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

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.

Full text

Citation: 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
Academic Editor: Minghao Li
Received: 31 December 2023
Revised: 1 February 2024
Accepted: 6 February 2024
Published: 8 February 2024
Copyright: © 2024 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
molecules
Article
Visible Light-Mediated Monofluoromethylation/Acylation of
Olefins by Dual Organo-Catalysis
Jiuli Xia 1, Yunliang Guo 2, Zhiguang Lv 1, Jiaqiong Sun 2,*, Guangfan Zheng 1,* and Qian Zhang 1,3
1Key Laboratory of Functional Organic Molecule Design & Synthesis of Jilin Province, Department of
Chemistry, Northeast Normal University, Changchun 130024, China; xiajl699@nenu.edu.cn (J.X.);
lvzhiguang@nenu.edu.cn (Z.L.); zhangq651@nenu.edu.cn (Q.Z.)
2School of Environment, Northeast Normal University, Changchun 130117, China; guoyl367@nenu.edu.cn
3State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese
Academy of Sciences, 345 Lingling Road, Shanghai 200032, China
*Correspondence: sunjq295@nenu.edu.cn (J.S.); zhenggf265@nenu.edu.cn (G.Z.)
Abstract: Monofluoromethyl (CH
2
F) 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 CH
2
F-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 CH
2
F radical generation strategy from NaSO
2
CFH
2
holds potential for further applications
in fluoroalkyl radical chemistry.
Keywords: metal-free; NHCs; organic photocatalyst; monofluoromethylation/acylation; alkenes
1. Introduction
The incorporation of fluoroalkyl groups into readily available molecules has gar-
nered increasing attention due to the prevalence of fluoroalkyl-containing compounds
in bioactive molecules and drug discovery [
1
–
5
]. Among various methodologies [
6
], the
radical approach [
7
–
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, CH
2
F, as a distinct fluoroalkyl group, has been
recognized for its potential as a metabolically stable and lipophilic bioisostere for NH
2
, 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 instal-
lation of CF
3
or CF
2
H and CF
2
R groups, radical monofluoromethylation [
18
–
37
] repre-
sents an emerging area with great demand. Olefins, being fundamental and prevalent
chemical feedstocks, have witnessed considerable progress in transition metal (TM) catal-
ysis including radical hydromonofluoromethylation [
25
] and monofluoromethylative di-
functionalization [
26
–
31
], where TMs serve as redox catalysts [
25
–
27
] or photocatalysts
(PC) [
28
–
31
]. Metal-free transformations mediated by visible light are particularly at-
tractive 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 monoflu-
oromethylation/acylation of olefins, while the Gouverneur [
33
] and Gaunt [
34
] groups
independently developed radical hydrofluoromethylation of alkenes using CH
2
FI. The
utilization of organo-photocatalysts has further enriched the initiation pathways for CH
2
F
Molecules 2024,29, 790. https://doi.org/10.3390/molecules29040790 https://www.mdpi.com/journal/molecules

Molecules 2024,29, 790 2 of 19
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 accomplish-
ments, developing a novel organic PC-catalyzed radical difunctionalization system with a
bench-stable and cost-effective CFH2source was highly desirable.
Molecules 2024, 29, x FOR PEER REVIEW 2 of 20
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 accom-
plishments, 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-aached persistent Breslow intermediate
radicals (BIR) [42–44] have emerged as valuable acyl radical equivalents, enabling radical-
radical cross-coupling and thereby paving the way for a new paradigm in radical acyla-
tion chemistry [45–48]. In radical NHC catalysis, persistent BIR and transient radical spe-
cies can be concurrently generated at a comparable rate through a single electron transfer
process. The highly selective radical addition/coupling (RAC) scenario [49–51] 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 [52–60], Schedit [61–67], and others [68–74], 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 [52–57,67–73], 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–
78] and greener transformation [79–81], we now report our discovery in visible light-me-
diated 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.
Scheme 1. Motivation for visible light-mediated organocatalyzed monofluoromethylation/acylation
of alkenes.
Scheme 1. Motivation for visible light-mediated organocatalyzed monofluoromethylation/acylation
of alkenes.
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
–
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 chem-
istry [
45
–
48
]. In radical NHC catalysis, persistent BIR and transient radical species can
be concurrently generated at a comparable rate through a single electron transfer pro-
cess. The highly selective radical addition/coupling (RAC) scenario [
49
–
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
–
60
], Schedit [
61
–
67
], and others [
68
–
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
–
57
,
67
–
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

