Journal of Fluorine Chemistry 168 (2014) 50–54

Visible-light-mediated trifluoroethylation of 2-isocyanobiaryl withtrifluoroethyl iodide: Synthesis of 6-trifluoroethyl-phenanthridines

Weijun Fu a,*, Mei Zhu a, Chen Xu a, Guanglong Zou b,*, Zhiqiang Wang a, Baoming Ji a

a College of Chemistry and Chemical Engineering, Luoyang Normal University, Luoyang 471022, PR Chinab School of Chemistry and Enviromental Science, Guizhou Minzu Univeristy, Guiyang 550025, PR China

A R T I C L E I N F O

Article history:

Received 7 July 2014

Received in revised form 28 August 2014

Accepted 29 August 2014

Available online 8 September 2014

Keywords:

Trifluoroethylation

Phenanthridines

Photoredox

Radical reactions

Isocyanobiaryl

A B S T R A C T

A practical strategy has been described for the preparation of 6-trifluoroethyl-phenanthridine

derivatives using a visible-light-promoted trifluoroethylation reaction of 2-isocyanobiaryl with

trifluoroethyl iodide. These reactions could be carried out at room temperature in good to excellent

chemical yields with good functional group tolerance.

� 2014 Elsevier B.V. All rights reserved.

Contents lists available at ScienceDirect

Journal of Fluorine Chemistry

jo ur n al h o mep ag e: www .e lsev ier . c om / loc ate / f luo r

1. Introduction

The incorporation of fluorine or fluorine-containing functionalgroups can effectively improves the physicochemical properties ofparent molecules. As a result, fluorinated compounds are widelyused in pharmaceuticals, agrochemicals, and materials because oftheir unique lipophilicity and bioactivities [1–6]. Among variousfluorinated moieties, the trifluoromethyl group (CF3) has attractedincreasing attention owing to its capacity to act as a lipophilicelectron-withdrawing group [7,8]. In the past decade, manydistinct methods for the incorporation of CF3 groups into targetmolecules have been developed [9–16]. Yet, compared totrifluoromethylation chemistry, the analogous trifluoroethylation(selective introduction of a CF3CH2 into organic molecules) is muchless studied. Recently, significant progress has been achieved forthe preparation of trifluoroethylated organic compounds is thedirect generation of C–CH2CF3 bonds. Transition-metal-catalyzedcross-coupling trifluoroethylation reactions starting from arylhalides [17,18], boronic acids [19,20], alkynes and alkynylcarboxylic acids [21,22] have emerged as a powerful methodsfor C(sp2/sp)–CH2CF3 bond formation. Another frequently used

* Corresponding author at: Luoyang Normal University, College of Chemistry and

Chemical Engineering, Luoyang 471022, China. Tel.: +81 03969810261.

E-mail address: wjfu@lynu.edu.cn (W. Fu).

http://dx.doi.org/10.1016/j.jfluchem.2014.08.022

0022-1139/� 2014 Elsevier B.V. All rights reserved.

strategy is the utilization of high reactivity of CF3CH2 radical. Forexample, Baran et al. reported direct C–H trifluoroethylation ofnitrogen-containing heterocyclic compounds with the combina-tion of (CF3CH2SO2)2Zn and tBuOOH [23]. However, most of themethods still require prefunctionalized substrates or expensiveBaran’s reagent, which greatly limits its general application inchemical syntheses. Therefore, the development of alternativedirect trifluoroethylation reactions performed at milder conditionsis highly desirable.

On the other hand, visible-light photoredox catalysis hasattracted substantial attention because of its environmentalcompatibility and versatility in promoting a large number ofsynthetically important reactions [24–31]. Recently, visible-lightphotocatalyzed direct trifluoromethyl ation of arenes, heteroar-enes, arylboronic acids and alkenes have been explored [32–37]. Incontrast to these impressive progresses, until recently there wererather few practical methods for related visible-light photocata-lyzed trifluoroethylation. For instance, Carreira reported a cobalt-catalyzed photochemical synthesis of allylic trifluoromethanesfrom styrene derivatives using 2,2,2-trifluoroethyl iodide [38]. Onthe basis of this work and in connection with our interest radicalcyclizations [39–43], we communicate herein our recent studieson the visible-light-promoted trifluoroethylation of 2-isocyano-biaryl using the cheap and available reagent CF3CH2I as the sourceof the CH2CF3 group to afford 6-trifluoroethyl-phenanthridinederivatives (Scheme 1) [44–53].

I) Previou s work

II) This w ork

CF3

CH2CF3

ref. [45-47]

(Trifluorome thylation of Is onitriles)

visible-li ght

(Trifluo roethylation of Ison itriles)

NCF3

N CR1

R2 R1 R2

N CR1

R2

NCH2CF3

R1 R2

or Umemotoʼs reag ent

Scheme 1. The main approaches to CF3-containing phenanthridines.

