Study on the selectivity in the electrophilic monofluorination of 2,3-allenoates with Selectfluor™: an efficient synthesis of 4-fluoro-2(5H)-furanones and 3-fluoro-4-oxo-2(E)-alkenoates

Abstract

Different from the reaction of 2,3-allenoic acids with Selectfluor™, 4-fluoro-2(5H)-furanones and (E)-3-fluoro-4-oxo-2-alkenoates were highly selectively generated from 2,4-disubstituted 2,3-allenoates with Selectfluor™ under different conditions in moderate yields. The reaction of 2,4,4-trisubstituted 2,3-allenoates afforded the corresponding 4-fluoro-2(5H)-furanones highly selectively with up to 95% yield under different conditions. The scope of the substrates has been carefully explored. Due to the more readily availability of 2,3-allenoates as compared to 2,3-allenoic acids, new 4-fluoro-2(5H)-furanones were prepared. Based on the isolation and characterization of the minor fluorohydroxylation product E-5m, a mechanism has been proposed.

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Introduction

Many fluorinated organic compounds have been identified as biologically active molecules,¹ probably due to the fact that the fluorine most closely resembles hydrogen in size among the atoms but is much more electronegative than oxygen.² Monofluorination has been usually conducted using the common but very dangerous and environmentally unfriendly fluorine gas. Considering this problem, chemists have developed a series of highly efficient and easily controlled electrophilic fluorination reagents such as DAST,³ CF₃OF,⁴ XeF₂,⁵N-fluoropyridinium triflate,⁶ NFSI,⁷ Selectfluor™,^8,9etc. Among these reagents, Selectfluor™ has been proven to be a highly efficient fluorination reagent, and thus, has been widely used in organic synthesis.

In 2008, we reported that 4-fluoro-2(5H)-furanones could be synthesized conveniently by the cyclization of 2,3-allenoic acid in the presence of Selectfluor™.^8a Recently, this type of fluorocyclization reaction using 4,5-allenoic acid and Selectfluor™ has also been reported by Zhao, Zhu, and their co-workers.⁹ Since the acids are usually prepared from the hydrolysis of esters,¹⁰ it is desirable to prepare lactones directly from 2,3-allenoates.^11a,b In this paper, we wish to report our recent study on the reaction of 2,3-allenoates with Selectfluor™, which affords 4- fluoro-2(5H)-furanones and 3-fluoro-4-oxo-2(E)-alkenoates under different reaction conditions, respectively.¹²

Results and discussion

The initial experiment was carried out by using ethyl 2-methyl-4-phenyl-2,3-butadienoate 1a and 1.2 equiv of Selectfluor™2 in MeCN at 80 °C (Table 1, entry 1). Interestingly, 4-fluoro-3-methyl-5-phenyl-2(5H)-furanone 4a was formed together with an unknown product. However, from ¹H NMR and ¹³C NMR, IR, MS and HRMS analysis, we identified this new product as ethyl 3-fluoro-2-methyl-4-oxo-4-phenyl-2(E)-butenoate 3a.^13,14

Table 1 Fluorination reaction of 1a under different conditions

Entry	2^a	Solvent	Additive (equiv)	Time/h	NMR Yield (%)^b		Ratio (3a/4a)^b	1a (%)^c
					E-3a	4a
a Equivalents of 2.b Determined by ^1H NMR analysis of the crude reaction mixture using 1,3,5-trimethylbenzene as the internal standard.c 1a recovered after the reaction.d Determined by ^19F NMR analysis.e The reaction was carried out under N2; MeCN was refluxed in the presence of calcium hydride for 10 h and distilled immediately before use.
1	1.2	MeCN	—	19.5	19	35	35/65	7
2	1.2	MeCN	Li2CO3 (2.0)	11.5	12.5	4.5	74/26	8
3	2.0	MeCN	Li2CO3 (2.0)	14	32	13	71/29	—
4	2.0	MeCN	Na2CO3 (2.0)	19.3	9	3	75/25	3.5
5	2.0	MeCN	K2CO3 (2.0)	19.3	10	—	87/13^d	28
6	2.0	MeCN	Cs2CO3 (2.0)	19	Trace	Trace	—	33
7	3.0	MeCN^e	—	9	26	—	98/2^d	—
8	3.0	MeCN^e	H2O(0.5)	10.5	60	1.6	97/3	—
9	3.0	MeCN^e	H2O (1.0)	10	26	1.3	95/5	—
10	1.5	MeCN–H2O = 5/1		12	—	54	1/99 ^d	3
11	1.5	MeCN–H2O = 3/1		11.5	—	50	1/99^d	2
12	1.5	MeCN–H2O = 2/1		11.5	—	57	1/99^d	4
13	1.5	MeCN–H2O = 1/1		10.5	—	44	1/99^d	—
14	1.7	MeCN/H2O = 2/1		14.7	—	56	1/99^d	—

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With the addition of Li₂CO₃,¹³ the selectivity for the formation of 3a was improved; however, the yield was still very low, indicating the difference of the reaction of 2,3-allenoates with PhSeCl and Selectfluor™ (Table 1, entry 2). Increasing the amount of Selectfluor™ could also improve the yield (Table 1, entry 3). Other bases such as Na₂CO₃, K₂CO₃, and Cs₂CO₃ are also unsuitable in this reaction (Table 1, entries 4–6). The carbonyl functionality formed in compound 3a should have something to do with the trace amount of water in the commercially available MeCN or air, thus, the reaction was carried out under N₂ in anhydrous MeCN, which had been refluxed in the presence of calcium hydride for 10 h and distilled immediately before use, to afford E-3a in 26% yield with a selectivity of 3a/4a as high as 98/2 (Table 1, entry 7). Encouraged by these results, a series of experiments were carried out by adding a fixed amount of water (Table 1, entries 8–9). The best results were given when 0.5 equiv of water was used to afford E-3a in 60% yield with the 3a/4a ratio being 97/3 (Table 1, entry 8, Conditions A). In addition, it is interesting to observe that further increasing the amount of water led to almost exclusive formation of 4a (Table 1, entries 10–13). When running the reaction with 1.7 equiv of Selectfluor™ in MeCN–H₂O = 2/1 at 80 °C, lactone 4a was formed as the only product in 56% yield (Table 1, entry 14, Conditions B).

The configuration of the carbon–carbon double bond in E-3a was determined by ¹H–¹⁹F HOESY analysis (heteronuclear Overhauser effect spectroscopy, see Fig. 1 and ESI†).

Fig. 1 ¹H–¹⁹F HOESY analysis of E-3a and E-5m.

The scope of selective fluorination of 2,3-allenoates to form (E)-3-fluoro-4-oxo-2-butenoates 3 was then explored under Conditions A. Some typical results are summarized in Table 2. The R¹ group could be substituted phenyl group; R² could be alkyl or benzyl group.

