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Perfluorophenylation of aromatic and heteroaromatic compounds with pentafluorobenzenesulfonyl chloride catalyzed by a ruthenium (II) phosphine complex
ELSEVIER
Journal
of Fluorine Chemistry X7 ( 1998) 91-95
Perfluorophenylation of aromatic and heteroaromatic compounds with pentafluorobenzenesulfonyl chloride catalyzed by a ruthenium ( II) phosphine complex Nobumasa Kamigata *, Manabu Yoshikawa, Toshio Shimizu Depurtment
of Chemists.
Graduntr
Schoo;
ofScience.
Tokyo
Metropolitcm
University
Minrimi-ohscr~~L1,
Hachioji,
Tokw
192.03,
Jupun
Received 27 May 1997: revised I ? September 1997; accepted IS September I997
Abstract The reactions of pentafluorobenzenesulfonyl chloride with benzene and thiophene derivatives in the presence of a ruthenium( II) catalyst proceeded at 24(X, with extrusion of sulfur ‘dioxide and hydrogen chloride. to give the corresponding perfluorophenylated compounds. 8 1998Elsevier Science S.A. Keywords:
Perfluorophenylation; Ruthenium(U) catalyst: Aromatic and heteroaromatic compounds
1. Introduction Recently, much attention hasbeen focused on fluorinated compoundsdue to the characteristic features of the fluorine atom, particularly in the field of medicinal and agricultural chemistry, and materials science [ l-S), and exploration of efficient synthetic methodshas been widely required. Previously, we have reported a novel perRuoroalkylation of alkenes[6,7], arenes[8-l 11, and silyl enol ethers1121with pertluoroalkanesulfonyl chloride catalyzed by a ruthenium( II) phosphinecomplex. During our systematicinvestigations on the reactions of sulfonyl chlorides with alkenes and arenesin the presenceof a catalytic amount of ruthenium( 11) phosphinecomplex, we found that the reaction of pentafluorobenzenesulfonylchloride with arenesin the presence of this ruthenium(U) catalyst gave perfluorophenylated compoundin moderateyields with extrusion of sulfur dioxide and hydrogen chloride. The resultsare describedherein.
2. Results and discussion When a solution containing pentafluorobenzenesulfonyl chloride (1) (2.0 mmol), dichlorotris( triphenylphosphine)ruthenium(I1) (0.02 mmol) in benzene (4.0 cm’) was degassed and heated at 120°C in a sealed tube for 24 h, no * Corresponding author. Tel.: + 8 l-426-77-3556; fax: + 8 I-426-772525. 0022-I 139/98/$19.00 6 1998 Elsevier Science S.A. All rights reserved PI1 SOO22I 139( 97 ) 00 120-6
reaction took place and unchanged starting materials were recovered, although the reactionsof perfluoroalkanesulfonyl chlorides with aromatic compoundshad beenfound to proceedvery smoothly under similar conditions to give perfluoroalkylated compoundsin good to high yields [S-l I ] . Then, the ruthenium( II) catalyzed reaction of 1 with benzenewas carried out by raising the reaction temperatureat 240°C since Blum [ 131 and Blum and Scharf [ 141 have reported that various sulfonyl chloride desulfonylated at 240°C in the presence of a transition metal catalyst. The reaction now proceeded smoothly and was completed within 24 h. Flash column chromatography on silica gel with hexane, followed by gel permeation chromatography using chloroform, gave 2.3,4.5,6-pentafluorobiphenyl (3a. Ar = C,HS) in 73% yield. KuCklPPh~,r
C,F,SO,Cl + ArH I 2
-+ 24occ
GhAr 3
The reactionsof 1 with severalaromaticcompounds2 were carried out in the presenceof the ruthenium( II) phosphine complex under similar conditions, and the results are summarized in Table 1. As shownin Table 1, chlorobenzeneand p-xylene were perfluorophenylated in good to high yields. However, anisole.p-dimethoxybenzene, and p-isopropyltoluene were perfluorophenylated in very low yields. In the casesof the reactionswith anisoleandp-dimethoxybenzene, a lot of resinousblack tar was also formed as a by-product. The results show that the product once formed was easily decomposed
under the high temperature
reaction
conditions
92 Table 1 Reactions
N. Kamiguta
of pentafluorobenzenesulfonyl
chloride
et al. /Journul
(X) with aromatic
qfFluorine
compounds
Chemist?
87 (lY98)
91-95
(2) in the presence of a ruthenium(II)
phosphine
complex”
Run
Substrate
Time (h)
Product
Yield
I
2a C,H, 2b C,H,OCH, 2c C,H,Cl 2d C,H,CN 2e p-CH,C,H,CH, 2fp-CH,C,H,CH(CH?)Z 2g p-CH,OC,H,OCH,
24 4 8 4 4 4 2
3a C,FX,H,
13
3b C,F,C,H,OCH; 3c C,F,C,H,CI” 3d C,F,C,H,CN“ 3e C,F5C,H3(CH3)2 3fCH,C,H,(C,F,)CH(CH,)~ 3gC,F,C,H,(OCH,)Z
14 87 39 59 14 5
2 3 4 5 6 7
“The reactions were carried out at 240°C in a degassed sealed tube containing pentafluorohenzenesulfonyl and the ruthenium( II) catalyst (0.02 mmol). %omer distribution: o-, 43%; m-, 16%:~., 41%. ‘Isomer distribution: o-, 42%; m-, 3 1%; p-, 274. ‘Isomer distribution: o-, 27%; m-, 4370; p-, 30%. ‘Isomer distribution: 2-pentafluorophenyl-4-isopropyltoluene. 69%; 3-pentafluorophenyl-4-isopropyltoluene,
chloride
(2.0 mmol).
aromatic
(%)
compound(4 cm’)
3 1%.
with thiophene afforded 2-pentafluorophenylthiophene (Sa) and 3-pentafluorophenylthiophene (Sb) in 22 and 6% yields, respectively. /
[C,F,SO&lj;
+ R”“’
RuC’#‘Ph,), 240°C
6
Scheme
I
when the substituent on aromatic ring was amethoxy group. ’ The low yield in the reaction of 1 with p-isopropyltoluene may be due to the steric effect of the bulky isopropyl group. The proposed reaction mechanism of these perfluorophenylations is given in Scheme 1. The redox-transfer reaction between pentafluorobenzenesulfonyl chloride 1 and the ruthenium( II) catalyst affords anion radical 4 of compound 1, which cleaves homolytically to give the pentatluorobenzenesulfonyl radical 5 and Run’-Cl. Pentafluorophenyl radical 6, formed from radical 5 by extrusion of sulfur dioxide, adds to the aromatic nucleus to give cyclohexadienyl radical 7. The subsequent hydrogen-atom abstraction by a Ruur-Cl species from radical 7 affords pentafluorophenylbenzene 3a and hydrogen chloride, and the rutt-,enium(II) catalyst is regenerated. Radicals 5,6, and 7 are considered to be confined in the coordination sphere of the ruthenium complex [ 15 1. The perfluorophenylation of various thiophenes by 1 was also investigated in the presence of the ruthenium( II) phosphine complex under similar conditions. The reaction of 1 ’ Anisole and p-dimethoxybenzene were pcrfluoroalkylated in good to high yields in the reactions of perfluoroalkanesulfonyl chlorides in the presence of the ruthenium( 11) complex at 120°C (see Ref. 18-l 11).
