Rational Design and Development of Low-Price, Scalable, Shelf-Stable and Broadly Applicable Electrophilic Sulfonium Ylide-Based Trifluoromethylating Reagents

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of Chemistry

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Accepted Article

Title: Rational Design and Development of Low-Price, Scalable, Shelf-Stable and

Broadly Applicable Electrophilic Sulfonium Ylide-Based Trifluoromethylating

Reagents

Authors: Yafei Liu, Yijing Ling, Hangming Ge Long Lu* and Qilong Shen*

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This work may now be cited as: Chin. J. Chem. 2021, 39, 10.1002/cjoc.202100107.

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Shen Qilong (Orcid ID: 0000-0001-5622-153X)

Cite this paper: Chin. J. Chem. 2021, 39, XXX—XXX. DOI: 10.1002/cjoc.202100XXX

Rational Design and Development of Low-Price, Scalable,

Shelf-Stable and Broadly Applicable Electrophilic Sul-

fonium Ylide-Based Trifluoromethylating Reagents

Yafei Liu,^aYijing Ling,^aHangming Ge^aLong Lu*^,band Qilong Shen*^,a

^aKey Laboratory of Organofluorine chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, Chi-

nese Academy of Sciences, 345 Lingling Road, shanghai 200032, P. R. China

^bShanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, shanghai 200032, P. R. China

Keywords

fluorine | trifluoromethyl | ylide | electrophilic | reagent

Main observation and conclusion

The development of two highly reactive electrophilic trifluoromethylating reagents (trifluorome-

thyl)(4-nitrophenyl)bis(carbomethoxy)methylide 1g and (trifluoromethyl)(3-chlorophenyl)bis(carbomethoxy)methylide 1j through

structure-activity study were described. Under mild conditions, reagent 1g reacted with β-ketoesters and silyl enol ethers to give

α-trifluoromethylated-β-ketoesters or α-trifluoromethylated ketones in high yields. In addition, reagent 1g could be served as a tri-

fluoromethyl radical for a variety of trifluoromethylative transformations under visible light irradiation, including radical trifluoro-

methylation of electron-rich indoles and pyrroles and sodium aryl sulfinates as well as trifluoromethylative difunctionalization with

styrene derivatives. On the other hand, as a complimentary, under reductive coupling conditions, reagent 1j reacted with a variety of

(hetero)aryl iodides for the formation of trifluoromethylated (hetero)arenes.

Comprehensive Graphic Content

*E-mail:shenql@mail.sioc.ac.cn; lulong@mail.sioc.ac.cn .

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Supporting Information

Liu and Ling contribute equally.

Chin. J. Chem. 2021, 39, XXX－XXX

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through the copyediting, typesetting, pagination and proofreading process which may lead to

differences between this version and the Version of Record. Please cite this article as doi:

10.1002/cjoc.202100107

First author et al.

Report

reagent 2a plays a pivotal role in enhancing its reactivity, since

less than 2% conversion was observed when a pa-

Background and Originality Content

ra-methoxyphenyl substituted selenium ylide 2b was subjected to

the identical reaction conditions for the α-trifluoromethylation

reaction of β-ketoesters.^[3]Moreover, related studies on other

sulfonium ylides based electrophilic difluoromethylating,^[5]

monomethylating^[6]and pentafluoroethylating reagents^[7]also

disclosed that reagents with a strong electron-withdrawing group

exhibit much higher reactivities than those parent ylides in the

absence of such a group.

In 2015, during the study of the reactivity of a remotely

alkenyl-substituted alkyltrifluoromethylthioether with dimethyl

diazomalonate in the presence of a rhodium catalyst, we found

that the formation of an expected [2+1]-cycloaddition product

was not observed. Instead, a trifluoromethyl-substituted sul-

fonium ylide was generated in high yield.^[1]This serendipitous

discovery led us to invent an electrophilic trifluoromethylating

reagent-(trifluoromethyl)(phenyl)bis(carbomethoxy)methylide 1a,

which reacted with β-ketoesters as well as aryl iodides to give the

corresponding α-trifluoromethyl-substituted β-ketoesters and

trifluoromethylarenes in moderate to good yields.^[2]Nevertheless,

reagent 1a is not a highly reactive electrophilic trifluoromethylat-

ing reagent since both reactions required high temperature (100

^oC) to occur in full conversion. Subsequent studies revealed that

an analogous trifluoromethyl-substituted selenium ylide 2a bear-

ing an electron-withdrawing 4-nitrophenyl substituent exhibits

much higher reactivity and broader substrate scope.^[3]For in-

stance, reaction of β-ketoesters with reagent 2a using DBU as the

base, which occurred to full conversion after 2.0 h at room tem-

perature, was much faster than that with reagent 1a. In addition,

reagent 2a reacted with various silyl enol ethers or (hetero)aryl

boronic acids in the presence of a copper catalyst under mild con-

ditions. As a comparison, the same reaction with reagent 1a did

not occur at all. Furthermore, reagent 2a could be used as a tri-

fluoromethyl radical precursor for a variety of trifluoromethylating

reactions. For example, under irradiation of blue LED, reagent 2a

reacted with electron-rich arenes and heteroarenes in DMSO to

give trifluoromethyl(hetero)arenes which are the pharmaceutical-

ly important structural moieties in high yields, even in the absence

of a photoredox catalyst. In the presence of a photoredox catalyst

and a Lewis acid cocatalyst, reagent 2a was enabled to react with

alkenes and a variety of nucleophiles to give trifluoromethylative

difunctionlized products in good to excellent yields.^[4]Struc-

ture-activity studies showed the installation of the strong elec-

tron-withdrawing nitro group on the selenium ylide skeleton of

In light of the fact that the reactivity and the scope of the

fluoroalkyl-substituted sulfonium or selenium ylide could be

greatly improved by the installation of a strong elec-

tron-withdrawing group, we envisaged whether replacing sub-

stituents on the phenyl group in reagent 1a by an elec-

tron-withdrawing group could create a more general, highly reac-

tive and potentially broadly applicable electrophilic trifluorometh-

ylating reagent. We reasoned that there are several advantages of

using a sulfonium ylide over a selenium ylide as the electrophilic

trifluoromethylating reagent. 1) The starting materials for the

preparation of sulfonium ylide are much cheaper than those for

the preparation of selenium ylide. For example, KSeCN is three

times more expensive than 4-nitrophenyl disulfide. Consequently,

trifluoromethylating reagent based on sulfonium ylide should be

much cheaper and more accessible than that based on selenium

ylide. 2) The preparation of selenium ylide typically used

4-nitrobenzenediazonium tetrafluoroborate as the starting mate-

rial, which is not commercially available and needs to be prepared

in situ. In addition, diazonium salt is potentially explosive when

used in bulk quantities. 3) It was found that the selenium moiety

in the selenium ylide was transformed into diselenoether, seleno-

ether and several unidentified compounds that often complicated

the purification process, while dimethyl 2-(arylthio)malonate was

the only side product for the reaction using sulfonium ylide which

could be easily separated.

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Running title

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Herein, we report that we successfully identified (trifluoro-

methyl)(4-nitrophenyl)bis(carbomethoxy)methylide 1g to be an

easily available, cheap, scalable and broadly applicable electro-

philic trifluoromethylating reagent through structure-activity

study of trifluoromethyl-substituted sulfonium ylide. In addition,

we also discovered a complimentary reagent 1j with a me-

ta-chloro group on the phenyl moiety of the ylide which reacted

with a variety of (hetero)aryl iodides for the formation of trifluo-

romethylated (hetero)arenes under mild conditions (Figure 1).

Figure 2 Preparation of Substituted trifluoromethyl sulfonium ylides.

then allowed to react with dimethyl diazomalonate in the pres-

ence of 100 ppm Rh₂(esp)₂to give the ylides 1a-l in 30-85% yields.

Figure 1 Substituted trifluoromethyl sulfonium ylides for struc-

ture-activity study.

To determine whether a highly reactive electrophilic trifluo-

romethylating reagent would be a commonly used, the price an-

davailability of the reagent are two of the most important factors

to consider.^[^10]Obviously, the methodologies developed for

small-scale preparation of the trifluoromethylated sulfonium

ylides were not suitable for large-scale synthesis since both

methods required the use of stoichiometric amount of expensive

AgSCF₃for the preparation of CuSCF₃or electrophilic trifluorome-

thylthiolating reagent ((2-phenylpropan-2-yl)oxy)(trifluoromethyl)

-thioether. We, therefore, seek to develop a scalable route for the

preparation of the trifluoromethyl-substituted sulfonium ylide

using cheap and commercially available 4-nitrophenyl disulfide

and TMSCF₃as the starting materials.^[11]It was found that treat-

ment of a mixture of 4-nitrophenyl disulfide and TMSCF₃with 3.0

equivalences of LiO^tBu in DMF gave the desired

(4-nitrophenyl)(trifluoromethyl)thioether in 67% yield on a 20

mmol-scale after 1.0 h at room temperature. Subsequent reaction

of (4-nitrophenyl)(trifluoromethyl)thioether with dimethyl diazo-

malonate using 0.1 mol% Rh₂(esp)₂conducted on a 10 gram-scale

generated ylide 1g in 68% yield (Figure 1, Eq. 2). Overall, an inex-

pensive, easy-operation and scalable procedure for the prepara-

tion of reagent 1g is established and paves the way for its further

broad applications.

Results and Discussion

Design and Preparation of various trifluoromethylated sul-

fonium ylides. With the aforementioned considerations in mind,

we initially used reagent 1a as a template for structural modifica-

tions. Considering that the electron-withdrawing group in the

phenyl moiety might significantly affect the electrophilicity of the

reagents, we designed five trifluoromethyl-substituted sulfonium

ylides 1b-e and 1g with different electron-withdrawing substitu-

ents at the para-position of the benzene in the sulfonium ylide

skeleton. As a control, we also designed a trifluorome-

thyl-substituted sulfonium ylide 1f with a strong electron-donating

methoxy group. To probe whether the position of the substituent

will have an effect on the reactivity of the ylide, ylides 1h-i with

the nitro group at the ortho- and meta-position as well as ylide 1j

with a 3-chloro-substitution were designed. To evaluate the effect

of the malonate moiety of the ylide, we designed two analogs of

ylide 1a including ylide 1k with a bulkier ethyl group and ylide 1l

with a less sterically hindered cyclized Meldrum's acid moiety.

Two general methods were employed for the small-scale

preparation of aryl thioethers that were the starting materials for

the synthesis of trifluoromethyl-substituted sulfonium ylides for

late on structure-activity study (Figure 1, Eq 1). The first route

utilized commercially available aryl boronic acids to couple with

((2-phenylpropan-2-yl)oxy)(trifluoromethyl)thioether, an electro-

philic trifluoromethylthiolating reagent previously developed in

our laboratory,^[^8]using a combination of 10 mol% of

Cu(MeCN)₄BF₄and 20 mol% of 2,2’-bipyridine (bpy) as the catalyst

and K₂CO₃as the base. The desired aryl trifluoromethylthi-

oethers could then be obtained in 55-90% yields in sub-gram

scale. Alternatively, aryl trifluoromethylthioethers could be syn-

thesized by reactions of the aryl diazonium tetrafluoroborate salts

with CuSCN, followed by the addition of TMSCF₃in good yields.^[9]

The aryl trifluoromethylthioethers were

Structure-activity study of the trifluoromethyl-substituted

sulfonium ylides. With the substituted trifluoromethylated sul-

fonium ylides in hands, the stage was now set for evaluation of

their reactivities. We chose the reaction of β-ketoesters with the

ylides as a platform to test their activity since high temperature

was required for full conversion for the reaction of β-ketoester

with reagent 1a,^[^2]and any improvement in the reactivity of the

reagent would lead to the decrease in the temperature. On the

other hand, previous studies showed that reaction of β-ketoesters

with selenium ylide 2a occurred at room temperature in high yield

and therefore,^[^3]room temperature was chosen as the bar for

examination of the reactivities of the reagents.^[^13]It was found

that reaction of β-ketoester with ylide 1a-e without any substi-

tuted group or with a weakly electron-withdrawing group such as

chloride, bromide, trifluoromethyl or ester group at the pa-

ra-position of the benzene moiety occurred in less than 11% yields

(Scheme 1, entries 1-5). Likewise, reaction with ylide 1j with me-

ta-chloro substituent occurred in 2% yield (Scheme 1, entry 10).

Chin. J. Chem. 2021, 39, XXX－XXX

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Not surprisingly, ylide 1f that contains an electron-donating pa-

ra-methoxy group was unreactive at all (Scheme 1, entry 6). In

uct 3i in much lower 72% yield (Scheme 2, 3i). Not only

β-ketoesters derived from indanone but also those derived from

tetralone, or 1-benzosuberone reacted with reagent 1g to give the

corresponding products 3j-l in good yields (Scheme 2, 3j-l). Nev-

ertheless, the yields of these substrates were much lower than

those of β-ketoesters derived from indanones. The superior

Scheme 1 Structure-activity study of reagents 1a-l with β-ketoester at

room temperature.

Scheme 2 Structure-activity study of reagents 1a-l with β-ketoester at

room temperature.

^aConditions: β-ketoesters (0.1 mmol), reagent 1a-l (0.12 mmol), K₂CO₃

(0.12 mmol) in DMF (0.5 mL) at room temperature for 24 h; Yields were

determined by ¹⁹F NMR spectroscopy using trifluoromethylbenzene as an

internal standard.

contrast, reaction of β-ketoester with ylide 1g bearing a strongly

electron-withdrawing nitro group occurred much faster to give the

corresponding α-trifluoromethyl-β-ketoester in 75% yield

(Scheme 1, entry 7). The position of the nitro group did not affect

the reactivity significantly since ylides 1h-i with 2-nitro and 3-nitro

group reacted to give the trifluoromethylated product in 85% and

73% yields, respectively (Scheme 1, entries 8-9). These results

highlight the importance of the electron-withdrawing ability of the

substituents to tune the electrophilicity of the reagents.

^aConditions: β-ketoesters (0.5 mmol), reagent 1g (1.25 mmol), K₂CO₃(0.6

mmol) in DMF (3.0 mL) at 40 ^oC for 24 h; Isolated yields. ^bβ-ketoesters (0.1

mmol), reagent 1a (0.25mmol), K₂CO₃(0.12 mmol) in DMF (0.5 mL) at 100

^oC for 2.0 h; Yields were determined by ¹⁹F NMR spectroscopy using tri-

fluoromethylbenzene as an internal standard.

To probe whether the steric hindrance of malonate moiety of

the ylide will affect the reactivity of the reagent, we examined

reactions of β-ketoester with reagent 1k and 1l with either bulkier

ethyl group or less steric hindered cyclic esters. Nevertheless, the

formation of the α-trifluoromethyl-β-ketoester was observed in

less than 2.0 % yield.

Finally, further optimization of the reaction conditions showed

that the yield of the reaction with reagent 1g could be improved

to 91% when the reaction temperature was increased to 40 ^oC.

Reaction with β-ketoesters. Having determined that reagent

1g is a highly reactive electrophilic trifluoromethylating reagent,

we next examined the generality of its reaction with a variety of

β-ketoesters. In general, β-ketoesters with both electron-donating

substituents and electron-withdrawing groups reacted to give the

corresponding α-trifluoromethyl-β-ketoesters in good to excellent

yields. Yet, reactions of β-ketoesters with electron-donating sub-

stituents often occurred in higher yields than those with elec-

tron-withdrawing groups. For example, reaction of methyl

5-methoxy-1-oxo-2,3-dihydro-1H-indene-2-carboxylate with rea-

gent 1g occurred under the optimized conditions to give com-

pound 3b in 98% yield, while reaction of methyl

5-chloro-1-oxo-2,3-dihydro-1H-indene-2-carboxylate occurred in

77% yield, indicating the importance of the nucleophilicity of the

nucleophiles (Scheme 2, 3b and 3d). The steric hindrance of the

ester groups of the β-ketoesters did not affect the yield of the

reaction significantly but with one exception. For instance, reac-

tions of methyl, ethyl or isopropyl 1-oxo-2,3-dihydro-1H

reactivity of reagent 1g over reagent 1a is obvious in reactions of

those less nucleophilic β-ketoesters. For example, methyl

5-bromo-1-oxo-2,3-dihydro-1H-indene-2-carboxylate and methyl

7-bromo-1-oxo-1,2,3,4-tetrahydronaphthalene-2-carboxylate

reacted with reagent 1g after 24 h at 40 ^oC to generate products

3d, 3e and 3k in 77%, 71% and 69% yields respectively. On the

other hand, the same reaction with reagent 1a occurred after 2 h

at 100 ^oC to give products 3d, 3e and 3k in much lower 30%, 18%

and 16% yields, respectively (Scheme 2, 3d, 3e and 3k).

To compare the reactivity of electrophilic trifluoromethylating

reagent 1g based on sulfonium ylide skeleton and reagent 2 based

on selenium ylide skeleton, we conducted two parallel reactions

of β-ketoester with ylide 1g and 2. Because the reaction of

β-ketoester with selenium ylide 2 did not occur in high conversion

when K₂CO₃was used as the base, we chose the conditions using

DBU as the base for comparison.^[^3]It was found that both reac-

tions in a mixed DMF/CH₃CN (v:v = 1:1) solution occurred to full

conversion after 2.0 h at 0 ^oC to give the trifluoromethylated

products in quantitative yields for both ylide 1g and ylide 2, sug-

-indene-2-carboxylate with reagent 1g occurred in 88%, 84% and

97% yields, respectively (Scheme 2, 3f-h). However, reaction of

tert-butyl 1-oxo-2,3-dihydro-1H-indene-2-carboxylate gave prod-

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gesting that the reactivities of two reagents are comparable (Eq.

3).

aryl bromide functional group remains intact (4i), thus providing

opportunity for further transformation via classic cross-coupling

reactions.

Reaction with (hetero)aryl iodides. Previously, we found that

reagent 1a reacted with a variety of aryl iodides in the presence of

2.0 equivalents of copper powders.^[^2,12]Nevertheless, this reduc-

tive trifluoromethylating reaction required 3.0 h at 100 ^oC to occur

in full conversion. To probe whether this reaction could be con-

ducted under mild conditions, we studied the reactions of

4-biphenyl iodide with reagents 1b-l. It was found that while these

reactions conducted at 40 ^oC gave low conversions,

Radical trifluoromethylation with electron-rich (het-

ero)arenes. One limitation for the reaction of aryl iodides is the

requirement of the use of pre-iodo-functionalized arenes that are

expensive and not broadly available. To circumstance such a di-

lemma, we developed a visible light-promoted protocol for direct

trifluoromethylation of electron-rich (hetero)arenes.^[14]During the

study of the reaction of reagent 1g with β-ketoester using DBU as

the base, we found that the color turned to red immediately when

a solution of reagent 1g in DMF with 1.0 equivalent of DBU. UV-vis

absorption study showed a broad new peak at 340-600 nm

Scheme 3 Scope for copper-mediated reductive trifluoromethylation of

(hetero)aryl iodides with reagent 1j.^a

Scheme 4 Scope for visible light-mediated trifluoromethylation of (het-

ero)arenes with reagent 1g.^a

^aConditions: aryl iodide (0.4 mmol), reagent 1j (1.0 mmol), copper powder

(0.8 mmol) in DMF (3.0 mL) at 60 ^oC for 12 h; Isolated yields.

reactions with reagent 1a-c, 1g-j and 1l conducted at 60 ^oC did

occur in high to full conversion and generated the trifluoromethyl

biphenyl in 48-92% yields (See supporting information for detailed

optimization and structure-activity study). More specifically, reac-

tion with reagent 1j in DMF occurred after 12 h at 60 ^oC in full

conversion and quantitative yield.

