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Article

Visible Light-Mediated Monofluoromethylation/Acylation of Olefins by Dual Organo-Catalysis

by
Jiuli Xia
1,
Yunliang Guo
2,
Zhiguang Lv
1,
Jiaqiong Sun
2,*,
Guangfan Zheng
1,* and
Qian Zhang
1,3
1
Key Laboratory of Functional Organic Molecule Design & Synthesis of Jilin Province, Department of Chemistry, Northeast Normal University, Changchun 130024, China
2
School of Environment, Northeast Normal University, Changchun 130117, China
3
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China
*
Authors to whom correspondence should be addressed.
Molecules 2024, 29(4), 790; https://doi.org/10.3390/molecules29040790
Submission received: 31 December 2023 / Revised: 1 February 2024 / Accepted: 6 February 2024 / Published: 8 February 2024
(This article belongs to the Special Issue Green Catalysis in Organic Synthesis)
Browse Figures
Versions Notes

Abstract

:
Monofluoromethyl (CH2F) motifs exhibit unique bioactivities and are considered privileged units in drug discovery. The radical monofluoromethylative difunctionalization of alkenes stands out as an appealing approach to access CH2F-containing compounds. However, this strategy remains largely underdeveloped, particularly under metal-free conditions. In this study, we report on visible light-mediated three-component monofluoromethylation/acylation of styrene derivatives employing NHC and organic photocatalyst dual catalysis. A diverse array of α-aryl-β-monofluoromethyl ketones was successfully synthesized with excellent functional group tolerance and selectivity. The mild and metal-free CH2F radical generation strategy from NaSO2CFH2 holds potential for further applications in fluoroalkyl radical chemistry.

Graphical Abstract

1. Introduction

The incorporation of fluoroalkyl groups into readily available molecules has garnered increasing attention due to the prevalence of fluoroalkyl-containing compounds in bioactive molecules and drug discovery [1,2,3,4,5]. Among various methodologies [6], the radical approach [7,8,9,10,11,12,13,14] has emerged as particularly noteworthy due to its mild conditions, broad substrate scope, and high selectivity, offering compelling alternatives for synthesizing fluoroalkyl-containing compounds. Notably, CH2F, as a distinct fluoroalkyl group, has been recognized for its potential as a metabolically stable and lipophilic bioisostere for NH2, OH, SH, etc. and is thus considered a privileged unit in drug discovery (Scheme 1A, Left) [15,16]. For example, fluticasone is a widely used corticosteroid drug, and β-fluorinated amino acid could act as an enzyme inhibitor and be suitable against Parkinson’s disease (Scheme 1A, Right) [17]. However, compared with the well-established well-developed radical installation of CF3 or CF2H and CF2R groups, radical monofluoromethylation [18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37] represents an emerging area with great demand. Olefins, being fundamental and prevalent chemical feedstocks, have witnessed considerable progress in transition metal (TM) catalysis including radical hydromonofluoromethylation [25] and monofluoromethylative difunctionalization [26,27,28,29,30,31], where TMs serve as redox catalysts [25,26,27] or photocatalysts (PC) [28,29,30,31]. Metal-free transformations mediated by visible light are particularly attractive owing to their mild conditions and the potential to reduce costs and toxicity associated with metal catalysts. In this context, in 2021, the Chen and Wang group [32] achieved σ-hole effect-facilitated photolysis of phosphonium iodide salts for the monofluoromethylation/acylation of olefins, while the Gouverneur [33] and Gaunt [34] groups independently developed radical hydrofluoromethylation of alkenes using CH2FI. The utilization of organo-photocatalysts has further enriched the initiation pathways for CH2F radicals. Koike, Akita, and co-workers [35,36] developed a highly reducing organic PC (1,4-bis(diphenylamino)naphthalene) to catalyze the hydroxy-monofluoromethylation of alkenes via a radical–polar crossover strategy. Despite the significance of these accomplishments, developing a novel organic PC-catalyzed radical difunctionalization system with a bench-stable and cost-effective CFH2 source was highly desirable.
On the other hand, stemming from the groundbreaking contributions of Studer [37,38], Ohmiya [39,40], and Chi [41] et al., NHC-attached persistent Breslow intermediate radicals (BIR) [42,43,44] have emerged as valuable acyl radical equivalents, enabling radical-radical cross-coupling and thereby paving the way for a new paradigm in radical acylation chemistry [45,46,47,48]. In radical NHC catalysis, persistent BIR and transient radical species can be concurrently generated at a comparable rate through a single electron transfer process. The highly selective radical addition/coupling (RAC) scenario [49,50,51] involving olefins, wherein transient radicals add to double bonds and are subsequently trapped by BIR, provides alternative routes for the precise construction of functionalized ketone units. As demonstrated by Studer [52,53,54,55,56,57,58,59,60], Schedit [61,62,63,64,65,66,67], and others [68,69,70,71,72,73,74], carboxylic acid derivatives can act as both sources of BIR and oxidants under the cooperation of NHC with PC, which in combination with reductive radical sources realizing radical acylative functionalization of olefins [52,53,54,55,56,57,67,68,69,70,71,72,73], make it a promising area of research. However, the photoredox cycle has predominantly focused on the reductive quenching mechanism. Inspired by those elegant approaches and our continuous interests in NHC catalysis [75,76,77,78] and greener transformation [79,80,81], we now report our discovery in visible light-mediated dual organocatalyzed three-component radical monofluoromethylation/acylation of olefins, in which BIR was generated by oxidative quenching [67,75] of PC* by NHC-acyl adduct.

2. Results and Discussion

We tested the monofluoromethylation/acylation system by employing styrene (1a), benzoyl fluoride (2a), and H2FCSO2Na (3) as model substrates; NHC-1 as a catalyst; 4-CzIPN as a PC; Cs2CO3 as a base; and dichloromethane (DCM) as the solvent under blue LED irradiation. To our delight, the desired β-monofluoromethylated ketone 4 was separated in 50% yield (Table 1, Entry 1). Switching the PC to an Ir-based photocatalyst could generate 4 in slightly lower yields (Entries 2–4). Screening of NHCs (Entries 5–8) indicates that NHC-2 is the optimal choice (Entry 5). Alternative solvents were tested, and it was found that dichloroethane (DCE, 55%), acetone (61%), toluene (64%), and chloroform (65%) exhibited similar efficiency to DCM, while benzo trifluoride (PhCF3, 36%) and tetrahydrofuran (THF, 20%) provided substantially reduced yields (Entries 9–15). Fortunately, by switching the solvent to acetonitrile (CH3CN), the desired 4 was isolated in an 89% yield and 12% ee (Entry 14). Further evaluation of bases was carried out, and decreased yields were obtained for 4 (Entries 16–17). Because of the challenges originated from chiral induction of radical–radical cross-coupling (RRCC), no satisfied enantioselectivity was observed (see Figure S1). Employment of racemic NHC-2 has no apparent effect on the reaction efficiency, and 4 could be separated in 90% yield (Entry 18); thus, these conditions were identified as conditions A for evaluation of the substrate scope.
With the optimized conditions in hand, the application scope and limitations of the olefins were evaluated by employing benzoyl fluoride (2a) as an acylating reagent and H2FCSO2Na as a CH2F radical precursor, and the results are summarized in Scheme 2. Aryl olefins bearing electron-donating (alkyl, alkoxy, phenyl), halogen (F, Cl, Br), and electron-withdrawing groups (cyano, carbonyl, and ester carbonyl) at the para-position of aryl rings were well tolerated, affording monofluoromethylation/acylation products 4–16 in 46–95% yields. Aryl alkenes with electron-donating groups exhibit extremely high reactivity (82–95% yields), while halogen (50–66%) and electron-withdrawing groups (45–77%) deliver targets with moderate yields. Moreover, the benzyl chloride motif was also tolerated in our catalytic system, as identified by the formation of 16 (42%). Ortho- and meta-substituted aryl alkenes proved to be valuable substrates, delivering 17–20 in 60–80% yields. High reactivity (17, 80%; 18, 71%) was observed for ortho-substituted aryl olefins, indicating excellent compatibility with sterically hindered olefins. Di-substituted aryl olefins were well tolerated, generating 21 in 83% yield. Fused carbon ring (naphthalene, anthracene)- and fused heterocyclic (quinoline, dibenzo[b,d]furan, 1,3-benzodioxole, indole, benzofuran)-substituted olefins were also suitable for this transformation, delivering the desired ketones 22–28 in 37–83% yields. Michael alkenes could deliver monofluoromethylation/acylation product 29 in 23% yield. Various non-activated aliphatic olefins, including terminal, internal, and cyclo-olefins, were tested but did not work at all, which might be due to hindrance by a polar mismatch of nucleophilic H2FC radical and aliphatic olefin. Additionally, substrate scope regarding aroyl fluoride was subsequently investigated under the established photocatalytic system (Scheme 3). In general, the reactions proceed smoothly with various substituted aroyl fluorides 2, 4-methylstyrene (1b), and H2FCSO2Na. Para-substituted aroyl fluorides were first investigated, and electron-rich (30, 31) and halogen-substituted (32, 33) aroyl fluorides reacted well, with desired products being obtained in 53–80% yields. Electron-withdrawing groups (CN, OCF3) could also be tolerated, albeit with low reactivity compared to electron-rich ones; for strong electron-withdrawing trifluoromethoxy substituted 34, only a 27% yield was observed. Ortho- (36, 54%), meta- (37, 50%; 38, 42%) substituted, and 3,5-disubstituted (39, 50%) aroyl fluorides were applicable, indicating tolerance to steric effect. Finally, the aroyl fluorides could be extended to naphthyl or thiophene ones, delivering 40 and 41 in 61% and 54% yields, respectively. Broad substrate scope and good functional group tolerance were observed for this metal-free monofluoromethylation/acylation system.

