manganese(iii) acetate mediated synthesis of 3-trifluoroacetyl-4,5-dihydrofurans and...

www.elsevier.com/locate/fluor

Journal of Fluorine Chemistry 126 (2005) 401–406

Manganese(III) acetate mediated synthesis of 3-trifluoroacetyl-4,

5-dihydrofurans and 3-(dihydrofuran-2(3H)-ylidene)-1,1,

1-trifluoroacetones by free radical cyclization. Part 1

Mehmet Yılmaz *, A. Tarık Pekel

Ankara University, Science Faculty, Department of Chemistry, Tandogan, 06100 Ankara, Turkey

Received 20 August 2004; received in revised form 2 February 2005; accepted 2 February 2005

Available online 8 March 2005

Abstract

2-Trifluoroacetyl-4,5-dihydrofurans were obtained by manganese(III) acetate mediated radical cyclization of trifluoromethyl-1,3-

dicarbonyl compounds (1a–c) with conjugated alkenes (2a–h). The reaction of 1,1,1-trifluoropentane-2,4-dione (1a) with propenylbenzene

and 1,1-diphenyl-1-butene surprisingly yielded 3-(dihydrofuran-2(3H)-ylidene)-1,1,1-trifluoroacetones besides 3-trifluoroacetyl-4,5-dihy-

drofurans.

# 2005 Published by Elsevier B.V.

Keywords: Manganese(III) acetate; 3-Trifluoroacetyl-4,5-dihydrofuran; Radical cyclization; Trifluoromethyl-1,3-dicarbonyl; Oxidative addition

1. Introduction

The use of fluorine as a substituent in the synthesis

of important pharmaceutical compounds is developing.

Fluorinated molecules are widespread in pharmaceutical

applications like proteaz and phosphodiestereaz inhibition,

anti-parasitic agents, anti-cancer compounds, antibacterials,

and anesthetics [1,2].

Methods, like direct fluorination [3–5], fluoroalkylation

[6], enzymatic [7] and transition metal salts mediated

building-block [8,9], are used in the synthesis of fluorine

containing organic compounds. However, the increased

demand on fluorinated organic compounds increases the

need for new methods in this area.

It is well known that C–C bonds are formed during the

transition metal salt mediated oxidative addition of 1,3-

dicarbonyl compounds to unsaturated systems. Especially,

Mn(OAc)3 is effectively used in the synthesis of furans

[10–12], dihydrofurans [13–16], lactones [17], biologically

active compounds and natural products [17–21] but up to date

this method has not been applied to the Mn(OAc)3 mediated

* Corresponding author. Tel.: +90 312 2126720; fax: +90 312 2232395.

E-mail address: [email protected] (M. Yılmaz).

0022-1139/$ – see front matter # 2005 Published by Elsevier B.V.

doi:10.1016/j.jfluchem.2005.02.002

reaction of the trifluormethyl-1,3-dicarbonyl compounds with

alkenes. In this study, we have obtained 3-trifluoroacetyl-4,5-

dihydrofuran and 3-(dihydrofuran-2(3H)-ylidene)-1,1,1-tri-

fluoroacetone compounds by Mn(OAc)3 mediated radical

cyclization of 4,4,4-trifluoro-1-thien-2ylbutane-1,3-dione

(1a), 4,4,4-trifluoro-1-phenylbutane-1,3-dione (1b), and 1,

1,1-trifluoropentane-2,4-dione (1c) with various conjugated

alkenes.

2. Results and discussion

In this study, we report the synthesis of 3-trifluoroacetyl-

4,5-dihydrofurans and 3-(dihydrofuran-2(3H)-ylidene)-1,

1,1-trifluoroacetones by Mn(OAc)3 mediated radical cycliza-

tion of 1a–c with conjugated alkenes (2a–h) in a 2:1:1.2 molar

ratio, respectively. During the radical cyclizationexperiments,

effects of solvents like C6H6, CH3CN, and HOAc on product

yields have been investigated; the best results have been

obtained at 80 8C in HOAc. All the compounds synthesized

have been characterized by 1H, 13C, 19F NMR, MS, and

microanalysis. The results and the reaction pathway are given

in Table 1.

M. Yılmaz, A.T. Pekel / Journal of Fluorine Chemistry 126 (2005) 401–406402

Table 1

Radical cyclization of trifluoromethyl-1,3-dicarbonyl compounds with alkenes

Entry 1a–c Alkenes R2 R3 R4 Product and yield (%)a

1 1a 2a H H Ph 3a (28)

2 1a 2b H Me Ph 3b (67)

3 1a 2c H Ph Ph 3c (78)

4 1a 2d Ph H Ph 3d (22)

5 1a 2e H 4-Me-C6H4 4-Me-C6H4 3e (85)

6 1a 2f Me H Ph 3f (49)

7 1b 2b 3g (48)

8 1b 2c 3h (63)

9 1b 2e 3i (70)

10 1b 2f 3j (42)

11 1c 2b 3k (54)

12 1c 2f 3l (35), 4a (20)

13 1c 2g Et Ph Ph 3m (28), 4b (34)

a Yield of isolated product based on the 1,3-dicarbonyl compound.

