Making Carbonyls of Amides Nucleophilic and Hydroxyls of Alcohols Electrophilic Mediated by SO2F2 for Synthesis of Esters from Amides

Article abstract of DOI:10.1021/acs.orglett.9b03274

We discovered that with the promotion of sulfuryl fluoride, the carbonyl groups of amides performed as nucleophiles while the hydroxyl groups of alcohols were activated to functionalize as electrophiles. This study displayed that the amide C-N bonds could be easily cleaved with delicate nucleophiles to form the ester C-O bonds at room temperature without using transition metals. The broad substrate scope and excellent functional group compatibility were proved with 44 examples in up to 99% yields.

Full text of DOI:10.1021/acs.orglett.9b03274

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Making Carbonyls of Amides Nucleophilic and Hydroxyls of Alcohols
Electrophilic Mediated by SO2F2 for Synthesis of Esters from Amides
Wan-Yin Fang,# Gao-Feng Zha,# and Hua-Li Qin*
State Key Laboratory of Silicate Materials for Architectures and School of Chemistry, Chemical Engineering and Life Sciences,
Wuhan University of Technology, 205 Luoshi Road, Wuhan 430070, P. R. China
S
* Supporting Information
ABSTRACT: We discovered that with the promotion of
sulfuryl fluoride, the carbonyl groups of amides performed as
nucleophiles while the hydroxyl groups of alcohols were
activated to functionalize as electrophiles. This study displayed
that the amide C−N bonds could be easily cleaved with delicate
nucleophiles to form the ester C−O bonds at room temperature
without using transition metals. The broad substrate scope and excellent functional group compatibility were proved with 44
examples in up to 99% yields.
attention (Scheme 1b)7 since the seminal work by the Garg
he discovery of new reactions for facile construction of
group.8
Tvarious chemical bonds in molecules to achieve complex-
ity lies at the center of organic chemistry.1 Direct
Our previous research revealed that under SO2F2 atmos-
phere,9 the hydroxyl groups of alcohols were activated as
leaving groups, and the oxygen anion tautomerized from
sulfur−oxygen double bonds of DMSO served as a nucleophile
to perform substitution reactions (Scheme 2a).9m We envision
functionalization of sp3 C−O bonds of aliphatic alcohols
without excessive chemical transformations has been a long-
lasting challenge for organic synthesis, because alcohols are
usually unreactive as electrophiles and the hydroxyl (−OH)
groups in alcoholic molecules cannot be easily replaced by
nucleophilic reagents.2 On the other hand, the electrophilic
carbonyl groups are exceptionally reactive toward nucleophiles;
therefore, scarce endeavors have been geared toward utilizing
carbonyl groups as nucleophiles for chemical manipulations.3
The amide motifs are ubiquitous in synthetic intermediates,
natural products, proteins, and various other molecules of
importance, which profoundly influence the biological and
material properties of molecules.4 To date, numerous methods
for the formation of amide bonds have been extensively
developed, which include the nucleophilic substitution of
carboxylic esters with amines (Scheme 1a).5 However, because
of the high stability and rigidity of the amidic linkages,
surmounting the high kinetic and thermodynamic barriers to
harness amides as synthetic building blocks in C−N bond
cleavage reactions has remained underdeveloped.6 Recently,
the transformation of amides to esters has gained significant
Scheme 2. Proposed Esterification of Alcohols Using
Amides
Scheme 1. Studies on the Formation of Amides and Esters
that oxygen anion tautomerized from carbon−oxygen double
bonds of amides would also serve as nucleophiles to react with
SO2F2-activated alcohols (Scheme 2b) in the consequence of
breaking the amide C−N bonds with simultaneous formation
of the ester C−O bonds. Herein, we report the exploration of
amide carbonyls to functionalize as nucleophiles and SO2F2-
Received: September 16, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.9b03274
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
activated alcohols to perform as electrophiles for the synthesis
of esters from amides.
Our investigation of the esterification feasibility commenced
with testing of reacting 4-biphenylmethanol (1a) with DMF
(2a) under sulfuryl fluoride (SO2F2) atmosphere. Accordingly,
a large variety of conditions were screened, and some
representative examples were collected in Table 1 (see the
scope exploration and functional group compatibility exami-
nation.
