Visible-light-induced ortho-Perfluoroalkylation of para-Substituted Phenols and Anilines†

doi:10.7503/cjcu20170374

Abstract

Abstract:

A simple, clean visible-light-induced ortho-selective perfluoroalkylation of various phenols/anilines was developed. Using economic bromides/iodidesas as radical source and Ru(bpy)₃Cl₂ as catalyst, a series of para-substituted phenols/anilines underwent perfluoroalkylation efficiently under the irradiation of blue LEDs, leading to various perfluoroalkylated arenes in 80%—92% yields. Notably, various of perfluorinated moieties including C₃F₇, C₄F₉, C₆F₁₃, C₈F₁₇ and CF₂CO₂Et were incorporated efficiently into the phenols/aniline motifs without the protecting groups on the N/O-atom. The reaction proceeded under mild condition(room temperature) and green catalytic system. Arguably, it provides an effective and quick approach to fluoro-contained phenols/anilines with pharmaceutical value and biological activity.

Key words: Visible-light-induced, ortho-Perfluoroalkylation, Phenols, Aromatic anline

TrendMD:

YUAN Li, LI Zengzeng, JIANG Shengming, ZHU Yong, XIA Lülu, LI Lan, ZHAO Chuanqi, JIANG Ting, LEI Qian, TANG Shi. Visible-light-induced ortho-Perfluoroalkylation of para-Substituted Phenols and Anilines^†[J]. Chem. J. Chinese Universities, 2018, 39(2): 241.

Figures/Tables 5

References 20

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Compd.	Appearance	Yield^*(%)	m. p./℃	HRMS(calcd. ), m/z(M+H)⁺
3a	Pale yellow solid	92	28.3—29.3	390.9378(390.9375)
3b	Pale yellow solid	91	26.5—27.5	346.9876(346.9880)
3c	Rufous oil	80		342.0542(342.0540)
3d	Rufous oil	85		346.0042(346.0040)
3e	Yellow oil	86		340.9410(340.9407)
3f	White solid	89	63.3—64.3	490.9314(490.9311)
3g	Yellow oil	90		446.9819(446.9817)
3h	Pale yellow solid	88	78.1—78.7	590.9245(590.9247)
3i	Yellow oil	89		322.0247(322.0249)
3j	Rufous oil	85		417.9850(417.9853)
3k	Pale yellow solid	80	79.1—79.6	590.9245(590. 9247)

Compd.	Appearance	Yield^*(%)	m. p./℃	HRMS(calcd. ), m/z(M+H)⁺
3a	Pale yellow solid	92	28.3—29.3	390.9378(390.9375)
3b	Pale yellow solid	91	26.5—27.5	346.9876(346.9880)
3c	Rufous oil	80		342.0542(342.0540)
3d	Rufous oil	85		346.0042(346.0040)
3e	Yellow oil	86		340.9410(340.9407)
3f	White solid	89	63.3—64.3	490.9314(490.9311)
3g	Yellow oil	90		446.9819(446.9817)
3h	Pale yellow solid	88	78.1—78.7	590.9245(590.9247)
3i	Yellow oil	89		322.0247(322.0249)
3j	Rufous oil	85		417.9850(417.9853)
3k	Pale yellow solid	80	79.1—79.6	590.9245(590. 9247)