3. Mechanistic Investigation

Preliminary mechanistic investigations were carried out to gain insight into this transformation (Scheme 4). The control experiment indicates that the NHCs, PC, and LED irradiation were indispensable for the formation of 4 (Scheme 4A). The addition of the radical scavenger 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO; 2.0 equiv) could completely inhibit the formation of 4; CH2F-trapped byproduct 42 (12%) and benzoyl-trapped byproduct (43, 43%) were observed (Scheme 4B), indicating the possibility of involvement of radical species. Acyl NHC-adduct 44 exhibits good catalytic reactivity, suggesting the intermediacy of 44 (Scheme 4C). Light on/off experiments were carried out employing CD3CN as solvents, demonstrating that formation 5 only occurs under blue LED irradiation; thus, the radical chain mechanism seems not preferred (Scheme 4D). Stern–Volmer quenching studies were carried out to gain insight into the photo redox cycle (Scheme 4E). Emission of excited state PC* was preferentially quenched by 44 instead of alkene 1a or H2FCSO2Na. Thus, the oxidative quenching progress of PC* by 44 seems more favorable than the reductive quenching cycles.
Based on the above mechanistic investigations and previous reports, a plausible reaction mechanism is depicted in Scheme 5. Firstly, benzoyl fluoride 3a undergoes substitution by NHC, generating NHC-adduct I (44). Oxidative quenching between PC* and I might occur, delivering BIR III and oxidative state PC+•. Single electron oxidation of CH2FSO2Na by PC+• affords CH2F radical via sequential release of SO2. Selective addition of CH2F radical to double bonds generates benzyl radicals that are trapped by persistent BIR, delivering VI and realizing the RA/RACC cascade. Finally, NHC-fragmentation of VI could provide target 4 and regenerate the NHC catalyst. The excellent regioselectivity may originate from the persistent radical effect [82].

4. Materials and Methods

4.1. Materials and Instruments

All reactions were conducted under a nitrogen atmosphere. Reagents were sourced from commercial suppliers and utilized without further purification unless stated otherwise. Anhydrous solvents were employed as per distillation procedures. Reaction progress was monitored using thin-layer chromatography (TLC) on 0.25 mm pre-coated silica gel plates.
1H NMR spectra were recorded at 25 °C using either a Bruker 600 or 500, Varian 500 MHz instrument, while 13C NMR spectra were obtained at 25 °C using a Bruker 151, Varian 126 MHz instrument, both in CDCl3 with TMS as the internal standard. 19F NMR spectra were recorded at 25 °C using a Bruker 565 MHz spectrometer. Chemical shifts for 1H and 13C NMR spectra are reported in parts per million (ppm) relative to the internal standards tetramethylsilane (0 ppm for 1H NMR) and CDCl3 (77.0 ppm for 13C NMR), respectively. 19F NMR chemical shifts were determined relative to CFCl3 as the external standard; low field was positive.
The designations m, s, d, t, and q represent multiplet, singlet, doublet, triplet, and quartet, respectively. High-resolution mass spectra (HRMS) were acquired using a Bruck micrOTOF instrument.
For photochemical reactions, we employed the RLH-18 8-position Photo Reaction System manufactured by Beijing Rogertech Co. Ltd. based in Beijing, China. This photo reactor is equipped with 8 blue light 40 W LEDs. The energy peak wavelength of these 10 W blue light LEDs is 453.6 nm, with a peak width at half-height of 20.4. The irradiation vessel is a borosilicate glass test tube, with LED irradiation passing through a high-reflection channel to the test tube. The path length is 2 cm, and there is no filter between the LED and the test tube.

