Photoredox-Catalyzed C-F Bond Allylation of Perfluoroalkylarenes at the Benzylic Position

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Photoredox-Catalyzed C−F Bond Allylation of Perﬂuoroalkylarenes

at the Benzylic Position

Naoki Sugihara, Kensuke Suzuki, Yoshihiro Nishimoto,* and Makoto Yasuda*

Cite This: J. Am. Chem. Soc. 2021, 143, 9308 −9313

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sı Supporting Information

ABSTRACT: Site-selective and direct C−F bond transformation of perﬂuoroalkylarenes was achieved with allylic stannanes via an

iridium photoredox catalyst system. The present deﬂuoroallylation proceeds exclusively at the benzylic position through

perﬂuoroalkyl radicals generated by a single-electron transfer from an excited photoredox catalyst to perﬂuoroalkylarenes. A variety

of perﬂuoroalkyl groups are applicable: linear perﬂuoroalkyl-substituted arenes such as Ar− C F and Ar− C F and

6 13

heptaﬂuoroisopropylarenes (Ar−CF(CF ) ) underwent site-selective deﬂuoroallylation. DFT calculation studies revealed that the

in situ generated Bu SnF traps F to prevent a retroreaction from the unstable perﬂuoroalkyl radical intermediate, and the radical

−

intermediate favorably reacts with allylic stannanes. The synthesis of a bis(triﬂuoromethyl)methylene unit containing compound,

which is an analog that is useful as a pharmaceutical agent for the prophylaxis or treatment of diabetes and inﬂammatory diseases,

demonstrated the utility of this reaction.

−

he importance of organic ﬂuorides is well established in

chemical method or Mg metal generates [ArCFCF ] species

the production of pharmaceutical, agrochemical, and

as key intermediates and accomplishes either a nucleophilic

organic electronic materials. In particular, polyﬂuoroalkyl

substances have attracted great interest because polyﬂuoroalkyl

moieties dramatically enhance thermal stability and exert a

addition to CO

or a nucleophilic substitution with

Me SiCl, respectively. Additionally, as far as double C−F

activation of CF CF group, Ichikawa reported Ni-mediated [3

unique surface eﬀect on surfactants and lubricants. The most

practical synthetic method is the installation of perﬂuoroalkyl

+ 2] cycloaddition of 2-pentaﬂuoroethyl-1-alkene with 4-

octyne. These methods, however, have never been applied to

longer perﬂuoroalkyl compounds most likely due to steric

hindrance and the electron-withdrawing eﬀect of perﬂuoroalkyl

groups that decrease the nucleophilicity of the corresponding

carbanions (Figure 1B, n ≥ 3). Instead of a two-electron

reduction, we focused on a mechanism via SET (Figure 1C)

wherein the reduction of perﬂuoroalkylarene 1 by an excited

groups (−C F₂_n₊₁) to organic compounds, and fully ﬂuorinated

alkyl group-substituted compounds (R−C F ) can be easily

2n+1

prepared by many well-established methods (Figure 1A).

Further functionalization of perﬂuoroalkyl units is rare,

however, despite the fact that the C−F bond activation of

readily available R−C F

has shown huge potential for

2n+1

−

access to functionalized perﬂuoroalkyl compounds. The

transformation of C−F bonds has intrinsic problems with

site selectivity due to the harsh conditions and highly reactive

photoredox catalyst (PC*) followed by F elimination from

10,11

radical anion A selectively gives benzylic carbon radical B.

Even in this case, the perﬂuoroalkyl groups cause serious

reagents that are needed to activate the robust C−F bonds.

These factors lead to undesired non-site-selective trans-

problems such as destabilization of the generated radical B

and inhibition of a sequential bond-forming reaction via large

formations and multiactivations of C−F bonds.

steric hindrance. As a result, a retroprocess that includes back

Many groups have reported single C−F bond trans-

−

electron transfer (BET) and F addition returns the reaction to

formations of the CF group in which the issue of site-

its starting point. We speculated that the utilization of

selectivity is not included (Figure 1B, n = 1). Hosoya and

Yoshida reported the transformation of ArCF₃bearing a

hydrosilyl group. Young reported a frustrated Lewis-pair-

mediated transformation. Following a report by Mattay that

described a photoinduced C−F bond activation, many

methodologies involving a single-electron transfer (SET)

mechanism have been developed. Recently, photoredox

organometallic reagents (R−M) would overcome these

problems. The eﬃcient reactivity of R−M toward a radical

−

intermediate and the trapping of F by M kinetically and

thermodynamically favored the progress of the reaction.