W. Fu et al. / Journal of Fluorine Chemistry 168 (2014) 50–54 51

2. Results and discussion

At the outset of this investigation, 2-isocyanobiphenyl 1a andICH2CF3 were chosen as the model substrates to optimize thereaction conditions. As shown in Table 1, irradiation of the solutionof 1a and ICH2CF3 in DMF with a 5 W blue LED bulb in the presence ofRu(bpy)3Cl2�6H2O (2 mol%; bpy = 2,20-bipyridine) and N,N-diisopro-pylethylamine (DIPEA, 2.0 equiv) at room temperature afforded thedesired product 2a in 53% yield (Table 1, entry 1). Changing thecatalyst to [fac-Ir(III) (ppy)3] (ppy = 2-phenyl pyridine), a complexwith superior reduction capacity in the excited state, dramaticallyenhanced the yield to 82% (Table 1, entry 2). Other photocatalysts,such as, [Ir(ppy)2(dtbbpy)]PF6, Ru(bpy)3(PF6)2, eosin Y were alsotested, but none of them gave better results than [fac-Ir(III) (ppy)3](Table 1, entries 3–5). A brief screen of the bases revealed that K2CO3

was the best choice for the reaction. The base did not affect thistransformation significantly and other organic or inorganic bases,such as Et3N, (nBu)3N, Na2CO3 and NaHCO3 also gave good yields ofthe isolated products (Table 1, entries 6–10). The reaction proceeds

Table 1Optimization of reaction conditions for 2aa.

NCH2CF3

1a 2a

Photocatalyst, Base

Solvent, 5 W blue LED+ CF3CH2I

N C

Entry Catalyst Ba

1 Ru(bpy)3Cl2�6H2O (iP

2 fac-Ir(ppy)3 (iP

3 [Ir(ppy)2(dtbbpy)]PF6 (iP

4c Ru(bpy)3(PF6)2 (iP

5 Eosin Y (iP

6 fac-Ir(ppy)3 Et

7 fac-Ir(ppy)3 (n

8 fac-Ir(ppy)3 K2

9 fac-Ir(ppy)3 Na

10 fac-Ir(ppy)3 Na

11 fac-Ir(ppy)3 K2

12 fac-Ir(ppy)3 K2

13 fac-Ir(ppy)3 K2

14 – K2

15c fac-Ir(ppy)3 K2

a Reaction conditions: 1a (0.3 mmol, 1.0 equiv), CF3CH2I (0.9 mmol, 3.0 equiv), base (0

(3.0 mL) was irradiated with a 5 W blue LED for 24 h.b Isolated yield.c No irradiation.

well in DMF and CH3CN provided slightly lower yield, while othersolvents such as DMSO and CH2Cl2 were found to be less effective forthis reaction (Table 1, entries 11–13). In the control experiments, noproduct was observed in the absence of either light or the catalyst,and large amounts of starting materials remained unreacted(Table 1, entries 14–15).

With the optimized reaction conditions in hand, we furtherexplored the scope of trifluoroethylation with a variety ofbiphenyl isocyanides (Table 2). The effect of substituents on thearene (Ar2) undergoing the cyclization reaction was firstexamined. This aromatic ring was found to be tolerant of bothelectron-rich groups such as methyl (2b), ethyl (2c) and methoxy(2e) and electron-deficient groups such as trifluoromethyl (2h)and cyano (2i) on the para-position. The Cl-containing substrate(2g) was also compatible and gave the corresponding products ingood yields, which allows further functionalization of thephenanthridines. The reaction was more sensitive to the positionof the substituents. For ortho-substituted substrates, thecorresponding phenanthridines (2k) were obtained in low yieldsdue to the steric effect. Additionally, when a bulky 1-naphthyl1m was used, the desired product was obtained in low yield(2m). The use of 2-naphthyl substrate 1l resulted in a mixture ofthe products 2l and 2l’ with regioselectivity (12:1). Next, thesubstituent effect at the arene moiety Ar1 was evaluated. In allcases, substrates 1n–r proceeded smoothly to give the corre-sponding trifluoroethylated phenanthridines 2n–r in moderateto good yields.

To gain mechanistic insight into the photoredox-catalyzedcyclization, the reaction was performed in presence of the radicalscavenger TEMPO (2,2,6,6-tetramethylpiperidine 1-oxyl). Underthese conditions, the reaction was completely shut off, which couldindicate that this reaction involves radical intermediates (Scheme 2).

On the basis of the experimental observation and literatures[44–53], catalytic cycle is proposed for this transformation(Scheme 3). First, the photocatalyst [fac-Ir(III)(ppy)3] is irradiatedto the excited state [fac-Ir(III)(ppy)3

*] which is oxidativelyquenched by CF3CH2I with the generation of a [fac-Ir(IV)(ppy)3]+

complex and a trifluoroethyl radical species A. The addition of the

se Solvent Yieldb (%)

r)2NEt DMF 53

r)2NEt DMF 82

r)2NEt DMF 74

r)2NEt DMF 55

r)2NEt DMF 42

3N DMF 80

Bu)3N DMF 85

CO3 DMF 88

2CO3 DMF 84

HCO3 DMF 83

CO3 CH3CN 77

CO3 DMSO 43

CO3 CH2Cl2 30

CO3 DMF NR

CO3 DMF NR

.6 mmol, 2.0 equiv), and photocatalyst (0.006 mmol, 2.0 mol%) in indicated solvent

Table 2Trifluoroethylation of substituted 2-isocyanobiaryla.

a Reaction conditions: 1 (0.3 mmol), CF3CH2I (0.9 mmol, 3.0 equiv), base (0.6 mmol,

2.0 equiv), and fac-Ir(ppy)3 (0.006 mmol, 2.0 mol%) in DMF (3.0 mL) was irradiated

with a 5 W blue LED for 24 h.b The ratio of regioisomers based on 19F NMR analysis.