4.2. General Procedure for the Synthesis of 4

In a nitrogen-filled glove box, a vial equipped with a magnetic stir bar was charged with rac-NHC-2 (6.3 mg, 0.015 mmol), Cs2CO3 (65.2 mg, 0.2 mmol), PC-1 (1.2 mg, 0.0015 mmol), 3 (36.0 mg, 0.3 mmol) and CH3CN (2.0 mL). Then 1a (0.1 mmol) and sulfinate 2a (0.3 mmol) were added. The vial was removed from the glovebox, and then the reaction mixture was irradiated with blue LED at 30 °C for 12 h. After that, the residue was purified by flash column chromatography (petroleum ether/ethyl acetate = 100:1) to give the corresponding product 4.
  • 4-fluoro-1,2-diphenylbutan-1-one (4) Purification by column chromatography on silica- gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound as a yellow oil (yield 22.3 mg, 92%). 1H NMR (500 MHz, Chloroform-d) δ 7.99–7.92 (m, 2H), 7.51–7.46 (m, 1H), 7.39 (d, J = 7.9 Hz, 2H), 7.34–7.29 (m, 4H), 7.26–7.18 (m, 1H), 4.84 (t, J = 7.4 Hz, 1H), 4.57–4.29 (m, 2H), 2.74–2.46 (m, 1H), 2.34–2.08 (m, 1H). 13C NMR (151 MHz, Chloroform-d) δ 199.07, 138.49, 136.46, 133.01, 129.14, 128.79, 128.54, 128.35, 127.35, 81.76 (d, J = 164.1 Hz), 49.02 (d, J = 3.1 Hz), 34.41 (d, J = 19.2 Hz). 19F NMR (565 MHz, Chloroform-d) δ −221.37 (tdd, J = 45.20, 28.25, 22.60 Hz, 1F). HRMS (ESI) (m/z): calcd for C16H15FNaO ([M + Na]+), 265.0999; found, 265.1003.
  • 4-fluoro-1-phenyl-2-(p-tolyl)butan-1-one (5) Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound as a yellow oil (yield 24.4 mg, 92%). 1H NMR (500 MHz, Chloroform-d) δ 8.13–7.84 (m, 2H), 7.49–7.44 (m, 1H), 7.37 (t, J = 7.7 Hz, 2H), 7.22–7.14 (m, 2H), 7.10 (d, J = 7.9 Hz, 2H), 4.80 (t, J = 7.4 Hz, 1H), 4.55–4.27 (m, 2H), 2.62–2.50 (m, 1H), 2.28 (s, 3H), 2.24–2.08 (m, 1H). 13C NMR (151 MHz, Chloroform-d) δ 199.20, 137.03, 136.50, 135.42, 132.94, 129.84, 128.78, 128.51, 128.21, 81.81 (d, J = 163.7 Hz), 48.62 (d, J = 3.1 Hz), 34.37 (d, J = 19.5 Hz), 21.01. 19F NMR (565 MHz, Chloroform-d) δ -221.34 (tdd, J = 45.20, 28.25, 22.60 Hz, 1F). HRMS (ESI) (m/z): calcd for C17H17FNaO ([M + Na]+), 279.1156; found, 279.1162.
  • 2-(4-ethylphenyl)-4-fluoro-1-phenylbutan-1-one (6) Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound as a yellow oil (yield 21.8 mg, 82%). 1H NMR (500 MHz, Chloroform-d) δ 7.97 (dd, J = 8.1, 1.4 Hz, 2H), 7.52–7.44 (m, 1H), 7.38 (t, J = 7.7 Hz, 2H), 7.22 (d, J = 7.9 Hz, 2H), 7.13 (d, J = 7.8 Hz, 2H), 4.82 (t, J = 7.4 Hz, 1H), 4.54–4.31 (m, 2H), 2.58 (q, J = 7.6 Hz, 3H), 2.30–2.10 (m, 1H), 1.19 (t, J = 7.7 Hz, 3H). 13C NMR (151 MHz, Chloroform-d) δ 199.22, 143.31, 136.51, 135.58, 132.95, 128.81, 128.62, 128.52, 128.25, 81.85 (d, J = 163.8 Hz), 48.59 (d, J = 3.2 Hz), 34.42 (d, J = 19.2 Hz), 28.39, 15.31. 19F NMR (565 MHz, Chloroform-d) δ −221.37 (tdd, J = 45.20, 28.25, 22.60 Hz, 1F). HRMS (ESI) (m/z): calcd for C18H19FNaO ([M + Na]+), 293.1312; found, 293.1307.
  • 2-(4-(tert-butyl)phenyl)-4-fluoro-1-phenylbutan-1-one (7) Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound as a yellow oil (yield 25.2 mg, 85%). 1H NMR (500 MHz, Chloroform-d) δ 8.02–7.96 (m, 2H), 7.51–7.46 (m, 1H), 7.43–7.35 (m, 2H), 7.33–7.28 (m, 2H), 7.24–7.21 (m, 2H), 4.82 (t, J = 7.4 Hz, 1H), 4.52–4.29 (m, 2H), 2.63–2.48 (m, 1H), 2.24–2.09 (m, 1H), 1.26 (s, 9H). 13C NMR (151 MHz, Chloroform-d) δ 199.25, 150.19, 136.57, 135.22, 132.95, 128.83, 128.52, 127.93, 126.02, 81.88 (d, J = 163.7 Hz), 48.40 (d, J = 3.5 Hz), 34.52, 34.41 (d, J = 7.0 Hz), 31.27. 19F NMR (565 MHz, Chloroform-d) δ -221.32 (tdd, J = 45.20, 28.25, 22.60 Hz, 1F). HRMS (ESI) (m/z): calcd for C20H23FNaO ([M + Na]+), 321.1625; found, 321.1625.
  • 4-fluoro-2-(4-methoxyphenyl)-1-phenylbutan-1-one (8) Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound as a yellow oil (yield 22.6 mg, 83%). 1H NMR (500 MHz, Chloroform-d) δ 8.03–7.89 (m, 2H), 7.51–7.46 (m, 1H), 7.39 (t, J = 7.7 Hz, 2H), 7.34–7.29 (m, 4H), 4.86 (t, J = 7.3 Hz, 1H), 4.52 (s, 3H), 4.51–4.26 (m, 2H), 2.65–2.49 (m, 1H), 2.26–2.08 (m, 1H). 13C NMR (151 MHz, Chloroform-d) δ 198.86, 138.73, 136.60, 136.32, 133.17, 129.36, 128.77, 128.72, 128.62, 81.65 (d, J = 164.1 Hz), 48.60 (d, J = 3.3 Hz), 45.73, 34.39 (d, J = 19.5 Hz). 19F NMR (565 MHz, Chloroform-d) δ -221.42 (tdd, J = 45.20, 28.25, 22.60 Hz, 1F). HRMS (ESI) (m/z): calcd for C17H17FNaO2 ([M + Na]+), 295.1105; found, 295.1107.
  • 2-([1,1’-biphenyl]-4-yl)-4-fluoro-1-phenylbutan-1-one (9) Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound as a yellow oil (yield 28.6 mg, 90%). 1H NMR (500 MHz, Chloroform-d) δ 8.27–8.12 (m, 2H), 8.06–7.94 (m, 2H), 7.73–7.59 (m, 1H), 7.54–7.46 (m, 3H), 7.39 (dt, J = 21.2, 7.8 Hz, 3H), 7.27–7.19 (m, 2H), 7.12 (dd, J = 7.9, 2.3 Hz, 1H), 4.90 (t, J = 7.3 Hz, 1H), 4.60–4.25 (m, 2H), 2.67–2.40 (m, 1H), 2.36–2.13 (m, 1H). 13C NMR (151 MHz, Chloroform-d) δ 198.78, 164.92, 151.46, 140.12, 136.31, 133.66, 133.24, 130.16, 130.11, 129.40, 128.80, 128.66, 128.59, 125.86, 121.55, 120.85, 81.62 (d, J = 164.2 Hz), 48.65 (d, J = 3.3 Hz), 34.48 (d, J = 19.2 Hz). 19F NMR (565 MHz, Chloroform-d) δ -221.44 (tdd, J = 45.20, 28.25, 22.60 Hz, 1F). HRMS (ESI) (m/z): calcd for C22H19FNaO ([M + Na]+), 341.1312; found, 341.1309.
  • 7. 4-fluoro-2-(4-fluorophenyl)-1-phenylbutan-1-one (10) Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound as a yellow oil (yield 14.3 mg, 55%). 1H NMR (500 MHz, Chloroform-d) δ 8.07–7.88 (m, 2H), 7.53–7.47 (m, 1H), 7.39 (dd, J = 8.5, 7.1 Hz, 2H), 7.31–7.24 (m, 2H), 7.03–6.94 (m, 2H), 4.84 (t, J = 7.4 Hz, 1H), 4.63–4.20 (m, 2H), 2.65–2.48 (m, 1H), 2.30–2.06 (m, 1H). 13C NMR (151 MHz, Chloroform-d) δ 199.04, 162.04 (d, J = 246.3 Hz), 161.22, 136.28, 134.14 (d, J = 3.5 Hz), 133.18, 129.91 (d, J = 8.1 Hz), 128.74, 128.62, 116.06 (d, J = 21.4 Hz), 81.65 (d, J = 164.2 Hz), 48.08 (d, J = 3.1 Hz), 34.42 (d, J = 19.3 Hz).19F NMR (565 MHz, Chloroform-d) δ −114.93–−115.04 (m, 1F), −221.57 (tdd, J = 45.20, 28.25, 22.60 Hz, 1F). HRMS (ESI) (m/z): calcd for C16H14F2NaO ([M + Na]+), 283.0904; found, 283.0900.
  • 2-(4-chlorophenyl)-4-fluoro-1-phenylbutan-1-one (11) Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound as a yellow oil (yield 18.2 mg, 66%). 1H NMR (500 MHz, Chloroform-d) δ 7.95–7.91 (m, 2H), 7.54–7.48 (m, 1H), 7.39 (t, J = 7.7 Hz, 2H), 7.31–7.20 (m, 4H), 4.83 (t, J = 7.4 Hz, 1H), 4.63–4.22 (m, 2H), 2.64–2.49 (m, 1H), 2.30–2.06 (m, 1H). 13C NMR (151 MHz, Chloroform-d) δ 198.78, 136.93, 136.19, 133.35, 133.26, 129.70, 129.34, 128.74, 128.65, 81.55 (d, J = 164.2 Hz), 48.24 (d, J = 3.2 Hz), 34.31 (d, J = 19.3 Hz). 19F NMR (565 MHz, Chloroform-d) δ −221.55 (tdd, J = 45.20, 28.25, 22.60 Hz, 1F). HRMS (ESI) (m/z): calcd for C16H14ClFNaO ([M + Na]+), 299.0609; found, 299.0613.