Under the optimized reaction conditions, the generality of
this SO2F2-mediated esterification was subsequently inves-
tigated using a large number of structurally and electronically
diverse benzylic alcohols as summarized in Scheme 3. Not
a b
,
Scheme 3. Esterification of Benzylic Alcohols
a
Table 1. Reaction Conditions Optimization
conversion
b
yield
b
entry
base (equiv)
DMAP (2.0)
Na2CO3 (2.0) DMF (2a)
K2CO3 (2.0)
KF (2.0)
Cs2CO3 (2.0)
Cs2CO3 (2.0)
Cs2CO3 (2.0)
solvent
(1a, %)
(3a, %)
1
2
3
4
5
DMF (2a)
100
76
84
92
100
97
56
100
98
93
0
34
75
83
91
99
54
40
99
94
90
0
DMF (2a)
DMF (2a)
DMF (2a)
MeCN
c
6
c
7
acetone
8
Cs2CO3 (1.2) DMF (2a)
9
10
Cs2CO3 (1.0)
Cs2CO3 (1.2)
none
DMF (2a)
DMF (2a)
DMF (2a)
d
11
a
Reaction conditions: 4-biphenylmethanol (1a, 0.2 mmol), base,
a
General conditions: benzylic alcohol (1, 2 mmol), Cs2CO3 (782 mg,
2.4 mmol), DMF (2a, 15 mL), and SO2F2 gas (balloon), r.t., 12 h.
solvent (1.5 mL), SO2F2 (Toxic by inhalation. Operate in fume hoods.),
r.t., 12 h. The yields and conversions were determined by HPLC
using 3a or 1a as the external standards, respectively (t3a = 5.0 min,
b
b
c
Isolated yields. Cs2CO3 (1.56 g, 4.8 mmol) and DMF (2a, 30 mL)
d
e
were used. N.D. = not detectable. N,N-Dimethylacetamide (DMA)
was used in the place of DMF.
λmax = 252 nm; t1a = 3.4 min, λmax = 289 nm; MeOH/H2O = 75:25
c
(v/v)). DMF (2a, 2.0 mmol, 10 equiv) was added to the reaction
d
mixture. DMF (2a, 0.2 M, 1.0 mL) was used as sole solvent.
surprisingly, most of the alcohols reacted with DMF smoothly
to deliver their corresponding esters (3a−3v) in good to
excellent yields (76%−99%). Notably, the benzylic alcohols
bearing electron-donating substituents on the aryl rings usually
afforded the corresponding products in slightly higher yields
than their electron-deficient counterparts (e.g., 3b compared to
3h and 3p compared to 3q). Delightfully, the halogen motif
and acetal skeleton on the substrates remained intact in a
standard 2.0 mmol scale (3c−3e, 3l, 3o, and 3r). The
polycyclic benzylic alcohols (1s and 1t) provided their
esterified products (3s and 3t) in nearly quantitative yields.
For alcohol 1u containing two hydroxyl groups, the efficiency
of the desired transformation was not deteriorated when the
stoichiometry of the reagents was adjusted accordingly to
generate 3u in 93% yield. Excitingly, the highly functionalized
alcohol 1v, a precursor to Rosuvastain (CrestorTM, a
blockbuster HMG-CoA reductase inhibitor),11 was also
smoothly converted to its ester derivate 3v in quantitative
yield. Furthermore, secondary benzylic alcohols 1w and 1x
were also smoothly esterified albeit in somewhat lower yields
(3w, 3x compared to 3j), owing to the steric hindrance effect.
The conversion of a tertiary benzylic alcohol 1y to the
corresponding ester 3y was completely hampered. Switching
the amide from DMF to DMA for reacting with secondary
alcohol 1z was also accomplished to provide the corresponding
acetylated derivate 3z in 69% yield.
