I₂/TBHP-Promoted Approach to α-Keto Esters from Trifluoromethyl β-Diketones and Alcohols via C–C Bond Cleavage

Abstract

A metal-free oxidative coupling reaction of trifluoromethyl β-diketones with alcohols for the synthesis of α-keto esters in good to excellent yields has been developed. Preliminary mechanistic studies suggest that an I₂/TBHP promoted sequential iodination, C–C bond cleavage, C–O bond formation and oxidation pathway is involved in this reaction.

Key words

trifluoromethyl β-diketones - α-keto esters - C–C bond cleavage - C–O coupling - alcohols

• References

• 1a Nie Y. Xiao R. Xu Y. Montelione GT. Org. Biomol. Chem. 2011; 9: 4070
• 1b Elsebai MF. Kehraus S. Lindequist U. Sasse F. Shaaban S. Gütschow M. Josten M. Sahl H.-G. König GM. Org. Biomol. Chem. 2011; 9: 802
• 1c Hemeon I. Bennet AJ. Synthesis 2007; 1899
• 1d Wardrop DJ. Zhang W. Tetrahedron Lett. 2002; 43: 5389
• 1e Aoki Y. Tanimoto S. Takahashi D. Toshima K. Chem. Commun. 2013; 1169
• 2a Gravenfors Y. Viklund J. Blid J. Ginman T. Karlström S. Kihlström J. Kolmodin K. Lindström J. Berg S. Kieseritzky F. Slivo C. Swahn B.-M. Olsson L.-L. Johansson P. Eketjäll S. Fälting J. Jeppsson F. Strömberg K. Janson J. Rahm F. J. Med. Chem. 2012; 55: 9297
• 2b Boughton BA. Hor L. Gerrard JA. Hutton CA. Bioorg. Med. Chem. 2012; 20: 2419
• 2c Sarabu R. Bizzarro FT. Corbett WL. Dvorozniak MT. Geng W. Grippo JF. Haynes N.-E. Hutchings S. Garofalo L. Guertin KR. Hilliard DW. Kabat M. Kester RF. Ka W. Liang Z. Mahaney PE. Marcus L. Matschinsky FM. Moore D. Racha J. Radinov R. Ren Y. Qi L. Pignatello M. Spence CL. Steele T. Tengi J. Grimsby J. J. Med. Chem. 2012; 55: 7021
• 2d Ntaganda R. Milovic T. Tiburcio J. Thadani AN. Chem. Commun. 2008; 4052
• 2e Zhou W. Li P. Zhang Y. Wang L. Adv. Synth. Catal. 2013; 355: 2343
• 2f Rao KR. Raghunadh A. Kalita D. Laxminarayana E. Pal M. Meruva SB. Pharma Chem. 2015; 7: 77
• 2g Miller EJ. Zhao W. Herr JD. Radosevich AT. Angew. Chem. Int. Ed. 2012; 51: 10605
• 2h Zhao W. Fink DM. Labutta CA. Radosevich AT. Org. Lett. 2013; 15: 3090
• 2i Wang SR. Radosevich AT. Org. Lett. 2015; 17: 3810
• 2j Zhao W. Yan PK. Radosevich AT. J. Am. Chem. Soc. 2015; 137: 616
• 2k Chavannavar AP. Oliver AG. Ashfeld BL. Chem. Commun. 2014; 10853
• 2l Otte RD. Sakata T. Guzei IA. Lee D. Org. Lett. 2005; 7: 495
• 2m Fourmy K. Voituriez A. Org. Lett. 2015; 17: 1537
• 2n Mbofana CT. Miller SJ. ACS Catal. 2014; 4: 3671
• 3a Lee A. Scheidt KA. Angew. Chem. Int. Ed. 2014; 53: 7594
• 3b Takahashi M. Murata Y. Ishida M. Yagishita F. Sakamoto M. Sengoku T. Yoda H. Org. Biomol. Chem. 2014; 12: 7686
• 3c Blay G. Fernández I. Muñoz MC. Pedro JR. Recuenco A. Vila C. J. Org. Chem. 2011; 76: 6286
• 3d Wilson EE. Rodriguez KX. Ashfeld BL. Tetrahedron 2015; 71: 5765
• 3e Jing Z. Bai X. Chen W. Zhang G. Zhu B. Jiang Z. Org. Lett. 2016; 18: 260
• 3f Yanagisawa A. Miyake R. Yoshida K. Eur. J. Org. Chem. 2014; 4248
• 3g Ishihara K. Ogura Y. Org. Lett. 2015; 17: 6070
• 3h Sánchez-Larios E. Thai K. Bilodeau F. Gravel M. Org. Lett. 2011; 13: 4942
• 3i Enders D. Stöckel BA. Rembiak A. Chem. Commun. 2014; 4489
• 3j Luo W. Zhao J. Ji J. Lin L. Liu X. Mei H. Feng X. Chem. Commun. 2015; 10042
• 4a Zhuang J. Wang C. Xie F. Zhang W. Tetrahedron 2009; 65: 9797
• 4b Zhang C. Jiao N. Org. Chem. Front. 2014; 1: 109
• 4c Sagar A. Vidyacharan S. Sharada DS. RSC Adv. 2014; 4: 37047
• 5a Xu X. Ding W. Lin Y. Song Q. Org. Lett. 2015; 17: 516
• 5b Zhang Z. Su J. Zha Z. Wang Z. Chem. Eur. J. 2013; 19: 17711
• 6a Moriyama K. Takemura M. Togo H. J. Org. Chem. 2014; 79: 6094
• 6b Alamsetti SK. Sekar G. Chem. Commun. 2010; 7235
• 6c Shen D. Miao C. Xu D. Xia C. Sun W. Org. Lett. 2015; 17: 54
• 7a Ozawa F. Kawasaki N. Yamamoto T. Yamamoto A. Chem. Lett. 1985; 14: 567
• 7b Sakakura T. Yamashita H. Kobayashi T. Hayashi T. Tanaka M. J. Org. Chem. 1987; 52: 5733
• 8a Shimizu H. Murakami M. Chem. Commun. 2007; 2855
• 8b Zhang C. Feng P. Jiao N. J. Am. Chem. Soc. 2013; 135: 15257
• 8c Nagaki A. Ichinari D. Yoshida J. Chem. Commun. 2013; 3242
• 8d Ang WJ. Lam Y. Org. Biomol. Chem. 2015; 13: 1048