^aConditions: (Hetero)arene (0.5 mmol), reagent 1g (0.75 mmol), DBU (0.75

mmol) in DMSO (10.0 mL) under blue LED at room temperature for 12 h;

Isolated yields.

showed up, indicating the formation of a donor-acceptor complex

between reagent 1g and DBU. Upon irradiation with blue LED, this

donor-acceptor complex reacted with 3-methylindole smoothly to

give 3-methyl-2-trifluoromethylindole in 70% yield. Further opti-

mization of the reaction conditions disclosed that reaction in

DMSO gave the highest 72% yield. Structure-activity study showed

that reactions using 1a-f, 1j-l as the trifluoromethylating reagent

were not effective at all, while reactions using reagents 1h and 1i

with the nitro group at the ortho- or meta-position gave slightly

low 69% and 50% yields, respectively (See supporting information

for details). These studies also emphasize the importance of the

strong electron-withdrawing nitro group on the reactivity of the

sulfonium ylide reagents.

The reaction conditions were applicable towards a variety of

aryl and heteroaryl iodides, as summarized in Scheme 3. In gen-

eral, both electron-rich aryl iodides and electron-poor aryl iodides

reacted with reagent 1j gave the corresponding trifluoromethyl-

ated arenes in good to excellent yields. For example, reactions of

1-(4-iodophenyl)ethan-1-one and 5-iodo-1,2,3-trimethoxy ben-

zene with reagent 1j afforded trifluoromethylated arenes 4b and

4g in 79% and 75% yields, respectively (Scheme 3, 4b, 4g). In addi-

tion, not only aryl iodides but heteroaryl iodides reacted in high

yields. Reactions of 1-iodoisoquinoline with reagent 1j gave

1-trifluoromethylisoquinoline in 70% yield, while reaction of elec-

tron-rich 4-iododibenzo[b,d]thiophene occurred in 95% yield

(Scheme 3, 4m-n). Because of the neutral reaction conditions, a

variety of common functional groups such as enolizable ketone

(4b), ester (4c), protected phenoxylic hydroxyl group (4d), nitro

(4e) and cyano (4f). Notably, under the optimized conditions, the

We next studied the scope of the reaction. And it was found

that under the blue LED irradiation conditions, a variety of deriva-

tives of indoles and pyrroles reacted with reagent 1g to give tri-

fluoromethylated indoles and pyrroles in high yields (Scheme 4).

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Specifically, reactions of indoles with 2-substituents usually gave

3-trifluoromethylated indoles, while 2-trifluoromethylated indole

was obtained as the major product when 3-position of indole was

occupied (Scheme 5, 5l-m). Reactions of pyrroles with N-arylated

substituted groups occurred to give 2-trifluoromethylated pyrrole

derivatives in good yields (Scheme 4, 5h-k). While reaction of

benzene occurred in low conversion, reaction of electron-rich

1,3,5-trimethoxybenzene afforded the trifluoromethylated arene

5n in 66% yield.

reagent 1g. Not surprisingly, the reaction occurred smoothly to

give the corresponding trifluoromethylsulfone derivatives in

67-88% yields (Scheme 5). The reaction was inhibited by the addi-

tion of 1.0 equivalent of TEMPO or BHT. Likewise, the same reac-

tion under air was completely inhibited. These results suggest the

involvement of a free radical, and in this case, we reasoned that

DMSO might act as the donor to interact with reagent 1g to form

a donor-acceptor complex, which is excited to generate a trifluo-

romethyl radical upon irradiation with blue LED.

To gain some understandings about the mechanism of the re-

action, we conducted several experiments. It was found that reac-

tion in the presence of TEMPO resulted in dramatically decrease in

the yield (9%). Likewise, the yield of the reaction under air

dropped significantly to 24%. To probe whether a sin-

gle-electron-transfer (SET) process takes place, we studied the

reaction in the presence of 1.0 equivalent of 1,4-dinitrobenzene.

Interestingly, it was found that the yield of the reaction decreased

Photocatalytic trifluoromethylative difunctionalization of

styrene derivatives. Encouraged by the easy generation of the

trifluoromethyl radical from reagent 1g under irradiation of visible

light, we next envisaged that if the generated trifluoromethyl

radical could be utilized for difunctionalization of alkenes since

several other broadly investigated electrophilic trifluoromethylat-

ing reagents have been employed in the same type of reac-

tions.^[15]The reaction conditions were then carefully optimized in

terms of the photoredox catalysts, the solvents and the additives.

It was found that the addition of 10 mol% of Lewis acid Sc(OTf)₃

was crucial for the high yielding formation of the

Scheme 5 Scope for visible light-mediated trifluoromethylation of (het-

ero)arenes with reagent 1g.^a

Scheme 6. Scope for photoredox-catalyzed trifluoromethylative difunc-

tionalization of styrenes with reagent 1g.^a

^aConditions: sodium benezesulfinate (0.5 mmol), reagent 1g (0.6 mmol) in

DMSO (10.0 mL) under blue LED at room temperature for 12 h; Isolated

yields.

slightly to 72%, suggesting that the donor-acceptor complex be-

tween DBU and reagent 1g is stable enough to resist the disrup-

tion by the addition of 1,4-dinitrobenzene. Based on these results

and previous work by Yu and coworkers who demonstrated that a

trifluoromethyl radical may be generated upon irradiation of the

donor-acceptor complex from an electrophilic trifluoromethylat-

ing reagent such as Umemoto or Togni reagent,^[^14]we proposed

that the visible light promoted trifluoromethylation of elec-

tron-rich arenes occurred via a similar mechanism. First, a do-

nor-acceptor between DBU and reagent 1g is formed. Upon irra-

diation with blue LED, the donor-acceptor complex is excited to

generate a trifluoromethyl radical and a DBU cation. Because the

strong electron-withdrawing nature of the fluorine, the trifluoro-

methyl radical is electrophilic and would like to attack elec-

tron-rich arene to give a carbon radical, which is further oxidized

by the DBU cation to become a cation. α-Hydrogen elimination in

the presence of DBU gives the final product.

Radical trifluoromethylation with sodium benezesulfinate

derivatives. Previously, we have determined that the trifluoro-

methyl radical generated from reagent 2 in DMSO under the irra-

diation of blue LED reacted with sodium benezesulfinates to give

trifluoroemthylated sulfones in good yields. We, thus, would like

to examine analogous reaction of sodium benezesulfinates with

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^aConditions: styrene (0.5 mmol), reagent 1g (0.6 mmol), Ir(ppy)₃(0.0025

mmol), Sc(OTf)₃(0.05 mmol) and alcohol or H₂O (0.25 mL) in CH₃CN (2.5

mL) under blue LED at room temperature for 10 h; Isolated yields.

ined the reaction of vinyl acetates that are much electron-richer

than styrene derivatives. It was found that using 2.0 mol% of

Ir(ppy)₃as the catalyst and 10 mol% of Sc(OTf)₃as the cocatalyst,

vinyl acetate reacted with reagent 1g under the irradiation of blue

LED in acetonitrile to give trifluoromethylated acetals in good

yields. Addition of 1.0 equivalent of H₂O to the reaction mixture

smoothly converted the acetals to ketones that were easy to be

isolated. Not only the vinyl acetate derived from acetophenone

but also from other ketones including 2,3-dihydro-1H-inden-1-one

and 3,4-dihydronaphthalen-1(2H) -one all reacted under the op-

timized conditions to give the corresponding

CF₃/MeO difunctionalized product (See supporting information for

details) because the generation of the desired product was not

observed in the absence of Sc(OTf)₃. Previously, we found that

Sc(OTf)₃was able to react with selenium yilde 2a to form a stable

Lewis acid-Lewis base complex. Upon irradiation with blue LED,

the photoredox catalyst [Ir(ppy)₃] is excited and gives an electron

to reagent 2a. Consequently, Radical anion 2a^−•quickly undergoes

Se-C cleavage to give trifluoromethyl radical.^[4]Presumptively,

Sc(OTf)₃may play a similar role to activate reagent 1g to generate

trifluoromethyl radical. In addition, excess methanol were re-

quired to ensure high conversion and typically methanol was used

as cosolvent with acetonitrile in a ratio of 1:10. Commonly used

photoredox catalyst Ir(ppy)₃was identified as the best catalyst

and the amount of this catalyst could be reduced to 0.5 mol%.

α-trifluoromethylated ketones in good yields (Scheme 7). In addi-

tion, trisubstituted vinyl acetate also reacted to give the corre-

sponding ketone 9f in 65% yield (Scheme 7). The current protocol

thus provided a general method for the preparation of

α-trifluoromethylated ketones.

Conclusions

Under these optimized conditions, electron-neutral and

In this paper, we developed a highly reactive electrophilic tri-

fluoromethylating reagents (trifluoromethyl)(4-nitrophenyl)bis

(carbomethoxy)methylide 1g through structure-activity study.

Under mild conditions, reagent 1g reacted with β-ketoesters to

give α-trifluoromethylated-β-ketoesters in high yields. In addition,

reagent 1g could be served as a trifluoromethyl radical for a vari-

ety of trifluoromethylative transformations under visible light

irradiation. For example, it reacted with electron-rich indoles and

pyrroles to give trifluoromethylated indoles and pyrroles in good

yields. In addition, it reacted with sodium aryl sulfinates to give

trifluoromethylsulfones in high yields. Furthermore, in the pres-

ence of photoredox catalyst, it reacted with styrene derivatives to

give various β-trifluoromethyl-α-benzyl ethers, alcohol or

α-trifluoromethylketones in good yields. On the other hand, as a

complimentary, under reductive coupling conditions, reagent 1j

was developed to react with a variety of (hetero)aryl iodides for

the formation of trifluoromethylated (hetero)arenes that are im-

portant structural motifs in drug design.

electron-rich styrenes were successfully difunctionalized in good

yields, as shown in Scheme 6. In addition, reaction of

1,1-diarylsubstituted alkene also reacted to give the

Scheme 7. Scope for photoredox-catalyzed trifluoromethylative difunc-

tionalization of vinyl acetates with reagent 1g.^a

Here are some advantages of using reagents 1g/1j as electro-

philic trifluoromethylating reagents:

1. Easy preparation. Reagent 1g was synthesized from com-

mercially available (4-nitrophenyl)(trifluoromethyl)thioether,

CF₃TMS and dimethyl diazomalonate in two steps in overall 50%

yield. Preparation of reagent 1j required the use of

4-nitrobenzene diazonium salt as the starting material to react

with in situ generated CuSCF₃. If we think that the generation of

CuSCF₃from AgSCF₃as a step, reagent 1j could be synthesized

from commercially available starting materials within three steps.

2. Scalable and potential low price. Since all of the starting

materials for the preparation of reagent 1g are purchasable and

the prices for (4-nitrophenyl)(trifluoromethyl)thioether, CF₃TMS

and dimethyl diazomalonate were all less than $500/Kg, the over-

all price for reagent 1g is less than $500/kg. And it is well-known

that the price will be even lower if the preparation is further

scale-up.

3. High reactivity and broad substrate scope. As we demon-

strated in the paper, reagent 1g can serve as an electrophilic tri-

fluoromethylating reagent to react with a range of substrates

including β-ketoesters, electron-rich (hetero)arenes, sodium aryl-

sulfinates, styrene derivatives and vinyl acetates. We are currently

further investigating its reactions to broad its applications.

4. Stability. In the solid state, we found that the reagent un-

der nitrogen is rather stable and no decomposition was observed

after one-month storage in the refrigerator. In addition, differen-

^aReaction conditions: aryl vinyl acetate (0.5 mmol), reagent 1g (0.6 mmol),

Ir(ppy)₃(0.01 mmol), Sc(OTf)₃(0.05 mmol), H₂O (0.5 mmol) in CH₃CN (2.5

mL) under blue LED for 10 h; Isolated yields.

trifluoromethylated product with a quaternary carbon center in

good yield (Scheme 6, 7i). Reactions of electron-poor styrene de-

rivatives, however, occurred in less than 10% conversions. Not

only methanol, other alcohols such as ethanol, isopropanol or

cyclopropanol could also be employed as the nucleophiles for the

difunctionalization reaction (Scheme 6, 7j-l). Furthermore, we

found that water could also be used as the nucleophile for the

current difunctionalization protocol (Scheme 6, 8a-j). The nitrogen

nucleophiles such as anilines or alkyl amines, however, were not

compatible under the optimization.

Photocatalytic trifluoromethylation of vinyl acetate. Consid-

ering that under the photocatalytic difunctionalization reaction

conditions, the electron-rich styrenes reacted much faster and

higher yields than those of electron-poor styrenes, we thus exam-

Chin. J. Chem. 2021, 39, XXX－XXX

www.cjc.wiley-vch.de

First author et al.

Report

tial scanning calorimetry (DSC) analysis suggests that the reagent

is not explosive at all.

149.07, 135.99, 132.40 (q, J = 2.2 Hz), 128.91 (q, J = 308.7 Hz),

124.22 ppm.

Overall, the easy in its preparation, low cost, high reactivity,

broad substrates and high thermal stability render reagent 1g a

potentially common electrophilic trifluoromethylating reagent

with broadly applications. The reactions of reagent 1g with other

types of substrates are investigating currently in our laboratory.

p-Nitrophenyl trifluoromethyl sulfide (12.1 g, 54.0 mmol),

Rh₂(esp)₂(41 mg, 0.054 mmol) and dichloromethane (100 mL)

were placed into a 350 mL Schlenk tube equipped with a magnetic

stirring bar under an atmosphere of argon. Dimethyl diazomalo-

nate (8.54 g, 54.0 mmol) was added slowly. The reaction was

stirred at 40 °C for 24 h. After that, the mixture was cooled to

room temperature and then concentrated in vacuo. The residue

was purified by flash chromatography (Eluent: ethyl ace-

tate/petroleum ether = 1/3, R_f= 0.3) to give ylide 1g as a yellow

solid (12.9 g, 68% yield, Mp: 91-93 °C).

Experimental

General Information. All solvents were purified by standard

method. ¹H NMR spectra were recorded on a 500 MHz, 400 MHz

or 300 MHz. ¹⁹F NMR were recorded on a 376 MHz or 282 MHz

spectrometer. ¹³C NMR spectra were recorded on a Bruker AM400

spectrometer and Agilent 400 or 500 MHz spectrometer. ¹H NMR

and ¹³C NMR chemical shifts were determined relative to internal

standard TMS at δ 0.0 and ¹⁹F NMR chemical shifts were deter-

mined relative to CFCl₃as inter standard. Chemical shifts (δ) are

reported in ppm, and coupling constants (J) are in Hertz (Hz). The

following abbreviations were used to explain the multiplicities: s =

singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br =

broad. Flash column chromatograph was carried out using

300-400 mesh silica gel at medium pressure. Elemental analysis

was conducted on the VARIO EL III. X-ray structure was obtained

on BRUKER SMART APEX CCD.

Trifluoromethyl-phenyl bis(carbomethoxy) methylide 1a.

White solid (113 mg, 92%). ¹H NMR (400 MHz, CDCl₃, 293 K, TMS)

δ 7.72 (d, J = 7.7 Hz, 2 H), 7.63 (t, J = 7.3 Hz, 1 H), 7.57 (t, J = 7.4

Hz, 2 H), 3.74 (s, 6 H); ¹⁹F NMR (375 MHz, CDCl₃) δ -51.1 (s, 3 F);

¹³C NMR (100.7 MHz, CDCl₃, 293 K, TMS) δ 165.74, 132.84, 130.19,

128.47, 125.78, 123.69 (q, J = 333.1 Hz), 54.16, 51.63 ppm. IR

(KBr): ν_max= 3528, 3065, 2995, 2952, 2843, 1736, 1705, 1667,

1579, 1477, 1436, 1301, 1243, 1182, 1077, 1023 cm^-1. MS (ESI):

308.9 (M⁺+H). HRMS (ESI): Calcdfor C₁₂H₁₂O₄SF₃: 309.0399 (M⁺+H),

Found: 309.0403.

Trifluoromethyl-((4-chloro)-phenyl) bis(carbomethoxy) me-

thylide 1b. Pink solid (97 mg, 71%). ¹H NMR (400 MHz, CDCl₃, 293

K, TMS) δ 7.68 (d, J = 8.6 Hz, 2 H), 7.54 (d, J = 8.9 Hz, 2 H), 3.74 (s,

6 H); ¹⁹F NMR (375 MHz, CDCl₃) δ -51.1 (s, 3 F); ¹³C NMR (100.7

MHz, CDCl₃, 293 K, TMS) δ 165.58, 139.87, 130.49, 130.08, 124.12,

123.55 (q, J = 333.6 Hz), 54.35, 51.72 ppm. IR (KBr): ν_max= 3090,

2994, 2952, 2843, 2251, 1736, 1702, 1667, 1572, 1478, 1395,

1316, 1184, 1081, 1009 cm^-1. MS (ESI): 342.7 (M⁺+H). HRMS (ESI):

Calculated for C₁₂H₁₁O₄ClSF₃: 343.0010 (M⁺+H), Found: 343.0013.

Aryl trifluoromethylthioethers were prepared according to the

procedures reported by Shen and coworkers^8bor by Goossen and

coworkers phenyltrifluoromethylthioether^9band all other rea-

gents were received from commercial sources. Solvents were

freshly dried and degassed according to the purification handbook

Purification of Laboratory Chemicals before using.

General Procedure for Rh Catalyzed Addition of Diazomalo-

nate with Trifluoromethylthioether. ArSCF₃(0.50 mmol, 1.0

equiv.), Rh₂(esp)₂(1.5 mL from stock solution A, 0.01 mol%) were

placed into an oven-dried Schlenk tube that was equipped with a

stirring bar under N₂. Diazomalonate (0.40 mmol, 0.8 equiv.) was

added. The tube was quickly sealed with a rubber stopper. The

reaction was stirred at 40 ^oC for 24 h. The mixture was cooled to

room temperature, then concentrated in vacuo. The product was

purified by flash chromatography.

Trifluoromethyl-(4-bromo)phenyl bis(carbomethoxy) me-

thylide 1c. White solid (108 mg, 70%). ¹H NMR (400 MHz, CDCl₃,

293 K, TMS) δ 7.71 (d, J = 8.8 Hz, 2 H), 7.61 (d, J = 8.7 Hz, 2 H), 3.74

(s, 6 H); ¹⁹F NMR (375 MHz, CDCl₃) δ -51.0 (s, 3 F); ¹³C NMR (101

MHz, CDCl₃, 293 K, TMS) δ 165.6, 133.5, 130.1, 128.2, 124.9, 123.5

(q, J = 333.7 Hz), 54.3, 51.7 ppm. IR (KBr): ν_max= 3088, 3018, 2989,

2946, 2902, 2839, 1709, 1671, 1562, 1518, 1474, 1434, 1390,

1330, 1277, 1246, 1176, 1119, 1078, 1002 cm^-1. MS (ESI): 386.8

(M⁺+ H). HRMS (ESI): Calcd for C₁₂H₁₁O₄BrSF₃: 386.9508 (M⁺+ H),

Found: 386.9505.

Stock solution A (2.67 × 10^-2M). 4.0 mg of Rh₂(esp)₂was dis-

solved in 15 mL of CH₂Cl₂. 2.0 mL of the solution was diluted to

20.0 mL with CH₂Cl₂. The resulting solution was stirred at room

temperature for one minute before use.

