Controlled TfOH- or AuCl-catalyzed cycloisomerization and tandem hydrolytic defluorination of 1,2-allenyl perfluoroalkyl ketones

Abstract

An efficient TfOH- or AuCl-catalyzed cycloisomerization reaction of easily available n-perfluoroalkyl 1,2-allenyl ketones occurring smoothly to form 2-perfluoroalkyl furans has been reported. In the presence of TfOH and H₂O, a corresponding tandem hydrolytic defluorination afforded multi-substituted furan-2-yl n-perfluoroalkyl ketones.

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Introduction

As one of the ubiquitous heterocyclic cores, furan plays a significant role in organic synthesis,¹ and also broadly exists in natural products² and useful materials.³ Many efforts have been made to construct intricate furan derivatives,^4–10among which transition metal-catalyzed (such as Ag, Au, Pd, Rh, etc.) cycloisomerization of allenones^6–10 (Scheme 1a) was found to be apposite due to the substituent-loading capability of the unique substrates. On the other hand, due to their extensive application in the field of functional materials and the importance of organofluorine compounds,¹¹ the development of synthetic methodologies for generating perfluoroalkyl substituted heterocycles is of current interest. In our previous work, we reported a TfOH-catalyzed¹² direct formation of furanyl perfluoroalkyl ketones from easily available n-perfluoroalkyl allenones¹³ (Scheme 1b).¹⁴ In this study, we wish to describe a TfOH- or AuCl-catalyzed controlled cycloisomerization of perfluoroalkyl allenones, affording perfluoroalkyl furans first, which may be converted to corresponding hydrolytically defluorinated ketones in the presence of TfOH and water.

Scheme 1 Cyclization reactions of ordinary allenones and perfluoroalkyl allenones.

Results and discussion

We started to explore the cycloisomerization reaction with fully-substituted perfluoroalkyl allenone 1a as the model substrate. No reaction occurred when AuCl was used as the catalyst (entry 1, Table 1), while AuCl₃ produced perfluoroalkyl furan 2a in only 46% NMR yield (entry 2, Table 1). It was interesting to observe that aged triflic acid could catalyze the conversion of perfluoroalkyl substituted allenone 1a to form furan 2a together with furanyl ketone 3a (entry 3, Table 1). To our delight, furan 2a was formed in 96% NMR yield as the sole product (entry 5, Table 1) with a catalytic amount of newly purchased TfOH (5 mol%) in toluene at 60 °C for 10 h.

Table 1 Optimization of the cycloisomerization reaction of 1a^a

Entry	Cat. (mol%)	Time (h)	NMR yield^b (%)		Recovery of 1a^b (%)
			2a	3a
a The reactions were conducted on a 0.2 mmol scale in toluene (2 mL). b Determined using ^1H NMR analysis with CH2Br2 as the internal standard. c Aged reagent, may contain water. d 1 equiv. H2O was added with newly purchased TfOH. e The reaction was conducted at 60 °C and mesitylene was used instead of CH2Br2 as the internal standard.
1	AuCl (10)	21	0	0	82
2	AuCl3 (10)	19	46	0	51
3	TfOH^c (10)	2	35	59	0
4	TfOH^d (10)	2.5	0	98	0
5^e	TfOH (5)	10	96	0	0

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The reaction scope was then explored using the optimized reaction conditions presented in entry 5 of Table 1. For the 1,1-diphenyl-substituted allenyl perfluoroalkyl ketones 1a–1c, no matter whether R³ = propyl or methyl, with R_f = n-perfluoropropyl or pentyl, the corresponding products 2a–2c could be formed exclusively (entries 1–3, Table 2). Although 2d could be obtained as a single product in good yield (entry 4, Table 2), on changing R¹ from Et to Me, furan 2e (69%) was formed together with ketone 3e¹⁴ (30%) (entry 5, Table 2).

Table 2 Cycloisomerization reactions of fully-substituted allenyl perfluoroalkyl ketones 1^a

Entry	R^1	R^2	Rf	Time (h)	Yield of 2^b (%)
a Conditions: substrate (0.5 mmol), TfOH (5 mol%) and toluene (5 mL), at 60 °C. b Isolated yield. c The reaction was conducted on a 0.2 mmol scale. d TfOH (2 mol%) was used and the reaction was conducted on a 0.3 mmol scale. e 3e was also afforded in 30% isolated yield.
1^c	Ph	n-Pr	n-C3F7 (1a)	10	96 (2a)
2^d	Ph	n-Pr	n-C5F11 (1b)	2	91 (2b)
3	Ph	Me	n-C3F7 (1c)	2.5	89 (2c)
4	Et	Et	n-C3F7 (1d)	4	75 (2d)
5	Me	Et	n-C3F7 (1e)	1.5	69 (2e)^e

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However, when we attempted to extend this cycloisomerization to 1-mono-substituted allenyl ketone 1f, only 9% of furan 2f was afforded with 87% recovery of 1f (entry 1, Table 3). When trifluoromethanesulfonates such as Cu(OTf)₂ ^9f,g and AgOTf^9f,g were applied as the catalyst, there was still 88% and 56% recovery of 1f, respectively (entries 2 and 3, Table 3). Interestingly, 2f was obtained efficiently with a catalytic amount of AuCl in toluene at 100 °C (entry 4, Table 3). It should be mentioned that AuCl has been identified as a catalyst for the selective cycloisomerization of allenones for the first time.⁹ⁱ Then a series of other cheaper Lewis acids was screened: although 43% of 2f could be produced when FeCl₃ was used (entry 6, Table 3), only 11% and 9% of 2f were detected using NMR under the catalysis of SnCl₄ and BF₃·2H₂O (entries 7 and 8, Table 3), respectively; BF₃·Et₂O and CuI^9a failed to catalyze the reaction (entries 9 and 10, Table 3); while with TiCl₄, complete decomposition of 1f occurred (entry 11, Table 3). Thus, the reaction conditions presented in entry 4 of Table 3 were defined as the standard conditions for further study.

Table 3 Optimization of the cycloisomerization reaction of 1f^a

Entry	Cat. (equiv.)	Time (h)	NMR yield^b (%)		Recovery of 1f^b (%)
			2f	3f
a The reactions were conducted on a 0.1 mmol scale in toluene (1 mL). b Determined using ^1H NMR analysis with CH2Br2 as the internal standard and the isolated yield is shown in the brackets. c The reaction was conducted at 60 °C. d The reaction was conducted on a 0.5 mmol scale. e The reaction was conducted on a 0.2 mmol scale.
1^c	TfOH (0.05)	11	9	2	87
2	Cu(OTf)2 (0.1)	11	10	2	88
3	AgOTf (0.1)	11	42	2	56
4^d	AuCl (0.05)	5	98 (90)	0	0
5^e	AuCl3 (0.05)	9	96	0	0
6	FeCl3 (0.1)	24	43	0	55
7	SnCl4 (1.0)	14	11	5	54
8	BF3·2H2O (3.0)	48	9	3	81
9	BF3·Et2O (3.0)	27	0	5	84
10	CuI (0.1)	19	0	0	88
11	TiCl4 (1.0)	22	Complicated mixture of products		0

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With the optimized conditions in hand we then studied the generality of the AuCl-catalyzed cycloisomerization reaction using tri-substituted allenyl perfluorobutyl ketones 1f–1l. The electronic effects of the substituent groups of the aryl group have almost no effect on the conversion (entries 4 and 5, Table 4). A heterocyclic 2-thienyl group and an acyclic alkyl group could be compatible as well (entries 6 and 7, Table 4).

