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Synthesis 2012; 44(16): 2547-2554
DOI: 10.1055/s-0031-1289791
DOI: 10.1055/s-0031-1289791
special topic
Synthesis of an Isoindoline-Annulated, Tricyclic Sultam Library via Microwave-Assisted, Continuous-Flow Organic Synthesis (MACOS)
Further Information
Publication History
Received: 17 April 2012
Accepted: 11 May 2012
Publication Date:
04 July 2012 (online)
Abstract
A microwave-assisted, continuous-flow organic synthesis (MACOS) protocol for the synthesis of an isoindoline-annulated, tricyclic sultam library, utilizing a Heck–aza-Michael (HaM) strategy, is reported. This sequence involves a Heck reaction on vinylsulfonamides with batch microwave heating followed by a one-pot, sequential intramolecular aza-Michael cyclization/Boc-deprotection using MACOS. Subsequent cyclization with either 1,1′-carbonyldiimidazole or chloromethyl pivalate using MACOS provided an array of tricyclic sultams. This efficient three-step protocol requires only a few hours to produce the target sultams starting from simple starting materials. Using this strategy, a 38-member library of isoindoline-annulated sultams was generated in good to excellent overall yields (53–87%).
Supporting Information
- for this article is available online at http://www.thieme-connect.com/ejournals/toc/synthesis.
- Supporting Information
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References
- 1a Tierney PJ, Lidstrom P. Microwave Assisted Organic Synthesis . Blackwell Publishing; Oxford: 2005
- 1b Kappe CO. Angew. Chem. Int. Ed. 2004; 43: 6250
- 2a Jähnisch K, Hessel V, Löwe H, Baerns M. Angew. Chem. Int. Ed. 2004; 43: 406
- 2b Pennemann H, Watts P, Haswell SJ, Hessel V, Lowe H. Org. Process Res. Dev. 2004; 8: 422
- 3a Bremner S, Organ MG. J. Comb. Chem. 2007; 9: 14
- 3b Comer E, Organ MG. J. Am. Chem. Soc. 2005; 127: 8160
- 3c Organ MG, Comer E. Chem.–Eur. J. 2005; 11: 7223
- 3d Bagley MC, Jenkins RL, Lubinu MC, Mason C, Wood R. J. Org. Chem. 2005; 70: 7003
- 3e Saaby S, Baxendale IR, Ley SV. Org. Biomol. Chem. 2005; 3: 3365
- 3f He P, Haswell SJ, Fletcher PD. I. Appl. Catal., A 2004; 274: 111
- 3g Cablewski T, Faux AF, Strauss CR. J. Org. Chem. 1994; 59: 3408
- 4a Shore G, Yoo W.-J, Li C.-J, Organ MG. Chem.–Eur. J. 2010; 16: 126
- 4b Shore G, Organ MG. Chem. Commun. 2008; 838
- 4c Shore G, Organ MG. Chem.–Eur. J. 2008; 14: 9641
- 4d Shore G, Morin S, Mallik D, Organ MG. Chem.–Eur. J. 2008; 14: 1351
- 4e Shore G, Morin S, Organ MG. Angew. Chem. Int. Ed. 2006; 45: 2761
- 5 Achanta S, Liautard V, Paugh R, Organ MG. Chem.–Eur. J. 2010; 16: 12797
- 6 Painter TO, Thornton PD, Orestano M, Santini C, Organ MG, Aubé J. Chem.–Eur. J. 2011; 17: 9595
- 7a Organ MG, Hanson PR, Rolfe A, Samarakoon TB, Ullah F. J. Flow Chem. 2011; 1: 32
- 7b Zang Q, Javed S, Ullah F, Zhou A, Knudtson CA, Bi D, Basha FZ, Organ MG, Hanson PR. Synthesis 2011; 2743