  • 9. 2-(4-bromophenyl)-4-fluoro-1-phenylbutan-1-one (12) Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound as a yellow oil (yield 16.1 mg, 50%). 1H NMR (500 MHz, Chloroform-d) δ 7.98–7.88 (m, 2H), 7.50 (t, J = 7.5 Hz, 1H), 7.45–7.37 (m, 4H), 7.19 (d, J = 8.4 Hz, 2H), 4.82 (t, J = 7.4 Hz, 1H), 4.54–4.28 (m, 2H), 2.65–2.42 (m, 1H), 2.23–2.03 (m, 1H). 13C NMR (151 MHz, Chloroform-d) δ 198.68, 137.46, 136.16, 133.29, 132.30, 130.06, 128.74, 128.67, 121.46, 81.54 (d, J = 164.2 Hz), 48.31 (d, J = 3.2 Hz), 34.27 (d, J = 19.3 Hz). 19F NMR (565 MHz, Chloroform-d) δ −221.54 (tdd, J = 45.20, 28.25, 22.60 Hz, 1F). HRMS (ESI) (m/z): calcd for C16H15BrFO ([M + H]+), 321.0285; found, 321.0283.
  • 4-(4-fluoro-1-oxo-1-phenylbutan-2-yl)benzonitrile (13) Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound as a yellow oil (yield 12.0 mg, 45%). 1H NMR (500 MHz, Chloroform-d) δ 7.96–7.89 (m, 2H), 7.60 (d, J = 8.4 Hz, 2H), 7.55–7.50 (m, 1H), 7.48–7.37 (m, 4H), 4.93 (t, J = 7.3 Hz, 1H), 4.58–4.16 (m, 2H), 2.68–2.52 (m, 1H), 2.24–2.08 (m, 1H). 13C NMR (151 MHz, Chloroform-d) δ 198.09, 143.85, 135.97, 133.61, 132.89, 129.19, 128.81, 128.71, 118.42, 111.51, 81.76 (d, J = 164.2 Hz), 48.84 (d, J = 3.2 Hz), 34.32 (d, J = 19.3 Hz). 19F NMR (565 MHz, Chloroform-d) δ −221.48 (tdd, J = 45.20, 28.25, 22.60 Hz, 1F). HRMS (ESI) (m/z): calcd for C17H14FNNaO ([M + Na]+), 290.0952; found, 290.0961.
  • 2-(4-acetylphenyl)-4-fluoro-1-phenylbutan-1-one (14) Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound as a yellow oil (yield 13.9 mg, 49%). 1H NMR (500 MHz, Chloroform-d) δ 7.99–7.94 (m, 2H), 7.92 (d, J = 1.9 Hz, 1H), 7.81 (dt, J = 7.8, 1.4 Hz, 1H), 7.56–7.48 (m, 2H), 7.40 (td, J = 7.6, 5.6 Hz, 3H), 4.94 (t, J = 7.4 Hz, 1H), 4.58–4.17 (m, 2H), 2.68–2.59 (m, 1H), 2.57 (s, 3H), 2.26–2.10 (m, 1H). 13C NMR (151 MHz, Chloroform-d) δ 198.75, 197.74, 139.19, 137.92, 136.18, 133.32, 132.90, 129.43, 128.76, 128.70, 128.11, 127.55, 81.56 (d, J = 164.2 Hz), 48.71 (d, J = 3.4 Hz), 34.46 (d, J = 19.3 Hz), 26.69. 19F NMR (565 MHz, Chloroform-d) δ −221.30 (tdd, J = 45.20, 28.25, 22.60 Hz, 1F). HRMS (ESI) (m/z): calcd for C18H17FNaO2 ([M + Na]+), 307.1104; found, 307.1112.
  • methyl-4-(4-fluoro-1-oxo-1-phenylbutan-2-yl)benzoate (15) Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound as a yellow oil (yield 23.1 mg, 77%). 1H NMR (500 MHz, Chloroform-d) δ 7.97 (d, J = 8.2 Hz, 2H), 7.94 (dd, J = 7.0, 5.5 Hz, 2H), 7.52–7.46 (m, 1H), 7.38 (dd, J = 8.2, 6.5 Hz, 4H), 4.92 (t, J = 7.3 Hz, 1H), 4.61–4.27 (m, 2H), 3.87 (s, 3H), 2.63–2.57 (m, 1H), 2.24–2.10 (m, 1H). 13C NMR (151 MHz, Chloroform-d) δ 198.99, 169.26, 149.89, 136.33, 135.87, 133.18, 129.34, 128.77, 128.62, 122.19, 81.65 (d, J = 164.0 Hz), 48.20 (d, J = 3.0 Hz), 34.49 (d, J = 19.5 Hz), 21.11. 19F NMR (565 MHz, Chloroform-d) δ −221.35 (tdd, J = 45.20, 28.25, 22.60 Hz, 1F). HRMS (ESI) (m/z): calcd for C18H17FNaO3 ([M + Na]+), 323.1054; found, 323.1053.
  • 2-(4-(chloromethyl)phenyl)-4-fluoro-1-phenylbutan-1-one (16) Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound as a yellow oil (yield 12.2 mg, 42%). 1H NMR (500 MHz, Chloroform-d) δ 7.99–7.90 (m, 2H), 7.54–7.47 (m, 1H), 7.39 (t, J = 7.7 Hz, 2H), 7.35–7.28 (m, 4H), 4.86 (t, J = 7.3 Hz, 1H), 4.52 (s, 2H), 4.51–4.28 (m, 2H), 2.66–2.49 (m, 1H), 2.27–2.10 (m, 1H). 13C NMR (151 MHz, Chloroform-d) δ 198.86, 138.73, 136.60, 136.32, 133.17, 129.35, 128.77, 128.71, 128.61, 81.65 (d, J = 164.2 Hz), 48.61 (d, J = 3.1 Hz), 45.73, 34.38 (d, J = 19.2 Hz). 19F NMR (565 MHz, Chloroform-d) δ −221.43 (tdd, J = 45.20, 28.25, 22.60 Hz, 1F). HRMS (ESI) (m/z): calcd for C17H16ClFNaO ([M + Na]+), 313.0765; found, 313.0763.
  • 4-fluoro-1-phenyl-2-(o-tolyl)butan-1-one (17) Purification by column chromatography on silica- gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound as a yellow oil (yield 20.5 mg, 80%). 1H NMR (500 MHz, Chloroform-d) δ 7.85–7.82 (m, 2H), 7.46 (t, J = 7.4 Hz, 1H), 7.36 (t, J = 7.7 Hz, 2H), 7.21 (d, J = 7.3 Hz, 1H), 7.14–7.04 (m, 3H), 4.97 (dd, J = 8.1, 6.1 Hz, 1H), 4.63–4.30 (m, 2H), 2.67–2.56 (m, 1H), 2.54 (s, 3H), 2.23–1.97 (m, 1H). 13C NMR (151 MHz, Chloroform-d) δ 199.84, 137.38, 136.82, 135.46, 132.91, 131.22, 128.55, 128.45, 127.29 (d, J = 3.5 Hz), 126.82, 81.87 (d, J = 164.5 Hz), 45.32 (d, J = 2.9 Hz), 34.12(d, J = 19.6 Hz), 19.59. 19F NMR (565 MHz, Chloroform-d) δ −219.78 (tt, J = 45.20, 22.60 Hz, 1F). HRMS (ESI) (m/z): calcd for C17H17FNaO ([M + Na]+), 279.1155; found, 279.1159.
  • 4-fluoro-2-(2-methoxyphenyl)-1-phenylbutan-1-one (18) Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound as a yellow oil (yield 19.3 mg, 71%). 1H NMR (500 MHz, Chloroform-d) δ 8.06–7.89 (m, 2H), 7.44 (t, J = 7.4 Hz, 1H), 7.34 (t, J = 7.8 Hz, 2H), 7.18 (ddd, J = 8.2, 7.4, 1.7 Hz, 1H), 7.11 (dd, J = 7.6, 1.7 Hz, 1H), 6.94–6.82 (m, 2H), 5.25 (t, J = 7.2 Hz, 1H), 4.54–4.34 (m, 2H), 3.90 (s, 3H), 2.72–2.47 (m, 1H), 2.19–2.03 (m, 1H). 13C NMR (151 MHz, Chloroform-d) δ 199.80, 156.22, 136.46, 132.80, 128.57, 128.51 128.49, 128.35, 127.41, 111.09, 82.22 (d, J = 164.1 Hz), 55.62, 41.48 (d, J = 4.5 Hz), 33.40 (d, J = 19.9 Hz). 19F NMR (565 MHz, Chloroform-d) δ −219.92 (tt, J = 45.20, 22.60 Hz, 1F). HRMS (ESI) (m/z): calcd for C17H17FNaO2 ([M + Na]+), 295.1104; found, 295.1104.
  • 4-fluoro-1-phenyl-2-(m-tolyl)butan-1-one (19) Purification by column chromatography on silica- gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound as a yellow oil (yield 20.2 mg, 79%). 1H NMR (500 MHz, Chloroform-d) δ 8.02–7.93 (m, 2H), 7.54–7.43 (m, 1H), 7.38 (dd, J = 8.4, 7.0 Hz, 2H), 7.19 (td, J = 7.4, 1.2 Hz, 1H), 7.11 (d, J = 7.7 Hz, 2H), 7.02 (d, J = 7.6 Hz, 1H), 4.80 (t, J = 7.3 Hz, 1H), 4.55–4.28 (m, 2H), 2.64–2.48 (m, 1H), 2.30 (s, 3H), 2.23–2.09 (m, 1H). 13C NMR (151 MHz, Chloroform-d) δ 199.17, 138.86, 138.40, 136.52, 133.00, 128.99, 128.84, 128.82, 128.54, 128.16, 125.53, 81.69 (d, J = 165.1 Hz), 48.96 (d, J = 3.1 Hz), 34.45 (d, J = 19.3 Hz), 21.42. 19F NMR (565 MHz, Chloroform-d) δ −221.30 (tdd, J = 45.20, 28.25, 22.60 Hz, 1F). HRMS (ESI) (m/z): calcd for C17H17FNaO ([M + Na]+), 279.1155; found, 279.1147.