*
&F,+
t-j”
8b 8a Similarly, the perfluorophenylations of 2-methylthiophene, 3-methylthiophene, 2-bromothiophene, 3-bromothiophene and 2-trimethylthiophene by 1 in the presence of the ruthenium( II) catalyst were investigated. In the presentreaction, thiophene and 2- and 3-substituted thiophenes were also perfluorophenylated at the P-position together with the (Yposition. In contrast, the ruthenium( II) catalyzed reactions of perfluorohexanesulfonyl chlorides with thiophenes at 120°C gave only 2-(perlluorohexyl) thiophenes and no 3(perfluorohexyl) thiophene was detected [9-l I]. These differences on the regioselectivity between the perfluoroalkylation and present perfluorophenylation may be due to the difference of the reaction temperature; i.e., the present pertluorophenylation is carried out at fairly high temperature (240”(Z), and therefore the regioselectivity is considered to be lowered. 2,5Disubstituted thiophenes such as 2,S-dimethylthiophene, 2,5-dibromothiophene and 2,5-bis( trimethylsilyl) thiophene were perfluorophenylated at the B-position under similar conditions to give 2,5-dimethyl-3-(pentafluorophenyl)thiophene (14), 2,5-dibromo-3-(pentafluorophenyl) thiophene ( 15) and 2,5-bis( trimethylsilyl) 3-( pentafluorophenyl) thiophene (16), respectively. The results are summarized in Table 2. The trimethylsilyl groups of 2,5-bis( trimethylsilyl) -3( pentafluorophenyl) thiophene ( 16) was removed by treatment with tetrabutylammonium fluoride, and 3-( pentafluorophenyl)thiophene (8b) was obtained in 72% isolated yield. Therefore, bistrimethylsilylation of thiophene at the 2and 5-positions, perfluorophenylation of 2,5-bis( trimethylsilyl) thiophene and subsequent desilylation will be an
N. Kmnigutn Table Reactions presence
et al. / Jourrml
of Fluorinr
2 of pentaAuorobenzenesulfony1 of a ruthenium(H) phosphine
chloride complex”
with
thiophenes
in the
Chemistt~
87 (1998)
91-95
trometer by electron impact (EI) at 70 eV. Gas-liquid chromatography (GLC) were performed using a Hitachi G-300 gas chromatograph with OV- 1 ( 10%) 25 m capillary column. Gel-permeation chromatography (GPC) was performed using a JAI LC-08 and JAI LC-908 liquid chromatograph with two JAIGEL-1H columns (20 mm X 600 mm) with chloroform as eluent. Combustion analyses were performed on a Perkin-Elmer 240-C Analyzer. All solvents were distilled and stored under nitrogen. Dichlorotris( triphenylphosphine)ruthenium( 11) was prepared ( mp 123°C) by the method described in the literature [1618 1. Pentafluorobenzenesulfonyl chloride from Fluorochem was used without further purification. Anisole, chlorobenzene and thiophene from Wako Chemicals were distilled and stored under nitrogen. I ,4-Dimethoxybenzene, benzonitrile, 2-methylthiophene, 3-methylthiophene, 2-bromothiophene, 3-bromothiophene and 2,5-dimethylthiophene from Tokyo Kasei Chemicals were distilled and stored under nitrogen. I?Xylene from Nakarai Chemicals and 2,S-dibromothiophene from Aldrich Chemicals were distilled and stored under nitrogen. 2-Trimethylsilylthiophene and 2,S-bis( trimethylsilyl) thiophene were prepared by the trimethylsilylation of thiophene according to the method in the literature [ 191. 3. I. General procedure,fbr prntci~uluomhen,-enesulf~n~l thiophene derivatives
“The reactions
were
carried
out at 240°C
for
15 min
excellent method for the regioselective fluorophenylthiophene (8b).
--
synthesis of 3-per-
1) BuLi SiMe 3
2) Me,SiCl
C,F,SO,CI
I 8b
RuCI,(PPh,),,
240 “C
16
3. Experimental Mps were determined on a Yamato MP21 apparatus and are uncorrecled. IR spectra were determined on a Hitachi 260-10 spectrometer with samples either neat liquids or KBr disks. ‘H and “C NMR spectra were determined on a JEOL JNM-EX 400 FT NMR spectrometer at 400 and 100 MHz. respectively, using Me,Si as an internal standard. ‘“F NMR spectra were taken on a JEOL JNM-EX 400 FT NMR spectrometer at 376 MHz using CFCI, as an external standard. Mass spectra were measured on a JEOL JMS-AX 500 spec-
93
the reaction of chloride with benzene or
A solution containing pentafluorobenzenesulfonyl chloride 1 (533 mg, 2.0 mmol), benzene (or thiophene) derivative (2.0 ml) and dichlorotris( triphenylphosphine)ruthenium( II) (20 mg, 0.02 mmol) was degassedby a freeze-pump-thaw cycle, sealedin an ampoule, and heated at 240°C for an adequatetime (Tables 1 and 2). In the case of the reaction with thiophene derivatives, more ruthenium( 11) catalyst was employed (40 mg, 0.04 mmol). The reaction mixture was subjectedto short-columnchromatography on silica-gel with hexane or benzene as eluent to remove the metal complex. The products were purified from the reaction mixture by useof GPC and/or column chromatography over silica-gel (Wakogel C-60). Each of the o-, tit-, and p-isomers of pentafluorophenylated products could not be always isolated by column chromatography or gelpermeationchromatography (sometimesonly o&o-isomer was separatedand the other times only Pam-isomerwasseparated). Therefore, the structureand ratio of the isomerswere determinedby using ‘H NMR and/or gas chromatography. The physical and spectral data for the compoundsobtained are as follows. 2,3.4,5.6-Pentafluorobiphenyl (3a) mp 109.5-I 1OS”C (Ill-112°C [20]); v,,,,(KBr)/cm--’ 1530, 1500. 1440, 1070, 1060and 980; & (400 MHz, CDCI,) 7.40-7.5 1 (5H. m); 6o ( 100 MHz. CDCI,) 126.6, 128.8, 129.4 and 130.3; m/z 244 (M+ ), 224,205 and 175. Pentafluorophenylanisole [201 (3b) 8” (400 MHz, CDC13) o-isomer: 3.80 (3H, s). 7.03 (IH,t,J=8.2Hz),7.06 (lH.d,J=8.2Hz),7.23 (1H.