Herein, we report a photoredox-catalyzed, selective C−F

bond allylation of perﬂuoroalkyl-substituted arenes by using

catalysis has become a signiﬁcant protocol; Konig and Jui

Received: April 11, 2021

Published: June 2, 2021

independently reported eﬃcient C−F bond transformations of

ArCF with alkenes. In contrast to the CF group, the single

C−F bond activation of longer perﬂuoroalkyl groups is rare,

and only two reports are known to have described a

transformation of the CF CF group (Figure 1B, n = 2). The

two-electron reduction of ArCF CF via either an electro-

2021 American Chemical Society

Journal of the American Chemical Society

J. Am. Chem. Soc. 2021, 143, 9308−9313

308

Communication

Table 1. Optimization of Photoredox-Catalyzed

Deﬂuoroallylation of Nonaﬂuorobutyl Arene 1a with Allyl

Metal Reagents

Conditions: 1a (0.4 mmol), allyl metal (1.2 mmol), Ir(ppy) (0.004

mmol), Pr EtN (0.4 mmol), DME (2 mL), irradiation with 40 W

blue LEDs at 35 °C. Yields were determined by H NMR

spectroscopy using 1,1,1,2-tetrachloroethane as an internal standard.

No irradiation with 40 W blue LEDs. Without Ir(ppy) . Without

Pr EtN.

Table 2. Scope of Allylic Stannanes in Deﬂuoroallylation of

Figure 1. Site-selective C−F bond transformation of perﬂuoroalkyl

compounds.

allylic stannanes (Figure 1D). This is the ﬁrst achievement of a

selective C−F bond transformation in long perﬂuoroalkyl

groups (n ≥ 3).

We chose allylmetal reagents that possess an eﬃcient level of

reactivity to carbon radical species in the reaction of

nonaﬂuorobutyl arene 1a with Ir(ppy)₃(1 mol %) and

Pr EtN (1 equiv) under irradiation from 40 W blue LEDs

(

Table 1). The use of allyltrimethylsilane (entry 1),

allylboronic ester (entry 2), or allyltriﬂuoroborate salt (entry

) resulted in no reaction. On the other hand, allyltributyl-

stannane 2a gave the desired allylated compound 3aa in 52%

yield (entry 4). In this reaction, allylation occurred exclusively

at the benzylic position without the formation of multiallylated

products because the reduction of deﬂuoroallylated product

Conditions: 1a (0.4 mmol), 2 (1.2 mmol), Pr EtN (0.4 mmol), and

Ir(ppy) (0.004 mmol), DME (2 mL), irradiation with blue LEDs at

35 °C for 24 h. Isolated yields are shown.

aa would be more diﬃcult than that of starting material 1a

due to its high reduction potential. Both Ir(ppy) and

photoirradiation were essential to the reaction progress

yield of 3aa was decreased and a large consumption of 2a was

observed (entry 7). As described above, we discovered that

(

entries 5 and 6). Under the conditions without Pr EtN, the

allylstannane 2a showed outstanding eﬃciency toward

309

J. Am. Chem. Soc. 2021, 143, 9308−9313

Journal of the American Chemical Society

Communication

Table 3. Deﬂuoroallylation of Various Perﬂuoroalkylarenes

Using Methallylstannane 2b

Figure 2. Stern−Volmer luminescence quenching studies of photo-

catalyst Ir(ppy) (excitation 380 nm, emission 514 nm).

Table 2 shows the scope of the allylic stannanes 2 in the

reaction of 1a with the optimized reaction conditions (Table 1,

entry 4). Methallylstannane 2b aﬀorded the deﬂuoroallylated

product 3ab in a higher yield than 2a (entries 1 and 2).