  • 2-(3-chlorophenyl)-4-fluoro-1-phenylbutan-1-one (20). Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound as a yellow oil (yield 16.6 mg, 60%). 1H NMR (500 MHz, Chloroform-d) δ 7.96 (d, J = 6.9 Hz, 2H), 7.56–7.49 (m, 1H), 7.41 (t, J = 7.7 Hz, 2H), 7.32 (d, J = 1.8 Hz, 1H), 7.28–7.18 (m, 3H), 4.84 (t, J = 7.4 Hz, 1H), 4.61–4.22 (m, 2H), 2.69–2.49 (m, 1H), 2.34–2.07 (m, 1H). 13C NMR (151 MHz, Chloroform-d) δ 198.52, 140.45, 136.18, 134.94, 133.31, 130.36, 128.76, 128.69, 128.39, 127.68, 126.60, 81.56 (d, J = 164.3 Hz), 80.97, 48.50 (d, J = 3.0 Hz), 34.39 (d, J = 19.5 Hz). 19F NMR (565 MHz, Chloroform-d) δ −221.47 (tdd, J = 45.20, 28.25, 22.60 Hz, 1F). HRMS (ESI) (m/z): calcd for C16H14ClFNaO ([M + Na]+), 299.0609; found, 299.0602.
  • 2-(3,5-dimethylphenyl)-4-fluoro-1-phenylbutan-1-1 (21) Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound as a yellow oil (yield 22.4 mg, 83%).1H NMR (500 MHz, Chloroform-d) δ 7.97 (dd, J = 8.4, 1.4 Hz, 2H), 7.52–7.46 (m, 1H), 7.38 (dd, J = 8.4, 7.1 Hz, 2H), 6.91 (s, 2H), 6.84 (s, 1H), 4.76 (t, J = 7.3 Hz, 1H), 4.57–4.30 (m, 2H), 2.62–2.46 (m, 1H), 2.28–2.22 (m, 6H), 2.20–2.09 (m, 1H). 13C NMR (151 MHz, Chloroform-d) δ 199.20, 138.65, 138.32, 136.57, 132.94, 129.05, 128.81, 128.51, 126.03, 81.76 (d, J = 165.3 Hz), 48.89 (d, J = 3.4 Hz), 34.49 (d, J = 19.2 Hz), 21.28. 19F NMR (565 MHz, Chloroform-d) δ −221.23 (tdd, J = 45.20, 28.25, 22.60 Hz, 1F). HRMS (ESI) (m/z): calcd for C18H19FNaO ([M + Na]+), 271.1492; found, 271.1495.
  • 4-fluoro-2-(naphthalen-2-yl)-1-phenylbutan-1-one (22) Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound as a yellow oil (yield 17.0 mg, 58%). 1H NMR (500 MHz, Chloroform-d) δ 8.00 (d, J = 7.7 Hz, 2H), 7.82–7.75 (m, 4H), 7.45 (dt, J = 8.1, 2.3 Hz, 4H), 7.37 (d, J = 7.7 Hz, 2H), 5.01 (t, J = 7.3 Hz, 1H), 4.64–4.14 (m, 2H), 2.77–2.51 (m, 1H), 2.45–2.17 (m, 1H). 13C NMR (151 MHz, Chloroform-d) δ 199.03, 136.43, 135.95, 133.64, 133.06, 132.56, 129.04, 128.83, 128.57, 127.78, 127.65, 127.38, 126.34, 126.11, 126.06, 81.72 (d, J = 164.9 Hz), 49.14 (d, J = 3.2 Hz), 34.42 (d, J = 19.3 Hz). 19F NMR (565 MHz, Chloroform-d) δ -221.32 (tdd, J = 45.20, 28.25, 22.60 Hz, 1F). HRMS (ESI) (m/z): calcd for C20H17FNaO ([M + Na]+), 315.1155; found, 315.1159.
  • 2-(anthracen-2-yl)-4-fluoro-1-phenylbutan-1-one (23) Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound as a yellow oil (yield 28.4 mg, 83%). 1H NMR (500 MHz, Chloroform-d) δ 8.18 (d, J = 7.0 Hz, 2H), 7.99 (d, J = 7.7 Hz, 2H), 7.63 (d, J = 7.4 Hz, 1H), 7.56–7.49 (m, 3H), 7.40 (dt, J = 20.8, 7.8 Hz, 3H), 7.28–7.20 (m, 2H), 7.12 (dd, J = 8.1, 2.3 Hz, 1H), 4.90 (t, J = 7.4 Hz, 1H), 4.63–4.19 (m, 2H), 2.68–2.50 (m, 1H), 2.28–2.07 (m, 1H). 13C NMR (151 MHz, Chloroform-d) δ 198.79, 164.93, 151.46, 140.13, 136.31, 133.67, 133.24, 130.17, 130.12, 129.40, 128.81, 128.66, 128.59, 125.87, 121.55, 120.86, 82.17, 81.09, 48.65 (d, J = 3.3 Hz), 34.48 (d, J = 19.4 Hz). 19F NMR (565 MHz, Chloroform-d) δ −221.44 (tdd, J = 45.20, 28.25, 22.60 Hz, 1F). HRMS (ESI) (m/z): calcd for C24H19FNaO ([M + Na]+), 365.1312; found, 365.1315.
  • 4-fluoro-1-phenyl-2-(quinolin-6-yl)butan-1-one (24) Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound as a yellow oil (yield 10.8 mg, 37%). 1H NMR (500 MHz, Chloroform-d) δ 8.92–8.83 (m, 1H), 8.08 (dd, J = 10.6, 8.4 Hz, 2H), 8.00 (s, 2H), 7.79–7.69 (m, 2H), 7.47 (t, J = 7.4 Hz, 1H), 7.40–7.35 (m, 3H), 5.06 (t, J = 7.3 Hz, 1H), 4.60–4.28 (m, 2H), 2.74–2.58 (m, 1H), 2.33–2.20 (m, 1H). 13C NMR (151 MHz, Chloroform-d) δ 198.81, 150.57, 147.51, 136.88, 136.28, 135.92, 133.26, 130.53, 129.88, 128.79, 128.66, 121.48, 81.61 (d, J = 164.4 Hz), 48.83 (d, J = 3.2 Hz), 34.50 (d, J = 19.5 Hz). 19F NMR (565 MHz, Chloroform-d) δ −221.36 (tdd, J = 45.20, 28.25, 22.60 Hz, 1F). HRMS (ESI) (m/z): calcd for C19H16FNNaO ([M + Na]+), 316.1108; found, 316.1113.
  • 2-(5a,9a-dihydrodibenzo[b,d]furan-3-yl)-4-fluoro-1-phenylbutan-1-one (25) Purification- by column chromatography on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound as a yellow oil (yield 13.3 mg, 40%). 1H NMR (500 MHz, Chloroform-d) δ 8.50 (d, J = 1.7 Hz, 1H), 8.01 (dd, J = 8.7, 1.8 Hz, 1H), 7.90 (d, J = 8.1 Hz, 1H), 7.81 (dd, J = 8.5, 3.5 Hz, 2H), 7.58–7.53 (m, 2H), 7.53–7.48 (m, 2H), 7.30 (t, J = 7.6 Hz, 2H), 7.20 (t, J = 7.4 Hz, 1H), 5.01 (t, J = 7.3 Hz, 1H), 4.60–4.31 (m, 2H), 2.73–2.56 (m, 1H), 2.31–2.15 (m, 1H). 13C NMR (151 MHz, Chloroform-d) δ 199.05, 138.60, 135.49, 133.79, 132.44, 130.60, 129.67, 129.17, 128.51, 128.39, 128.35, 127.66, 127.36, 126.69, 124.43, 81.83 (d, J = 163.7 Hz), 49.07 (d, J = 3.3 Hz), 34.46 (d, J = 19.2 Hz). 19F NMR (565 MHz, Chloroform-d) δ −221.34 (tdd, J = 50.85, 33.90, 28.25 Hz, 1F). HRMS (ESI) (m/z): calcd for C22H17FNaO2 ([M + Na]+), 355.1104; found, 355.1104.
  • 2-(benzo[d][1,3]dioxol-5-yl)-4-fluoro-1-phenylbutan-1-one (26) Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound as a yellow oil (yield 23.2 mg, 81%). 1H NMR (500 MHz, Chloroform-d) δ 8.04–7.84 (m, 2H), 7.52–7.46 (m, 1H), 7.40 (d, J = 7.7 Hz, 2H), 6.77 (d, J = 7.4 Hz, 2H), 6.73 (d, J = 8.0 Hz, 1H), 5.92–5.87 (m, 2H), 4.75 (t, J = 7.4 Hz, 1H), 4.56–4.28 (m, 2H), 2.60–2.45 (m, 1H), 2.19–2.01 (m, 1H). 13C NMR (151 MHz, Chloroform-d) δ 199.02, 148.23, 146.89, 136.39, 133.04, 132.04, 128.76, 128.56, 121.87, 108.79, 108.45, 101.14, 81.73 (d, J = 165.1 Hz), 48.51 (d, J = 3.1 Hz), 34.34 (d, J = 19.2 Hz), 29.71. 19F NMR (565 MHz, Chloroform-d) δ −221.48 (tdd, J = 50.85, 33.90, 22.60 Hz, 1F). HRMS (ESI) (m/z): calcd for C17H15FNaO3 ([M + Na]+), 309.0897; found, 309.0896.
  • 4-fluoro-1-phenyl-2-(1-tosyl-1H-indol-5-yl)butan-1-one (27) Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound as a yellow oil (yield 21.7 mg, 50%). 1H NMR (500 MHz, Chloroform-d) δ 7.95 (dd, J = 8.4, 1.4 Hz, 2H), 7.90 (d, J = 8.6 Hz, 1H), 7.80–7.72 (m, 2H), 7.52 (d, J = 3.7 Hz, 1H), 7.49–7.41 (m, 2H), 7.36 (t, J = 7.7 Hz, 2H), 7.29–7.22 (m, 1H), 7.21 (d, J = 8.1 Hz, 2H), 6.57 (d, J = 3.7 Hz, 1H), 4.91 (t, J = 7.4 Hz, 1H), 4.54–4.23 (m, 2H), 2.65–2.50 (m, 1H), 2.32 (s, 3H), 2.23–2.07 (m, 1H). 13C NMR (151 MHz, Chloroform-d) δ 199.17, 145.02, 136.41, 135.32, 133.98, 133.41, 133.04, 131.34, 129.94, 128.81, 128.55, 126.86, 126.85, 124.94, 121.04, 114.05, 108.68, 81.59 (d, J = 164.1 Hz), 48.61 (d, J = 3.3 Hz), 34.72 (d, J = 19.3 Hz), 21.56. 19F NMR (565 MHz, Chloroform-d) δ −221.38 (tdd, J = 45.20, 28.25, 22.60 Hz, 1F). HRMS (ESI) (m/z): calcd for C25H22FNNaO3S ([M + Na]+), 458.1196; found, 458.1198.