Table 4 AuCl-catalyzed cycloisomerization of tri-substituted allenyl perfluorobutyl ketones 1^a

Entry	R	R^3	Time (h)	Yield of 2^b (%)
a Conditions: substrate (0.5 mmol), AuCl (5 mol%) and toluene (5 mL), at 100 °C. b Isolated yield. c The reaction was carried out on a 0.2 mmol scale in toluene (2 mL). d AuCl (10 mol%) was used. e Purity is 94.0%.
1	Ph	n-Pr (1f)	5	90 (2f)
2	Ph	Et (1g)	3	93 (2g)
3	Ph	Me (1h)	5	92 (2h)
4^c	p-MeC6H4	n-Pr (1i)	12	98 (2i)
5	p-FC6H4	n-Pr (1j)	3	90 (2j)
6^c^,^d	2-Thienyl	n-Pr (1k)	16	88 (2k)
7^c	n-C7H15	n-Pr (1l)	11	56^e (2l)

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As shown in entry 3 of Table 1, besides the normal cycloisomerization product furan 2a, a corresponding hydrolytic defluorination product ketone 3a¹⁴ could be obtained in 59% NMR yield as well. Thus, we attempted to form 3a from 2a in the presence of acid and water. To our delight, TfOH performed the best among the various acids used. Moreover, 99% of 3a could be generated with 1.5 equiv. of water (entry 2, Table 5).

Table 5 Optimization of the hydrolytic defluorination reaction of 2a^a

Entry	Cat.	H2O (equiv.)	NMR yield of 3a^b (%)	Recovery of 2a^b (%)
a The reactions were conducted on a 0.1 mmol scale in toluene (1 mL) under a N2 atmosphere. b Determined using ^1H NMR analysis with CH2Br2 as the internal standard. c The reaction was conducted on a 0.2 mmol scale in toluene (2 mL) under a N2 atmosphere. d The dosage of the catalyst was 10 mol%. e The dosage of the catalyst was 1.0 equiv.
1	TfOH	1.0	97	0
2^c	TfOH	1.5	99	0
3	TfOH	2.0	98	0
4	TfOH	5.0	94	0
5^d	TFA	1.5	0	94
6^e	TsOH·H2O	1.5	39	61

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Using the optimized reaction conditions presented in entry 2 of Table 5, we studied the scope of this hydrolytic defluorination reaction. When R¹ = Ph, R² = acyclic alkyl, and R_f = n-C₃F₇ or n-C₅F₁₁, the ketone products 3a–3c could all be obtained with excellent yields (entries 1–3, Table 6). R¹ and R² could both be alkyl groups: 3e was produced with a 71% isolated yield (entry 4, Table 6).

Table 6 Hydrolytic defluorination reactions of perfluoroalkyl furans 2^a

Entry	R^1	R^2	Rf	Time (h)	Yield of 3^b (%)
a Conditions: substrate (0.2 mmol), TfOH (5 mol%) and H2O (1.5 equiv.), in toluene (2 mL), at 100 °C. b Isolated yield.
1	Ph	n-Pr	n-C3F7 (2a)	12	97 (3a)
2	Ph	n-Pr	n-C5F11 (2b)	10	95 (3b)
3	Ph	Me	n-C3F7 (2c)	10	95 (3c)
4	Me	Et	n-C3F7 (2e)	3	71 (3e)

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Furthermore, when tri-substituted furan 2f was treated with TfOH (5 mol%) and H₂O (1.5 equiv.), the corresponding ketone 3f could also be formed with a good yield (eqn (1)).

Considering that 2f could be efficiently prepared from 1f with AuCl as the catalyst (entry 4, Table 3) and that the acid-catalyzed reaction of 2f would form 3f (eqn (1)), a two-step process was thus established (Table 7): the addition of 1.5 equiv. of H₂O to the reaction vessel afforded 3f exclusively in the highest yield (entry 2, Table 7).

Table 7 Optimization of the dosage of water in the two-step one-pot process for the tandem cycloisomerization/hydrolytic defluorination reaction of 1f^a

Entry	H2O (equiv.)	Time 1/time 2 (h)	NMR yield^b (%)
			2f	3f
a The reactions were conducted on a 0.1 mmol scale in toluene (1.0 mL). b Determined using ^1H NMR analysis with CH2Br2 as the internal standard. c A complicated mixture of products was obtained.
1	1	3.5/24	4	63
2	1.5	12/8	0	84
3	2	3.5/3	0	79
4	3	12/8	6	61
5	5	4/5	7	75
6^c	10	4/5	Trace	50

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With a reliable procedure in hand, we next turned our attention to studying the scope of the two-step one-pot transformation: with Ar = Ph, the tandem reactions could all proceed efficiently, no matter whether R¹ was a propyl, an ethyl, or a methyl group (entries 1–4, Table 8); the substituent of the aryl group had almost no significant effect on the reaction (entries 5 and 6, Table 8); a 2-thienyl group may also be compatible, albeit with a lower yield (entry 7, Table 8). To demonstrate the practicality of the procedure, a gram scale (2.50 mmol) reaction of 1f was also conducted, providing the product in good yield (78%) as shown in entry 2, Table 8.

Table 8 The two-step one-pot tandem cycloisomerization/hydrolytic defluorination reaction of 3-aryl-substituted allenyl perfluorobutyl ketones 1^a

a Conditions: substrate (0.5 mmol), AuCl (5 mol%) and toluene (5 mL), at 100 °C for time 1, then TfOH (5 mol%) and H2O (1.5 equiv.) were added. b Isolated yield. c The reaction was conducted on a 1.0 mmol scale. d The reaction was carried out on a gram scale. e The reaction was carried out on a 0.2 mmol scale.
Entry	Ar	R^1	Time 1/time 2 (h)	Yield of 3^b (%)
1^c	Ph	n-Pr (1f)	3/3	76 (3f)
2^d	Ph	n-Pr (1f)	3/3.5	78 (3f)
3	Ph	Et (1g)	13/10	86 (3g)
4^c	Ph	Me (1h)	3.5/13	86 (3h)
5	p-MeC6H4	n-Pr (1i)	11/5	88 (3i)
6	p-FC6H4	n-Pr (1j)	12/10	82 (3j)
7^e	2-Thienyl	n-Pr (1k)	13/10	43 (3k)

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Conclusions

In conclusion, we have developed an efficient controlled cycloisomerization of allenyl perfluoroalkyl ketones under the catalysis of AuCl (for 3-monoaryl allenones) or TfOH (for fully-substituted allenones) to afford 2-perfluoroalkyl furans. In the presence of water and a catalytic amount of TfOH, these furans could be efficiently transformed into corresponding furan-2-yl perfluoroalkyl ketones. Further studies in this area are still ongoing in our laboratory.

Experimental section

General

The perfluoroalkyl allenones were prepared according to the literature procedures.¹³ Toluene was distilled from Na wire/benzophenone. TfOH (Alfa) was stored in a glovebox, and transferred with a microsyringe. The other commercially available chemicals were purchased and used without additional purification. The reactions were performed under an atmosphere of nitrogen using standard Schlenk tubes unless otherwise stated. Petroleum ether with a boiling point range from 30 to 60 °C was used. Flash-column chromatography was carried out on silica gel H (10–40 μm). ¹H NMR spectra (300 MHz) were recorded using TMS as an internal standard (δ 0 ppm). ¹³C NMR spectra (75 MHz) were recorded using CDCl₃ as an internal standard (δ 77.00 ppm). ¹⁹F NMR spectra (282 MHz) were recorded using CFCl₃ as an internal standard (δ 0 ppm). IR spectra were recorded with a Perkin-Elmer 983G instrument. Mass spectrometry was performed with an HP 5989A system. High-resolution mass spectrometry was conducted with a Finnigan MAT 8430 or Bruker APEXIII instrument. The structures of 2d, 2e, 2g, 2k, and 2l were established through NOE studies.