- 7c Ullah F, Samarakoon TB, Rolfe A, Kurtz RD, Hanson PR, Organ MG. Chem.–Eur. J. 2010; 16: 10959
- 7d Moseley JD. Org. Process Res. Dev. 2008; 12: 967
- 7e Styring P, Parracho AI. R. Beilstein J. Org. Chem. 2009; 5: 29
- 7f Rolfe A, Ullah F, Samarakoon TB, Kurtz RD, Porubsky P, Neunswander B, Lushington G, Santini C, Organ MG, Hanson PR. ACS Comb. Sci. 2011; 13: 653
- 8a Drews J. Science (Washington, D.C.) 2000; 287: 1960
- 8b Scozzafava A, Owa T, Mastrolorenzo A, Supuran CT. Curr. Med. Chem. 2003; 10: 925
- 9a Lebegue N, Gallet S, Flouquet N, Carato P, Pfeiffer B, Renard P, Léonce S, Pierré A, Chavatte P, Berthelot P. J. Med. Chem. 2005; 48: 7363
- 9b Silvestri R, Marfè G, Artico M, La Regina G, Lavecchia A, Novellino E, Morgante M, Di Stefano C, Catalano G, Filomeni G, Abruzzese E, Ciriolo MR, Russo MA, Amadori S, Cirilli R, La Torre F, Salimei PS. J. Med. Chem. 2006; 49: 5840
- 10 McKerrecher D, Pike KG, Waring MJ. PCT Int. Appl WO 2006125972, 2006
- 11 Brzozowski Z, Saczewski F, Neamati N. Bioorg. Med. Chem. Lett. 2006; 16: 5298
- 12 Wroblewski T, Graul A, Castaner J. Drugs Future 1998; 23: 365
- 13 Rabasseda X, Hopkins SJ. Drugs Today 1994; 30: 557
- 14 Inagaki M, Tsuri T, Jyoyama H, Ono T, Yamada K, Kobayashi M, Hori Y, Arimura A, Yasui K, Ohno K, Kakudo S, Koizumi K, Suzuki R, Kato M, Kawai S, Matsumoto S. J. Med. Chem. 2000; 43: 2040
- 15 Wells GJ, Tao M, Josef KA, Bihovsky R. J. Med. Chem. 2001; 44: 3488
- 16 Tanimukai H, Inui M, Harigushi S, Kaneko J. Biochem. Pharmacol. 1965; 14: 961
- 17a Tan DS. Nat. Chem. Biol. 2005; 1: 74
- 17b Thomas GL, Spandl RJ, Glansdorp FG, Welch M, Bender A, Cockfield J, Lindsay JA, Bryant C, Brown DF. J, Loiseleur O, Rudyk H, Ladlow M, Spring DR. Angew. Chem. Int. Ed. 2008; 47: 2808
- 17c Spandl RJ, Diaz-Gavilan M, O’Connell KM. G, Thomas GL, Spring DR. Chem. Rec. 2008; 8: 129
- 17d Shaw JT. Nat. Prod. Rep. 2009; 26: 11
- 17e Thomas GL, Wyatt EE, Spring DR. Curr. Opin. Drug Discovery Dev. 2006; 9: 700
- 18 Zhou A, Rayabarapu D, Hanson PR. Org. Lett. 2009; 11: 531
- 19a Samarakoon TB, Hur MY, Kurtz RD, Hanson PR. Org. Lett. 2010; 12: 2182
- 19b Rolfe A, Samarakoon TB, Hanson PR. Org. Lett. 2010; 12: 1216
- 20 Rolfe A, Lushington GH, Hanson PR. Org. Biomol. Chem. 2010; 8: 2198
- 21 Zang Q, Javed S, Porubsky P, Ullah F, Neuenswander B, Lushington GH, Basha FZ, Organ MG, Hanson PR. ACS Comb. Sci. 2012; 14: 211
- 22a Mazik M, Kuschel M. Eur. J. Org. Chem. 2008; 1517
-
22b Julian LD, Hartwig JF. J. Am. Chem. Soc. 2010; 132: 13813
- 23 Shendage DM, Froehlich R, Haufe G. Org. Lett. 2004; 6: 3675
- 24a Routier S, Saugé L, Ayerbe N, Coudert G, Mérour J. Tetrahedron Lett. 2002; 43: 589
- 24b El Kazzouli S, Koubachi J, Berteina-Raboin S, Mouaddib A, Guillaumet G. Tetrahedron Lett. 2006; 47: 8575
- 25 Sakai N, Ohfune Y. J. Am. Chem. Soc. 1992; 114: 998
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