94
N. Kamigntcl
et cd. /Journal
of Fluorir~e
d, J=8.2 HZ) and 7.45 (lH, t. J= 8.2 Hz); m-isomer: 3.58 (3H, s), 6.95 (lH, s), 7.00-7.04 (21-I, m) and 7.41 (IH, t, .J=7.8 Hz);p-isomer: 3.87 (3H, s), 7.02 I 2H, d.J= 8.8 HZ) and 7.37 (2H, d, .I= 8.8 Hz). m/z 274 (M’) and 259. Pentafluorophenylchlorobenzene [ 2 1 ] (3~) 6, (400 MHz. CDCl,) o-isomer: 7.31 ( lH, dd, J=7.5 and 1.8 Hz), 7.39 (IH. td. 3=7.5 and 1.2Hz), 7.44 (lH,ddd,.l=7.8,7.5 and 1.8Hz) and7.55 (lH,dd,J=7.8and 1.2Hz);nz-isomer: 7.31 (lH, d, J=6.7 Hz), 7.439 (IH, d, J=6.7 Hz), 7.441 ( 1H. t, J= 6.‘7Hz) and 7.47 ( 1H, s) ; p-isomer: 7.36 (2H, d, Jz8.5 HZ) and 7.48 (2H, d, .I=85 Hz). m/z 278 (M+), 243.242 and 167. Pentafluorophenylbenzonitrile [ 221 (.3d) &, (400 MHz, CDCl,) o-isomer: 7.40 (IH, d, J=7.8 Hz), 7.54 (1H. t, J=7.8Hz),‘7.66(1H,t.J=7.8Hz) and7.76(IH,d,/=7.8 Hz); m-isomer:7.64 ( lH, t, 5=7.8 Hz), 7.68 ( lH, d. J=7.8 HZ), 7.74 ( BH, s) and 7.77 ( 1H, d, J = 7.8 Hz) ; p-isomer: 7.56 (2H,d.J=8.4Hz) and7.80 (2H,d,J=&.4Hz).ml=. 269 (M+), 249,242 and 167. 2,3,4,5,6-Pentafluoro-2’,5’-dimethylbiphenyl (3e) : mp 69%70°C(59-6 1“C [ 201) ; v,,,,~( KBr) /cm - ’ 3020, 2920, 1520, 1480, 1060,980 and 820: S, (400 MHz, CDCI,) 2.13 (3H,s),2.35(3H,s),7.00(1H.s),7.1S~(1H,d,J=8.lHz) and 7.23 (lH, d, J=8.1 Hz): 6, (100 MHz, CDCl,) 19.2. 20.8, 125.6, 130.3, 130.4. 131.0, 134.1 and 135.5; m/; 272 (M+), 257.237,201, 188and 167. Pentafluorophenyl-4-isopropyltoluerw (3f) : 2-( Pentafluorophenyl)-4-isopropyltoluene: S, (400 MHz, CDCI,) I .25 (6H,d,J=6.8Hz),2.14(3H,s),2.91 (lH,sep,J=68Hz), 7.04 (IH, s) and 7.23-7.35 (2H, m); ml: 300 (M’), 285, 270,250,237.219 and201; HRMS ml;: 300.0950, C,,HIjFs requires 300.0938. 3-(Pentafluorophenyl)4-isopropyltoluene: S, (400 MHz, CDCl,) I.15 (6H, d, 5=6.8 Hz), 2.35 (3H, sj, 2.59 (IH, sep,J=6.8 Hz), 6.94 (1H. s) and7.237.35 (2H, m); ml:: 300 (M+), 285,270.250? 237,219 and 201; HRM:S m/z 300.0956, C,,H,,F, requires300.0938. 2,3,4,5,6-Pentafluoro-2’,5’-dimethoxylbiphenyl (3g) : mp 58-59°C (62°C [23] ); v,,,( KBrj /err-’ 3020,2950, 1520, 1500, 1280, 1220 and980; &, (400 MHz, CDCI?) 3.76 (3H, s), 3.79 (3H, s), 6.79 (IH, d, J= 2.9 Hz), 6.96 ( lH, d. 5=8.8 Hz). and 6.99 (IH, dd, J=8.8 and 2.9 Hz); 6, (100 MHz, CD(&) 55.8, 56.2, 112.1, 112.3, 115.9, 117.3, 151.4 and 153.4; mlz 304 (M+), 289,261,218 and 192. 2- ( PentafluoroPentafluorophenylthiophene (8): phenyljthiophene (Sa); 6, (400MHz, CDCI,) 7.19 (IH, t, J=4.9 Hz), 7.53 (lH, m) and7.55 ( 1H, d, J=4.9 Hz); ml z 250 (M+), 218, 205 and 167. 3-Pentafluorophenylthiophene(Sbj; &, (400MHz, CDCI,) 7.36 ( lH,m), 7.46 (IH, m) and7.65 (IH, m); S, (376 MHz, CDCl,) 162.0 (2F, dd, J=20.7 and 6.8 Hz), 176.2 (IF, t, Jz20.7 Hz) and 182.3 (2F, td, J=20.7 and 6.8 Hz); ml,: 250 (M+), 218,205 and 167.HRMS (mixtureof 8aandSb) m/2249.9892, C,,H3FsS requires2’49.9876. Pentafluorophenyl-2-methylthiophene (9): 5-Pentafluorophenyl-2-methylthiophene (9a) ; &, (400 MHz, CDCl,) 2.55 (3H. s), 6.83 (IH, d, 5=3.4 Hz) and 7.32 (IH, d,
Chernistq
87 (1998)
91-95
.1=3.4 HZ); m/z 264 (M’ ), 245 and 231. 4-Pentahuorophenyl-2-methylthiophene (9b) ; 6, (400 MHz, CDCl,) 2.54 (3H. sj, 6.99 (IH. dd, .I= 1.5 Hz) and 7.38 (lH, d. ./=I.5 HZ); m/z 264 (M+), 245, and 231. 3-Pentafluorophenyl-2-methylthiophene (SC) ; au (400 MHz, CDCl,) 2.14 (3H. s). 7.00 (IH, d, J=5.4 Hz) and 7.44 (IH, d, J=5.4 Hz); wr/: 264 (M+ ), 245 and 23 1. HRMS (mixture of 9a, 9b andSC) m/z 264.0045, C, ,H,F,S requires264.0032.Pentafluorophenyl-3-methylthiophene ( 10) : 2-Pentafluorophenyl-4-methylthiophene ( 10a) ; 6, (400 MHz, CDCI,) 2.33 (3H. s). 7.12 (IH, s) and 7.31 (lH, s); Sc ( IOOMHz, CDCI,) 15.6. 123.8, 132.29, 132.34 and 138.0; ml: 264 (M’ j. 245 and 97. 2-Pentafluorophenyl-3-methylthiophene (lob); 6~ (400 MHz, CDCI,) 2.14 (3H, s), 7.00 (lH, d, 5~5.4 HZ) and 7.44 (IH, d, J=5.4 Hz); m/z 264 (M’) and 245. 