For selected examples of C–O bond formation catalyzed by I₂ or iodide/TBHP catalytic system, see:
• 9a Uyanik M. Hayashi H. Ishihara K. Science 2014; 345: 291
• 9b Uyanik M. Okamoto H. Yasui T. Ishihara K. Science 2010; 328: 1376
• 9c Uyanik M. Suzuki D. Yasui T. Ishihara K. Angew. Chem. Int. Ed. 2011; 50: 5331
• 9d Xu W. Nachtsheim BJ. Org. Lett. 2015; 17: 1585
• 9e Zi Y. Cai Z.-J. Wang S.-Y. Ji S.-J. Org. Lett. 2014; 16: 3094
• 9f Shi E. Shao Y. Chen S. Hu H. Liu Z. Zhang J. Wan X. Org. Lett. 2012; 14: 3384
• 9g Wei W. Zhang C. Xu Y. Wan X. Chem. Commun. 2011; 10827
• 9h Boominathan SS. K. Hu W.-P. Senadi GC. Vandavasi JK. Wang J.-J. Chem. Commun. 2014; 6726
• 9i Yu H. Shen J. Org. Lett. 2014; 16: 3204
• 9j Majji G. Guin S. Gogoi A. Rout SK. Patel BK. Chem. Commun. 2013; 3031
• 9k Tan B. Toda N. Barbas III CF. Angew. Chem. Int. Ed. 2012; 51: 12538
• 9l Zhang S. Guo L.-N. Wang H. Duan X.-H. Org. Biomol. Chem. 2013; 11: 4308
• 9m Feng J. Liang S. Chen S.-Y. Zhang J. Fu S.-S. Yu X.-Q. Adv. Synth. Catal. 2012; 354: 1287
• 9n Majji G. Guin S. Rout SK. Behera A. Patel BK. Chem. Commun. 2014; 12193
• 9o Uyanik M. Hayashi H. Iwata H. Ishihara K. Chem. Lett. 2016; 45: 353

For selected examples of C–C or C–X bond formation catalyzed by I₂ or iodide/TBHP catalytic system, see:
• 10a Dhineshkumar J. Lamani M. Alagiri K. Prabhu KR. Org. Lett. 2013; 15: 1092
• 10b Sun K. Lv Y. Wang J. Sun J. Liu L. Jia M. Liu X. Li Z. Wang X. Org. Lett. 2015; 17: 4408
• 10c Vadagaonkar KS. Kalmode HP. Prakash S. Chaskar AC. Synlett 2015; 26: 1677
• 10d Xue Q. Xie J. Xu P. Hu K. Cheng Y. Zhu C. ACS Catal. 2013; 3: 1365
• 10e Yu H. Huang W. Zhang F. Eur. J. Org. Chem. 2014; 3156
• 10f Zhu Y.-P. Liu M.-C. Jia F.-C. Yuan J.-J. Gao Q.-H. Lian M. Wu A.-X. Org. Lett. 2012; 14: 3392