N CH2CF 3

Me

N CH2CF 3

Et

N CH2CF 3

nPr

N CH2CF 3

OMe2b, 88% 2c, 87% 2d, 90%

2e, 91%N CH2CF 3

F

N CH2CF 3

Cl

N CH2CF 3

CF3

N CH2CF 3

CN2f, 77% 2g, 80%

2h, 72% 2i, 70%

2l+2l' , 64% (12:1)b

NCH2CF 3

NCH2CF 3

+

N CH2CF 3

Me

2o, 81%

2q, 72%

N CH2CF 3

F

2n, 77%

N CH2CF 3F3CN CH2CF 3

Me

Me

N CH2CF 3

Cl

Cl2p, 80% 2r, 73%

N CH2CF 3

Ph

2j, 75%

2k, 60%N CH2CF 3

Me

NCH2CF 3

2m, 58%

NCH2CF 3

+ CF3CH 2I

N C

K2CO 3, DMF

2 mol% fac-Ir( ppy)3

5W blue LED

Ar1Ar1 Ar2Ar2

1 2

Stand ard cond itions

3.0 equiv TEMPO

not de tected

NCH2CF31a 2a

+ CF3CH2I

N C

Scheme 2. The control experiments using TEMPO.

W. Fu et al. / Journal of Fluorine Chemistry 168 (2014) 50–5452

trifluoroethyl radical to 1a generates imidoyl radical intermediateB, which undergoes intramolecular homolytic aromatic substitu-tion to give the radical intermediate C. The intermediate C is thenoxidized by [fac-Ir(IV)(ppy)3]+ to form the cyclohexadienyl cation

CF3CH2I

Ir(III )

CF3CH2 Ir( IV)+

Ir(III )*visible

C

A

1a

N

B

NCH2CF3

Scheme 3. Plausible re

D and regenerates [fac-Ir(III)(ppy)3]. Ultimately deprotonationassisted by base yields the product 2a.

3. Conclusion

In conclusion, we have reported a facile assembly of6-trifluoroethyl-phenanthridines through visible-light-promotedtandem carbotrifluoroethylation of biphenyl isocyanides withICH2CF3. The reaction was found to tolerate a wide range offunctional groups. Most importantly, the trifluoroethyl moiety(CH2CF3) could be easily introduced into the scaffold of phenan-thridine under mild and environmentally friendly conditions.

4. Experimental

4.1. General

All reactions were performed in a 20 mL tube equipped with arubber septum at room temperature. Photo-irradiation was carriedout with a 5 W blue LED. Solvents were purified or dried in astandard manner. Reactions were monitored by TLC on silica gelplates (GF254), and the analytical thin-layer chromatography(TLC) was performed on precoated, glass-backed silica gel plates.1H NMR spectra and 13C NMR spectra were measured in CDCl3 andrecorded on a 400 or 500 MHz NMR spectrometers with TMS as aninternal standard. 19F NMR was recorded on a Varian 500 spec-trometer (CFCl3 as an internal standard). The 19F NMR data forproducts 2f, 2l, and 2n were measured under H-decouplingmanner. HRMS analyses were recorded on Waters Q-TOF Globalmass spectrometer. For chromatography, 300–400 mesh silica gel(Qingdao, China) was employed.

4.2. Typical procedure for synthesis of 6-trifluoroethyl-

phenanthridines

To a mixture of 1a–r (0.3 mmol) CF3CH2I (0.9 mmol), and K2CO3

(0.6 mmol) in 3.0 mL of DMF was added fac-Ir(ppy)3 (0.006 mmol,

2a

ligh t

D-H+

Base

N CH2CF3

CH2CF3

N CH2CF3

action mechanism.

W. Fu et al. / Journal of Fluorine Chemistry 168 (2014) 50–54 53

2.0 mol%) under N2 atmosphere. The solution was stirred at roomtemperature under 5 W blue LED irradiation for 24 h. Then thereaction mixture was diluted by adding EtOAc and brine. Theaqueous layer was extracted with EtOAc The combined organiclayer was dried over MgSO4, filtered and concentrated. The residuewas purified by flash column chromatography (petroleum ether/ethyl acetate 20:1 as the eluant) on silica gel to give the desiredphenanthridines 2a–r.

4.2.1. 6-(2,2,2-Trifluoroethyl)phenanthridine (2a)

White solid, mp 99–101 8C; 1H NMR (400 MHz, CDCl3): d = 8.57(d, J = 8.4 Hz, 1H), 8.49 (d, J = 8.0 Hz, 1H), 8.14 (t, J = 8.4 Hz, 2H),7.79 (t, J = 7.6 Hz, 1H), 7.62–7.74 (m, 3H), 4.17 (q, J = 10.4 Hz, 2H);13C NMR (125 MHz, CDCl3): d = 151.1 (q, J = 2.0 Hz), 143.4, 133.2,130.8, 130.1, 128.9, 127.6, 127.5, 126.2, 125.7 (q, J = 276.2 Hz),125.5, 124.0, 122.5, 122.0, 40.5 (q, J = 28.8 Hz). 19F NMR (470 MHz,CDCl3) d = �62.4 (t, J = 10.3 Hz, 3F). HRMS: calc. for [M + H]+

C15H11F3N: 262.0838, found: 262.0840.

