An Expedient Route to 3-Chlorothioxanthen-9-one-10,10-dioxide and Derivation by Palladium-Catalyzed Coupling

Abstract

Chemistry has been developed that allows for the synthesis of a series of novel tricyclic thioxanthen-9-one-10,10-dioxides. A regioselective synthesis of the novel core substrate 3-chlorothioxanthen-9-one-10,10-dioxide was achieved in 85% yield over three steps without the need for chromatographic purification. Subsequent microwave-assisted coupling methodology afforded the desired novel 3-substituted tricyclic compounds in good to excellent yield.

Key words

catalysis - heterocycles - palladium - Suzuki reaction - thioxanthenone dioxide

References and Notes

• For selected examples, see:
• 1a Azuine MA. Tokuda H. Takayasu J. Enjyo F. Mukainaka T. Konoshima T. Nishino H. Kapadia GJ. Pharm. Res.  2004,  49:  161 
• 1b Kostakis IK. Pouli N. Marakos P. Mikros E. Skaltsounis A.-L. Leonce S. Atassi G. Renard P. Bioorg. Med. Chem.  2001,  9:  2793 
• For representative examples, see:
• 2a Rokach J, Rooney CS, and Cragoe EJ. inventors; US  4536507.  ; Chem. Abstr. 1985, 104, 19801124
• 2b Rokach J, Rooney CS, and Cragoe EJ. inventors; US  77-773232.  ; Chem. Abstr. 1980, 93, 46648
• 2c Batchelor JF, and Gorvin JH. inventors; DE  73-2344800.  ; Chem. Abstr. 1974, 80, 133449
• 2d Hodson HF, and Batchelor JF. inventors; US  4103015.  ; Chem. Abstr. 1979, 90, 22816
• For selected examples, see:
• 3a Harfenist M. Heuser DJ. Joyner CT. Batchelor JF. White HL. J. Med. Chem.  1996,  39:  1857 
• 3b Harfenist M. Joyner CT. Mize PD. White HL. J. Med. Chem.  1994,  37:  2085 
• 4a Miller TC, Collins JC, Mattes KC, Wentland MP, Perni RB, Corbett TH, and Guiles JW. inventors; US  5346917.  ; Chem. Abstr. 1994, 122, 55895
• 4b Mahishi NB. Sattur PB. Nargund KS. J. Karnatak Univ.  1957,  2:  50 
• 4c Okabayashi I. Fujiwara H. Tanaka C. J. Heterocycl. Chem.  1991,  23:  1977 
• 5a Zhao J. Larock RC. Org. Lett.  2005,  7:  4273 
• 5b Kristensen JL. Vedsó P. Begtrup M. J. Org. Chem.  2003,  68:  4091 
• 5c Kwon C.-H. He H.-Z. Synth. Commun.  2003,  33:  2437 
• 5d Beaulieu F. Snieckus V. J. Org. Chem.  1994,  59:  6508 
• 6a Costantino L. Ferrari AM. Gamberini MC. Rastelli G. Bioorg. Med. Chem.  2002,  10:  3923 
• 6b Bonnet B. Soullez D. Girault S. Maes L. Landry V. Davioud-Charvet E. Sergheraert C. Bioorg. Med. Chem.  2000,  8:  95 
• 6c Slight variation of reported reaction between 2-iodo-5-methylbenzoic acid and thiophenol: Valenta V. Jílek J. Pomykáček J. Dlabač A. Valchář M. Metyš J. Protiva M. Collect. Czech. Chem. Commun.  1979,  44:  2677 ; and references cited therein
• 7 Hodson HF, and Batchelor JF. inventors; GB  1447032.  ; Chem. Abstr. 1976, 86, 55284
• 8a Balicki R. J. Prakt. Chem.  1999,  341:  184 
• 8b Su W. Tetrahedron Lett.  1994,  35:  4955 
• 8c Denny WA. Rewcastle GW. Atwell GJ. Palmer BD. Boyd PD. Baguley BC. J. Med. Chem.  1991,  34:  491 
• 8d Carpino LA. Gao H.-S. Ti G.-S. Segev D. J. Org. Chem.  1989,  54:  5887 
• 8e Varvoglis A. Spyroudis S. Barbas D. J. Chem. Res., Synop.  1985,  186 
• 9 Kappe CO. Angew. Chem. Int. Ed.  2004,  43:  6250 
• 10 Sauer DR. Wang Y. Org. Lett.  2004,  6:  2793 
• 11 For a recent reported example on the use of simultaneous cooling in microwave-assisted chemistry, see: Arvela RK. Leadbeater NE. Org. Lett.  2005,  7:  2101 
• Yields of Suzuki coupling reactions utilizing non-activated chloro substrates can be often optimized by using palladacyclic complexes, palladium complexes of phosphine oxides or di(2-pyridyl)methylamine-based palladium complexes. For selected reported examples, see:
• 12a Chen CL. Liu YH. Peng SM. Liu ST. Tetrahedron Lett.  2005,  46:  521 
• 12b Miao G. Ye P. Yu L. Baldino CM. J. Org. Chem.  2005,  70:  2332 
• 12c Nájera C. Gil-Moltó J. Karlström S. Adv. Synth. Catal.  2004,  346:  1798 
• 12d Navarro O. Kelly RA. Nolan SP. J. Am. Chem. Soc.  2003,  125:  16194