Crotylstannane 2c was not suitable due to steric hindrance

(

entry 3). Allylic stannanes bearing substituents at the β-

position of the Sn atom were applicable substrates. Ph-,

AcOCH -, and MeOCH -substituted substrates (2d, 2e, and

f) aﬀorded the corresponding products (entries 4−6).

The scope of perﬂuoroalkyl arenes was investigated using

methallylstannane 2b (Table 3). Selective allylation of the

benzylic C−F bonds of C F and C F groups other than the

2 5

C F group proceeded smoothly (3bb, 3cb, 3db, and 3gb).

The CF group was also applicable to this allylation (3eb).

C(sp )−F and C(sp )−Cl bonds were tolerated and a benzylic

F group was selectively substituted (3fb, 3jb, 3sb, and 3ib). An

electron-withdrawing group on the benzene ring decreases the

reduction potential of substrate 1 to accelerate SET from

excited Ir(ppy) to 1, and CN, CO Me, CO H, and SO Ar

groups were suitable substituents (e.g., 3bb, 3gb, 3kb, 3jb).

On the other hand, perﬂuoroalkylarenes 1 without electron-

withdrawing groups were not available due to their higher

reduction potential. Functional groups such as methanesul-

fonyloxy, methyl, phenyl, and acetylamino groups were

compatible with this reaction system (3ob, 3mb, 3nb, 3rb).

The structure of 3ob was determined by X-ray diﬀraction

analysis (Figure S8). Perﬂuoroalkyl-substituted pyridine

smoothly gave the desired allylated product 3qb. The present

reaction system was applicable to a heptaﬂuoroisopropyl

(

CF(CF ) ) group regardless of the large steric hindrance,

3 2

and the benzylic C−F bond selectively underwent allylation

(

3tb and 3ub).

The Stern−Volmer luminescence quenching experiments

provided the information for electron transfer involving the Ir

catalyst and reagents (Figure 2). The experiments using

perﬂuoroalkylarene 1a, Pr EtN, and allylic stannane 2b

Conditions: 1 (0.4 mmol), 2b (1.2 mmol), Pr EtN (0.4 mmol), and

revealed that the principal interaction with the excited state

of Ir(ppy) was performed by 1a, and by comparison, Pr EtN

and 2b exhibited a much less eﬃcient quenching eﬀect.

Based on the above results, a plausible mechanism for the

Ir(ppy) (0.004 mmol), DME (2 mL), irradiation with blue LEDs at

5 °C for 24 h. Isolated yields are shown. 48 h. The yield of 3kb

was determined by H NMR spectroscopy using 1,1,1,2-tetrachloro-

ethane as an internal standard.

reaction of 1c with 2a is illustrated in Figure 3A. The blue-

light-excited Ir(ppy) (E = −1.73 V vs SCE) reduces 1c

red

deﬂuoroalkylation of perﬂuoroalkylarene because control

(E_r_e_d= −1.84 V vs SCE) via SET, aﬀording the Ir(IV)

species and radical anion A, although this step is an uphill

experiments in our hands based on either the Ko

nig or the

Jui systems were not applicable to perﬂuoroalkylarene 1a

Schemes S1 and S2).

reaction with respect to the redox potential. The elimination of

−

F from the benzylic position of A aﬀords radical B. Bu SnF,

310

Journal of the American Chemical Society

J. Am. Chem. Soc. 2021, 143, 9308−9313

Communication

Scheme 1. Synthesis of Bis(triﬂuoromethyl)methylene Unit

Containing Compound 11, an Analog Useful as a

Pharmaceutical Agent

activation energy for this step is 4.4 kcal/mol. The addition of

B to allyl stannane 2g occurs via TS2 with a much higher

activation barrier (19.6 kcal/mol) than the retroreaction from

INT1 to A (11.8 kcal/mol). Therefore, the retroprocess

including a back electron transfer from A to the Ir(IV) species

easily occurs in the absence of Me SnF. In the presence of

−

Me SnF, however, F coordinates to Me SnF to generate

Me SnF , and this complexation creates thermodynamical

−

stabilization (ΔG = 13.3 kcal/mol) in the system (INT3).