4.2.2. 8-Methyl-6-(2,2,2-trifluoroethyl)phenanthridine (2b)

White solid, mp 92–94 8C; 1H NMR (400 MHz, CDCl3): d = 8.42(d, J = 8.0 Hz, 2H), 8.13 (d, J = 8.0 Hz, 1H), 8.78 (s, 1H), 7.65–7.69 (m,1H), 7.58–7.62 (m, 2H), 4.14 (q, J = 10.0 Hz, 2H), 2.55 (s, 3H); 13CNMR (125 MHz, CDCl3): d = 147.1 (q, J = 32.2 Hz), 142.8, 135.8,135.6, 133.5, 131.5, 128.5, 128.4, 127.4, 126.6, 126.5, 124.3 (q,J = 3.6 Hz), 123.2, 122.1 (q, J = 275.6 Hz), 27.1. 19F NMR (470 MHz,CDCl3) d = �62.4 (t, J = 10.3 Hz, 3F). HRMS: calc. for [M + H]+

C16H13F3N: 276.0955, found: 276.0955.

4.2.3. 8-Ethyl-6-(2,2,2-trifluoroethyl)phenanthridine (2c)

White solid, mp 104–106 8C; 1H NMR (400 MHz, CDCl3):d = 8.46–8.51 (m, 2H), 8.14 (d, J = 8.0 Hz, 1H), 7.93 (s, 1H), 7.60–7.70 (m, 3H), 4.18 (q, J = 10.4 Hz, 2H), 2.87 (q, J = 8.0 Hz, 2H), 1.35 (t,J = 8.0 Hz, 3H); 13C NMR (125 MHz, CDCl3): d = 150.9 (q, J = 4.1 Hz),143.9, 143.1, 131.5, 131.3, 130.1, 129.1, 128.5, 127.5, 125.73,125.74 (q, J = 277.5 Hz), 124.5, 124.2, 122.5, 121.8, 40.5 (q,J = 28.9 Hz), 29.2, 15.6. 19F NMR (470 MHz, CDCl3) d = �62.3 (t,J = 10.3 Hz, 3F). HRMS: calc. for [M + H]+ C17H15F3N: 290.1151,found: 290.1150.

4.2.4. 8-Propyl-6-(2,2,2-trifluoroethyl)phenanthridine (2d)

White solid, mp 100–102 8C; 1H NMR (400 MHz, CDCl3):d = 8.47–8.52 (m, 2H), 8.14 (d, J = 8.0 Hz, 1H), 7.92 (s, 1H),7.60–7.70 (m, 3H), 4.18 (q, J = 10.4 Hz, 2H), 2.82 (t, J = 7.2 Hz,2H), 1.73–1.78 (m, 2H), 0.99 (t, J = 7.2 Hz, 3H); 13C NMR (125 MHz,CDCl3): d = 150.9 (q, J = 3.5 Hz), 143.1, 142.4, 131.9, 131.3, 130.0,128.4, 127.8, 125.8 (q, J = 276.6 Hz), 125.6, 125.2, 124.2, 122.4,121.8, 40.5 (q, J = 28.9 Hz), 38.2, 24.6, 13.7. 19F NMR (470 MHz,CDCl3) d = �62.3 (t, J = 10.8 Hz, 3F). HRMS: calc. for [M + H]+

C18H17F3N: 304.1308, found: 304.1310.

4.2.5. 6-(2,2,2-Trifluoroethyl)-8-methoxyphenanthridine (2e)

White solid, mp 106–107 8C; 1H NMR (400 MHz, CDCl3):d = 8.49 (d, J = 8.4 Hz, 1H), 8.41 (d, J = 8.0 Hz, 1H), 8.13 (d,J = 8.0 Hz, 1H), 7.60–7.68 (m, 2H), 7.43–7.45 (m, 2H), 4.13 (q,J = 10.0 Hz, 2H), 3.96 (s, 3H); 13C NMR (125 MHz, CDCl3): d = 158.8,150.2 (q, J = 2.4 Hz), 142.6, 130.1, 127.9, 127.6, 127.5, 126.8, 125.8(q, J = 276.4 Hz), 124.2, 121.5, 121.3, 106.4, 55.5, 40.7 (q,J = 28.8 Hz). 19F NMR (470 MHz, CDCl3) d = �62.3 (t, J = 10.3 Hz,3F). HRMS: calc. for [M + H]+ C16H13F3NO: 292.0944, found:292.0950.

4.2.6. 8-Fluoro-6-(2,2,2-trifluoroethyl)phenanthridine (2f)White solid, mp 111–113 8C; 1H NMR (400 MHz, CDCl3):

d = 8.55–8.59 (m, 1H), 8.42 (d, J = 8.0 Hz, 1H), 8.15 (d, J = 8.4 Hz,1H), 7.63–7.77 (m, 3H), 7.54–7.59 (m, 1H), 4.11 (q, J = 10.4 Hz, 2H);

13C NMR (125 MHz, CDCl3): d = 161.4 (d, J = 247.6 Hz), 150.2, 143.1,130.3, 129.8, 128.8, 127.9, 126.6 (d, J = 4.1 Hz), 125.5 (q,J = 288.8 Hz), 125.1 (d, J = 9.6 Hz), 123.5, 121.7, 120.0 (d,J = 23.6 Hz), 110.8 (d, J = 22.3 Hz), 40.6 (q, J = 30.0 Hz). 19F NMR(470 MHz, CDCl3) d = �62.5 (s, 3F), �111.2 (s, 1F). HRMS: calc. for[M + H]+ C15H10F4N: 280.0744, found: 280.0744.