3-Pentafluorophenyl-4-methylthiophene (10~); an (4OOMHz.CDC1,) 2.13 (3H,s).7.11 (lH,d,J=2.9Hz) and7.31 (lH,d,.l=2.9Hz);m/,:264(M’) and245,HRMS (mixture of lOa, lob and 10~) m/: 264.0065, C,,H,F,S requires264.0032. 2-Bromo(pentafluoropheny1)thiophene (11): 2-Bromo5-( pentafluorophenyl j thiophene ( lla) ; 6, (400 MHz, CDCl,) 7.13 (IH. d, J=3.9 Hz) and 7.29 (IH. d, 5=3.9 Hzj; m/z 330 (M+, ” Br). 249, 230 and 205. 2-Bromo-4( pentafluorophenyl) thiophene ( llb) ; t$, (400 MHz, CDCl,)7.29(lH,~)and7.53(1H,s);ml=.330(M+.~’Br). 249,230 and205.2-Bromo-3-( pentafluorophenyl)thiophene (11~); S, (400 MHz, CDCI,) 6.91 (IH, d. J=5.8 Hz) and 7.26 (IH, d,J=5.8 HZ); m/z 330 (M’, “Br), 249,230and 205. HRMS (mixture of lla. llb and llc) m/r 329.8957, C,,,H,F:‘BrS requires329.8960. 3-Bromo( pentafluorophenyl) thiophene ( 12) : 4-Bromo2-( pentafluorophenyl) thiophene ( 12a) ; 6, (400 MHz, CDCI,) 7.25 (lH,s) and7.42 ( 1H.s);m/:264(M+,X’Br). 245 and 97. 3-Bromo-2-(pentaAuorophenyl)thiophene (12b); Su (400 MHz, CDC13)7.15 ( lH, d, .I= 5.6 Hz) and 7.53 ( IH, d, J= 5.6 Hz); m/z 330 (Mt. “Br), 249,230 and 205. 3-Bromo-4-( pentafluorophenyl) thiophene ( 12~) ; 6, (400 MHz, CDCI,) 7.41 (lH, d, 5~3.4 Hz) and 7.45 (IH, d, J=3.4 Hz): m/z 330 (M+, “Br). 249, 230 and 205. HRMS (mixture of 12a, 12b and 12~) m/z 329.8959, C,,,H,F:‘BrS requires329.8960. Pentafluorophenyl-2-trimethylsilylthiophene (13) :2-Pentatluorophenyl-5-( trimethylsilyl)thiophene (13a); 6, (400 MHz, CDC13) 0.37 (9H, s), 7.29 (1H. d. J= 3.2 Hz) and 7.56 (IH, d, 5~3.2 Hz); s, (376 MHz, CDCl,) 140.2 (2F. m). 156.6 ( IF. t, J=22.6 Hz), and 162.7 (2F, m); ml; 320 and 307. 4-Pentafluorophenyl-2-( trimethylsiCM+) lyl) thiophene ( 13b) ; 6, (400 MHZ, CDCI,) 0.36 (9H, s) , 7.43 (lH, s) and 7.85 (lH, s); 6, (376 MHz, CDCI,) 142.2 (2F. m), 155.4 (lF, t. J=22.6 Hz) and 162.7 (2F, m); ml; 320 (M’ ) and 307. 3-Pentafluorophenyl-2-(trimethylsilyl)thiophene (13~); 6, (400 MHz. CDC13) 0.16 (9H. s), 7.06 (lH, d. J=4.8 Hz) and 7.67 (IH, d, J=4.8 Hz); S, (376 MHz, CDCl?) 139.7 (2F, m), 160.0 (lF, t, J=22.6 Hz) and 162.9 (2F, m); ml,- 320 (MC) and 307. HRMS
(mixture of 13a, 13b and 13~) nz/: 322.02’79, C,,H, ,F,SSi requires 322.027 I. 3-Pentatluomphenyl-2,5-dimethylthiophene (14) : v,,,(neat)/cm-’ 2940, 1520, 1500 and 980; S,, (400 MHz. CDCI,) 2.28 (3H, s), 2.45 (3H, s) and 61.57 ( IH, s); S, (100 MHz, CDCI,) 13.8, 15.0, 121.5. 126.5, 136.8 and 137.6; m/z, 278 (M+), 268, 243 and 111; HRMS: m/z 278.0187, C,,H,SF, requires 278.0189. 2,5-Dibromo-3-( pentafluorophenyl) thiophene (15): v,,,( KBr) /cm-’ 1520,1490, 1100, 1000 and 990; 6h (400 MHz, CDC&) 66.92 ( IH, s); 6, (100 MHz, CDCI,) 112.9, 114.8, 127.7 and 132.1; m/z 408 (M’, ‘“Br, *‘Br) and 283; HRMS: m/z 407.8088, C,,H,SF:“BrX’Br requires407.8066. 2.5Bis( trimethylsilyl)-3-( pentafluorophenyl) thiophene (16): ~,,,(KBr)/cm-’ 2970, 1530, 1500, 1250, 1100,980 and 840; S, (400 MHz, CDCI,) 0.18 (9H.. s), 0.36 (9H. s) and7.16 (lH,s);& (lOOMHz,CDCI,) -0.2, -0.1, 131.9, 137.3, 146.2and 146.3; m/z, 394 (M+), 379 and 267. Calcd. forC,,H,,SF,Si:C.48.71;H,4.85.Found:C,48.96;H,4.97. 3.2. Reuction of 2,5-bis(trimethylsilyl)-3(pentc$uorophenyl)thiophenewith tetrubutylammonium jluoride To a solution of 2,5-bis( trimethylsilyl) -3-( pentafluorophenyl)thiophene (16) (50 mg, 0.13 mmol) in benzene (2 cm3) was added a THF solution of tetrabutylammonium fluoride (1 M solution, 0.3 cm3, 0.3 mmol) and stirred at room temperaturefor I h. Water ( 10 cm3) was addedto the reaction mixture and the organic component was extracted with ether (5 cm3 X 3). The combined organic extract was washedwith ‘waterand dried over magnesiumsulfate. After removal of the solvent, the residuewas purified by gel-per-
meationchromatography and afforded 23 mg (72%) of pure 3-( pentafluorophenyl) thiophene (8b).