Supporting Information for details). Pleasingly, the desired
product ester 3a was achieved in 34% HPLC yield when the
transformation proceeded with the promotion of widely used
organic base DMAP (4-dimethylaminopyridine) at room
temperature for 12 h (Table 1, entry 1). Encouraged by the
initial success, the subsequent screening of various inorganic
bases was conducted because of their salient advantages on the
easy workup and purification compared with organic bases.
Among the examined inorganic bases, Cs2CO3 was found to be
the most suitable base promoting the esterification efficiently
to provide the product 3a in quantitative yield, although good
results were also obtained by using Na2CO3, K2CO3, and KF
(Table 1, entries 2−5). Because solvents can act in a static
sense to change the energies of the reactants and products,10
the influence of the solvents was also assessed, and the research
results indicated that the use of a large excess of amide (DMF)
was essential since performing reactions with 10 equiv of DMF
in other solvents provided the desired ester 3a in moderate
yields (Table 1, entries 6 and 7). Further optimization revealed
that 1.2-fold excess of Cs2CO3 appeared to be crucial, as
reducing the loading of base to 1.0 equiv slightly affected the
efficiency of the esterification process (Table 1, entries 5, 8,
and 9). Elevating the concentration of the reaction from 0.13
to 0.2 M slightly decreased the yield of ester 3a (Table 1, entry
8 vs entry 10). In accordance with our expectation, ester 3a
was observed at an undetectable level without the presence of
base as a promoter (Table 1, entry 11), and the condition of
entry 8 was eventually taken as an optimal one for the substrate
Subsequent substrate examination revealed that the
developed system was also suitable for preparation of esters
from long-chain aliphatic alcohols in good to excellent yields
(Scheme 4, 5a−5c, 64%−96%). A slightly lower yield of ester
B
DOI: 10.1021/acs.orglett.9b03274
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
tional group compatibility of this esterification method.
Delightfully, acetyl amides (2b, 2c, and 2d) functionalized
with different substituents on the nitrogen-atom center were all
transformed to [1,1′-biphenyl]-4-ylmethyl acetate 6a in good
to excellent yields (74−93%) after reacting with 4-
biphenylmethanol 1a. It is worth noting that the secondary
amide 2e was also converted to acetate 6a although a lower
yield was obtained compared to its tertiary amide counterparts
(2b, 2c, and 2d). However, the primary amides were not
suitable for synthesizing their corresponding esters using this
developed method. In addition, the examination of the
carbonyl part of amides (2f−2i) was also performed under
optimized reaction conditions, and their corresponding
products (6b−6e) were subsequently furnished in moderate
to good yields (33−81%). Remarkably, the melted solid amide
2j also reacted with 4-biphenylmethanol 1a at 50 °C to afford
the desired ester 6f in 48% yield.
Scheme 4. Esterification of Aliphatic and Propargylic
Alcohols
a b
,
As illustrated in Scheme 6, in order to gain more insight into
the mechanism of this SO2F2-mediated esters formation
a
General conditions: aliphatic or propargylic alcohol (4, 2 mmol),
Cs2CO3 (782 mg, 2.4 mmol), DMF (2a, 15 mL), and SO2F2 gas
b
(balloon), r.t., 12 h. Isolated yields.
Scheme 6. Mechanism Studies
5d was observed for the secondary alcohol 4d bearing some
steric hindrance. Pleasingly, the long-chain alcoholic substrates
possessing unsaturated moieties (4e−4i) were also smoothly
converted to their corresponding ester products (5e−5i)
without destroying the double or triple bond scaffolds. More
importantly, the Z-configuration of CC bonds of alcohols
4e−4g remained the same after being converted to their
corresponding esters 5e−5g. Furthermore, propargylic alcohol
4j which is fragile to various reaction conditions was also
smoothly transformed to the corresponding ester 5j under this
condition.
As depicted in Scheme 5, evaluation of various liquid amides
(2b−2i) was further conducted to demonstrate good func-
process, several investigations were conducted accordingly.
Performing the reaction of alcohol 1a in dry DMF resulted in
the formation of product 3a in 82% yield (Scheme 6a). The
use of 18O-labeled water provided ester in nearly quantitative
yield (99%), in which, 53% was the 18O-labeled ester product
3a′, revealing that a trace amount of H2O also played an
important role in this transformation to facilitate the formation
of ester (Scheme 6b). Bubbling the SO2F2 into DMF at room
temperature for 12 h did not form the intermediate 7, which
excluded the generation of the Vilsmeier-type reagent12 during
this ester formation process (Scheme 6c).