Thus, Bu SnF suppresses the retroreaction and allows the

desired reaction to proceed eﬀectively. In the use of simple

alkenes like Konig’s and Jui’s systems (Schemes S1 and

S2 ), the addition of perﬂuoroalkyl radicals to alkenes is slow

due to their larger steric hindrance than that of diﬂuoromethyl

radicals derived from CF₃groups so the retroreaction

preferentially occurs. On the other hand, the high reactivity

Figure 3. (A) Plausible mechanism for photoredox-catalyzed

deﬂuoroallylation of 1c with 2a. (B) Free energy proﬁle for tin

ﬂuoride-accelerated deﬂuoroallylation. (C) SOMO of radical anion A.

of allylic stannanes accelerates the capture of perﬂuoroalkyl

−

radicals, and Bu SnF traps F to disturb the retroreaction.

Thus, the use of allylic stannanes is the most important key to

accomplish the C−F bond activation of perﬂuoroalkyl groups.

The SOMO of radical anion A is displayed in Figure 3C.

Compound 1c receives an electron from the excited Ir(III)

that delocalizes in a π orbital on the benzene ring and also in

−

which is generated as a byproduct, complexes with F to give

−

Bu SnF and avoid the retroreaction step. Then, B adds to

a to give radical C. Reduction of the Ir(IV) species by

•+ 25

Pr EtN regenerates Ir(III) with radical cation Pr EtN .

the σ* orbitals of two benzylic C−F bonds (C −F and C −

•+

Pr EtN oxidizes C, which generates Pr EtN and cation D.

Bu SnF assists in the elimination of the stannyl cation, which

leads to product E and Bu SnF. Light ON/OFF experiments

suggested that the contribution of the radical chain mechanism

to this reaction was small. Density functional theory by

means of the (U)ω97XD/6-31+G(d) method (Figure 3B)

revealed the details of the key process from A to C, in which

Bu SnF participated (Me groups on a Sn atom instead of Bu

groups were adopted for DFT calculation). Elimination of

F ), and these C−F bonds of A are lengthened by comparison

−

with those of neutral 1c (from 1.365 to 1.402 Å). Therefore,

the separation of a benzylic F atom exclusively occurs to give

benzylic radical B, which accomplishes the site-selective

deﬂuoroallylation.

In pharmaceutical compounds, the replacement of alkyl

groups by perﬂuoroalkyl groups is an important issue because

signiﬁcant changes are often found in the biological properties.

Therefore, we targeted compound 11, which is the bis-

(triﬂuoromethyl) analogue of compound 12 with ASK1

−

the F from radical anion A exergonically proceeds, and the

311

J. Am. Chem. Soc. 2021, 143, 9308−9313

Journal of the American Chemical Society

https://pubs.acs.org/10.1021/jacs.1c03760

Communication

inhibitory action that is useful for the prophylaxis or treatment

Authors

of diabetes and inﬂammatory diseases (Scheme 1). Substrate

t was employed in the deﬂuoroallylation system using 2a

Naoki Sugihara − Department of Applied Chemistry,

Graduate School of Engineering, Osaka University, Suita,

Osaka 565-0871, Japan; orcid.org/0000-0002-5778-

5369

Kensuke Suzuki − Department of Applied Chemistry,

Graduate School of Engineering, Osaka University, Suita,

Osaka 565-0871, Japan; orcid.org/0000-0001-9513-

under standard conditions to give bis(triﬂuoromethyl)

compound 3ta in 88% yield. Hydrolysis of the CN group

followed by esteriﬁcation of the carboxyl group of 4 aﬀorded

benzyl ester 5. The vinyl group in 5 was transformed to a

terminal hydroxyl moiety via hydroboration−oxidation, giving

464X

6. The subsequent oxidation of 6 with pyridinium dichromate

(

PDC) in DMF was followed by esteriﬁcation to provide

Complete contact information is available at:

diester 8. After deprotection of the benzyl ester moiety, the

amidation of carboxylic acid 9 with amine 10 gave the targeted

compound 11.

