Deoxyfluorination of Carboxylic Acids with CpFluor: Access to Acyl Fluorides and Amides

Article abstract of DOI:10.1021/acs.orglett.1c00190

3,3-Difluoro-1,2-diphenylcyclopropene (CpFluor), a bench-stable fluorination reagent, has been developed in the deoxyfluorination of carboxylic acids to afford various acyl fluorides. This all-carbon-based fluorination reagent enabled the efficient transformation of (hetero)aryl, alkyl, alkenyl, and alkynyl carboxylic acids to the corresponding acyl fluorides under the neutral conditions. This deoxyfluorination method was featured by the synthesis of acyl fluorides with in-situ formed CpFluor, as well as the one-pot amidation reaction of carboxylic acids via in-situ formed acyl fluorides.

Full text of DOI:10.1021/acs.orglett.1c00190

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Letter
Deoxyfluorination of Carboxylic Acids with CpFluor: Access to Acyl
Fluorides and Amides
Xiu Wang, Fei Wang, Fengfeng Huang, Chuanfa Ni, and Jinbo Hu*
Cite This: Org. Lett. 2021, 23, 1764−1768
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ABSTRACT: 3,3-Difluoro-1,2-diphenylcyclopropene (CpFluor), a
bench-stable fluorination reagent, has been developed in the deoxyfluori-
nation of carboxylic acids to afford various acyl fluorides. This all-carbon-
based fluorination reagent enabled the efficient transformation of
(hetero)aryl, alkyl, alkenyl, and alkynyl carboxylic acids to the
corresponding acyl fluorides under the neutral conditions. This
deoxyfluorination method was featured by the synthesis of acyl fluorides
with in-situ formed CpFluor, as well as the one-pot amidation reaction of carboxylic acids via in-situ formed acyl fluorides.
Scheme 1. Representative Fluorination Reagents in
Deoxyfluorination of Carboxylic Acids
ecently, acyl fluorides have attracted much attention in
organic synthesis, owing to their unique balance of
R
stability and reactivity.1 They are widely used as acyl,2 aryl,3
and fluoride sources.4 Acyl fluorides are superior synthons
compared to their corresponding carboxylic acid derivatives in
terms of stability, reactivity, and transmetalation ability.1,3
Therefore, the development of a reliable and general method
to prepare acyl fluorides is highly appealing, among which the
deoxyfluorination of carboxylic acids with a fluorination
reagent has become a routine method.1b−d In this context, a
bench-stable, readily available and efficient fluorination reagent
is highly desirable.
Until now, two types of conventional fluorination reagents
have been established in the synthesis of acyl fluorides. One is
nitrogen-containing fluorination reagents (NCF reagents)
(Scheme 1a),5−8 such as cyanuric fluoride,6 TFFH,7 and
perfluoroalkylamines.8 The other is sulfur-containing fluorina-
tion reagents (S(C)F reagents) (Scheme 1b),9−12 such as
DAST,10 Deoxo-Fluor,11 and (Me4N)SCF3.12 The introduc-
tion of a heteroatom is of great importance to stabilize and
improve the reactivity of fluorination reagents for carbonyl
compounds. However, these fluorination reagents have some
drawbacks, such as sensitivity to air and moisture, tediousness,
and costly synthetic routes, as well as the requirement of an
additional base, which limit their applications in the synthesis
of acyl fluorides.
3,3-Difluoro-1,2-diarylcyclopropenes, a class of carbon-based
fluorinating reagents (also called CpFluors), could be
synthesized by stable and inexpensive 1,2-diarylalkynes with
difluorocarbene reagents via [2 + 2] cycloaddition.13 With our
continuous efforts in organofluoine chemistry, we found that
CpFluors could not only convert a variety of alcohols to alkyl
fluorides14 but also efficiently convert a diversity of carboxylic
acids to acyl fluorides. Herein, we describe a practicable and
straightforward approach to acyl fluorides via deoxyfluorination
of carboxylic acids with CpFluor (Scheme 1c).