4.2.7. 8-Chloro-6-(2,2,2-trifluoroethyl)phenanthridine (2g)

White solid, mp 108–110 8C; 1H NMR (400 MHz, CDCl3):d = 8.51 (d, J = 8.8 Hz, 1H), 8.44 (d, J = 8.0 Hz, 1H), 8.15 (d, J = 8.0 Hz,1H), 8.10 (s, 1H), 7.72–7.77 (m, 1H), 7.65–7.67 (m, 1H), 4.13 (q,J = 10.4 Hz, 2H); 13C NMR (125 MHz, CDCl3): d = 150.0 (q, J = 2.8 Hz),143.3, 133.7, 131.5, 131.3, 130.3, 129.3, 128.0, 126.3, 125.5, 125.4 (q,J = 277.6 Hz), 124.2, 123.4, 121.8, 40.4 (q, J = 30.1 Hz). 19F NMR(470 MHz, CDCl3) d = �62.4 (t, J = 10.3 Hz, 3F). HRMS: calc. for[M + H]+ C15H10ClF3N: 296.0449, found: 296.0453.

4.2.8. 6-(2,2,2-Trifluoroethyl)-8-(trifluoromethyl)phenanthridine

(2h)

White solid, mp 122–124 8C; 1H NMR (400 MHz, CDCl3):d = 8.77 (d, J = 8.8 Hz, 1H), 8.57 (d, J = 8.4 Hz, 1H), 8.45 (s, 1H),8.22 (d, J = 8.4 Hz, 1H), 8.06 (d, J = 8.8 Hz, 1H), 7.83 (t, J = 8.0 Hz,1H), 7.75 (d, J = 8.0 Hz, 1H), 4.24 (q, J = 10.0 Hz, 2H); 13C NMR(125 MHz, CDCl3): d = 151.0 (q, J = 3.4 Hz), 144.1, 135.4, 130.5,130.2, 129.5 (q, J = 33.5 Hz), 128.2, 126.7, 126.6, 125.4 (q,J = 276.9 Hz), 124.8, 123.9 (q, J = 270.9 Hz), 123.7, 123.1,122.3,40.6 (q, J = 29.7 Hz). 19F NMR (470 MHz, CDCl3) d = �62.3 (s, 3F),�62.6 (t, J = 9.9 Hz, 3F). HRMS: calc. for [M + H]+ C16H10F6N:330.0712, found: 330.0711.

4.2.9. 6-(2,2,2-Trifluoroethyl)phenanthridine-8-carbonitrile (2i)White solid, mp 117–119 8C; 1H NMR (400 MHz, CDCl3):

d = 8.76 (d, J = 8.8 Hz, 1H), 8.54–8.58 (m, 2H), 8.23 (d, J = 8.0 Hz,1H), 8.04 (d, J = 8.4 Hz, 1H), 7.87 (t, J = 8.0 Hz, 1H), 7.77 (t, J = 8.0 Hz,1H), 4.21 (q, J = 10.4 Hz, 2H); 13C NMR (125 MHz, CDCl3): d = 150.4(q, J = 4.1 Hz), 144.4, 135.8, 132.0, 131.6, 130.8, 130.6, 128.5, 125.3(q, J = 277.5 Hz), 125.0, 124.0, 122.8, 122.5, 118.3, 111.3, 40.5 (q,J = 29.5 Hz). 19F NMR (470 MHz, CDCl3) d = �62.5 (t, J = 10.8 Hz,3F). HRMS: calc. for [M + H]+ C16H10F3N2: 287.0791, found:287.0801.

4.2.10. 6-(2,2,2-Trifluoroethyl)-8-phenylphenanthridine (2j)White solid, mp 101–103 8C; 1H NMR (400 MHz, CDCl3):

d = 8.65 (d, J = 8.4 Hz, 1H), 8.52 (d, J = 8.4 Hz, 1H), 8.33 (s, 1H),8.17 (d, J = 8.0 Hz, 1H), 8.05 (d, J = 8.8 Hz, 1H), 7.64–7.74 (m, 4H),7.52 (t, J = 7.2 Hz, 2H), 7.41–7.45 (m, 1H), 4.24 (q, J = 10.4 Hz, 2H);13C NMR (125 MHz, CDCl3): d = 151.2 (q, J = 3.1 Hz), 143.4, 140.6,140.2, 132.2, 130.2, 129.2, 128.9, 128.1, 127.7, 127.5, 125.9, 125.7(q, J = 277.6 Hz), 124.4, 123.9, 123.1, 122.0, 40.6 (q, J = 28.8 Hz). 19FNMR (470 MHz, CDCl3) d = �62.3 (t, J = 10.3 Hz, 3F). HRMS: calc. for[M + H]+ C21H15F3N: 338.1151, found: 338.1155.