TfOH-catalyzed cycloisomerization reactions of fully-substituted allenyl perfluoroalkyl ketones 1a–1e

Synthesis of 4,5-diphenyl-2-(n-perfluorobutyl)-3-(n-propyl)furan (2a).
Typical procedure I: to a dried Schlenk tube, 1,1-diphenylhexa-1,2-dien-3-yl perfluorobutyl ketone 1a (0.0961 g, 0.20 mmol)/rinsed with toluene (2 mL) and TfOH (0.9 μL, d = 1.695 g mL⁻¹, 0.0015 g, 0.01 mmol) were added at room temperature under a nitrogen atmosphere. The resulting reaction mixture was placed in a pre-heated oil bath at 60 °C and stirred for 10 h, and monitored using TLC. After being cooled to room temperature, the crude reaction mixture was transferred to a round bottom flask. After removing the solvent via rotary evaporation, column chromatography on silica gel (chromatography eluent: petroleum ether) afforded 2a (0.0924 g, 96%) as a waxy solid: ¹H NMR (300 MHz, CDCl₃) δ 7.49–7.33 (m, 5 H, ArH), 7.33–7.26 (m, 2 H, ArH), 7.25–7.18 (m, 3 H, ArH), 2.42 (t, J = 8.0 Hz, 2 H, CH₂), 1.42–1.28 (m, 2 H, CH₂), 0.78 (t, J = 7.4 Hz, 3 H, CH₃); ¹³C NMR (75 MHz, CDCl₃) δ 151.2, 134.4 (t, J = 31.7 Hz), 132.54, 132.49, 130.1, 129.7, 129.0, 128.4, 128.3, 128.1, 126.0, 124.4, 25.0, 23.6, 13.9; ¹⁹F NMR (282 MHz, CDCl₃) δ −81.4 (t, J = 9.7 Hz, 3 F), −110.5 to −110.8 (m, 2 F), −123.6 to −123.8 (m, 2 F), −126.5 to −126.7 (m, 2 F); IR (neat) ν (cm⁻¹) 3078, 3029, 2981, 2951, 2917, 1642, 1610, 1494, 1448, 1432, 1405, 1315, 1294, 1268, 1213, 1157, 1132, 1095, 1057; MS (70 eV, EI) m/z (%) 480 (M⁺, 50.59), 311 (100); HRMS calcd for C₂₃H₁₇F₉O (M⁺): 480.1136, found: 480.1124.

The following compounds 2b–2e were prepared following typical procedure I.

Synthesis of 4,5-diphenyl-2-(n-perfluorohexyl)-3-(n-propyl)furan (2b).
The reaction of 1,1-diphenylhexa-1,2-dien-3-yl n-perfluorohexyl ketone 1b (0.1735 g, 0.30 mmol) with TfOH (99%, 0.54 μL, d = 1.695 g mL⁻¹, 0.0009 g, 0.006 mmol) in toluene (3 mL) at 60 °C for 2 h afforded 2b (0.1574 g, 91%) (chromatography eluent: petroleum ether) as a solid: m.p. 53.4–55.2 °C (recrystallization solvent: n-hexane/ethyl acetate); ¹H NMR (300 MHz, CDCl₃) δ 7.53–7.37 (m, 5 H, ArH), 7.37–7.30 (m, 2 H, ArH), 7.29–7.10 (m, 3 H, ArH), 2.45 (tt, J₁ = 7.8 Hz, J₂ = 1.8 Hz, 2 H, CH₂), 1.46–1.30 (m, 2 H, CH₂), 0.81 (t, J = 7.4 Hz, 3 H, CH₃); ¹³C NMR (75 MHz, CDCl₃) δ 151.2, 134.5 (t, J = 32.2 Hz), 132.6, 132.5, 130.1, 129.7, 129.0, 128.4, 128.3, 128.1, 126.0, 124.4, 25.1, 23.6, 13.8; ¹⁹F NMR (282 MHz, CDCl₃) δ −81.3 (t, J = 9.7 Hz, 3 F), −110.5 (t, J = 12.3 Hz, 2 F), −122.2 to −122.6 (m, 2 F), −122.6 to −122.9 (m, 2 F), −123.0 to −123.5 (m, 2 F), −126.5 to −126.8 (m, 2 F); IR (KBr) ν (cm⁻¹) 3064, 3033, 2967, 2937, 2877, 1623, 1605, 1583, 1561, 1505, 1482, 1467, 1447, 1402, 1382, 1362, 1333, 1239, 1095, 1073, 1057, 1029; MS (70 eV, EI) m/z (%) 581 (31.20), 580 (M⁺, 100); Elemental analysis calcd for C₂₅H₁₇F₁₃O: C, 51.74; H, 2.95; found: C, 51.74; H, 3.12.

Synthesis of 4,5-diphenyl-3-methyl-2-(n-perfluorobutyl)furan (2c).
The reaction of 1,1-diphenylbuta-1,2-dien-3-yl n-perfluorobutyl ketone 1c (0.2265 g, 0.50 mmol) with TfOH (99%, 2.3 μL, d = 1.695 g mL⁻¹, 0.0039 g, 0.026 mmol) in toluene (5 mL) at 60 °C for 2.5 h afforded 2c (0.2020 g, 89%) (chromatography eluent: petroleum ether/ethyl acetate = 100/1) as a solid: m.p. 52.3–53.2 °C (recrystallization solvent: n-hexane/ethyl acetate); ¹H NMR (300 MHz, CDCl₃) δ 7.58–7.02 (m, 10 H, ArH), 2.03 (s, 3 H, CH₃); ¹³C NMR (75 MHz, CDCl₃) δ 151.0, 134.5 (t, J = 31.8 Hz), 132.1, 130.1, 129.7, 129.0, 128.4, 128.3, 128.0, 127.6, 126.1, 124.7, 8.5; ¹⁹F NMR (282 MHz, CDCl₃) δ −81.5 (t, J = 9.7 Hz, 3 F), −111.2 to −111.6 (m, 2 F), −123.9 to −124.4 (m, 2 F), −126.5 to −126.9 (m, 2 F); IR (KBr) ν (cm⁻¹) 3064, 3033, 2936, 1629, 1605, 1584, 1563, 1505, 1481, 1447, 1402, 1351, 1335, 1235, 1203, 1135, 1110, 1081, 1030, 1006; MS (70 eV, EI) m/z (%) 452 (M⁺, 48.75), 283 (100); Elemental analysis calcd for C₂₁H₁₃F₉O: C, 55.76; H, 2.90; found: C, 55.96; H, 3.19.