Encouraged by our previous work on deoxyfluorination of
alcohols with CpFluors,14 the deoxyfluorination of 3-
methylbenzoic acid (1a) via nucleophilic attack of 3,3-
difluoro-1,2-diphenylcyclopropene (CpFluor 2) was evaluated
Received: January 18, 2021
Published: February 15, 2021
https://dx.doi.org/10.1021/acs.orglett.1c00190
© 2021 American Chemical Society
Org. Lett. 2021, 23, 1764−1768
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a b
,
(Table 1). As expected, acyl fluoride 3a was obtained in 13%
yield at room temperature (entry 1). Conducting the reaction
Scheme 2. Deoxyfluorination of Carboxylic Acids
a
Table 1. Optimization of the Reaction Conditions
b
entry
2 (equiv)
temp (°C)
3a (%)
1
2
3
4
5
6
1.2
1.2
1.2
1.2
1.6
2.0
25
30
50
70
50
50
13
53
57
53
76 (70)
65
a
Reaction conditions: 1a (0.5 mmol), CH2Cl2 (2.5 mL), 4 h.
b
Determined by 19F NMR analysis of the crude mixture, using
benzotrifluoride as an internal standard. An isolated yield is given in
parentheses.
at an elevated temperature (50 °C) provided the desired
product 3a in 57% yield (entry 3). Furthermore, the use of 1.6
equiv of CpFluor 2 improved the yield of 3a to 76% (entry 5).
However, the use of 2 equiv of CpFluor 2 resulted in the
formation of more anhydride, as well as a low yield of target
product 3a (entry 6), probably arising from the increased
concentration of intermediate I at the initiation stage (see
Scheme 4). Notably, no bases or additives are required in this
deoxyfluorination process, and the byproduct 2,3-diphenyl-
cycloprop-2-en-1-one (5) can be easily separated from the
target molecule.
The generality of this protocol was explored with a wide
range of carboxylic acids as shown in Scheme 2. Naphthyl
substrates provided the corresponding acyl fluorides 3b and 3c
in good yields. Nonsubstituted benzoyl fluoride 3d was
observed with moderate yield. In addition, benzoic acid
bearing electron-donating groups such as p-tert-butyl, p-
methoxyl, and acetyl substituents were well tolerated, affording
aroyl fluorides 3e−3g in 70−84% yields. The introduction of
electron-withdrawing groups such as halogens, bromomethyl,
and nitro groups onto benzoic acid in the para-position gave
the target products 3h−3k in 71%−77% yields. Benzoic acid
with electronically diverse functional groups in the ortho- and
meta-positions also successfully converted into the desired
aroyl fluorides (3l−3o), which illustrated that the present
reaction is insensitive to electronic effect and steric hindrance.
In addition, disubstituted acyl fluorides 3p and 3q were
obtained in 79% and 61% yields, respectively. Other hetero-
cycles including pyridyl (1r) and benzothiophene (1s) were
also compatible in this reaction. Particularly, alkenyl acyl
fluorides (3t and 3u) were accommodated during the reaction
regardless of the electronic nature of the aromatic ring. To
prove the utility of our method, carboxylic acid-containing
drugs were examined; probenecid coupled with CpFluor
yielded 3v in 82% yield, whereas bexarotene only afforded
3w in 38% isolated yield. The reaction could further be
extended to the aliphatic and alkynyl carboxylic acids; however,
low yields of desired products were observed due to the
instability of the formed acyl fluorides during isolation by silica
gel flash column chromatography.
a
Reaction conditions: 1 (0.5 mmol), 2 (0.8 mmol), CH2Cl2 (2.5 mL),
b
c
50 °C, 4 h. Isolated yields. 19F NMR yields using benzotrifluoride as
an internal standard. The isolated yield of the reaction performed on
1 mmol scale is given in parentheses.