References I I 1 R. Filler. Y. Kobayashi, Biomedicinal Aspects of Fluorine Chemistry. Elsevier Biomedical Press and Kodansha. 1982. [?I J.T. Welch. Tetrahedron 43 (1987) 3123. I31 M. Hudlicky, Chemistry of Organic Fluorine Compounds, ElIi Horwood, New York. 1976. [ 4 1 R.E. Banks. Organo FluorineCompounds andTheir Applications. Ellis Horwood, Chichester, 1979. I.51 K. Uneyama, 3. Synth. Org. Chem. Jpn. 49 ( 1991) 612. I61 N. Kamigata. T. Fukushima. M. Yoshida. J. Chem. Sot.. Chem. Commun.. 1989, 1433. I 7 I N. Kamigata. T. Fukushima, Y. Terakawa, M. Yoshida, H. Sawada, J. Chem. Sot., Perkin Trans., 1991, 627. [Sl N. Kamigata, T. Fukushima, M. Yoshida, Chem. Lett., 1990.649. 191 N. Kamigata, T. Ohthuka, T. Shimizu, Sulfur Lett., 1994,69. [ 101 N. Karnigata, T. Ohtsuka, M. Yoshida, T. Shimizu. Synthetic Cornmun., 1994. 2049. [ 111 N. Kamigata, T. Ohtsuka. T. Fukushima. M. Yoshida. T. Shim& I. Chcm. Sot.. Perkin Trans., 1994. 1339. [ 121 N. Kamigata. K. Udodaira, T. Shimizu. Phosphorus, Sulfur, and Silicon, in press. 1131 J. Blum, Tetrahedron Lett., 1966. 3041. [ 141 J. Blum. G. Scharf. J. Org. Chem. 35 (1970) 1895. I 151 M. Kameyama, N. Kamigata, M. Kobayashi, J. Org. Chem. 52 ( 1987) 33 I2 and references cited therein. I 16 1 T.A. Stephenson, G. Wilkinson, J. Inorg. Nucl. Chem. 28 ( 1966) 945. I 171 P.S. Hallam. T.A. Stephenson, G. Wilkinson, Inorg. Synth. 12 ( 1972) 238. [ 181 T.A. Stephenson, G. Wilkinson. J. Chem. Sot. A, 1970. 2497. 1 191 D.J. Chadwick, C. Willbe, J. Chem. Sot., Perkin Trans., 1977, 587. [ 20) Q.Y. Chen, Z.-T. Li. J. Org. Chem. 58 ( 1993) 2599. [ 21 I P.A. Claret, C.H. Williams, J. Co&on, J. Chem. Sot. C, 1968, 34 I. [ 22 1 H.J. Frohn. A. Klose. V.V. Bardin, J. Fluorine Chem. 64 ( 1993) 201. [ 23 1 Q.Y. Chen, Z.-T. Li, J. Chem. Sot., Perkin Trans., 1993, 1705.
Journal
of Fluorine Chemistry X7 ( 1998) 91-95
Perfluorophenylation of aromatic and heteroaromatic compounds with pentafluorobenzenesulfonyl chloride catalyzed by a ruthenium ( II) phosphine complex Nobumasa Kamigata *, Manabu Yoshikawa, Toshio Shimizu Depurtment
of Chemists.
Graduntr
Schoo;
ofScience.
Tokyo
Metropolitcm
University
Minrimi-ohscr~~L1,
Hachioji,
Tokw
192.03,
Jupun
Received 27 May 1997: revised I ? September 1997; accepted IS September I997
Abstract The reactions of pentafluorobenzenesulfonyl chloride with benzene and thiophene derivatives in the presence of a ruthenium( II) catalyst proceeded at 24(X, with extrusion of sulfur ‘dioxide and hydrogen chloride. to give the corresponding perfluorophenylated compounds. 8 1998Elsevier Science S.A. Keywords:
Perfluorophenylation; Ruthenium(U) catalyst: Aromatic and heteroaromatic compounds
1. Introduction Recently, much attention hasbeen focused on fluorinated compoundsdue to the characteristic features of the fluorine atom, particularly in the field of medicinal and agricultural chemistry, and materials science [ l-S), and exploration of efficient synthetic methodshas been widely required. Previously, we have reported a novel perRuoroalkylation of alkenes[6,7], arenes[8-l 11, and silyl enol ethers1121with pertluoroalkanesulfonyl chloride catalyzed by a ruthenium( II) phosphinecomplex. During our systematicinvestigations on the reactions of sulfonyl chlorides with alkenes and arenesin the presenceof a catalytic amount of ruthenium( 11) phosphinecomplex, we found that the reaction of pentafluorobenzenesulfonylchloride with arenesin the presence of this ruthenium(U) catalyst gave perfluorophenylated compoundin moderateyields with extrusion of sulfur dioxide and hydrogen chloride. The resultsare describedherein.
2. Results and discussion When a solution containing pentafluorobenzenesulfonyl chloride (1) (2.0 mmol), dichlorotris( triphenylphosphine)ruthenium(I1) (0.02 mmol) in benzene (4.0 cm’) was degassed and heated at 120°C in a sealed tube for 24 h, no * Corresponding author. Tel.: + 8 l-426-77-3556; fax: + 8 I-426-772525. 0022-I 139/98/$19.00 6 1998 Elsevier Science S.A. All rights reserved PI1 SOO22I 139( 97 ) 00 120-6
reaction took place and unchanged starting materials were recovered, although the reactionsof perfluoroalkanesulfonyl chlorides with aromatic compoundshad beenfound to proceedvery smoothly under similar conditions to give perfluoroalkylated compoundsin good to high yields [S-l I ] . Then, the ruthenium( II) catalyzed reaction of 1 with benzenewas carried out by raising the reaction temperatureat 240°C since Blum [ 131 and Blum and Scharf [ 141 have reported that various sulfonyl chloride desulfonylated at 240°C in the presence of a transition metal catalyst. The reaction now proceeded smoothly and was completed within 24 h. Flash column chromatography on silica gel with hexane, followed by gel permeation chromatography using chloroform, gave 2.3,4.5,6-pentafluorobiphenyl (3a. Ar = C,HS) in 73% yield. KuCklPPh~,r
C,F,SO,Cl + ArH I 2
-+ 24occ
GhAr 3
The reactionsof 1 with severalaromaticcompounds2 were carried out in the presenceof the ruthenium( II) phosphine complex under similar conditions, and the results are summarized in Table 1. As shownin Table 1, chlorobenzeneand p-xylene were perfluorophenylated in good to high yields. However, anisole.p-dimethoxybenzene, and p-isopropyltoluene were perfluorophenylated in very low yields. In the casesof the reactionswith anisoleandp-dimethoxybenzene, a lot of resinousblack tar was also formed as a by-product. The results show that the product once formed was easily decomposed
under the high temperature
reaction
conditions
92 Table 1 Reactions
N. Kamiguta
of pentafluorobenzenesulfonyl
chloride
et al. /Journul
(X) with aromatic
qfFluorine
compounds
Chemist?
87 (lY98)
91-95
(2) in the presence of a ruthenium(II)
phosphine
complex”
Run
Substrate
Time (h)
Product
Yield
I
2a C,H, 2b C,H,OCH, 2c C,H,Cl 2d C,H,CN 2e p-CH,C,H,CH, 2fp-CH,C,H,CH(CH?)Z 2g p-CH,OC,H,OCH,
24 4 8 4 4 4 2
3a C,FX,H,
13
3b C,F,C,H,OCH; 3c C,F,C,H,CI” 3d C,F,C,H,CN“ 3e C,F5C,H3(CH3)2 3fCH,C,H,(C,F,)CH(CH,)~ 3gC,F,C,H,(OCH,)Z
14 87 39 59 14 5
2 3 4 5 6 7
“The reactions were carried out at 240°C in a degassed sealed tube containing pentafluorohenzenesulfonyl and the ruthenium( II) catalyst (0.02 mmol). %omer distribution: o-, 43%; m-, 16%:~., 41%. ‘Isomer distribution: o-, 42%; m-, 3 1%; p-, 274. ‘Isomer distribution: o-, 27%; m-, 4370; p-, 30%. ‘Isomer distribution: 2-pentafluorophenyl-4-isopropyltoluene. 69%; 3-pentafluorophenyl-4-isopropyltoluene,
chloride
(2.0 mmol).
aromatic
(%)
compound(4 cm’)
3 1%.
