Harnessing the catalytic behaviour of 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP): An expeditious synthesis of thioesters

Article abstract of DOI:10.1016/j.tetlet.2017.04.004

A novel, efficient, metal-, base- and acid-free straightforward protocol has been developed for the construction of useful thioesters. The immense catalytic potential of HFIP for promoting the thiocarbonylation of acyl halides and thiols is disclosed. HFIP was recovered with ease and reused for further reactions without any loss of reactivity. Both aryl and alkyl thiols bearing electron-donating and electron-withdrawing groups as well as aryl- and alkyl acyl halides worked well in this reaction. Inexpensive precursors, short reaction time, obviating workup, high atom economy, and gram-scale preparation are the significant features of the developed eco-friendly route for S-carbonylation of thiols.

Full text of DOI:10.1016/j.tetlet.2017.04.004

Accepted Manuscript
Harnessing the catalytic behaviour of 1,1,1,3,3,3-hexafluoro-2-propanol
(HFIP): An expeditious synthesis of thioesters
Pallavi Singh, Rama Krishna Peddinti
PII:
S0040-4039(17)30431-8
DOI:
http://dx.doi.org/10.1016/j.tetlet.2017.04.004
TETL 48796
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
25 January 2017
29 March 2017
2 April 2017
Please cite this article as: Singh, P., Peddinti, R.K., Harnessing the catalytic behaviour of 1,1,1,3,3,3-hexafluoro-2-
propanol (HFIP): An expeditious synthesis of thioesters, Tetrahedron Letters (2017), doi: http://dx.doi.org/10.1016/
j.tetlet.2017.04.004
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers
we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and
review of the resulting proof before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Graphical Abstract
Leave this area blank for abstract info.
Harnessing the catalytic behaviour of 1,1,1,3,3,3-hexafluoro-2-propanol
(HFIP): An expeditious synthesis of thioesters
Pallavi Singh, Rama Krishna Peddinti*

1
Tetrahedron Letters
journal homepage: www.els evier.com
Harnessing the catalytic behaviour of 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP):
An expeditious synthesis of thioesters
Pallavi Singh, Rama Krishna Peddinti∗
Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India
ARTICLE INFO
ABSTRACT
A novel, efficient, metal-, base- and acid-free straightforward protocol has been developed for
the construction of useful thioesters. The immense catalytic potential of HFIP for promoting the
thiocarbonyaltion of acyl halides and thiols is disclosed. HFIP was recovered with ease and
reused for further reactions without any loss of reactivity. Both aryl and alkyl thiols bearing
electron-donating and electron-withdrawing groups as well as aryl- and alkyl acyl halides
worked well in this reaction. Inexpensive precursors, short reaction time, obviating workup, high
atom economy, and gram-scale preparation are the significant features of the developed eco-
friendly route for S-carbonylation of thiols.
Article history:
Received
Received in revised form
Accepted
Available online
Keywords:
HFIP catalysis
Metal-free
Base-free
2009 Elsevier Ltd. All rights reserved.
Acid-free
High atom economy
As a category of activated carboxylic acid derivatives, the
emergence of thioesters is a gift to synthetic chemist due to its
acyl donor ability in organic syntheis and chemical biology.1 Not
only do they play important roles in various biological
processes,2 but they are highly desirable synthetic target for the
construction of various natural products.3 Moreover, substitution
of sulfur-containing leaving group with a variety of nucleophiles
can be achieved under relatively mild reaction conditions.
Magnificent applications of thioester in organic synthesis are
illustrated in Scheme 1. Palladium based catalytic system has
been developed by Fukuyama and co-workers to facilitate the
chemoselective synthesis of ketones by employing thioesters.4 A
variety of thioesters have been reported for the synthesis of
acylsilanes,5 acetylene ketones,6 and amides.7 In addition, the
synthesis of aldehydes or alcohols in different experimental
conditions from the carboxylic acid derivatives has been
highlighted.8 Sekiya and Laweson reported the successful
replacement of oxygen atom of thioester by sulfur or CCl2
group.9 The benzothiolate product was also implemented for the
excellent synthesis of sulfur-containing heterocyclic compounds.
Furthermore, it is possible to synthesize 2-methylthio-1,3-
oxazoles from both alkyl and aryl thioesters employing N-
(ethoxycarbonylmethyl)-iminodithiocarbonate.10
Thiocarbonylation between thiols, acyl halides and acetic
anhydride are clean and straightforward processes to
construct the variety of thioesters. The S-carbonylation of
thiols is commonly carried out by using acid chlorides or
acid anhydrides in the presence of pyridine or triethylamine
along with 4-(dimethylamino)pyridine11 or Bu3P.12
O
O
O
R1
O
R1
N
S
O
O
OR1
1
10
2
S
9
3
O
R
S
S
NRR1
4
8
O
Cl
Cl
7
5
6
6
S
O
OH
O
S
H
Scheme 1 Examples of application of thiolates as building
blocks in organic synthesis
A wide range of Lewis acid catalysts are engaged for this
purpose, such as MgBr2,13 LiClO4,14 Sc(OTf)2,15 CoCl2,16
Sc(NTf2)3,17 Bi(OTf)3,18 TMSOTf,19 Cu(OTf)2,20 InCl3,21
———
∗ Corresponding author. Tel.: +91-133-228-5438; fax: +91-133-227-3560
e-mail: rkpedfcy@iitr.ac.in, ramakpeddinti@gmail.com