Treatment of 1a with 2a and 2d gave moderate yields.

While we obtained 3f by the cyclization of 1a with 2f with

49% yield, dihydrofuran 3b was synthesized with 67% yield

by the cyclization of 1a with 1,1-disubstituted alkene 2b.

Treatment of other 1,1-disubstituted alkenes 2c, and 2e with

1a gave 3-trifluoroacetyl-4,5-dihydrofurans 3c (78%), and 3e(85%), respectively. Generally, higher yields were obtained

with 1,1-disubstituted alkenes. This may be due to the higher

stability of radical intermediates arising from the attack of

a-carbon radicals generated first to these alkenes. Similar

results were obtained in the reactions of 1b with 2f, 2b, and 2c,

where the yields of the reactions increase in the same order.

We obtained 3k (54%) with the treatment of 1c with

2b. However, during the formation of dihydrofuran 3l(35%) by the treatment of 1c with 2f, we unexpectedly

obtained 3-(dihydrofuran-2(3H)-ylidene)-1,1,1-trifluoroa-

cetone 4a (20%). We did not observe any formation of

compound 4 during the treatment of 1c with 1,1-

disubstituted alkene 2b. This led us to investigate the

reaction of 1c with 1,1,2-trisubstituted alkene 2g, which

resulted in the formation of 3m (28%), and 4b (34%). It is

possible to conclude that compounds 4 form when R2 is an

alkyl. Mn(OAc)3 mediated treatment mechanisms of 1,3-

dicarbonyls, b-ketoesters and carboxylic acids have been

given in detail in the literature [16,17]. In Scheme 1, we

propose the mechanism of 3-trifluoroacetyl-4,5-dihydro-

furans (3a–n) and 3-(dihydrofuran-2(3H)-ylidene)-1,1,1-

trifluoroacetones (4a, 4b) reactions.

According to this mechanism, Mn(OAc)3 (MnL3) gives

manganese(III)-enolate complex A or B with the enol form

of trifluoromethyl-1,3-dicarbonyl. In structure A, an a-

carbon radical is formed in 1,3-dicarbonyl compound, while

MnIII is reduced to MnII. D forms by the addition of this

radical to an alkene and the following oxidation of the

intermediate product by MnIII. This carbocation intermedi-

ate can lead to compound 3 following pathway i or Efollowing pathway ii because this product can have two

tautomeric forms. The chemical shift values of the carbon

atom neighbouring the –CF3 group has been found at 174–

177 ppm (q, J = 34–35 Hz) in the 13C-NMR spectra of the

compounds. Thus the –CF3 group is neighbour to the

carbonyl group, so the isolated compounds are 3-trifluor-

oacetyl-4,5-dihydrofurans (3a–m). However, this mechan-

ism cannot explain the formation of the compounds 4a and

4b. The mechanism could follow the pathway explained

below. Mn(III)-dienolate complex C forms with the removal

of HL from B, and here MnIII is reduced forming a terminal

radical carbon. This mechanism is similar to the Mn(OAc)3

mediated terminal radical formation from diketene [22]. F is

formed by the addition of the radical to the alkene and a

subsequent oxidation to a carbocation. From F, 4 can be

obtained following pathway i or G following pathway ii.From the 13C NMR spectra of the compounds isolated we

concluded that the –CF3 group is adjacent to the carbonyl

group, so 4a and 4b are derivatives of 3-(dihydrofuran-

2(3H)-ylidene)-1,1,1-trifluoroacetone.

3. Experimental

Melting points were determined on a Gallencamp

capillary melting point apparatus and are uncorrected. IR

spectra (KBr disc, CHCl3) were obtained with a Matson

1000 FT-IR in the 400–4000 cm�1 range with 4 cm�1

M. Yılmaz, A.T. Pekel / Journal of Fluorine Chemistry 126 (2005) 401–406 403

Scheme 1.

resolution. 1H NMR (400 MHz), 13C NMR (100 MHz) and19F NMR (376 MHz) spectra were recorded on a Bruker

DPX 400 MHz high performance digital FT NMR, in CDCl3solution using TMS as an internal standard. The electron

impact mass spectra (EIMS 70 eV) were measured on

Micromass UK Platform-II LC/MS spectrophotometer.

Elemental analyses were performed on a Leco 932

CHNS-O instrument.

Manganese(III) acetate dihydrate (98%) was prepared by

an electrochemical method according to the literature [23].

2c, 2e, 2f and 2g conjugated alkenes were obtained by the

use of suitable carbonyl compounds and Grignard reagents.

Other alkenes and trifluoromethyl-1,3-dicarbonyl com-

pounds were purchased from ABCR.