d
One-pot deoxyfluorination/amidation of several selected
carboxylic acids were investigated using benzylamine as the
substrate. Acyl fluorides were formed by an optimized
deoxyfluorination procedure, followed by the addition of 1.5
equiv of benzylamine activated by 1 equiv of 4-dimethylami-
nopyridine (DMAP), and then direct amidation proceeded
smoothly at 50 °C for another 4 h (Table 2). Notably, benzylic
(1x and 1y), aliphatic (1z), and alkynyl (1aa) carboxylic acids
were well participated in the formation of acyl fluorides at
room temperature, affording the corresponding acyl fluorides
3x−3aa in good to excellent yields. Meanwhile, the one-pot
amidation process furnished target products 4x−4aa in
moderate to good yields. On the other hand, representative
aromatic carboxylic acid 1ab and alkenyl carboxylic acid 1ac
were also subjected to the one-pot deoxyfluorination/
amidation. Besides, carboxylic acid containing bioactive
molecules, including bindazac 1ad and sulindac 1ae, were
proved to be effective coupling partners at the elevated
temperature, providing 4ad−4ae in 78% and 75% yields,
respectively. In some cases, in situ formed 2,3-diphenylcyclo-
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Table 2. One-Pot Deoxyfluorination/Amidation of
Carboxylic Acids via in Situ Formed Acyl Fluorides
Scheme 3. Two-Step [2 + 1] Cycloaddition/
Deoxyfluorination for the Synthesis of Acyl Fluorides
a
a b
,
a
Reaction conditions: (1) diphenylacetylene (0.88 mmol),
TMSCF2Br (1.32 mmol), nBu4NBr (0.026 mmol), toluene (2.0
mL), 110 °C, 2 h; (2) Toluene was removed under the vacuum,
b
added acid (0.5 mmol), CH2Cl2 (2 mL), rt or 50 °C, 4 h. Isolated
c
yields. Determined by 19F NMR analysis of the crude mixture, using
benzotrifluoride as an internal standard.
Scheme 4. Proposed Mechanism
a
Reaction conditions: 1 (0.5 mmol), 2 (0.8 mmol), CH2Cl2 (2.5 mL),
rt, 4 h. Then BnNH2 (1.5 equiv), DMAP (1 equiv), 50 °C, 4 h.
b
Determined by 19F NMR analysis of the crude mixture, using
c
d
benzotrifluoride as an internal standard. Isolated yields. Deoxy-
fluorination step was performed at 50 °C.
prop-2-en-1-one (5) in the deoxyfluorination step could also
react with benzylamine, which decreased the amount of
benzylamine for the amidation procedure and resulted in the
low efficiency of the subsequent amidation.
Intermediate II resulting from the combination of a cyclo-
propenium cation and carboxylate anion of I is activated by a
proton to afford intermediate III, which further undergoes
competitive nucleophilic substitution reaction with a carbox-
ylate anion and bifluoride anion to provide anhydride 6 and
acyl fluoride 3, respectively. In the fluorination stage, the
formation of a carboxylate anion is inhibited due to the
accumulation of HF; thus, HF acts as the activator. In this
stage, the formation of intermediate III is dominated by the
direct attack of carboxylic acid 1 on the cyclopropenium cation
and the formation of acyl fluoride 3 is the main pathway.
In summary, we have disclosed the high fluorination ability
of gem-difluorocyclopropene in deoxyfluorination of carboxylic
acids to synthesize a wide range of acyl fluorides. This
deoxyfluorination method was featured by the synthesis of acyl
fluorides with in situ formed CpFluor, as well as the one-pot
amidation reaction of carboxylic acids via in situ formed acyl
fluorides.
To evaluate the utility of this approach, deoxyfluorination of
carboxylic acids with in situ formed CpFluor was tested in
Scheme 3. Initially, CpFluor 2 was prepared by [2 + 1]
cycloaddition reaction of diphenyl acetylene with commercially
available Me3SiCF2Br without further purification. Subse-
quently, 1 equiv of aromatic or benzylic carboxylic acid was
directly added under the identical reaction conditions.
Fortunately, 1-naphthoyl fluoride 3c and 2-(naphthalen-2-
yl)acetyl fluoride 3x were obtained without a great loss
compared to reaction with isolated CpFluor. This set of studies
revealed that the present methodology is complementary to
the deoxyfluorination of carboxylic acids without presynthesis
of a fluorination reagent.
Based on our experimental results as well as the reported
aromatic cation activation mode of gem-dihalocyclopropene in
nucleophilic halogenation of alcohols and carboxylic acids,14,15
the proposed mechanism of deoxyfluorination of carboxylic
acids to acyl fluorides was reasoned as shown in Scheme 4. In
the initiation stage, CpFluor (2) is prone to be in equilibrium
with cyclopropenium salt I in the presence of carboxylic acids.
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Acyl Electrophiles in Suzuki−Miyaura Coupling. Eur. J. Org. Chem.
2017, 2017, 4324−4327. (e) Boreux, A.; Indukuri, K.; Gagosz, F.;
Riant, O. Acyl Fluorides as Efficient Electrophiles for the Copper-
Catalyzed Boroacylation of Allenes. ACS Catal. 2017, 7, 8200−8204.