Table 2 Synthesis of (E)-3-fluoro-4-oxo-2-butenoates 3 from the reaction of 2,4-disubstituted 2,3-allenoates with Selectfluor™ under Conditions A^a

Entry	1	R^1	R^2	Time/h	Product	Yield (%)^b	3/4^c
a Conditions A: A solution of 1 (0.2–0.3 mmol), 2 (3 equiv), and water (0.5 equiv) was stirred in 2–3 mL of anhydrous MeCN under N2 at 80 °C.b Isolated yield.c The ratio of 3/4 was determined by ^19F NMR spectra of crude products.
1	1a	Ph	Me	10.5	E-3a	55	97/3
2	1b	Ph	Et	10	E-3b	56	98/2
3	1c	Ph	n-Pr	11	E-3c	53	98/2
4	1d	Ph	Bn	11.5	E-3d	45	98/2
5	1e	p-FC6H4	Me	10	E-3e	45	99/1
6	1f	p-ClC6H4	Me	10.5	E-3f	46	98/2
7	1g	p-BrC6H4	Me	12	E-3g	55	98/2
8	1h	p-BrC6H4	n-Pr	10.5	E-3h	46	98/2
9	1i	p-MeC6H4	Me	10	E-3i	43	98/2
10	1j	p-MeC6H4	Et	9.5	E-3j	39	98/2

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However, the reaction could not be extended to 4-alkyl-substituted 2,3-allenoate 1k (Scheme 1). The reaction of ethyl 4-(2-chlorophenyl)-2-methyl-2,3-butadienoate (1l) afforded ketone E-3l together with lactone 4l in a ratio of 87/13 (3l/4l) (Scheme 1).

Scheme 1

The fluorolactonization of 2,3-allenoates was also demonstrated under Conditions B (Table 3): When R² is ethyl or propyl, 2.5 equiv of Selectfluor™ were required to form the corresponding lactones (Table 3, entries 2 and 3). The reaction of fully substituted 1m afforded 4m under Conditions B in 86% yield together with the fluorohydroxylation product, i.e., ethyl 3-fluoro-4-hydroxyl-4,4-diphenyl-2-propyl-2(E)-butenoate (5m) in 7% yield, indicating the existence of a 5m-type intermediate for this type of transformation (Scheme 2). Treatment of 1m with Selectfluor™ under Conditions A still led to the formation of lactone 4m in 93% isolated yield together with E-5m in 5% isolated yield (Scheme 2). The configuration of the carbon–carbon double bond in E-5m was determined by ¹H-¹⁹F HOESY analysis (see Fig. 1 and ESI†). Further screening led us to observe that 4m could be afforded when 1m was treated with just 1.2 equiv of Selectfluor™ in MeCN at 80 °C (Conditions C) in 90% isolated yield with a selectivity of 4m/5m being 98/2 as determined by ¹⁹F NMR analysis of the crude reaction mixture (Scheme 2).

Table 3 Synthesis of 4-fluoro-2(5H)-furanones 4 from the reaction of 2,3-allenoates with 2

Entry	1			Conditions^a	t/h	Yield (%)^b	4/3^b	4/5^b
	R^1	R^3	R^2
a Conditions B: A solution of 1 (0.2–0.4 mmol) and 2 (1.7 equiv) was stirred in 2–4 mL of MeCN–H2O (2/1 (v/v)) at 80 °C; Conditions C: A solution of 1 (0.2 mmol) and 2 (1.2 equiv) was stirred in 2 mL of MeCN at 80 °C.b The ratios of 4/3 and 4/5 were determined by the ^19F NMR analysis of the crude products.c A quantity of 2.5 equiv of 2 was used.d MeNO2 was used instead of MeCN.
1	Ph	H	Me (1a)	B	14.7	51 (4a)	>99/1	—
2	Ph	H	Et (1b)	B^c	23.5	50 (4b)	>99/1	—
3	Ph	H	n-Pr (1c)	B^c	23.5	47 (4c)	>99/1	—
4	p-FC6H4	H	Me (1e)	B	26	60 (4e)	>99/1	—
5	p-BrC6H4	H	Me (1g)	B	21.5	42 (4g)	>99/1	—
6	p-MeC6H4	H	Me (1i)	B	21	64 (4i)	>99/1	—
7	Ph	Me	Me (1n)	C	5.3	80 (4n)	—	99/1
8	Ph	Ph	Me (1o)	C	5.5	93 (4o)	—	99/1
9	Ph	Et	Me (1p)	C	5.5	95 (4p)	—	98/2
10	Ph	Et	n-Pr (1q)	C	5	91 (4q)	—	99/1
11	Ph	Et	H (1r)	C	5	76 (4r)	—	98/2
12	-(CH2)5-		Me (1s)	C	11	30 (4s)	—	98/2
13	-(CH2)5-		Me (1s)	C^d	10.8	42 (4s)	—	98/2

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Scheme 2

A series of 4,4-disubstituted 4-aryl 2,3-allenoates were then treated with Selectfluor™ under Conditions C. The corresponding 4-fluoro-2(5H)-furanones could also be afforded in excellent yields (Table 3, entries 7–11, Conditions C). MeNO₂ is more effective than MeCN leading the lactonization reaction of 2,4,4-trialkyl substituted ethyl 3-cyclohexylidene-2-methylacrylate (1s) to afford 4s in relatively higher yields (Table 3, entries 12 and 13).

However, complicated products were observed when 2,4-disubstituted 2,3-allenoate 1k was treated with Selectfluor™ under either Conditions B or Conditions C (Scheme 3). For 4,4-dialkyl substituted allenoate 1t, either in MeCN or in MeNO₂, the corresponding lactone could not be afforded (Scheme 3).

Scheme 3

A plausible mechanism was proposed for this reaction (Scheme 4): The relatively electron-rich carbon–carbon double bond of 2,3-allenoate firstly interacts with F⁺ in Selectfluor™ to form cyclic intermediate 6, which explains the E-stereoselectivity observed here. Hydroxylation at the 5-position would lead to the formation of fluorohydroxylation product 5, which was confirmed by the isolation and characterization of E-5m (Scheme 2). If R³ = H, subsequent oxidation by Selectfluor™¹⁵ would form ketone 3 (Path I, Scheme 4). Corresponding dealkylation of intermediate 6 may lead to lactonization to form 4 (Path II, Scheme 4).

Scheme 4

This reaction may easily be carried out with 5 mmol of ethyl 4-phenyl-2,3-butadienoate 1a to afford 3a and 4a, respectively (Scheme 5).