3.1. General procedure

A solution of manganese(III) acetate dihydrate (5 mmol,

1.35 g) in 30 mL in glacial acetic acid was heated under

nitrogen atmosphere at 80 8C until it dissolved. After

Mn(OAc)3 dissolved completely, the solution was cooled

down to 60 8C. A solution of trifluoromethyl-1,3-dicarbonyl


compound (2.5 mmol) and alkene (3 mmol) in 5 mL acetic

acid was added to this mixture and the temperature was raised

to 80 8C. The reaction was complete when the dark brown

colour of the solution disappeared. Acetic acid was

evaporated under reduced pressure. Water was added to the

residue and extraction was performed with EtOAc or

CHCl3 (3 � 20 mL). The combined organic extracts were

neutralized with satd. NaHCO3 solution, and dried over

anhydrous Na2SO4 and evaporated to give oil. Products were

purified by flash chromatography on silica gel, eluting with

hexane:EtOAc (6:1).

3.1.1. 2,2,2-Trifluoro-1-(5-phenyl-2-thien-2-yl-4,

5-dihydrofuran-3-yl)ethanone (3a)

Yellow oil; 1H NMR: d 3.48 (1H, ddq, J = 14.7, 8.0 Hz,5JH–F = 0.7 Hz, H-4), 3.90 (1H, ddq, J = 14.7, 10.2 Hz, 5JH–

F = 0.9 Hz, H0-4), 6.01 (1H, dd, J = 10.2, 8.7 Hz, H-5), 7.34

(1H, dd, J = 5.0, 4.0 Hz), 7.54 (5H, m), 7.83 (1H, dd, J = 5.0,

1.1 Hz), 8.68 (1H, dd, J = 4.6, 1.1 Hz); 13C NMR: d 37.9 (q,4JC–F = 0.4 Hz, C-4), 84.9 (C-5), 103.4 (C-3), 119.0 (q, 1JC–

F = 291.0 Hz, –CF3), 126.1, 128.1, 129.2, 129.3, 131.1,

134.2, 135.7, 140.2, 166.9 (C-2), 174.7 (q, 2JC–F = 34.1 Hz,

C O); 19F NMR: d �84.0 (s, CF3); IR nmax: 2922, 1662

(C O), 1533 (C C), 1199, 752, 700; MS (m/z, %): 325

(M+ + 1, 1.52), 324 (M+, 1.92), 255 (M+ � CF3, 2.14), 227

(M+ � CF3CO, 2.99), 150 (M+ � CF3–PhCO, 2.88), 116

(M+ � CF3CO–C5H3OS, 6.66), 111 (C5H3OS+, 100.00),

105 (PhCO+, 42.76), 91 (PhCH2+, 15.95), 77 (C6H5

+, 52.96),

69 (CF3, 24.01); Anal. calc. for C16H11F3O2S (%): C 59.25;

H 3.4; S 9.9; Found (%): C 59.3; H 3.4; S 9.9.

3.1.2. 2,2,2-Trifluoro-1-(5-methyl-5-phenyl-2-thien-2-yl-

4,5-dihydrofuran-3-yl) ethanone (3b)

Yellow oil; 1H NMR: d 1.87 (3H, s, –CH3), 3.50 (1H, dd,

J = 14.5 Hz, 5JH–F = 0.8 Hz, H-4), 3.64 (1H, d, J = 14.3 Hz,

H0-4), 7.25 (1H, dd, J = 4.9, 4.0 Hz), 7.40–7.47 (5H, m),

7.73 (1H, dd, J = 5.0, 1.1 Hz), 8.63 (1H, dd, J = 3.9, 1.0 Hz);13C NMR: d 29.5 (CH3), 43.9 (q, 4JC–F = 3.5 Hz, C-4), 90.9

(C-5), 103.3 (C-3), 119.1 (q, 1JC–F = 291 Hz, –CF3), 124.5,

127.6, 127.7, 129.0, 131.5, 134.1, 135.6, 145.2, 174.4 (C-2),

175.1 (q, 2JC–F = 34 Hz, C O); 19F NMR: d �76.4 (s, CF3);

IR nmax: 3046, 1671 (C O), 1537 (C C), 1215, 729, 700;

MS (m/z, %): 339 (M+ + 1, 5.14), 338 (M+, 27.20), 320

(MH+�F, 8.48), 305 (MH+�F–CH3, 3.30), 269 (M+ � CF3,

6.25), 241 (M+ � CF3CO, 4.41), 227 (M+ � C5H3OS,

32.35), 185 (M+ � CF3–C4H3S, 49.26), 111 (C5H3OS+,

100.00), 91 (PhCH2+, 2.94), 77 (C6H5

+, 8.08), 69 (CF3+,

1.47); Anal. calc. for C17H13F3O2S (%): C 60.35; H 3.9; S

9.5; Found (%): C 60.4; H 3.85; S 9.6.

