Bifunctional Thiourea Catalyzed Asymmetric Mannich Reaction Using Trifluoromethyl Aldimine as Trifluoromethyl Building Blocks

Abstract

An efficient bifunctional thiourea catalyzed asymmetric Mannich reaction with trifluoromethyl aldimine as trifluoromethyl building block was achieved to give the products in good diastereoselectivity and enantioselectivity.

Key words

thiourea catalysts - trifluoromethyl aldimine - β-keto esters - Mannich reaction - bifunctional organocatalyst

• References and Notes

• 1 Purser S, Moore PR, Swallow S, Gouverneur V. Chem. Soc. Rev. 2008; 37: 320
• 2 Hagmann WK. J. Med. Chem. 2008; 51: 4359
• 3a Saito S, Yamamoto H. Acc. Chem. Res. 2004; 37: 570
• 3b Böhm H.-J, Banner D, Bendels S, Kansy M, Kuhn B, Müller K, Obst-Sander U, Stahl M. ChemBioChem 2004; 5: 637
• 4a Welch JT. Tetrahedron 1987; 43: 3123
• 4b Shimizu M, Hiyama T. Angew. Chem. Int. Ed. 2005; 44: 214
• 4c Schlosser M. Angew. Chem. Int. Ed. 2006; 45: 5432
• 4d Müller K, Faeh C, Diederich F. Science 2007; 317: 1881
• 4e Kirsch P. Modern Fluoroorganic Chemistry: Synthesis, Reactivity, Applications. Wiley-VCH; Weinheim: 2004
• 4f Bonnet-Delpon D. Bioorganic and Medicinal Chemistry of Fluorine. Wiley-VCH; Hoboken, NJ: 2008
• 4g Ojima I. Fluorine in Medicinal Chemistry and Chemical Biology. Wiley-Blackwell; Chichester: 2009
• 4h Lin G.-Q, You Q.-D, Cheng J.-F. Chiral Drugs: Chemistry and Biological Action. Wiley-VCH; Hoboken: 2011
• 5a Schäcke H, Schottelius A, Döcke W.-D, Strehlke P, Jaroch S, Schmees N, Rehwinkel H, Hennekes H, Asadullah K. Proc. Natl. Acad. Sci. U.S.A. 2004; 101: 227
• 5b Gauthier JY, Chauret N, Cromlish W, Desmarais S, Duong LT, Falgueyret J.-P, Kimmel DB, Lamontagne S, Léger S, LeRiche T, Li CS, Massé F, McKay DJ, Nicoll-Griffith DA, Oballa RM, Palmer JT, Percival MD, Riendeau D, Robichaud J, Rodan GA, Rodan SB, Seto C, Thérien M, Truong V.-L, Venuti MC, Wesolowski G, Young RN, Zamboni R, Black WC. Bioorg. Med. Chem. Lett. 2008; 18: 923
• 5c Caron S, Do NM, Sieser JE, Arpin P, Vazquez E. Org. Process. Res. Dev. 2007; 11: 1015
• 5d Corbett JW, Ko SS, Rodgers JD, Gearhart LA, Magnus NA, Bacheler LT, Diamond S, Jeffrey S, Klabe RM, Cordova BC, Garber S, Logue K, Trainor GL, Anderson PS, Erickson-Viitanen SK. J. Med. Chem. 2000; 43: 2019
• 5e Barker M, Clackers M, Copley R, Demaine DA, Humphreys D, Inglis GG. A, Johnston MJ, Jones HT, Haase MV, House D, Loiseau R, Nisbet L, Pacquet F, Skone PA, Shanahan SE, Tape D, Vinader VM, Washington M, Uings I, Upton R, McLay IM, Macdonald SJ. F. J. Med. Chem. 2006; 49: 4216
• 5f Black WC, Bayly CI, Davis DE, Desmarais S, Falgueyret J.-P, Léger S, Li CS, Massé F, McKay DJ, Palmer JT, Percival MD, Robichaud J, Tsou N, Zamboni R. Bioorg. Med. Chem. Lett. 2005; 15: 4741