Synthesis of 3,5-diethyl-4-phenyl-2-(n-perfluorobutyl)furan (2d).
The reaction of 3-phenylhepta-3,4-dien-5-yl n-perfluorobutyl ketone 1d (0.2090 g, 0.50 mmol) with TfOH (99%, 2.3 μL, d = 1.695 g mL⁻¹, 0.0039 g, 0.026 mmol) in toluene (5 mL) at 60 °C for 4 h afforded 2d (0.1569 g, 75%) (chromatography eluent: petroleum ether) as a liquid: ¹H NMR (300 MHz, CDCl₃) δ 7.50–7.31 (m, 3 H, ArH), 7.31–7.20 (m, 2 H, ArH), 2.59 (q, J = 7.5 Hz, 2 H, CH₂), 2.50 (q, J = 7.4 Hz, 2 H, CH₂), 1.18 (t, J = 7.5 Hz, 3 H, CH₃), 0.93 (t, J = 7.5 Hz, 3 H, CH₃); ¹³C NMR (75 MHz, CDCl₃) δ 156.6, 133.1 (t, J = 32.0 Hz), 132.3, 132.2, 129.7, 128.6, 127.5, 123.2, 19.9, 16.5, 15.0, 12.6; ¹⁹F NMR (282 MHz, CDCl₃) δ −81.5 (t, J = 10.4 Hz, 3 F), −111.0 (t, J = 10.6 Hz, 2 F), −123.9 to −124.3 (m, 2 F), −126.6 to −127.0 (m, 2 F); IR (neat) ν (cm⁻¹) 3035, 2979, 2941, 2883, 1630, 1576, 1496, 1466, 1408, 1378, 1353, 1324, 1276, 1236, 1135, 1091, 1062, 1004; MS (70 eV, EI) m/z (%) 418 (M⁺, 66.28), 249 (100); HRMS calcd for C₁₈H₁₅F₉O (M⁺): 418.0979, found: 418.0977.

Synthesis of 3-ethyl-5-methyl-2-(n-perfluorobutyl)-4-phenylfuran (2e) and (3-ethyl-5-methyl-4-phenylfuran-2-yl) n-perfluoropropyl ketone (3e).
The reaction of 2-phenylhexa-2,3-dien-4-yl perfluorobutyl ketone 1e (0.2025 g, 0.50 mmol) with TfOH (99%, 2.3 μL, d = 1.695 g mL⁻¹, 0.0039 g, 0.026 mmol) in toluene (5 mL) at 60 °C for 1.5 h afforded 2e (0.1389 g, 69%) and 3e (0.0567 g, 30%) (chromatography eluent: petroleum ether, then petroleum ether/ethyl acetate = 200/1).

2e (liquid, less polar): ¹H NMR (300 MHz, CDCl₃) δ 7.49–7.32 (m, 3 H, ArH), 7.29–7.20 (m, 2 H, ArH), 2.51 (q, J = 7.5 Hz, 2 H, CH₂), 2.26 (s, 3 H, CH₃), 0.93 (t, J = 7.5 Hz, 3 H, CH₃); ¹³C NMR (75 MHz, CDCl₃) δ 151.7, 133.2 (t, J = 31.8 Hz), 132.4, 132.2, 129.6, 128.6, 127.5, 123.9, 16.5, 15.0, 12.1; ¹⁹F NMR (282 MHz, CDCl₃) δ −81.5 (t, J = 9.7 Hz, 3 F), −110.9 (t, J = 10.7 Hz, 2 F), −123.7 to −124.1 (m, 2 F), −126.6 to −126.9 (m, 2 F); IR (neat) ν (cm⁻¹) 3084, 3061, 3036, 2978, 2941, 2883, 1633, 1578, 1497, 1467, 1445, 1411, 1354, 1279, 1235, 1135, 1091, 1055, 1012; MS (70 eV, EI) m/z (%) 404 (M⁺, 52.43), 235 (100); HRMS calcd for C₁₇H₁₃F₉O (M⁺): 404.0823, found: 404.0815.

3e (liquid, more polar): ¹H NMR (300 MHz, CDCl₃) δ 7.51–7.33 (m, 3 H, ArH), 7.29–7.21 (m, 2 H, ArH), 2.78 (q, J = 7.5 Hz, 2 H, CH₂), 2.38 (s, 3 H, CH₃), 1.10 (t, J = 7.4 Hz, 3 H, CH₃); ¹⁹F NMR (282 MHz, CDCl₃) δ −81.0 (t, J = 9.0 Hz, 3 F), −117.6 to −118.1 (m, 2 F), −126.2 to −126.6 (m, 2 F).

AuCl-catalyzed cycloisomerization of 3-monoaryl-substituted allenyl perfluorobutyl ketones 1f–1l

Synthesis of 2-(n-perfluorobutyl)-5-phenyl-3-(n-propyl)furan (2f).
Typical procedure II: to a dried Schlenk tube, anhydrous AuCl (97%, 0.0062 g, 0.026 mmol), 1-phenylhexa-1,2-dien-3-yl n-perfluorobutyl ketone 1f (0.2022 g, 0.50 mmol), and anhydrous toluene (5 mL) were added at room temperature under a N₂ atmosphere. The resulting mixture was then placed in a pre-heated oil bath at 100 °C and stirred for 5 h, and monitored using TLC. After being cooled to room temperature, the crude reaction mixture was filtered through a short column of silica gel and eluted with 60 mL of Et₂O. After removing the solvent via rotary evaporation, column chromatography on silica gel (chromatography eluent: petroleum ether) afforded 2f (0.1818 g, 90%) as an oil: ¹H NMR (300 MHz, CDCl₃) δ 7.73–7.63 (m, 2 H, ArH), 7.46–7.27 (m, 3 H, ArH), 6.62 (s, 1 H, =CH), 2.56 (tt, J₁ = 7.5 Hz, J₂ = 1.8 Hz, 2 H, CH₂), 1.74–1.56 (m, 2 H, CH₂), 0.98 (t, J = 7.4 Hz, 3 H, CH₃); ¹³C NMR (75 MHz, CDCl₃) δ 155.9, 134.5 (t, J = 32.3 Hz), 132.6, 129.4, 128.8, 128.7, 124.4, 107.9, 26.3, 23.2, 13.7; ¹⁹F NMR (282 MHz, CDCl₃) δ −81.5 (t, J = 10.0 Hz, 3 F), −110.7 (t, J = 10.6 Hz, 2 F), −123.9 to −124.3 (m, 2 F), −126.5 to −126.9 (m, 2 F); IR (neat) ν (cm⁻¹) 3066, 3038, 2965, 2933, 2876, 1948, 1877, 1802, 1750, 1621, 1605, 1584, 1551, 1487, 1451, 1397, 1350, 1313, 1235, 1135, 1095, 1057; MS (70 eV, EI) m/z (%) 404 (M⁺, 30.78), 235 (100); HRMS calcd for C₁₇H₁₃F₉O (M⁺): 404.0823, found: 404.0836.

The following compounds 2g–2l were prepared following typical procedure II.

Synthesis of 3-ethyl-2-(n-perfluorobutyl)-5-phenylfuran (2g).
The reaction of 1-phenylpenta-1,2-dien-3-yl n-perfluorobutyl ketone 1g (0.1951 g, 0.50 mmol) with AuCl (99%, 0.0056 g, 0.024 mmol) in toluene (5 mL) at 100 °C for 3 h afforded 2g (0.1808 g, 93%) (chromatography eluent: petroleum ether) as a liquid: ¹H NMR (300 MHz, CDCl₃) δ 7.73–7.61 (m, 2 H, ArH), 7.46–7.27 (m, 3 H, ArH), 6.64 (s, 1 H, =CH), 2.71–2.50 (m, 2 H, CH₂), 1.23 (t, J = 7.7 Hz, 3 H, CH₃); ¹³C NMR (75 MHz, CDCl₃) δ 156.0, 134.2, 134.0 (t, J = 31.7 Hz), 129.5, 128.8, 128.7, 124.4, 107.6, 17.8, 14.5; ¹⁹F NMR (282 MHz, CDCl₃) δ −81.5 (t, J = 9.9 Hz, 3 F), −111.1 (t, J = 10.6 Hz, 2 F), −124.1 to −124.4 (m, 2 F), −126.6 to −127.1 (m, 2 F); IR (neat) ν (cm⁻¹) 3067, 3039, 2980, 2942, 2884, 1621, 1605, 1585, 1551, 1487, 1466, 1452, 1398, 1380, 1351, 1282, 1235, 1135, 1091, 1003; MS (70 eV, EI) m/z (%) 390 (M⁺, 37.26), 221 (100); HRMS calcd for C₁₆H₁₁F₉O (M⁺): 390.0666, found: 390.0664.