  • 2-(benzofuran-5-yl)-4-fluoro-1-phenylbutan-1-one (28) Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound as a yellow oil (yield 51.9 mg, 62%). 1H NMR (500 MHz, Chloroform-d) δ 7.99 (dd, J = 8.4, 1.4 Hz, 2H), 7.70 (dd, J = 7.5, 1.6 Hz, 1H), 7.54 (s, 1H), 7.53–7.48 (m, 1H), 7.45 (dd, J = 7.6, 1.2 Hz, 1H), 7.39 (t, J = 7.6 Hz, 2H), 7.33–7.25 (m, 2H), 5.08 (t, J = 7.3 Hz, 1H), 4.68–4.31 (m, 2H), 2.72–2.55 (m, 1H), 2.42–2.24 (m, 1H).13C NMR (151 MHz, Chloroform-d) δ 198.49, 155.52, 142.98, 136.06, 133.33, 128.67, 128.58, 126.48, 124.75, 122.95, 119.93, 117.81, 111.73, 81.69 (d, J = 164.2 Hz), 38.70 (d, J = 3.3 Hz), 32.95 (d, J = 19.4 Hz). 19F NMR (565 MHz, Chloroform-d) δ −221.32 (tdd, J = 45.20, 28.25, 22.60 Hz, 1F). HRMS (ESI) (m/z): calcd for C18H15FNaO2 ([M + Na]+), 305.0948; found, 305.0956.
  • phenyl-2-benzoyl-4-fluorobutanoate (29) Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound as a yellow oil (yield 6.5 mg, 23%). 1H NMR (500 MHz, Chloroform-d) δ 8.12–8.04 (m, 1H), 7.64 (td, J = 7.2, 1.3 Hz, 0H), 7.53 (t, J = 7.8 Hz, 1H), 7.38–7.29 (m, 1H), 7.24–7.17 (m, 1H), 6.98 (dd, J = 8.5, 1.3 Hz, 1H), 4.85 (dd, J = 7.8, 6.2 Hz, 0H), 4.75–4.54 (m, 1H), 2.60–2.41 (m, 1H).13C NMR (151 MHz, Chloroform-d) δ 193.34, 167.18, 149.34, 134.64, 132.98, 128.42, 127.94, 127.79, 125.15, 120.16, 80.58 (d, J = 165.6 Hz), 48.89 (d, J = 2.9 Hz), 28.86 (d, J = 19.6 Hz).19F NMR (565 MHz, Chloroform-d) δ −220.48 (tdd, J = 45.20, 28.25, 22.60 Hz, 1F). HRMS (ESI) (m/z): calcd for C17H15FNaO3 ([M + Na]+), 309.0897; found, 309.0891.
  • 4-fluoro-1,2-di-p-tolylbutan-1-one (30) Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound as a yellow oil (yield 18.9 mg, 70%). 1H NMR (500 MHz, Chloroform-d) δ 7.86 (d, J = 8.4 Hz, 2H), 7.21–7.12 (m, 4H), 7.09 (d, J = 7.9 Hz, 2H), 4.78 (t, J = 7.4 Hz, 1H), 4.53–4.28 (m, 2H), 2.62–2.46 (m, 1H), 2.33 (s, 3H), 2.27 (s, 3H), 2.23–2.06 (m, 1H). 13C NMR (151 MHz, Chloroform-d) δ 198.80, 143.77, 136.92, 135.67, 133.95, 129.79, 129.21, 128.92, 128.17, 81.89 (d, J = 163.8 Hz), 48.44 (d, J = 3.2 Hz), 34.36 (d, J = 19.3 Hz), 21.58, 21.01. 19F NMR (565 MHz, Chloroform-d) δ −221.31 (tdd, J = 50.85, 33.90, 28.25 Hz, 1F). HRMS (ESI) (m/z): calcd for C18H19FNaO ([M + Na]+), 293.1312; found, 293.1315.
  • 1-(4-(tert-butyl)phenyl)-4-fluoro-2-(p-tolyl)butan-1-one (31) Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound as a yellow oil (yield 24.9 mg, 80%). 1H NMR (500 MHz, Chloroform-d) δ 8.09–7.79 (m, 2H), 7.39 (d, J = 8.5 Hz, 2H), 7.20 (d, J = 8.0 Hz, 2H), 7.11 (d, J = 8.0 Hz, 2H), 4.80 (t, J = 7.4 Hz, 1H), 4.57–4.25 (m, 2H), 2.60–2.48 (m, 1H), 2.28 (s, 3H), 2.23–2.06 (m, 1H), 1.28 (s, 9H). 13C NMR (151 MHz, Chloroform-d) δ 198.72, 156.68, 136.93, 135.69, 133.86, 129.80, 128.77, 128.20, 125.50, 81.89 (d, J = 163.8 Hz), 48.44 (d, J = 3.3 Hz), 35.06, 34.47 (d, J = 19.3 Hz), 31.02, 21.02. 19F NMR (565 MHz, Chloroform-d) δ −221.28 (tdd, J = 45.20, 28.25, 22.60 Hz, 1F). HRMS (ESI) (m/z): calcd for C21H25FNaO ([M + Na]+), 335.1781; found, 335.1786.
  • 1-(4-chlorophenyl)-4-fluoro-2-(p-tolyl)butan-1-one (32) Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound as a yellow oil (yield 15.4 mg, 68%). 1H NMR (500 MHz, Chloroform-d) δ 7.88 (d, J = 8.7 Hz, 2H), 7.34 (d, J = 8.6 Hz, 2H), 7.15 (d, J = 8.1 Hz, 2H), 7.11 (d, J = 7.9 Hz, 2H), 4.73 (t, J = 7.3 Hz, 1H), 4.62–4.22 (m, 2H), 2.62–2.38 (m, 1H), 2.28 (s, 3H), 2.23–2.04 (m, 1H). 13C NMR (151 MHz, Chloroform-d) δ 197.96, 139.38, 137.25, 135.09, 134.73, 130.20, 129.96, 128.84, 128.15, 81.69 (d, J = 163.9 Hz), 48.74 (d, J = 3.3 Hz), 34.23 (d, J = 19.2 Hz), 21.03. 19F NMR (565 MHz, Chloroform-d) δ −221.51 (tdd, J = 45.20, 28.25, 22.60 Hz, 1F). HRMS (ESI) (m/z): calcd for C17H16ClFNaO ([M + Na]+), 313.0765; found, 313.0765.
  • 1-(4-bromophenyl)-4-fluoro-2-(p-tolyl)butan-1-one (33) Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound as a yellow oil (yield 17.7 mg, 53%). 1H NMR (500 MHz, Chloroform-d) δ 7.80 (d, J = 8.4 Hz, 2H), 7.50 (d, J = 8.3 Hz, 2H), 7.14 (d, J = 7.8 Hz, 2H), 7.10 (d, J = 7.9 Hz, 2H), 4.72 (t, J = 7.3 Hz, 1H), 4.53–4.24 (m, 2H), 2.62–2.46 (m, 1H), 2.28 (s, 3H), 2.20–2.04 (m, 1H). 13C NMR (151 MHz, Chloroform-d) δ 198.15, 137.26, 135.15, 135.06, 131.83, 130.30, 129.96, 128.14, 81.67 (d, J = 163.7 Hz), 48.74 (d, J = 3.2 Hz), 34.21 (d, J = 19.5 Hz), 21.01. 19F NMR (565 MHz, Chloroform-d) δ −221.52 (tdd, J = 50.85, 33.90, 28.25 Hz, 1F). HRMS (ESI) (m/z): calcd for C17H16BrFNaO ([M + Na]+), 357.0260; found, 357.0265.
  • 4-fluoro-2-(p-tolyl)-1-(4-(trifluoromethoxy)phenyl)butan-1-one (34) Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound as a yellow oil (yield 9.2 mg, 27%). 1H NMR (500 MHz, Chloroform-d) δ 7.80 (d, J = 8.4 Hz, 2H), 7.50 (d, J = 8.3 Hz, 2H), 7.14 (d, J = 7.8 Hz, 2H), 7.10 (d, J = 7.9 Hz, 2H), 4.72 (t, J = 7.3 Hz, 1H), 4.53–4.24 (m, 2H), 2.62–2.46 (m, 1H), 2.28 (s, 3H), 2.20–2.04 (m, 1H). 13C NMR (151 MHz, Chloroform-d) δ 198.80, 137.05, 136.18, 133.34, 129.73, 128.75, 128.70, 121.54, 120.04 (d, J = 259.2 Hz), 81.52 (d, J = 164.3 Hz), 48.07 (d, J = 2.9 Hz), 34.47 (d, J = 19.2 Hz), 21.02. 19F NMR (565 MHz, Chloroform-d) δ −57.88 (s, 3F), −221.36 (tdd, J = 50.85, 33.90, 28.25 Hz, 1F). HRMS (ESI) (m/z): calcd for C18H16F4NaO2 ([M + Na]+), 363.0978; found, 363.0971.
  • 4-(4-fluoro-2-(p-tolyl)butanoyl)benzonitrile (35) Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound as a yellow oil (yield 14.0 mg, 50%). 1H NMR (500 MHz, Chloroform-d) δ 7.73 (d, J = 8.2 Hz, 2H), 7.65 (d, J = 8.2 Hz, 2H), 7.14 (d, J = 7.9 Hz, 2H), 7.10 (d, J = 8.0 Hz, 2H), 4.71 (t, J = 7.3 Hz, 1H), 4.54–4.29 (m, 2H), 2.62–2.44 (m, 1H), 2.28 (s, 3H), 2.21–2.03 (m, 1H). 13C NMR (151 MHz, Chloroform-d) δ 198.44, 137.84, 137.26, 135.67, 135.04, 130.19, 129.97, 128.15, 100.98, 81.68 (d, J = 163.7 Hz), 48.67 (d, J = 3.0 Hz), 34.18 (d, J = 19.4 Hz), 21.03. 19F NMR (565 MHz, Chloroform-d) δ −221.51 (tdd, J = 45.20, 28.25, 22.60 Hz, 1F). HRMS (ESI) (m/z): calcd for C18H16FNNaO ([M + Na]+), 304.1108; found, 304.1105.
