Abstract
A new protocol has been developed for the synthesis of α-trifluoromethyl ketones via organocatalyzed decarboxylative trifluoromethylation of β-ketoacids with Togni’s reagent. Among various simple amine catalysts, primary amines and secondary amines were identified to be more effective than tertiary amines, with piperazine being the most effective. Mechanistic investigations suggested that the primary or secondary amine-catalyzed reactions proceed mainly through trifluoromethylation of an enamine intermediate, which is more effective than the tertiary amine-catalyzed pathway that involves an enol intermediate. By using piperazine as the optimal organocatalyst, various β-ketoacids, including the sterically hindered α,α-disubstituted ones, were converted into the corresponding α-trifluoromethyl ketones in good yields. This research not only provides a useful strategy for the efficient synthesis of a wide range of α-trifluoromethyl ketones under mild conditions, but also constitutes one of the few studies on decarboxylative alkylation of β-ketoacids, which can intrigue further exploitation on organocatalyzed asymmetric decarboxylative alkylation reactions.
Graphical Abstract
Similar content being viewed by others
Notes
It was found that when 1 equiv of K2CO3 was used, the yield of 3a dropped dramatically to 13%, indicating that the carboxylate anion of 1a itself is not the reactive species for trifluoromethylation. In this context, we rationalized that 1a and its salt worked together to promote the trifluoromethylation, where the salt of 1a plays a similar role as TMEDA, for a plausible explanation, see the supplementary material.
References
Kirsch P (2013) Modern fluoroorganic chemistry: synthesis, reactivity applications, 2nd edn. Wiley-VCH, Weinheim
Furuya T, Kamlet AS, Ritter T (2011) Nature 473:470
Wang J, Sánchez-Roselló M, Aceña JL, del Pozo C, Sorochinsky AE, Fustero S, Soloshonok VA, Liu H (2014) Chem Rev 114:2432
Zhu W, Wang J, Wang S, Gu Z, Aceña JL, Izawa K, Liu H, Soloshonok VA (2014) J Fluor Chem 167:37
Zhou Y, Wang J, Gu Z, Wang S, Zhu W, Aceña JL, Soloshonok VA, Izawa K, Liu H (2016) Chem Rev 116:422
Prakash GKS, Yudin A (1997) Chem Rev 97:757
Liu X, Xu C, Wang M, Liu Q (2015) Chem Rev 115:683
Umemoto T (1996) Chem Rev 96:1757
Charpentier J, Früh N, Togni A (2015) Chem Rev 115:650
Studer A (2012) Angew Chem Int Ed 51:8950
Chu L, Qing FL (2014) Acc Chem Res 47:1513
Liu Q, Ni C, Hu J (2017) Natl Sci Rev 4:303
Tomashenko OA, Grushin VV (2011) Chem Rev 111:4475
Besset T, Schneider C, Cahard D (2012) Angew Chem Int Ed 51:5048
Liu T, Shen Q (2012) Eur J Org Chem 2012:6679
Wu XF, Neumann H, Beller M (2012) Chem Asian J 7:1744
Liu H, Gu Z, Jiang X (2013) Adv Synth Catal 355:617
Alonso C, de Marigorta EM, Rubiales G, Palacios F (2015) Chem Rev 115:1847
19 Xu J, Liu X, Fu Y (2014) Tetrahedron Lett 55:585
Merino E, Nevado C (2014) Chem Soc Rev 43:6598
Egami H, Sodeoka M (2014) Angew Chem Int Ed 53:8294
Yang X, Wu T, Phipps RJ, Toste FD (2015) Chem Rev 115:826
Guo X, Xiao YL, Wang X, Zhang X (2018) Angew Chem Int Ed. https://doi.org/10.1002/anie.201711463
Parsons AT, Buchwald SL (2011) Angew Chem Int Ed 50:9120
Xu J, Fu Y, Luo DF, Jiang YY, Xiao B, Liu ZJ, Gong TJ, Liu L (2011) J Am Chem Soc 133:15300
Wang X, Ye Y, Zhang S, Feng J, Xu Y, Zhang Y, Wang J (2011) J Am Chem Soc 133:16410
Xu J, Xiao B, Xie CQ, Luo DF, Liu L, Fu Y (2012) Angew Chem Int Ed 51:12551
Wu X, Chu L, Qing FL (2013) Angew Chem Int Ed 52:2198
He Z, Hu M, Luo T, Li L, Hu J (2012) Angew Chem Int Ed 51:11545
He Z, Tan P, Hu J (2016) Org Lett 18:72
He Z, Zhang R, Hu M, Li L, Ni C, Hu J (2013) Chem Sci 4:3478