Notes

In conclusion, a direct and site-selective C(sp )−F bond

The authors declare no competing ﬁnancial interest.

allylation in perﬂuoroalkylarenes with allylic stannanes was

accomplished via the use of Ir(ppy) . This deﬂuoroallylation

ACKNOWLEDGMENTS

■

proceeds exclusively at the benzylic position through

perﬂuoroalkyl radicals generated by SET between excited

Ir(ppy)₃and perﬂuoroalkylarenes. The mild conditions

promoted compatibility among various functional groups.

This work was supported by JST CREST Grant Number

JPMJCR20R3, Japan. It was also supported by JSPS

KAKENHI Grant Number JP19K05455.

DFT calculation studies showed that when Bu SnF is

generated as a byproduct, it traps F⁻and prevents the

retroreaction from an unstable perﬂuoroalkyl-substituted

carbon radical, which allows the reaction of the radical

intermediate with allylic stannanes to proceed. The synthesis of

a bis(triﬂuoromethyl)methylene unit containing compound 11

demonstrated the signiﬁcance of this reaction to medicinal

chemistry.

REFERENCES

■

1) (a) Jeschke, P. The Unique Role of Fluorine in the Design of

Active Ingredients for Modern Crop Protection. ChemBioChem 2004 ,

, 570 −589. (b) Mu

Pharmaceuticals: Looking Beyond Intuition. Science 2007, 317 , 1881 −

886. (c) Ametamey, S. M.; Honer, M.; Schubiger, P. A. Molecular

ller, K.; Faeh, C.; Diederich, F. Fluorine in

Imaging with PET. Chem. Rev. 2008, 108, 1501−1516. (d) Zhu, Y.;

Han, J.; Wang, J.; Shibata, N.; Sodeoka, M.; Soloshonok, V. A.;

Coelho, J. A. S.; Toste, F. D. Modern Approaches for Asymmetric

Construction of Carbon −Fluorine Quaternary Stereogenic Centers:

Synthetic Challenges and Pharmaceutical Needs. Chem. Rev. 2018,

118, 3887−3964. (e) Gillis, E. P.; Eastman, K. J.; Hill, M. D.;

Donnelly, D. J.; Meanwell, N. A. Applications of Fluorine in Medicinal

Chemistry. J. Med. Chem. 2015, 58, 8315−8359.

ASSOCIATED CONTENT

■

sı Supporting Information

The Supporting Information is available free of charge at

https://pubs.acs.org/doi/10.1021/jacs.1c03760.

(

2) (a) Kirsch, P. Modern Fluoroorganic Chemistry: Synthesis,

Reactivity, Applications, 2nd ed.; Wiley-VCH, 2013. (b) Banks, R.

E.; Smart, B. E.; Tatlow, J. C. Organoﬂuorine Chemistry: Principles and

Commercial Applications; Plenum, 1994. (c) Uneyama, K. Organo-

ﬂuorine Chemistry; Blackwell Publishing, 2006.

Experimental details, characterization data, NMR

spectra, and DFT calculation details (PDF)

Accession Codes

(3) (a) Umemoto, T. Electrophilic Perfluoroalkylating Agents.

CCDC 2070966 contains the supplementary crystallographic

data for this paper. These data can be obtained free of charge

via www.ccdc.cam.ac.uk/data_request/cif, or by emailing

data_request@ccdc.cam.ac.uk, or by contacting The Cam-

bridge Crystallographic Data Centre, 12 Union Road,

Cambridge CB2 1EZ, UK; fax: +44 1223 336033.

Chem. Rev. 1996 , 96 , 1757 −1777. (b) Macé, Y.; Magnier, E. The New

Age of Electrophilic Perfluoroalkylation Reactions. Eur. J. Org. Chem.

2012 , 2012 , 2479 −2494. (c) Ma, J.; Cahard, D. Asymmetric

Fluorination, Trifluoromethylation, and Perfluoroalkylation Reac-

tions. Chem. Rev. 2004, 104 , 6119 −6146. (d) Barata-Vallejo, S.;

Bonesi, S. M.; Postigo, A. Perfluoroalkylation Reactions of (Hetero)-

arenes. RSC Adv. 2015 , 5 , 62498 −62518. (e) Barata-Vallejo, S.;

Bonesi, S. M.; Postigo, A. Photocatalytic Fluoroalkylation Reactions of

Organic Compounds. Org. Biomol. Chem. 2015, 13, 11153 −11183.