  • 4-fluoro-1-(2-methoxyphenyl)-2-(p-tolyl)butan-1-one (36) Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound as a yellow oil (yield 15.4 mg, 54%). 1H NMR (500 MHz, Chloroform-d) δ 7.55 (dd, J = 7.8, 1.4 Hz, 1H), 7.51–7.46 (m, 1H), 7.27 (t, J = 8.1 Hz, 1H), 7.18 (d, J = 7.8 Hz, 2H), 7.10 (d, J = 7.9 Hz, 2H), 7.02 (dd, J = 8.2, 2.7 Hz, 1H), 4.78 (t, J = 7.4 Hz, 1H), 4.54–4.27 (m, 2H), 3.79 (s, 3H), 2.66–2.46 (m, 1H), 2.28 (s, 3H), 2.23–2.06 (m, 1H). 13C NMR (151 MHz, Chloroform-d) δ 198.99, 159.71, 137.81, 137.05, 135.43, 129.86, 129.48, 128.18, 121.43, 119.53, 113.04, 81.81 (d, J = 163.9 Hz), 55.36, 48.75 (d, J = 3.2 Hz), 34.38 (d, J = 19.3 Hz), 21.03. 19F NMR (565 MHz, Chloroform-d) δ −221.34 (tdd, J = 58.85, 33.90, 28.25 Hz, 1F). HRMS (ESI) (m/z): calcd for C18H19FNaO2 ([M + Na]+), 309.1261; found, 309.1261.
  • 4-fluoro-1-(m-tolyl)-2-(p-tolyl)butan-1-one (37) Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound as a yellow oil (yield 14.6 mg, 50%). 1H NMR (500 MHz, Chloroform-d) δ 7.57 (d, J = 7.7 Hz, 1H), 7.28 (d, J = 7.4 Hz, 1H), 7.20–7.04 (m, 6H), 4.64 (t, J = 7.4 Hz, 1H), 4.56–4.30 (m, 2H), 2.67–2.51 (m, 1H), 2.31 (s, 3H), 2.27 (s, 3H), 2.21–2.06 (m, 1H). 13C NMR (151 MHz, Chloroform-d) δ 203.29, 138.39, 138.09, 137.03, 134.59, 131.61, 130.94, 129.69, 128.32, 128.04, 125.46, 81.97 (d, J = 164.0 Hz), 51.55 (d, J = 3.5 Hz), 33.79 (d, J = 19.1 Hz), 21.04, 20.78. 19F NMR (565 MHz, Chloroform-d) δ −221.33 (tdd, J = 45.20, 33.90, 28.25 Hz, 1F). HRMS (ESI) (m/z): calcd for C18H19FNaO ([M + Na]+), 293.1312; found, 293.1312.
  • 4-fluoro-1-(3-fluorophenyl)-2-(p-tolyl)butan-1-one (38) Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound as a yellow oil (yield 11.5 mg, 42%). 1H NMR (500 MHz, Chloroform-d) δ 7.73 (dd, J = 7.8, 1.5 Hz, 1H), 7.62 (dt, J = 9.6, 2.1 Hz, 1H), 7.34 (td, J = 8.0, 5.5 Hz, 1H), 7.20–7.13 (m, 3H), 7.11 (d, J = 8.0 Hz, 2H), 4.73 (t, J = 7.3 Hz, 1H), 4.74–4.43 (m, 2H), 2.59–2.047 (m, 1H), 2.28 (s, 3H), 2.23–2.06 (m, 1H). 13C NMR (151 MHz, Chloroform-d) δ 197.94 (d, J = 2.2 Hz), 163.57, 161.93, 138.57 (d, J = 6.2 Hz), 137.28, 134.93, 130.14 (d, J = 7.5 Hz), 129.97, 128.17, 124.51 (d, J = 2.9 Hz), 119.96 (d, J = 21.5 Hz), 115.52 (d, J = 22.5 Hz), 81.66 (d, J = 164.1 Hz), 48.94 (d, J = 3.3 Hz), 34.28 (d, J = 19.5 Hz), 21.03. 19F NMR (565 MHz, Chloroform-d) δ -111.88 (d, J = 14.0 Hz, 1F), −221.41 (tdd, J = 50.85, 33.90, 28.25 Hz, 1F). HRMS (ESI) (m/z): calcd for C17H16F2NaO ([M + Na]+), 297.1061; found, 297.1066.
  • 1-(3,5-dimethylphenyl)-4-fluoro-2-(p-tolyl)butan-1-one (39) Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound as a yellow oil (yield 14.2 mg, 50%).1H NMR (500 MHz, Chloroform-d) δ 7.56 (s, 2H), 7.18 (d, J = 7.8 Hz, 2H), 7.10 (d, J = 8.1 Hz, 3H), 4.79 (t, J = 7.4 Hz, 1H), 4.53–4.28 (m, 2H), 2.61–2.46 (m, 1H), 2.30 (s, 6H), 2.27 (s, 3H), 2.19–2.07 (m, 1H).13C NMR (151 MHz, Chloroform-d) δ 199.62, 138.09, 136.90, 136.60, 135.54, 134.67, 129.77, 128.16, 126.56, 81.92 (d, J = 163.6 Hz), 48.44 (d, J = 3.1 Hz), 34.43 (d, J = 19.3 Hz), 21.25, 21.02. 19F NMR (565 MHz, Chloroform-d) δ −221.29 (tdd, J = 50.85, 33.90, 28.25 Hz, 1F). HRMS (ESI) (m/z): calcd for C19H21FNaO ([M + Na]+), 307.1468; found, 307.1473.
  • 4-fluoro-1-(naphthalen-2-yl)-2-(p-tolyl)butan-1-one (40) Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound as a yellow oil (yield 18.7 mg, 61%). 1H NMR (500 MHz, Chloroform-d) δ 8.36 (d, J = 8.5 Hz, 1H), 7.90 (d, J = 8.3 Hz, 1H), 7.85 (dd, J = 7.2, 1.2 Hz, 1H), 7.80 (dd, J = 8.0, 1.5 Hz, 1H), 7.55–7.43 (m, 3H), 7.42 (t, J = 7.7 Hz, 1H), 7.19 (d, J = 7.9 Hz, 2H), 7.06 (d, J = 7.8 Hz, 2H), 4.83 (t, J = 7.4 Hz, 1H), 4.63–4.29 (m, 2H), 2.80–2.64 (m, 1H), 2.30–2.17 (m, 4H). 13C NMR (151 MHz, Chloroform-d) δ 203.07, 137.06, 136.38, 134.74, 133.86, 132.37, 130.54, 129.75, 128.29, 128.26, 127.76, 127.27, 126.35, 125.60, 124.28, 82.00 (d, J = 164.0 Hz), 52.06 (d, J = 3.4 Hz), 34.12 (d, J = 19.2 Hz), 21.01. 19F NMR (565 MHz, Chloroform-d) δ −221.21 (tdd, J = 50.85, 33.90, 28.25 Hz, 1F). HRMS (ESI) (m/z): calcd for C21H20NaO ([M + H]+), 307.1492; found, 307.1485.
  • 4-fluoro-1-(thiophen-2-yl)-2-(p-tolyl)butan-1-one (41) Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound as a yellow oil (yield 14.1 mg, 54%). 1H NMR (500 MHz, Chloroform-d) δ 7.71 (dd, J = 3.9, 1.1 Hz, 1H), 7.56 (dd, J = 5.0, 1.1 Hz, 1H), 7.22 (d, J = 7.9 Hz, 2H), 7.12 (d, J = 7.8 Hz, 2H), 7.04 (dd, J = 4.9, 3.8 Hz, 1H), 4.62 (t, J = 7.4 Hz, 1H), 4.56–4.27 (m, 2H), 2.61–2.45 (m, 1H), 2.28 (s, 3H), 2.18–2.03 (m, 1H). 13C NMR (151 MHz, Chloroform-d) δ 198.44, 137.84, 137.26, 135.67, 135.04, 130.19, 129.97, 128.15, 100.98, 81.68 (d, J = 163.7 Hz), 48.67 (d, J = 3.0 Hz), 34.18 (d, J = 19.4 Hz), 21.03. 19F NMR (565 MHz, Chloroform-d) δ −221.51 (tdd, J = 45.20, 28.25, 22.60 Hz, 1F). HRMS (ESI) (m/z): calcd for C15H15FNaOS ([M + Na]+), 285.0719; found, 285.0724.
  • 2,2,6,6-tetramethylpiperidin-1-yl benzoate (43) Purification by column chromatography on silica gel (petroleum ether/ethyl acetate = 3:1, v/v) affords the title compound as a red solid (yield 11.2 mg, 43%). 1H NMR (500 MHz, Chloroform-d) δ 8.08 (d, J = 7.0 Hz, 2H), 7.58 (t, J = 7.5 Hz, 1H), 7.46 (t, J = 7.5 Hz, 2H), 1.83–1.74 (m, 2H), 1.75–1.66 (m, 1H), 1.61–1.57 (m, 2H), 1.50–1.43 (m, 1H), 1.28 (s, 6H), 1.12 (s, 6H). 13C NMR (151 MHz, Chloroform-d) δ 166.42, 132.88, 129.79, 129.60, 128.49, 60.44, 39.11, 32.01, 20.89, 17.05. HRMS (ESI) (m/z): calcd for C16H23NNaO2, ([M + Na]+), 284.1621, found 284.1614.
  • (5aR,10bS)-1-benzoyl-2-mesityl-2,5a,6,10b-tetrahydro-4H-indeno [2,1-b][1,2,4]tri-zolo [4,3d][1,4]oxazin-11-ium tetrafluoroborate (44) The white precipitate was filtered off and washed with diethyl ether. Drying under vacuum afforded the corresponding product as a white solid. 1H NMR (500 MHz, Chloroform-d) δ 8.24 (d, J = 7.8 Hz, 2H), 7.78 (t, J = 7.4 Hz, 1H), 7.70 (t, J = 7.6 Hz, 2H), 7.35 (d, J = 4.4 Hz, 2H), 7.28–7.23 (m, 2H), 7.11 (d, J = 7.7 Hz, 1H), 7.01 (s, 1H), 6.93 (s, 1H), 5.72 (d, J = 3.3 Hz, 1H), 5.51 (d, J = 16.3 Hz, 1H), 5.49–5.46 (m, 1H), 5.12 (d, J = 16.3 Hz, 1H), 3.30 (dd, J = 17.1, 4.0 Hz, 1H), 3.20 (d, J = 17.1 Hz, 1H), 2.32 (s, 3H), 2.17 (d, J = 13.6 Hz, 6H). 13C NMR (151 MHz, Chloroform-d) δ 179.11, 150.88, 147.75, 142.66, 140.83, 138.21, 135.66, 135.31, 132.10, 131.04, 130.72, 130.25, 130.13, 129.86, 129.40, 127.82, 126.34, 123.02, 63.80, 60.82, 37.25, 21.20, 17.58, 17.47. 19F NMR (565 MHz, Chloroform-d) δ −151.49. HRMS (ESI) (m/z): calcd for C28H26N3O2+, 437.2098; found, 437.2090.

