wiley-VCH; Weinheim: 2010: 1-49 3a Vishwakarma LC, Stringer OD, Davis FA. Org. Synth. 1988; 66: 203 3b Jennings WB, Lovely CJ. Tetrahedron 1991; 47: 5561 3c Love BE, Raje PS, Williams TC. Synlett 1994; 493 3d Ram RN, Khan AA. Synth. Commun. 2001; 31: 841 3e Lee KY, Lee CG, Kim JN. Tetrahedron Lett. 2003; 44: 1231 For alternative approaches, see: 4a Albrecht R, Kresze G, Mlakar B. Chem. 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Lett. 2005; 7: 179 10b Yang Q, Shang G, Gao W, Deng J, Zhang X. Angew. Chem. Int. Ed. 2006; 45: 3832 10c Chen S, Zhao Y, Wang J. Synthesis 2006; 1705 11a Siewert J, Sandmann R, von Zezschwitz P. Angew. Chem. Int. Ed. 2007; 46: 7122 11b Kolb A, Hirner S, Harms K, von Zezschwitz P. Org. Lett. 2012; 14: 1978 11c Kolb A, Zuo W, Siewert J, Harms K, von Zezschwitz P. Chem. Eur. J. 2013; 19: 16366 11d Westmeier J, Pfaff C, Siewert J, von Zezschwitz P. Adv. Synth. Catal. 2013; 355: 2651 12a McMahon JP, Ellman JA. Org. Lett. 2005; 7: 5393 12b Sirvent JA, Foubelo F, Yus M. Chem. Commun. 2012; 48: 2543 13 The E/Z configuration of imines 2 was assigned based on NOE signals between the aromatic protons and either the proton(s) at C-6 or C-2, respectively. Moreover, the proton(s) at either C-6 or C-2 are deshielded in the case of (E)-2a or (Z)-2a, respectively. 14 Lin Y.-D, Kao J.-Q, Chen C.-T. Org. Lett. 2007; 9: 5195 15 Acyclic aliphatic enones such as butenone or (E)-5-methylhex-3-en-2-one decomposed under these conditions. For a synthesis of the N-phenylsulfonyl imine of butenone by Hudson reaction in a 15% yield, see reference 5b. 16 Wuts PG. M, Greene TW. Greene’s Protective Groups in Organic Synthesis . John Wiley & Sons, Inc; Hoboken: 2007. 4th ed 17 Sun P, Weinreb SM, Shang M. J. Org. Chem. 1997; 62: 8604 18 Bergström MA, Andersson SI, Broo K, Luthman K, Karlberg A.-T. J. Med. Chem. 2008; 51: 2541 19a Hutchins RO, Adams J, Rutledge MC. J. Org. Chem. 1995; 60: 7396 19b Hutchins RO, Rao SJ, Adams J, Hutchins MK. J. Org. Chem. 1998; 63: 8077 20 N-(Cyclohex-2-en-1-ylidene)-4-methylbenzene-sulfonamide (2a); Typical Procedure: To a solution of TiCl(OEt)3 (4.37 g, 20.0 mmol) in toluene (10 mL) was added Et3N (2.79 mL, 20.0 mmol). The resulting mixture was stirred for 5 min at r.t. before TsNH2 (3.42 g, 20.0 mmol) was added, and the reaction mixture was heated to reflux for 15 min. A solution of 1a (961 mg, 10.0 mmol) in toluene (20 mL) was added dropwise over 15 min to the refluxing solution, and stirring was continued for 1 h. The reaction mixture was poured into a stirred and precooled (0 °C) suspension of NaHCO3 (5.0 g) in acetone–H2O (200 mL, 100:1), diluted with pentane (100 mL), dried over MgSO4, and filtered. The filtrate was concentrated under reduced pressure, and the crude product was purified by flash chromatography (CH2Cl2; R f = 0.26) on silica gel to furnish ketimine 2a (1.65 g, 66%) as a pale-yellow oil that crystallized in the freezer. 1H NMR (300 MHz, CDCl3): δ (62:38 E/Z-ratio, asterisk denotes minor isomer peaks) = 7.86 (mc, 2 H), 7.32 (mc, 2 H), 7.32* (mc, 1 H), 6.94 (mc, 1 H), 6.14 (dt, J = 10.0, 1.9 Hz, 1 H), 3.18 (mc, 2 H), 2.54* (mc, 2 H), 2.43 (s, 3 H), 2.40–2.30 (m, 2 H), 2.01–1.90 (m, 2 H). 13C NMR (75.5 MHz, CDCl3): δ = 180.1, 178.0*, 151.6*, 150.6, 143.4, 138.6, 130.1, 129.4, 127.1*, 127.0, 124.1*, 35.5*, 31.4, 26.0*, 25.2, 22.1*, 21.53, 21.49. HRMS (ESI+): m/z [M + Na]+ calcd. for C13H15NO2SNa: 272.0716; found: 272.0711. N-(Cyclohex-2-en-1-ylidene)-tert-butanesulfonamide (3a); Typical Procedure: To a solution of 1a (500 mg, 5.20 mmol) in MeOH–H2O (9:1, 5.0 mL) in a 10 mL microwave reaction vessel were added hydroxylamine hydrochloride (398 mg, 5.72 mmol) and sodium acetate (512 mg, 6.24 mmol). The vessel was sealed, and the mixture was heated in a microwave reactor at 135 °C for 5 min and then cooled to r.t. The reaction mixtures of three such batches were combined, poured into H2O (30 mL) and extracted with CHCl3 (3 × 30 mL). The combined organic phases were washed with sat. NaHCO3 (3 × 30 mL), dried over MgSO4, and concentrated under reduced pressure to give the crude oxime (1.70 g). The crude oxime was dissolved in Et2O (30 mL), Et3N (3.18 mL, 23.0 mmol) was added, and the solution was cooled to –35 °C. Then, tert-butylsulfinyl chloride (4.28 g, 30.6 mmol) was added dropwise, and the resulting suspension was stirred at –35 °C for 1.5 h before the cooling bath was removed. Stirring was continued for 16 h, and the reaction mixture was then filtered over Celite and concentrated under vacuum. Purification by flash chromatography (pentane–EtOAc, 5:1; R f = 0.38) on silica gel furnished ketimine 3a (1.62 g, 48%) as a pale-yellow oil that crystallized in the freezer. 1H NMR (300 MHz, CDCl3): δ (62:38 E/Z-ratio, asterisk denotes minor isomer peaks) = 7.12* (dt, J = 10.2, 2.0 Hz, 1 H), 6.90–6.80 (m, 1 H), 6.12 (dt, J = 10.0, 2.0 Hz, 1 H), 3.04 (t, J = 6.7 Hz, 2 H), 2.51* (t, J = 6.7 Hz, 2 H), 2.35–2.25 (m, 2 H), 1.97–1.83 (m, 2 H), 1.42 (s, 9 H). 13C NMR (75.5 MHz, CDCl3): δ = 180.7, 178.7*, 150.4*, 149.8, 130.2, 124.5*, 58.7, 35.5*, 31.5, 26.0*, 25.2, 23.9, 22.2*, 21.5. HRMS (ESI+): m/z [M + H]+ calcd. for C10H18NO2S: 216.1053; found: 216.1054. Supplementary Material Supplementary Material Supporting Information