Scheme 5. Substrate Scope Examination with Different
a b
,
Amides
Based on the results of mechanism investigations and
previous studies,9g,j,m,p a plausible mechanism of this SO2F2-
mediated coupling of alcohols with amides for generation of
esters was proposed in Scheme 7. The hydroxyl of alcohol 1
initially proceeded a nucleophilic substitution with sulfuryl
fluoride (SO2F2) in the presence of base to afford the
fluorosulfate A together with releasing of the fluoride ion to
serve as an additional base13 to participate in the following
chemical transformations. The iminium 2′ tautomerized from
amide 2 functionalized as an oxygen nucleophile to undergo a
SN2 type of nucleophilic displacement with fluorosulfate A to
generate the iminium intermediate B. In wet solvent, the
addition of water to iminium B provided the corresponding
adduct C, which was subsequently cleaved to ester 3 with the
promotion of base (Path 1); alternatively, in dry solvent, this
reaction could proceed through Path 2, in which the OSO2F
anion underwent a nucleophilic addition to iminium B to form
a
General conditions: 4-biphenylmethanol (1a, 2 mmol), Cs2CO3
(782 mg, 2.4 mmol), amide (2, 15 mL), and SO2F2 gas (balloon),
b
c
r.t., 12 h. Isolated yields. The reaction was performed at 50 °C using
solid amide (2j, 10 g).
C
DOI: 10.1021/acs.orglett.9b03274
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
́
́
(2) (a) Alonso, F.; Foubelo, F.; Gonzalez-Gomez, J. C.; Martínez,
Scheme 7. Proposed Reaction Pathway
́
R.; Ramon, D. J.; Riente, P.; Yus, M. Efficiency in chemistry: from
hydrogen autotransfer to multicomponent catalysis. Mol. Diversity
2010, 14, 411−424. (b) Hartshorn, S. R. Aliphatic Nucleophilic
Substitution; Cambridge University Press: London, 1973. (c) Anslyn,
E. V.; Dougherty, D. A. Substitutions at Aliphatic Centers and
Thermal Isomerizations/Rearrangements. Modern Physical Organic
Chemistry; University Science Books: Sausalito, CA, 2006; Chapter
11.
(3) (a) Larock, R. C. Comprehensive organic transformations: a guide
to functional group preparations; Wiley-VCH: New York, 1999; Vol. 1,
pp 1−2640. (b) Frohning, C. D.; Kohlpaintner, C. W. In Applied
Homogeneous Catalysis with Organometallic Compounds; Cornils, B.,
Herrmann, W. A., Eds.; Wiley-VCH: 1996; pp 29−104.
(4) (a) Greenberg, A.; Breneman, C. M.; Liebman, J. F. The Amide
Linkage: Structural Significance in Chemistry, Biochemistry, and
Materials Science; Wiley-Interscience: New York, 2000. (b) Humphrey,
J. M.; Chamberlin, A. R. Chemical Synthesis of Natural Product
Peptides: Coupling Methods for the Incorporation of Noncoded
Amino Acids into Peptides. Chem. Rev. 1997, 97, 2243−2266.
(c) Lundberg, H.; Tinnis, F.; Selander, N.; Adolfsson, H. Catalytic
amide formation from non-activated carboxylic acids and amines.
Chem. Soc. Rev. 2014, 43, 2714−2742. (d) El-Faham, A.; Albericio, F.
Peptide Coupling Reagents, More than a Letter Soup. Chem. Rev.
2011, 111, 6557−6602. (e) Valeur, E.; Bradley, M. Amide bond
formation: beyond the myth of coupling reagents. Chem. Soc. Rev.
2009, 38, 606−631.
(5) (a) Montalbetti, C. A. G. N.; Falque, V. Amide bond formation
and peptide coupling. Tetrahedron 2005, 61, 10827−10852.