Molecules 2024,29, 790 3 of 19
catalysis [
75
–
78
] and greener transformation [
79
–
81
], we now report our discovery in
visible light-mediated dual organocatalyzed three-component radical monofluoromethyla-
tion/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 H
2
FCSO
2
Na (3) as model substrates; NHC-1 as a catalyst; 4-
CzIPN as a PC; Cs
2
CO
3
as a base; and dichloromethane (DCM) as the solvent under blue
LED irradiation. To our delight, the desired
β
-monofluoromethylated ketone 4was sepa-
rated in 50% yield (Table 1, Entry 1). Switching the PC to an Ir-based photocatalyst could
generate 4in 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 (PhCF
3
, 36%) and tetrahy-
drofuran (THF, 20%) provided substantially reduced yields (
Entries 9–15
). Fortunately,
by switching the solvent to acetonitrile (CH
3
CN), the desired 4was 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 4could be separated in 90% yield (Entry 18); thus, these conditions
were identified as conditions A for evaluation of the substrate scope.
Table 1. Optimization of alkene monofluoromethylation/acylation.
Molecules 2024, 29, x FOR PEER REVIEW 3 of 20
2. Results and Discussions
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 sepa-
rated 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 tet-
rahydrofuran (THF, 20%) provided substantially reduced yields (Entries 9–15). Fortu-
nately, 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 de-
creased yields were obtained for 4 (Entries 16–17). Because of the challenges originated
from chiral induction of radical–radical cross-coupling (RRCC), no satisfied enantioselec-
tivity 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.
Table 1. Optimization of alkene monofluoromethylation/acylation.
Entry NHCs
(15 mol%)
PC
(1.5 mol%)
Solvent
(X mL)
Base
(2.0 equiv)
Yield
(%)
1 NHC-1 PC-1 DCM Cs2CO3 50
2 NHC-1 PC-2 DCM Cs2CO3 38
3 NHC-1 PC-3 DCM Cs2CO3 49
4 NHC-1 PC-4 DCM Cs2CO3 37
5 NHC-2 PC-1 DCM Cs2CO3 60
6 NHC-3 PC-1 DCM Cs2CO3 47
7 NHC-4 PC-1 DCM Cs2CO3 6
8 NHC-5 PC-1 DCM Cs2CO3 55
9 NHC-2 PC-1 PhCF3 Cs2CO3 36
10 NHC-2 PC-1 THF Cs2CO3 20
11 NHC-2 PC-1 DCE Cs2CO3 55
12 NHC-2 PC-1 Acetone Cs2CO3 61
13 NHC-2 PC-1 Toluene Cs2CO3 64
14 NHC-2 PC-1 CH3CN Cs2CO3 89
15 NHC-2 PC-1 CHCl3 Cs2CO3 65
16 NHC-2 PC-1 CH3CN K2CO3 32
17 NHC-2 PC-1 CH3CN K3PO4 25
Entry NHCs
(15 mol%)
PC
(1.5 mol%)
Solvent
(X mL)
Base
(2.0 equiv)
Yield
(%)
1 NHC-1 PC-1 DCM Cs2CO350
2 NHC-1 PC-2 DCM Cs2CO338
3 NHC-1 PC-3 DCM Cs2CO349
4 NHC-1 PC-4 DCM Cs2CO337
5 NHC-2 PC-1 DCM Cs2CO360
6 NHC-3 PC-1 DCM Cs2CO347
7 NHC-4 PC-1 DCM Cs2CO36
8 NHC-5 PC-1 DCM Cs2CO355
9 NHC-2 PC-1 PhCF3Cs2CO336
10 NHC-2 PC-1 THF Cs2CO320
11 NHC-2 PC-1 DCE Cs2CO355
12 NHC-2 PC-1 Acetone Cs2CO361