Xu X, Chen H, He J, Xu H (2017) Chin J Chem 35:1665
Tan X, Liu Z, Shen H, Zhang P, Zhang Z, Li C (2017) J Am Chem Soc 139:12430
He Z, Luo T, Hu M, Cao Y, Hu J (2012) Angew Chem Int Ed 51:3944
Li Z, Cui Z, Liu ZQ (2013) Org Lett 15:406
Patra T, Deb A, Manna S, Sharma U, Maiti D (2013) Eur J Org Chem 2013:5247
Xu P, Abdukader A, Hu K, Cheng Y, Zhu C (2014) Chem Commun 50:2308
Yin J, Li Y, Zhang R, Jin K, Duan C (2014) Synthesis 46:607
Shang XJ, Li Z, Liu ZQ (2015) Tetrahedron Lett 56:233
Zhang HR, Chen DQ, Han YP, Qiu YF, Jin DP, Liu XY (2016) Chem Commun 52:11827
Li G, Wang T, Fei F, Su YM, Li Y, Lan Q, Wang XS (2016) Angew Chem Int Ed 55:3491
Lai YL, Lin DZ, Huang JM (2017) J Org Chem 82:597
Wei XJ, Boon W, Hessel V, Noël T (2017) ACS Catal 7:7136
Tang WK, Feng YS, Xu ZW, Cheng ZF, Xu J, Dai JJ, Xu HJ (2017) Org Lett 19:5501
Wang ZL (2013) Adv Synth Catal 355:2745
Patra T, Maiti D (2017) Chem Eur J 23:7382
Wei Y, Hu P, Zhang M, Su W (2017) Chem Rev 117:8864
Blaquiere N, Shore DG, Rousseaux S, Fagnou K (2009) J Org Chem 74:6190
Huang DK, Lei ZL, Zhu YJ, Liu ZJ, Hu XJ, Mao HF (2017) Tetrahedron Lett 58:3394
Zhang R, Ni C, He Z, Hu J (2017) J Fluor Chem 203:166
Westheimer FH, Jones WA (1941) J Am Chem Soc 63:3283
Guthrie JP, Jordan F (1972) J Am Chem Soc 94:9136
Spetnagel WJ, Klotz IM (1976) J Am Chem Soc 98:8199
Leussing DL, Raghavan NV (1980) J Am Chem Soc 102:5635
Haynes WM, Lide DR, Bruno TJ (eds) (2016) CRC handbook of chemistry and physics, 97th edn. CRC Press, Boca Raton
Yang CF, Wang JY, Tian SK (2011) Chem Commun 47:8343
Yang CF, Shen C, Li HH, Tian SK (2012) Chin Sci Bull 57:2377
Chen Y, Tian SK (2013) Chin J Chem 31:37
Han F, Zhang X, Hu M, Jia L (2015) Org Biomol Chem 13:11466
Berton M, Mello R, Williard PG, González-Núñez ME (2017) J Am Chem Soc 139:17414
Murphy JA, Patterson CW (1993) J Chem Soc Perkin Trans 1:405
He H, Zheng XJ, Li Y, Dai LX, You SL (2007) Org Lett 9:4339
Evans DA, Mito S, Seidel D (2007) J Am Chem Soc 129:11583
Lu Y, Li Y, Zhang R, Jin K, Duan C (2014) J Fluor Chem 161:128
Prakash GKS, Paknia F, Vaghoo H, Rasul G, Mathew T, Olah GA (2010) J Org Chem 75:2219
Sato K, Yuki T, Yamaguchi R, Hamano T, Tarui A, Omote M, Kumadaki I, Ando A (2009) J Org Chem 74:3815
Saidalimu I, Suzuki S, Tokunaga E, Shibata N (2016) Chin J Chem 34:485
Acknowledgements
Support of our work by the National Basic Research Program of China (2015CB931900), the National Key Research and Development Program of China (2016YFB0101200 and 2016YFB0101204), the National Natural Science Foundation of China (21632009, 21472221, 21421002, 21402227, and 21372246), the Key Programs of the Chinese Academy of Sciences (KGZD-EW-T08), the Key Research Program of Frontier Sciences of CAS (QYZDJ-SSW-SLH049), Shanghai Academic Research Leader Program (15XD1504400), and the Youth Innovation Promotion Association CAS (2014231) is gratefully acknowledged.
Author information
Authors and Affiliations
Corresponding author
Additional information
In memory of Professor George A. Olah (1927–2017)
Electronic supplementary material
Below is the link to the electronic supplementary material.
11244_2018_973_MOESM1_ESM.docx
Supplementary material 1 (DOCX 1334 KB). Results for Cu(OAc)2-catalyzed decarboxylative trifluoromethylation of β-ketoacids 1; NMR spectra of compounds 3
Rights and permissions
About this article
Cite this article
Zhang, R., Ni, C., He, Z. et al. Organocatalyzed Decarboxylative Trifluoromethylation of β-Ketoacids. Top Catal 61, 664–673 (2018). https://doi.org/10.1007/s11244-018-0973-7
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11244-018-0973-7