• 5g Betageri R, Zhang Y, Zindell RM, Kuzmich D, Kirrane TM, Bentzien J, Cardozo M, Capolino AJ, Fadra TN, Nelson RM, Paw Z, Shih D.-T, Shih C.-K, Zuvela-Jelaska L, Nabozny G, Thomson DS. Bioorg. Med. Chem. Lett. 2005; 15: 4761
• 5h Biggadike K, Boudjelal M, Clackers M, Coe DM, Demaine DA, Hardy GW, Humphreys D, Inglis GG. A, Johnston MJ, Jones HT, House D, Loiseau R, Needham D, Skone PA, Uings I, Veitch G, Weingarten GG, McLay IM, Macdonald SJ. F. J. Med. Chem. 2007; 50: 6519
• 5i Pierce ME, Parsons RL, Radesca LA, Lo YS, Silverman S, Moore JR, Islam Q, Choudhury A, Fortunak JM. D, Nguyen D, Luo C, Morgan SJ, Davis WP, Confalone PN, Chen C.-Y, Tillyer RD, Frey L, Tan L, Xu F, Zhao D, Thompson AS, Corley EG, Grabowski EJ. J, Reamer R, Reider PJ. J. Org. Chem. 1998; 63: 8536
• 6 Shibata N, Mizuta S, Kawai H. Tetrahedron: Asymmetry 2008; 19: 2633
• 7a Prakash GK. S, Krishnamurti R, Olah GA. J. Am. Chem. Soc. 1989; 111: 393
• 7b Stahly GP, Bell DR. J. Org. Chem. 1989; 54: 2873
• 7c Joubert J, Roussel S, Christophe C, Billard T, Langlois BR, Vidal T. Angew. Chem. Int. Ed. 2003; 42: 3133
• 7d Xu X, Furukawa T, Okino T, Miyabe H, Takemoto Y. Chem. Eur. J. 2006; 12: 466
• 7e Kawai H, Kusuda A, Nakamura S, Shiro M, Shibata N. Angew. Chem. Int. Ed. 2009; 48: 6324
• 7f Prakash GK. S, Mandal M. J. Am. Chem. Soc. 2002; 124: 6538
• 7g Sakavuyi K, Petersen KS. Tetrahedron Lett. 2013; 54: 6129
• 8a Ma J.-A, Cahard D. J. Fluorine Chem. 2007; 128: 975
• 8b Barata-Vallejo S, Lantaño B, Postigo A. Chem. Eur. J. 2014; 20: 16806
• 8c Shibata N, Matsnev A, Cahard D. Beilstein J. Org. Chem. 2010; 6: 65
• 8d Macé Y, Magnier E. Eur. J. Org. Chem. 2012; 2479
• 8e Zhang C. Org. Biomol. Chem. 2014; 12: 6580
• 8f Blazejewski J.-C, Wilmshurst MP, Popkin MD, Wakselman C, Laurent G, Nonclercq D, Cleeren A, Ma Y, Seo H.-S, Leclercq G. Bioorg. Med. Chem. 2003; 11: 335
• 8g Matsnev A, Noritake S, Nomura Y, Tokunaga E, Nakamura S, Shibata N. Angew. Chem. Int. Ed. 2010; 49: 572
• 8h Sigman MS, Vachal P, Jacobsen EN. Angew. Chem. Int. Ed. 2000; 39: 1279
• 8i Koller R, Stanek K, Stolz D, Aardoom R, Niedermann K, Togni A. Angew. Chem. Int. Ed. 2009; 48: 4332
• 8j Umemoto T, Adachi K. J. Org. Chem. 1994; 59: 5692
• 8k Mikami K, Kotera O, Motoyama Y, Sakaguchi H. Synlett 1995; 975
• 9 Valero G, Companyó X, Rios R. Chem. Eur. J. 2011; 17: 2018
• 10a Allen AE, MacMillan DW. C. J. Am. Chem. Soc. 2010; 132: 4986
• 10b Matoušek V, Togni A, Bizet V, Cahard D. Org. Lett. 2011; 13: 5762
• 11a Ma J.-A, Cahard D. Chem. Rev. 2008; 108: PR1
• 11b Nicewicz DA, MacMillan DW. C. Science 2008; 322: 77