3.1.3. 1-(5,5-Diphenyl-2-thien-2-yl-4,5-dihydrofuran-3-

yl)-2,2,2-trifluoroethanone (3c)

Yellow oil; 1H NMR: d 4.01 (2H, s, H-4), 7.24–7.49

(11H, m), 7.79 (1H, dd, J = 7.2, 1.3 Hz), 8.64 (1H, dd,

J = 3.7, 0.8 Hz); 13C NMR: d 43.6 (q, 4JC–F = 3.6 Hz, C-4),

94.3 (C-5), 104.3 (C-3), 119.8 (q, 1JC–F = 291 Hz, –CF3),

126.7, 129.2, 129.3, 129.5, 129.8, 131.3, 132.1, 133.6,

135.1, 136.5, 138.8, 144.8, 166.5 (C-2), 175.6 (q, 2JC–

F = 34.5 Hz, C O); 19F NMR: d �76.4 (s, CF3); IR nmax:

1672 (C O), 1538 (C C), 1209, 729, 700; MS (m/z, %):

401 (M+ + 1, 7.35), 400 (M+, 30.88), 382 (MH+ � F,

16.91), 331 (M+ � CF3, 8.08), 316 (MH+ � C4H3S, 16.17),

303 (M+ � CF3CO, 5.88), 289 (M+ � C5H3OS, 64.70), 247

(MH+ � C6H5, 66.91), 191 (M+ � C5H3OS–CF3CO,

24.26), 165 (Ph2C+, 23.52), 111 (C5H3OS+, 100.00), 97

(CF3CO+, 2.73), 77 (C6H5+, 5.51); Anal. calc. for

C22H15F3O2S (%): C 66.0; H 3.8; S 8.0; Found (%): C

66.1; H 3.75; S 8.0.

3.1.4. 1-(4,5-Diphenyl-2-thien-2-yl-4,5-dihydrofuran-3-

yl)-2,2,2-trifluoroethanone (3d)

Yellow oil; 1H NMR: d 4.72 (1H, dq, J = 3.9 Hz, 5JH–

F = 1.2 Hz, H-4), 5.60 (1H, d, J = 3.9 Hz, H-5), 7.28 (6H, m),

7.42 (5H, m), 7.80 (1H, dd, J = 5.0, 1.0 Hz), 8.64 (1H, dd,

J = 3.8, 1.0 Hz); 13C NMR: d 57.0 (q, 4JC–F = 2.4 Hz, C-4),

93.4 (C-5), 108.2 (C-3), 119.3 (q, 1JC–F = 291 Hz, –CF3),

126.2, 128.2, 128.8, 129.2, 130.1, 130.3, 130.3, 131.6,

135.4, 136.9, 141.1, 144.2, 168.4 (C-2), 177.2 (q, 2JC–

F = 35 Hz, C O); 19F NMR: d�74.5 (s, CF3); IR nmax: 3030,

1670 (C O), 1533 (C C), 1207, 756, 700; MS (m/z, %): 400

(M+, 10.55), 398 (M�2, 10.02), 331 (M+ � CF3, 1.85),

247 (M+ � H–CF3–C4H3S, 6.46), 197 (M+ � 2H–C5H3OS–

PhCH2, 29.11), 111 (C5H3OS+, 100.00), 91 (PhCH2+,

10.23), 77 (C6H5+, 36.71), 69 (CF3

+, 13.92); Anal. calc.

for C22H15F3O2S (%): C 66.0; H 3.8; S 8.0; Found (%): C

66.05; H 3.7; S 8.0.

3.1.5. 1-(5,5-Bis(4-methylphenyl)-2-thien-2-yl-4,5-

dihydrofuran-3-yl)-2,2,2-trifluoro-ethanone (3e)

Yellow oil; 1H NMR: d 2.39 (6H, s, –CH3), 4.03 (2H, s,

–CH2), 7.23 (4H, d, J = 8.0 Hz), 7.27 (1H, dd, J = 4.9,

3.9 Hz), 7.38 (4H, d, J = 8.4 Hz), 7.75 (1H, dd, J = 4.9,

1.1 Hz), 8.69 (1H, dd, J = 3.9, 1.1 Hz); 13C NMR: d 21.5

(–CH3), 43.6 (q, 4JC–F = 3.3 Hz, C-4), 94.4 (C-5), 104.3

(C-3), 119.8 (q, 1JC–F = 291 Hz, –CF3), 126.7, 129.1,

130.4, 132.2, 134.9, 136.4, 139.1, 142.0, 166.6 (C-2),

175.6 (q, 2JC–F = 34 Hz, C O); 19F NMR: d �76.4 (s,

CF3); IR nmax: 2922, 1671 (C O), 1539 (C C), 1207,

1136, 729; MS (m/z, %): 428 (M+, 4.81), 426 (M+ � 2H,

5.51), 408 (M+ � HF, 4.65), 331 (M+ � CF3CO, 4.07),

316 (M+ � CF3CO–CH3, 17.75), 221 (M+ � CF3CO–

C5H3OS, 13.13), 110 (C5H2OS+, 100.00); Anal. calc.

for C24H19F3O2S (%): C 67.3; H 4.5; S 7.5; Found (%): C

67.25; H 4.5; S 7.6.