AUTHOR INFORMATION

■

Fluoroalkylation Reactions. ACS Catal. 2018 , 8 , 7287 −7307.

f) Barata-Vallejo, S.; Cooke, M. V.; Postigo, A. Radical

4) (a) O ’Hagan, D. Understanding Organofluorine Chemistry. An

Corresponding Authors

Yoshihiro Nishimoto − Department of Applied Chemistry,

Graduate School of Engineering, Osaka University, Suita,

Osaka 565-0871, Japan; Innovative Catalysis Science

Division, Institute for Open and Transdisciplinary Research

Initiatives (ICS-OTRI), Osaka University, Suita, Osaka 565-

Introduction to the C −F Bond. Chem. Soc. Rev. 2008 , 37 , 308 −319.

(b) Amii, H.; Uneyama, K. C −F Bond Activation in Organic

Synthesis. Chem. Rev. 2009, 109, 2119−2183.

(5) (a) Bentel, M. J.; Yu, Y.; Xu, L.; Li, Z.; Wong, B. M.; Men, Y.;

Liu, J. Defluorination of Per- and Polyfluoroalkyl Substances (PFASs)

with Hydrated Electrons: Structural Dependence and Implications to

PFAS Remediation and Management. Environ. Sci. Technol. 2019, 53,

871, Japan; orcid.org/0000-0002-7182-0503;

Email: nishimoto@chem.eng.osaka-u.ac.jp

Makoto Yasuda − Department of Applied Chemistry,

Graduate School of Engineering, Osaka University, Suita,

Osaka 565-0871, Japan; Innovative Catalysis Science

Division, Institute for Open and Transdisciplinary Research

Initiatives (ICS-OTRI), Osaka University, Suita, Osaka 565-

718−3728. (b) Liu, J.; Van Hoomissen, D. J.; Liu, T.; Maizel, A.;

Huo, X.; Fernández, S. R.; Ren, C.; Xiao, X.; Fang, Y.; Schaefer, C. E.;

Higgins, C. P.; Vyas, S.; Strathmann, T. J. Reductive Defluorination of

Branched Per- and Polyfluoroalkyl Substances with Cobalt Complex

Catalysts. Environ. Sci. Technol. Lett. 2018, 5, 289−294.

(6) (a) Yoshida, S.; Shimomori, K.; Kim, Y.; Hosoya, T. Single C −F

Bond Cleavage of Trifluoromethylarenes with an ortho -Silyl Group.

871, Japan; orcid.org/0000-0002-6618-2893;

Email: yasuda@chem.eng.osaka-u.ac.jp

312

J. Am. Chem. Soc. 2021, 143, 9308−9313

Journal of the American Chemical Society

Y.; Shimomori, K.; Hosoya, T.; Yoshida, S. Single C −F Trans-

Communication

Angew. Chem., Int. Ed. 2016, 55, 10406−10409. (b) Idogawa, R.; Kim,

formations of o -Hydrosilyl Benzotrifluorides with Trityl Compounds

as All-in-One Reagents. Org. Lett. 2020, 22, 9292−9297. (c) Kim, Y.;

Kanemoto, K.; Shimomori, K.; Hosoya, T.; Yoshida, S. Functionaliza-

tion of a Single C −F Bond of Trifluoromethylarenes Assisted by an

ortho-Silyl Group Using a Trityl-Based All-in-One Reagent with

Ytterbium Triflate Catalyst. Chem. - Eur. J. 2020, 26, 6136−6140.

Acceptors Using a Photoredox Catalyst. Chem. - Eur. J. 2018 , 24 ,

312 −316. (b) Suzuki, I.; Esumi, N.; Yasuda, M. Photoredox α -

Allylation of α -Halocarbonyls with Allylboron Compounds Accel-

erated by Fluoride Salts under Visible Light Irradiation. Asian J. Org.

Chem. 2016 , 5 , 179 −182. (c) Gontala, A.; Jang, G. S.; Woo, S. K.