Synthesis of 3-methyl-2-(n-perfluorobutyl)-5-phenylfuran (2h).
The reaction of 1-phenylbuta-1,2-dien-3-yl n-perfluorobutyl ketone 1h (0.1891 g, 0.50 mmol) with AuCl (97%, 0.0062 g, 0.026 mmol) in toluene (5 mL) at 100 °C for 5 h afforded 2h (0.1749 g, 92%) (chromatography eluent: petroleum ether) as a liquid: ¹H NMR (300 MHz, CDCl₃) δ 7.74–7.60 (m, 2 H, ArH), 7.46–7.26 (m, 3 H, ArH), 6.56 (s, 1 H, =CH), 2.21 (s, 3 H, CH₃); ¹³C NMR (75 MHz, CDCl₃) δ 155.8, 134.8 (t, J = 31.9 Hz), 129.4, 128.8, 128.7, 127.6, 124.4, 109.4, 10.0; ¹⁹F NMR (282 MHz, CDCl₃) δ −81.5 (t, J = 9.4 Hz, 3 F), −111.2 to −111.6 (m, 2 F), −124.2 to −124.6 (m, 2 F), −126.6 to −127.1 (m, 2 F); IR (neat) ν (cm⁻¹) 3067, 3039, 2936, 1949, 1878, 1802, 1751, 1626, 1606, 1585, 1551, 1488, 1451, 1401, 1384, 1350, 1235, 1135, 1087, 1056, 1027, 1005; MS (70 eV, EI) m/z (%) 376 (M⁺, 47.65), 207 (100); HRMS calcd for C₁₅H₉F₉O (M⁺): 376.0510, found: 376.0515.

Synthesis of 5-(4′-methylphenyl)-2-(n-perfluorobutyl)-3-(n-propyl)furan (2i).
The reaction of 1-(4′-methylphenyl)hexa-1,2-dien-3-yl perfluorobutyl ketone 1i (0.0832 g, 0.20 mmol) with AuCl (97%, 0.0023 g, 0.010 mmol) in toluene (2 mL) at 100 °C for 12 h afforded 2i (0.0812 g, 98%) (chromatography eluent: petroleum ether) as a liquid: ¹H NMR (300 MHz, CDCl₃) δ 7.56 (d, J = 8.1 Hz, 2 H, ArH), 7.20 (d, J = 8.1 Hz, 2 H, ArH), 6.56 (s, 1 H, =CH), 2.55 (t, J = 7.7 Hz, 2 H, CH₂), 2.37 (s, 3 H, CH₃), 1.74–1.54 (m, 2 H, CH₂), 0.97 (t, J = 7.4 Hz, 3 H, CH₃); ¹³C NMR (75 MHz, CDCl₃) δ 156.1, 138.7, 134.0 (t, J = 32.3 Hz), 132.6, 129.5, 126.7, 124.3, 107.2, 26.3, 23.2, 21.3, 13.7; ¹⁹F NMR (282 MHz, CDCl₃) δ −81.5 (t, J = 9.4 Hz, 3 F), −110.8 (t, J = 11.6 Hz, 2 F), −124.0 to −124.3 (m, 2 F), −126.6 to −126.9 (m, 2 F); IR (neat) ν (cm⁻¹) 3029, 2967, 2935, 2876, 1906, 1621, 1581, 1557, 1498, 1468, 1417, 1393, 1350, 1315, 1235, 1135, 1094, 1053; MS (70 eV, EI) m/z (%) 418 (M⁺, 20.78), 249 (100); HRMS calcd for C₁₈H₁₅F₉O (M⁺): 418.0979, found: 418.0978.

Synthesis of 5-(4′-fluorophenyl)-2-(n-perfluorobutyl)-3-(n-propyl)furan (2j).
The reaction of 1-(4′-fluorophenyl)hexa-1,2-dien-3-yl n-perfluorobutyl ketone 1j (0.2120 g, 0.50 mmol) with AuCl (97%, 0.0061 g, 0.026 mmol) in toluene (5 mL) at 100 °C for 3 h afforded 2j (0.1909 g, 90%) (chromatography eluent: petroleum ether) as a liquid: ¹H NMR (300 MHz, CDCl₃) δ 7.63 (dd, J₁ = 8.4 Hz, J₂ = 5.4 Hz, 2 H, ArH), 7.08 (t, J = 8.7 Hz, 2 H, ArH), 6.54 (s, 1 H, =CH), 2.55 (t, J = 7.5 Hz, 2 H, CH₂), 1.72–1.56 (m, 2 H, CH₂), 0.98 (t, J = 7.4 Hz, 3 H, CH₃); ¹³C NMR (75 MHz, CDCl₃) δ 163.0 (d, J = 247.4 Hz), 155.1, 134.6 (t, J = 31.6 Hz), 132.8, 126.3 (d, J = 8.1 Hz), 125.9 (d, J = 2.3 Hz), 115.9 (d, J = 21.9 Hz), 107.6, 26.3, 23.2, 13.6; ¹⁹F NMR (282 MHz, CDCl₃) δ −81.4 to −81.6 (m, 3 F), −110.6 to −111.0 (m, 2 F), −112.4 to −112.7 (m, 1 F), −123.9 to −124.3 (m, 2 F), −126.5 to −126.9 (m, 2 F); IR (neat) ν (cm⁻¹) 3052, 2969, 2937, 2878, 1891, 1621, 1607, 1559, 1496, 1469, 1421, 1392, 1351, 1235, 1135, 1097, 1054, 1014; MS (70 eV, EI) m/z (%) 422 (M⁺, 65.02), 253 (100); HRMS calcd for C₁₇H₁₂F₁₀O (M⁺): 422.0728, found: 422.0730.

Synthesis of 2-(n-perfluorobutyl)-3-(n-propyl)-5-(2-thienyl)furan (2k).
The reaction of 1-(2-thienyl)hexa-1,2-dien-3-yl n-perfluorobutyl ketone 1k (0.0828 g, 0.20 mmol) with AuCl (97%, 0.0049 g, 0.020 mmol) in toluene (2 mL) at 100 °C for 16 h afforded 2k (0.0727 g, 88%) (chromatography eluent: petroleum ether) as a liquid: ¹H NMR (300 MHz, CDCl₃) δ 7.38–7.26 (m, 2 H, ArH), 7.05 (dd, J₁ = 4.8 Hz, J₂ = 3.9 Hz, 1 H, ArH), 6.46 (s, 1 H, =CH), 2.53 (t, J = 7.5 Hz, 2 H, CH₂), 1.71–1.55 (m, 2 H, CH₂), 0.97 (t, J = 7.4 Hz, 3 H, CH₃); ¹³C NMR (75 MHz, CDCl₃) δ 151.5, 134.0 (t, J = 32.0 Hz), 132.7, 132.1, 127.8, 125.8, 124.5, 107.8, 26.3, 23.2, 13.6; ¹⁹F NMR (282 MHz, CDCl₃) δ −81.5 (t, J = 10.2 Hz, 3 F), −110.7 (t, J = 11.0 Hz, 2 F), −123.9 to −124.2 (m, 2 F), −126.6 to −126.9 (m, 2 F); IR (neat) ν (cm⁻¹) 3110, 3081, 2967, 2935, 2877, 1792, 1620, 1575, 1495, 1468, 1424, 1400, 1350, 1235, 1135, 1094, 1051, 1019; MS (70 eV, EI) m/z (%) 410 (M⁺, 32.52), 241 (100); HRMS calcd for C₁₅H₁₁F₉OS (M⁺): 410.0387, found: 410.0387.