4.2.11. 6-(2,2,2-Trifluoroethyl)-10-methylphenanthridine (2k)

White solid, mp 78–80 8C; 1H NMR (400 MHz, CDCl3): d = 8.82 (d,J = 8.4 Hz, 1H), 8.22 (d, J = 8.0 Hz, 1H), 8.13 (d, J = 8.0 Hz, 1H),7.63–7.78 (m, 4H), 4.23 (q, J = 10.0 Hz, 2H), 3.15 (s, 3H); 13C NMR(125 MHz, CDCl3): d = 151.7 (q, J = 2.25 Hz), 144.6, 135.8, 135.1,132.8, 130.5, 128.1, 127.0, 126.7, 126.6, 125.5, 125.7 (q, J = 275.5 Hz),124.8, 122.0, 40.1 (q, J = 29.0 Hz), 26.9. 19F NMR (470 MHz, CDCl3)d = �62.3 (t, J = 10.3 Hz, 3F). HRMS: calc. for [M + H]+ C16H13F3N:276.0955, found: 276.0961.

4.2.12. 5-(2,2,2-Trifluoroethyl)benzo[i]phenanthridine and

6-(2,2,2-Trifluoroethyl)benzo[j]phenanthridine (2l:2l0 = 12:1)

White solid. 1H NMR (400 MHz, CDCl3): d = 8.54–8.57 (m, 3H),8.21 (d, J = 8.4 Hz, 1H), 8.10 (d, J = 8.8 Hz,1H), 8.00 (d, J = 8.0 Hz,1H),

W. Fu et al. / Journal of Fluorine Chemistry 168 (2014) 50–5454

7.64–7.79 (m, 4H), 4.56 (q, J = 9.6 Hz, 2H); 13C NMR (125 MHz,CDCl3): d = 149.0, 143.6, 134.3, 133.3, 132.2, 129.7, 129.4, 129.3,129.2, 127.3, 126.8, 126.3, 125.8 (q, J = 276.7 Hz), 123.4, 122.6,122.5, 120.2, 44.3 (q, J = 27.6 Hz), 19F NMR (470 MHz, CDCl3)d = �60.79 (s, 3F), �60.80 (s, 0.25F). HRMS: calc. for [M + H]+

C19H13F3N: 312.0995, found: 312.0995.

4.2.13. 6-(2,2,2-Trifluoroethyl)benzo[k]phenanthridine (2m)

White solid, mp 93–95 8C; 1H NMR (400 MHz, CDCl3):d = 9.13–9.16 (m, 1H), 9.02 (d, J = 8.4 Hz, 1H), 8.30 (d, J = 8.4 Hz,1H), 8.03–8.12 (m, 3H), 7.74–7.81 (m, 4H), 4.29 (q, J = 10.0 Hz, 2H);13C NMR (125 MHz, CDCl3): d = 150.1, 145.4, 134.6, 132.6, 130.0,129.0, 128.7, 128.68, 128.6, 128.2, 127.2, 127.1, 127.0, 125.7 (q,J = 275.6 Hz), 124.3, 122.3, 40.7 (q, J = 29.5 Hz). 19F NMR (470 MHz,CDCl3) d = �61.1 (t, J = 10.3 Hz, 3F). HRMS: calc. for [M + H]+

C19H13F3N: 312.0995, found: 312.0997.

4.2.14. 2-Fluoro-6-(2,2,2-trifluoroethyl)phenanthridine (2n)

White solid, mp 114–116 8C; 1H NMR (400 MHz, CDCl3):d = 8.46 (d, J = 8.4 Hz, 1H), 8.08–8.18 (m, 3H), 7.84 (7, J = 8.0 Hz,1H), 7.73 (7, J = 8.0 Hz, 1H), 7.43–7.48 (m, 1H), 4.16 (q, J = 10.4 Hz,2H); 13C NMR (125 MHz, CDCl3): d = 161.6 (d, J = 246.4 Hz), 150.4(d, J = 3.5 Hz), 140.3, 132.6 (d, J = 4.3 Hz), 132.4 (d, J = 9.1 Hz),130.9, 128.3, 126.3, 125.6 (q, J = 276.6 Hz), 125.5, 125.4, 122.7,117.8 (d, J = 23.1 Hz), 106.9 (q, J = 23.1 Hz), 40.3 (q, J = 30.1 Hz). 19FNMR (470 MHz, CDCl3) d = �62.6 (s, 3F), �112.7 (s, 1F). HRMS: calc.for [M + H]+ C15H10F4N: 280.0744, found: 280.0749.

4.2.15. 6-(2,2,2-Trifluoroethyl)-2-methylphenanthridine (2o)

White solid, mp 106–108 8C; 1H NMR (400 MHz,CDCl3):d = 8.57 (d, J = 8.0 Hz, 1H), 8.27 (s, 1H), 8.12 (d, J = 8.0 Hz,1H), 8.04 (d, J = 8.4 Hz, 1H), 7.79 (t, J = 7.6 Hz, 1H), 7.66 (t, J = 7.6 Hz,1H), 7.53 (d, J = 8.4 Hz, 1H), 4.15 (q, J = 10.4 Hz, 2H), 2.58 (s, 3H); 13CNMR (125 MHz, CDCl3): d = 150.0 (q, J = 4.25 Hz), 141.7, 137.5,132.9, 130.6, 130.5, 129.8, 127.4, 126.1, 125.7 (q, J = 276.5 Hz),125.5, 123.9, 122.4, 121.6, 40.4 (q, J = 29.0 Hz), 22.0. 19F NMR(470 MHz, CDCl3) d = �62.5 (t, J = 10.3 Hz, 3F). HRMS: calc. for[M + H]+ C16H13F3N: 276.0955, found: 276.0957.