Trifluoromethyl-(4-trifluoromethylphenyl)

bis(carbomethoxy) methylide 1d. Colorless liquid (51 mg, 34%).

¹H NMR (400 MHz, CDCl₃, 293 K, TMS) δ 7.83 (s, 4 H), 3.74 (s, 6 H);

¹⁹F NMR (375 MHz, CDCl₃) δ -50.4 (s, 3 F), -63.4 (s, 3 F); ¹³C NMR

(101 MHz, CDCl₃, 293 K, TMS) δ 168.8, 165.4, 134.7 (q, J = 33.5

Hz), 128.7, 127.2 (q, J = 3.7 Hz), 123.6 (q, J = 334.3 Hz), 122.9 (q, J

= 273.1 Hz), 52.9, 51.8 ppm. IR (KBr): ν_max= 2955, 1736, 1709,

1670, 1606, 1437, 1404, 1328, 1246, 1180, 1135, 1114, 1089,

1069, 1011 cm^-1. MS (ESI): 376.9 (M⁺+ H). HRMS (ESI): Calcd for

C₁₃H₁₁O₄SF₆: 377.0277 (M⁺+ H), Found: 377.0275.

Scalable route for preparation of the trifluorome-

thyl-substituted sulfonium ylide 1g. 4,4'-Dinitrodiphenyl disulfide

(6.17 g, 20.0 mmol), Lithium tert-butoxide (4.80 g, 60.0 mmol) and

DMF (25.0 mL) were placed into a 100 mL Schlenk tube equipped

with a magnetic stirring bar under an atmosphere of argon. The

mixture was stirred for 5 min at room temperature, followed by

dropwise addition of TMSCF₃(5.90 mL, 40.0 mmol). The reaction

was stirred at room temperature for another 1 hour. After that,

the reaction was quenched with aqueous HCl (1.0 M concentra-

tion) and extracted with ethyl acetate. The organic phases were

collected, washed with brine, dried over Na₂SO₄, filtered and then

concentrated in vacuo. The residue was purified by flash chroma-

tography (Eluent: ethyl acetate/petroleum ether = 1/20, R_f= 0.7)

to give p-nitrophenyl trifluoromethyl sulfide as a yellow liquid

(2.97 g, 67% yield). ¹H NMR (400 MHz, CDCl₃, 293 K, TMS) δ 8.25

(d, J = 8.9 Hz, 2 H), 7.81 (d, J = 8.8 Hz, 2 H); ¹⁹F NMR (376 MHz,

CDCl₃) δ -41.60 (s, 3 F); ¹³C NMR (101 MHz, CDCl₃, 293 K, TMS) δ

Trifluoromethyl-(4-carbomethoxy-phenyl) bis(carbomethoxy)

1

methylide 1e. White solid (124 mg, 85%). H NMR (400 MHz,

CDCl₃, 293 K, TMS) δ 8.20 (d, J = 8.8 Hz, 2 H), 7.74 (d, J = 8.3 Hz, 2

H), 3.95 (s, 3 H), 3.73 (s, 6 H); ¹⁹F NMR (375 MHz, CDCl₃) δ -50.5 (s,

3 F); ¹³C NMR (100.7 MHz, CDCl₃, 293 K, TMS) δ 165.43, 165.13,

134.01, 131.04, 130.26, 127.95, 123.54 (q, J = 334.2 Hz), 53.41,

52.73, 51.71 ppm. IR (KBr): ν_max= 2998, 2954, 2845, 2252, 1732,

1671, 1596, 1436, 1400, 1317, 1282, 1244, 1187, 1084, 1013 cm^-1.

www.cjc.wiley-vch.de

Chin. J. Chem. 2021, 39, XXX－XXX

Running title

Chin. J. Chem.

MS (ESI): 366.9 (M⁺+H). HRMS (ESI): Calculated for C₁₄H₁₄O₆SF₃:

367.0453 (M⁺+H), Found: 367.0448.

Trifluoromethyl-phenyl

2,2-dimethyl-4,6-dioxo-1,3-dioxane-5-yl methylide 1l. Yellow

1

Trifluoromethyl-(4-methoxylphenyl) bis(carbomethoxy) me-

solid (38 mg, 30%). H NMR (400 MHz, CDCl₃, 293 K, TMS) δ 8.08

1

thylide 1f. Colorless oil (107 mg, 79%). H NMR (400 MHz, CDCl₃,

(d, J = 8.0 Hz, 2 H), 7.75 (t, J = 7.5 Hz, 1 H), 7.64 (t, J = 7.8 Hz, 2 H),

1.74 (s, 6 H); ¹⁹F NMR (375 MHz, CDCl₃) δ -50.5 (s, 3 F); ¹³C NMR

(101 MHz, CDCl₃, 293 K, TMS) δ 162.8, 134.8, 131.4, 130.8, 123.5

293 K, TMS) δ 7.78 (d, J = 8.9 Hz, 2 H), 7.03 (d, J = 8.9 Hz, 2 H), 3.86

(s, 3 H), 3.73 (s, 6 H); ¹⁹F NMR (375 MHz, CDCl₃) δ -52.4 (s, 3 F); ¹³

C

NMR (101 MHz, CDCl₃, 293 K, TMS) δ 165.9, 163.6, 132.0, 123.7 (q,

J = 332.3 Hz), 116.1, 115.6, 56.4, 55.7, 51.5 ppm. IR (KBr): ν_max

2952, 1732, 1701, 1667, 1591, 1497, 1436, 1320, 1265, 1242,

1182, 1088, 1024 cm^-1. MS (ESI): 339.0 (M⁺+ H). HRMS (ESI): Calcd

for C₁₃H₁₄O₅SF₃: 339.0509 (M⁺+ H), Found: 339.0507.

(q, J = 330.6 Hz) , 123.6, 104.5, 55.9, 26.3 ppm. IR (KBr): ν_max=

=

3093, 3032, 3011, 2992, 2945, 1719, 1678, 1504, 1484, 1450,

1393, 1382, 1308, 1206, 1100, 1066 cm^-1. MS (ESI): 262.9

([M-C₃H₆O]⁺+ H). HRMS (ESI): Calcd for C₁₂H₁₀O₃SF₃: 291.0297

([M-CHO]⁺), Found: 291.0295.

Trifluoromethyl-(4-nitrophenyl) bis(carbomethoxy) methyl-

ide 1g. Yellow solid (97 mg, 69%). ¹H NMR (400 MHz, CDCl₃, 293 K,

TMS) δ 8.41 (d, J = 8.9 Hz, 2 H), 7.89 (d, J = 8.8 Hz, 2 H), 3.74 (s, 6

H); ¹⁹F NMR (375 MHz, CDCl₃) δ -50.0 (s, 3 F); ¹³C NMR (101 MHz,

CDCl₃, 293 K, TMS) δ 165.3, 150.2, 132.6, 129.2, 125.1, 123.5 (q, J

= 335.1 Hz), 53.3, 51.9 ppm. IR (KBr): ν_max= 3108, 2964, 1725,

1652, 1609, 1578, 1530, 1476, 1448, 1425, 1400, 1364, 1350,

1309, 1287, 1257, 1182, 1114, 1094, 1080, 1005 cm^-1. MS (ESI):

353.9 (M⁺+ H). HRMS (ESI): Calcd for C₁₂H₁₁O₆NSF₃: 354.0254 (M⁺

+ H), Found: 354.0253.

General Procedure for Triﬂuoromethylation of β-Ketoester.

β-ketoester (0.50 mmol, 1.0 equiv.), K₂CO₃(0.60 mmol, 1.2

equiv.), and reagent 1g (0.60 mmol, 1.2 equiv.) were placed into

an oven-dried Schlenk tube that was equipped with a stirring bar

under N₂. The tube was quickly sealed with a rubber stopper and

3.0 mL of freshly distilled DMF was added. The reaction was

stirred at 40 ^oC for 24 h. The mixture was cooled to room temper-

ature, and 20 mL of distilled water and 20 mL of Et₂O were added

and the organic phase was separated. The aqueous phase was

extracted with Et₂O (20 mL × 3) and the combined organic extracts

were dried over anhydrous Na₂SO₄, and concentrated in vacuo.

The crude product was purified by flash chromatography on silica

gel or further purified by preparation HPLC.

Trifluoromethyl-(2-nitrophenyl) bis(carbomethoxy) methyl-

ide 1h. Yellow solid (48 mg, 34%). ¹H NMR (400 MHz, CDCl₃, 293 K,

TMS) δ 8.43 (d, J = 7.6 Hz, 1 H), 8.07 (d, J = 7.7 Hz, 1 H), 8.04 – 7.73

(m, 2 H), 3.75 (s, 6 H); ¹⁹F NMR (375 MHz, CDCl₃) δ -48.5 (s, 3 F);

¹³C NMR (101 MHz, CDCl₃, 293 K, TMS) δ 165.6, 146.5, 134.9,

133.8, 132.2, 126.6, 123.4 (q, J = 335.1 Hz), 122.6, 54.0, 51.8 ppm.

IR (KBr): ν_max= 3093, 3078, 2956, 1736, 1666, 1591, 1540, 1458,

1436, 1352, 1327, 1221, 1182, 1150, 1073, 1050, 1024 cm^-1. MS

(ESI): 353.9 (M⁺+ H). HRMS (ESI): Calcd for C₁₂H₁₁O₆NSF₃:

354.0254 (M⁺+ H), Found: 354.0254.

Methyl 6-methyl-1-oxo-2-(trifluoromethyl)-2,3-dihydro-1H

1

-indene-2-carboxylate 3a. Yellow solid (121 mg, 89%). H NMR

(400 MHz, CDCl₃, 293 K, TMS) δ 7.63 (s, 1 H), 7.51 (d, J = 8.7 Hz, 1

H), 7.41 (d, J = 7.9 Hz, 1 H), 3.77 (s, 3 H), 3.68 (d, J = 17.6 Hz, 1 H),

3.54 (d, J = 17.6 Hz, 1 H), 2.42 (s, 3 H); ¹⁹F NMR (375 MHz, CDCl₃) δ

-69.4 (s, 3 F); ¹³C NMR (100.7 MHz, CDCl₃, 293 K, TMS) δ 192.91,

165.75, 149.14, 138.74, 137.63, 134.57, 125.97, 125.42, 123.55 (q,

J = 281.5 Hz), 63.32 (q, J = 26.1 Hz), 53.52, 33.86, 21.04 ppm. IR

(KBr): ν_max= 2960, 1760, 1725, 1618, 1586, 1497, 1436, 1384,

1313, 1280, 1224, 1248, 1186, 1160, 1125, 1084, 1046 cm^-1. MS

(ESI): 272.9 (M⁺+H). HRMS (ESI): Calcd for C₁₃H₁₂O₃F₃: 273.07

(M⁺+H), Found: 273.0733.

Methyl 5-methoxy-1-oxo-2-(trifluoromethyl)-2,3-dihydro-1H

-indene-2-carboxylate 3b.^[16]White solid (141 mg, 98%). ¹H NMR

(400 MHz, CDCl₃, 293 K, TMS) δ 7.75 (d, J = 8.6 Hz, 1 H), 6.97 (dd, J

= 8.6, 2.2 Hz, 1 H), 6.93 (d, 1 H), 3.91 (s, 3 H), 3.77 (s, 3 H), 3.68 (d,

J = 17.8 Hz, 1 H), 3.51 (d, J = 17.8 Hz, 1 H); ¹⁹F NMR (375 MHz,

CDCl₃) δ -69.5 (s, 3 F); ¹³C NMR (100.7 MHz, CDCl₃, 293 K, TMS) δ

190.71, 166.53, 165.81, 154.86, 136.00, 127.28, 123.57 (q, J =

281.5 Hz), 116.70, 109.35, 63.27 (q, J = 26.1 Hz), 55.86, 53.45,

34.00 ppm.

Trifluoromethyl-(3-nitrophenyl) bis(carbomethoxy) methyl-

ide 1i. Yellow solid (89 mg, 63%). ¹H NMR (400 MHz, CDCl₃, 293 K,

TMS) δ 8.55 (s, 1 H), 8.49 (d, J = 8.3 Hz, 1 H), 8.07 (d, J = 8.0 Hz, 1

H), 7.82 (t, J = 8.1 Hz, 1 H), 3.77 (s, 6 H); ¹⁹F NMR (375 MHz, CDCl₃)

δ -50.08 (s, 3 F); ¹³C NMR (101 MHz, CDCl₃, 293 K, TMS) δ 165.3,

148.9, 133.8, 131.3, 128.4, 127.4, 123.7, 123.6 (q, J = 334.7 Hz),

54.0, 52.0 ppm. IR (KBr): ν_max= 3098, 3078, 3027, 2962, 1701,

1700, 1601, 1541, 1439, 1354, 1316, 1248, 1215, 1176, 1091 cm^-1.

MS (ESI): 354.0 (M⁺+ H). HRMS (ESI): Calcd for C₁₂H₁₁O₆NSF₃:

354.0254 (M⁺+ H), Found: 354.0252.

Trifluoromethyl-(3-chlorophenyl) bis(carbomethoxy) me-

1

thylide 1j. Pink solid (82 mg, 60%). H NMR (400 MHz, CDCl₃, 293

K, TMS) δ 7.69 (s, 1 H), 7.61 (t, J = 7.3 Hz, 2 H), 7.52 (t, J = 8.0 Hz, 1

H), 3.75 (s, 6 H); ¹⁹F NMR (375 MHz, CDCl₃) δ -50.6 (s, 3 F); ¹³C

NMR (101 MHz, CDCl₃, 293 K, TMS) δ 165.5, 136.4, 133.1, 131.2,

128.2, 127.6, 126.4, 123.6 (q, J = 333.8 Hz), 53.8, 51.8 ppm. IR

(KBr): ν_max= 3096, 3074, 3010, 2956, 1702, 1671, 1576, 1461,

1440, 1423, 1413, 1314, 1248, 1215, 1176, 1110, 1084 cm^-1. MS

(ESI): 342.9 (M⁺+ H). HRMS (ESI): Calcd for C₁₂H₁₁O₄ClSF₃:

343.0013 (M⁺+ H), Found: 343.0013.

Methyl 5,6-dimethoxy-1-oxo-2-(trifluoromethyl)-2,3-dihydro

-1H-indene-2–carboxylate 3c.^[13]White solid (135 mg, 85%). ¹H

NMR (400 MHz, CDCl₃, 293 K, TMS) δ 7.19 (s, 1 H), 6.91 (s, 1 H),

3.98 (s, 3 H), 3.90 (s, 3 H), 3.77 (s, 3 H), 3.62 (d, J = 17.5 Hz, 1 H),

3.47 (d, J = 17.5 Hz, 1 H); ¹⁹F NMR (375 MHz, CDCl₃) δ -69.4 (s, 3 F);

¹³C NMR (100.7 MHz, CDCl₃, 293 K, TMS) δ 191.15, 165.84, 156.78,

150.21, 147.57, 127.06, 123.56 (q, J = 281.5 Hz), 106.94, 105.28,

63.30 (q, J = 26.0 Hz), 56.42, 56.14, 53.43, 33.78 ppm.

Trifluoromethyl-phenyl bis(carboethoxy) methylide 1k. Col-

orless oil (156 mg, 58%). ¹H NMR (400 MHz, CDCl₃, 293 K, TMS) δ

7.63 (d, J = 7.7 Hz, 2 H), 7.58 – 7.44 (m, 3 H), 4.12 (q, J = 7.1 Hz, 4

H), 1.16 (t, J = 7.1 Hz, 6 H); ¹⁹F NMR (375 MHz, CDCl₃) δ -51.3 (s, 3

F); ¹³C NMR (100.7 MHz, CDCl₃, 293 K, TMS) δ 165.24, 132.58,

130.03, 128.12, 126.04, 123.71 (q, J = 333.6 Hz), 60.31, 53.84,

14.27 ppm. IR (KBr): ν_max= 3065, 2982, 2905, 1776, 1701, 1654,

1579, 1532, 1478, 1446, 1391, 1369, 1299, 1234, 1179, 1085, 1022

cm^-1. MS (ESI): 337.0 (M⁺+H). HRMS (ESI): Calculated for

Methyl

5-chloro-1-oxo-2-(trifluoromethyl)-2,3-dihydro-1H

-indene-2-carboxylate 3d.^[3]Yellow solid (112 mg, 77%). H NMR

(400 MHz, CDCl₃, 293 K, TMS) δ 7.77 (d, J = 8.2 Hz, 1 H), 7.53 (s, 1

H), 7.45 (d, J = 8.3 Hz, 1 H), 3.79 (s, 3 H), 3.73 (d, J = 17.9 Hz, 1 H),

3.56 (d, J = 17.9 Hz, 1 H); ¹⁹F NMR (375 MHz, CDCl₃) δ -69.4 (s, 3 F);

¹³C NMR (101 MHz, CDCl₃, 293 K, TMS) δ 191.3, 165.2 (q, J = 2.1

Hz), 153.0, 143.1, 132.8 (d, J = 1.6 Hz), 129.4, 126.6, 123.3 (q, J =

281.7 Hz), 63.2 (q, J = 26.5 Hz), 53.7, 33.8 (d, J = 1.9 Hz) ppm. IR

1

C₁₄H₁₆O₄SF₃: 337.0714 (M⁺+H), Found: 337.0716.

Chin. J. Chem. 2021, 39, XXX－XXX

www.cjc.wiley-vch.de

First author et al.

Report

(KBr): ν_max= 2966, 2924, 2853, 1754, 1723, 1600, 1466, 1449,

1440, 1421, 1328, 1294, 1267, 1251, 1215, 1199, 1180, 1158,

1110, 1089, 1070, 1044 cm^-1. MS (EI): 292 (M⁺). HRMS (EI): Calcd

for C₁₂H₈O₃ClF₃: 292.0114 (M⁺), Found: 292.0108.

165.77, 142.07, 134.32, 131.33, 128.69, 128.38, 127.26, 123.77 (q,

J = 284.1 Hz), 61.93 (q, J = 24.2 Hz), 53.57, 27.68, 25.02 ppm.

Methyl

7-bromo-1-oxo-2-(trifluoromethyl)-1,2,3,4

-tetrahydronaphthalene-2-Carboxylate 3k. White solid (120 mg,

69%). ¹H NMR (400 MHz, CDCl₃, 293 K, TMS) δ 8.22 (d, J = 1.9 Hz, 1

H), 7.63 (dd, J = 8.2, 2.1 Hz, 1 H), 7.14 (d, J = 8.2 Hz, 1 H), 3.77 (s, 3

H), 2.96 (dd, J = 10.8, 3.9 Hz, 2 H), 2.83 (dt, J = 13.6, 3.9 Hz, 1 H),

2.45 (ddd, J = 13.7, 10.9, 6.2 Hz, 1 H); ¹⁹F NMR (375 MHz, CDCl₃) δ

-68.9 (s, 3 F); ¹³C NMR (101 MHz, CDCl₃, 293 K, TMS) δ 185.8,

165.4, 140.7, 137.1, 132.9, 131.2, 130.5, 123.6 (q, J = 284.1 Hz),

Methyl

5-bromo-1-oxo-2-(trifluoromethyl)-2,3-dihydro-1H

1

-Indene-2-carboxylate 3e.^[3]White solid (119 mg, 71%). H NMR

(400 MHz, CDCl₃, 293 K, TMS) δ 7.72 (s, 1 H), 7.70 (d, J = 8.2 Hz, 1

H), 7.61 (d, J = 8.2 Hz, 1 H), 3.79 (s, 3 H), 3.73 (d, J = 17.9 Hz, 1 H),

3.57 (d, J = 17.9 Hz, 1 H); ¹⁹F NMR (375 MHz, CDCl₃) δ -69.4 (s, 3 F);

¹³C NMR (101 MHz, CDCl₃, 293 K, TMS) δ 191.6, 165.2, 153.0,

133.2, 132.3, 132.0, 129.7, 126.6, 123.3 (q, J = 281.6 Hz), 63.1 (q, J

= 26.6 Hz), 53.7, 33.7 ppm. IR (KBr): ν_max= 2965, 2922, 2852, 1755,

1724, 1596, 1581, 1449, 1440, 1417, 1327, 1292, 1266, 1248,

1214, 1198, 1175, 1157, 1107, 1088, 1057, 1044 cm^-1. MS (EI):

337, 339 (M⁺+ H). HRMS (EI): Calcd for C₁₂H₈O₃BrF₃: 335.9612

(M⁺), Found: 335.9609.