(f) Ogiwara, Y.; Sakurai, Y.; Hattori, H.; Sakai, N. Palladium-
Catalyzed Reductive Conversion of Acyl Fluorides via Ligand-
Controlled Decarbonylation. Org. Lett. 2018, 20, 4204−4208.
(g) Pan, F.-F.; Guo, P.; Li, C.-L.; Su, P.; Shu, X.-Z. Enones from
Acid Fluorides and Vinyl Triflates by Reductive Nickel Catalysis. Org.
Lett. 2019, 21, 3701−3705. (h) Ogiwara, Y.; Iino, Y.; Sakai, N.
Catalytic C−H/C−F Coupling of Azoles and Acyl Fluorides. Chem. -
Eur. J. 2019, 25, 6513−6516. (i) Wang, Z.; Wang, X.; Nishihara, Y.
PPh3-Assisted Esterification of Acyl Fluorides with Ethers via C(sp3)−
O Bond Cleavage Accelerated by TBAT. Catalysts 2019, 9, 574.
(j) Han, J.; Zhou, W.; Zhang, P.-C.; Wang, H.; Zhang, R.; Wu, H.-H.;
Zhang, J. Design and Synthesis of WJ-Phos, and Application in Cu-
Catalyzed Enantioselective Boroacylation of 1,1-Disubstituted Al-
lenes. ACS Catal. 2019, 9, 6890−6895.
(3) (a) Keaveney, S. T.; Schoenebeck, F. Palladium-Catalyzed
Decarbonylative Trifluoromethylation of Acid Fluorides. Angew.
Chem., Int. Ed. 2018, 57, 4073−4077. (b) Malapit, C. A.; Bour, J.
R.; Brigham, C. E.; Sanford, M. S. Base-free nickel-catalysed
decarbonylative Suzuki−Miyaura coupling of acid fluorides. Nature
2018, 563, 100−104. (c) Okuda, Y.; Xu, J.; Ishida, T.; Wang, C. A.;
Nishihara, Y. Nickel-Catalyzed Decarbonylative Alkylation of Aroyl
Fluorides Assisted by Lewis-Acidic Organoboranes. ACS Omega 2018,
3, 13129−13140. (d) Wang, Z.; Wang, X.; Nishihara, Y. Nickel-
catalysed decarbonylative borylation of aroyl fluorides. Chem.
Commun. 2018, 54, 13969−13972. (e) Sakurai, S.; Yoshida, T.;
Tobisu, M. Iridium-catalyzed Decarbonylative Coupling of Acyl
Fluorides with Arenes and Heteroarenes via C−H Activation. Chem.
Lett. 2019, 48, 94−97. (f) Wang, X.; Wang, Z.; Liu, L.; Asanuma, Y.;
Nishihara, Y. Nickel-Catalyzed Decarbonylative Stannylation of Acyl
Fluorides under Ligand-Free Conditions. Molecules 2019, 24, 1671.
(g) Wang, X.; Wang, Z.; Nishihara, Y. Nickel/copper-cocatalyzed
decarbonylative silylation of acyl fluorides. Chem. Commun. 2019, 55,
10507−10510. (h) Zhang, C.; Zhao, R.; Dagnaw, W. M.; Liu, Z.; Lu,
Y.; Wang, Z.-X. Density Functional Theory Mechanistic Insight into
the Base-Free Nickel-Catalyzed Suzuki−Miyaura Cross-Coupling of
Acid Fluoride: Concerted versus Stepwise Transmetalation. J. Org.
Chem. 2019, 84, 13983−13991. (i) Malapit, C. A.; Bour, J. R.;
Laursen, S. R.; Sanford, M. S. Mechanism and Scope of Nickel-
Catalyzed Decarbonylative Borylation of Carboxylic Acid Fluorides. J.
Am. Chem. Soc. 2019, 141, 17322−17330. (j) Kayumov, M.; Zhao, J.-
N.; Mirzaakhmedov, S.; Wang, D.-Y.; Zhang, A. Synthesis of
Arylstannanes via Palladium-Catalyzed Decarbonylative Coupling of
Aroyl Fluorides. Adv. Synth. Catal. 2020, 362, 776−781.
(4) (a) Kalow, J. A.; Doyle, A. G. Enantioselective Ring Opening of
Epoxides by Fluoride Anion Promoted by a Cooperative Dual-
Catalyst System. J. Am. Chem. Soc. 2010, 132, 3268−3269. (b) Kalow,
J. A.; Doyle, A. G. Mechanistic Investigations of Cooperative Catalysis
in the Enantioselective Fluorination of Epoxides. J. Am. Chem. Soc.