• 11c Nagib DA, MacMillan DW. C. Nature (London, U.K.) 2011; 480: 224
• 11d Hafner A, Bräse S. Angew. Chem. Int. Ed. 2012; 51: 3713
• 11e Ye Y, Lee SH, Sanford MS. Org. Lett. 2011; 13: 5464
• 11f Tiers GV. D. J. Am. Chem. Soc. 1960; 82: 5513
• 11g Itoh Y, Mikami K. Tetrahedron 2006; 62: 7199
• 11h Langlois BR, Laurent E, Roidot N. Tetrahedron Lett. 1991; 32: 7525
• 11i Nagib DA, Scott ME, MacMillan DW. J. Am. Chem. Soc. 2009; 131: 10875
• 11j Ji Y, Brueckl T, Baxter RD, Fujiwara Y, Seiple IB, Su S, Blackmond DG, Baran PS. Proc. Natl. Acad. Sci. U.S.A. 2011; 108: 14411
• 12a Zhao Q.-Y, Yuan Z.-L, Shi M. Adv. Synth. Catal. 2011; 353: 637
• 12b Qing F.-L, Zheng F. Synlett 2011; 1052
• 12c Palacio C, Connon SJ. Org. Lett. 2011; 13: 1298
• 12d Hara N, Tamura R, Funahashi Y, Nakamura S. Org. Lett. 2011; 13: 1662
• 12e Leuger J, Blond G, Fröhlich R, Billard T, Haufe G, Langlois BR. J. Org. Chem. 2006; 71: 2735
• 12f Li P, Zhao G, Zhu S. Chin. J. Chem. 2011; 29: 2749
• 12g Gao J.-R, Wu H, Xiang B, Yu W.-B, Han L, Jia Y.-X. J. Am. Chem. Soc. 2013; 135: 2983
• 12h Prakash GK. S, Paknia F, Mathew T, Mlostoń G, Joschek JP, Olah GA. Org. Lett. 2011; 13: 4128
• 12i Gao X, Zhang YJ, Krische MJ. Angew. Chem. Int. Ed. 2011; 50: 4173
• 12j Ohshima T, Kawabata T, Takeuchi Y, Kakinuma T, Iwasaki T, Yonezawa T, Murakami H, Nishiyama H, Mashima K. Angew. Chem. Int. Ed. 2011; 50: 6296
• 13 Zheng Y, Ma J.-A. Adv. Synth. Catal. 2010; 352: 2745
• 14 Noritake S, Shibata N, Nomura Y, Huang Y, Matsnev A, Nakamura S, Toru T, Cahard D. Org. Biomol. Chem. 2009; 7: 3599
• 15a Sondenecker A, Cvengroš J, Aardoom R, Togni A. Eur. J. Org. Chem. 2011; 78
• 15b Deng QH, Wadepohl H, Gade LH. J. Am. Chem. Soc. 2012; 134: 10769
• 16a Kawai H, Mizuta S, Tokunaga E, Shibata N. J. Fluorine Chem. 2013; 152: 46
• 16b Kawai H, Kusuda A, Mizuta S, Nakamura S, Funahashi Y, Masuda H, Shibata N. J. Fluorine Chem. 2009; 130: 762
• 16c Mizuta S, Shibata N, Akiti S, Fujimoto H, Nakamura S, Toru T. Org. Lett. 2007; 9: 3707
• 16d Zhao H, Qin B, Liu X, Feng X. Tetrahedron 2007; 63: 6822
• 16e Hu X, Wang J, Li W, Lin L, Liu X, Feng X. Tetrahedron Lett. 2009; 50: 4378
• 16f Nagao H, Yamane Y, Mukaiyama T. Chem. Lett. 2007; 36: 666
• 17 Nie J, Guo H.-C, Cahard D, Ma J.-A. Chem. Rev. 2011; 111: 455
• 18a List B. Chem. Rev. 2007; 107: 5413
• 18b Mukherjee S, Yang JW, Hoffmann S, List B. Chem. Rev. 2007; 107: 5471
• 18c Doyle AG, Jacobsen EN. Chem. Rev. 2007; 107: 5713
• 18d Bertelsen S, Jorgensen KA. Chem. Soc. Rev. 2009; 38: 2178
• 18e Nielsen M, Jacobsen CB, Holub N, Paixão MW, Jørgensen KA. Angew. Chem. Int. Ed. 2010; 49: 2668