3.1.6. 2,2,2-Trifluoro-1-(4-methyl-5-phenyl-2-thien-2-yl-

4,5-dihydrofuran-3yl)ethanone (3f)Yellow oil; 1H NMR: d 1.70 (3H, d, J = 6.7 Hz, –CH3),

3.84 (1H, qd, J = 6.6, 3.6 Hz, H-4), 5.60 (1H, d, J = 3.0 Hz,

H-5), 7.42 (1H, t, J = 4.7 Hz), 7.57 (5H, m), 7.91 (1H, d,

J = 5.0 Hz), 8.73 (1H, d, J = 3.9 Hz); 13C NMR: d 22.8 (–

CH3), 42.2 (C-4), 91.8 (C-5), 110.0 (C-3), 119.0 (q, 1JC–

M. Yılmaz, A.T. Pekel / Journal of Fluorine Chemistry 126 (2005) 401–406 405

F = 291 Hz, –CF3), 126.2, 129.1, 129.7, 129.8, 133.2, 135.1,

136.7, 140.9, 167.7 (C-2), 176.6 (q, 2JC–F = 35 Hz, C O);19F NMR: d �74.4 (s, CF3); IR nmax: 1658 (C O), 1529

(C C), 1176, 727, 700; MS (m/z, %): 339 (M+, 5.04),

338 (M+, 8.81), 242 (MH+ � CF3CO, 13.41), 227

(M+ � C5H3OS, 12.89), 150 (M+ � CF3CO–PhCH2,

12.26), 111 (C5H3OS+, 100.00), 105 (PhCO+, 46.08), 91

(PhCH2+, 20.94), 77 (C6H5

+, 37.25), 69 (CF3+, 23.43); Anal.

Calc. for C17H13F3O2S (%): C 60.35; H 3.9; S 9.5; Found

(%): C 60.4; H 3.9; S 9.4.

3.1.7. 2,2,2-Trifluoro-1-(5-methyl-2,5-diphenyl-4,

5-dihydrofuran-3-yl)ethanone (3g)

Pale yellow oil; 1H NMR: d 1.88 (3H, s, –CH3), 3.47 (1H,

dq, J = 14.4 Hz, 5JH–F = 0.9 Hz, H-4), 3.61 (1H, dq,

J = 14.4 Hz, 5JH–F = 0.3 Hz, H-4), 7.36 (2H, m), 7.35–

7.55 (8H, m), 7.93 (2H, dt, J = 8.1, 1.5 Hz); 13C NMR: d 29.3

(CH3), 43.7 (q, 4JC–F = 3.4 Hz, C-4), 91.0 (C-5), 103.5 (C-

3), 118.2 (q, 1JC–F = 290 Hz, –CF3), 124.8, 128.6, 128.6,

128.7, 129.5, 130.4, 131.9, 132.8, 134.4, 135.9, 145.7,

166.5, 173.4 (C-2), 175.5 (q, 2JC–F = 34 Hz, C O); 19F

NMR: d �76.4 (s, CF3); IR nmax: 3061, 1683 (C O), 1554

(C C), 1211, 758, 696; MS (m/z, %): 333 (MH+, 1.31), 332

(M+, 1.04), 314 (MH+ � F, 2.31), 263 (M+ � CF3, 6.21), 227

(M+ � PhCO, 22.29), 130 (M+ � PhCO–CF3CO, 5.84), 105

(PhCO+, 100.00), 77 (C6H5+, 67.25), 69 (CF3

+, 10.26); Anal.

calc. for C19H15F3O2 (%): C 68.7; H 4.55; Found (%): C

68.7; H 4.5.

3.1.8. 2,2,2-Trifluoro-1-(2,5,5-triphenyl-4,5-dihydrofuran-

3-yl)ethanone (3h)

Pale yellow oil; 1H NMR: d 4.03 (2H, s, –CH2), 7.36 (2H,

m), 7.40 (4H, m), 7.47 (6H, m), 7.56 (1H, tt, J = 7.3, 1.3 Hz),

7.94 (2H, dt, J = 7.1, 1.4 Hz); 13C NMR: d 43.8 (q, 4JC–

F = 3.0 Hz, C-4), 94.6 (C-5), 106.0 (C-3), 119.5 (q, 1JC–

F = 291 Hz, –CF3), 126.8, 129.2, 129.3, 129.9, 130.1, 130.9,

133.4, 145.0, 173.4 (C-2), 176.7 (q, 2JC–F = 35 Hz, C O);19F NMR: d �76.3 (s, CF3); IR nmax: 3061, 1685 (C O),