2011, 133, 16001−16012. (c) Kalow, J. A.; Doyle, A. G.
Enantioselective fluoride ring opening of aziridines enabled by
cooperative Lewis acid catalysis. Tetrahedron 2013, 69, 5702−5709.
(d) Ogiwara, Y.; Hosaka, S.; Sakai, N. Benzoyl Fluorides as
Fluorination Reagents: Reconstruction of Acyl Fluorides via
Reversible Acyl C−F Bond Cleavage/Formation in Palladium
Catalysis. Organometallics 2020, 39, 856−861.
(5) Mukaiyama, T.; Tanaka, T. A Convenient Method for The
Preparation of Carboxylic Acid Fluorides. Chem. Lett. 1976, 5, 303−
306.
(6) (a) Olah, G. A.; Nojima, M.; Kerekes, I. Synthetic Methods and
Reactions; IV. Fluorination of Carboxylic Acids with Cyanuric
Fluoride. Synthesis 1973, 1973, 487−488. (b) Groß, S.; Laabs, S.;
Scherrmann, A.; Sudau, A.; Zhang, N.; Nubbemeyer, U. Improved
Syntheses of Cyanuric Fluoride and Carboxylic Acid Fluoride. J. Prakt.
Chem. 2000, 342, 711−714.
More detailed results of deoxyfluorination of carboxylic
acids and characterization data of the representative
starting materials and products (PDF)
AUTHOR INFORMATION
Corresponding Author
■
Jinbo Hu − Key Laboratory of Organofluorine Chemistry,
Center for Excellence in Molecular Synthesis, Shanghai
Institute of Organic Chemistry, Shanghai 200032, China;
orcid.org/0000-0003-3537-0207; Email: jinbohu@
sioc.ac.cn
Authors
Xiu Wang − Key Laboratory of Organofluorine Chemistry,
Center for Excellence in Molecular Synthesis, Shanghai
Institute of Organic Chemistry, Shanghai 200032, China
Fei Wang − Key Laboratory of Organofluorine Chemistry,
Center for Excellence in Molecular Synthesis, Shanghai
Institute of Organic Chemistry, Shanghai 200032, China
Fengfeng Huang − Key Laboratory of Organofluorine
Chemistry, Center for Excellence in Molecular Synthesis,
Shanghai Institute of Organic Chemistry, Shanghai 200032,
China
Chuanfa Ni − Key Laboratory of Organofluorine Chemistry,
Center for Excellence in Molecular Synthesis, Shanghai
Institute of Organic Chemistry, Shanghai 200032, China
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.1c00190
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the National Key Research and
Development Program of China (2016YFB0101200), the
National Natural Science Foundation of China (21632009),
the Key Programs of the Chinese Academy of Sciences
(KGZD-EW-T08), the Key Research Program of Frontier
Sciences of CAS (QYZDJ-SSW-SLH049), and Shanghai
Science and Technology Program (18JC1410601).
REFERENCES
■
(1) For recent reviews for transformations of acyl fluorides, see:
(a) Blanchard, N.; Bizet, V. Acid Fluorides in Transition-Metal
Catalysis: A Good Balance between Stability and Reactivity. Angew.
Chem., Int. Ed. 2019, 58, 6814−6817. (b) Ogiwara, Y.; Sakai, N. Acyl
Fluorides in Late-Transition-Metal Catalysis. Angew. Chem., Int. Ed.
2020, 59, 574−594. (c) Foth, P. J.; Malig, T. C.; Yu, H.; Bolduc, T.
G.; Hein, J. E.; Sammis, G. M. Halide-Accelerated Acyl Fluoride
Formation Using Sulfuryl Fluoride. Org. Lett. 2020, 22, 6682−6686.
(d) Liang, Y.; Zhao, Z.; Taya, A.; Shibata, N. Acyl Fluorides from
Carboxylic Acids, Aldehydes, or Alcohols under Oxidative Fluorina-
tion. Org. Lett. 2021, 23, 847−852.
(2) (a) Braden, R.; Himmler, T. Katalytische Reduktion von
̈
aromatischen Carbonsaurefluoriden zu Aldehyden. J. Organomet.