Visible-Light Photoredox-Catalyzed α -Allylation of α -Bromocarbonyl

Compounds Using Allyltrimethylsilane. Bull. Chem. Korea Chem. Soc.

2021, 42, 506−509.

7) (a) Mandal, D.; Gupta, R.; Jaiswal, A. K.; Young, R. D.

(19) An electron transferred from an excited Ir catalyst to 1a is

localized on the arene ring. Therefore, the electron-withdrawing eﬀect

Frustrated Lewis-Pair-Meditated Selective Single Fluoride Substitu-

tion in Trifluoromethyl Groups. J. Am. Chem. Soc. 2020 , 142 , 2572 −

of the C F group decreases the reduction potential of 1a to accelerate

4 9

578. (b) Cabrera-Trujillo, J. J.; Fernández, I. Understanding the C −

the single electron transfer. The electron-withdrawing eﬀect of a

monoallylated-perﬂuoroalkyl group is lower than that of a

perﬂuoroalkyl group, so deﬂuoroallylated product 3aa has a higher

reduction potential than 1a.

F Bond Activation Mediated by Frustrated Lewis Pairs: Crucial Role

of Non-covalent Interactions. Chem. - Eur. J. 2021, 27, 3823−3831.

(8) Mattay, J.; Runsink, J.; Rumbach, T.; Ly, C.; Gersdorf, J.

Selectivity and Charge Transfer in Photoreactions of α ,α ,α -

Trifluorotoluene with Olefins. J. Am. Chem. Soc. 1985, 107, 2557−

(20) The extensive screening of photoredox catalysts, solvents,

reaction time, temperature, and equivalents of components was

conducted and is presented in Supporting Information (Tables S1, S2,

and S3).

2558.

9) (a) Kako, M.; Morita, T.; Torihara, T.; Nakadaira, Y.

(

21) Scheme S3 in Supporting Information shows perﬂuoroalkylar-

enes 1 that were not available in this reaction system.

22) Nguyen, J. D.; D ’Amato, E. M.; Narayanam, J. M. R.;

Photoinduced Novel Silylation of CF -substituted Benzenes with

Disilane and Trisilane. J. Chem. Soc., Chem. Commun. 1993, 678−680.

(

(b) Clavel, P.; Lessene, G.; Biran, C.; Bordeau, M.; Roques, N.;

Stephenson, C. R. J. Engaging Unactivated Alkyl, Alkenyl and

Aryliodides in Visible-light-mediated Free Radicalreactions. Nat.

Chem. 2012, 4, 854−859.

Trevin, S.; Montauzon, D. d. Selective Electrochemical Synthesis and

Reactivity of Functional Benzylic Fluorosilylsynthons. J. Fluorine

Chem. 2001, 107 , 301 −310. (c) Amii, H.; Hatamoto, Y.; Seo, M.;

Uneyama, K. A New C-F Bond-Cleavage Route for the Synthesis of

Octafluoro[2.2]paracyclophane. J. Org. Chem. 2001 , 66 , 7216 −7218.

(23) A cyclic voltammetry measurement of 1a and 1c was carried

out (Figure S3 ).

24) (a) Blunden, S. J.; Hill, R. Quaternary Ammonium

Tributyldifluorostannates: Their Structure in Solution, Including a

d) Luo, C.; Bandar, J. S. Selective Defluoroallylation of

Trifluoromethylarenes. J. Am. Chem. Soc. 2019, 141, 14120 −14125.

10) Chen, K.; Berg, N.; Gschwind, R.; König, B. Selective Single

−

Novel Trans-F Bridged Species, {(Bu SuF) F} . J. Organomet. Chem.

1989 , 371 , 145 −154. (b) Gingras, M. Tetrabutylammonium

Difluorotriphenylstannate as a New Anhydrous Synthetic Equivalent

to TBAF. Tetrahedron Lett. 1991 , 32 , 7381 −7384. (c) Mitchell, T. M.;

Godry, B. Multinuclear Magnetic Resonance Studies on Intra-

molecular Chalcogen-Tin Coordination in Compounds of the Type

Me Sn(X)CH CH P(E)Ph (X = Halogen, E = Chalcogen). J.