121.4, 61.8 (q, J = 24.4 Hz), 53.7, 27.5, 24.7 ppm. IR (KBr): ν_max

=

3075, 2967, 2924, 2850, 1732, 1702, 1589, 1475, 1453, 1434,

1406, 1346, 1314, 1290, 1266, 1226, 1197, 1176, 1167, 1138,

1112, 1074, 1049 cm^-1. MS (EI): 350, 352 (M⁺). HRMS (EI): Calcd for

C₁₃H₁₀O₃BrF₃: 349.9765 (M⁺), Found: 349.9758.

Methyl 5-oxo-6-(trifluoromethyl)-6,7,8,9-tetrahydro-5H

-benzo[7]annulene-6 -carboxylate 3l. White solid (73 mg, 51%). ¹H

NMR (400 MHz, CDCl₃, 293 K, TMS) δ 7.47 (d, J = 7.6 Hz, 1 H), 7.40

(t, J = 7.2 Hz, 1 H), 7.30 (t, J = 7.5 Hz, 1 H), 7.14 (d, J = 7.5 Hz, 1 H),

3.69 (s, 3 H), 2.96 (ddd, J = 14.7, 9.0, 5.4 Hz, 1 H), 2.85 (dt, J = 15.5,

5.9 Hz, 1 H), 2.56 (ddd, J = 14.0, 6.9, 5.4 Hz, 1 H), 2.21 (ddd, J =

13.8, 8.2, 5.4 Hz, 1 H), 2.11 – 1.90 (m, 2 H); ¹⁹F NMR (375 MHz,

CDCl₃) δ -67.5 (s, 3 F); ¹³C NMR (100.7 MHz, CDCl₃, 293 K, TMS) δ

197.15, 166.16, 138.71, 137.80, 131.97, 129.10, 129.04, 126.82,

123.79 (q, J = 285.1 Hz), 66.14 (q, J = 23.2 Hz), 53.30, 31.72, 27.59,

22.44 ppm. IR (KBr): ν_max= 2956, 2875, 1751, 1699, 1599, 1484,

1449, 1361, 1264, 1199, 1164, 1119, 1075, 1026, 1012 cm^-1. MS

(ESI): 286.9 (M⁺+H). HRMS (ESI): Calculated for C₁₄H₁₄O₃F₃: 287.09

(M⁺+H), Found: 287.0890.

Methyl 1-oxo-2-(trifluoromethyl)-2,3-dihydro-1H-indene-2

-carboxylate 3f. ^[13]Pale yellow solid (115 mg, 88%). ¹H NMR (400

MHz, CDCl₃, 293 K, TMS) δ 7.84 (d, J = 7.7 Hz, 1 H), 7.70 (t, J = 7.8

Hz, 1 H), 7.53 (d, J = 7.7 Hz, 1 H), 7.47 (t, J = 7.5 Hz, 1 H), 3.78 (s, 3

H), 3.74 (d, J = 17.8 Hz, 1 H), 3.60 (d, J = 17.8 Hz, 1 H); ¹⁹F NMR

(375 MHz, CDCl₃) δ -69.4 (s, 3 F); ¹³C NMR (100.7 MHz, CDCl₃, 293

K, TMS) δ 192.83, 165.61, 151.64, 136.28, 134.35, 128.50, 126.30,

125.59, 123.47 (q, J = 281.6 Hz), 62.99 (q, J = 26.3 Hz), 53.55, 34.16

ppm.

Ethyl 1-oxo-2-(trifluoromethyl)-2,3-dihydro-1H-indene-2

-carboxylate 3g.^[13]Pale yellow solid (114 mg, 84%). ¹H NMR (400

MHz, CDCl₃, 293 K, TMS) δ 7.81 (d, J = 7.8 Hz, 1 H), 7.68 (t, J = 7.5

Hz, 1 H), 7.52 (d, J = 8.3 Hz, 1 H), 7.44 (t, J = 7.5 Hz, 1 H), 4.22 (q, J

= 7.1 Hz, 2 H), 3.72 (d, J = 17.7 Hz, 1 H), 3.58 (d, J = 17.7 Hz, 1 H),

1.21 (t, J = 7.1 Hz, 3 H); ¹⁹F NMR (375 MHz, CDCl₃) δ -69.3 (s, 3 F);

¹³C NMR (100.7 MHz, CDCl₃, 293 K, TMS) δ 192.97, 165.06, 151.65,

136.19, 134.30, 128.39, 126.26, 125.38, 123.48 (q, J = 281.6 Hz),

63.01 (q, J = 26.0 Hz), 62.71, 34.08, 13.71 ppm.

General Procedure for Triﬂuoromethylation of (Hetero)aryl

Iodides. (Hetero)aryl iodide (0.40 mmol, 1.0 equiv.), Cu powder

(0.8 mmol, 2.0 equiv.), and reagent 1j (1.0 mmol, 2.5 equiv.) were

placed into an oven-dried Schlenk tube that was equipped with a

stirring bar under N₂. The tube was quickly sealed with a rubber

stopper and 3.0 mL of freshly distilled DMF was added. The reac-

tion was stirred at 60 ^oC for 12 h. The mixture was cooled to room

temperature, and 20 mL of distilled water and 20 mL of Et₂O was

added and the organic phase was separated. The aqueous phase

was extracted with Et₂O (20 mL × 3) and the combined organic

extracts were dried over anhydrous Na₂SO₄, and concentrated in

vacuo. The product was purified by flash chromatography on silica

gel or further purified by Kugelrohr distillation.

Isopropyl 1-oxo-2-(trifluoromethyl)-2,3-dihydro-1H-indene-2

-carboxylate 3h.^[13]White solid (138 mg, 97%). ¹H NMR (400 MHz,

CDCl₃, 293 K, TMS) δ 7.84 (d, J = 7.8 Hz, 1 H), 7.69 (t, J = 7.1 Hz, 1

H), 7.53 (d, J = 7.8 Hz, 1 H), 7.46 (t, J = 7.5 Hz, 1 H), 5.10 (hept, J =

6.0 Hz, 1 H), 3.71 (d, J = 17.6 Hz, 1 H), 3.58 (d, J = 17.7 Hz, 1 H),

1.23 (d, J = 6.3 Hz, 6 H); ¹⁹F NMR (375 MHz, CDCl₃) δ -69.2 (s, 3 F);

¹³C NMR (100.7 MHz, CDCl₃, 293 K, TMS) δ 193.05, 164.64, 151.69,

136.11, 134.48, 128.40, 126.24, 125.49, 123.54 (q, J = 281.5 Hz),

70.86, 63.24 (q, J = 25.8 Hz), 34.15, 21.36, 21.28 ppm.

4-(Trifluoromethyl)biphenyl 4a.^[17]White solid (109 mg, 99%).

¹H NMR (400 MHz, CDCl₃, 293 K, TMS) δ 7.70 (s, 4 H), 7.61 (d, J =

7.2 Hz, 2 H), 7.49 (t, J = 7.4 Hz, 2 H), 7.42 (t, J = 6.7 Hz, 1 H); ¹⁹F

NMR (375 MHz, CDCl₃) δ -62.4 (s, 3 F); ¹³C NMR (100.7 MHz, CDCl₃,

293 K, TMS) δ 144.69, 139.74, 129.30 (q, J = 32.5 Hz), 128.97,

128.17, 127.40, 127.26, 125.69 (q, J = 3.8 Hz), 124.24 (q, J = 262.2

Hz) ppm.

tert-Butyl 1-oxo-2-(trifluoromethyl)-2,3-dihydro-1H-indene-2

-carboxylate 3i.^[13]White solid (109 mg, 72%). ¹H NMR (400 MHz,

CDCl₃, 293 K, TMS) δ 7.83 (d, J = 7.8 Hz, 1 H), 7.67 (t, J = 7.5 Hz, 1

H), 7.52 (d, J = 7.8 Hz, 1 H), 7.44 (t, J = 7.5 Hz, 1 H), 3.68 (d, J = 17.7

Hz, 1 H), 3.56 (d, J = 17.6 Hz, 1 H), 1.42 (s, 9 H); ¹⁹F NMR (375 MHz,

CDCl₃) δ -69.1 (s, 3 F); ¹³C NMR (100.7 MHz, CDCl₃, 293 K, TMS) δ

193.39, 164.04, 151.67, 135.98, 134.61, 128.31, 126.20, 125.38,

123.58 (q, J = 281.3 Hz), 84.27, 63.81 (q, J = 25.8 Hz), 34.24, 27.65

ppm.

1-(4-(Trifluoromethyl)phenyl)ethenone 4b.^[17]White solid (74

mg, 79%). ¹H NMR (400 MHz, CDCl₃, 293 K, TMS) δ 8.06 (d, J = 8.1

Hz, 2 H), 7.73 (d, J = 8.2 Hz, 2 H), 2.64 (s, 3 H); ¹⁹F NMR (375 MHz,

CDCl₃) δ -63.2 (s, 3 F); ¹³C NMR (100.7 MHz, CDCl₃, 293 K, TMS) δ

196.97, 139.63, 134.40 (q, J = 32.7 Hz), 128.60, 125.66 (q, J = 3.8

Hz), 123.57 (q, J = 272.7 Hz), 26.78 ppm.

Methyl 1-oxo-2-(trifluoromethyl)-1,2,3,4-tetrahydro naph-

thalene-2-carboxylate 3j.^[13]White solid (68 mg, 50%). ¹H NMR

(400 MHz, CDCl₃, 293 K, TMS) δ 8.10 (d, J = 8.8 Hz, 1 H), 7.53 (td, J

= 7.5, 1.3 Hz, 1 H), 7.36 (t, J = 7.6 Hz, 1 H), 7.25 (d, J = 8.5 Hz, 1 H),

3.75 (s, 3 H), 3.02 (dd, J = 8.4, 3.9 Hz, 2 H), 2.82 (dt, J = 13.6, 4.0

Hz, 1 H), 2.47 (dt, J = 13.6, 8.5 Hz, 1 H); ¹⁹F NMR (375 MHz, CDCl₃)

δ -68.8 (s, 3 F); ¹³C NMR (100.7 MHz, CDCl₃, 293 K, TMS) δ 186.97,

Methyl 4-(trifluoromethyl)benzoate 4c.^[17]Colorless liquid (86

mg, 84%). ¹H NMR (400 MHz, CDCl₃, 293 K, TMS) δ 8.16 (d, J = 8.1

Hz, 2 H), 7.71 (d, J = 8.2 Hz, 2 H), 3.96 (s, 3 H); ¹⁹F NMR (375 MHz,

CDCl₃) δ -63.2 (s, 3 F); ¹³C NMR (100.7 MHz, CDCl₃) δ 165.87,

www.cjc.wiley-vch.de

Chin. J. Chem. 2021, 39, XXX－XXX

Running title

Chin. J. Chem.

134.45 (q, J = 32.7 Hz), 133.36, 129.98, 125.41 (q, J = 3.6 Hz),

123.63 (q, J = 272.8 Hz), 52.51 ppm.

H), 3.94 (s, 2 H); ¹⁹F NMR (375 MHz, CDCl₃) δ -61.7 (s, 3 F); ¹³

C

NMR (101 MHz, CDCl₃, 293 K, TMS) δ 145.0 (d, J = 1.3 Hz), 143.8,

143.4, 140.2, 128.9 (d, J = 264.3 Hz), 128.6 (d, J = 32.2 Hz), 127.9,

127.0, 125.2, 124.0 (q, J = 3.9 Hz), 121.9 (q, J = 3.8 Hz), 120.6,

119.8, 36.8 ppm. IR (KBr): ν_max= 3024, 2905, 1681, 1619, 1576,

1492, 1468, 1427, 1399, 1347, 1328, 1304, 1286, 1231, 1203,

1184, 1162, 1113, 1064, 1025 cm^-1. MS (EI): 165 (100), 234. HRMS

(EI): Calcd for C₁₄H₉F₃: 234.0656, Found: 234.0661.

1-(Benzyloxy)-4-(trifluoromethyl)benzene 4d.^[17]White solid

(95 mg, 75%). ¹H NMR (400 MHz, CDCl₃, 293 K, TMS) δ 7.55 (d, J =

8.9 Hz, 2 H), 7.42 (q, J = 8.0 Hz, 4 H), 7.36 – 7.30 (m, J = 8.0 Hz, 1

H), 7.04 (d, J = 8.8 Hz, 2 H), 5.11 (s, 2 H); ¹⁹F NMR (375 MHz, CDCl₃)

δ -61.5 (s, 3 F); ¹³C NMR (100.7 MHz, CDCl₃) δ 161.12, 136.17,

128.70, 128.24, 127.44, 126.91 (q, J = 3.8 Hz), 124.40 (q, J = 271.0

Hz), 123.1 (q, J = 32.9 Hz), 114.81, 70.13 ppm.

9-(Trifluoromethyl)phenanthrene 4l. Colorless liquid (85 mg,

86%). ¹H NMR (400 MHz, CDCl₃, 293 K, TMS) δ 8.78 – 8.73 (m, 1

H), 8.69 (d, J = 8.4 Hz, 1 H), 8.25 (ddd, J = 7.9, 3.9, 1.8 Hz, 1 H),

8.18 (s, 1 H), 7.96 (d, J = 8.0 Hz, 1 H), 7.82 – 7.63 (m, 4 H); ¹⁹F NMR

(375 MHz, CDCl₃) δ -60.3 (s, 3 F); ¹³C NMR (101 MHz, CDCl₃, 293 K,

TMS) δ 131.7, 130.9, 129.8, 129.4, 128.9, 127.4, 127.3, 127.3,

127.0 (q, J = 6.3 Hz), 126.7, 125.1 (q, J = 2.6 Hz), 124.6 (q, J = 273.5

Hz), 124.6 (q, J = 29.8 Hz), 123.1, 122.6 ppm. IR (KBr): ν_max= 3069,

2930, 1629, 1605, 1574, 1532, 1498, 1451, 1403, 1351, 1328,

1299, 1264, 1248, 1216, 1190, 1172, 1146, 1108, 1050 cm^-1. MS

(EI): 246. HRMS (EI): Calcd for C₁₅H₉F₃: 246.0656, Found: 246.0652.

1-Nitro-4-(trifluoromethyl)benzene 4e.^[17]White solid (86 mg,

90%). ¹H NMR (400 MHz, CDCl₃, 293 K, TMS) δ 8.37 (d, J = 8.5 Hz, 2

H), 7.85 (d, J = 8.5 Hz, 2 H); ¹⁹F NMR (375 MHz, CDCl₃) δ -63.2 (s, 3

F); ¹³C NMR (100.7 MHz, CDCl₃) δ 150.01, 136.10 (q, J = 33.4 Hz),

126.78 (q, J = 3.7 Hz), 124.09, 122.9 (q, J = 273.1 Hz) ppm.

4-(Trifluoromethyl)benzonitrile 4f.^[9a]White solid (71 mg,

84%). ¹H NMR (400 MHz, CDCl₃, 293 K, TMS) δ 7.81 (d, J = 8.3 Hz, 2

H), 7.76 (d, J = 8.3 Hz, 2 H); ¹⁹F NMR (375 MHz, CDCl₃) δ -63.6 (s, 3

F); ¹³C NMR (100.7 MHz, CDCl₃) δ 134.56 (q, J = 33.4 Hz), 132.67,

126.18 (q, J = 3.7 Hz), 123.02 (q, J = 273.0 Hz), 117.43, 116.04

ppm.

4-(Trifluoromethyl)dibenzo[b,d]thiophene 4m. White solid

(96 mg, 95%). ¹H NMR (400 MHz, CDCl₃, 293 K, TMS) δ 8.30 (d, J =

7.9 Hz, 1 H), 8.17 (dd, J = 6.4, 2.2 Hz, 1 H), 7.89 (dd, J = 6.5, 2.0 Hz,

1 H), 7.76 (d, J = 7.5 Hz, 1 H), 7.60 – 7.45 (m, 3 H); ¹⁹F NMR (375

MHz, CDCl₃) δ -63.0 (s, 3 F); ¹³C NMR (101 MHz, CDCl₃, 293 K, TMS)

δ 139.4 (q, J = 1.7 Hz), 137.3, 136.4, 134.2, 127.6, 125.4 (q, J = 33.7

Hz), 124.8, 124.7 (q, J = 0.8 Hz), 124.2 (q, J = 5.5 Hz), 124.2, 124.2

(q, J = 272.8 Hz), 122.5, 121.7 ppm. IR (KBr): ν_max= 3070, 1599,

1588, 1574, 1459, 1444, 1403, 1351, 1335, 1319, 1302, 1253,

1200, 1174, 1133, 1108, 1074, 1029 cm^-1. MS (EI): 252. HRMS (EI):

Calcd for C₁₃H₇SF₃: 252.0221, Found: 252.0219.

1,2,3-Trimethoxy-5-(trifluoromethyl)benzene 4g.^[18]White

solid (89 mg, 75%). ¹H NMR (400 MHz, CDCl₃, 293 K, TMS) δ 6.83

(s, 2 H), 3.90 (s, 6 H), 3.88 (s, 3 H); ¹⁹F NMR (375 MHz, CDCl₃) δ

-62.1 (s, 3 F); ¹³C NMR (100.7 MHz, CDCl₃) δ 153.38, 140.55,

125.70 (q, J = 32.6 Hz), 124.03 (q, J = 271.9 Hz), 102.50 (q, J = 3.8

Hz), 60.89, 56.26 ppm.

6-(Trifluoromethyl)quinolone 4h.^[9a]White solid (72 mg, 72%).

¹H NMR (400 MHz, CDCl₃, 293 K, TMS) δ 8.95 (d, J = 4.0 Hz, 1 H),

8.14 (d, J = 8.5 Hz, 2 H), 8.04 (s, 1 H), 7.80 (d, J = 8.8 Hz, 1 H), 7.41

(dd, J = 8.3, 4.2 Hz, 1 H); ¹⁹F NMR (375 MHz, CDCl₃) δ -62.4 (s, 3 F);

¹³C NMR (100.7 MHz, CDCl₃) δ 152.31, 148.95, 136.66, 130.55,

128.24 (q, J = 32.6 Hz), 127.01, 125.63 (q, J = 4.4 Hz), 124.93 (q, J =

3.0 Hz), 123.84 (q, J = 272.3 Hz), 122.10 ppm.

1-(Trifluoromethyl)isoquinoline 4n.^[18]White solid (69 mg,

70%). ¹H NMR (400 MHz, CDCl₃, 293 K, TMS) δ 8.58 (d, J = 5.5 Hz, 1

H), 8.30 (d, J = 8.5 Hz, 1 H), 7.92 (d, J = 8.1 Hz, 1 H), 7.84 (d, J = 5.6

Hz, 1 H), 7.77 (t, J = 7.6 Hz, 1 H), 7.71 (t, J = 7.6 Hz, 1 H); ¹⁹F NMR

(375 MHz, CDCl₃) δ -63.0 (s, 3 F); ¹³C NMR (101 MHz, CDCl₃) δ

146.42 (q, J = 33.2 Hz), 140.76, 137.14, 130.90, 128.84, 127.52,

124.63 (q, J = 2.9 Hz), 124.59, 124.55, 122.24 (q, J = 276.2 Hz)

ppm.