Molecules 2024,29, 790 4 of 19
Table 1. Cont.
Entry NHCs
(15 mol%)
PC
(1.5 mol%)
Solvent
(X mL)
Base
(2.0 equiv)
Yield
(%)
13 NHC-2 PC-1 Toluene Cs2CO364
14 NHC-2 PC-1 CH3CN Cs2CO389
15 NHC-2 PC-1 CHCl3Cs2CO365
16 NHC-2 PC-1 CH3CN K2CO332
17 NHC-2 PC-1 CH3CN K3PO425
18 rac-NHC-2 PC-1 CH3CN Cs2CO390
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), Cs
2
CO
3
(0.2 mmol), and PC (0.0015 mmol) in solvent (2 mL) at 30
◦
C with 10 W
blue LEDs for 12 h.
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
H
2
FCSO
2
Na as a CH
2
F 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, in-
dole, benzofuran)-substituted olefins were also suitable for this transformation, delivering
the desired ketones 22–28 in 37–83% yields. Michael alkenes could deliver monofluo-
romethylation/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 investi-
gated under the established photocatalytic system (Scheme 3). In general, the reactions
proceed smoothly with various substituted aroyl fluorides 2, 4-methylstyrene (1b), and
H
2
FCSO
2
Na. 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, OCF
3
) 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.

Molecules 2024,29, 790 5 of 19
Molecules 2024, 29, x FOR PEER REVIEW 5 of 20
Scheme 2. Substrate scope for monofluoromethylation/acylation of olefins. Reaction conditions: un-
less 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 Cs
2
CO
3
(0.2 mmol) in CH
3
CN (2 mL)
under N
2
, 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 2024,29, 790 6 of 19
Molecules 2024, 29, x FOR PEER REVIEW 6 of 20
Scheme 3. Substrate scope for monofluoromethylation/acylation of olefins. Reaction conditions: un-
less 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) un-
der N2, 30 °C, and irradiation with blue LED (453.5 nm, 10 W) for 12 h. Isolated yield.
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 com-
pletely 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 irradia-
tion; 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.
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 Cs
2
CO
3
(0.2 mmol) in CH
3
CN (2 mL)
under N2, 30 ◦C, and irradiation with blue LED (453.5 nm, 10 W) for 12 h. Isolated yield.
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; CH
2
F-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 CD
3
CN as solvents, demonstrating that formation 5only 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 H
2
FCSO
2
Na. Thus, the oxidative quenching progress of PC* by 44 seems more
favorable than the reductive quenching cycles.

Molecules 2024,29, 790 7 of 19
Molecules 2024, 29, x FOR PEER REVIEW 7 of 20
Scheme 4. Mechanistic investigation.
Based on the above mechanistic investigations and previous reports, a plausible re-
action mechanism is depicted in Scheme 5. Firstly, benzoyl fluoride 3a undergoes substi-
tution 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].
Scheme 4. Mechanistic investigation.
Based on the above mechanistic investigations and previous reports, a plausible reac-
tion mechanism is depicted in Scheme 5. Firstly, benzoyl fluoride 3a undergoes substitution
by NHC, generating NHC-adduct I(44). Oxidative quenching between PC* and Imight
occur, delivering BIR III and oxidative state PC
+•
. Single electron oxidation of CH
2
FSO
2
Na
by PC
+•
affords CH
2
F radical via sequential release of SO
2
. Selective addition of CH
2
F radi-
cal 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 4and regenerate the NHC catalyst. The excellent regioselectivity may originate from
the persistent radical effect [82].