(b) Pattabiraman, V. R.; Bode, J. W. Rethinking amide bond
synthesis. Nature 2011, 480, 471−479. (c) Lundberg, H.; Tinnis, F.;
Selander, N.; Adolfsson, H. Catalytic amide formation from non-
activated carboxylic acids and amines. Chem. Soc. Rev. 2014, 43,
2714−2742.
(6) (a) Pauling, L. The Nature of the Chemical Bond; Oxford
University Press: London, 1940. (b) Mujika, J. I.; Mercero, J. M.;
Lopez, X. Water-Promoted Hydrolysis of a Highly Twisted Amide:
Rate Acceleration Caused by the Twist of the Amide Bond. J. Am.
Chem. Soc. 2005, 127, 4445−4453. (c) Kemnitz, C. R.; Loewen, M. J.
“Amide Resonance” Correlates with a Breadth of C−N Rotation
Barriers. J. Am. Chem. Soc. 2007, 129, 2521−2528. (d) Meng, G.; Shi,
S.; Lalancette, R.; Szostak, R.; Szostak, M. Reversible Twisting of
Primary Amides via Ground State N−C(O) Destabilization: Highly
Twisted Rotationally Inverted Acyclic Amides. J. Am. Chem. Soc.
2018, 140, 727−734.
(7) (a) Ruider, S. A.; Maulide, N. Strong Bonds Made Weak:
Towards the General Utility of Amides as Synthetic Modules. Angew.
Chem., Int. Ed. 2015, 54, 13856−13858. (b) Lavoie, C. M.;
MacQueen, P. M.; Stradiotto, M. Nickel-Catalyzed N-Arylation of
Primary Amides and Lactams with Activated (Hetero)aryl Electro-
philes. Chem. - Eur. J. 2016, 22, 18752−18755. (c) Dander, J. E.;
Weires, N. A.; Garg, N. K. Benchtop Delivery of Ni(cod)2 using
Paraffin Capsules. Org. Lett. 2016, 18, 3934−3936. (d) Dander, J. E.;
Garg, N. K. Breaking Amides using Nickel Catalysis. ACS Catal. 2017,
7, 1413−1423. (e) Dey, A.; Sasmal, S.; Seth, K.; Lahiri, G. K.; Maiti,
D. Nickel-Catalyzed Deamidative Step-Down Reduction of Amides to
Aromatic Hydrocarbons. ACS Catal. 2017, 7, 433−437. (f) Deguchi,
T.; Xin, H.-L.; Morimoto, H.; Ohshima, T. Direct Catalytic
Alcoholysis of Unactivated 8-Aminoquinoline Amides. ACS Catal.
2017, 7, 3157−3161. (g) Bourne-Branchu, Y.; Gosmini, C.; Danoun,
G. Cobalt-Catalyzed Esterification of Amides. Chem. - Eur. J. 2017, 23,
10043−10047. (h) Wu, H.; Guo, W.; Daniel, S.; Li, Y.; Liu, C.; Zeng,
Z. Fluoride-Catalyzed Esterification of Amides. Chem. - Eur. J. 2018,
24, 3444−3447. (i) Wybon, C. C. D.; Mensch, C.; Hollanders, K.;
Gadais, C.; Herrebout, W. A.; Ballet, S.; Maes, B. U. W. Zn-Catalyzed
tert-Butyl Nicotinate-Directed Amide Cleavage as a Biomimic of
Metallo-Exopeptidase Activity. ACS Catal. 2018, 8, 203−218. (j) Li,
G.; Lei, P.; Szostak, M. Transition-Metal-Free Esterification of
the corresponding intermediate D, whose S−O bond was
further cleaved under basic conditions to generate the
corresponding ester 3.
In summary, we have discovered an unusual reaction, in
which, with the assistance of SO2F2, the carbonyls of amides
performed as nucleophiles while the hydroxyl groups of
alcohols were activated to play as electrophiles to break the
amide C−N bonds and form the ester C−O bonds. The
versatility of this reaction feathered with wide substrate scope
(44 examples) and excellent functional group compatibility
provides a new portal to esters construction from readily
available alcohols and amides.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.9b03274.