4-Bromo-4'-(trifluoromethyl)-1,1'-biphenyl 4i. White solid

(119 mg, 99%). ¹H NMR (400 MHz, CDCl₃, 293 K, TMS) δ 7.71 (d, J =

8.1 Hz, 2 H), 7.65 (d, J = 8.2 Hz, 2 H), 7.61 (d, J = 8.3 Hz, 2 H), 7.46

(d, J = 8.3 Hz, 2 H); ¹⁹F NMR (375 MHz, CDCl₃) δ -62.5 (s, 3 F); ¹³

C

NMR (101 MHz, CDCl₃, 293 K, TMS) δ 143.5 (d, J = 1.2 Hz), 138.6,

132.1, 129.7 (d, J = 32.5 Hz), 128.8, 127.2, 125.8 (q, J = 3.7 Hz),

124.2 (d, J = 272.0 Hz), 122.6 ppm. IR (KBr): ν_max= 3049, 1615,

1587, 1557, 1477, 1417, 1389, 1326, 1158, 1126, 1108, 1069,

1019, 1003 cm^-1. MS (EI): 300, 302. HRMS (EI): Calcd for C₁₃H₈BrF₃:

299.9761, Found: 299.9758.

General Procedure for Triﬂuoromethylation of (Het-

ero)arenes. (Hetero)arene (0.50 mmol, 1.0 equiv.), DBU (0.75

mmol, 1.5 equiv.), and reagent 1g (0.75 mmol, 1.5 equiv.) were

placed into an oven-dried Schlenk tube that was equipped with a

stirring bar under N₂. The tube was quickly sealed with a rubber

stopper and 10.0 mL of freshly distilled DMSO was added. The

reaction was stirred at room temperature for 12 h under irradia-

tion of blue LED. The mixture was cooled to room temperature,

and 20 mL of distilled water and 20 mL of Et₂O was added and the

organic phase was separated. The aqueous phase was extracted

with Et₂O (20 mL × 3) and the combined organic extracts were

dried over anhydrous Na₂SO₄, and concentrated in vacuo. The

product was purified by flash chromatography on silica gel.

N,N-diphenyl-4-(trifluoromethyl)aniline 4j. Colorless liquid

(115 mg, 92%). ¹H NMR (400 MHz, CDCl₃, 293 K, TMS) δ 8.47 (s, 1

H), 8.21 (d, J = 7.7 Hz, 1 H), 7.68 (d, J = 7.8 Hz, 1 H), 7.65 (d, J = 7.5

Hz, 2 H), 7.57 (s, 2 H), 7.54 (d, J = 10.0 Hz, 2 H), 7.49 (d, J = 8.4 Hz,

2 H), 7.45 (d, J = 8.2 Hz, 2 H), 7.38 (t, J = 7.2 Hz, 1 H); ¹⁹F NMR (375

MHz, CDCl₃) δ -60.1 (s, 3 F); ¹³C NMR (101 MHz, CDCl₃, 293 K, TMS)

δ 142.3, 141.6, 136.9, 130.0, 128.0, 127.1, 126.9, 125.2 (q, J =

271.4 Hz), 123.0, 122.8, 122.7 (q, J = 3.6 Hz), 122.1 (q, J = 32.1 Hz),

120.7, 120.5, 117.9 (q, J = 4.0 Hz), 110.2, 109.9 ppm. IR (KBr): ν_max

= 3063, 3042, 2923, 1629, 1600, 1502, 1480, 1460, 1437, 1366,

1340, 1326, 1270, 1237, 1161, 1131, 1110, 1074, 1056, 1025,

1013, 942 cm^-1. MS (EI): 311 (100), 313. HRMS (EI): Calcd for

C₁₉H₁₂NF₃(M – 2H): 311.0922, Found: 311.0929.

3-Methyl-2-(trifluoromethyl)-1H-indole 5a.^[3]Yellow solid (70

1

mg, 70%). H NMR (400 MHz, CDCl₃, 293 K, TMS) δ 8.18 (br, 1 H),

7.64 (d, J = 8.0 Hz, 1 H), 7.39 (d, J = 8.2 Hz, 1 H), 7.33 (t, J = 7.5 Hz,

1 H), 7.20 (t, J = 7.4 Hz, 1 H), 2.45 (d, J = 1.3 Hz, 3 H); ¹⁹F NMR (375

MHz, CDCl₃) δ -59.0 (s, 3 F) ppm. IR (KBr): ν_max= 3393, 2960, 2925,

2851, 1594, 1570, 1454, 1376, 1319, 1261, 1197, 1163, 1112,

1080, 1031, 1003 cm^-1. MS (EI): 199 (100). HRMS (EI): Calcd for

C₁₀H₈F₃N: 199.0609, Found: 199.0607.

2-(Trifluoromethyl)-9H-fluorene 4k. White solid (109 mg,

99%). ¹H NMR (400 MHz, CDCl₃, 293 K, TMS) δ 7.85 (d, J = 6.2 Hz, 1

H), 7.83 (d, J = 4.8 Hz, 1 H), 7.79 (s, 1 H), 7.65 (d, J = 8.0 Hz, 1 H),

7.59 (d, J = 6.9 Hz, 1 H), 7.43 (t, J = 7.1 Hz, 1 H), 7.41 – 7.36 (m, 1

Chin. J. Chem. 2021, 39, XXX－XXX

www.cjc.wiley-vch.de

First author et al.

Report

2-(Naphthalen-2-yl)-3-(trifluoromethyl)-1H-indole 5b. Yellow

1265, 1225, 1215, 1170, 1150, 1136, 1104, 1062, 1016 cm^-1. MS

(EI): 313 (100), 315 (36.71). HRMS (EI): Calcd for C₁₅H₈F₄ClN:

313.0281, Found: 313.0275.

liquid (80 mg, 51%). ¹H NMR (400 MHz, CDCl₃, 293 K, TMS) δ 8.43

(br, 1 H), 8.07 (s, 1 H), 7.95 (d, J = 8.5 Hz, 1 H), 7.92 (d, J = 3.7 Hz, 1

H), 7.89 (d, J = 9.6 Hz, 2 H), 7.70 (d, J = 8.3 Hz, 1 H), 7.60 – 7.55 (m,

2 H), 7.46 – 7.41 (m, 1 H), 7.36 – 7.27 (m, 2 H); ¹⁹F NMR (375 MHz,

CDCl₃) δ -52.7 (s, 3 F); ¹³C NMR (101 MHz, CDCl₃, 293 K, TMS) δ

138.5 (q, J = 4.0 Hz), 135.0, 133.4, 132.9, 128.5 (q, J = 1.1 Hz),

128.4, 128.4, 128.3, 127.8, 127.1, 126.8, 126.3 (q, J = 1.6 Hz),

125.7 (q, J = 1.8 Hz), 124.8 (q, J = 264.9 Hz), 123.5, 121.7, 120.0 (q,

J = 1.6 Hz), 111.1, 103.7 (q, J = 35.8 Hz) ppm. IR (KBr): ν_max= 3411,

3058, 1621, 1605, 1584, 1558, 1507, 1474, 1456, 1443, 1431,

1371, 1341, 1314, 1280, 1232, 1213, 1166, 1148, 1096, 1017 cm^-1.

MS (EI): 311 (100). HRMS (EI): Calcd for C₁₉H₁₂F₃N: 311.0922,

Found: 311.0926.

Ethyl 3-(trifluoromethyl)-1H-indole-2-carboxylate 5g.^[3]Yel-

low solid (41 mg, 32%). ¹H NMR (400 MHz, CDCl₃, 293 K, TMS) δ

9.47 (br, 1 H), 7.92 (d, J = 8.2 Hz, 1 H), 7.47 (d, J = 8.3 Hz, 1 H), 7.39

(t, J = 7.5 Hz, 1 H), 7.29 - 7.26 (m, 1 H), 4.48 (q, J = 7.1 Hz, 2 H),

1.45 (t, J = 7.1 Hz, 3 H); ¹⁹F NMR (375 MHz, CDCl₃) δ -53.8 (s, 3 F);

¹³C NMR (101 MHz, CDCl₃, 293 K, TMS) δ 160.3, 134.5, 126.1,

125.9 (q, J = 4.0 Hz), 125.0 (q, J = 1.5 Hz), 123.8 (q, J = 268.2 Hz),

122.7, 122.0 (q, J = 3.1 Hz), 112.1, 110.0 (q, J = 37.9 Hz), 62.2, 14.0

ppm. IR (KBr): ν_max= 3310, 2991, 1690, 1544, 1474, 1461, 1444,

1403, 1385, 1376, 1366, 1338, 1289, 1266, 1226, 1200, 1157,

1134, 1120, 1029, 1016 cm^-1. MS (EI): 28 (100), 211, 257. HRMS

(EI): Calcd for C₁₂H₁₀F₃NO₂: 257.0664, Found: 257.0675.

2-(4-Clorophenyl)-3-(trifluoromethyl)-1H-indole 5c. Yellow

solid (73 mg, 50%). ¹H NMR (400 MHz, CDCl₃, 293 K, TMS) δ 8.34

(br, 1 H), 7.82 (d, J = 7.8 Hz, 1 H), 7.51 (d, J = 8.5 Hz, 2 H), 7.45 (d, J

= 8.4 Hz, 2 H), 7.40 (d, J = 8.0 Hz, 1 H), 7.33 – 7.23 (m, 2 H); ¹⁹F

NMR (375 MHz, CDCl₃) δ -52.9 (s, 3 F); ¹³C NMR (101 MHz, CDCl₃,

293 K, TMS) δ 137.1 (q, J = 4.0 Hz), 135.6, 134.9, 130.2 (q, J = 1.4

Hz), 129.4, 128.9, 125.5 (q, J = 1.8 Hz), 124.6 (q, J = 267.4 Hz),

123.7, 121.9, 120.0 (q, J = 1.5 Hz), 111.1, 103.9 (q, J = 35.8 Hz)

ppm. IR (KBr): ν_max= 3404, 3058, 2928, 1619, 1601, 1572, 1556,

1518, 1492, 1444, 1401, 1373, 1344, 1320, 1280, 1225, 1212,

1167, 1151, 1112, 1017 cm^-1. MS (EI): 295 (100), 297 (35.2). HRMS

(EI): Calcd for C₁₅H₉F₃NCl: 295.0376, Found: 295.0380.

1-Phenyl-2-(trifluoromethyl)-pyrrole 5h^[3]Colorless liquid (85

mg, 80%). ¹H NMR (400 MHz, CDCl₃, 293 K, TMS) δ 7.47 – 7.42 (m,

3 H), 7.40 – 7.35 (m, 2 H), 6.91 – 6.86 (m, 1 H), 6.77 – 6.71 (m, 1

H), 6.28 (t, J = 3.2 Hz, 1 H); ¹⁹F NMR (375 MHz, CDCl₃) δ -55.9 (s, 3

F); ¹³C NMR (101 MHz, CDCl₃, 293 K, TMS) δ 139.5, 129.3, 128.8,

127.6, 126.9, 122.6 (q, J = 38.2 Hz), 121.6 (q, J = 266.9 Hz), 113.1

(q, J = 3.4 Hz), 108.6 ppm. IR (KBr): ν_max= 3071, 2925, 1598, 1552,

1501, 1466, 1438, 1369, 1323, 1285, 1215, 1150, 1108, 1076, 1039

cm^-1. MS (EI): 211 (100). HRMS (EI): Calcd for C₁₁H₈NF₃: 211.0609,

Found: 211.0608.

1-(4-Chlorophenyl)-2-(trifluoromethyl)-pyrrole 5i. Yellow liq-

uid (105 mg, 86%). H NMR (400 MHz, CDCl₃, 293 K, TMS) δ 7.43

2-Phenyl-3-(trifluoromethyl)-1H-indole 5d. Yellow solid (90

mg, 69%). ¹H NMR (400 MHz, CDCl₃, 293 K, TMS) δ 8.34 (br, 1 H),

7.82 (d, J = 7.7 Hz, 1 H), 7.59 (m, 2 H), 7.48 (d, J = 2.0 Hz, 1 H), 7.47

(d, J = 1.9 Hz, 2 H), 7.41 (d, J = 7.5 Hz, 1 H), 7.32 – 7.23 (m, 2 H); ¹⁹F

NMR (375 MHz, CDCl₃) δ -52.9 (s, 3 F); ¹³C NMR (101 MHz, CDCl₃,

293 K, TMS) δ 138.5 (q, J = 3.9 Hz), 134.9, 131.1, 129.4, 129.0,

128.6, 125.6, 124.7 (q, J = 267.1 Hz), 123.4, 121.7, 120.0, 111.1,

103.5 (q, J = 35.8 Hz) ppm. IR (KBr): ν_max= 3404, 3060, 1597, 1582,

1557, 1494, 1453, 1435, 1375, 1344, 1328, 1311, 1283, 1240,

1221, 1176, 1153, 1105, 1075, 1031 cm^-1. MS (EI): 142 (100), 261.

HRMS (EI): Calcd for C₁₅H₁₀F₃N: 261.0765, Found: 261.0771.

1

(m, 2 H), 7.33 (d, J = 8.7 Hz, 2 H), 6.87 - 6.86 (m, 1 H), 6.76 - 6.75

(m, 1 H), 6.30 - 6.29 (m, 1 H); ¹⁹F NMR (375 MHz, CDCl₃) δ -56.9 (s,

3 F); ¹³C NMR (101 MHz, CDCl₃, 293 K, TMS) δ 138.0, 134.9, 129.6,

128.2, 127.5 (q, J = 1.9 Hz), 122.7 (q, J = 38.3 Hz), 121.4 (q, J =

266.8 Hz), 113.4 (q, J = 3.4 Hz), 109.0 ppm. IR (KBr): ν_max= 3130,

2924, 1598, 1499, 1466, 1438, 1367, 1320, 1286, 1214, 1153,

1108, 1076, 1038, 1017 cm^-1. MS (EI): 245 (100), 247 (35.5). HRMS

(EI): Calcd for C₁₁H₇NClF₃: 245.0219, Found: 245.0223.

2-(Trifluoromethyl)-1-(4-(trifluoromethyl)phenyl)-pyrrole 5j.

1

Colorless liquid (111 mg, 80%). H NMR (400 MHz, CDCl₃, 293 K,

2-(4-Fluorophenyl)-3-(trifluoromethyl)-1H-indole 5e. Yellow

solid (85 mg, 61%). ¹H NMR (400 MHz, CDCl₃, 293 K, TMS) δ 8.27

(br, 1 H), 7.82 (d, J = 7.5 Hz, 1 H), 7.56 (dd, J = 8.1, 5.5 Hz, 2 H),

7.40 (d, J = 7.7 Hz, 1 H), 7.33 – 7.23 (m, 2 H), 7.17 (t, J = 8.6 Hz, 2

H); ¹⁹F NMR (375 MHz, CDCl₃) δ -53.0 (s, 3 F), -111.2 – -111.4 (m, 1

F); ¹³C NMR (101 MHz, CDCl₃, 293 K, TMS) δ 163.4 (d, J = 250.0 Hz),

137.5 (q, J = 4.2 Hz), 134.9, 131.0 (q, J = 1.4 Hz), 130.9 (q, J = 1.3

Hz), 127.2 (d, J = 3.5 Hz), 125.5 (q, J = 1.6 Hz), 124.7 (q, J = 267.4

Hz), 123.6, 121.9, 120.1 (q, J = 1.5 Hz), 115.9, 115.7, 111.1, 103.8

(q, J = 35.7 Hz) ppm. IR (KBr): ν_max= 3401, 3064, 1607, 1594, 1560,

1505, 1446, 1408, 1374, 1321, 1283, 1228, 1215, 1171, 1110,

1097, 1014 cm^-1. MS (EI): 199 (100), 237, 279. HRMS (EI): Calcd for

C₁₅H₉F₄N: 279.0671, Found: 279.0674.

TMS) δ 7.74 (d, J = 8.3 Hz, 2 H), 7.53 (d, J = 8.2 Hz, 2 H), 6.91 (t, 1

H), 6.79 (s, 1 H), 6.33 (t, J = 3.0 Hz, 1 H); ¹⁹F NMR (375 MHz, CDCl₃)

δ -55.8 (s, 3 F), -62.7 (s, 3 F); ¹³C NMR (101 MHz, CDCl₃, 293 K,

TMS) δ 142.1, 130.7 (q, J = 33.0 Hz), 127.0 (q, J = 1.8 Hz), 126.7 (q,

J = 0.6 Hz), 126.3 (q, J = 3.7 Hz), 123.7 (q, J = 267.2 Hz), 122.3 (q, J

= 38.4 Hz), 121.0 (q, J = 267.1 Hz), 113.7 (q, J = 3.4 Hz), 109.1 ppm.

IR (KBr): ν_max= 3134, 2926, 1618, 1557, 1523, 1468, 1440, 1420,

1366, 1327, 1284, 1217, 1155, 1105, 1080, 1066, 1037, 1020 cm^-1.

MS (EI): 279 (100). HRMS (EI): Calcd for C₁₂H₇NF₆: 279.0483,

Found: 279.0491.

1-(3-Bromophenyl)-2-(trifluoromethyl)-pyrrole 5k. Yellow liq-

uid (112 mg, 78%). ¹H NMR (400 MHz, CDCl₃, 293 K, TMS) δ 7.59 -

7.57 (m, 2 H), 7.35 - 7.31 (m, 2 H), 6.87 (t, 1 H), 6.75 (s, 1 H), 6.30

(t, 1 H); ¹⁹F NMR (375 MHz, CDCl₃) δ -55.9 (s, 3 F); ¹³C NMR (101

MHz, CDCl₃, 293 K, TMS) δ 140.5, 132.0, 130.6, 130.0, 127.5 (q, J =

1.8 Hz), 125.6, 122.7, 122.6 (q, J = 38.4 Hz), 121.4 (q, J = 265.8 Hz),

113.6 (q, J = 6.9, 3.4 Hz), 109.1 ppm. IR (KBr): ν_max= 3070, 2924,

1699, 1593, 1554, 1486, 1464, 1440, 1400, 1366, 1322, 1285,

1260, 1216, 1152, 1112, 1078, 1039 cm^-1. MS (EI): 289 (100), 291

(97.1). HRMS (EI): Calcd for C₁₁H₇NBrF₃: 288.9714, Found:

288.9720.

2-(3-Chloro-4-fluorophenyl)-3-(trifluoromethyl)-1H-indole 5f.