Molecules 2024,29, 790 8 of 19
Molecules 2024, 29, x FOR PEER REVIEW 8 of 20
Scheme 5. Proposed reaction pathway.
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 other-
wise. Anhydrous solvents were employed as per distillation procedures. Reaction pro-
gress 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, Var-
ian 126 MHz instrument, both in CDCl3 with TMS as the internal standard. 19F NMR spec-
tra 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 stand-
ards tetramethylsilane (0 ppm for 1H NMR) and CDCl3 (77.0 ppm for 13C NMR), respec-
tively. 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-reflec-
tion 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 corre-
sponding product 4.
Scheme 5. Proposed reaction pathway.
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.
1
H NMR spectra were recorded at 25
◦
C using either a Bruker 600 or 500, Varian
500 MHz
instrument, while
13
C NMR spectra were obtained at 25
◦
C using a Bruker 151,
Varian 126 MHz instrument, both in CDCl
3
with TMS as the internal standard.
19
F NMR
spectra were recorded at 25
◦
C using a Bruker 565 MHz spectrometer. Chemical shifts for
1
H and
13
C NMR spectra are reported in parts per million (ppm) relative to the internal
standards tetramethylsilane (0 ppm for
1
H NMR) and CDCl
3
(77.0 ppm for
13
C NMR),
respectively.
19
F NMR chemical shifts were determined relative to CFCl
3
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), Cs
2
CO
3
(65.2 mg, 0.2 mmol), PC-1 (1.2 mg,
0.0015 mmol)
,3
(36.0 mg, 0.3 mmol) and CH
3
CN (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

Molecules 2024,29, 790 9 of 19
(yield 22.3 mg, 92%).
1
H 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).
13
C 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).
19
F NMR (565 MHz, Chloroform-d)
δ−
221.37
(tdd, J= 45.20, 28.25, 22.60 Hz, 1F). HRMS (ESI) (m/z): calcd for C
16
H
15
FNaO ([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%).
1
H 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).
13
C 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.
19
F NMR (565 MHz,
Chloroform-d)
δ
-221.34 (tdd, J= 45.20, 28.25, 22.60 Hz, 1F). HRMS (ESI) (m/z): calcd for
C17H17 FNaO ([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%).
1
H 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).
13
C 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.
19
F NMR (565 MHz, Chloroform-d)
δ−
221.37 (tdd,
J= 45.20
,
28.25, 22.60 Hz, 1F). HRMS (ESI) (m/z): calcd for C
18
H
19
FNaO ([M + Na]
+
), 293.1312; found,
293.1307.
2-(4-(tert-butyl)phenyl)-4-fluoro-1-phenylbutan-1-one (7) Purification by column chromatogra-
phy on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound
as a yellow oil (yield 25.2 mg, 85%).
1
H 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).
13
C
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.
19
F NMR (
565 MHz
, Chloroform-d)
δ
-221.32 (tdd, J= 45.20, 28.25, 22.60 Hz, 1F). HRMS
(ESI) (m/z): calcd for C20 H23FNaO ([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%).
1
H 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).
13
C 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).
19
F NMR (565 MHz,
Chloroform-d)
δ
-221.42 (tdd, J= 45.20, 28.25, 22.60 Hz, 1F). HRMS (ESI) (m/z): calcd for
C17H17 FNaO2([M + Na]+), 295.1105; found, 295.1107.
2-([1,1’-biphenyl]-4-yl)-4-fluoro-1-phenylbutan-1-one (9) Purification by column chromatogra-
phy on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound
as a yellow oil (yield 28.6 mg, 90%).
1
H 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).
13
C 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).
19
F NMR