Synthesis of 2-(n-perfluorobutyl)-5-heptyl-3-(n-propyl)furan (2l).
The reaction of trideca-4,5-dien-4-yl n-perfluorobutyl ketone 1l (0.0854 g, 0.20 mmol) with AuCl (99%, 0.0023 g, 0.01 mmol) in toluene (2 mL) at 100 °C for 11 h afforded 2l (0.0513 g, purity of 94.0% determined using CH₂Br₂ as the internal standard, 56% yield) (chromatography eluent: petroleum ether) as an oil: ¹H NMR (300 MHz, CDCl₃) δ 5.98 (s, 1 H, =CH), 2.59 (t, J = 7.7 Hz, 2 H, CH₂), 2.52–2.42 (m, 2 H, CH₂), 1.68–1.50 (m, 4 H, 2 × CH₂), 1.35–1.23 (m, 8 H, 4 × CH₂), 0.93 (t, J = 7.4 Hz, 3 H, CH₃), 0.88 (t, J = 6.8 Hz, 3 H, CH₃); ¹³C NMR (75 MHz, CDCl₃) δ 159.4, 133.2 (t, J = 31.9 Hz), 131.5, 108.5, 31.7, 29.0, 28.9, 27.9, 27.6, 26.3, 23.2, 22.6, 14.0, 13.7; ¹⁹F NMR (282 MHz, CDCl₃) δ −81.5 (t, J = 9.9 Hz, 3 F), −110.8 (t, J = 11.0 Hz, 2 F), −124.3 to −124.5 (m, 2 F), −126.8 to −127.0 (m, 2 F); IR (neat) ν (cm⁻¹) 2962, 2930, 2859, 1700, 1625, 1563, 1468, 1403, 1351, 1235, 1135, 1092, 1048; MS (70 eV, EI) m/z (%) 426 (M⁺, 26.24), 257 (100); HRMS calcd for C₁₈H₂₃F₉O (M⁺): 426.1605, found: 426.1602.

Hydrolytic defluorination reactions of fully substituted furans 2a–2e

Synthesis of (4,5-diphenyl-3-(n-propyl)furan-2-yl) n-perfluoropropyl ketone (3a).
Typical procedure III: to a dried Schlenk tube, furan 2a (0.0962 g, 0.20 mmol)/rinsed with toluene (2 mL), TfOH (0.9 μL, d = 1.695 g mL⁻¹, 0.0015 g, 0.01 mmol), and H₂O (5.4 μL, d = 1.0 g mL⁻¹, 0.0054 g, 0.3 mmol) were added at room temperature under a nitrogen atmosphere. The resulting reaction mixture was placed in a pre-heated oil bath at 100 °C and stirred for 12 h, and monitored using TLC. After being cooled to room temperature, the crude reaction mixture was transferred to a round bottom flask with Et₂O (3 × 10 mL). After removing the solvent via rotary evaporation, column chromatography on silica gel (chromatography eluent: petroleum ether/ethyl acetate = 100/1) afforded 3a¹⁴ (0.0889 g, 97%) as a solid: m.p. 54.4–56.5 °C (n-hexane/ethyl acetate); ¹H NMR (300 MHz, CDCl₃) δ 7.53–7.43 (m, 5 H, ArH), 7.35–7.24 (m, 5 H, ArH), 2.76–2.63 (m, 2 H, CH₂), 1.57–1.41 (m, 2 H, CH₂), 0.86 (t, J = 7.4 Hz, 3 H, CH₃); ¹³C NMR (75 MHz, CDCl₃) δ 170.5 (t, J = 25.8 Hz), 154.5, 145.9, 143.4, 131.4, 130.0, 129.7, 129.2, 128.9, 128.7, 128.5, 127.0, 126.8, 26.6, 22.6, 14.0; ¹⁹F NMR (282 MHz, CDCl₃) δ −80.9 (t, J = 9.6 Hz, 3 F), −117.7 to −117.9 (m, 2 F), −126.1 to −126.3 (m, 2 F).

The following compounds 3b–3e were prepared following typical procedure III.

Synthesis of (4,5-diphenyl-3-(n-propyl)furan-2-yl) n-perfluoropentyl ketone (3b).
The reaction of furan 2b (0.1162 g, 0.20 mmol) with TfOH (99%, 0.9 μL, d = 1.695 g mL⁻¹, 0.0015 g, 0.01 mmol), and H₂O (5.4 μL, d = 1.0 g mL⁻¹, 0.0054 g, 0.3 mmol) in toluene (2 mL) at 100 °C for 10 h afforded 3b¹⁴ (0.1059 g, 95%) (chromatography eluent: petroleum ether/ethyl acetate = 100/1) as an oil: ¹H NMR (300 MHz, CDCl₃) δ 7.53–7.42 (m, 5 H, ArH), 7.36–7.25 (m, 5 H, ArH), 2.76–2.62 (m, 2 H, CH₂), 1.57–1.41 (m, 2 H, CH₂), 0.86 (t, J = 7.5 Hz, 3 H, CH₃); ¹³C NMR (75 MHz, CDCl₃) δ 170.5 (t, J = 26.1 Hz), 154.5, 146.0, 143.4, 131.4, 130.0, 129.7, 129.2, 128.9, 128.7, 128.5, 127.0, 126.8, 26.6, 22.6, 14.0; ¹⁹F NMR (282 MHz, CDCl₃) δ −81.2 (tt, J₁ = 9.7 Hz, J₂ = 2.4 Hz, 3 F), −116.8 to −117.1 (m, 2 F), −121.7 to −122.1 (m, 2 F), −122.6 to −123.0 (m, 2 F), −126.4 to −126.8 (m, 2 F).

Synthesis of (4,5-diphenyl-3-methylfuran-2-yl) n-perfluoropropyl ketone (3c).
The reaction of furan 2c (0.0903 g, 0.20 mmol) with TfOH (99%, 0.9 μL, d = 1.695 g mL⁻¹, 0.0015 g, 0.01 mmol), and H₂O (5.4 μL, d = 1.0 g mL⁻¹, 0.0054 g, 0.3 mmol) in toluene (2 mL) at 100 °C for 10 h afforded 3c¹⁴ (0.0812 g, 95%) (chromatography eluent: petroleum ether/ethyl acetate = 100/1) as a solid: m.p. 55.3–56.7 °C (recrystallization solvent: n-hexane/ethyl acetate); ¹H NMR (300 MHz, CDCl₃) δ 7.55–7.44 (m, 5 H, ArH), 7.37–7.25 (m, 5 H, ArH), 2.33 (s, 3 H, CH₃); ¹³C NMR (75 MHz, CDCl₃) δ 170.9 (t, J = 26.0 Hz), 154.5, 143.6, 141.2, 131.2, 129.9, 129.8, 129.2, 128.9, 128.7, 128.5, 127.2, 126.9, 10.9; ¹⁹F NMR (282 MHz, CDCl₃) δ −80.9 (t, J = 9.0 Hz, 3 F), −117.8 to −118.1 (m, 2 F), −126.1 to −126.3 (m, 2 F).

