Synlett, Table of Contents Synlett 2013; 24(2): 177-180DOI: 10.1055/s-0032-1317922 letter © Georg Thieme Verlag Stuttgart · New York New Thiochromans via Reductive Cyclization of Thiophenol Derivatives André Niermann Freie Universität Berlin, Institut für Chemie und Biochemie, Takustrasse 3, 14195 Berlin, Germany Fax: +49(30)83855367 Email: hans.reissig@chemie.fu-berlin.de , Janine E. Grössel Freie Universität Berlin, Institut für Chemie und Biochemie, Takustrasse 3, 14195 Berlin, Germany Fax: +49(30)83855367 Email: hans.reissig@chemie.fu-berlin.de , Hans-Ulrich Reissig* Freie Universität Berlin, Institut für Chemie und Biochemie, Takustrasse 3, 14195 Berlin, Germany Fax: +49(30)83855367 Email: hans.reissig@chemie.fu-berlin.de › Author Affiliations Recommend Article Abstract Buy Article All articles of this category Abstract Reductive cyclization of sulfur-containing substrates 1 and 5 with samarium diiodide afforded the corresponding thiochroman derivatives with excellent diastereoselectivities. Cyclization of 1 is facilitated by geminal dimethyl substitution, which accelerates the reductive coupling and prevents samarium diiodide induced dehalogenation. Bromo-substituted dihydrothiochroman derivative 8 was further functionalized in subsequent reactions. Analogously, bromo-substituted hexahydroquinoline derivative 10 was diastereoselectively prepared in satisfying yield. Key words Key wordssamarium diiodide - radical - cyclization - thiochroman - geminal disubstitution - γ-aryl ketone Full Text References References and Notes For selected reviews, see: 1a Molander GA, Harris CR. Tetrahedron 1998; 54: 3321 1b Krief A, Laval A.-M. Chem. Rev. 1999; 99: 745 1c Kagan HB. Tetrahedron 2003; 59: 10351 1d Edmonds DJ, Johnston D, Procter DJ. Chem. Rev. 2004; 104: 3371 1e Berndt M, Gross S, Hölemann A, Reissig H.-U. Synlett 2004; 422 1f Gopalaiah K, Kagan HB. New J. Chem. 2008; 32: 607 1g Nicolaou KC, Ellery S, Chen J. Angew. Chem. Int. Ed. 2009; 48: 7140 ; Angew. Chem. 2009, 121, 7276 1h Procter DJ, Flowers RA. II, Skrydstrup T. Organic Synthesis using Samarium Diiodide: A Practical Guide . Royal Society of Chemistry; Cambridge: 2010 1i Beemelmanns C, Reissig H.-U. Chem. Soc. Rev. 2011; 40: 2199 1j Harb HY, Procter DJ. Synlett 2012; 23: 6 2a Dinesh CU, Reissig H.-U. Angew. Chem. Int. Ed. 1999; 38: 789 ; Angew. Chem. 1999, 111, 874 2b Nandanan E, Dinesh CU, Reissig H.-U. Tetrahedron 2000; 56: 4267 2c Berndt M, Reissig H.-U. Synlett 2001; 1290 2d Ohno H, Maeda S.-I, Okumura M, Wakayama R, Tanaka T. Chem. Commun. 2002; 316 2e Ohno H, Wakayama R, Maeda S.-I, Iwasaki H, Okumura M, Iwata C, Mikamiyama H, Tanaka T. J. Org. Chem. 2003; 68: 5909 2f Ohno H, Okumura M, Maeda S.-I, Iwasaki H, Wakayama R, Tanaka T. J. Org. Chem. 2003; 68: 7722 2g Wefelscheid UK, Berndt M, Reissig H.-U. Eur. J. Org. Chem. 2008; 3635 2h Niermann A, Reissig H.-U. Synlett 2011; 525 2i Berndt M, Hölemann A, Niermann A, Bentz C, Zimmer R, Reissig H.