Molecules 2024,29, 790 10 of 19
(565 MHz, Chloroform-d) δ-221.44 (tdd, J= 45.20, 28.25, 22.60 Hz, 1F). HRMS (ESI) (m/z):
calcd for C22H19 FNaO ([M + Na]+), 341.1312; found, 341.1309.
7. 4-fluoro-2-(4-fluorophenyl)-1-phenylbutan-1-one (10) Purification by column chromatogra-
phy on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound as
a yellow oil (yield 14.3 mg, 55%).
1
H 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).
13
C 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).
19
F 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 C
16
H
14
F
2
NaO
([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%).
1
H 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).
13
C 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).
19
F NMR (565 MHz, Chloroform-d)
δ−
221.55 (tdd,
J= 45.20, 28.25, 22.60 Hz, 1F). HRMS (ESI) (m/z): calcd for C
16
H
14
ClFNaO ([M + Na]
+
),
299.0609; found, 299.0613.
9. 2-(4-bromophenyl)-4-fluoro-1-phenylbutan-1-one (12) Purification by column chromatogra-
phy on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound as
a yellow oil (yield 16.1 mg, 50%).
1
H 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).
13
C 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).
19
F NMR (565 MHz, Chloroform-d)
δ−
221.54
(tdd, J= 45.20, 28.25, 22.60 Hz, 1F). HRMS (ESI) (m/z): calcd for C
16
H
15
BrFO ([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%).
1
H 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).
13
C 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).
19
F NMR (565 MHz, Chloroform-d)
δ−
221.48
(tdd, J= 45.20, 28.25, 22.60 Hz, 1F). HRMS (ESI) (m/z): calcd for C
17
H
14
FNNaO ([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%).
1
H 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).
13
C 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.
19
F NMR (565 MHz, Chloroform-d)
δ−
221.30 (tdd, J= 45.20,
28.25, 22.60 Hz, 1F). HRMS (ESI) (m/z): calcd for C
18
H
17
FNaO
2
([M + Na]
+
), 307.1104;
found, 307.1112.
methyl-4-(4-fluoro-1-oxo-1-phenylbutan-2-yl)benzoate (15) Purification by column chromatog-
raphy on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound

Molecules 2024,29, 790 11 of 19
as a yellow oil (yield 23.1 mg, 77%).
1
H 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).
13
C 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.
19
F NMR (565 MHz, Chloroform-d)
δ−
221.35 (tdd, J= 45.20, 28.25, 22.60 Hz, 1F).
HRMS (ESI) (m/z): calcd for C18 H17FNaO3([M + Na]+), 323.1054; found, 323.1053.
2-(4-(chloromethyl)phenyl)-4-fluoro-1-phenylbutan-1-one (16) Purification by column chro-
matography on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title
compound as a yellow oil (yield 12.2 mg, 42%).
1
H 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).
13
C
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).
19
F
NMR (
565 MHz
, Chloroform-d)
δ−
221.43 (tdd, J= 45.20, 28.25, 22.60 Hz, 1F). HRMS (ESI)
(m/z): calcd for C17 H16ClFNaO ([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%).
1
H 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).
13
C 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.
19
F NMR (565 MHz, Chloroform-d)
δ−
219.78 (tt, J= 45.20, 22.60 Hz,
1F). HRMS (ESI) (m/z): calcd for C17 H17FNaO ([M + Na]+), 279.1155; found, 279.1159.
4-fluoro-2-(2-methoxyphenyl)-1-phenylbutan-1-one (18) Purification by column chromatogra-
phy on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound as
a yellow oil (yield 19.3 mg, 71%).
1
H 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).
13
C 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).
19
F NMR (565 MHz, Chloroform-d)
δ−
219.92 (tt,
J= 45.20, 22.60 Hz, 1F). HRMS (ESI) (m/z): calcd for C
17
H
17
FNaO
2
([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%).
1
H 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).
13
C 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.
19
F NMR (565 MHz, Chloroform-d)
δ
−
221.30 (tdd, J= 45.20, 28.25, 22.60 Hz, 1F). HRMS (ESI) (m/z): calcd for C
17
H
17
FNaO ([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%).
1
H 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).
13
C 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
).
19
F NMR