5. Conclusions

In summary, we have developed a robust method for visible light-mediated monofluoromethylation/acylation of olefins, employing dual organo-catalysis. A cost-effective and bench-stable sodium monofluorosulfite (NaSO2CH2F) served as a CH2F radical source, while benzoyl fluoride acted as an acylating reagent under redox-neutral and metal-free conditions. Mechanistic investigations reveal that the reaction is initiated through the oxidative quenching of PC* by acylazolium, generating Breslow intermediate radicals (BIR) and proceeds through a sequential selective radical addition/radical-radical cross-coupling (RA/RRCC) cascade. This transformation features mild conditions, ease of operation, and a broad substrate scope, represents an attractive alternative for synthesizing versatile α-aryl-β-monofluoromethyl ketones. Further applications of this mild and metal-free CH2F radical generation strategy are actively being pursued in our laboratory.

Supplementary Materials

The following supporting information can be downloaded at https://www.mdpi.com/article/10.3390/molecules29040790/s1: 1H and 13C NMR data and spectra for all compounds. Refs. [83,84,85] are cited in Supplementary Materials.

Author Contributions

J.X., Y.G. and Z.L. performed the experiments. J.S., G.Z. and Q.Z. conceived the concept, directed the project, and wrote the paper. All the authors participated in the analysis of the experimental data. All authors have read and agreed to the published version of the manuscript.

Funding

We thank the NSFC (22193012, 22001157, 21831002, and 22201033), Natural Science Foundation of Jilin Province (20230101047JC, YDZJ202201ZYTS338), Jilin Educational Committee (JJKH20231295KJ, JJKH20231302KJ), and the Fundamental Research Funds for the Central Universities (2412022ZD012, 2412022QD016, 2412021QD007) for their generous financial support.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

The data presented in this study are available in the Supplementary Materials.

Acknowledgments

The authors are grateful for the support from Northeast Normal University.

Conflicts of Interest

The authors declare no conflicts of interest.

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Molecules 29 00790 sch001
Scheme 1. Motivation for visible light-mediated organocatalyzed monofluoromethylation/acylation of alkenes.
Scheme 1. Motivation for visible light-mediated organocatalyzed monofluoromethylation/acylation of alkenes.
Molecules 29 00790 sch001
Molecules 29 00790 sch002
Scheme 2. Substrate scope for monofluoromethylation/acylation of olefins. Reaction conditions: unless otherwise noted, all the reactions were carried out with 1 (0.1 mmol), 2a (0.3 mmol), 3 (0.3 mmol), rac-NHC-2 (0.015 mmol), PC-3 (0.0015 mmol), and Cs2CO3 (0.2 mmol) in CH3CN (2 mL) under N2, 30 °C, and irradiation with blue LED (453.5 nm, 10 W) for 12 h. Isolated yield. a Acyl fluoride (0.5 mmol) for 18 h.
Scheme 2. Substrate scope for monofluoromethylation/acylation of olefins. Reaction conditions: unless otherwise noted, all the reactions were carried out with 1 (0.1 mmol), 2a (0.3 mmol), 3 (0.3 mmol), rac-NHC-2 (0.015 mmol), PC-3 (0.0015 mmol), and Cs2CO3 (0.2 mmol) in CH3CN (2 mL) under N2, 30 °C, and irradiation with blue LED (453.5 nm, 10 W) for 12 h. Isolated yield. a Acyl fluoride (0.5 mmol) for 18 h.
Molecules 29 00790 sch002
Molecules 29 00790 sch003
Scheme 3. Substrate scope for monofluoromethylation/acylation of olefins. Reaction conditions: unless otherwise noted, all the reactions were carried out with 1b (0.1 mmol), 2 (0.3 mmol), 3 (0.3 mmol), rac-NHC-2 (0.015 mmol), PC-3 (0.0015 mmol), and Cs2CO3 (0.2 mmol) in CH3CN (2 mL) under N2, 30 °C, and irradiation with blue LED (453.5 nm, 10 W) for 12 h. Isolated yield.
Scheme 3. Substrate scope for monofluoromethylation/acylation of olefins. Reaction conditions: unless otherwise noted, all the reactions were carried out with 1b (0.1 mmol), 2 (0.3 mmol), 3 (0.3 mmol), rac-NHC-2 (0.015 mmol), PC-3 (0.0015 mmol), and Cs2CO3 (0.2 mmol) in CH3CN (2 mL) under N2, 30 °C, and irradiation with blue LED (453.5 nm, 10 W) for 12 h. Isolated yield.
Molecules 29 00790 sch003
Molecules 29 00790 sch004
Scheme 4. Mechanistic investigation.
Scheme 4. Mechanistic investigation.
Molecules 29 00790 sch004
Molecules 29 00790 sch005
Scheme 5. Proposed reaction pathway.
Scheme 5. Proposed reaction pathway.
Molecules 29 00790 sch005
Table 1. Optimization of alkene monofluoromethylation/acylation.
Table 1. Optimization of alkene monofluoromethylation/acylation.
Molecules 29 00790 i001
EntryNHCs
(15 mol%)		PC
(1.5 mol%)		Solvent
(X mL)		Base
(2.0 equiv)		Yield
(%)
1NHC-1PC-1DCMCs2CO350
2NHC-1PC-2DCMCs2CO338
3NHC-1PC-3DCMCs2CO349
4NHC-1PC-4DCMCs2CO337
5NHC-2PC-1DCMCs2CO360
6NHC-3PC-1DCMCs2CO347
7NHC-4PC-1DCMCs2CO36
8NHC-5PC-1DCMCs2CO355
9NHC-2PC-1PhCF3Cs2CO336
10NHC-2PC-1THFCs2CO320
11NHC-2PC-1DCECs2CO355
12NHC-2PC-1AcetoneCs2CO361
13NHC-2PC-1TolueneCs2CO364
14NHC-2PC-1CH3CNCs2CO389
15NHC-2PC-1CHCl3Cs2CO365
16NHC-2PC-1CH3CNK2CO332
17NHC-2PC-1CH3CNK3PO425
18rac-NHC-2PC-1CH3CNCs2CO390
Reaction conditions: Unless otherwise noted, all the reactions were carried out with 1a (0.1 mmol), 2a (0.3 mmol), 3 (0.3 mmol), NHCs (0.015 mmol), Cs2CO3 (0.2 mmol), and PC (0.0015 mmol) in solvent (2 mL) at 30 °C with 10 W blue LEDs for 12 h.
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Xia, J.; Guo, Y.; Lv, Z.; Sun, J.; Zheng, G.; Zhang, Q. Visible Light-Mediated Monofluoromethylation/Acylation of Olefins by Dual Organo-Catalysis. Molecules 2024, 29, 790. https://doi.org/10.3390/molecules29040790

AMA Style

Xia J, Guo Y, Lv Z, Sun J, Zheng G, Zhang Q. Visible Light-Mediated Monofluoromethylation/Acylation of Olefins by Dual Organo-Catalysis. Molecules. 2024; 29(4):790. https://doi.org/10.3390/molecules29040790

Chicago/Turabian Style

Xia, Jiuli, Yunliang Guo, Zhiguang Lv, Jiaqiong Sun, Guangfan Zheng, and Qian Zhang. 2024. "Visible Light-Mediated Monofluoromethylation/Acylation of Olefins by Dual Organo-Catalysis" Molecules 29, no. 4: 790. https://doi.org/10.3390/molecules29040790

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