Experimental procedures, characterization data, and
NMR spectra (PDF)
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: qinhuali@whut.edu.cn.
ORCID
Gao-Feng Zha: 0000-0001-9240-8721
Hua-Li Qin: 0000-0002-6609-0083
Author Contributions
#W.-Y.F. and G.-F.Z. contributed equally to this work.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are grateful to the National Natural Science Foundation of
China (Grant No. 21772150), the Wuhan applied fundamental
research plan of Wuhan Science and Technology Bureau
(Grant No. 2017060201010216), the 111 Project (Grant No.
B18038), the Fundamental Research Funds for the Central
Universities (2019-YB-001), and Wuhan University of
Technology for the financial support.
REFERENCES
■
(1) (a) Labinger, J. A.; Bercaw, J. E. Understanding and exploiting
C−H bond activation. Nature 2002, 417, 507−514. (b) Godula, K.;
Sames, D. C-H Bond Functionalization in Complex Organic
Synthesis. Science 2006, 312, 67−72.
D
DOI: 10.1021/acs.orglett.9b03274
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Amides via Selective N−C Cleavage under Mild Conditions. Org. Lett.
2018, 20, 5622−5625.
Drug Rev. 2002, 20, 303−328. (b) McTaggart, F.; Jones, P. Effects of
Statins on High-Density Lipoproteins: A Potential Contribution to
Cardiovascular Benefit. Cardiovasc. Drugs Ther. 2008, 22, 321−338.
(12) Marson, C. M. Reactions of carbonyl compounds with
(monohalo) methyleniminium salts (Vilsmeier reagents). Tetrahedron
1992, 48, 3659−3726.
(8) (a) Hie, L.; Fine Nathel, N. F.; Shah, T. K.; Baker, E. L.; Hong,
X.; Yang, Y.-F.; Liu, P.; Houk, K. N.; Garg, N. K. Conversion of
Amides to Esters by the Nickel-Catalysed Activation of Amide C−N
bonds. Nature 2015, 524, 79−83. (b) Hie, L.; Baker, E. L.; Anthony,
S. M.; Desrosiers, J.-N.; Senanayake, C.; Garg, N. K. Nickel-Catalyzed
Esterification of Aliphatic Amides. Angew. Chem., Int. Ed. 2016, 55,
15129−15132.
(13) Clark, J. H. Fluoride ion as a base in organic synthesis. Chem.
Rev. 1980, 80, 429−452.
(9) Sulfuryl fluoride (SO2F2) has been produced annually at more
than 3 million kg per year since 2000, with a price as low as $1/kg,
see: (a) Sulbaek Andersen, M. P.; Blake, D. R.; Rowland, F. S.;
Hurley, M. D.; Wallington, T. J. Atmospheric chemistry of sulfuryl
fluoride: reaction with OH radicals, Cl atoms and O3, atmospheric
lifetime, IR spectrum, and global warming potential. Environ. Sci.
Technol. 2009, 43, 1067−1070. For reviews of SO2F2 utilization, see:
(b) Revathi, L.; Ravindar, L.; Leng, J.; Rakesh, K. P.; Qin, H.-L.
Synthesis and chemical transformations of fluorosulfates. Asian J. Org.
Chem. 2018, 7, 662−682. (c) Barrow, A. S.; Smedley, C. J.; Zheng,
Q.; Li, S.; Dong, J.; Moses, J. E. The growing applications of SuFEx
click chemistry. Chem. Soc. Rev. 2019, 48, 4731−4758. (d) Lekkala,
R.; Lekkala, R.; Moku, B.; Rakesh, K. P.; Qin, H.-L. Applications of
sulfuryl fluoride (SO2F2) in chemical transformations. Org. Chem.