C(sp )−F Bond Cleavage in Trifluoromethylarenes: Merging Visible-

Light Catalysis with Lewis Acid Activation. J. Am. Chem. Soc. 2017,

39, 18444−18447.

11) (a) Wang, H.; Jui, N. T. Catalytic Defluoroalkylation of

Trifluoromethylaromatics with Unactivated Alkenes. J. Am. Chem. Soc.

018 , 140 , 163 −166. (b) Vogt, D. B.; Seath, C. P.; Wang, H.; Jui, N.

Organomet. Chem. 1995, 490, 45−49.

T. Selective C −F Functionalization of Unactivated Trifluoromethy-

larenes. J. Am. Chem. Soc. 2019, 141, 13203−13211.

12) Yamauchi, Y.; Sakai, K.; Fukuhara, T.; Hara, S.; Senboku, H.

25) An excess amount of iPr EtN would be needed to eﬀectively

regenerate the Ir(III) catalyst to disturb a back electron transfer from

A to the Ir(IV) species.

Synthesis of 2-Aryl-2,3,3,3-tetrafluoropropanoic Acids, Tetrafluori-

nated Fenoprofen and Ketoprofen by Electrochemical Carboxylation

of Pentafluoroethylarenes. Synthesis 2009, 2009 , 3375 −3377.

(26) The results of light ON/OFF experiments are shown in Figure

S2.

(

27) The complete description of energy proﬁles for the

(13) Utsumi, S.; Katagiri, T.; Uneyama, K. Cu-deposits on Mg Metal

de ﬂ uoroallylation without or with Me SnF are shown in Figures S6

Surfaces Promote Electron Transfer Reactions. Tetrahedron 2012, 68,

085−1091.

14) Ichitsuka, T.; Fujita, T.; Arita, T.; Ichikawa, J. Double C −F

Bond Activation through β -Fluorine Elimination: Nickel-Mediated [3

2] Cycloaddition of 2-Trifluoromethyl-1-alkenes with Alkynes.

Angew. Chem., Int. Ed. 2014, 53, 7564 −7568.

15) Chandra, A. K.; Uchimaru, T. A DFT Study on the C-H Bond

and S7.

28) We observed that the addition of Bu SnF accelerated the

deﬂuoroallylation of 1a with 2b (Figure S4 ).

29) Uchikawa, O.; Sakai, N.; Terao, Y.; Suzuki, H. Fused

(

Heterocyclic Compound. International Patent WO 2008016131 A1,

May 13, 2009.

Dissociation Enthalpies of Haloalkanes: Correlation between the

(30) Details of experimental procedures for each step are described

Bond Dissociation Enthalpies and Activation Energies for Hydrogen

Abstraction. J. Phys. Chem. A 2000, 104, 9244 −9249.

in the Supporting Information.

(16) (a) Bott, G.; Field, L. D.; Sternhell, S. Steric Effects. A Study of

a Rationally Designed System. J. Am. Chem. Soc. 1980 , 102 , 5618 −

5626. (b) Schlosser, M.; Michel, M. About the “Physiological Size ” of

Fluorine Substituents: Comparison of Sensorially Active Compounds

with Fluorine and Methyl Substituted Analogues. Tetrahedron 1996 ,

52 , 99 −108. (c) Wolf, C.; Konig, W. A.; Roussel, C. Influence of

Substituents on the Rotational Energy Barrier of Atropisomeric

Biphenyls. Studies by Polarimetry and Dynamic Gas Chromatog-

raphy. Liebigs Ann. 1995 , 1995 , 781 −786. (d) Leroux, F.

Atropisomerism, Biphenyls, and Fluorine: a Comparison of Rotational

Barriers and Twist Angles. ChemBioChem 2004 , 5 , 644 −649.

(

17) Romero, N. A.; Nicewicz, D. A. Organic Photoredox Catalysis.

Chem. Rev. 2016, 116, 10075−10166.

18) (a) Esumi, N.; Suzuki, K.; Nishimoto, Y.; Yasuda, M.

Generation of α -Iminyl Radicals from α -Bromo Cyclic N-

Sulfonylimines and Application to Coupling with Various Radical

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