Chem. 1989, 367, C12−C14. (b) Zhang, Y.; Rovis, T. A Unique
Catalyst Effects the Rapid Room-Temperature Cross-Coupling of
Organozinc Reagents with Carboxylic Acid Fluorides, Chlorides,
Anhydrides, and Thioesters. J. Am. Chem. Soc. 2004, 126, 15964−
15965. (c) Ogiwara, Y.; Maegawa, Y.; Sakino, D.; Sakai, N. Palladium-
catalyzed Coupling of Benzoyl Halides with Aryltrifluorosilanes
Leading to Diaryl Ketones. Chem. Lett. 2016, 45, 790−792.
(d) Ogiwara, Y.; Sakino, D.; Sakurai, Y.; Sakai, N. Acid Fluorides as
1767
https://dx.doi.org/10.1021/acs.orglett.1c00190
Org. Lett. 2021, 23, 1764−1768

Organic Letters
pubs.acs.org/OrgLett
Letter
(7) (a) Carpino, L. A.; El-Faham, A. Tetramethylfluoroformamidi-
nium Hexafluorophosphate: A Rapid-Acting Peptide Coupling
Reagent for Solution and Solid Phase Peptide Synthesis. J. Am.
Chem. Soc. 1995, 117, 5401−5402. (b) Fiammengo, R.; Licini, G.;
Nicotra, A.; Modena, G.; Pasquato, L.; Scrimin, P.; Broxterman, Q. B.;
Kaptein, B. Duality of Mechanism in the Tetramethylfluoroformami-
dinium Hexafluorophosphate-Mediated Synthesis of N-Benzyloxycar-
bonylamino Acid Fluorides. J. Org. Chem. 2001, 66, 5905−5910.
(8) (a) Takaoka, A.; Iwakiri, H.; Ishikawa, N. F-Propene-Dialkyl-
amine Reaction Products as Fluorinating Agents. Bull. Chem. Soc. Jpn.
1979, 52, 3377−3380. (b) Petrov, V. A.; Swearingen, S.; Hong, W.;
Petersen, W. C. 1,1,2,2-Tetrafluoroethyl-N,N-dimethylamine: a new
selective fluorinating agent. J. Fluorine Chem. 2001, 109, 25−31.
(9) (a) Hasek, W. R.; Smith, W. C.; Engelhardt, V. A. The
Chemistry of Sulfur Tetrafluoride. II. The Fluorination of Organic
Carbonyl Compounds. J. Am. Chem. Soc. 1960, 82, 543−551.
(b) Markovskij, L. N.; Pashinnik, V. E.; Kirsanov, A. V. Stereoselective
cis and trans Addition of Hydrogen Chloride to Olefins. Synthesis
1973, 1973, 787−789. (c) Beaulieu, F.; Beauregard, L.-P.;
Courchesne, G.; Couturier, M.; LaFlamme, F.; L’Heureux, A.
Aminodifluorosulfinium Tetrafluoroborate Salts as Stable and
Crystalline Deoxofluorinating Reagents. Org. Lett. 2009, 11, 5050−
5053. (d) L’Heureux, A.; Beaulieu, F.; Bennett, C.; Bill, D. R.;
Clayton, S.; LaFlamme, F.; Mirmehrabi, M.; Tadayon, S.; Tovell, D.;
Couturier, M. Aminodifluorosulfinium Salts: Selective Fluorination
Reagents with Enhanced Thermal Stability and Ease of Handling. J.
Org. Chem. 2010, 75, 3401−3411. (e) Singh, R. P.; Umemoto, T. 4-
Fluoropyrrolidine-2-carbonyl Fluorides: Useful Synthons and Their
Facile Preparation with 4-tert-Butyl-2,6-dimethylphenylsulfur Tri-
fluoride. J. Org. Chem. 2011, 76, 3113−3121. (f) Smedley, C. J.;
Barrow, A. S.; Spiteri, C.; Giel, M.-C.; Sharma, P.; Moses, J. E. Sulfur-
Fluoride Exchange (SuFEx)-Mediated Synthesis of Sterically
Hindered and Electron-Deficient Secondary and Tertiary Amides
via Acyl Fluoride Intermediates. Chem. - Eur. J. 2017, 23, 9990−9995.