Compd.	¹H NMR, δ(400 MHz, CDCl₃)	¹³C NMR, δ(101 MHz, CDCl₃)	¹⁹F NMR, δ(376 MHz, CDCl₃)
3a	7.81(m, 2H), 7.29(d, J=1.2 Hz, 1H), 1.28(s, 1H)	153.0, 136.1(t, J=8.5 Hz), 118.6, 115.8(d, J=11.3 Hz), 112.7, 115.9—110.9(m)	-80.1—-80.9(m, 3F), -109.3—-109.4(m, 2F), -122.7—-122.9(m, 2F), -125.7—-125.8(m, 2F)
3b	7.67(s, 2H), 7.28(s, 1H), 1.61(s, 1H)	152.5, 133.3(d, J=8.9 Hz), 126.3, 121.8, 119.9, 118.3, 116.1—110.6(m)	-80.8—-80.9(m, 3F), -108.3—-108.4(m, 2F), -122.2—-122.3(m, 2F), -125.8—-125.9(m, 2F)
3c	6.96(dd, J=8.8, 2.9 Hz, 1H), 6.86(d, J=2.9 Hz, 1H), 6.71(d, J=8.9 Hz, 1H), 3.96(s, 2H), 3.78(s, 3H)	151.8, 139.8, 120.4, 119.5, 112.9(t, J=9.1 Hz), 100.0, 55.9	-80.9—-81.0(m, 3F), -108.8—-108.9(m, 2F), -112.6(d, J_F—F=274.3 Hz, 2F), -125.8—-125.9(m, 2F)
3d	7.38—7.13(m, 2H), 6.68(d, J=8.6 Hz, 1H), 4.27(s, 1H), 1.59(s, 1H)	153.1, 136.1, 118.8—118.4(m), 115.1—115.8(m), 112.7, 111.1—109.9(m), 108.9—105.9(m)	-80.8—-80.9(m, 3F), -109.2—-109.3(m, 2F), -122.6—-122.7(m, 2F), -125.8—-125.9(m, 2F)
3e	7.78(s, 2H), 7.31(s, 1H), 1.39—1.19(m, 1H)	152.9, 136.0(t, J=8.4 Hz), 118.6, 118.43—118.33(m), 117.98(d, J=53.9 Hz), 117.7—117.6(m), 115.2, 112.8, 111.7—107.2(m), 108.7	-80.1(t, J=9.8 Hz, 3F), -109.0—-109.1(m, 2F), -125.8—-125.9(m, 2F)
3f	7.69(s, 2H), 7.34(s, 1H), 1.27(s, 1H)	153.1, 136.1, 118.6, 115.9(t, J=26.7 Hz), 113.0—112.9(m), 111.69—108.98(m)	-80.9(t, J=8.2 Hz, 3F), -108.1(d, J_F—F=267 Hz, 1F), -109.7(d, J_F—F=263 Hz, 1F), -121.6(br, 2F), -122.8(br, 2F), -125.2—-126.8(m, 4F)
3g	7.68(s, 2H), 7.28(s, 1H), 1.28(s, 1H)	152.5, 133.3(t, J=8.8 Hz), 126.3, 118.6, 118.4, 118.2, 116.0—110.4(m)	-80.4(t, J=8.1 Hz, 3F), -108.5(d, J_F—F=267 Hz, 1F), -109.1(d, J_F—F=263 Hz, 1F), -121.7(br, 2F), -122.6(br, 2F), -125.4—-126.7(m, 4F)
3h	7.68(s, 2H), 7.29(s, 1H), 1.28(s, 1H)	155.2, 133.2(d, J=8.9 Hz), 126.1, 118.4, 116.0, 115.8—110.6(m)	-80.8(t, J=7.9 Hz, 3F), -108.1—-108.2(m, 1F), -109.7(d, J_F—F=270 Hz, 1F), -121.3—-121.9(m, 4F), -126.0(br, 4F), -126.1—-126.8(m, 4F)
3i	7.79—7.61(m, 1H), 7.42—7.17(m, 2H), 2.65(s, 6H)	154.9, 136.1, 131.9, 126.2, 119.2—117.9(m), 118.5, 113.4, 46.5, 29.7	-80.8—-80.9(m, 3F), -104.8(d, J_F—F=273.6 Hz, 2F), -124.8(d, J_F—F=274.3 Hz, 2F), -125.9—-126.0(m, 2F)
3j	7.84(s, 1H), 7.62(d, J=8.4 Hz, 1H), 7.31—7.17(m, 1H), 4.32(dd, J=13.3, 6.4 Hz, 2H), 2.56(s, 6H), 1.33(t, J=6.8 Hz, 3H)	151.5, 135.0, 132.9, 129.5(t, J=7.2 Hz), 124.5, 118.5, 110.6, 62.4, 45.3, 14.2	-97.6(d, ddd, J=264.2, 24.3, 9.0 Hz, 1F), -101.8(ddd, J=264.2, 23.9, 18.3 Hz, 1F)
3k	7.69(s, 2H), 7.34(s, 1H), 1.27(s, 1H)	153.1, 136.1, 118.6, 115.9(t, J=26.7 Hz), 113.0—112.9(m), 111.69—108.98(m)	-80.9(t, J=8.2 Hz, 3F), -108.1(d, J_F—F=267 Hz, 1F), -109.7(d, J_F—F=263 Hz, 1F), -121.6(br, 2F), -122.8(br, 2F), -125.2— -126.8(m, 4F)