1556 (C C), 1211, 754, 696; MS (m/z, %): 395 (MH+, 1.13),

394 (M+, 2.21), 325 (M+ � CF3, 3.05), 297 (M+ � CF3CO,

2.20), 289 (M+ � PhCO, 15.50), 220 (M+ � CF3CO–C6H5,

11.16), 166 (Ph2CO+, 28.42), 105 (PhCO+, 59.32), 77

(C6H5+, 100.00), 69 (CF3

+, 53.20); Anal. calc. for

C24H17F3O2 (%): C 73.1; H 4.3; Found (%): C 73.0; H 4.4.

3.1.9. 2,2,2-Trifluoro-(5,5-bis(4-methylphenyl)-2-phenyl-

4,5-dihydrofuran-3-yl) ethanone (3i)Slightly yellow oil; 1H NMR: d 2.17 (6H, s, –CH3), 3.81

(2H, s, –CH2), 7.02 (4H, d, J = 8.2 Hz), 7.16 (4H, d,

J = 8.2 Hz), 7.27 (2H, t, J = 7.9 Hz), 7.33 (1H, t, J = 7.4 Hz),

7.73 (2H, dd, J = 8.8, 1.4 Hz); 19F NMR: d �76.2 (s, CF3);

IR nmax: 1685 (C O), 1556 (C C), 1209, 758, 692; MS (m/z,

%): 422 (M+, 2.21), 325 (M+ � CF3CO, 5.30), 220

(M+ � CF3CO–PhCO, 14.42), 105 (PhCO+, 83.98), 104

(C8H8+, 100.00), 77 (C6H5


C26H21F3O2 (%): C 73.9; H 5.0; Found (%): C 73.9; H 5.1.

3.1.10. 2,2,2-Trifluoro-1-(4-methyl-2,5diphenyl-4,5-

dihydrofuran-3-yl)ethanone (3j)Slightly yellow oil; 1H NMR: d 1.61 (3H, d, J = 6.7 Hz, –

CH3), 3.76 (1H, qd, J = 6.5, 5.2 Hz, H-4), 5.45 (1H, d,

J = 4.9 Hz, H-5), 7.51–7.64 (8H, m), 7.89 (2H, dt, J = 7.1,

2.0 Hz); 13C NMR: d 21.2 (–CH3), 45.8 (C-4), 91.9 (C-5),

111.3 (C-3), 115.1 (q, 1JC–F = 290 Hz, –CF3), 125.4, 128.6,

128.7, 129.2, 129.3, 129.7, 131.9, 139.5, 172.3 (C-2), 177.0

(q, 2JC–F = 35 Hz, C O); 19F NMR: d�73.7 (s, CF3); IR nmax:

1660 (C O), 1585 (C C), 1197, 756, 696; MS (m/z, %): 334

(M+2, 0.54), 332 (M+, 1.90), 235 (M+ � CF3CO, 3.63), 227

(M+ � PhCO, 1.27), 145 (MH+ � CF3–PhCO–CH3, 8.82),

105 (PhCO+, 100.00), 91 (PhCH2+, 27.06), 77 (C6H5

+,

100.00), 50 (CF2, 100.00), 69 (CF3+, 23.43); Anal. calc. for

C19H15F3O2 (%): C 68.7; H 4.55; Found (%): C 68.7; H 4.6.

3.1.11. 1-(2,5-Dimethyl-5-phenyl-4,5-dihydrofuran-3-yl)-

2,2,2-trifluoroethanone (3k)

Oil; 1H NMR: d 1.77 (3H, s, –CH3), 2.46 (3H, s, –CH3),

3.02 (1H, d, J = 14.0 Hz, H-4), 3.34 (1H, d, J = 14.0 Hz, H-

4), 7.37 (5H, m); 13C NMR: d 16.0 (–CH3), 29.3 (–CH3),

42.4 (q, 4JC–F = 3.1 Hz, C-4), 91.8 (C-5), 105.1 (C-3), 118.2

(q, 1JC–F = 290 Hz, –CF3), 124.0, 127.7, 128.7, 144.9, 176.5

(q, 2JC–F = 34 Hz, C O) 176.6 (C-2); 19F NMR: d �77.1 (s,

CF3); IR nmax: 1685 (C O), 1575 (C C), 1199, 764, 700;

MS (m/z, %): 271 (MH+, 1.96), 270 (M+, 1.64), 227

(M+ � CH3CO, 5.38), 201 (M+ � CF3, 2.02), 158

(M+ � CF3CO–CH3, 3.62), 130 (M+ � CF3CO–CH3CO+,

5.19), 105 (PhCO+, 8.30), 97 (CF3CO+, 2.15), 77 (C6H5+,

39.73), 69 (CF3+, 100.00), 43 (CH3CO+, 100.00); Anal. calc.

for C14H13F3O2 (%): C 62.2; H 4.85; Found (%): C 62.3; H

4.9.