Yellow liquid (99 mg, 63%). ¹H NMR (400 MHz, CDCl₃, 293 K, TMS)

δ 8.33 (br, 1 H), 7.82 (d, J = 7.7 Hz, 1 H), 7.63 (dd, J = 6.8, 1.8 Hz, 1

H), 7.50 – 7.44 (m, 1 H), 7.41 (d, J = 7.9 Hz, 1 H), 7.31 (dd, J = 11.2,

4.0 Hz, 1 H), 7.29 – 7.22 (m, 2 H); ¹⁹F NMR (375 MHz, CDCl₃) δ

-53.0 (s, 3 F), -113.6 (ddd, J = 8.5, 7.1, 4.7 Hz, 1 F); ¹³C NMR (101

MHz, CDCl₃, 293 K, TMS) δ 158.7 (d, J = 252.6 Hz), 135.8 (q, J = 4.0

Hz), 134.9, 131.2, 129.2 (q, J = 1.5 Hz, 1H), 129.1 (q, J = 1.6 Hz, 1H),

128.2 (d, J = 4.1 Hz), 125.3 (q, J = 1.6 Hz), 124.5 (q, J = 267.5 Hz),

123.9, 122.0, 120.1 (d, J = 1.5 Hz), 116.9 (d, J = 21.5 Hz), 111.2,

104.4 (q, J = 36.0 Hz) ppm. IR (KBr): ν_max= 3460, 3399, 3062, 1622,

1608, 1563, 1497, 1456, 1444, 1390, 1373, 1343, 1319, 1284,

Ethyl 2,4-dimethyl-5-(trifluoromethyl)-1H-pyrrole-3

-carboxylate 5l. White solid (65 mg, 55%). ¹H NMR (400 MHz,

www.cjc.wiley-vch.de

Chin. J. Chem. 2021, 39, XXX－XXX

Running title

Chin. J. Chem.

CDCl₃, 293 K, TMS) δ 8.62 (br, 1 H), 4.28 (q, J = 7.1 Hz, 2 H), 2.50 (s,

3 H), 2.34 (q, J = 1.3 Hz, 3 H), 1.35 (t, J = 7.1 Hz, 3 H); ¹⁹F NMR (375

MHz, CDCl₃) δ -57.9 (s, 3 F); ¹³C NMR (101 MHz, CDCl₃, 293 K, TMS)

δ 165.5, 136.8, 123.9 (q, J = 2.8 Hz), 121.7 (q, J = 267.2 Hz), 115.3

1 H); ¹⁹F NMR (375 MHz, CDCl₃) δ -78.1 (s, 3 F); ¹³C NMR (101 MHz,

CDCl₃, 293 K, TMS) δ 136.7, 136.4, 133.2 (q, J = 1.0 Hz), 131.1,

130.6, 128.8, 119.6 (q, J = 326.0 Hz) ppm. IR (KBr): ν_max= 3092,

2927, 1580, 1462, 1411, 1374, 1305, 1216, 1147, 1117, 1103, 1075

cm^-1. MS (EI): 111 (100), 175, 244 (19.29), 246 (7.2). HRMS (EI):

Calcd for C₇H₄SClO₂F₃: 243.9573, Found: 243.9578.

(q, J = 37.5 Hz), 112.7, 59.6, 14.4, 13.9, 10.6 ppm. IR (KBr): ν_max

=

3250, 2990, 1671, 1602, 1490, 1438, 1389, 1349, 1301, 1274,

1208, 1151, 1104, 1038 cm^-1. MS (EI): 190 (100), 206, 235. HRMS

(EI): Calcd for C₁₀H₁₂NO₂F₃: 235.0820, Found: 235.0828.

3-Fluorophenyl trifluoromethyl sulfone 6d. Yellow liquid (100

mg, 88%). ¹H NMR (400 MHz, CDCl₃, 293 K, TMS) δ 7.87 (d, J = 7.8

Hz, 1 H), 7.75 (d, J = 7.3 Hz, 1 H), 7.70 (td, J = 8.1, 5.1 Hz, 1 H), 7.56

(td, J = 8.2, 1.7 Hz, 1 H); ¹⁹F NMR (375 MHz, CDCl₃) δ -78.1 (s, 3 F),

-107.5 (td, J = 7.7, 5.3 Hz, 1 F); ¹³C NMR (101 MHz, CDCl₃, 293 K,

TMS) δ 162.6 (d, J = 254.6 Hz), 133.3 (dd, J = 7.0, 1.4 Hz), 131.8 (d,

J = 7.7 Hz), 126.7 (d, J = 3.5 Hz), 124.0 (d, J = 21.2 Hz), 119.7 (q, J =

325.9 Hz), 117.9 (d, J = 25.0 Hz) ppm. IR (KBr): ν_max= 3083, 2925,

1596, 1479, 1436, 1374, 1310, 1276, 1218, 1129, 1082, 1067, 1000

cm^-1. MS (EI): 111 (100), 175, 228. HRMS (EI): Calcd for C₇H₄SO₂F₄:

227.9868, Found: 227.9875.

3-Acetyl-5-trifluoromethyl-2,4-dimethylpyrrole 5m. White

1

solid (70 mg, 68%). H NMR (400 MHz, CDCl₃, 293 K, TMS) δ 8.63

(br, 1 H), 2.52 (s, 3 H), 2.44 (s, 3 H), 2.36 (s, 3 H); ¹⁹F NMR (375

MHz, CDCl₃) δ -50.9 (s, 3 F); ¹³C NMR (101 MHz, CDCl₃, 293 K, TMS)

δ 195.6, 136.3, 123.0 (q, J = 2.6 Hz), 122.9, 122.0 (q, J = 267.4 Hz),

116.0 (q, J = 37.0 Hz), 31.5, 15.4, 11.8 ppm. IR (KBr): ν_max= 3240,

3110, 3040, 2826, 1633, 1599, 1532, 1479, 1436, 1418, 1388,

1343, 1304, 1263, 1204, 1162, 1110, 1051, 1035 cm^-1. MS (EI): 190

(100), 205. HRMS (EI): Calcd for C₉H₁₀NOF₃: 205.0714, Found:

205.0712.

4-Trifluoromethoxyphenyl trifluoromethyl sulfone 6e. Yellow

solid (84 mg, 57%). ¹H NMR (400 MHz, CDCl₃, 293 K, TMS) δ 8.11

(d, J = 8.9 Hz, 2 H), 7.49 (d, J = 8.2 Hz, 2 H); ¹⁹F NMR (375 MHz,

CDCl₃) δ -57.7 (s, 3 F), -78.3 (s, 3 F); ¹³C NMR (101 MHz, CDCl₃, 293

K, TMS) δ 155.6, 133.6, 129.5, 121.5, 120.5 (q, J = 261.2 Hz), 120.0

(q, J = 325.6 Hz) ppm. IR (KBr): ν_max= 3111, 3069, 2963, 1589,

1494, 1410, 1374, 1261, 1170, 1076, 1017 cm^-1. MS (EI): 95 (100),

161, 225, 294. HRMS (EI): Calcd for C₈H₄SO₃F₆: 293.9785, Found:

293.9789.

1,3,5-Trimethoxy-2-(trifluoromethyl)benzene 5n. Yellow solid

(78 mg, 66%). ¹H NMR (400 MHz, CDCl₃, 293 K, TMS) δ 6.13 (s, 2

H), 3.83 (s, 9 H); ¹⁹F NMR (375 MHz, CDCl₃) δ -54.1 (s, 3 F); ¹³

C

NMR (101 MHz, CDCl₃, 293 K, TMS) δ 163.5, 160.4 (q, J = 1.2 Hz),

124.3 (q, J = 273.3 Hz), 100.4 (q, J = 30.2 Hz), 91.3, 56.2, 55.4 ppm.

IR (KBr): ν_max= 3016, 2955, 2849, 1608, 1592, 1499, 1474, 1440,

1422, 1356, 1290, 1233, 1210, 1198, 1166, 1115, 1069, 1024 cm^-1.

MS (EI): 236 (100). HRMS (EI): Calcd for C₁₀H₁₁F₃O₃: 236.0660,

Found: 236.0665.

4-Acetylphenyl trifluoromethyl sulfone 6f. White solid (94

mg, 75%). ¹H NMR (400 MHz, CDCl₃, 293 K, TMS) δ 8.20 (d, J = 8.7

Hz, 2 H), 8.15 (d, J = 8.5 Hz, 2 H), 2.69 (s, 3 H); ¹⁹F NMR (375 MHz,

CDCl₃) δ -80.6 (s, 3 F); ¹³C NMR (101 MHz, CDCl₃, 293 K, TMS) δ

196.2, 143.0, 135.0 (q, J = 1.0 Hz), 131.2, 129.3, 119.6 (q, J = 325.9

Hz), 26.9 ppm. IR (KBr): ν_max= 3100, 3074, 3048, 1686, 1574, 1489,

1368, 1292, 1262, 1220, 1197, 1340, 1081, 1013 cm^-1. MS (EI): 237

(100), 252. HRMS (EI): Calcd for C₉H₇SO₃F₃: 252.0068, Found:

252.0063.

General Procedure for Triﬂuoromethylation of Sodium ben-

zenesulfinates. Sodium benzenesulfinate (0.50 mmol, 1.0 equiv.),

and reagent 1g (0.60 mmol, 1.2 equiv.) were placed into an ov-

en-dried Schlenk tube that was equipped with a stirring bar under

an atmosphere of nitrogen. The tube was quickly sealed with a

rubber stopper and 10.0 mL of freshly distilled DMSO was added.

The reaction was stirred at room temperature for 12 h under irra-

diation of blue LED. The mixture was cooled to room temperature,

and 20 mL of distilled water and 20 mL of Et₂O was added and the

organic phase was separated. The aqueous phase was extracted

with Et₂O (20 mL × 3) and the combined organic extracts were

dried over anhydrous Na₂SO₄, and concentrated in vacuo. The

product was purified by flash chromatography on silica gel.

General procedure for trifluoromethylative difunctionaliza-

tion of styrene derivatives. Into a 25 mL Schlenk tube equipped

with a magnetic stirring bar was added styrenes (0.5 mmol), ylide

reagent (212 mg, 0.600 mmol), Ir(ppy)₃(2.0 mg, 0.25 mol%),

Sc(OTf)₃(25 mg, 0.050 mmol), acetonitrile (2.5 mL) and ROH (0.25

mL) under an atmosphere of argon. The mixture was stirred under

blue LED at ambient temperature for 10 h. After that, the solvent

was evaporated under vacuum and the residue was purified by

flash chromatograph to give the product.

Phenyl trifluoromethyl sulfone 6a. Colorless liquid (70 mg,

67%). ¹H NMR (400 MHz, CDCl₃, 293 K, TMS) δ 8.06 (d, J = 7.8 Hz, 2

H), 7.85 (t, J = 7.5 Hz, 1 H), 7.69 (t, J = 7.8 Hz, 2 H); ¹⁹F NMR (375

MHz, CDCl₃) δ -78.5 (s, 3 F); ¹³C NMR (101 MHz, CDCl₃, 293 K, TMS)

δ 136.5, 131.4 (q, J = 1.6 Hz), 130.8, 129.9, 119.8 (q, J = 325.8 Hz)

ppm. IR (KBr): ν_max= 3072, 2926, 1584, 1450, 1369, 1317, 1288,

1220, 1142, 1074, 1024 cm^-1. MS (EI): 77 (100), 141, 210. HRMS

(EI): Calcd for C₇H₅SO₂F₃: 209.9962, Found: 209.9967.

4-(3,3,3-Trifluoro-1-methoxypropyl)-1,1'-biphenyl 7a. White

solid (129 mg, 92%), mp: 41-43 °C. Eluent: ethyl ace-

tate/petroleum ether (1:30, R_f= 0.6). ¹H NMR (400 MHz, CDCl₃,

293 K, TMS) δ 7.66-7.62 (m, 4 H), 7.50-7.37 (m, 5 H), 4.55 (dd, J =

8.6, 4.1 Hz, 1 H), 3.30 (s, 3 H), 2.79-2.66 (m, 1 H), 2.51-2.38 (m, 1

3-Bromophenyl trifluoromethyl sulfone 6b. Colorless liquid

(127 mg, 88%). ¹H NMR (400 MHz, CDCl₃, 293 K, TMS) δ 8.17 (s, 1

H), 7.98 (t, J = 7.2 Hz, 2 H), 7.57 (t, J = 8.0 Hz, 1 H); ¹⁹F NMR (375

MHz, CDCl₃) δ -78.0 (s, 3 F); ¹³C NMR (101 MHz, CDCl₃, 293 K, TMS)

δ 139.6, 133.3, 133.3 (q, J = 1.3 Hz), 131.3, 129.3, 123.9, 119.6 (q, J

= 326.0 Hz) ppm. IR (KBr): ν_max= 3089, 2926, 1571, 1460, 1406,

1373, 1302, 1215, 1145, 1113, 1092, 1073 cm^-1. MS (EI): 77 (100),

141, 288, 289. HRMS (EI): Calcd for C₇H₄SBrO₂F₃: 287.9067, Found:

287.9068.

H); ¹⁹F NMR (376 MHz, CDCl₃) δ -63.67 (t, J = 10.5 Hz, 3 F); ¹³

C

NMR (101 MHz, CDCl₃, 293 K, TMS) δ 141.32, 140.53, 138.95,

128.80, 127.48, 127.46, 127.06, 126.91, 125.67 (q, J = 278.8 Hz),

77.50 (q, J = 2.0 Hz), 56.70, 42.17 (q, J = 27.5 Hz) ppm. IR (KBr):

ν

_max= 3030, 2990, 2936, 2882, 2827, 1601, 1488, 1381, 1290,

1251, 1215, 1128, 1104, 1048 cm^-1. MS (EI): 280 (M⁺). HRMS (EI)

for C₁₆H₁₅OF₃(M⁺): Calcd: 280.1075; Found: 280.1072.

1-(tert-Butyl)-4-(3,3,3-trifluoro-1-methoxypropyl)benzene

7b. Colorless liquid (107 mg, 82%). Eluent: ethyl ace-

3-Chlorophenyl trifluoromethyl sulfone 6c. Yellow liquid (100

mg, 82%). ¹H NMR (400 MHz, CDCl₃, 293 K, TMS) δ 8.01 (s, 1 H),

7.93 (d, J = 7.8 Hz, 1 H), 7.80 (d, J = 8.0 Hz, 1 H), 7.62 (t, J = 8.0 Hz,

tate/petroleum ether (1:50, R_f= 0.6). ¹H NMR (400 MHz, CDCl₃,

293 K, TMS) δ 7.40 (d, J = 8.4 Hz, 2 H), 7.24 (d, J = 8.4 Hz, 2 H), 4.44

Chin. J. Chem. 2021, 39, XXX－XXX

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First author et al.

Report

(dd, J = 8.9, 3.8 Hz, 1 H), 3.23 (s, 3 H), 2.71-2.57 (m, 1 H), 2.42-2.29

(m, 1 H), 1.33 (s, 9 H); ¹⁹F NMR (376 MHz, CDCl₃) δ -63.86 (t, J =

10.6 Hz, 3 F); ¹³C NMR (101 MHz, CDCl₃, 293 K, TMS) δ 151.34,

136.88, 126.13, 125.73 (q, J = 277.4 Hz), 125.63, 77.47 (q, J = 3.0

ether (1:50, R_f= 0.6). ¹H NMR (400 MHz, CDCl₃, 293 K, TMS) δ 7.26

(d, J = 8.6 Hz, 2 H), 7.23 (d, J = 8.5 Hz, 2 H), 4.41 (dd, J = 8.5, 4.3 Hz,

1 H), 3.20 (s, 3 H), 2.70-2.56 (m, 1 H), 2.49 (s, 3 H), 2.41-2.28 (m, 1

H); ¹⁹F NMR (376 MHz, CDCl₃) δ -63.71 (t, J = 10.5 Hz, 3 F); ¹³

C

Hz), 56.66, 42.19 (q, J = 27.4 Hz), 34.59, 31.32 ppm. IR (KBr): ν_max

=

NMR (126 MHz, CDCl₃, 293 K, TMS) δ 138.80, 136.65, 127.00,

126.63, 125.58 (q, J = 277.3 Hz), 77.31 (q, J = 2.5 Hz), 56.54, 42.06

(q, J = 27.3 Hz), 15.58 ppm. IR (KBr): ν_max= 2989, 2928, 2827,

1600, 1495, 1428, 1384, 1328, 1291, 1251, 1214, 1127, 1104, 1046

cm^-1. MS (EI): 250 (M⁺). HRMS (EI) for C₁₁H₁₃OF₃S (M⁺): Calcd:

250.0639; Found: 250.0644.

2964, 1383, 1325, 1290, 1251, 1217, 1128, 1108, 1048, 1018 cm^-1.

MS (EI): 260 (M⁺). HRMS (EI) for C₁₄H₁₉OF₃(M⁺): Calcd: 260.1388;

Found: 260.1389.

1-Methoxy-4-(3,3,3-trifluoro-1-methoxypropyl)benzene 7c.

Colorless liquid (75.0 mg, 64%). Eluent: ethyl acetate/petroleum

ether (1:50, R_f= 0.5). ¹H NMR (400 MHz, CDCl₃, 293 K, TMS) δ 7.23

(d, J = 8.7 Hz, 2 H), 6.91 (d, J = 8.7 Hz, 2 H), 4.40 (dd, J = 8.4, 4.4 Hz,

1 H), 3.82 (s, 3 H), 3.19 (s, 3 H), 2.71-2.58 (m, 1 H), 2.41-2.28 (m, 1

5-(3,3,3-Trifluoro-1-methoxypropyl)benzofuran 7h. Colorless

liquid (90.0 mg, 74%). Eluent: ethyl acetate/petroleum ether

(1:50, R_f= 0.6). ¹H NMR (400 MHz, CDCl₃, 293 K, TMS) δ 7.64 (d, J =

2.0 Hz, 1 H), 7.56 (s, 1 H), 7.51 (d, J = 8.5 Hz, 1 H), 7.25 (dd, J = 8.5,

1.5 Hz, 1 H), 6.77-6.76 (m, 1 H), 4.55 (dd, J = 8.5, 4.3 Hz, 1 H), 3.22

(s, 3 H), 2.77-2.63 (m, 1 H), 2.47-2.34 (m, 1 H); ¹⁹F NMR (376 MHz,

CDCl₃) δ -63.74 (t, J = 10.6 Hz, 3 F); ¹³C NMR (126 MHz, CDCl₃, 293

K, TMS) δ 154.85, 145.72, 134.61, 127.71, 125.68 (q, J = 277.6 Hz),

122.62, 119.37, 111.72, 106.56, 77.87 (q, J = 2.5 Hz), 56.51, 42.57

(q, J = 27.5 Hz) ppm. IR (KBr): ν_max= 2990, 2937, 2829, 1538, 1470,

1449, 1385, 1333, 1285, 1262, 1208, 1107, 1047, 1032 cm^-1. MS

(EI): 244 (M⁺). HRMS (EI) for C₁₂H₁₁O₂F₃(M⁺): Calcd: 244.0711;

Found: 244.0716.

H); ¹⁹F NMR (376 MHz, CDCl₃) δ -63.75 (t, J = 10.6 Hz, 3 F); ¹³

C

NMR (151 MHz, CDCl₃, 293 K, TMS) δ 159.66, 131.95, 127.78,

125.69 (q, J = 277.2 Hz), 114.12, 77.29 (q, J = 4.5 Hz), 56.38, 55.29,

42.19 (q, J = 27.3 Hz) ppm. IR (KBr): ν_max= 2955, 2917, 2849, 1513,

1463, 1289, 1248, 1213, 1174, 1112, 1035 cm^-1. MS (EI): 234 (M⁺).