Compd.	¹H NMR, δ(400 MHz, CDCl₃)	¹³C NMR, δ(101 MHz, CDCl₃)	¹⁹F NMR, δ(376 MHz, CDCl₃)
3a	7.81(m, 2H), 7.29(d, J=1.2 Hz, 1H), 1.28(s, 1H)	153.0, 136.1(t, J=8.5 Hz), 118.6, 115.8(d, J=11.3 Hz), 112.7, 115.9—110.9(m)	-80.1—-80.9(m, 3F), -109.3—-109.4(m, 2F), -122.7—-122.9(m, 2F), -125.7—-125.8(m, 2F)
3b	7.67(s, 2H), 7.28(s, 1H), 1.61(s, 1H)	152.5, 133.3(d, J=8.9 Hz), 126.3, 121.8, 119.9, 118.3, 116.1—110.6(m)	-80.8—-80.9(m, 3F), -108.3—-108.4(m, 2F), -122.2—-122.3(m, 2F), -125.8—-125.9(m, 2F)
3c	6.96(dd, J=8.8, 2.9 Hz, 1H), 6.86(d, J=2.9 Hz, 1H), 6.71(d, J=8.9 Hz, 1H), 3.96(s, 2H), 3.78(s, 3H)	151.8, 139.8, 120.4, 119.5, 112.9(t, J=9.1 Hz), 100.0, 55.9	-80.9—-81.0(m, 3F), -108.8—-108.9(m, 2F), -112.6(d, J_F—F=274.3 Hz, 2F), -125.8—-125.9(m, 2F)
3d	7.38—7.13(m, 2H), 6.68(d, J=8.6 Hz, 1H), 4.27(s, 1H), 1.59(s, 1H)	153.1, 136.1, 118.8—118.4(m), 115.1—115.8(m), 112.7, 111.1—109.9(m), 108.9—105.9(m)	-80.8—-80.9(m, 3F), -109.2—-109.3(m, 2F), -122.6—-122.7(m, 2F), -125.8—-125.9(m, 2F)
3e	7.78(s, 2H), 7.31(s, 1H), 1.39—1.19(m, 1H)	152.9, 136.0(t, J=8.4 Hz), 118.6, 118.43—118.33(m), 117.98(d, J=53.9 Hz), 117.7—117.6(m), 115.2, 112.8, 111.7—107.2(m), 108.7	-80.1(t, J=9.8 Hz, 3F), -109.0—-109.1(m, 2F), -125.8—-125.9(m, 2F)
3f	7.69(s, 2H), 7.34(s, 1H), 1.27(s, 1H)	153.1, 136.1, 118.6, 115.9(t, J=26.7 Hz), 113.0—112.9(m), 111.69—108.98(m)	-80.9(t, J=8.2 Hz, 3F), -108.1(d, J_F—F=267 Hz, 1F), -109.7(d, J_F—F=263 Hz, 1F), -121.6(br, 2F), -122.8(br, 2F), -125.2—-126.8(m, 4F)
3g	7.68(s, 2H), 7.28(s, 1H), 1.28(s, 1H)	152.5, 133.3(t, J=8.8 Hz), 126.3, 118.6, 118.4, 118.2, 116.0—110.4(m)	-80.4(t, J=8.1 Hz, 3F), -108.5(d, J_F—F=267 Hz, 1F), -109.1(d, J_F—F=263 Hz, 1F), -121.7(br, 2F), -122.6(br, 2F), -125.4—-126.7(m, 4F)
3h	7.68(s, 2H), 7.29(s, 1H), 1.28(s, 1H)	155.2, 133.2(d, J=8.9 Hz), 126.1, 118.4, 116.0, 115.8—110.6(m)	-80.8(t, J=7.9 Hz, 3F), -108.1—-108.2(m, 1F), -109.7(d, J_F—F=270 Hz, 1F), -121.3—-121.9(m, 4F), -126.0(br, 4F), -126.1—-126.8(m, 4F)
3i	7.79—7.61(m, 1H), 7.42—7.17(m, 2H), 2.65(s, 6H)	154.9, 136.1, 131.9, 126.2, 119.2—117.9(m), 118.5, 113.4, 46.5, 29.7	-80.8—-80.9(m, 3F), -104.8(d, J_F—F=273.6 Hz, 2F), -124.8(d, J_F—F=274.3 Hz, 2F), -125.9—-126.0(m, 2F)
3j	7.84(s, 1H), 7.62(d, J=8.4 Hz, 1H), 7.31—7.17(m, 1H), 4.32(dd, J=13.3, 6.4 Hz, 2H), 2.56(s, 6H), 1.33(t, J=6.8 Hz, 3H)	151.5, 135.0, 132.9, 129.5(t, J=7.2 Hz), 124.5, 118.5, 110.6, 62.4, 45.3, 14.2	-97.6(d, ddd, J=264.2, 24.3, 9.0 Hz, 1F), -101.8(ddd, J=264.2, 23.9, 18.3 Hz, 1F)
3k	7.69(s, 2H), 7.34(s, 1H), 1.27(s, 1H)	153.1, 136.1, 118.6, 115.9(t, J=26.7 Hz), 113.0—112.9(m), 111.69—108.98(m)	-80.9(t, J=8.2 Hz, 3F), -108.1(d, J_F—F=267 Hz, 1F), -109.7(d, J_F—F=263 Hz, 1F), -121.6(br, 2F), -122.8(br, 2F), -125.2— -126.8(m, 4F)