4.2.16. 6-(2,2,2-Trifluoroethyl)-3-(trifluoromethyl)phenanthridine

(2p)

White solid, mp 118–120 8C; 1H NMR (400 MHz, CDCl3):d = 8.57–8.62 (m, 2H), 8.45 (s, 1H), 8.21 (d, J = 8.4 Hz, 1H), 7.90(t, J = 7.6 Hz, 1H), 7.77–7.84 (m, 2H), 4.19 (q, J = 10.4 Hz, 2H); 13CNMR (125 MHz, CDCl3): d = 152.8, 142.6, 132.4, 131.4, 130.9, 128.8,127.7, 126.4, 126.2, 126.0, 125.6 (q, J = 275.5 Hz), 123.6 (q,J = 271.6 Hz), 123.3, 123.1, 122.9, 40.4 (q, J = 29.2 Hz). 19F NMR(470 MHz, CDCl3) d = �62.3 (s, 3F), �62.4 (t, J = 10.3 Hz, 3F). HRMS:calc. for [M + H]+ C16H10F6N: 330.0712, found: 330.0716.

4.2.17. 6-(2,2,2-Trifluoroethyl)-2,4-dimethylphenanthridine (2q)

White solid, mp 103–105 8C; 1H NMR (400 MHz, CDCl3):d = 8.54 (d, J = 8.4 Hz, 1H), 8.09 (s, 1H), 8.06 (d, J = 8.4 Hz, 1H),7.73 (t, J = 7.6 Hz, 1H), 7.60 (t, J = 7.6 Hz, 1H), 7.37 (s, 1H), 4.11 (q,J = 10.4 Hz, 2H), 2.79 (s, 3H), 2.53 (s, 3H); 13C NMR (125 MHz,CDCl3): d = 148.3 (q, J = 3.8 Hz), 140.5, 137.8, 136.8, 133.1, 131.3,130.1, 127.1, 125.7, 125.9 (q, J = 276.0 Hz), 125.2, 123.6, 122.7,119.3, 40.2 (q, J = 29.0 Hz), 22.0, 18.1. 19F NMR (470 MHz, CDCl3)d = �62.5 (t, J = 10.3 Hz, 3F). HRMS: calc. for [M + H]+ C17H15F3N:290.1151, found: 290.1158.

4.2.18. 2,4-Dichloro-6-(2,2,2-trifluoroethyl)phenanthridine (2r)

White solid, mp 123–124 8C; 1H NMR (400 MHz, CDCl3):d = 8.38 (d, J = 8.4 Hz, 1H), 8.25–8.31 (m, 1H), 8.18 (d, J = 2.4 Hz,1H), 8.04–8.10 (m, 1H), 7.88–7.92 (m, 1H), 7.82 (d, J = 2.4 Hz, 1H),

4.20 (q, J = 10.4 Hz, 2H); 13C NMR (125 MHz, CDCl3): d = 152.8 (q,J = 4.1 Hz), 142.6, 132.4, 131.4, 128.8, 127.7 (q, J = 3.5 Hz), 126.4,126.3, 126.1, 125.1, 123.3, 123.1, 122.9, 125.4 (q, J = 275.8 Hz), 40.4(q, J = 29.5 Hz). 19F NMR (470 MHz, CDCl3) d = �62.6 (t, J = 10.3 Hz,3F). HRMS: calc. for [M + H]+ C15H9Cl2F3N: 330.0059, found:330.0061.

Acknowledgment

We are grateful to the National Natural Science Foundation ofChina (Project nos. U1204205, 21202078, 21272110, 21363004).

References

[1] P. Kirsch, Modern Fluoroorganic Chemistry, Wiley-VCH, Weinheim, 2004.[2] K. Muller, C. Faeh, F. Diederich, Science 317 (2007) 1881–1886.[3] W.K. Hagmann, J. Med. Chem. 51 (2008) 4359–4369.[4] S. Purser, P.R. Moore, S. Swallow, V. Gouverneur, Chem. Soc. Rev. 37 (2008)

320–330.[5] M. Shimizu, T. Hiyama, Angew. Chem. Int. Ed. 44 (2005) 214–231.[6] K. Uneyama, J. Fluorine Chem. 129 (2008) 550–576.[7] T. Yamazaki, T. Taguchi, I. Ojima, Fluorine in Medicinal Chemistry and Chemical

Biology, Wiley-Blackwell, Chichester, 2009.[8] G.G. Dubinina, H. Furutachi, D.A. Vicic, J. Am. Chem. Soc. 130 (2008) 8600–8601.[9] O.A. Tomashenko, V.V. Grushin, Chem. Rev. 111 (2011) 4475–4521.

[10] X.F. Wu, H. Neumann, M. Beller, Chem.—Asian J. 7 (2012) 1744–1754.[11] A. Studer, Angew. Chem. Int. Ed. 51 (2012) 8950–8958.[12] H. Liu, Z. Gu, X. Jiang, Adv. Synth. Catal. 355 (2013) 617–626.[13] R.J. Lundgren, M. Stradiotto, Angew. Chem. Int. Ed. 49 (2010) 9322–9324.[14] S. Roy, B.T. Gregg, G.W. Gribble, V.-D. Le, Tetrahedron 67 (2011) 2161–2195.[15] T. Besset, C. Chneider, D. Cahard, Angew. Chem. Int. Ed. 51 (2012) 5048–5050.[16] T. Koike, M. Akita, Top. Catal. 57 (2014) 967–974.[17] V.C.R. McLoughlin, J. Thrower, Tetrahedron 25 (1969) 5921–5940.[18] S. Xu, H.-H. Chen, J.-J. Dai, H.-J. Xu, Org. Lett. 16 (2014) 2306–2309.[19] Y.-C. Zhao, J.-B. Hu, Angew. Chem. Int. Ed. 51 (2012) 1033–1036.[20] A.-P. Liang, X.-J. Li, D.-F. Liu, J.-Y. Li, D.-P. Zou, Y.-J. Wu, Y.-S. Wu, Chem. Commun.