Scheme 5

Conclusions

In conclusion, we have developed an efficient way to synthesize 3-fluoro-4-oxo-2(E)-alkenoates and 4-fluoro-2(5H)-furanones from the same starting materials 4-aryl-2-alkyl or benzyl-2,3-allenoates and Selectfluor™ in acetonitrile. The reaction of fully substituted 2,3-allenoates with Selectfluor™ afforded 4-fluoro-2(5H)-furanones highly selectively in excellent yields under Conditions A, B, and C. A mechanism has been proposed based on the isolation and characterization of the minor fluorohydroxylation product E-5m. Due to the readily availability of 2,3-allenoates and the formation of different types of monofluorinated products with functionalities for further elaboration under different conditions, this method shows more potential than that of 2,3-allenoic acids. Further studies in this area are being conducted in our laboratory.

Experimental section

1. Preparation of 3-fluoro-4-oxo-2(E)-butenoates (3a–j)

(1) Preparation of ethyl 3-fluoro-2-methyl-4-oxo-4-phenyl-2(E)-butenoate (3a). Typical procedure (Conditions A). Ethyl 2-methyl-4-phenyl-2,3-butadienoate (1a) (39.9 mg, 0.20 mmol) and 1 mL of H₂O–MeCN (premixed, 0.9 μL mL⁻¹) were added into a flame-dried Schlenk vessel, which was pre-evacuated and backfilled with nitrogen three times. Selectfluor™ (95%, 223.2 mg, 0.60 mmol) and another 1 mL of H₂O–MeCN (premixed, 0.9 μL mL⁻¹) were added sequentially under nitrogen. The resulting mixture was heated at 80 °C with a preheated oil bath. After 10.5 h, the reaction was complete as monitored by TLC. The reaction mixture was then quenched with 10 mL of H₂O, extracted with ether (40 mL + 2 × 10 mL), washed with 10 mL of brine, and dried over anhydrous Na₂SO₄. Filtration, evaporation, and purification by chromatography (petroleum ether–ethyl acetate = 80 : 1) on silica gel afforded 3a (25.8 mg, 55%): liquid; ¹H NMR (300 MHz, CDCl₃) δ 7.96–7.89 (m, 2H), 7.66–7.58 (m, 1H), 7.53–7.45 (m, 2H), 3.99 (q, J = 7.2 Hz, 2H), 2.05 (d, J = 4.2 Hz, 3H), 0.98 (t, J = 7.4 Hz, 3H); ¹³C NMR (75 MHz, CDCl₃) δ 187.2 (d, J = 28.1 Hz), 166.1 (d, J = 17.4 Hz), 158.9 (d, J = 276.2), 134.6, 134.1, 129.2, 128.8, 114.9 (d, J = 16.9 Hz), 61.4, 13.4, 10.7 (d, J = 5.4 Hz); ¹⁹F NMR (282 MHz, CDCl₃) δ−100.5; IR (neat) ν/cm⁻¹ 3064, 2984, 2936, 1725, 1682, 1598, 1583, 1451, 1369, 1302, 1202, 1176, 1113, 1082, 1019; MS (70 eV, EI) m/z (%): 236 (M⁺, 7.13), 105 (100); HRMS calcd for C₁₃H₁₃O₃F (M⁺): 236.0849. Found: 236.0842.

The following compounds were prepared according to this typical procedure.

(2) Ethyl 2-ethyl-3-fluoro-4-oxo-4-phenyl-2(E)-butenoate (3b). The reaction of 1b (64.1 mg, 0.30 mmol) and Selectfluor™ (95%, 336.2 mg, 0.90 mmol) in 3 mL of H₂O–MeCN (premixed, 0.9 μL mL⁻¹) at 80 °C under nitrogen afforded 3b (41.5 mg, 56%) as a liquid; ¹H NMR (300 MHz, CDCl₃) δ 7.95–7.88 (m, 2H), 7.66–7.58 (m, 1H), 7.54–7.46 (m, 2H), 4.01 (q, J = 7.1 Hz, 2H), 2.53 (qd, J = 7.6 Hz and 3.6 Hz, 2H), 1.91 (t, J = 7.6 Hz, 3H), 1.01 (t, J = 7.1 Hz, 3H); ¹³C NMR (75 MHz, CDCl₃) δ 187.1 (d, J = 28.8 Hz), 165.9 (d, J = 16.5 Hz), 158.0 (d, J = 276.8 Hz), 134.7, 134.1, 129.2 (d, J = 2.0 Hz), 128.8, 121.5 (d, J = 15.4 Hz), 61.4, 19.2 (d, J = 4.4 Hz), 13.4, 12.8 (d, J = 2.0 Hz); ¹⁹F NMR (282 MHz, CDCl₃) δ−104.5; IR (neat) ν/cm⁻¹ 2981, 2940, 1727, 1683, 1598, 1582, 1450, 1369, 1309, 1276, 1256, 1201, 1176, 1122, 1024; MS (70 eV, EI) m/z (%): 250 (M⁺, 6.31), 105 (100); HRMS calcd for C₁₄H₁₅O₃F (M⁺): 250.1005. Found: 250.1007.

(3) Ethyl 3-fluoro-4-oxo-4-phenyl-2-propyl-2(E)-butenoate (3c). The reaction of 1c (70.2 mg, 0.31 mmol) and Selectfluor™ (95%, 339.3 mg, 0.91 mmol) in 3 mL of H₂O–MeCN (premixed, 0.9 μL mL⁻¹) at 80 °C under nitrogen afforded 3c (42.8 mg, 53%) as a liquid; ¹H NMR (300 MHz, CDCl₃) δ 7.96–7.89 (m, 2H), 7.65–7.58 (m, 1H), 7.54–7.46 (m, 2H), 4.00 (q, J = 7.2 Hz, 2H), 2.53–2.45 (m, 2H), 1.68–1.54 (m, 2H), 1.02 (t, J = 7.4 Hz, 3H), 1.00 (t, J = 7.2 Hz, 3H); ¹³C NMR (75 MHz, CDCl₃) δ 187.1 (d, J = 29.0 Hz), 166.0 (d, J = 16.6 Hz), 158.4 (d, J = 275.2 Hz), 134.7, 134.1, 129.2 (d, J = 1.4 Hz), 128.8, 120.1 (d, J = 16.0 Hz), 61.4, 27.5 (d, J = 3.4 Hz), 21.4 (d, J = 1.9 Hz), 13.8, 13.4; ¹⁹F NMR (282 MHz, CDCl₃) δ−103.9; IR (neat) ν/cm⁻¹ 3065, 2966, 2936, 2875, 1728, 1682, 1598, 1582, 1451, 1369, 1305, 1275, 1229, 1200, 1177, 1124, 1033, 1002; MS (70 eV, EI) m/z (%): 264 (M⁺, 10.02), 105 (100); HRMS calcd for C₁₅H₁₇O₃F (M⁺): 264.1162. Found: 264.1166.

