Subscribe to RSS
DOI: 10.1055/s-0030-1261167
Cascade Radical Reaction Induced by Polarity-Mismatched Perfluoroalkylation
Publication History
Publication Date:
10 August 2011 (online)

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
- For general information details for radical reactions, see:
- 1a
Renaud P.Gerster M. Angew. Chem. Int. Ed. 1998, 37: 2562Reference Ris Wihthout Link - 1b
Sibi MP.Porter NA. Acc. Chem. Res. 1999, 32: 163Reference Ris Wihthout Link - 1c
Radicals
in Organic Synthesis
Vol. 1:
Renaud P.Sibi MP. Wiley-VCH; Weinheim: 2001.Reference Ris Wihthout Link - 1d
Radicals
in Organic Synthesis
Vol. 2:
Renaud P.Sibi MP. Wiley-VCH; Weinheim: 2001.Reference Ris Wihthout Link - 1e
Bar G.Parsons AF. Chem. Soc. Rev. 2003, 32: 251Reference Ris Wihthout Link - 1f
Sibi MP.Manyem S.Zimmerman J. Chem. Rev. 2003, 103: 3263Reference Ris Wihthout Link - 1g
Tojino M.Ryu I. Multicomponent ReactionsZhu J.Bienayme H. Wiley-VCH; Weinheim: .Reference Ris Wihthout Link - 1h
Zimmerman J.Sibi MP. Top. Curr. Chem. 2006, 263: 107Reference Ris Wihthout Link - 1i
Godineau E.Landais Y. Chem. Eur. J. 2009, 15: 3044Reference Ris Wihthout Link - 1j
Rowlands GJ. Tetrahedron 2009, 65: 8603Reference Ris Wihthout Link - 1k
Rowlands GJ. Tetrahedron 2010, 66: 1593Reference Ris Wihthout Link - 2a
Miyabe H.Takemoto Y. Chem. Eur. J. 2007, 13: 7280Reference Ris Wihthout Link - 2b
Yoshioka E.Kohtani S.Miyabe H. Heterocycles 2009, 79: 229Reference Ris Wihthout Link - 3a
Nishida M.Hayashi H.Nishida A.Kawahara N. Chem. Commun. 1996, 579Reference Ris Wihthout Link - 3b
Hiroi K.Ishii M. Tetrahedron Lett. 2000, 41: 7071Reference Ris Wihthout Link - 4a
Yang D.Gu S.Yan Y.-L.Zhu N.-Y.Cheung K.-K. J. Am. Chem. Soc. 2001, 123: 8612Reference Ris Wihthout Link - 4b
Yang D.Gu S.Yan Y.-L.Zhao H.-W.Zhu N.-Y. Angew. Chem. Int. Ed. 2002, 41: 3014Reference Ris Wihthout Link - 4c
Yang D.Zheng B.-F.Gao Q.Gu S.Zhu N.-Y. Angew. Chem. Int. Ed. 2006, 45: 255Reference Ris Wihthout Link - 5a
Curran DP.Liu W.Chen CH.-T. J. Am. Chem. Soc. 1999, 121: 11012Reference Ris Wihthout Link - 5b
Bruch A.Ambrosius A.Fröhlich R.Studer A.Guthrie DB.Zhang H.Curran DP. J. Am. Chem. Soc. 2010, 132: 11452Reference Ris Wihthout Link - 6a
Aechtner T.Dressel M.Bach T. Angew. Chem. Int. Ed. 2004, 43: 5849Reference Ris Wihthout Link - 6b
Bauer A.Westkämper F.Grimme S.Bach T. Nature (London) 2005, 436: 1139Reference Ris Wihthout Link - 6c
Breitenlechner S.Bach T. Angew. Chem. Int. Ed. 2008, 47: 7957Reference Ris Wihthout Link - 7
Gansäuer A.Shi L.Otte M. J. Am. Chem. Soc. 2010, 132: 11858 - 8a
Beeson TD.Mastracchio A.Hong J.-B.Ashton K.MacMillan DWC. Science 2007, 316: 582Reference Ris Wihthout Link - 8b
Jang H.-Y.Hong J.-B.MacMillan DWC. J. Am. Chem. Soc. 2007, 129: 7004Reference Ris Wihthout Link - 8c
Conrad JC.Kong J.Laforteza BN.MacMillan DWC. J. Am. Chem. Soc. 2009, 131: 11640Reference Ris Wihthout Link - 8d
Rendler S.MacMillan DWC. J. Am. Chem. Soc. 2010, 132: 5027Reference Ris Wihthout Link - 9a
Nicolaou KC.Reingruber R.Sarlah D.Bräse S.