For selected examples of the synthesis of heterocycles catalyzed by I₂ or iodide/TBHP catalytic system, see:
• 11a Jiang H. Huang H. Cao H. Qi C. Org. Lett. 2010; 12: 5561
• 11b Gao W.-C. Hu F. Huo Y.-M. Chang H.-H. Li X. Wei W.-L. Org. Lett. 2015; 17: 3914
• 11c Yoshimura A. Zhu C. Middleton KR. Todora AD. Kastern BJ. Maskaev AV. Zhdankin VV. Chem. Commun. 2013; 4800
• 11d Zhang J. Zhu D. Yu C. Wan C. Wang Z. Org. Lett. 2010; 12: 2841
• 11e Vadagaonkar KS. Kalmode HP. Murugan K. Chaskar AC. RSC Adv. 2015; 5: 5580
• 11f Chen Z. Li H. Dong W. Miao M. Ren H. Org. Lett. 2016; 18: 1334
• 12a Zhang XB. Wang L. Green Chem. 2012; 14: 2141
• 12b Wei W. Shao Y. Hu H. Zhang F. Zhang C. Xu Y. Wan X. J. Org. Chem. 2012; 77: 7157
• 12c Zhao Q. Miao T. Zhang X. Zhou W. Wang L. Org. Biomol. Chem. 2013; 11: 1867
• 12d Kalmode HP. Vadagaonkar KS. Chaskar AC. Synthesis 2015; 47: 429
• 12e Mupparapu N. Vishwakarma RA. Ahmed QN. Tetrahedron 2015; 71: 3417
• 13a Saidalimu I. Fang X. Lv W. Yang X. He X. Zhang J. Wu F. Adv. Synth. Catal. 2013; 355: 857
• 13b Saidalimu I. Fang X. He X.-P. Liang J. Yang X. Wu F. Angew. Chem. Int. Ed. 2013; 52: 5566
• 14a Sloop JM. Boyle PD. Fountain AW. Pearman WF. Swann JA. Eur. J. Org. Chem. 2011; 936
• 14b Sloop JC. Bumgardner CL. Washington G. Loehle WD. Sankar SS. Lewis AB. J. Fluorine Chem. 2006; 127: 780
• 15a Bartoli S. Jensen KB. Kilburn JD. J. Org. Chem. 2003; 68: 9416
• 15b Shao T. Fang X. Yang X. Synlett 2015; 26: 1835
• 16 Zhu C. Zhang Y. Zhao H. Huang S. Zhang M. Su W. Adv. Synth. Catal. 2015; 357: 331
• 17 Typical Procedure for the Synthesis of 3 from 1 To a mixture of 1k (126 mg, 0.5 mmol), methanol 2a (48 mg, 1.5 mmol), I₂ (140 mg, 0.55 mmol), tert-butyl hydroperoxide (112.7 mg, 1.25 mmol) and Na₂CO₃ (53 mg, 0.5 mmol) was added 1,2-dichloroethane (1.5 mL) at room temperature. The reaction mixture was then stirred at 60 °C for 7 h. When the reaction was complete (monitored by TLC), the reaction was quenched with 2 mL of saturated NH₄Cl and 4 mL of saturated Na₂S₂O₃ aqueous solution. After extraction with EtOAc and drying with Na₂SO₄, the organic layer was concentrated under reduced pressure and the residue was purified by column chromatography on silica gel using hexanes/EtOAc (100:1 to 50:1) as eluent to afford the desired products 3ak (99 mg, 99% yield). Methyl 2-(3,4-Difluorophenyl)-2-oxoacetate (3ak) White solid; m.p. 38.7–40.2 °C. ¹H NMR (400 MHz, CDCl₃): δ = 7.96–7.91 (m, 1 H), 7.90–7.86 (m, 1 H), 7.34–7.28 (m, 1 H), 3.99 (s, 3 H). ¹³C NMR (101 MHz, CDCl₃): δ = 182.9, 162.9, 154.8 (dd, J ₁ = 261.6 Hz, J ₂ = 13.1 Hz), 150.5 (dd, J ₁ = 253.5 Hz, J ₂ = 13.1 Hz), 129.5 (t, J = 4.0 Hz), 127.7 (dd, J ₁ = 8.1 Hz, J ₂ = 4.0 Hz), 119.3 (dd, J ₁ = 18.2 Hz, J ₂ = 2.0 Hz), 117.9 (d, J = 18.2 Hz). ¹⁹F NMR (CDCl₃, 376 MHz): δ = –125.53 to –125.65 (m, 1 F), –134.76 to –134.87 (m, 1 F). EI-MS: m/z (%) = 63, 93, 113, 141 (100), 142, 153, 172, 184, 200. HRMS: m/z calcd for [C₉H₆F₂O₃]⁺: 200.0285; found: 200.028.