(4) Ethyl 2-benzyl-3-fluoro-4-oxo-4-phenyl-2(E)-butenoate (3d). The reaction of 1d (83.9 mg, 0.30 mmol) and Selectfluor™ (95%, 336.1 mg, 0.90 mmol) in 3 mL of H₂O–MeCN (premixed, 0.9 μL mL⁻¹) at 80 °C under nitrogen afforded 3d (42.1 mg, 45%) as a liquid; ¹H NMR (300 MHz, CDCl₃) δ 7.97–7.88 (m, 2H), 7.66–7.57 (m, 1H), 7.53–7.44 (m, 2H), 7.36–7.21 (m, 5H), 3.93 (q, J = 7.2 Hz, 2H), 3.85 (d, J = 3.6 Hz, 2H), 0.90 (t, J = 7.2 Hz, 3H); ¹³C NMR (75 MHz, CDCl₃) δ 186.9 (d, J = 28.4 Hz), 165.3 (d, J = 17.0 Hz), 159.2 (d, J = 278.6 Hz), 137.6 (d, J = 2.6 Hz), 134.5, 134.2, 129.2, 128.9, 128.7, 128.6, 126.7, 118.3 (d, J = 14.4 Hz), 61.5, 31.1 (d, J = 4.0 Hz), 13.2; ¹⁹F NMR (282 MHz, CDCl₃) δ−100.3; IR (neat) ν/cm⁻¹ 3084, 3064, 3030, 2983, 2937, 1724, 1682, 1598, 1582, 1495, 1451, 1370, 1310, 1276, 1203, 1182, 1103, 1037, 1022; MS (70 eV, EI) m/z (%): 312 (M⁺, 4.06), 266 (100); HRMS calcd for C₁₉H₁₇O₃F (M⁺): 312.1162. Found: 312.1168.

(5) Ethyl 3-fluoro-4-(4′-fluorophenyl)-2-methyl-4-oxo-2(E)-butenoate (3e). The reaction of 1e (65.8 mg, 0.30 mmol) and Selectfluor™ (95%, 335.6 mg, 0.90 mmol) in 3 mL of H₂O–MeCN (premixed, 0.9 μL mL⁻¹) at 80 °C under nitrogen afforded 3e (34.1 mg, 45%) as a liquid; ¹H NMR (300 MHz, CDCl₃) δ 8.00–7.92 (m, 2H), 7.22–7.12 (m, 2H), 4.04 (q, J = 7.2 Hz, 2H), 2.05 (d, J = 4.5 Hz, 3H), 1.03 (t, J = 7.2 Hz, 3H); ¹³C NMR (75 MHz, CDCl₃) δ 185.6 (d, J = 28.8 Hz), 166.3 (d, J = 256.1 Hz), 166.0 (d, J = 16.8 Hz), 158.6 (d, J = 276.5 Hz), 132.0 (dd, J = 9.8 Hz and 1.4 Hz), 131.1 (d, J = 3.2 Hz), 116.2 (d, J = 22.1 Hz), 115.2 (d, J = 16.0 Hz), 61.5, 13.5, 10.8 (d, J = 5.8 Hz); ¹⁹F NMR (282 MHz, CDCl₃) δ−101.2, −102.7; IR (neat) ν/cm⁻¹ 3078, 2985, 2937, 1727, 1683, 1600, 1507, 1446, 1413, 1370, 1306, 1240, 1202, 1155, 1114, 1082, 1018; MS (70 eV, EI) m/z (%): 254 (M⁺, 6.93), 123 (100); HRMS calcd for C₁₃H₁₂O₃F₂ (M⁺): 254.0755. Found: 254.0761.

(6) Ethyl 4-(4′-chlorophenyl)-3-fluoro-2-methyl-4-oxo-2(E)-butenoate (3f). The reaction of 1f (71.4 mg, 0.30 mmol) and Selectfluor™ (95%, 335.4 mg, 0.90 mmol) in 3 mL of H₂O–MeCN (premixed, 0.9 μL mL⁻¹) at 80 °C under nitrogen afforded 3f (37.2 mg, 46%) as a liquid; ¹H NMR (300 MHz, CDCl₃) δ 7.90–7.83 (m, 2H), 7.50–7.44 (m, 2H), 4.03 (q, J = 7.2 Hz, 2H), 2.04 (d, J = 4.2 Hz, 3H), 1.04 (t, J = 7.2 Hz, 3H); ¹³C NMR (75 MHz, CDCl₃) δ 185.9 (d, J = 29.0 Hz), 166.0 (d, J = 16.6 Hz), 158.4 (d, J = 276.3 Hz), 140.7, 133.0, 130.6 (d, J = 1.5 Hz), 129.2, 115.4 (d, J = 16.1 Hz), 61.5, 13.5, 10.8 (d, J = 4.7 Hz); ¹⁹F NMR (282 MHz, CDCl₃) δ−101.7; IR (neat) ν/cm⁻¹ 2984, 2937, 1728, 1682, 1589, 1572, 1488, 1445, 1402, 1369, 1304, 1203, 1173, 1113, 1015; MS (70 eV, EI) m/z (%): 272 (M⁺(³⁷Cl), 2.93), 270 (M⁺(³⁵Cl), 8.83), 139 (100); HRMS calcd for C₁₃H₁₂O₃³⁵ClF (M⁺): 270.0459. Found: 270.0453.

(7) Ethyl 4-(4′-bromophenyl)-3-fluoro-2-methyl-4-oxo-2(E)-butenoate (3g). The reaction of 1g (83.8 mg, 0.30 mmol) and Selectfluor™ (95%, 335.5 mg, 0.90 mmol) in 3 mL of H₂O–MeCN (premixed, 0.9 μL mL⁻¹) at 80 °C under nitrogen afforded 3g (51.5 mg, 55%) as a liquid; ¹H NMR (300 MHz, CDCl₃) δ 7.78 (d, J = 8.4 Hz, 2H), 7.64 (d, J = 8.4 Hz, 2H), 4.03 (q, J = 7.2 Hz, 2H), 2.04 (d, J = 4.2 Hz, 3H), 1.04 (t, J = 7.2 Hz, 3H); ¹³C NMR (75 MHz, CDCl₃) δ 186.1 (d, J = 28.7 Hz), 166.0 (d, J = 15.9 Hz), 158.3 (d, J = 276.6 Hz), 133.4, 132.2, 130.6 (d, J = 1.0 Hz), 129.5, 115.5 (d, J = 16.0 Hz), 61.5, 13.5, 10.8 (d, J = 5.2 Hz); ¹⁹F NMR (282 MHz, CDCl₃) δ−101.8; IR (neat) ν/cm⁻¹ 3091, 2984, 2936, 2872, 1728, 1682, 1586, 1484, 1446, 1399, 1369, 1304, 1202,1173, 1112, 1069, 1012; MS (70 eV, EI) m/z (%): 316 (M⁺(⁸¹Br), 17.93), 314 (M⁺(⁷⁹Br), 17.55), 185 (99.06), 183 (100); HRMS calcd for C₁₃H₁₂O₃⁷⁹BrF (M⁺): 313.9954. Found: 313.9952.