48 (2012) 8273–8275.[21] Y.-S. Feng, C.-Q. Xie, W.-L. Qiao, H.-J. Xu, Org. Lett. 15 (2013) 936–939.[22] J. Hwang, K. Park, J. Choe, H. Min, K.H. Song, S. Lee, J. Org. Chem. 79 (2014)

3267–3271.[23] Y. Fujiwara, J.A. Dixon, F. O’Hara, E.D. Funder, D.D. Dixon, R.A. Rodriguez, R.D.

Baxter, B. Herle, N. Sach, M.R. Collins, Y. Ishihara, P.S. Baran, Nature 492 (2012)95–100.

[24] C.K. Prier, D.A. Rankic, D.W.C. MacMillan, Chem. Rev. 113 (2013) 5322–5363.[25] K. Zeitler, Angew. Chem. Int. Ed. 48 (2009) 9785–9789.[26] J. Xuan, W.-J. Xiao, Angew. Chem. Int. Ed. 51 (2012) 6828–6838.[27] F. Teply, Collect. Czech. Chem. Commun. 76 (2011) 859–917.[28] D. Ravelli, M. Fagnoni, ChemCatChem 4 (2012) 169–171.[29] J.W. Tucker, C.R.J. Stephenson, J. Org. Chem. 77 (2012) 1617–1622.[30] J.M.R. Narayanam, C.R.J. Stephenson, Chem. Soc. Rev. 40 (2011) 102–113.[31] T.P. Yoon, ACS Catal. 3 (2013) 895–902.[32] N. Iqbal, S. Choi, E. Kim, E.J. Cho, J. Org. Chem. 77 (2012) 11383–11387.[33] Y. Yasu, T. Koike, M. Akita, Chem. Commun. 49 (2013) 2037–2039.[34] D.J. Wilger, N.J. Gesmundoa, D.A. Nicewicz, Chem. Sci. 4 (2013) 3160–3165.[35] D.A. Nagib, D.W.C. MacMillan, Nature 480 (2011) 224–228.[36] N. Iqbal, S. Choi, E. Ko, E.J. Cho, Tetrahedron Lett. 53 (2012) 2005–2008.[37] Y. Ye, M.S. Sanford, J. Am. Chem. Soc. 134 (2012) 9034–9037.[38] L.M. Kreis, S. Krautwald, N. Pfeiffer, R.E. Martin, E.M. Carreira, Org. Lett. 15 (2013)

1634–1637.[39] W. Fu, F. Xu, Y. Fu, C. Xu, S. Li, D. Zou, Eur. J. Org. Chem. (2014) 709–712.[40] M. Zhu, W. Fu, G. Zou, C. Xu, Z. Wang, J. Fluorine Chem. 163 (2014) 23–27.[41] W. Fu, M. Zhu, F. Xu, Y. Fu, C. Xu, D. Zou, RSC Adv. 4 (2014) 17226–17229.[42] M. Zhu, Z. Wang, F. Xu, J. Yu, W. Fu, J. Fluorine Chem. 156 (2013) 21–25.[43] W. Fu, F. Xu, Y. Fu, M. Zhu, J. Yu, C. Xu, D. Zou, J. Org. Chem. 78 (2013) 12202–

12206.[44] M. Tobisu, K. Koh, T. Furukawa, N. Chatani, Angew. Chem. Int. Ed. 51 (2012)

11363–11366.[45] B. Zhang, C. Muck-Lichtenfeld, C.G. Daniliuc, A. Studer, Angew. Chem. Int. Ed. 52

(2013) 10792–10795.[46] Q. Wang, X. Dong, T. Xiao, L. Zhou, Org. Lett. 15 (2013) 4846–4849.[47] Y. Cheng, H. Jiang, Y. Zhang, S. Yu, Org. Lett. 15 (2013) 5520–5523.[48] X. Sun, S. Yu, Org. Lett. 16 (2014) 2938–2941.[49] D. Leifert, C.G. Daniliuc, A. Studer, Org. Lett. 15 (2013) 6286–6289.[50] B. Zhang, C.G. Daniliuc, A. Studer, Org. Lett. 16 (2014) 250–253.[51] H. Jiang, Y. Cheng, R. Wang, M. Zheng, Y. Zhang, S. Yu, Angew. Chem. Int. Ed. 52

(2013) 13289–13292.[52] J. Liu, C. Fan, H. Yin, C. Qin, G. Zhang, X. Zhang, H. Yi, A. Lei, Chem. Commun. 50

(2014) 2145–2147.[53] T. Xiao, L. Li, G. Lin, Q. Wang, P. Zhang, Z. Mao, L. Zhou, Green Chem. 16 (2014)

2418–2421.