with thiophene afforded 2-pentafluorophenylthiophene (Sa) and 3-pentafluorophenylthiophene (Sb) in 22 and 6% yields, respectively. /
[C,F,SO&lj;
+ R”“’
RuC’#‘Ph,), 240°C
6
Scheme
I
when the substituent on aromatic ring was amethoxy group. ’ The low yield in the reaction of 1 with p-isopropyltoluene may be due to the steric effect of the bulky isopropyl group. The proposed reaction mechanism of these perfluorophenylations is given in Scheme 1. The redox-transfer reaction between pentafluorobenzenesulfonyl chloride 1 and the ruthenium( II) catalyst affords anion radical 4 of compound 1, which cleaves homolytically to give the pentatluorobenzenesulfonyl radical 5 and Run’-Cl. Pentafluorophenyl radical 6, formed from radical 5 by extrusion of sulfur dioxide, adds to the aromatic nucleus to give cyclohexadienyl radical 7. The subsequent hydrogen-atom abstraction by a Ruur-Cl species from radical 7 affords pentafluorophenylbenzene 3a and hydrogen chloride, and the rutt-,enium(II) catalyst is regenerated. Radicals 5,6, and 7 are considered to be confined in the coordination sphere of the ruthenium complex [ 15 1. The perfluorophenylation of various thiophenes by 1 was also investigated in the presence of the ruthenium( II) phosphine complex under similar conditions. The reaction of 1 ’ Anisole and p-dimethoxybenzene were pcrfluoroalkylated in good to high yields in the reactions of perfluoroalkanesulfonyl chlorides in the presence of the ruthenium( 11) complex at 120°C (see Ref. 18-l 11).
*
&F,+
t-j”
8b 8a Similarly, the perfluorophenylations of 2-methylthiophene, 3-methylthiophene, 2-bromothiophene, 3-bromothiophene and 2-trimethylthiophene by 1 in the presence of the ruthenium( II) catalyst were investigated. In the presentreaction, thiophene and 2- and 3-substituted thiophenes were also perfluorophenylated at the P-position together with the (Yposition. In contrast, the ruthenium( II) catalyzed reactions of perfluorohexanesulfonyl chlorides with thiophenes at 120°C gave only 2-(perlluorohexyl) thiophenes and no 3(perfluorohexyl) thiophene was detected [9-l I]. These differences on the regioselectivity between the perfluoroalkylation and present perfluorophenylation may be due to the difference of the reaction temperature; i.e., the present pertluorophenylation is carried out at fairly high temperature (240”(Z), and therefore the regioselectivity is considered to be lowered. 2,5Disubstituted thiophenes such as 2,S-dimethylthiophene, 2,5-dibromothiophene and 2,5-bis( trimethylsilyl) thiophene were perfluorophenylated at the B-position under similar conditions to give 2,5-dimethyl-3-(pentafluorophenyl)thiophene (14), 2,5-dibromo-3-(pentafluorophenyl) thiophene ( 15) and 2,5-bis( trimethylsilyl) 3-( pentafluorophenyl) thiophene (16), respectively. The results are summarized in Table 2. The trimethylsilyl groups of 2,5-bis( trimethylsilyl) -3( pentafluorophenyl) thiophene ( 16) was removed by treatment with tetrabutylammonium fluoride, and 3-( pentafluorophenyl)thiophene (8b) was obtained in 72% isolated yield. Therefore, bistrimethylsilylation of thiophene at the 2and 5-positions, perfluorophenylation of 2,5-bis( trimethylsilyl) thiophene and subsequent desilylation will be an
N. Kmnigutn Table Reactions presence
et al. / Jourrml
of Fluorinr
2 of pentaAuorobenzenesulfony1 of a ruthenium(H) phosphine
chloride complex”
with
thiophenes
in the
Chemistt~
87 (1998)
91-95
trometer by electron impact (EI) at 70 eV. Gas-liquid chromatography (GLC) were performed using a Hitachi G-300 gas chromatograph with OV- 1 ( 10%) 25 m capillary column. Gel-permeation chromatography (GPC) was performed using a JAI LC-08 and JAI LC-908 liquid chromatograph with two JAIGEL-1H columns (20 mm X 600 mm) with chloroform as eluent. Combustion analyses were performed on a Perkin-Elmer 240-C Analyzer. All solvents were distilled and stored under nitrogen. Dichlorotris( triphenylphosphine)ruthenium( 11) was prepared ( mp 123°C) by the method described in the literature [1618 1. Pentafluorobenzenesulfonyl chloride from Fluorochem was used without further purification. Anisole, chlorobenzene and thiophene from Wako Chemicals were distilled and stored under nitrogen. I ,4-Dimethoxybenzene, benzonitrile, 2-methylthiophene, 3-methylthiophene, 2-bromothiophene, 3-bromothiophene and 2,5-dimethylthiophene from Tokyo Kasei Chemicals were distilled and stored under nitrogen. I?Xylene from Nakarai Chemicals and 2,S-dibromothiophene from Aldrich Chemicals were distilled and stored under nitrogen. 2-Trimethylsilylthiophene and 2,S-bis( trimethylsilyl) thiophene were prepared by the trimethylsilylation of thiophene according to the method in the literature [ 191. 3. I. General procedure,fbr prntci~uluomhen,-enesulf~n~l thiophene derivatives
“The reactions
were
carried
out at 240°C
for
15 min
excellent method for the regioselective fluorophenylthiophene (8b).
--
synthesis of 3-per-
1) BuLi SiMe 3
2) Me,SiCl
C,F,SO,CI
I 8b
RuCI,(PPh,),,
240 “C
16
3. Experimental Mps were determined on a Yamato MP21 apparatus and are uncorrecled. IR spectra were determined on a Hitachi 260-10 spectrometer with samples either neat liquids or KBr disks. ‘H and “C NMR spectra were determined on a JEOL JNM-EX 400 FT NMR spectrometer at 400 and 100 MHz. respectively, using Me,Si as an internal standard. ‘“F NMR spectra were taken on a JEOL JNM-EX 400 FT NMR spectrometer at 376 MHz using CFCI, as an external standard. Mass spectra were measured on a JEOL JMS-AX 500 spec-
93
the reaction of chloride with benzene or
A solution containing pentafluorobenzenesulfonyl chloride 1 (533 mg, 2.0 mmol), benzene (or thiophene) derivative (2.0 ml) and dichlorotris( triphenylphosphine)ruthenium( II) (20 mg, 0.02 mmol) was degassedby a freeze-pump-thaw cycle, sealedin an ampoule, and heated at 240°C for an adequatetime (Tables 1 and 2). In the case of the reaction with thiophene derivatives, more ruthenium( 11) catalyst was employed (40 mg, 0.04 mmol). The reaction mixture was subjectedto short-columnchromatography on silica-gel with hexane or benzene as eluent to remove the metal complex. The products were purified from the reaction mixture by useof GPC and/or column chromatography over silica-gel (Wakogel C-60). Each of the o-, tit-, and p-isomers of pentafluorophenylated products could not be always isolated by column chromatography or gelpermeationchromatography (sometimesonly o&o-isomer was separatedand the other times only Pam-isomerwasseparated). Therefore, the structureand ratio of the isomerswere determinedby using ‘H NMR and/or gas chromatography. The physical and spectral data for the compoundsobtained are as follows. 2,3.4,5.6-Pentafluorobiphenyl (3a) mp 109.5-I 1OS”C (Ill-112°C [20]); v,,,,(KBr)/cm--’ 1530, 1500. 1440, 1070, 1060and 980; & (400 MHz, CDCI,) 7.40-7.5 1 (5H. m); 6o ( 100 MHz. CDCI,) 126.6, 128.8, 129.4 and 130.3; m/z 244 (M+ ), 224,205 and 175. Pentafluorophenylanisole [201 (3b) 8” (400 MHz, CDC13) o-isomer: 3.80 (3H, s). 7.03 (IH,t,J=8.2Hz),7.06 (lH.d,J=8.2Hz),7.23 (1H.