(8) Ethyl 4-(4′-bromophenyl)-3-fluoro-4-oxo-2-propyl-2(E)-butenoate (3h). The reaction of 1h (91.1 mg, 0.29 mmol) and Selectfluor™ (95%, 330.6 mg, 0.89 mmol) in 3 mL of H₂O–MeCN (premixed, 0.9 μL mL⁻¹) at 80 °C under nitrogen afforded 3h (46.7 mg, 46%) (flash chromatography, eluent: petroleum ether–ethyl acetate = 100 : 1) as a liquid; ¹H NMR (300 MHz, CDCl₃) δ 7.81–7.73 (m, 2H), 7.67–7.60 (m, 2H), 4.05 (q, J = 7.2 Hz, 2H), 2.54–2.42 (m, 2H), 1.67–1.55 (m, 2H), 1.06 (t, J = 7.2 Hz, 3H), 1.01 (t, J = 7.4 Hz, 3H); ¹³C NMR (75 MHz, CDCl₃) δ 186.0 (d, J = 30.0 Hz), 165.9 (d, J = 15.4 Hz), 157.8 (d, J = 275.0 Hz), 133.5, 132.2, 130.6 (d, J = 2.0 Hz), 129.4, 120.8 (d, J = 16.0 Hz), 61.5, 27.6 (d, J = 3.5 Hz), 21.3 (d, J = 2.2 Hz), 13.8, 13.5; ¹⁹F NMR (282 MHz, CDCl₃) δ 105.3; IR (neat) ν/cm⁻¹ 2965, 2935, 2874, 1728, 1687, 1586, 1484, 1464, 1399, 1369, 1311, 1272, 1228, 1199, 1173, 1124, 1070, 1011; MS (70 eV, EI) m/z (%): 344 (M⁺(⁸¹Br), 20.01), 342 (M⁺(⁷⁹Br), 20.23), 185 (98.06), 183 (100); HRMS calcd for C₁₅H₁₆O₃⁷⁹BrF (M⁺): 342.0267. Found: 342.0263.

(9) Ethyl 3-fluoro-2-methyl-4-(4′-methylphenyl)-4-oxo-2(E)-butenoate (3i). The reaction of 1i (64.6 mg, 0.30 mmol) and Selectfluor™ (95%, 335.9 mg, 0.90 mmol) in 3 mL of H₂O–MeCN (premixed, 0.9 μL mL⁻¹) at 80 °C under nitrogen afforded 3i (32.4 mg, 43%) as a liquid; ¹H NMR (300 MHz, CDCl₃) δ 7.85–7.79 (m, 2H), 7.31–7.26 (m, 2H), 3.99 (q, J = 7.2 Hz, 2H), 2.42 (s, 3H), 2.04 (d, J = 4.2 Hz, 3H), 0.99 (t, J = 7.2 Hz, 3H); ¹³C NMR (75 MHz, CDCl₃) δ 186.8 (d, J = 28.2 Hz), 166.1 (d, J = 17.6 Hz), 159.3 (d, J = 277.2 Hz), 145.3, 132.2, 129.5, 129.4 (d, J = 1.2 Hz), 114.4 (d, J = 15.4 Hz), 61.4, 21.8, 13.4, 10.7 (d, J = 5.5 Hz); ¹⁹F NMR (282 MHz, CDCl₃) δ 99.9; IR (neat) ν/cm⁻¹ 3033, 2984, 2934, 2872, 1727, 1681, 1606, 1574, 1446, 1410, 1369, 1299, 1202, 1177, 1113, 1081, 1019; MS (70 eV, EI) m/z (%): 250 (M⁺, 8.05), 119 (100); HRMS calcd for C₁₄H₁₅O₃F (M⁺): 250.1005. Found: 250.1003.

(10) Ethyl 2-ethyl-3-fluoro-4-(4′-methylphenyl)-4-oxo-2(E)-butenoate (3j). The reaction of 1j (69.3 mg, 0.30 mmol) and Selectfluor™ (95%, 336.0 mg, 0.90 mmol) in 3 mL of H₂O–MeCN (premixed, 0.9 μL mL⁻¹) at 80 °C under nitrogen afforded 3j (30.7 mg, 39%) as a liquid; ¹H NMR (300 MHz, CDCl₃) δ 7.84–7.78 (m, 2H), 7.31–7.25 (m, 2H), 4.01 (q, J = 7.2 Hz, 2H), 2.52 (qd, J = 7.4 Hz and 3.6 Hz, 2H), 2.42 (s, 3H), 1.18 (t, J = 7.4 Hz, 3H), 1.01 (t, J = 7.2 Hz, 3H); ¹³C NMR (75 MHz, CDCl₃) δ 186.7 (d, J = 29.0 Hz), 165.9 (d, J = 16.6 Hz), 158.3 (d, J = 276.2 Hz), 145.2, 132.2, 129.5, 129.4 (d, J = 1.0 Hz), 121.0 (d, J = 16.0 Hz), 61.3, 21.8, 19.1 (d, J = 4.5 Hz), 13.4, 12.8 (d, J = 2.0 Hz); ¹⁹F NMR (282 MHz, CDCl₃) δ−103.9; IR (neat) ν/cm⁻¹ 3033, 2981, 2939, 2879, 1727, 1681, 1606, 1574, 1462, 1369, 1317, 1277, 1256, 1177, 1120, 1061, 1025; MS (70 eV, EI) m/z (%): 264 (M⁺, 6.53), 119 (100); HRMS calcd for C₁₅H₁₇O₃F (M⁺): 264.1162. Found: 264.1166.

2. Preparation of 4-fluoro-2(5H)-furanone (4a–i)

(1) Preparation of 4-fluoro-3-methyl-5-phenyl-2(5H)-furanone (4a). Typical procedure (Conditions B). A mixture of ethyl 2-methyl-4-phenyl-2,3-butadienoate (1a) (40.7 mg, 0.20 mmol) and Selectfluor™ (95%, 126.6 mg, 0.34 mmol) was stirred in a mixture of 1.4 mL of MeCN and 0.65 mL of water at 80 °C with a preheated oil bath. After 14.7 h, the reaction was complete as monitored by TLC. The reaction mixture was then quenched with 10 mL of H₂O, extracted with ether (40 mL + 2 × 10 mL), washed with 10 mL of brine, and dried over anhydrous Na₂SO₄. Filtration, evaporation, and purification by chromatography (petroleum ether–ethyl acetate = 30 : 1) on silica gel afforded 4a^8a (19.9 mg, 51%): liquid; ¹H NMR (300 MHz, CDCl₃) δ 7.45–7.38 (m, 3H), 7.36–7.30 (m, 2H), 5.79–5.75 (m, 1H), 1.88 (t, J = 1.8 Hz, 3H); ¹⁹F NMR (282 MHz, CDCl₃) δ−110.0.