Synthesis of (3-ethyl-5-methyl-4-phenylfuran-2-yl) n-perfluoropropyl ketone (3e).
The reaction of furan 2e (0.0809 g, 0.20 mmol) with TfOH (99%, 0.9 μL, d = 1.695 g mL⁻¹, 0.0015 g, 0.01 mmol), and H₂O (5.4 μL, d = 1.0 g mL⁻¹, 0.0015 g, 0.3 mmol) in toluene (2 mL) at 100 °C for 3 h afforded 3e¹⁴ (0.0543 g, 71%) (chromatography eluent: petroleum ether/ethyl acetate = 100/1) as an oil: ¹H NMR (300 MHz, CDCl₃) δ 7.51–7.37 (m, 3 H, ArH), 7.28–7.22 (m, 2 H, ArH), 2.78 (q, J = 7.5 Hz, 2 H, CH₂), 2.38 (s, 3 H, CH₃), 1.10 (t, J = 7.5 Hz, 3 H, CH₃); ¹³C NMR (75 MHz, CDCl₃) δ 170.1 (t, J = 26.0 Hz), 156.9, 146.2, 143.4, 130.8, 129.5, 128.8, 128.0, 127.1, 18.3, 13.5, 13.0; ¹⁹F NMR (282 MHz, CDCl₃) δ −81.0 (t, J = 8.9 Hz, 3 F), −117.8 to −117.9 (m, 2 F), −126.3 to −126.4 (m, 2 F).

Two-step one-pot tandem cycloisomerization/hydrolytic defluorination reactions of 3-monoaryl-substituted allenyl perfluorobutyl ketones 1f–1k

Synthesis of (5-phenyl-3-(n-propyl)furan-2-yl) n-perfluoropropyl ketone (3f).
Typical procedure IV: to a dried Schlenk tube, anhydrous AuCl (97%, 0.0121 g, 0.051 mmol), 1-phenylhexa-1,2-dien-3-yl n-perfluorobutyl ketone 1f (0.4035 g, 1.00 mmol), and anhydrous toluene (5 mL) were added at room temperature under a N₂ atmosphere. The resulting mixture was then placed in a pre-heated oil bath at 100 °C and stirred. After 3 h, the cycloisomerization reaction was over, as monitored using TLC. TfOH (99%, 4.5 μL, d = 1.695 g mL⁻¹, 0.0076 g, 0.050 mmol) and H₂O (27 μL, d = 1.0 g mL⁻¹, 0.0270 g, 1.50 mmol) were added to the above crude reaction mixture, and the resulting mixture was stirred at 100 °C for another 3 h, and monitored using TLC. After being cooled to room temperature, the reaction mixture was transferred to a round bottom flask. After removing the solvent via rotary evaporation, column chromatography on silica gel (chromatography eluent: petroleum ether, then petroleum ether/ethyl acetate = 500/1) afforded 3f¹⁴ (0.2910 g, 76%) as a liquid: ¹H NMR (300 MHz, CDCl₃) δ 7.84–7.71 (m, 2 H, ArH), 7.51–7.36 (m, 3 H, ArH), 6.82 (s, 1 H, =CH), 2.90 (t, J = 7.7 Hz, 2 H, CH₂), 1.80–1.59 (m, 2 H, CH₂), 1.01 (t, J = 7.5 Hz, 3 H, CH₃); ¹³C NMR (75 MHz, CDCl₃) δ 170.4 (t, J = 25.8 Hz), 159.1, 146.9, 143.9, 130.3, 129.1, 128.5, 125.4, 110.4, 28.4, 22.3, 13.8 (d, J = 2.1 Hz); ¹⁹F NMR (282 MHz, CDCl₃) δ −80.9 to −81.1 (m, 3 F), −118.0 (q, J = 8.8 Hz, 2 F), −126.3 (s, 2 F).

The following compounds 3f–3k were prepared following typical procedure IV.

Gram scale reaction for the synthesis of (5-phenyl-3-(n-propyl)furan-2-yl) n-perfluoropropyl ketone (3f).
The reaction of 1-phenylhexa-1,2-dien-3-yl n-perfluorobutyl ketone 1f (1.0102 g, 2.50 mmol) with AuCl (97%, 0.0301 g, 0.126 mmol) in toluene (12.5 mL) at 100 °C for 3 h afforded crude product 2f. Then TfOH (99%, 11.2 μL, d = 1.695 g mL⁻¹, 0.0188 g, 0.125 mmol) and H₂O (67.5 μL, d = 1.0 g mL⁻¹, 0.0675 g, 3.75 mmol) were added and reacted at 100 °C for another 3.5 h to afford 3f¹⁴ (0.7448 g, 78%) (chromatography eluent: petroleum ether/ethyl acetate = 500/1) as an oil: ¹H NMR (300 MHz, CDCl₃) δ 7.83–7.74 (m, 2 H, ArH), 7.54–7.39 (m, 3 H, ArH), 6.83 (s, 1 H, =CH), 2.91 (t, J = 7.7 Hz, 2 H, CH₂), 1.80–1.63 (m, 2 H, CH₂), 1.02 (t, J = 7.4 Hz, 3 H, CH₃); ¹³C NMR (75 MHz, CDCl₃) δ 170.4 (t, J = 25.9 Hz), 159.0, 146.8, 143.9, 130.2, 129.1, 128.5, 125.4, 110.3, 28.4, 22.3, 13.8; ¹⁹F NMR (282 MHz, CDCl₃) δ −81.0 (t, J = 8.9 Hz, 3 F), −118.0 (q, J = 9.5 Hz, 2 F), −126.3 (s, 2 F).

Synthesis of (3-ethyl-5-phenylfuran-2-yl) n-perfluoropropyl ketone (3g).
The reaction of 1-phenylpenta-1,2-dien-3-yl perfluorobutyl ketone 1g (0.1945 g, 0.50 mmol) with AuCl (97%, 0.0061 g, 0.026 mmol) in toluene (5 mL) at 100 °C for 13 h afforded crude product 2g. Then TfOH (99%, 2.3 μL, d = 1.695 g mL⁻¹, 0.0039 g, 0.026 mmol) and H₂O (13.5 μL, d = 1.0 g mL⁻¹, 0.0135 g, 0.75 mmol) were added and reacted at 100 °C for another 10 h to afford 3g¹⁴ (0.1581 g, 86%) (chromatography eluent: petroleum ether/ethyl acetate = 500/1) as a solid: m.p. 40.2–41.2 °C (recrystallization solvent: n-hexane/ethyl acetate); ¹H NMR (300 MHz, CDCl₃) δ 7.89–7.69 (m, 2 H, ArH), 7.59–7.33 (m, 3 H, ArH), 6.86 (s, 1 H, =CH), 2.96 (q, J = 7.4 Hz, 2 H, CH₂), 1.29 (t, J = 7.5 Hz, 3 H, CH₃); ¹³C NMR (75 MHz, CDCl₃) δ 170.3 (t, J = 26.3 Hz), 159.2, 148.3, 143.6, 130.3, 129.1, 128.5, 125.4, 109.8, 20.0, 13.1; ¹⁹F NMR (282 MHz, CDCl₃) δ −81.0 (t, J = 8.9 Hz, 3 F), −118.1 (q, J = 9.0 Hz, 2 F), −126.3 (s, 2 F).