Molecules 2024,29, 790 12 of 19
(565 MHz, Chloroform-d)
δ−
221.47 (tdd, J= 45.20, 28.25, 22.60 Hz, 1F). HRMS (ESI) (m/z):
calcd for C16H14 ClFNaO ([M + Na]+), 299.0609; found, 299.0602.
2-(3,5-dimethylphenyl)-4-fluoro-1-phenylbutan-1-1 (21) Purification by column chromatogra-
phy on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound
as a yellow oil (yield 22.4 mg, 83%).
1
H 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).
13
C 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.
19
F
NMR (565 MHz, Chloroform-d)
δ−
221.23 (tdd, J= 45.20, 28.25, 22.60 Hz, 1F). HRMS (ESI)
(m/z): calcd for C18 H19FNaO ([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%).
1
H 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).
13
C 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)
.
19
F
NMR (565 MHz, Chloroform-d)
δ
-221.32 (tdd, J= 45.20, 28.25, 22.60 Hz, 1F). HRMS (ESI)
(m/z): calcd for C20 H17FNaO ([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%).
1
H 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).
13
C 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).
19
F NMR
(565 MHz, Chloroform-d)
δ−
221.44 (tdd, J= 45.20, 28.25, 22.60 Hz, 1F). HRMS (ESI) (m/z):
calcd for C24H19 FNaO ([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%).
1
H 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).
13
C 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)
.
19
F NMR (565 MHz, Chloroform-d)
δ−
221.36 (tdd, J= 45.20, 28.25, 22.60 Hz,
1F). HRMS (ESI) (m/z): calcd for C19 H16FNNaO ([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 col-
umn 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%).
1
H 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).
13
C 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).
19
F NMR (565 MHz, Chloroform-d)
δ−
221.34
(tdd, J= 50.85, 33.90, 28.25 Hz, 1F). HRMS (ESI) (m/z): calcd for C
22
H
17
FNaO
2
([M + Na]
+
),
355.1104; found, 355.1104.

Molecules 2024,29, 790 13 of 19
2-(benzo[d][1,3]dioxol-5-yl)-4-fluoro-1-phenylbutan-1-one (26) Purification by column chro-
matography on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title
compound as a yellow oil (yield 23.2 mg, 81%).
1
H 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).
13
C 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.
19
F NMR (565 MHz, Chloroform-d)
δ−
221.48
(tdd, J= 50.85, 33.90, 22.60 Hz, 1F). HRMS (ESI) (m/z): calcd for C
17
H
15
FNaO
3
([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 chromatog-
raphy on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound
as a yellow oil (yield 21.7 mg, 50%).
1
H 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).
13
C 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.
19
F NMR (565 MHz,
Chloroform-d)
δ−
221.38 (tdd, J= 45.20, 28.25, 22.60 Hz, 1F). HRMS (ESI) (m/z): calcd for
C25H22 FNNaO3S ([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%).
1
H 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).
13
C 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).
19
F NMR (565 MHz,
Chloroform-d)
δ−
221.32 (tdd, J= 45.20, 28.25, 22.60 Hz, 1F). HRMS (ESI) (m/z): calcd for
C18H15 FNaO2([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%).
1
H 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).
13
C 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).
19
F NMR
(565 MHz, Chloroform-d)
δ−
220.48 (tdd, J= 45.20, 28.25, 22.60 Hz, 1F). HRMS (ESI) (m/z):
calcd for C17H15 FNaO3([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%).
1
H 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).
13
C 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.
19
F NMR (565 MHz, Chloroform-d)
δ
−
221.31 (tdd, J= 50.85, 33.90, 28.25 Hz, 1F). HRMS (ESI) (m/z): calcd for C
18
H
19
FNaO ([M
+ Na]+), 293.1312; found, 293.1315.
1-(4-(tert-butyl)phenyl)-4-fluoro-2-(p-tolyl)butan-1-one (31) Purification by column chromatog-
raphy on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound
as a yellow oil (yield 24.9 mg, 80%).
1
H NMR (500 MHz, Chloroform-d)
δ
8.09–7.79 (m, 2H),