HRMS (EI) for C₁₁H₁₃O₂F₃(M⁺): Calcd: 234.0868; Found: 234.0874.

2-Fluoro-1-methoxy-4-(3,3,3-trifluoro-1-methoxypropyl)benz

ene 7d. Light yellow liquid (101 mg, 80%). Eluent: ethyl ace-

tate/petroleum ether (1:50, R_f= 0.7). ¹H NMR (400 MHz, CDCl₃,

293 K, TMS) δ 7.07-7.01 (m, 2 H), 6.97-6.93 (m, 1 H), 4.38 (dd, J =

8.3, 4.5 Hz, 1 H), 3.89 (s, 3 H), 3.20 (s, 3 H), 2.68-2.55 (m, 1 H),

2.40-2.27 (m, 1 H); ¹⁹F NMR (376 MHz, CDCl₃) δ -63.75 (t, J = 10.5

Hz, 3 F), -134.25 (dd, J = 10.9, 8.9 Hz, 1 F); ¹³C NMR (151 MHz,

CDCl₃, 293 K, TMS) δ 152.61 (d, J = 247.4 Hz), 147.68 (d, J = 10.7

Hz), 132.98 (d, J = 5.1 Hz), 125.53 (q, J = 277.6 Hz), 122.50 (d, J =

3.3 Hz), 114.08 (d, J = 19.1 Hz), 113.46, 76.93, 56.52, 56.26, 42.10

(q, J = 27.6 Hz) ppm. IR (KBr): ν_max= 2940, 2830, 2042, 1624, 1589,

1518, 1434, 1385, 1276, 1225, 1204, 1113, 1048, 1029 cm^-1. MS

(EI): 252 (M⁺). HRMS (EI) for C₁₁H₁₂O₂F₄(M⁺): Calcd: 252.0773;

Found: 252.0779.

(3,3,3-Trifluoro-1-methoxypropane-1,1-diyl)dibenzene 7i.

White Solid (85.0 mg, 61%), mp: 54-56 °C. Eluent: ethyl ace-

tate/petroleum ether (1:50, R_f= 0.8). ¹H NMR (400 MHz, CDCl₃,

293 K, TMS) δ 7.33-7.27 (m, 8 H), 7.24-7.20 (m, 2 H), 3.22 (q, J =

10.1 Hz, 2 H), 3.12 (s, 3 H); ¹⁹F NMR (376 MHz, CDCl₃) δ -59.71 (t, J

= 10.1 Hz, 3 F); ¹³C NMR (126 MHz, CDCl₃, 293 K, TMS) δ 144.01,

128.33, 127.43, 126.73, 125.85 (q, J = 279.3 Hz), 79.87, 51.09,

38.82 (q, J = 26.4 Hz) ppm. IR (KBr): ν_max= 3062, 3027, 2943, 2839,

1493, 1449, 1371, 1265, 1233, 1193, 1139, 1077, 1031 cm^-1. MS

(EI): 280 (M⁺). HRMS (EI) for C₁₆H₁₅OF₃(M⁺): Calcd: 280.1075;

Found: 280.1085.

2-Chloro-1-methoxy-4-(3,3,3-trifluoro-1-methoxypropyl)benz

ene 7e. Colorless liquid (105 mg, 78%). Eluent: ethyl ace-

tate/petroleum ether (1:50, R_f= 0.7). ¹H NMR (400 MHz, CDCl₃,

293 K, TMS) δ 7.33 (d, J = 2.1 Hz, 1 H), 7.17 (dd, J = 8.4, 2.2 Hz, 1

H), 6.93 (d, J = 8.4 Hz, 1 H), 4.37 (dd, J = 8.3, 4.5 Hz, 1 H), 3.91 (s, 3

H), 3.20 (s, 3 H), 2.69-2.55 (m, 1 H), 2.40-2.27 (m, 1 H); ¹⁹F NMR

(376 MHz, CDCl₃) δ -63.73 (t, J = 10.5 Hz, 3 F); ¹³C NMR (126 MHz,

CDCl₃, 293 K, TMS) δ 154.99, 133.05, 128.32, 126.00, 125.50 (q, J =

277.6 Hz), 122.84, 112.10, 76.83 (q, J = 3.8 Hz), 56.56, 56.16, 42.08

(q, J = 27.9 Hz) ppm. IR (KBr): ν_max= 2941, 2829, 1606, 1501, 1384,

1290, 1257, 1211, 1119, 1065, 1048, 1024 cm^-1. MS (EI): 268 (M⁺).

HRMS (EI) for C₁₁H₁₂O₂F₃Cl (M⁺): Calcd: 268.0478; Found:

268.0477.

4-(1-ethoxy-3,3,3-trifluoropropyl)-1,1'-biphenyl 7j. White

solid (110 mg, 75%), mp: 52-54 °C. Eluent: dichloro-

methane/petroleum ether (1:1, R_f= 0.7). ¹H NMR (400 MHz,

CDCl₃, 293 K, TMS) δ 7.64-7.62 (m, 4 H), 7.49-7.36 (m, 5 H), 4.66

(dd, J = 8.7, 4.0 Hz, 1 H), 3.52-3.37 (m, 2 H), 2.79-2.65 (m, 1 H),

2.49-2.36 (m, 1 H), 1.24 (t, J = 7.0 Hz, 3 H); ¹⁹F NMR (376 MHz,

CDCl₃) δ -63.61 (t, J = 10.5 Hz, 3 F); ¹³C NMR (151 MHz, CDCl₃, 293

K, TMS) δ 141.15, 140.60, 139.77, 128.79, 127.42, 127.06, 126.80,

125.74 (q, J = 277.2 Hz), 75.58, 64.43, 42.33 (q, J = 27.3 Hz), 15.07

ppm. IR (KBr): ν_max= 3030, 2981, 2880, 1488, 1413, 1381, 1286,

1249, 1131, 1021 cm^-1. MS (EI): 294 (M⁺). HRMS (EI) for C₁₇H₁₇OF₃

(M⁺): Calcd: 294.1232; Found: 294.1222.

2-Bromo-1-methoxy-4-(3,3,3-trifluoro-1-methoxypropyl)benz

ene 7f. Colorless liquid (102 mg, 65%). Eluent: ethyl ace-

tate/petroleum ether (1:50, R_f= 0.6). ¹H NMR (400 MHz, CDCl₃,

293 K, TMS) δ 7.50 (d, J = 2.1 Hz, 1 H), 7.22 (dd, J = 8.4, 2.1 Hz, 1

H), 6.90 (d, J = 8.4 Hz, 1 H), 4.37 (dd, J = 8.3, 4.5 Hz, 1 H), 3.90 (s, 3

H), 3.20 (s, 3 H), 2.69-2.55 (m, 1 H), 2.40-2.27 (m, 1 H); ¹⁹F NMR

(376 MHz, CDCl₃) δ -63.70 (t, J = 10.5 Hz, 3 F); ¹³C NMR (126 MHz,

CDCl₃, 293 K, TMS) δ 155.85, 133.48, 131.39, 126.76, 125.48 (q, J =

277.3 Hz), 111.98, 111.93, 76.72 (q, J = 2.5 Hz), 56.56, 56.24, 42.09

(q, J = 27.3 Hz) ppm. IR (KBr): ν_max= 2942, 2904, 2828, 1604, 1497,

1441, 1383, 1288, 1256, 1210, 1131, 1053, 1022 cm^-1. MS (EI): 312

(M⁺). HRMS (EI) for C₁₁H₁₂O₂F₃Br (M⁺): Calcd: 311.9973; Found:

311.9981.

4-(3,3,3-trifluoro-1-isopropoxypropyl)-1,1'-biphenyl 7k.

White solid (103 mg, 67%), mp: 26-28 °C. Eluent: dichloro-

methane/petroleum ether (1:2, R_f= 0.6). ¹H NMR (400 MHz,

CDCl₃, 293 K, TMS) δ 7.64-7.62 (m, 4 H), 7.50-7.44 (m, 4 H),

7.41-7.36 (m, 1 H), 4.78 (dd, J = 9.0, 3.2 Hz, 1 H), 3.63-3.54 (m, 1

H), 2.74-2.60 (m, 1 H), 2.46-2.33 (m, 1 H), 1.23 (dd, J = 6.0, 2.2 Hz,

3 H), 1.15 (dd, J = 6.2, 2.2 Hz, 3 H); ¹⁹F NMR (376 MHz, CDCl₃) δ

-63.50 (td, J = 10.5, 3.0 Hz, 3 F); ¹³C NMR (151 MHz, CDCl₃, 293 K,

TMS) δ 141.00, 140.62, 128.79, 127.39, 127.36, 127.06, 126.76,

125.76 (q, J = 277.6 Hz), 72.90 (q, J = 2.7 Hz), 69.60, 42.69 (q, J =

27.0 Hz), 23.30, 20.86 ppm. IR (KBr): ν_max= 3030, 2976, 2886,

1488, 1378, 1286, 1248, 1119, 1028 cm^-1. MS (EI): 308 (M⁺). HRMS

(EI) for C₁₈H₁₉OF₃(M⁺): Calcd: 308.1388; Found: 308.1389.

Methyl(4-(3,3,3-trifluoro-1-methoxypropyl)phenyl)sulfane

7g. Yellow liquid (89.0 mg, 71%). Eluent: ethyl acetate/petroleum

4-(1-cyclopropoxy-3,3,3-trifluoropropyl)-1,1'-biphenyl 7l.

White solid (100 mg, 65%), mp: 60-62 °C. Eluent: dichloro-

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Chin. J. Chem.

methane/petroleum ether (1:1, R_f= 0.7). ¹H NMR (400 MHz, CDCl₃,

293 K, TMS) δ 7.68 (t, J = 7.1 Hz, 4 H), 7.53-7.49 (m, 4 H), 7.42 (t, J

= 7.3 Hz, 1 H), 4.81 (dd, J = 9.1, 3.5 Hz, 1 H), 3.29-3.25 (m, 1 H),

2.79-2.65 (m, 1 H), 2.50-2.37 (m, 1 H), 0.82-0.75 (m, 1 H),

0.72-0.66 (m, 1 H), 0.58-0.51 (m, 1 H), 0.48-0.41 (m, 1 H); ¹⁹F NMR

(376 MHz, CDCl₃) δ -63.55 (t, J = 10.4 Hz, 3 F); ¹³C NMR (126 MHz,

CDCl₃, 293 K, TMS) δ 141.25, 140.54, 139.38, 128.79, 127.44,

127.05, 126.99, 125.65 (q, J = 277.4 Hz), 76.02 (q, J = 2.5 Hz),

51.84, 41.94 (q, J = 27.5 Hz), 6.31, 4.99 ppm. IR (KBr): ν_max= 3010,

1488, 1387, 1287, 1250, 1131 cm^-1. MS (EI): 306 (M⁺). HRMS (EI)

for C₁₈H₁₇OF₃(M⁺): Calcd: 306.1226; Found: 306.1225.

8.5 Hz, 2 H), 7.24 (d, J = 8.5 Hz, 2 H), 5.02 (d, J = 7.9 Hz, 1 H),

2.67-2.54 (m, 1 H), 2.48 (s, 3 H), 2.45-2.35 (m, 1 H), 2.26 (s, 1 H);

¹⁹F NMR (376 MHz, CDCl₃) δ -63.73 (t, J = 10.6 Hz, 3 F); ¹³C NMR

(151 MHz, CDCl₃, 293 K, TMS) δ 139.06, 138.85, 126.76, 126.17,

125.80 (q, J = 277.8 Hz), 68.40 (q, J = 2.6 Hz), 42.74 (q, J = 27.0 Hz),

15.68 ppm. IR (KBr): ν_max= 3420, 2923, 1601, 1496, 1431, 1376,

1332, 1259, 1205, 1134, 1104, 1016 cm^-1. MS (EI): 236 (M⁺). HRMS

(EI) for C₁₀H₁₁OF₃S (M⁺): Calcd: 236.0483; Found: 236.0491.

3,3,3-Trifluoro-1-(naphthalen-2-yl)propan-1-ol 8f. Yellow liq-

uid (73.0 mg, 61%). Eluent: ethyl acetate/petroleum ether (1:10,

R_f= 0.4). ¹H NMR (400 MHz, CDCl₃, 293 K, TMS) δ 7.87-7.81 (m, 4

H), 7.55-7.50 (m, 2 H), 7.45 (dd, J = 8.5, 1.5 Hz, 1 H), 5.22 (dd, J =

8.8, 3.1 Hz, 1 H), 2.78-2.64 (m, 1 H), 2.60-2.47 (m, 2 H); ¹⁹F NMR

(376 MHz, CDCl₃) δ -63.64 (t, J = 10.6 Hz, 3 F); ¹³C NMR (151 MHz,

CDCl₃, 293 K, TMS) δ 139.56, 133.19, 128.78, 127.99, 127.71,

126.47, 126.32, 125.89 (q, J = 277.3 Hz), 124.66, 123.28, 68.89 (q, J

= 3.0 Hz), 42.71 (q, J = 26.9 Hz) ppm. IR (KBr): ν_max= 3405, 3058,

2916, 1603, 1509, 1429, 1364, 1254, 1135 cm^-1. MS (EI): 240 (M⁺).

HRMS (EI) for C₁₃H₁₁OF₃(M⁺): Calcd: 240.0762; Found: 240.0769.

1-([1,1'-Biphenyl]-4-yl)-3,3,3-trifluoropropan-1-ol 8a. White

solid (113 mg, 85%), mp: 82-84 °C. Eluent: ethyl ace-

tate/petroleum ether (1:10, R_f= 0.3). ¹H NMR (400 MHz, CDCl₃,

293 K, TMS) δ 7.64-7.61 (m, 4 H), 7.50-7.38 (m, 5 H), 5.13 (d, J =

8.9 Hz, 1 H), 2.75-2.61 (m, 1 H), 2.57-2.44 (m, 2 H); ¹⁹F NMR (376

MHz, CDCl₃) δ -63.62 (t, J = 10.6 Hz, 3 F); ¹³C NMR (126 MHz,

CDCl₃, 293 K, TMS) δ 141.27, 141.22, 140.41, 128.80, 127.47,

127.03, 126.09, 125.85 (q, J = 277.5 Hz), 68.50 (q, J = 3.8 Hz), 42.68

(q, J = 26.9 Hz) ppm. IR (KBr): ν_max= 3359, 1488, 1403, 1371, 1332,

1246, 1194, 1124, 1105, 1057 cm^-1. MS (EI): 266 (M⁺). HRMS (EI)

for C₁₅H₁₃OF₃(M⁺): Calcd: 266.0918; Found: 266.0923.

2-(4-(3,3,3-Trifluoro-1-hydroxypropyl)benzyl)isoindoline-1,3-

dione 8g. Light yellow solid (94.0 mg, 54%), mp: 129-131 °C. Elu-

ent: ethyl acetate/petroleum ether (1:10, R_f= 0.1). ¹H NMR (400

MHz, CDCl₃, 293 K, TMS) δ 7.82 (dd, J = 5.4, 3.1 Hz, 2 H), 7.70 (dd, J

= 5.4, 3.0 Hz, 2 H), 7.41 (d, J = 8.1 Hz, 2 H), 7.31 (d, J = 8.1 Hz, 2 H),

5.03 (d, J = 8.8 Hz, 1 H), 4.81 (s, 2 H), 2.64-2.50 (m, 2 H), 2.45-2.32

(m, 1 H); ¹⁹F NMR (376 MHz, CDCl₃) δ -63.75 (t, J = 10.6 Hz, 3 F);

¹³C NMR (126 MHz, CDCl₃, 293 K, TMS) δ 168.02, 142.04, 136.44,

134.05, 131.94, 129.00, 125.99, 125.78 (q, J = 277.3 Hz), 123.36,

68.39 (q, J = 2.5 Hz), 42.72 (q, J = 27.0 Hz), 41.15 ppm. IR (KBr):

1-(4-(tert-Butyl)phenyl)-3,3,3-trifluoropropan-1-ol 8b. Light

yellow liquid (91.0 mg, 74%). Eluent: ethyl acetate/petroleum

ether (1:10, R_f= 0.6). ¹H NMR (400 MHz, CDCl₃, 293 K, TMS) δ 7.42

(d, J = 8.2 Hz, 2 H), 7.31 (d, J = 8.2 Hz, 2 H), 5.05 (d, J = 8.9 Hz, 1 H),

2.70-2.57 (m, 1 H), 2.51-2.38 (m, 1 H), 2.20 (s, 1 H), 1.33 (s, 9 H);

¹⁹F NMR (376 MHz, CDCl₃) δ -63.80 (t, J = 10.6 Hz, 3 F); ¹³C NMR

(126 MHz, CDCl₃, 293 K, TMS) δ 151.49, 139.35, 125.93 (q, J =

277.0 Hz), 125.74, 125.39, 68.56 (q, J = 2.5 Hz), 42.69 (q, J = 26.9

Hz), 34.57, 31.26 ppm. IR (KBr): ν_max= 3393, 2965, 2871, 1615,

1514, 1463, 1366, 1332, 1267, 1110, 1019 cm^-1. MS (EI): 246 (M⁺).

HRMS (EI) for C₁₃H₁₇OF₃(M⁺): Calcd: 246.1232; Found: 246.1223.

ν

_max= 3557, 2889, 1767, 1709, 1614, 1428, 1396, 1332, 1255,

1228, 1133, 1093 cm^-1. MS (EI): 349 (M⁺). HRMS (EI) for

C₁₈H₁₄NO₃F₃(M⁺): Calcd: 349.0926; Found: 349.0931.

3,3,3-Trifluoro-1,1-diphenylpropan-1-ol 8h. Yellow liquid

(74.0 mg, 56%). Eluent: ethyl acetate/petroleum ether (1:10, R_f=

0.6). ¹H NMR (400 MHz, CDCl₃, 293 K, TMS) δ 7.42-7.40 (m, 4 H),

7.34-7.31 (m, 4 H), 7.27-7.23 (m, 2 H), 3.20 (q, J = 10.3 Hz, 2 H),

2.66 (s, 1 H); ¹⁹F NMR (376 MHz, CDCl₃) δ -58.21 (t, J = 10.3 Hz, 3

F); ¹³C NMR (126 MHz, CDCl₃, 293 K, TMS) δ 145.09, 128.37,

127.50, 125.68 (q, J = 279.3 Hz), 125.51, 75.60 (q, J = 2.5 Hz), 44.86

(q, J = 25.5 Hz) ppm. IR (KBr): ν_max= 3556, 3062, 3029, 1599, 1495,

1449, 1374, 1262, 1213, 1127, 1033 cm^-1. MS (EI): 266 (M⁺). HRMS

(EI) for C₁₅H₁₃OF₃(M⁺): Calcd: 266.0918; Found: 266.0921.

3,3,3-Trifluoro-1-(3-fluoro-4-methoxyphenyl)propan-1-ol 8c.