94
N. Kamigntcl
et cd. /Journal
of Fluorir~e
d, J=8.2 HZ) and 7.45 (lH, t. J= 8.2 Hz); m-isomer: 3.58 (3H, s), 6.95 (lH, s), 7.00-7.04 (21-I, m) and 7.41 (IH, t, .J=7.8 Hz);p-isomer: 3.87 (3H, s), 7.02 I 2H, d.J= 8.8 HZ) and 7.37 (2H, d, .I= 8.8 Hz). m/z 274 (M’) and 259. Pentafluorophenylchlorobenzene [ 2 1 ] (3~) 6, (400 MHz. CDCl,) o-isomer: 7.31 ( lH, dd, J=7.5 and 1.8 Hz), 7.39 (IH. td. 3=7.5 and 1.2Hz), 7.44 (lH,ddd,.l=7.8,7.5 and 1.8Hz) and7.55 (lH,dd,J=7.8and 1.2Hz);nz-isomer: 7.31 (lH, d, J=6.7 Hz), 7.439 (IH, d, J=6.7 Hz), 7.441 ( 1H. t, J= 6.‘7Hz) and 7.47 ( 1H, s) ; p-isomer: 7.36 (2H, d, Jz8.5 HZ) and 7.48 (2H, d, .I=85 Hz). m/z 278 (M+), 243.242 and 167. Pentafluorophenylbenzonitrile [ 221 (.3d) &, (400 MHz, CDCl,) o-isomer: 7.40 (IH, d, J=7.8 Hz), 7.54 (1H. t, J=7.8Hz),‘7.66(1H,t.J=7.8Hz) and7.76(IH,d,/=7.8 Hz); m-isomer:7.64 ( lH, t, 5=7.8 Hz), 7.68 ( lH, d. J=7.8 HZ), 7.74 ( BH, s) and 7.77 ( 1H, d, J = 7.8 Hz) ; p-isomer: 7.56 (2H,d.J=8.4Hz) and7.80 (2H,d,J=&.4Hz).ml=. 269 (M+), 249,242 and 167. 2,3,4,5,6-Pentafluoro-2’,5’-dimethylbiphenyl (3e) : mp 69%70°C(59-6 1“C [ 201) ; v,,,,~( KBr) /cm - ’ 3020, 2920, 1520, 1480, 1060,980 and 820: S, (400 MHz, CDCI,) 2.13 (3H,s),2.35(3H,s),7.00(1H.s),7.1S~(1H,d,J=8.lHz) and 7.23 (lH, d, J=8.1 Hz): 6, (100 MHz, CDCl,) 19.2. 20.8, 125.6, 130.3, 130.4. 131.0, 134.1 and 135.5; m/; 272 (M+), 257.237,201, 188and 167. Pentafluorophenyl-4-isopropyltoluerw (3f) : 2-( Pentafluorophenyl)-4-isopropyltoluene: S, (400 MHz, CDCI,) I .25 (6H,d,J=6.8Hz),2.14(3H,s),2.91 (lH,sep,J=68Hz), 7.04 (IH, s) and 7.23-7.35 (2H, m); ml: 300 (M’), 285, 270,250,237.219 and201; HRMS ml;: 300.0950, C,,HIjFs requires 300.0938. 3-(Pentafluorophenyl)4-isopropyltoluene: S, (400 MHz, CDCl,) I.15 (6H, d, 5=6.8 Hz), 2.35 (3H, sj, 2.59 (IH, sep,J=6.8 Hz), 6.94 (1H. s) and7.237.35 (2H, m); ml:: 300 (M+), 285,270.250? 237,219 and 201; HRM:S m/z 300.0956, C,,H,,F, requires300.0938. 2,3,4,5,6-Pentafluoro-2’,5’-dimethoxylbiphenyl (3g) : mp 58-59°C (62°C [23] ); v,,,( KBrj /err-’ 3020,2950, 1520, 1500, 1280, 1220 and980; &, (400 MHz, CDCI?) 3.76 (3H, s), 3.79 (3H, s), 6.79 (IH, d, J= 2.9 Hz), 6.96 ( lH, d. 5=8.8 Hz). and 6.99 (IH, dd, J=8.8 and 2.9 Hz); 6, (100 MHz, CD(&) 55.8, 56.2, 112.1, 112.3, 115.9, 117.3, 151.4 and 153.4; mlz 304 (M+), 289,261,218 and 192. 2- ( PentafluoroPentafluorophenylthiophene (8): phenyljthiophene (Sa); 6, (400MHz, CDCI,) 7.19 (IH, t, J=4.9 Hz), 7.53 (lH, m) and7.55 ( 1H, d, J=4.9 Hz); ml z 250 (M+), 218, 205 and 167. 3-Pentafluorophenylthiophene(Sbj; &, (400MHz, CDCI,) 7.36 ( lH,m), 7.46 (IH, m) and7.65 (IH, m); S, (376 MHz, CDCl,) 162.0 (2F, dd, J=20.7 and 6.8 Hz), 176.2 (IF, t, Jz20.7 Hz) and 182.3 (2F, td, J=20.7 and 6.8 Hz); ml,: 250 (M+), 218,205 and 167.HRMS (mixtureof 8aandSb) m/2249.9892, C,,H3FsS requires2’49.9876. Pentafluorophenyl-2-methylthiophene (9): 5-Pentafluorophenyl-2-methylthiophene (9a) ; &, (400 MHz, CDCl,) 2.55 (3H. s), 6.83 (IH, d, 5=3.4 Hz) and 7.32 (IH, d,
Chernistq
87 (1998)
91-95
.1=3.4 HZ); m/z 264 (M’ ), 245 and 231. 4-Pentahuorophenyl-2-methylthiophene (9b) ; 6, (400 MHz, CDCl,) 2.54 (3H. sj, 6.99 (IH. dd, .I= 1.5 Hz) and 7.38 (lH, d. ./=I.5 HZ); m/z 264 (M+), 245, and 231. 3-Pentafluorophenyl-2-methylthiophene (SC) ; au (400 MHz, CDCl,) 2.14 (3H. s). 7.00 (IH, d, J=5.4 Hz) and 7.44 (IH, d, J=5.4 Hz); wr/: 264 (M+ ), 245 and 23 1. HRMS (mixture of 9a, 9b andSC) m/z 264.0045, C, ,H,F,S requires264.0032.Pentafluorophenyl-3-methylthiophene ( 10) : 2-Pentafluorophenyl-4-methylthiophene ( 10a) ; 6, (400 MHz, CDCI,) 2.33 (3H. s). 7.12 (IH, s) and 7.31 (lH, s); Sc ( IOOMHz, CDCI,) 15.6. 123.8, 132.29, 132.34 and 138.0; ml: 264 (M’ j. 245 and 97. 2-Pentafluorophenyl-3-methylthiophene (lob); 6~ (400 MHz, CDCI,) 2.14 (3H, s), 7.00 (lH, d, 5~5.4 HZ) and 7.44 (IH, d, J=5.4 Hz); m/z 264 (M’) and 245. 