Synthesis of (3-methyl-5-phenylfuran-2-yl) n-perfluoropropyl ketone (3h).
The reaction of 1-phenylbuta-1,2-dien-3-yl perfluorobutyl ketone 1h (0.3763 g, 1.00 mmol) with AuCl (97%, 0.0111 g, 0.046 mmol) in toluene (5 mL) at 100 °C for 3.5 h afforded crude product 2h. Then TfOH (99%, 4.5 μL, d = 1.695 g mL⁻¹, 0.0076 g, 0.050 mmol) and H₂O (27 μL, d = 1.0 g mL⁻¹, 0.0270 g, 1.50 mmol) were added and reacted at 100 °C for another 13 h to afford 3h¹⁴ (0.3039 g, 86%) (chromatography eluent: petroleum ether/ethyl acetate = 500/1) as an oil: ¹H NMR (300 MHz, CDCl₃) δ 7.82–7.70 (m, 2 H, ArH), 7.53–7.38 (m, 3 H, ArH), 6.80 (s, 1 H, =CH), 2.52 (s, 3 H, CH₃); ¹³C NMR (75 MHz, CDCl₃) δ 170.5 (t, J = 26.2 Hz), 158.9, 144.2, 141.9, 130.3, 129.1, 128.4, 125.4, 111.6, 12.6; ¹⁹F NMR (282 MHz, CDCl₃) δ −80.5 (t, J = 9.2 Hz, 3 F), −117.5 to −117.9 (m, 2 F), −125.8 to −126.0 (m, 2 F).

Synthesis of (5-(4′-methylphenyl)-3-(n-propyl)furan-2-yl) n-perfluoropropyl ketone (3i).
The reaction of 1-(4′-methylphenyl)hexa-1,2-dien-3-yl perfluorobutyl ketone 1i (0.2101 g, 0.50 mmol) with AuCl (97%, 0.0058 g, 0.024 mmol) in toluene (5 mL) at 100 °C for 11 h afforded crude product 2i. Then TfOH (99%, 2.3 μL, d = 1.695 g mL⁻¹, 0.0039 g, 0.026 mmol) and H₂O (13.5 μL, d = 1.00 g mL⁻¹, 0.0135 g, 0.75 mmol) were added and reacted at 100 °C for another 5 h to afford 3i¹⁴ (0.1756 g, 88%) (chromatography eluent: petroleum ether/ethyl acetate = 500/1) as a solid: m.p. 33.5–34.0 °C (recrystallization solvent: n-hexane/ethyl acetate); ¹H NMR (300 MHz, CDCl₃) δ 7.67 (d, J = 7.8 Hz, 2 H, ArH), 7.27 (d, J = 7.8 Hz, 2 H, ArH), 6.78 (s, 1 H, =CH), 2.90 (t, J = 7.5 Hz, 2 H, CH₂), 2.41 (s, 3 H, CH₃), 1.77–1.63 (m, 2 H, CH₂), 1.01 (t, J = 7.4 Hz, 3 H, CH₃); ¹³C NMR (75 MHz, CDCl₃) δ 170.1 (t, J = 25.9 Hz), 159.4, 147.0, 143.7, 140.7, 129.8, 125.8, 125.5, 109.8, 28.4, 22.3, 21.5, 13.8; ¹⁹F NMR (282 MHz, CDCl₃) δ −81.0 (t, J = 8.3 Hz, 3 F), −118.0 (q, J = 8.7 Hz, 2 F), −126.4 (s, 2 F).

Synthesis of (5-(4′-fluorophenyl)-3-(n-propyl)furan-2-yl) n-perfluoropropyl ketone (3j).
The reaction of 1-(4′-fluorophenyl)hexa-1,2-dien-3-yl perfluorobutyl ketone 1j (0.2112 g, 0.50 mmol) with AuCl (97%, 0.0061 g, 0.026 mmol) in toluene (5 mL) at 100 °C for 12 h afforded crude product 2j. Then TfOH (99%, 2.3 μL, d = 1.695 g mL⁻¹, 0.0039 g, 0.026 mmol) and H₂O (13.5 μL, d = 1.0 g mL⁻¹, 0.0135 g, 0.75 mmol) were added and reacted at 100 °C for another 10 h to afford 3j¹⁴ (0.1648 g, 82%) (chromatography eluent: petroleum ether/ethyl acetate = 500/1) as an oil: ¹H NMR (300 MHz, CDCl₃) δ 7.77 (dd, J₁ = 8.3 Hz, J₂ = 5.6 Hz, 2 H, ArH), 7.17 (t, J = 8.4 Hz, 2 H, ArH), 6.78 (s, 1 H, =CH), 2.90 (t, J = 7.7 Hz, 2 H, CH₂), 1.78–1.62 (m, 2 H, CH₂), 1.02 (t, J = 7.4 Hz, 3 H, CH₃); ¹³C NMR (75 MHz, CDCl₃) δ 170.3 (t, J = 25.7 Hz), 163.8 (d, J = 250.4 Hz), 158.0, 146.9, 143.9, 127.5 (d, J = 7.7 Hz), 124.9 (d, J = 3.8 Hz), 116.4 (t, J = 22.2 Hz), 110.1, 28.4, 22.3, 13.8; ¹⁹F NMR (282 MHz, CDCl₃) δ 81.0 (t, J = 8.9 Hz, 3 F), −109.3 to −109.6 (m, 1 F), −118.0 (q, J = 8.9 Hz, 2 F), −126.4 (s, 2 F).

Synthesis of (3-(n-propyl)-5-(2′-thienyl)furan-2-yl) n-perfluoropropyl ketone (3k).
The reaction of 1-(2′-thienyl)hexa-1,2-dien-3-yl perfluorobutyl ketone 1k (0.0812 g, 0.20 mmol) with AuCl (97%, 0.0025 g, 0.010 mmol) in toluene (2 mL) at 100 °C for 13 h afforded crude product 2k. Then TfOH (99%, 0.9 μL, d = 1.695 g mL⁻¹, 0.0015 g, 0.010 mmol) and H₂O (5.4 μL, d = 1.0 g mL⁻¹, 0.0054 g, 0.30 mmol) were added and reacted at 100 °C for another 10 h to afford 3k¹⁴ (0.0331 g, 43%) (chromatography eluent: petroleum ether/ethyl acetate = 500/1) as an oil: ¹H NMR (300 MHz, CDCl₃) δ 7.52 (d, J = 3.6 Hz, 1 H, ArH), 7.45 (d, J = 4.8 Hz, 1 H, ArH), 7.13 (d, J = 4.4 Hz, 1 H, ArH), 6.67 (s, 1 H, =CH), 2.89 (t, J = 7.5 Hz, 2 H, CH₂), 1.79–1.60 (m, 2 H, CH₂), 1.01 (t, J = 7.4 Hz, 3 H, CH₃); ¹³C NMR (75 MHz, CDCl₃) δ 170.0 (t, J = 26.4 Hz), 154.4, 147.0, 143.3, 131.4, 128.38, 128.36, 127.0, 110.0, 28.4, 22.2, 13.8; ¹⁹F NMR (282 MHz, CDCl₃) δ −81.0 (t, J = 9.0 Hz, 3 F), −118.0 (q, J = 8.8 Hz, 2 F), −126.3 to −126.4 (m, 2 F).

Acknowledgements

Financial support from the National Natural Science Foundation of China (21572202) is greatly appreciated. Shengming Ma is a Qiu Shi Adjunct Professor at Zhejiang University. The results presented in entry 2 of Table 2 (WWT), entry 5 of Table 4 and entry 1 of Table 8 (ZJS) have been kindly reproduced by Mr Wangteng Wu and Dr Jiasheng Zhang.

Notes and references

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Footnote

† Electronic supplementary information (ESI) available: Copies of ¹H NMR, ¹³C NMR, ¹⁹F NMR and NOE spectra of all the compounds prepared. See DOI: 10.1039/c6qo00001k

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