Entry	Initiator	Base/additive	Solvent	Yield of 3a^b(%)
1	Ru(bpy)₃Cl₂	K₃PO₄	DMF	65
2	Ru(bpy)₃Cl₂	K₃PO₄	Dioxane	59
3	Ru(bpy)₃Cl₂	K₃PO₄	DMSO	37
4	Ru(bpy)₃Cl₂	K₃PO₄	CH₃CN	44
5	Ru(bpy)₃Cl₂	K₃PO₄	DCE	48
6	Ru(bpy)₃Cl₂	CH₃COOK	DMF	47
7	Ru(bpy)₃Cl₂	K₂HPO₄	DMF	46
8	Ru(bpy)₃Cl₂	K₂CO₃	DMF	72
9^c	fac-Ir(ppy)₃	K₂CO₃	DMF	57
10	Ru(bpy)₃Cl₂	K₂CO₃/LiBr₂	DMF/C₅H₁₁OH	75
11	Ru(bpy)₃Cl₂	K₂CO₃/MnSO₄	DMF/C₅H₁₁OH	79
12	Ru(bpy)₃Cl₂	K₂CO₃/TBAI	DMF/C₅H₁₁OH	85
13	Ru(bpy)₃Cl₂	K₂CO₃/TBAI	DMF/C₂H₅OH	87
14	Ru(bpy)₃Cl₂	K₂CO₃/TBAI	DMF/t-BuOH	82
15	Ru(bpy)₃Cl₂	K₂CO₃/TBAI	DMF/CH₃OH	92
16^d	Ru(bpy)₃Cl₂	K₂CO₃/TBAI	DMF/CH₃OH	Trace
17^e	Ru(bpy)₃Cl₂	K₂CO₃/TBAI	DMF/CH₃OH	53