(10) (a) Kaduk, C.; Wenschuh, H.; Beyermann, M.; Forner, K.;
Carpino, L. A.; Bienert, M. Synthesis of Fmoc-amino acid fluorides via
DAST, an alternative fluorinating agent. Lett. Pept. Sci. 1996, 2, 285−
288. (b) Gustafsson, T.; Gilmour, R.; Seeberger, P. H. Fluorination
reactions in microreactors. Chem. Commun. 2008, 3022−3024.
(11) (a) Lal, G. S.; Pez, G. P.; Pesaresi, R. J.; Prozonic, F. M. Bis(2-
methoxyethyl)aminosulfur trifluoride: a new broad-spectrum deoxo-
fluorinating agent with enhanced thermal stability. Chem. Commun.
1999, 215−216. (b) Lal, G. S.; Pez, G. P.; Pesaresi, R. J.; Prozonic, F.
M.; Cheng, H. Bis(2-methoxyethyl)aminosulfur Trifluoride: A New
Broad-Spectrum Deoxofluorinating Agent with Enhanced Thermal
Stability. J. Org. Chem. 1999, 64, 7048−7054. (c) White, J. M.;
Tunoori, A. R.; Turunen, B. J.; Georg, G. I. [Bis(2-methoxyethyl)-
amino]sulfur Trifluoride, the Deoxo-Fluor Reagent: Application
toward One-Flask Transformations of Carboxylic Acids to Amides.
J. Org. Chem. 2004, 69, 2573−2576.
Xiao, J.-C. Difluoromethylation and gem-difluorocyclopropenation
with difluorocarbene generated by decarboxylation. Chem. Commun.
2015, 51, 8805−8808.
(14) Li, L.; Ni, C.; Wang, F.; Hu, J. Deoxyfluorination of alcohols
with 3,3-difluoro-1,2-diarylcyclopropenes. Nat. Commun. 2016, 7,
13320−13331.
(15) (a) Kelly, B. D.; Lambert, T. H. Aromatic Cation Activation of
Alcohols: Conversion to Alkyl Chlorides Using Dichlorodiphenylcy-
clopropene. J. Am. Chem. Soc. 2009, 131, 13930−13931. (b) Hardee,
D. J.; Kovalchuke, L.; Lambert, T. H. Nucleophilic Acyl Substitution
via Aromatic Cation Activation of Carboxylic Acids: Rapid
Generation of Acid Chlorides under Mild Conditions. J. Am. Chem.
Soc. 2010, 132, 5002−5003.
(12) Scattolin, T.; Deckers, K.; Schoenebeck, F. Direct Synthesis of
Acyl Fluorides from Carboxylic Acids with the Bench-Stable Solid
Reagent (Me4N)SCF3. Org. Lett. 2017, 19, 5740−5743.
(13) (a) Xu, W.; Chen, Q.-Y. 3,3-Difluoro-1-iodocyclopropenes: A
Simple Synthesis and Their Reactions. J. Org. Chem. 2002, 67, 9421−
9427. (b) Oshiro, K.; Morimoto, Y.; Amii, H. Sodium Bromodi-
fluoroacetate: A Difluorocarbene Source for the Synthesis of gem-
Difluorocyclopropanes. Synthesis 2010, 2010, 2080−2084. (c) Wang,
F.; Luo, T.; Hu, J.; Wang, Y.; Krishnan, H. S.; Jog, P. V.; Ganesh, S.
K.; Praksh, G. K. S.; Olah, G. A. Synthesis of gem-Difluorinated
Cyclopropanes and Cyclopropenes: Trifluoromethyltrimethylsilane as
a Difluorocarbene Source. Angew. Chem., Int. Ed. 2011, 50, 7153−
7157. (d) Wang, F.; Zhang, W.; Zhu, J.; Li, H.; Huang, K.-W.; Hu, J.
Chloride ion-catalyzed generation of difluorocarbene for efficient
preparation of gem-difluorinated cyclopropenes and cyclopropanes.
Chem. Commun. 2011, 47, 2411−2413. (e) Li, L.; Wang, F.; Ni, C.;
Hu, J. Synthesis of gem-Difluorocyclopropa(e)nes and O-, S-, N-, and
P-Difluoromethylated Compounds with TMSCF2Br. Angew. Chem.,
Int. Ed. 2013, 52, 12390−12394. (f) Deng, X.-Y.; Lin, J.-H.; Zheng, J.;
1768
https://dx.doi.org/10.1021/acs.orglett.1c00190
Org. Lett. 2021, 23, 1764−1768