-U. Eur. J. Org. Chem. 2012; 1299 For related ketyl–aryl couplings, see: 3a Kise N, Suzumoto T, Shono T. J. Org. Chem. 1994; 59: 1407 3b Schmalz H.-G, Siegel S, Bats JW. Angew. Chem., Int. Ed. Engl. 1995; 34: 2383 ; Angew. Chem. 1995, 107, 2597 3c Shiue J.-S, Lin M.-H, Fang J.-M. J. Org. Chem. 1997; 62: 4643 3d Heimann J, Schäfer HJ, Fröhlich R, Wibbeling B. Eur. J. Org. Chem. 2003; 2919 4a Berndt M, Hlobilova I, Reissig H.-U. Org. Lett. 2004; 6: 957 4b Aulenta F, Berndt M, Brüdgam I, Hartl H, Sörgel S, Reissig H.-U. Chem. Eur. J. 2007; 13: 6047 4c Wefelscheid UK, Reissig H.-U. Adv. Synth. Catal. 2008; 350: 65 4d Wefelscheid UK, Reissig H.-U. Tetrahedron: Asymmetry 2010; 21: 1601 5a Gross S, Reissig H.-U. Synlett 2002; 2027 5b Kumaran RS, Brüdgam I, Reissig H.-U. Synlett 2008; 991 6a Gross S, Reissig H.-U. Org. Lett. 2003; 5: 4305 6b Blot V, Reissig H.-U. Synlett 2006; 2763 6c Blot V, Reissig H.-U. Eur. J. Org. Chem. 2006; 4989 6d Beemelmanns C, Reissig H.-U. Org. Biomol. Chem. 2009; 7: 4475 6e Beemelmanns C, Blot V, Gross S, Lentz D, Reissig H.-U. Eur. J. Org. Chem. 2010; 2716 6f Beemelmanns C, Reissig H.-U. Angew. Chem. Int. Ed. 2010; 49: 8021 ; Angew. Chem. 2010, 122, 8195 6g For a related electrochemical cyclization, see: Kise N, Mano T, Sakurai T. Org. Lett. 2008; 10: 4617 7 Aulenta F, Wefelscheid UK, Brüdgam I, Reissig H.-U. Eur. J. Org. Chem. 2008; 2325 8 Spruce LW, Gale JB, Berlin KD, Verma AK, Breitman TR, Ji X, Van der Helm D. J. Med. Chem. 1991; 34: 430 For selected publications dealing with the synthesis of thiochroman derivatives, see: 9a Takido T, Itabashi K, Takagi Y. J. Heterocycl. Chem. 1995; 32: 687 9b Nenajdenko V, Sanin A, Churakov A, Howard J, Balenkova E. Chem. Heterocycl. Compd. 1999; 35: 549 9c Kumar P, Bodas MS. Tetrahedron 2001; 57: 9755 9d Katritzky AR, Button MA. C. J. Org. Chem. 2001; 66: 5595 9e Bath S, Laso NM, Lopez-Ruiz H, Quiclet-Sire B, Zard SZ. Chem. Commun. 2003; 204 9f Saito T, Horikoshi T, Otani T, Matsuda Y, Karakasa T. Tetrahedron Lett. 2003; 44: 6513 9g Liepa AJ, Nguyen O, Saubern S. Aust. J. Chem. 2005; 58: 864 9h Jafarzadeh M, Amani K, Nikpour F. Tetrahedron Lett. 2005; 46: 7567 9i Wang W, Li H, Wang J, Zu L. J. Am. Chem. Soc. 2006; 128: 10354 9j Guha C, Pal R, Mallik AK. ARKIVOC 2012; (ix): 85 ; and references cited in this article 10 General Procedure for Samarium Diiodide Induced Cyclizations of Aryl Ketones: HMPA (10 equiv) was added to a previously prepared stock solution of SmI2 in THF (0.1 M, 2.05 equiv) under argon and the solution was stirred for 20 min. During this time the solution turned from dark blue to dark violet. In a separate flask, the substrate (1 equiv) and t-BuOH (2 equiv) were dissolved in THF (10 mL/mmol cyclization precursor) under argon. Argon was bubbled through the solution for 20 min. The substrate solution was then transferred with a syringe to the samarium diiodide solution and the resulting mixture was stirred at r.t. or –20 °C until the color changed from violet to grey. Saturated aq Na-K-tartrate solution was added, the organic layer was separated and the aqueous layer was extracted three times with Et2O. The combined organic layers were washed with H2O and brine, dried with MgSO4 and the solvents were removed under reduced pressure to give the crude product, which still contained small amounts of HMPA. Flash chromatography with aluminum oxide (activity grade III) yielded the cyclization products. 