3.1.12. 1-(2,4-Dimethyl-5-phenyl-4,5-dihydrofuran-3-yl)-

2,2,2-trifluoroethanone (3l)Oil; 1H NMR: d 1.50 (3H, d, J = 6.6 Hz, –CH3), 2.52 (3H,

s, –CH3), 3.57 (1H, m, H-4), 5.32 (1H, d, J = 5.0 Hz, H-5),

7.39 (2H, m), 7.50 (3H, m); 13C NMR: d 16.0 (–CH3), 21.2

(–CH3), 44.4 (C-4), 92.7 (C-5), 111.3 (C-3), 112.4, 118.0 (q,1JC–F = 289 Hz, –CF3), 125.3, 128.8, 128.9, 139.5, 176.3 (C-

2), 177.0 (q, 2JC–F = 35 Hz, C O); 19F NMR: d �74.8 (s,

CF3); IR nmax: 1700 (C O), 1569 (C C), 1186, 760, 700;

MS (m/z, %): 271 (MH+, 44.71), 270 (M+, 49.80), 255

(M+ � CH3, 11.27), 227 (M+ � CH3CO, 8.73), 201

(M+ � CF3, 10.20), 105 (PhCO+, 21.86), 97 (PhCH2+,

15.59), 77 (C6H5+, 23.04), 69 (CF3

+, 18.63), 43 (CH3CO+,

100.00); Anal. calc. for C14H13F3O2 (%): C 62.2; H 4.85;

Found (%): C 62.3; H 4.9.

3.1.13. (3E)-1,1,1-Trifluoro-3-(4-methyl-5-

phenyldihydrofuran-2(3H)-ylidene)acetone (4a)

Oily solid; 1H NMR: d 1.13 (3H, d, J = 2.0 Hz, –CH3),

2.40 (1H, m, H-4), 2.74 (1H, ddq, J = 19.0, 9.9, 1.7 Hz, H-

3’), 3.67 (1H, dd, J = 18.9, 7.8 Hz, H-3), 4.90 (1H, d,

J = 8.8 Hz, H-5), 6.01 (1H, s, Holef), 7.24 (2H, m), 7.33 (3H,

m); 13C NMR: d 15.9 (–CH3), 40.5 (C-4), 41.0 (C-3), 91.8


(C-5), 92.9 (C-30), 118.0 (q, 1JC–F = 288.5 Hz, –CF3), 126.1,

128.8, 129.0, 137.3, 180.1 (q, 2JC–F = 34 Hz, C O), 184.1

(C-2); 19F NMR: d �78.7 (s, CF3); MS (m/z, %): 271 (MH+,

15.21), 270 (M+, 17.34), 255 (MH+ � CH3, 16.46), 201

(M+ � CF3, 7.10), 173 (M+ � CF3CO, 6.60), 139

(M+ � C10H12, 100.00), 133 (M+ � C4H2F3O2, 46.84),

105 (PhCO+, 17.42), 91 (PhCH2+, 77.68), 69 (CF3

+,

36.32); Anal. calc. for C14H13F3O2 (%): C 62.2; H 4.85;

Found (%): C 62.2; H 4.8.

3.1.14. 1-(4-Ethyl-2-methyl-5,5-diphenyl-4,5-

dihydrofuran-3-yl)-2,2,2-trifluoro ethanone (3m)

Oil; 1H NMR: d 0.51 (3H, t, J = 7.4 Hz, –CH3), 1.40 (1H,

m), 1.50 (1H, m), 2.40 (3H, s, –CH3), 4.05 (1H, t, J = 5.3 Hz,

H-4), 7.29–7.37 (8H, m), 7.50 (2H, m); 13C NMR: d 10.2 (–

CH3), 16.2 (CH2), 24.7 (–CH3), 48.5 (C-4), 97.4 (C-5), 113.3

(C-3), 118.1 (q, 1JC–F = 289 Hz, –CF3), 126.0, 126.5, 127.4,

127.9, 128.1, 139.6, 143.9, 174.3 (C-2), 177.1 (q, 2JC–

F = 34 Hz, C O); 19F NMR: d �77.0 (s, CF3); MS (m/z, %):

361 (MH+, 0.49), 360 (M+, 0.69), 345 (M+ � CH3, 0.15), 317

(M+ � CH3CO, 17.17), 299 (M+ � PhCH2, 3.89), 249

(MH+ � CF3CO–CH3, 2.19), 166 (Ph2CH+, 25.82), 105

(PhCO+, 47.74), 91 (PhCH2+, 14.90), 97 (CF3CO+, 1.0), 77

(C6H5+, 24.33), 69 (CF3

+, 7.23), 43 (CH3CO+, 100.00);

Anal. calc. for C21H19F3O2 (%): C 70.0; H 5.3; Found (%): C

70.0; H 5.4.