The following compounds were prepared according to this typical procedure.

(2) 3-Ethyl-4-fluoro-5-phenyl-2(5H)-furanone (4b). The reaction of 1b (42.6 mg, 0.20 mmol) and Selectfluor™ (95%, 186.9 mg, 0.50 mmol) in a mixture of 1.3 mL of MeCN and 0.7 mL of H₂O at 80 °C afforded 4b (20.3 mg, 50%) as a liquid; ¹H NMR (300 MHz, CDCl₃) δ 7.45–7.39 (m, 3H), 7.36–7.27 (m, 2H), 5.77–5.73 (m, 1H), 2.35 (qt, J_H-H1 = 7.6 Hz, J_H-H2 = 1.2 Hz, J_H–F = 1.2 Hz, 2H), 1.20 (t, J = 7.6 Hz, 3H); ¹³C NMR (75 MHz, CDCl₃) δ 174.0 (d, J = 295.8 Hz), 171.2 (d, J = 22.0 Hz), 132.3 (d, J = 2.0 Hz), 129.9, 129.1, 126.6, 110.1 (d, J = 6.1 Hz), 77.5 (d, J = 22.5 Hz), 15.2 (d, J = 3.2 Hz), 11.7 (d, J = 2.0 Hz); ¹⁹F NMR (282 MHz, CDCl₃) δ 110.5; IR (neat) ν/cm⁻¹ 3069, 3033, 2978, 2940, 2877, 1778, 1715, 1497, 1456, 1362, 1313, 1265, 1091, 1062, 1035, 1005; MS (70 eV, EI) m/z (%): 207 (M⁺ + 1, 13.77), 206 (M⁺, 100); HRMS calcd for C₁₂H₁₁O₂F (M⁺): 206.0743. Found: 206.0741.

(3) 4-Fluoro-5-phenyl-3-propyl-2(5H)-furanone (4c). The reaction of 1c (46.5 mg, 0.20 mmol) and Selectfluor™ (95%, 187.3 mg, 0.50 mmol) in a mixture of 1.3 mL of MeCN and 0.7 mL of H₂O at 80 °C afforded 4c² (20.8 mg, 47%) as a liquid; ¹H NMR (300 MHz, CDCl₃) δ 7.45–7.40 (m, 3H), 7.35–7.30 (m, 2H), 5.78–5.74 (m, 1H), 2.34–2.26 (m, 2H), 1.70–1.57 (m, 2H), 0.96 (t, J = 7.5 Hz, 3H); ¹⁹F NMR (282 MHz, CDCl₃) δ−110.0.

(4) 4-Fluoro-5-(4′-fluorophenyl)-3-methyl-2(5H)-furanone (4e). The reaction of 1e (85.4 mg, 0.39 mmol) and Selectfluor™ (95%, 246.8 mg, 0.66 mmol) in a mixture of 2.7 mL of MeCN and 1.3 mL of H₂O at 80 °C afforded 4e (48.6 mg, 60%) as a white solid: mp: 52.5–53.5 °C (hexane). ¹H NMR (300 MHz, CDCl₃) δ 7.36–7.28 (m, 2H), 7.15–7.07 (m, 2H), 5.78–5.72 (m, 1H), 1.88 (t, J_H–H = 2.0 Hz, J_H–F = 2.0 Hz, 3H); ¹³C NMR (75 MHz, CDCl₃) δ 174.0 (d, J = 294.7 Hz), 171.3 (d, J = 21.4 Hz), 163.5 (d, J = 248.1 Hz), 128.7 (d, J = 7.7 Hz), 128.1 (t, J = 3.0 Hz), 116.2 (d, J = 21.7 Hz), 105.0 (d, J = 6.4 Hz), 77.1 (d, J = 23.1 Hz), 6.0 (d, J = 2.3 Hz); ¹⁹F NMR (282 MHz, CDCl₃) δ−110.3, −110.9; IR (KBr) ν/cm⁻¹ 2933, 1781, 1724, 1608, 1513, 1392, 1347, 1298, 1234, 1115, 1080, 1012; MS (70 eV, EI) m/z (%): 211 (M⁺ + 1, 11.85), 210 (M⁺, 90.78), 123 (100); Anal. Calcd. for C₁₁H₈F₂O₂ : C, 62.86; H, 3.84. Found: C, 62.65; H, 3.81%.

(5) 5-(4′-Bromophenyl)-4-fluoro-3-methyl-2(5H)-furanone (4g). The reaction of 1g (113.0 mg, 0.40 mmol) and Selectfluor™ (95%, 254.8 mg, 0.68 mmol) in a mixture of 2.7 mL of MeCN and 1.3 mL of H₂O at 80 °C afforded 4g (45.3 mg, 42%) as a white solid: mp: 62.4–64.2 °C (hexane). ¹H NMR (300 MHz, CDCl₃) δ 7.55 (dt, J = 8.7 Hz and 2.1 Hz, 2H), 7.24–7.17 (m, 2H), 5.75–5.70 (m, 1H), 1.87 (t, J_H–H = 2.0 Hz, J_H–F = 2.0 Hz, 3H); ¹³C NMR (75 MHz, CDCl₃) δ 173.9 (d, J = 295.2 Hz), 171.3 (d, J = 21.6 Hz), 132.3, 131.3 (d, J = 1.9 Hz), 128.2, 124.1, 105.0 (d, J = 7.2 Hz), 77.0 (d, J = 22.4 Hz), 6.1 (d, J = 1.8 Hz); ¹⁹F NMR (282 MHz, CDCl₃) δ−110.3; IR (KBr) ν/cm⁻¹ 3067, 2965, 2930, 2863, 1778, 1716, 1590, 1489, 1411, 1390, 1345, 1300, 1198, 1114, 1069, 1009; MS (70 eV, EI) m/z (%): 272 (M⁺(⁸¹Br), 27.78), 270 (M⁺(⁷⁹Br), 28.42), 191 (M⁺− Br, 100); Anal. Calcd. for C₁₁H₈BrFO₂: C, 48.74; H, 2.97. Found: C, 48.91; H, 2.88%.

