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Synlett 2023; 34(20): 2411-2416
DOI: 10.1055/a-2107-5496
DOI: 10.1055/a-2107-5496
cluster
Special Issue Dedicated to Prof. Hisashi Yamamoto
Access to Fluorinated Quaternary Stereogenic Centers via Palladium-Catalyzed Asymmetric Allylic C–H Alkylation
We are grateful for financial support from the National Key Research and Development Program of China (2021YFA1500100), Youth Innovation Promotion Association CAS (2020448), National Natural Science Foundation of China (NSFC, 22171254 and 22188101), Anhui Provincial Natural Science Foundation (2108085MB58 and 2208085QB37), USTC Research Funds of the Double First-Class Initiative (YD2060002024), Start-up Research Fund from University of Science and Technology of China (KY2060000216) and the Chinese Postdoctoral Science Foundation (2022M713031).
Abstract
A Pd-catalyzed branch- and enantioselective allylic C–H alkylation reaction has been developed for the rapid assembly of fluorinated quaternary stereogenic centers from allylarenes and prochiral α-fluorinated esters. Using chiral phosphoramidite as ligand and 2,5-diphenylquinone as oxidant, the reaction proceeds smoothly under mild conditions and tolerates a broad scope of substrates, resulting in α-quaternary fluorinated ester products with high levels of yields, enantioselectivities, and regioselectivities.
Key words
palladium catalysis - allylic C–H alkylation - phosphoramidite - quaternary stereogenic center - fluorinated carbonSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-2107-5496.
- Supporting Information
Publication History
Received: 20 April 2023
Accepted after revision: 07 June 2023
Accepted Manuscript online:
07 June 2023
Article published online:
13 July 2023
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References and Notes
- 1 Zhu Y, Han J, Wang J, Shibata N, Sodeoka M, Soloshonok VA, Coelho JA. S, Toste FD. Chem. Rev. 2018; 118: 3887
- 2 O’Hagan D. J. Fluorine Chem. 2010; 131: 1071
- 3 Mikami K, Itoh Y, Yamanaka M. Chem. Rev. 2004; 104: 1
- 4 Ma J.-A, Cahard D. Chem. Rev. 2004; 104: 6119
- 5a Trost BM, Crawley ML. Chem. Rev. 2003; 103: 2921
- 5b Pamies O, Margalef J, Canellas S, James J, Judge E, Guiry PJ, Moberg C, Backvall JE, Pfaltz A, Pericas MA, Dieguez M. Chem. Rev. 2021; 121: 4373
- 5c Susse L, Stoltz BM. Chem. Rev. 2021; 121: 4084
- 6 He ZT, Jiang X, Hartwig JF. J. Am. Chem. Soc. 2019; 141: 13066
- 7 Liu XJ, Jin S, Zhang WY, Liu QQ, Zheng C, You SL. Angew. Chem. Int. Ed. 2020; 59: 2039
- 8a Sripada A, Wolf C. J. Org. Chem. 2022; 87: 11880
- 8b Balaraman K, Wolf C. Angew. Chem. Int. Ed. 2017; 56: 1390
- 10a Wang P.-S, Gong L.-Z. Acc. Chem. Res. 2020; 53: 2841
- 10b Wang P.-S, Gong L.-Z. Chin. J. Chem. 2023; 41: 1841
- 11a Lin H.-C, Wang P.-S, Tao Z.-L, Chen Y.-G, Han Z.-Y, Gong L.-Z. J. Am. Chem. Soc. 2016; 138: 14354
- 11b Fan L.-F, Luo S.-W, Chen S.-S, Wang T.-C, Wang P.-S, Gong L.-Z. Angew. Chem. Int. Ed. 2019; 58: 16806
- 11c Lin HC, Xie PP, Dai ZY, Zhang SQ, Wang PS, Chen YG, Wang TC, Hong X, Gong LZ. J. Am. Chem. Soc. 2019; 141: 5824
- 11d Wang TC, Wang PS, Gong LZ. Sci. China Chem. 2020; 63: 454
- 11e Dai ZY, Wang PS, Gong LZ. Chem. Commun. 2021; 57: 6748
- 11f Liu R, Shen ML, Fan LF, Zhou XL, Wang PS, Gong LZ. Angew. Chem. Int. Ed. 2023; 62: e202211631
- 12a Wang TC, Fan LF, Shen Y, Wang PS, Gong LZ. J. Am. Chem. Soc. 2019; 141: 10616
- 12b Wang TC, Zhu L, Luo S, Nong ZS, Wang PS, Gong LZ. J. Am. Chem. Soc. 2021; 143: 20454
- 13 Nong Z.-S, Zhu L, Wang T.-C, Fan L.-F, Wang P.-S, Gong L.-Z. Nat. Synth. 2022; 1: 487
- 14a Teichert JF, Feringa BL. Angew. Chem. Int. Ed. 2010; 49: 2486
- 14b Zhang Z.-F, Xie F, Yang B, Yu H, Zhang W.-B. Chin. J. Org. Chem. 2011; 31: 429
- 15 Hamada Y, Shibata M, Sugiura T, Kato S, Shioiri T. J. Org. Chem. 2002; 52: 1252