• 18f Gruttadauria M, Giacalone F, Noto R. Adv. Synth. Catal. 2009; 351: 33
• 18g Park JH, Cho Y, Chung YK. Angew. Chem. Int. Ed. 2010; 49: 5138
• 18h Dondoni A, Massi A. Angew. Chem. Int. Ed. 2008; 47: 4638
• 18i Pellissier H. Tetrahedron 2007; 63: 9267
• 18j MacMillan DW. C. Nature (London, U.K.) 2008; 455: 304
• 19a Wang X, Lan Q, Shirakawa S, Maruoka K. Chem. Commun. 2010; 46: 321
• 19b Kim DY, Park EJ. Org. Lett. 2002; 4: 545
• 19c Appayee C, Brenner-Moyer SE. Org. Lett. 2010; 12: 3356
• 19d Ishimaru T, Shibata N, Horikawa T, Yasuda N, Nakamura S, Toru T, Shiro M. Angew. Chem. Int. Ed. 2008; 47: 4157
• 19e Dong X.-Q, Fang X, Wang C.-J. Org. Lett. 2011; 13: 4426
• 19f Schulte ML, Lindsley CW. Org. Lett. 2011; 13: 5684
• 19g Han X, Kwiatkowski J, Xue F, Huang K.-W, Lu Y. Angew. Chem. Int. Ed. 2009; 48: 7604
• 20 Xu J, Hu Y, Huang D, Wang K.-H, Xu C, Niu T. Adv. Synth. Catal. 2012; 354: 515
• 21 General Procedure for Preparing 4To the mixture of 2 (0.158 mmol, 1 equiv) and 3 (0.189 mmol, 1.2 equiv) in i-Pr₂O (2 mL), DIPEA (0.237 mmol, 1.5 equiv) and thiourea catalyst 1g (9.4 mg, 10 mol%) were added successively into a flame-dried flask at 10 °C under Ar atmosphere. The mixture was stirred at 10 °C for 72 h. When the reaction was completed, the mixture was concentrated under reduced pressure. The residue was purified by flash column chromatography using PE–EtOAc–CH₂Cl₂ (7:1:1) as eluent to obtain the desired product 4.Data of Compound 4a Yield 80%; white solid; mp 148–150 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.80–7.78 (d, J = 7.6 Hz, 1 H), 7.68–7.64 (t, J = 7.6 Hz, 1 H), 7.55–7.53 (d, J = 8.0 Hz, 1 H), 7.43–7.39 (t, J = 7.6 Hz, 1 H), 6.81 (s, 4 H), 5.23–5.15 (m, 1 H), 4.07–4.03 (d, J = 17.2 Hz, 1 H), 3.76 (s, 3 H), 3.71–3.68 (d, J = 11.6 Hz, 1 H), 3.56 (s, 3 H), 3.43–3.39 (d, J = 17.2 Hz, 1 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 196.7, 167.5, 153.7, 152.3, 139.4, 135.8, 133.9, 129.4–120.9 (q, J _C–F = 284.3 Hz), 128.0, 126.4, 125.1, 116.1, 114.7, 63.9, 60.9–60.1 (q, J _C–F = 27.8 Hz), 55.5, 53.3, 31.4 ppm. ¹⁹F NMR (376 MHz, CDCl₃): δ = –70.36 to –70.38 (d, J = 6.8 Hz) ppm. ESI-HRMS: m/z calcd for C₂₀H₁₈F₃NO₄ [M + H]⁺: 394.1261; found: 394.1258. IR (thin film): 3370, 3032, 2961, 1745, 1514, 1465, 1245, 1033, 828, 760 cm^–1. HPLC: major ee = 84%; minor ee = 88%; dr = 80:20 [Chiralpak AD-H, n-hexane–i-PrOH (90:10), 1 mL/min, 254 nm]: t ₁ (major isomer) = 17.70 min, t ₂ (major isomer) = 29.28 min; t ₃ (minor isomer) = 11.97 min, t ₄ (minor isomer) = 22.82 min.
• 22a Matsubara R, Berthiol F, Kobayashi S. J. Am. Chem. Soc. 2008; 130: 1804
• 22b Nakano J, Masuda K, Yamashita Y, Kobayashi S. Angew. Chem. Int. Ed. 2012; 51: 9525