11 Niermann A. Dissertation . Freie Universität Berlin: 2012 12 Cyclization of Compound 1: According to the general procedure, the samarium diiodide solution in THF (27.2 mL, 2.59 mmol), HMPA (2.21 mL, 12.6 mmol), 1 (0.361 g, 1.26 mmol), and t-BuOH (0.187 g, 2.52 mmol) afforded after purification by flash chromatography (hexane–EtOAc, 9:1) compound 8 in 73% yield (265 mg) as a colorless oil. Analytical data of (4R*,4aS*)-6-Bromo-2,2,4-trimethyl-3,4,4a,7-tetrahydro-2H-thiochromen-4-ol (8): 1H NMR (700 MHz, CDCl3): δ = 1.21, 1.30, 1.37 (3 × s, 3 H each, CH3), 1.57 (br s, 1 H, OH), 1.99, 2.02 (AB system, J AB = 13.4 Hz, 1 H each, 3-H), 3.02 (mc, 1 H, 4a-H), 3.07 (dddd, J = 1.2, 3.8, 7.5, 22.4 Hz, 1 H, 7-H), 3.17 (dddd, J = 1.9, 3.4, 7.4, 22.4 Hz, 1 H, 7-H), 5.96 (ddd, J = 1.3, 3.4, 3.8 Hz, 1 H, 8-H), 6.30 (ddd, J = 1.2, 1.9, 3.5 Hz, 1 H, 5-H). 13C NMR (176 MHz, CDCl3): δ = 24.6, 30.6, 32.7 (3 × q, CH3), 37.2 (t, C-7), 43.6 (s, C-2), 53.7 (d, C-4a), 56.8 (t, C-3), 73.6 (s, C-4), 119.6 (s, C-6), 126.2 (d, C-5), 126.9 (d, C-8), 129.3 (s, C-8a). IR (film): 3400 (O–H), 3010–2850 (=C–H, C–H), 1665 (C=C) cm–1. Anal. Calcd for C12H17BrOS (289.2): C, 49.83; H, 5.92. Found: C, 49.78; H, 5.77. 13 Large amounts of dehalogenated compounds were isolated indicating that the increase in rate due to geminal dimethyl substitution cannot compensate the very fast samarium diiodide mediated deiodination. 14 Oxidation of Compound 8 with m-CPBA: m-CPBA (0.313 g, 1.82 mmol) was added to a solution of alkenyl bromide 8 (0.150 g, 0.52 mmol) in CH2Cl2 (2 mL) at 0 °C. After stirring for 3 h at 0 °C, the solvent was removed under reduced pressure and the crude material was subjected to column chromatography on silica gel (hexane–EtOAc, 7:3). Sulfone 14 was isolated as a colorless solid (70 mg, 42%). Analytical data of (4R*,4aS*)-6-Bromo-2,2,4-trimethyl-1,1-dioxo-3,4,4a,7-tetrahydro-2H-benzo-thiopyran-4-ol (14): mp 160–164 °C. 1H NMR (500 MHz, CDCl3): δ = 1.24, 1.34, 1.41 (3 × s, 3 H each, CH3), 1.83 (br s, 1 H, OH), 1.88, 2.38 (2 × d, J = 14.4 Hz, 1 H each, 3-H), 3.26 (dddd, J = 1.3, 3.9, 7.8, 23.6 Hz, 1 H, 7-H), 3.36 (dddd, J = 2.0, 3.1, 7.5, 23.6 Hz, 1 H, 7-H), 3.63 (mc, 1 H, 4a-H), 6.29 (mc, 1 H, 5-H), 6.78 (mc, 1 H, 8-H). 13C NMR (126 MHz, CDCl3): δ = 22.0, 22.8, 24.5 (3 × q, Me), 36.0 (t, C-7), 49.7 (d, C-4a), 51.9 (t, C-3), 57.2 (s, C-2), 72.9 (s, C-4), 118.8 (s, C-6), 125.5 (d, C-5), 132.8 (s, C-8a), 135.2 (d, C-8). IR (film): 3480 (O–H), 2990–2855 (=C–H, C–H), 1130 (S=O) cm–1. HRMS (ESI–TOF–MS): m/z [M + Na]+ calcd for C12H17BrO3SNa: 342.9979; found: 342.9977.