Molecules 2024,29, 790 14 of 19
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.
19
F NMR (565 MHz, Chloroform-d)
δ−
221.28 (tdd, J= 45.20, 28.25, 22.60 Hz, 1F). HRMS
(ESI) (m/z): calcd for C21 H25FNaO ([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%).
1
H 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).
13
C 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.
19
F NMR (565 MHz,
Chloroform-d)
δ−
221.51 (tdd, J= 45.20, 28.25, 22.60 Hz, 1F). HRMS (ESI) (m/z): calcd for
C17H16 ClFNaO ([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%).
1
H 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).
13
C
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.
19
F NMR
(565 MHz, Chloroform-d)
δ−
221.52 (tdd, J= 50.85, 33.90, 28.25 Hz, 1F). HRMS (ESI) (m/z):
calcd for C17H16 BrFNaO ([M + Na]+), 357.0260; found, 357.0265.
4-fluoro-2-(p-tolyl)-1-(4-(trifluoromethoxy)phenyl)butan-1-one (34) Purification by column chro-
matography on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title
compound as a yellow oil (yield 9.2 mg, 27%).
1
H 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).
13
C 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.
19
F 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 C
18
H
16
F
4
NaO
2
([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%).
1
H 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).
13
C 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.
19
F NMR (565 MHz,
Chloroform-d)
δ−
221.51 (tdd, J= 45.20, 28.25, 22.60 Hz, 1F). HRMS (ESI) (m/z): calcd for
C18H16 FNNaO ([M + Na]+), 304.1108; found, 304.1105.
4-fluoro-1-(2-methoxyphenyl)-2-(p-tolyl)butan-1-one (36) Purification by column chromatogra-
phy on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound
as a yellow oil (yield 15.4 mg, 54%).
1
H 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).
13
C 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.
19
F NMR (565 MHz,

Molecules 2024,29, 790 15 of 19
Chloroform-d)
δ−
221.34 (tdd, J= 58.85, 33.90, 28.25 Hz, 1F). HRMS (ESI) (m/z): calcd for
C18H19 FNaO2([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%).
1
H 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).
13
C 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.
19
F NMR (565 MHz,
Chloroform-d)
δ−
221.33 (tdd, J= 45.20, 33.90, 28.25 Hz, 1F). HRMS (ESI) (m/z): calcd for
C18H19 FNaO ([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%).
1
H 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).
13
C 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.
19
F 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
C17H16 F2NaO ([M + Na]+), 297.1061; found, 297.1066.
1-(3,5-dimethylphenyl)-4-fluoro-2-(p-tolyl)butan-1-one (39) Purification by column chromatog-
raphy on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound
as a yellow oil (yield 14.2 mg, 50%).
1
H 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).
13
C 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.
19
F NMR (565 MHz, Chloroform-d)
δ−
221.29 (tdd, J= 50.85, 33.90, 28.25 Hz, 1F). HRMS (ESI) (m/z): calcd for C
19
H
21
FNaO
([M + Na]+), 307.1468; found, 307.1473.
4-fluoro-1-(naphthalen-2-yl)-2-(p-tolyl)butan-1-one (40) Purification by column chromatogra-
phy on silica gel (petroleum ether/ethyl acetate = 100:1, v/v) affords the title compound as
a yellow oil (yield 18.7 mg, 61%).
1
H 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).
13
C
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.
19
F NMR (565 MHz, Chloroform-d)
δ−
221.21
(tdd,
J= 50.85
, 33.90,
28.25 Hz
, 1F). HRMS (ESI) (m/z): calcd for C
21
H
20
NaO ([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%).
1
H 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).
13
C 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.
19
F NMR (565 MHz, Chloroform-d)
δ−
221.51 (tdd, J= 45.20,
28.25, 22.60 Hz, 1F). HRMS (ESI) (m/z): calcd for C
15
H
15
FNaOS ([M + Na]
+
), 285.0719;
found, 285.0724.

Molecules 2024,29, 790 16 of 19
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%).
1
H 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).
13
C 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 C16H23 NNaO2, ([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.
1
H 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).
13
C 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.
19
F NMR (565 MHz, Chloroform-d)
δ
−151.49. HRMS (ESI) (m/z): calcd for C28 H26N3O2+, 437.2098; found, 437.2090.
5. Conclusions
In summary, we have developed a robust method for visible light-mediated monofluo-
romethylation/acylation of olefins, employing dual organo-catalysis. A cost-effective and
bench-stable sodium monofluorosulfite (NaSO
2
CH
2
F) served as a CH
2
F 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 CH
2
F
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:
1
H and
13
C NMR data and spectra for all
compounds. Refs. [83–85] 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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