3.1.15. (3E)-(4-Ethyl-5,5-phenyldihydrofuran-2(3H)-

ylidene)-1,1,1-trifluoroaceton (4b)

Oily solid; 1H NMR: d 0.83 (1H, m), 0.98 (3H, t,

J = 7.3 Hz, –CH3), 1.54 (1H, m), 1.50 (1H, m), 3.08 (1H,

ddd, J = 19.6, 7.2, 1.3 Hz, H-2), 3.13 (1H, m, H-4), 3.52 (1H,

ddd, J = 20.8, 10.6, 1.1 Hz, H-20), 6.26 (1H, s, Holef), 7.10–

7.48 (10H, m); 13C NMR: d 12.3 (–CH3), 24.5 (CH2), 38.1

(C-4), 45.8 (C-3’), 91.9 (C-5), 97.5 (C-3), 118.1 (q, 1JC–

F = 290 Hz, –CF3), 126.0, 126.4, 127.7, 128.1, 128.4, 128.5,

140.2, 142.2, 180.1 (q, 2JC–F = 34 Hz, C O), 183.3 (C-2);19F NMR: d �76.5 (s, CF3); MS (m/z, %): 361 (MH+, 2.76),

360 (M+, 11.91), 331 (M+ � C2H5, 1.90), 291 (M+ � CF3,

4.01), 206 (M+ � 2C6H5, 124.90), 178 (M+ � Ph2CO,

15.99), 105 (PhCO+, 57.28), 91 (PhCH2+, 100.00), 77

(C6H5+, 34.14), 69 (CF3


C21H19F3O2 (%): C 70.0; H 5.3; Found (%): C 70.1; H 5.3.

Acknowledgements

The authors thank Ankara University Scientific Research

Projects Coordination Service (BAP 20030705076 coded

project), and The Scientific and Technical Research Council

of Turkey (TBAG-AY/239 coded project) for financial

support, as well as Prof. Dr. J.M. Mellor for supportive

discussions.

References

[1] J.M. Altenburger, D. Schirlin, Tetrahedron Lett. 32 (1991) 7255–7258.

[2] F.M.D. Ismail, J. Fluorine Chem. 118 (2002) 27–33.

[3] T. Kitazume, T. Yamazahi, Experimental Methods in Organic Fluorine

Chemistry, Amsterdam, 1998.

[4] G.M. Brooke, J. Fluorine Chem. 86 (1997) 1–76.

[5] N.O. Brace, J. Fluorine Chem. 93 (1999) 1–25.

[6] G.Q. Shi, Y.Y. Xu, M. Xu, Tetrahedron 47 (1991) 1629–1648.

[7] D. O’ Hagan, C. Schaffrath, S.L. Cobb, J.T.G. Hamilton, C.D. Murphy,

Nature 416 (2002) 279.

[8] S. Leconte, R. Ruzziconi, J. Fluorine Chem. 117 (2002) 167–172.

[9] Y. Wang, S. Zhu, Tetrahedron 57 (2001) 3383–3387.

[10] M. Yılmaz, A.T. Pekel, Synth. Commun. 31 (2001) 3871–3876.

[11] G.G. Melikyan, A.B. Sargsyan, Sh.O. Badanyan, Chem. Heterocycl.

Compd. (1989) 606–610.

[12] E.J. Corey, A.K. Ghosh, Chem. Lett. (1987) 223–226.

[13] M. Yılmaz, A.T. Pekel, Synth. Commun. 31 (2001) 2189–2194.

[14] J.M. Mellor, S. Mohammed, Tetrahedron Lett. 32 (1991) 7111–7114.

[15] J.M. Mellor, S. Mohammed, Tetrahedron 49 (1993) 7547–7556.

[16] S. Kajikawa, H. Nishino, K. Kurosawa, Heterocycles 54 (2001) 171–

183.

[17] G.G. Melikyan, Synthesis (1993) 833–850.

[18] B.B. Snider, Chem. Rev. 96 (1996) 339–363.

[19] D. Yang, X. Ye, S. Gu, X. Ming, J. Am. Chem. Soc. 121 (1999) 5579–

5580.

[20] B.B. Snider, J.Y. Kiselgof, B.M. Foxman, J. Org. Chem. 63 (1998)

7945–7952.

[21] B.B. Snider, L. Han, C. Xie, J. Org. Chem. 62 (1997) 6978–6984.

[22] H. Nishino, V. Nguyen, S. Yashinaga, K. Kurosawa, J. Org. Chem. 61

(1996) 8264–8271.

[23] A. Guvenc, A.T. Pekel, O.M. Kockar, Chem. Eng. J. 99 (2004) 257–

263.

manganese(iii) acetate mediated synthesis of 3-trifluoroacetyl-4,5-dihydrofurans and...

Documents