(6) 4-Fluoro-3-methyl-5-(4′-methylphenyl)-2(5H)-furanone (4i). The reaction of 1i (86.8 mg, 0.40 mmol) and Selectfluor™ (95%, 254.8 mg, 0.68 mmol) in a mixture of 2.7 mL of MeCN and 1.3 mL of H₂O at 80 °C afforded 4i (52.6 mg, 64%) as a liquid; ¹H NMR (300 MHz, CDCl₃) δ 7.25–7.18 (m, 4H), 5.75–5.70 (m, 1H), 2.36 (s, 3H), 1.87 (t, J_H–H = 2.1 Hz, J_H–F = 2.1 Hz, 3H); ¹³C NMR (75 MHz, CDCl₃) δ 174.3 (d, J = 294.8 Hz), 171.7 (d, J = 22.1 Hz), 139.9, 129.7, 129.1 (d, J = 2.8 Hz), 126.6, 104.7 (d, J = 6.3 Hz), 77.7 (d, J = 23.5 Hz), 21.2, 6.0 (d, J = 2.8 Hz); ¹⁹F NMR (282 MHz, CDCl₃) δ−110.0; IR (neat) ν/cm⁻¹ 2929, 1778, 1723, 1516, 1448, 1420, 1391, 1346, 1301, 1198, 1112, 1081, 1037, 1007; MS (70 eV, EI) m/z (%): 207 (M⁺ + 1, 13.76), 206 (M⁺, 100); HRMS calcd for C₁₂H₁₁O₂F (M⁺): 206.0743. Found: 206.0744.

3. Preparation of 4-fluoro-2(5H)-furanone (4m–s)

(1) 4-Fluoro-5,5-diphenyl-3-propyl-2(5H)-furanone (4m). Typical procedure (Conditions C). A mixture of ethyl 4,4-diphenyl-2-propyl-2,3-butadienoate (1m) (60.9 mg, 0.20 mmol) and Selectfluor™ (85.3 mg, 0.24 mmol) was stirred in 2 mL of MeCN at 80 °C with an oil bath. After 5.5 h, the reaction was complete as monitored by TLC. The reaction mixture was quenched with 10 mL of H₂O, extracted with ether (40 mL + 2 × 10 mL), washed with 10 mL of brine, and dried over Na₂SO₄. Filtration, evaporation, and purification by chromatography (petroleum ether–ethyl acetate = 30 : 1) on silica gel afforded 4-fluoro-5,5-diphenyl-3-propyl-2(5H)-furanone (4m)^8a (52.8 mg, 90%): liquid; ¹H NMR (300 MHz, CDCl₃) δ 7.41–7.35 (m, 10H), 2.31 (td, J = 7.5 Hz and 1.2 Hz, 2H), 1.72–1.58 (m, 2H), 0.95 (t, J = 7.4 Hz, 3H); ¹⁹F NMR (282 MHz, CDCl₃) δ−106.2.

The formation of 4m and E-5m under Conditions A:

The reaction of 1m (0.6162 g, 2.01 mmol) and Selectfluor™ (95%, 2.2435 g, 6.02 mmol) in 20 mL of H₂O–MeCN (premixed, 0.9 μL mL⁻¹) at 80 °C under nitrogen afforded 4m (0.5558 g, 93%) and E-5m (0.0375 g, 5%) (petroleum ether–ethyl acetate = 30 : 1 to 5 : 1) as a liquid.

4m: ¹H NMR (300 MHz, CDCl₃) δ 7.43–7.30 (m, 10H), 2.35–2.27 (m, 2H), 1.73-1.57 (m, 2H), 0.95 (t, J = 7.4 Hz, 3H).

E-5m: liquid; ¹H NMR (300 MHz, CDCl₃) δ 7.45–7.30 (m, 10H), 4.25 (q, J = 7.1 Hz, 2H), 2.92 (d, J = 2.1 Hz, 1H), 1.98–1.89 (m, 2H), 1.34–1.15 (m, 5H), 0.65 (t, J = 7.4 Hz, 3H); ¹³C NMR (75 MHz, CDCl₃) 167.6 (d, J = 5.0 Hz), 159.5 (d, J = 261.8 Hz), 142.7, 128.3, 127.5, 117.8 (d, J = 13.3 Hz), 80.7 (d, J = 30.4 Hz), 61.1, 28.6 (d, J = 3.2 Hz), 21.8 (d, J = 2.6 Hz), 14.2, 13.7; ¹⁹F NMR (282 MHz, CDCl₃) δ−96.5; IR (neat) ν/cm⁻¹ 3479, 3061, 3028, 2962, 2932, 2873, 1713, 1600, 1493, 1464, 1449, 1368, 1295, 1232, 1181, 1110, 1031; MS (ESI) m/z: 397 (M⁺ + Na + MeOH), 365 (M⁺ + Na), 360 (M⁺ + NH₄), 325 (M⁺− OH); HRMS calcd for C₂₁H₂₃FO₃Na (M⁺+Na): 365.1523. Found: 365.1536.

The formation of 4m under Conditions B:

The reaction of 1m (61.8 mg, 0.20 mmol) and Selectfluor™ (95%, 126.3 mg, 0.34 mmol) in a mixture of 1.3 mL of MeCN and 0.65 mL of H₂O at 80 °C afforded 4m (51.6 mg, 86%) and E-5m (4.9 mg, 7%) (petroleum ether–ethyl acetate = 20 : 1 to 5 : 1) as a liquid.

4m: ¹H NMR (300 MHz, CDCl₃) δ 7.42–7.33 (m, 10H), 2.36–2.27 (m, 2H), 1.73–1.58 (m, 2H), 0.96 (t, J = 7.4 Hz, 3H).

E-5m: ¹H NMR (300 MHz, CDCl₃) δ 7.45–7.30 (m, 10H), 4.25 (q, J = 7.1 Hz, 2H), 2.91 (d, J = 2.1 Hz, 1H), 1.98–1.88 (m, 2H), 1.35–1.14 (m, 5H), 0.65 (t, J = 7.4 Hz, 3H).

The following compounds were prepared according to the Conditions C.

(2) 4-Fluoro-3,5-dimethyl-5-phenyl-2(5H)-furanone (4n). The reaction of 1n (43.4 mg, 0.20 mmol) and Selectfluor™ (85.3 mg, 0.24 mmol) in 2 mL of MeCN at 80 °C afforded 4n^8a (33.0 mg, 80%) as a liquid; ¹H NMR (300 MHz, CDCl₃) δ 7.50–7.31 (m, 5H), 1.90 (s, 3H), 1.81 (d, J = 1.8 Hz, 3H); ¹⁹F NMR (282 MHz, CDCl₃) δ−111.2.

(3) 4-Fluoro-3-methyl-5,5-diphenyl-2(5H)-furanone (4o). The reaction of 1o (55.8 mg, 0.20 mmol) and Selectfluor™ (85.3 mg, 0.24 mmol) in 2 mL of MeCN at 80 °C afforded 4o^8a (49.9 mg, 93%) as a liquid; ¹H NMR (300 MHz, CDCl₃) δ 7.41–7.28 (m, 10H), 1.90 (d, J = 2.1 Hz, 3H); ¹⁹F NMR (282 MHz, CDCl₃) δ−106.1.

