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Synlett 2011(14): 2085-2089  
DOI: 10.1055/s-0030-1261167
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Cascade Radical Reaction Induced by Polarity-Mismatched Perfluoroalkylation

Eito Yoshioka, Kentefu, Xin Wang, Shigeru Kohtani, Hideto Miyabe*
School of Pharmacy, Hyogo University of Health Sciences, Minatojima, Kobe 650-8530, Japan
Fax: +81(78)3042794; e-Mail: miyabe@huhs.ac.jp;
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Publication History

Received 27 May 2011
Publication Date:
10 August 2011 (online)

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Abstract

Cascade radical addition-cyclization-trapping reaction proceeded via the unfavorable polarity-mismatched addition of electrophilic perfluoroalkyl radicals to electron-deficient acceptors.

Key word

radical - fluoro - cyclization - enantioselective - cascade

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The structures of cis-2a,b, trans-2a,b and 3a,b were confirmed by HMQC, HMBC, and NOESY experiments.

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The absolute configuration at the stereocenter of cis-2a-d was assumed by similarity between the present reaction and the previously reported study. See ref. 10a.

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Both cis-9 and trans-9 were respectively obtained as two diastereomers concerning the newly generated stereocenter at iodinated carbon.

24

General Procedure for Enantioselective Radical Reaction: A solution of substrate 1 or 8 (100 mg or 106 mg, 0.43 mmol), Zn(OTf)2 (156 mg, 0.43 mmol) and ligand 7 (153 mg, 0.43 mmol) in CH2Cl2 (4.3 mL) was stirred for 1 h under Ar atmosphere at 20 ˚C. To the reaction mixture were added RI (2.15 mmol) and Et3B (1.05 M in hexane, 2.05 mL, 2.15 mmol) at -78 ˚C. After being stirred at the same temperature for 1-5 d, the reaction mixture was diluted with sat. NaHCO3 and then extracted with CH2Cl2. The organic phase was dried over Na2SO4 and concentrated at reduced pressure. The residue was roughly purified by preparative TLC (hexane-EtOAc, 3:1) to give the mixture of products. The ratio of products was determined by ¹H NMR analysis of the mixture. Second purification of the mixture by preparative TLC (benzene-EtOAc, 10:1 or hexane-EtOAc, 6:1, 2-fold development) afforded the isolated products.
Representative Products: cis -2a: colorless crystals; mp 99-99.5 ˚C (hexane). IR (KBr): 2948, 1717, 1458 cm-¹. ¹H NMR (CDCl3): δ = 7.38-7.50 (m, 5 H), 5.04 (d, J = 11.0 Hz, 1 H), 5.02 (d, J = 11.0 Hz, 1 H), 3.50 (dd, J = 9.2, 6.6 Hz, 1 H), 3.19-3.30 (m, 2 H), 2.73 (t, J = 11.4 Hz, 1 H), 2.39-2.58 (m, 2 H), 2.26 (br dd, J = 37.0, 16.0 Hz, 1 H), 1.32 (d, J = 1.6 Hz, 3 H). ¹³C NMR (CDCl3): δ = 170.8, 134.7, 129.6, 129.3, 128.7, 118.3 (tt, J = 257, 31 Hz), 117.5 (qt, J = 289, 34 Hz), 108.4 (tsext, J = 265, 36 Hz), 76.9, 51.1, 44.5, 44.2, 31.0 (t, J = 21 Hz), 22.2, 4.1. ¹9F NMR (CDCl3): δ = -80.6 (t, J = 19.5 Hz, 3 F), -106.2 (dm, J = 273 Hz, 1 F), -116.0 (dm, J = 273 Hz, 1 F), -128.3 (br s, 2 F). MS (EI+): m/z = 528 (25)
[M + H+], 91 (100). HRMS (EI+): m/z [M + H+] calcd for C17H18F7INO2: 528.0270; found: 528.0260. Anal. Calcd for C17H17F7INO2: C, 38.73; H, 3.25; N, 2.66. Found: C, 38.74; H, 3.22; N, 2.60. HPLC (Chiralcel AD-H, hexane-2-propanol, 95:5; flow: 1.0 mL/min, l = 254 nm); t R (major) = 6.7 min, t R (minor) = 8.9 min. A sample of 87% ee by HPLC analysis gave [α]²4 D +28.3 (c = 0.40, CHCl3). 3a: colorless oil. IR (KBr): 2968, 2932, 1714, 1455 cm-¹. ¹H NMR (CDCl3): δ = 7.34-7.47 (m, 5 H), 5.09 (d, J = 11.0 Hz, 1 H), 5.04 (d, J = 11.0 Hz, 1 H), 3.48 (t, J = 8.5 Hz, 1 H), 3.37 (dd, J = 8.5, 1.8 Hz, 1 H), 3.23 (d, J = 11.0 Hz, 1 H), 3.05 (d, J = 11.0 Hz, 1 H), 2.45 (m, 1 H), 2.26-2.42 (br m, 2 H), 1.30 (s, 3 H). ¹³C NMR (CDCl3): δ = 170.1, 134.7, 129.5, 129.1, 128.6, 117.6 (qt, J = 288, 34 Hz), 117.4 (tt, J = 256, 32 Hz), 108.4 (tsext, J = 265, 38 Hz), 77.2, 50.1 (d, J = 5 Hz), 44.0, 33.9, 28.1 (t, J = 21 Hz), 25.0, 6.4. ¹9F NMR (CDCl3): δ =
-80.9 (t, J = 9 Hz, 3 F), -113.7 (dm, J = 273 Hz, 1 F), -116.0 (dm, J = 273 Hz, 1 F), -127.8 (dd, J = 290, 5 Hz, 1 F), -128.2 (dd, J = 290, 5 Hz, 1 F). HRMS (ESI): m/z [M + H+] calcd for C17H18F7INO2: 528.0270; found: 528.0269.