Yellow liquid (65.0 mg, 55%). Eluent: ethyl acetate/petroleum

ether (1:10, R_f= 0.3). ¹H NMR (400 MHz, CDCl₃, 293 K, TMS) δ

7.14-7.06 (m, 2 H), 6.97-6.93 (m, 1 H), 5.01 (d, J = 6.9 Hz, 1 H), 3.89

(s, 3 H), 2.67-2.53 (m, 1 H), 2.48–2.35 (m, 1 H), 2.20 (s, 1 H); ¹⁹

F

NMR (376 MHz, CDCl₃) δ -63.76 (t, J = 10.6 Hz, 3 F), -134.01 (dd, J =

11.3, 8.9 Hz, 1 F); ¹³C NMR (126 MHz, CDCl₃, 293 K, TMS) δ 152.41

(d, J = 246.9 Hz), 147.57 (d, J = 10.8 Hz), 135.27 (d, J = 5.4 Hz),

125.71 (q, J = 277.9 Hz), 121.50 (d, J = 3.2 Hz), 113.57 (d, J = 19.0

Hz), 113.43 (d, J = 2.1 Hz), 67.96, 56.29, 42.80 (q, J = 26.9 Hz) ppm.

IR (KBr): ν_max= 3436, 2942, 2846, 1755, 1625, 1589, 1521, 1445,

1376, 1266, 1185, 1027 cm^-1. MS (EI): 238 (M⁺). HRMS (EI) for

C₁₀H₁₀O₂F₄(M⁺): Calcd: 238.0617; Found: 238.0622.

1-(9H-Fluoren-2-yl)-3,3,3-trifluoropropan-1-ol 8i. Light yellow

solid (66.0 mg, 47%), mp: 96-98 °C. Eluent: ethyl ace-

tate/petroleum ether (1:10, R_f= 0.3). ¹H NMR (400 MHz, CDCl₃,

293 K, TMS) δ 7.78 (dd, J = 7.6, 3.8 Hz, 2 H), 7.57-7.55 (m, 2 H),

7.41-7.30 (m, 3 H), 5.16 (d, J = 7.2 Hz, 1 H), 3.91 (s, 2 H), 2.77-2.63

(m, 1 H), 2.58-2.45 (m, 1 H), 2.21 (s, 1 H); ¹⁹F NMR (376 MHz,

CDCl₃) δ -63.72 (t, J = 10.6 Hz, 3 F); ¹³C NMR (151 MHz, CDCl₃, 293

K, TMS) δ 143.89, 143.38, 142.05, 141.07, 140.87, 126.99, 126.85,

125.91 (q, J = 277.8 Hz), 125.08, 124.44, 122.35, 120.10, 120.01,

69.06 (q, J = 3.0 Hz), 43.01 (q, J = 26.9 Hz), 36.88 ppm. IR (KBr):

1-(3-Chloro-4-methoxyphenyl)-3,3,3-trifluoropropan-1-ol 8d.

Yellow liquid (89.0 mg, 70%). Eluent: ethyl acetate/petroleum

ether (1:10, R_f= 0.3). ¹H NMR (400 MHz, CDCl₃, 293 K, TMS) δ 7.40

(d, J = 2.2 Hz, 1 H), 7.23 (dd, J = 8.5, 2.2 Hz, 1 H), 6.92 (d, J = 8.5 Hz,

1 H), 5.01 (d, J = 8.7 Hz, 1 H), 3.90 (s, 3 H), 2.67-2.54 (m, 1 H),

2.48-2.35 (m, 1 H), 2.19 (s, 1 H); ¹⁹F NMR (376 MHz, CDCl₃) δ

-63.75 (t, J = 10.6 Hz, 3 F); ¹³C NMR (126 MHz, CDCl₃, 293 K, TMS)

δ 154.93, 135.41, 127.69, 125.71 (q, J = 278.0 Hz), 125.11, 122.80,

112.10, 67.90 (q, J = 3.8 Hz), 56.21, 42.80 (q, J = 27.0 Hz) ppm. IR

(KBr): ν_max= 3429, 2917, 1696, 1607, 1504, 1442, 1375, 1258,

1202, 1133, 1064, 1023 cm^-1. MS (EI): 254 (M⁺). HRMS (EI) for

C₁₀H₁₀O₂F₃Cl (M⁺): Calcd: 254.0321; Found: 254.0328.

ν

_max= 3394, 2920, 2850, 1683, 1618, 1428, 1394, 1321, 1277,

1117, 1057, 1003 cm^-1. MS (EI): 278 (M⁺). HRMS (EI) for C₁₆H₁₃OF₃

(M⁺): Calcd: 278.0918; Found: 278.0922.

(8R,9S,13S,14S)-13-Methyl-3-(3,3,3-trifluoro-1-hydroxypropyl

)-6,7,8,9,11,12,13,14,15,16-decahydro-17H-cyclopenta[a]phenan

thren-17-one 8j. White solid (95.0 mg, 52%), mp: 45-47 °C. Eluent:

ethyl acetate/petroleum ether (1:5, R_f= 0.3). ¹H NMR (400 MHz,

CDCl₃, 293 K, TMS) δ 7.31 (d, J = 8.0 Hz, 1 H), 7.15 (d, J = 8.1 Hz, 1

H), 7.12 (s, 1 H), 5.01 (d, J = 9.1 Hz, 1 H), 2.93 (dd, J = 8.7, 3.9 Hz, 2

3,3,3-Trifluoro-1-(4-(methylthio)phenyl)propan-1-ol 8e. Yel-

low liquid (70.0 mg, 59%). Eluent: ethyl acetate/petroleum ether

(1:10, R_f= 0.3). ¹H NMR (400 MHz, CDCl₃, 293 K, TMS) δ 7.28 (d, J =

Chin. J. Chem. 2021, 39, XXX－XXX

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First author et al.

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H), 2.69-2.38 (m, 5 H), 2.32-2.27 (m, 1 H), 2.19-1.93 (m, 4 H),

1.68-1.40 (m, 6 H), 0.90 (s, 3 H); ¹⁹F NMR (376 MHz, CDCl₃) δ

-63.73 (t, J = 10.7 Hz, 3 F); ¹³C NMR (126 MHz, CDCl₃, 293 K, TMS)

δ 220.89, 139.89, 137.01, 126.25, 126.20, 125.89 (q, J = 277.3 Hz),

125.76, 123.01, 68.42, 50.40, 47.90, 44.29, 42.68 (q, J = 26.9 Hz),

38.01, 35.76, 31.48, 29.36, 26.35, 25.65, 21.51, 13.74 ppm. IR

(KBr): ν_max= 3445, 2931, 2866, 1738, 1505, 1456, 1435, 1374,

1340, 1261, 1128, 1054, 1007 cm^-1. MS (EI): 366 (M⁺). HRMS (EI)

for C₂₁H₂₅O₂F₃(M⁺): Calcd: 366.1807; Found: 366.1805.

3,3,3-trifluoro-1-(4-methoxyphenyl)propan-1-one 9e. Yellow

solid (78 mg, 72%). Mp: 39-41 °C. Eluent: dichloro-

methane/petroleum ether = 1/1 (R_f= 0.4). ¹H NMR (400 MHz,

CDCl₃, 293 K, TMS) δ 7.89 (d, J = 8.7 Hz, 2 H), 6.94 (d, J = 8.7 Hz, 2

H), 3.86 (s, 3 H), 3.73 (q, J = 10.1 Hz, 2 H); ¹⁹F NMR (376 MHz,

CDCl₃) δ -62.05 (t, J = 10.1 Hz, 3 F); ¹³C NMR (126 MHz, CDCl₃, 293

K, TMS) δ 188.12 (q, J = 2.5 Hz), 164.30, 130.71, 128.83, 124.13 (q,

J = 276.9 Hz), 114.01, 55.47, 41.65 (q, J = 27.9 Hz) ppm. IR (KBr):

ν

_max= 2975, 1686, 1595, 1370, 1279, 1231, 1174, 1111 cm^-1. MS

(EI): 105 (100), 218. HRMS (EI): Calcd for C₁₀H₉O₂F₃: 218.0549,

Found: 218.0556.

General procedure for trifluoromethylation of vinyl acetates.

Into a 25 mL Schlenk tube equipped with a magnetic stirring bar

was added aryl enol acetate (0.5 mmol), ylide reagent (212 mg,

0.600 mmol), Ir(ppy)₃(6.5 mg, 1.0 mol%), Sc(OTf)₃(25 mg, 0.050

mmol), H₂O (9.0 µL, 0.50 mmol) and acetonitrile (2.5 mL) under an

atmosphere of Argon. The mixture was stirred under blue LED at

ambient temperature for 10 h. After that, the solvent was evapo-

rated under vacuum and the residue was purified by flash chro-

matograph to give the product.

3,3,3-trifluoro-2-methyl-1-phenylpropan-1-one 9f. Light yel-

low liquid (66 mg, 65%). Eluent: dichloromethane/petroleum

ether = 1/1 (R_f= 0.7). ¹H NMR (400 MHz, CDCl₃, 293 K, TMS) δ 7.96

(d, J = 8.4 Hz, 2 H), 7.63 (t, J = 7.4 Hz, 1 H), 7.51 (t, J = 7.9 Hz, 2 H),

4.32-4.20 (m, 1 H), 1.47 (d, J = 7.1 Hz, 3 H); ¹⁹F NMR (376 MHz,

CDCl₃) δ -68.32 (d, J = 8.0 Hz, 3 F); ¹³C NMR (126 MHz, CDCl₃, 293

K, TMS) δ 194.40 (q, J = 2.5 Hz), 135.62, 133.97, 128.88, 128.56,

125.30 (q, J = 280.1 Hz), 44.25 (q, J = 26.8 Hz), 11.64 (q, J = 2.9 Hz)

ppm. IR (KBr): ν_max= 2954, 1694, 1598, 1450, 1273, 1224, 1171,

1134, 1002 cm^-1. MS (EI): 105 (100), 202. HRMS (EI): Calcd for

C₁₀H₉OF₃: 202.0600, Found: 202.0608.

3,3,3-trifluoro-1-phenylpropan-1-one 9a. Yellow solid (62 mg,

66%). Mp: 30-32 °C. Eluent: dichloromethane/petroleum ether =

1/1 (R_f= 0.5). ¹H NMR (400 MHz, CDCl₃, 293 K, TMS) δ 7.92 (d, J =

7.4 Hz, 2 H), 7.62 (t, J = 7.4 Hz, 1 H), 7.50 (t, J = 7.7 Hz, 2 H), 3.79

(q, J = 10.0 Hz, 2 H); ¹⁹F NMR (376 MHz, CDCl₃) δ -62.07 (t, J = 10.0

Hz, 3 F); ¹³C NMR (151 MHz, CDCl₃, 293 K, TMS) δ 189.69, 135.80,

134.19, 128.93, 128.35, 123.98 (q, J = 276.8 Hz), 42.09 (q, J = 28.2

Hz) ppm. IR (KBr): ν_max= 2926, 2855, 1691, 1598, 1419, 1374,

1282, 1229, 1131, 1105, 1001 cm^-1. MS (EI): 105 (100), 188. HRMS

(EI): Calcd for C₉H₇OF₃: 188.0449, Found: 188.0455.

2-(trifluoromethyl)-2,3-dihydro-1H-inden-1-one 9g. Yellow

solid (69 mg, 69%). Mp: 55-57 °C. Eluent: dichloro-

methane/petroleum ether = 1/1 (R_f= 0.5). ¹H NMR (400 MHz,

CDCl₃, 293 K, TMS) δ 7.79 (d, J = 7.6 Hz, 1 H), 7.65 (t, J = 7.3 Hz, 1

H), 7.51 (d, J = 7.6 Hz, 1 H), 7.42 (t, J = 7.3 Hz, 1 H), 3.48-3.41 (m, 2

H), 3.38-3.28 (m, 1 H); ¹⁹F NMR (376 MHz, CDCl₃) δ -67.79 (d, J =

9.5 Hz, 3 F); ¹³C NMR (126 MHz, CDCl₃, 293 K, TMS) δ 196.83 (q, J =

1.3 Hz), 152.05, 135.78, 135.73 (q, J = 1.3 Hz), 128.11, 126.48,

124.90 (q, J = 278.4 Hz), 124.59, 49.68 (q, J = 27.5 Hz), 27.51 (q, J =

2.5 Hz) ppm. IR (KBr): ν_max= 2947, 1724, 1602, 1345, 1250, 1184,

1167, 1099 cm^-1. MS (EI): 131 (100), 200. HRMS (EI): Calcd for

C₁₀H₇OF₃: 200.0444, Found: 200.0446.

3,3,3-trifluoro-1-(4-fluorophenyl)propan-1-one 9b. White

solid (66 mg, 64%). Mp: 26-28 °C. Eluent: dichloro-

methane/petroleum ether = 1/1 (R_f= 0.5). ¹H NMR (400 MHz,

CDCl₃, 293 K, TMS) δ 7.97 (dd, J = 8.8, 5.3 Hz, 2 H), 7.18 (t, J = 8.5

Hz, 2 H), 3.78 (q, J = 9.9 Hz, 2 H); ¹⁹F NMR (376 MHz, CDCl₃) δ

-62.08 (t, J = 10.0 Hz, 3 F), -102.91 (m, 1 F); ¹³C NMR (126 MHz,

CDCl₃, 293 K, TMS) δ 188.13 (q, J = 2.5 Hz), 166.34 (d, J = 256.7

Hz), 132.26, 131.14 (d, J = 9.3 Hz), 123.87 (q, J = 277.1 Hz), 116.17

(d, J = 21.9 Hz), 42.08 (q, J = 28.3 Hz) ppm. IR (KBr): ν_max= 3076,

2943, 1692, 1602, 1512, 1371, 1225, 1097 cm^-1. MS (EI): 123 (100),

206. HRMS (EI): Calcd for C₉H₆OF₄: 206.0349, Found: 206.0345.

2-(trifluoromethyl)-3,4-dihydronaphthalen-1(2H)-one 9h.

Yellow solid (70 mg, 65%). Mp: 58-60 °C. Eluent: dichloro-

methane/petroleum ether = 1/1 (R_f= 0.5). ¹H NMR (400 MHz,

CDCl₃, 293 K, TMS) δ 8.04 (d, J = 7.9 Hz, 1 H), 7.52 (td, J = 7.6, 1.2

Hz, 1 H), 7.33 (t, J = 7.5 Hz, 1 H), 7.27 (d, J = 7.6 Hz, 1 H), 3.31-3.21

(m, 1 H), 3.15-3.02 (m, 2 H), 2.52-2.46 (m, J = 1 H), 2.30-2.20 (m, 1

H); ¹⁹F NMR (376 MHz, CDCl₃) δ -67.61 (d, J = 8.8 Hz, 3 F); ¹³C NMR

(126 MHz, CDCl₃, 293 K, TMS) δ 190.19, 143.07, 134.14, 131.85,

128.75, 127.72, 127.01, 125.04 (q, J = 279.9 Hz), 50.81 (q, J = 25.5

Hz), 27.45, 23.37 (q, J = 2.3 Hz) ppm. IR (KBr): ν_max= 2973, 2905,

1701, 1596, 1436, 1382, 1330, 1257, 1231, 1181, 1123, 1097, 1010

cm^-1. MS (EI): 118 (100), 214. HRMS (EI): Calcd for C₁₁H₉OF₃:

214.0605, Found: 214.0601.

1-(4-chlorophenyl)-3,3,3-trifluoropropan-1-one 9c. White

solid (72 mg, 65%). Mp: 51-53 °C. Eluent: dichloro-

methane/petroleum ether = 1/1 (R_f= 0.6). ¹H NMR (400 MHz,

CDCl₃, 293 K, TMS) δ 7.86 (d, J = 8.7 Hz, 2 H), 7.47 (d, J = 8.6 Hz, 2

H), 3.78 (q, J = 9.9 Hz, 2 H); ¹⁹F NMR (376 MHz, CDCl₃) δ -62.10 (t, J

= 9.9 Hz, 3 F); ¹³C NMR (126 MHz, CDCl₃, 293 K, TMS) δ 188.57 (q, J

= 1.3 Hz), 140.82, 134.05, 129.70, 129.25, 123.83 (q, J = 276.9 Hz),

42.04 (q, J = 28.3 Hz) ppm. IR (KBr): ν_max= 1701, 1592, 1424, 1371,

1269, 1226, 1104 cm^-1. MS (EI): 139 (100), 222. HRMS (EI): Calcd

for C₉H₆OClF₃: 222.0054, Found: 222.0064.

Supporting Information

The supporting information for this article is available on the

WWW under https://doi.org/10.1002/cjoc.2021xxxxx.

1-(4-bromophenyl)-3,3,3-trifluoropropan-1-one 9d. White

solid (72 mg, 54%). Mp: 65-67 °C. Eluent: dichloro-

methane/petroleum ether = 1/1 (R_f= 0.7). ¹H NMR (400 MHz,

CDCl₃, 293 K, TMS) δ 7.78 (d, J = 8.5 Hz, 2 H), 7.63 (d, J = 8.6 Hz, 2

H), 3.77 (q, J = 9.9 Hz, 2 H); ¹⁹F NMR (376 MHz, CDCl₃) δ -62.08 (t, J

= 9.9 Hz, 3 F); ¹³C NMR (126 MHz, CDCl₃, 293 K, TMS) δ 188.77 (q, J

= 1.3 Hz), 134.43 (q, J = 2.5 Hz), 132.25, 129.75, 129.60, 123.79 (q,

J = 276.9 Hz), 42.02 (q, J = 28.3 Hz) ppm. IR (KBr): ν_max= 1701,

1587, 1422, 1373, 1267, 1224, 1129, 1102 cm^-1. MS (EI): 183 (100),

266. HRMS (EI): Calcd for C₉H₆OBrF₃: 265.9549, Found: 265.9543.

Acknowledgement

The authors gratefully acknowledge the financial support from

National Natural Science Foundation of China (21625206,

21632009, 21572258) and the Strategic Priority Research Program

of the Chinese Academy of Sciences (XDB20000000).

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(The following will be filled in by the editorial staff)

Manuscript received: XXXX, 2021

Manuscript revised: XXXX, 2021

Chin. J. Chem. 2021, 39, XXX－XXX

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First author et al.

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Manuscript accepted: XXXX, 2021

Version of record online: XXXX, 2021

Accepted manuscript online: XXXX, 2021

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Chin. J. Chem. 2021, 39, XXX－XXX

Running title

Chin. J. Chem.

Entry for the Table of Contents

Rational Design and Development of Low-Price, Scalable, Shelf-Stable and Broadly Applicable Electrophilic Sulfonium

Ylide-Based Trifluoromethylating Reagents

Yafei Liu, Yijing Ling, Hangming Ge, Long Lu* and Qilong Shen*

Chin. J. Chem. 2021, 39, XXX—XXX. DOI: 10.1002/cjoc.202100XXX

A shelf-stable and highly reactive electrophilic trifluoromethylating reagents (trifluoromethyl)(4-nitrophenyl)bis(carbomethoxy)methylide 1g was

invented. A low cost and easy-to-handle process for the scalable preparation of reagent 1g was developed. Reagent 1g reacted with -ketoesters and

β

silyl enol ethers to give -trifluoromethylated- -ketoesters or -trifluoromethylated ketones in high yields, and could be served as a trifluoromethyl

α

β

α

radical for a variety of trifluoromethylative transformations under visible light irradiation, including radical trifluoromethylation of electron-rich in-

doles and pyrroles and sodium aryl sulfinates as well as trifluoromethylative difunctionalization with styrene derivatives. In addition, as a complimen-

tary, under reductive coupling conditions, reagent 1j reacted with a variety of (hetero)aryl iodides for the formation of trifluoromethylated (het-

ero)arenes.

Chin. J. Chem. 2021, 39, XXX－XXX

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Article Doi

Rational Design and Development of Low-Price, Scalable, Shelf-Stable and Broadly Applicable Electrophilic Sulfonium Ylide-Based Trifluoromethylating Reagents

DOI: 10.1002/cjoc.202100107

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