- 16a Fan L.-F, Wang P.-S, Gong L.-Z. Org. Lett. 2019; 21: 6720
- 16b Fan L.-F, Xie P.-P, Wang P.-S, Hong X, Gong L.-Z. CCS Chem. 2022; 4: 1366
- 17 Synthesis of Allylation Products 3ab–am; General Procedure: To a flame-dried and N2-purged Schlenk tube (10 mL) were added isopropyl 2-(benzo[d]thiazol-2-yl)-2-fluoroacetate (0.10 mmol, 25.3 mg, 1.0 equiv), Pd(dba)2 (0.005 mmol, 2.8 mg, 5 mol%), phosphoramidite L5 (0.0075 mmol, 5.8 mg, 7.5 mol%), Li2CO3 (0.050 mmol, 3.7 mg, 0.5 equiv), 2,5-diphenylquinone (0.12 mmol, 31.2 mg, 1.2 equiv) and a stirring bar. The Schlenk tube was then evacuated and filled with nitrogen. This cycle was repeated three times and followed by the addition of anhydrous 1,4-dioxane (1 mL) and allylarene (0.2 mmol, 2.0 equiv) via a syringe, then the resulting mixture was stirred at 60 °C for 12 h. The reaction mixture was concentrated in vacuo, and the residue was purified by column chromatography on silica gel (petroleum ether /ethyl acetate = 50:1) to provide the desired product. Isopropyl (2R,3R)-2-(Benzo[d]thiazol-2-yl)-2-fluoro-3-phenylpent-4-enoate (3aa): Compound 3aa was prepared according to the general procedure by using allylbenzene (23.6 mg). Eluent for column chromatography (petroleum ether/ethyl acetate = 50:1). Yield: 99% (36.6 mg); colorless oil; b/l > 20:1, dr = 6:1. Enantiomeric excess: 90%, determined by HPLC (CHIRALPAK IC, hexane/isopropanol = 95:5, flow rate 1.0 mL/min, T = 30 °C, 254 nm): tR = 4.743 (minor), 5.319 (major) min; [α]D 20 –11.4 (c 0.45, CHCl3). 1H NMR (400 MHz, CDCl3 ): δ = 8.17 (d, J = 8.1 Hz, 1 H), 7.93 (d, J = 7.7 Hz, 1 H), 7.53 (dd, J = 8.9, 7.7 Hz, 1 H), 7.50–7.41 (m, 3 H), 7.38–7.32 (m, 2 H), 7.31–7.27 (m, 1 H), 6.13–5.99 (m, 1 H), 5.08–4.98 (m, 2 H), 4.88–4.69 (m, 2 H), 1.00 (d, J = 6.3 Hz, 3 H), 0.93 (d, J = 6.3 Hz, 3 H). 19F NMR (376 MHz, CDCl3): δ = –163.59. 13C NMR (101 MHz, CDCl3): δ = 166.74 (d, J = 31.8 Hz), 165.77 (d, J = 26.0 Hz), 153.36, 137.49 (d, J = 1.3 Hz), 135.24 (d, J = 2.1 Hz), 133.90 (d, J = 5.4 Hz), 129.62 (d, J = 2.9 Hz), 128.64, 127.77, 126.43, 125.76, 123.97, 121.85, 119.93, 99.10 (d, J = 196.4 Hz), 70.87, 56.62 (d, J = 17.9 Hz), 21.30, 21.27. IR (KBr): 3064, 3031, 2982, 2854, 1754, 1637, 1602, 1511, 1455, 1264, 1103, 937, 819, 760, 730, 701 cm–1. HRMS (ESI): m/z [M + H]+ calcd for (C21H21FNO2S)+: 370.1272; observed: 370.1271. Isopropyl (2R,3R)-2-(Benzo[d]thiazol-2-yl)-2-fluoro-3-(4-(trifluoromethyl)phenyl)pent-4-enoate (3ak): The compound 3ak was prepared according to the general procedure by using 1-allyl-4-(trifluoromethyl)benzene (37.2 mg). Eluent for column chromatography (petroleum ether/ethyl acetate = 50:1). Yield: 93% (40.7 mg); white solid; b/l > 20:1, dr = 5:1. Enantiomeric excess: 92%, determined by HPLC (CHIRALPAK IG, hexane/isopropanol = 95:5, flow rate 1.0 mL/min, T = 30 °C, 254 nm): tR = 5.208 (major), 5.670 (minor) min; [α]D 20 –10.2 (c 0.77, CHCl3). 1H NMR (500 MHz, CDCl3): δ = 8.58 (d, J = 8.2 Hz, 1 H), 8.36 (d, J = 8.0 Hz, 1 H), 8.07–8.01 (m, 4 H), 7.99–7.93 (m, 1 H), 7.91–7.84 (m, 1 H), 6.50–6.39 (m, 1 H), 5.52–5.41 (m, 2 H), 5.39–5.15 (m, 2 H), 1.43 (d, J = 6.3 Hz, 3 H), 1.35 (d, J = 6.3 Hz, 3 H). 19F NMR (471 MHz, CDCl3): δ = –62.63, –163.68. 13C NMR (126 MHz, CDCl3): δ = 166.19 (d, J = 31.8 Hz), 165.55 (d, J = 25.8 Hz), 153.35, 141.73, 135.25 (d, J = 2.1 Hz), 133.17 (d, J = 5.3 Hz), 130.07 (d, J = 2.9 Hz), 130.06 (q, J = 32.5 Hz), 126.55, 125.92, 125.57 (q, J = 3.8 Hz), 125.28 (q, J = 272.6 Hz), 124.03, 121.90, 120.70, 98.79 (d, J = 197.0 Hz), 71.17, 56.17 (d, J = 17.9 Hz), 21.29, 21.21. IR (KBr): 3055, 2989, 2964, 2933, 1747, 1510, 1329, 1266, 1193, 1118, 1071, 1015, 802, 761, 733 cm–1. HRMS (ESI): m/z [M + H]+ calcd for (C22H20F4NO2S)+: 438.1145; observed: 438.1140.