(4) 5-Ethyl-4-fluoro-3-methyl-5-phenyl-2(5H)-furanone (4p). The reaction of 1p (45.5 mg, 0.20 mmol) and Selectfluor™ (85.1 mg, 0.24 mmol) in 2 mL of MeCN at 80 °C afforded 4p^8a (41.5 mg, 95%) as a liquid; ¹H NMR (300 MHz, CDCl₃) δ 7.48–7.32 (m, 5H), 2.33–2.20 (m, 1H), 2.19–2.06 (m, 1H), 1.80 (d, J = 2.4 Hz, 3H), 0.92 (t, J = 7.4 Hz, 3H); ¹⁹F NMR (282 MHz, CDCl₃) δ−110.3.

(5) 5-Ethyl-4-fluoro-5-phenyl-3-propyl-2(5H)-furanone (4q). The reaction of 1q (52.4 mg, 0.20 mmol) and Selectfluor™ (85.4 mg, 0.24 mmol) in 2 mL of MeCN at 80 °C afforded 4q^8a (45.7 mg, 91%) as a liquid; ¹H NMR (300 MHz, CDCl₃) δ 7.50–7.26 (m, 5H), 2.36–2.05 (m, 4H), 1.63–1.50 (m, 2H), 0.93 (t, J = 7.4 Hz, 3H), 0.91 (t, J = 7.5 Hz, 3H); ¹⁹F NMR (282 MHz, CDCl₃) δ−110.5.

(6) 5-Ethyl-4-fluoro-5-phenyl-2(5H)-furanone (4r). The reaction of 1r (43.2 mg, 0.20 mmol) and Selectfluor™ (84.8 mg, 0.24 mmol) in 2 mL of MeCN at 80 °C afforded 4r (31.4 mg, 76%) as a liquid; ¹H NMR (300 MHz, CDCl₃) δ 7.50–7.32 (m, 5H), 5.53 (d, J = 1.5 Hz, 1H), 2.36–2.09 (m, 2H), 0.96 (t, J = 7.5 Hz, 3H); ¹³C NMR (75 MHz, CDCl₃) 182.7 (d, J = 304.8 Hz), 169.0 (d, J = 23.4 Hz), 136.1 (d, J = 2.8 Hz), 128.8, 124.8, 124.7, 96.2 (d, J = 7.3 Hz), 86.6 (d, J = 18.6 Hz), 30.1 (d, J = 1.4 Hz), 7.6; ¹⁹F NMR (282 MHz, CDCl₃) δ−99.8; IR (neat) ν/cm⁻¹ 3124, 3064, 2979, 2941, 2883, 1771, 1674, 1601, 1496, 1450, 1357, 1328, 1288, 1222, 1174, 1098; MS (70 eV, EI) m/z (%): 207 (M⁺ + 1, 2.72), 206 (M⁺, 20.54), 177 (100); HRMS calcd for C₁₂H₁₁O₂F (M⁺): 206.0743. Found: 206.0746.

(7) 4-Fluoro-3-methyl-1-oxaspiro[4.5]3-decen-2-one (4s). The reaction of (1s) (39.7 mg, 0.20 mmol) and Selectfluor™ (95%, 90.9 mg, 0.24 mmol) in 2 mL of MeCN at 80 °C afforded 4s^8a (11.2 mg, 30%) as a liquid; ¹H NMR (300 MHz, CDCl₃) δ 1.82–1.60 (m, 12H), 1.36–1.20 (m, 1H); ¹⁹F NMR (282 MHz, CDCl₃) δ−112.8.

The reaction of (1s) (37.8 mg, 0.19 mmol) and Selectfluor™ (95%, 88.5 mg, 0.24 mmol) in 2 mL of MeNO₂ at 80 °C afforded 4s^8a (14.9 mg, 42%) as a liquid.¹H NMR (300 MHz, CDCl₃) δ 1.85–1.58 (m, 12H), 1.35–1.18 (m, 1H); ¹⁹F NMR (282 MHz, CDCl₃) δ−112.8.

4. Large scale reactions

(1) Ethyl 3-fluoro-2-methyl-4-oxo-4-phenyl-2(E)-butenoate (3a). Following Conditions A, a mixture of ethyl 2-methyl-4-phenyl-2,3-butadienoate (1a) (1.0130 g, 5.0 mmol), Selectfluor™ (95%, 5.5996 g, 15.0 mmol), and 50 mL of H₂O–MeCN (premixed, 0.9 μL mL⁻¹) were added into a flame-dried Schlenk vessel which was pre-evacuated and backfilled with nitrogen three times. The resulting mixture was then heated at 80 °C with an oil bath. After 11 h, the reaction was complete as monitored by TLC. The reaction mixture was quenched with 50 mL of H₂O, extracted with ether (100 mL + 2 × 25 mL), washed with 50 mL of brine, and dried over Na₂SO₄. Filtration, evaporation, and purification by chromatography (petroleum ether–ethyl acetate = 80 : 1 to 20 : 1) on silica gel afforded 3a (0.5162 g, 44%) and 4a (0.0323 g, 3%), respectively.

(2) 4-Fluoro-3-methyl-5-phenyl-2(5H)-furanone (4a). Following Conditions B, a mixture of ethyl 2-methyl-4-phenyl-2,3-butadienoate (1a) (1.0101 g, 5.0 mmol) and Selectfluor™ (95%, 3.1655 g, 8.5 mmol) were stirred in a mixture of 33.5 mL of MeCN and 16.5 mL of water at 80 °C in an oil bath. After 15 h, the reaction was complete as monitored by TLC. The reaction mixture was quenched with 50 mL of H₂O, extracted with ether (100 mL + 2 × 25 mL), washed with 50 mL of brine, and dried over Na₂SO₄. Filtration, evaporation, and purification by chromatography (petroleum ether–ethyl acetate = 30 : 1) on silica gel afforded 4a (0.5532 g, 58%).

Acknowledgements

Financial support from the National Basic Research Program of China (NO. 2009CB825300) and National Natural Sciences Foundation of China (20972135) is greatly appreciated. Shengming Ma is a Qiu Shi Adjunct Professor at Zhejiang University. We thank Mr Jing Li for reproducing the results presented in Table 2, entries 4 and 9 and Table 3 entries 5, 14, and 15.

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Footnote

† Electronic supplementary information (ESI) available: The synthesis of new 2,3-allenoates 1j, 1l, and 1q and ¹H, and ¹³C spectra for all compounds. See DOI: 10.1039/b917793k

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