3-Pentafluorophenyl-4-methylthiophene (10~); an (4OOMHz.CDC1,) 2.13 (3H,s).7.11 (lH,d,J=2.9Hz) and7.31 (lH,d,.l=2.9Hz);m/,:264(M’) and245,HRMS (mixture of lOa, lob and 10~) m/: 264.0065, C,,H,F,S requires264.0032. 2-Bromo(pentafluoropheny1)thiophene (11): 2-Bromo5-( pentafluorophenyl j thiophene ( lla) ; 6, (400 MHz, CDCl,) 7.13 (IH. d, J=3.9 Hz) and 7.29 (IH. d, 5=3.9 Hzj; m/z 330 (M+, ” Br). 249, 230 and 205. 2-Bromo-4( pentafluorophenyl) thiophene ( llb) ; t$, (400 MHz, CDCl,)7.29(lH,~)and7.53(1H,s);ml=.330(M+.~’Br). 249,230 and205.2-Bromo-3-( pentafluorophenyl)thiophene (11~); S, (400 MHz, CDCI,) 6.91 (IH, d. J=5.8 Hz) and 7.26 (IH, d,J=5.8 HZ); m/z 330 (M’, “Br), 249,230and 205. HRMS (mixture of lla. llb and llc) m/r 329.8957, C,,,H,F:‘BrS requires329.8960. 3-Bromo( pentafluorophenyl) thiophene ( 12) : 4-Bromo2-( pentafluorophenyl) thiophene ( 12a) ; 6, (400 MHz, CDCI,) 7.25 (lH,s) and7.42 ( 1H.s);m/:264(M+,X’Br). 245 and 97. 3-Bromo-2-(pentaAuorophenyl)thiophene (12b); Su (400 MHz, CDC13)7.15 ( lH, d, .I= 5.6 Hz) and 7.53 ( IH, d, J= 5.6 Hz); m/z 330 (Mt. “Br), 249,230 and 205. 3-Bromo-4-( pentafluorophenyl) thiophene ( 12~) ; 6, (400 MHz, CDCI,) 7.41 (lH, d, 5~3.4 Hz) and 7.45 (IH, d, J=3.4 Hz): m/z 330 (M+, “Br). 249, 230 and 205. HRMS (mixture of 12a, 12b and 12~) m/z 329.8959, C,,,H,F:‘BrS requires329.8960. Pentafluorophenyl-2-trimethylsilylthiophene (13) :2-Pentatluorophenyl-5-( trimethylsilyl)thiophene (13a); 6, (400 MHz, CDC13) 0.37 (9H, s), 7.29 (1H. d. J= 3.2 Hz) and 7.56 (IH, d, 5~3.2 Hz); s, (376 MHz, CDCl,) 140.2 (2F. m). 156.6 ( IF. t, J=22.6 Hz), and 162.7 (2F, m); ml; 320 and 307. 4-Pentafluorophenyl-2-( trimethylsiCM+) lyl) thiophene ( 13b) ; 6, (400 MHZ, CDCI,) 0.36 (9H, s) , 7.43 (lH, s) and 7.85 (lH, s); 6, (376 MHz, CDCI,) 142.2 (2F. m), 155.4 (lF, t. J=22.6 Hz) and 162.7 (2F, m); ml; 320 (M’ ) and 307. 3-Pentafluorophenyl-2-(trimethylsilyl)thiophene (13~); 6, (400 MHz. CDC13) 0.16 (9H. s), 7.06 (lH, d. J=4.8 Hz) and 7.67 (IH, d, J=4.8 Hz); S, (376 MHz, CDCl?) 139.7 (2F, m), 160.0 (lF, t, J=22.6 Hz) and 162.9 (2F, m); ml,- 320 (MC) and 307. HRMS
(mixture of 13a, 13b and 13~) nz/: 322.02’79, C,,H, ,F,SSi requires 322.027 I. 3-Pentatluomphenyl-2,5-dimethylthiophene (14) : v,,,(neat)/cm-’ 2940, 1520, 1500 and 980; S,, (400 MHz. CDCI,) 2.28 (3H, s), 2.45 (3H, s) and 61.57 ( IH, s); S, (100 MHz, CDCI,) 13.8, 15.0, 121.5. 126.5, 136.8 and 137.6; m/z, 278 (M+), 268, 243 and 111; HRMS: m/z 278.0187, C,,H,SF, requires 278.0189. 2,5-Dibromo-3-( pentafluorophenyl) thiophene (15): v,,,( KBr) /cm-’ 1520,1490, 1100, 1000 and 990; 6h (400 MHz, CDC&) 66.92 ( IH, s); 6, (100 MHz, CDCI,) 112.9, 114.8, 127.7 and 132.1; m/z 408 (M’, ‘“Br, *‘Br) and 283; HRMS: m/z 407.8088, C,,H,SF:“BrX’Br requires407.8066. 2.5Bis( trimethylsilyl)-3-( pentafluorophenyl) thiophene (16): ~,,,(KBr)/cm-’ 2970, 1530, 1500, 1250, 1100,980 and 840; S, (400 MHz, CDCI,) 0.18 (9H.. s), 0.36 (9H. s) and7.16 (lH,s);& (lOOMHz,CDCI,) -0.2, -0.1, 131.9, 137.3, 146.2and 146.3; m/z, 394 (M+), 379 and 267. Calcd. forC,,H,,SF,Si:C.48.71;H,4.85.Found:C,48.96;H,4.97. 3.2. Reuction of 2,5-bis(trimethylsilyl)-3(pentc$uorophenyl)thiophenewith tetrubutylammonium jluoride To a solution of 2,5-bis( trimethylsilyl) -3-( pentafluorophenyl)thiophene (16) (50 mg, 0.13 mmol) in benzene (2 cm3) was added a THF solution of tetrabutylammonium fluoride (1 M solution, 0.3 cm3, 0.3 mmol) and stirred at room temperaturefor I h. Water ( 10 cm3) was addedto the reaction mixture and the organic component was extracted with ether (5 cm3 X 3). The combined organic extract was washedwith ‘waterand dried over magnesiumsulfate. After removal of the solvent, the residuewas purified by gel-per-
meationchromatography and afforded 23 mg (72%) of pure 3-( pentafluorophenyl) thiophene (8b).
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