J. Am. Chem. Soc. 2009, 131: 2086Reference Ris Wihthout Link - 9b
Nicolaou KC.Reingruber R.Sarlah D.Bräse S. J. Am. Chem. Soc. 2009, 131: 6640Reference Ris Wihthout Link - We have reported the strategy using hydroxamate ester as a coordination tether with a chiral Lewis acid. See:
- 10a
Miyabe H.Asada R.Toyoda A.Takemoto Y. Angew. Chem. Int. Ed. 2006, 45: 5863Reference Ris Wihthout Link - 10b
Miyabe H.Toyoda A.Takemoto Y. Synlett 2007, 1885Reference Ris Wihthout Link - 11a
Yajima T.Nagano H. Org. Lett. 2007, 9: 2513Reference Ris Wihthout Link - 11b
Nagib DA.Scott ME.MacMillan DWC. J. Am. Chem. Soc. 2009, 131: 10875Reference Ris Wihthout Link - 12 For a review on perfluoroalkyl radicals,
see:
Dolbier WR. Chem. Rev. 1996, 96: 1557 - 13a
Miura K.Taniguchi M.Nozaki K.Oshima K.Utimoto K. Tetrahedron Lett. 1990, 31: 6391Reference Ris Wihthout Link - 13b
Avila DV.Ingold KU.Lusztyk J.Dolbier WR.Pan H.-Q.Muir M. J. Am. Chem. Soc. 1994, 116: 99Reference Ris Wihthout Link - 13c
Iseki K.Asada D.Takahashi M.Nagai T.Kobayashi Y. Tetrahedron: Asymmetry 1996, 7: 1205Reference Ris Wihthout Link - 13d
Tsuchii K.Ueta Y.Kamada N.Einaga Y.Nomoto A.Ogawa A. Tetrahedron Lett. 2005, 46: 7275Reference Ris Wihthout Link - 13e
Cao H.-P.Xiao J.-C.Chen Q.-Y. J. Fluorine Chem. 2006, 127: 1079Reference Ris Wihthout Link - 13f
Mikami K.Tomita Y.Ichikawa Y.Amikura K.Itoh Y. Org. Lett. 2006, 8: 4671Reference Ris Wihthout Link - 13g
Uenoyama Y.Fukuyama T.Morimoto K.Nobuta O.Nagai H.Ryu I. Helv. Chim. Acta 2006, 89: 2483Reference Ris Wihthout Link - 13h
Petrik V.Cahard D. Tetrahedron Lett. 2007, 48: 3327Reference Ris Wihthout Link - 13i
Tomita Y.Ichikawa Y.Itoh Y.Kawada K.Mikami K. Tetrahedron Lett. 2007, 48: 8922Reference Ris Wihthout Link - 13j
Ma Z.Ma S. Tetrahedron 2008, 64: 6500Reference Ris Wihthout Link - 13k
Li Y.Li H.Hu J. Tetrahedron 2009, 65: 478Reference Ris Wihthout Link - 14a
Qiu Z.-M.Burton DJ. J. Org. Chem. 1995, 60: 3465Reference Ris Wihthout Link - 14b
Yajima T.Nagano H.Saito C. Tetrahedron Lett. 2003, 44: 7027Reference Ris Wihthout Link - 14c
Tonoi T.Nishikawa A.Yajima T.Nagano H.Mikami K. Eur. J. Org. Chem. 2008, 1331Reference Ris Wihthout Link - 14d
Ueda M.Iwasada E.Miyabe H.Miyata O.Naito T. Synthesis 2010, 1999Reference Ris Wihthout Link - 16 In general, the copper(II) Lewis
acids are unsuitable for radical reactions due to extinction of
radical species. For a successful example of radical reaction using
copper(II) Lewis acids, see:
Friestad GK.Shen Y.Ruggles EL. Angew. Chem. Int. Ed. 2003, 42: 5061 - 17
Smart BE. In Chemistry of Organic Fluorine Compounds II, ACS Monograph 187Hudlicky M.Pavlath SE. American Chemical Society; Washington DC: 1995. p.979-1010 - For studies on reactivity and structure of perfluoroalkyl radicals, see:
- 18a
Krusic PJ.Bingham RC. J. Am. Chem. Soc. 1976, 98: 230Reference Ris Wihthout Link - 18b
Bernardi F.Cherry W.Shaik S.Epiotis ND. J. Am. Chem. Soc. 1978, 100: 1352Reference Ris Wihthout Link - 18c
Dewar MJS.Olivella S. J. Am. Chem. Soc. 1978, 100: 5290Reference Ris Wihthout Link - 18d
Wong MW.Pross A.Radom L. J. Am. Chem. Soc. 1994, 116: 11938Reference Ris Wihthout Link - 20
Avilla DV.Ingold KU.Lusztyk J.Dolbier WR.Pan H.-Q.Muir M. J. Am. Chem. Soc. 1994, 116: 99 - 22a
Sibi MP.Yang Y.-H. Synlett 2008, 83Reference Ris Wihthout Link - 22b
Evans DA.Kozlowski MC.Tedrow JS. Tetrahedron Lett. 1996, 37: 7481Reference Ris Wihthout Link
References and notes
The structures of cis-2a,b, trans-2a,b and 3a,b were confirmed by HMQC, HMBC, and NOESY experiments.
19The electrophilicity of perfluoroalkyl radicals followed the order 1˚ < 2˚ < 3˚; see ref. 12.
21The 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.
23Both 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.