Front. 2019, 6, 3490−3516. For some selected examples, see:
(e) Hanley, P. S.; Clark, T. P.; Krasovskiy, A. L.; Ober, M. S.; O’Brien,
J. P.; Staton, T. S. Palladium- and Nickel-catalyzed Amination of Aryl
Fluorosulfonates. ACS Catal. 2016, 6, 3515−3519. (f) Schimler, S. D.;
Cismesia, M. A.; Hanley, P. S.; Froese, R. D. J.; Jansma, M. J.; Bland,
D. C.; Sanford, M. S. Nucleophilic Deoxyfluorination of Phenols via
Aryl Fluorosulfonate Intermediates. J. Am. Chem. Soc. 2017, 139,
1452−1455. (g) Epifanov, M.; Foth, P. J.; Gu, F.; Barrillon, C.;
Kanani, S. S.; Higman, C. S.; Hein, J. E.; Sammis, G. M. One-Pot 1,1-
Dihydrofluoroalkylation of Amines Using Sulfuryl Fluoride. J. Am.
Chem. Soc. 2018, 140, 16464−16468. (h) Fang, W.-Y.; Leng, J.; Qin,
H.-L. SO2F2-Mediated One-Pot Synthesis of Aryl Carboxylic Acids
and Esters from Phenols through a Pd-Catalyzed Insertion of Carbon
Monoxide. Chem. - Asian J. 2017, 12, 2323−2331. (i) Zhao, C.; Fang,
W.-Y.; Rakesh, K. P.; Qin, H.-L. Pd-Catalyzed one-pot dehydrox-
ylative coupling of phenols with K4[Fe(CN)6] mediated by SO2F2: a
practical method for the direct conversion of phenols to aryl nitriles.
Org. Chem. Front. 2018, 5, 1835−1839. (j) Zha, G.-F.; Fang, W.-Y.; Li,
Y.-G.; Leng, J.; Chen, X.; Qin, H.-L. SO2F2-Mediated Oxidative
Dehydrogenation and Dehydration of Alcohols to Alkynes. J. Am.
Chem. Soc. 2018, 140, 17666−17673. (k) Zhang, X.; Rakesh, K. P.;
Qin, H.-L. Transition-metal-free regioselective construction of 1,5-
diaryl-1,2,3-triazoles through dehydrative cycloaddition of alcohols
with aryl azides mediated by SO2F2. Chem. Commun. 2019, 55, 2845−
2848. (l) Fang, W.-Y.; Qin, H.-L. Cascade Process for Direct
Transformation of Aldehydes (RCHO) to nitriles (RCN) Using
Inorganic Reagents NH2OH/Na2CO3/SO2F2 in DMSO. J. Org. Chem.
2019, 84, 5803−5812. (m) Zha, G.-F.; Fang, W.-Y.; Leng, J.; Qin, H.-
L. A Simple, Mild and General Oxidation of Alcohols to Aldehydes or
Ketones by SO2F2/K2CO3 Using DMSO as Solvent and Oxidant. Adv.
Synth. Catal. 2019, 361, 2262−2267. (n) Fang, W.-Y.; Zha, G.-F.;
Zhao, C.; Qin, H.-L. Regioselective installation of fluorosulfate-
(−OSO2F) functionality into aromatic C(sp2)−H bonds for the
construction of para-aminoarylfluorosulfates. Chem. Commun. 2019,
55, 6273−6276. (o) Gurjar, J.; Bater, J.; Fokin, V. V. Sulfuryl Fluoride
Mediated Conversion of Aldehydes to Nitriles. Chem. - Eur. J. 2019,
25, 1906−1909. (p) Foth, P. J.; Gu, F.; Bolduc, T. G.; Kanani, S. S.;
Sammis, G. M. New sulfuryl fluoride-derived alkylating reagents for
the 1,1-dihydrofluoroalkylation of thiols. Chem. Sci. 2019,
DOI: 10.1039/C9SC03570B, Note, sulfuryl fluoride is a neurotoxic
gas and also a particularly potent greenhouse gas, please handle with
care in fume hoods. .
(10) Reichardt, C. Solvents and Solvent Effects in Organic Chemistry,
3rd ed.; Wiley-VCH: Weinheim, Germany, 2003.
(11) (a) Olsson, A. G.; McTaggart, F.; Raza, A. Rosuvastatin: A
Highly Effective New HMG-CoA Reductase Inhibitor. Cardiovasc.
E
DOI: 10.1021/acs.orglett.9b03274
Org. Lett. XXXX, XXX, XXX−XXX