2
Tetrahedron
hydrotalcite,22
tris(pentafluorophenyl)borane,23
and
3fd was obtained in 20% yield after long reaction time and the
heteropoly acids.24 On the other hand, ruthenium(III)
chloride has also been recognized for convenient synthesis
of thioacetates in the presence of ionic liquids.25 The use of
CsF–celite and silica gel provide alternative protocol to
afford the thioesters.26 Albeit these are all certainly
remarkable processes, the major concerns are the necessity
of expensive metals and the toxicity associated with them,
solvents, elevated temperature, long reaction time, special
care for moisture/air sensitive reagents, use of non-green
solvents and carcinogenic promoters. In view of the above
limitations, there is a great desire of rapid, versatile,
environmentally friendly, non-corrosive and reusable
activator for the preparation of thioesters under mild
reaction conditions.
starting materials 2d and 1f were recovered (entry 11). When
we used toluene as solvent for the thioesterification, a complex
1
mixture was obtained in 12 h and no signal was observed in H
or 13C NMR spectrum corresponding to product(s) from toluene
or thiol 1f (entry 12). This reaction failed to produce the
corresponding product in the absence of HFIP, signifying
the role of fluorinated alcohol in direct synthesis of thioester
under mild conditions (entry 13).
With the emergence of several advancements in the
dimension of HFIP chemistry,32 we were delighted to
demonstrate the exclusive tuning of HFIP with
benzenemethanethiol (1f) and 4-nitrobenzoyl chloride (2d
)
that allowed optimum conditions for the direct and rapid
Table 1 Optimization of reaction conditionsa
Polyfluorinated alcohols exhibit unique properties in various
synthetic schemes.27 1,1,1,3,3,3-hexafluoroisopropanol (HFIP)
and trifluoroethanol (TFE) have emerged as remarkable solvents
in the modern organic synthesis.28 HFIP is flourished with
intriguing set of properties, including low nucleophilicity, mild
acidity, strong hydrogen bond donor ability, high ionizing power
and ability to stabilize the cationic species.29
O
O
Catalyst
Solvent
S
SH
Cl
rt
NO2
O2N
1f
2d
3fd
Catalyst
(mol%)
Entry
Solvent (mL)
Time Yieldb (%)
1
2
3
4
5
6
7
8
9c
10
11
12
13
HFIP (30)
HFIP (20)
HFIP (10)
–
–
–
<1 min
<1 min
<1 min
2 h
>99
>99
>99
90
92
98
85
31
73
34
To date, several literature reports demonstrated that the
HFIP has been used as a solvent, a promoter as well as an
additive in numerous synthetic protocols.30 However, the
direct use of HFIP as a catalyst rather than additive or
solvent in modern synthetic methodology is still surprisingly
remained a tempting research field. Herein, we describe our
advancement in HFIP chemistry and highly efficient, metal-
free, base-free as well as acid-free expeditious protocol for
the synthesis of thioesters is acknowledged.
HFIP (10) CH2Cl2 (0.5)
HFIP (30) CH2Cl2 (0.5)
HFIP (50) CH2Cl2 (0.5)
HFIP (50) CH3CN (0.5)
HFIP (50) THF (0.5)
2 h
2 h
6 h
6 h
2 h
5 h
26 h
12 h
12 h
HFIP (10)
–
–
–
TFE (10)
-PrOH (10)
Toluene (5)
i
20
nd
nd
–
Neat
–
Given the importance to thioesters and wide utility of
HFIP, we envisaged that combining the catalytic as well as
solvent effects of this polyfluorinated alcohol could facilitate
the reaction between thiols and acyl halides. The direct
The optimized condition is indicated in bold font.
aConditions: 1f (0.5 mmol) 2d (0.6 mmol), HFIP catalyst stirred at rt. nd = not
determined.
bYield of isolated product.
c0.4 mmol of 2d was used.
thiocarbonylation of benzenemethanethiol
(1f) and 4-
nitrobenzoyl chloride (2d) was chosen as a model reaction to
determine the optimal reaction conditions. Thus readily
available and inexpensive fluorinated alcohol HFIP was
synthesis of thioester 3fd. It is of interest to note that HFIP
played a dramatic role in the model scheme as a catalyst and
not as a solvent. Presumably, the electrophilic activation of
acyl halide contributed by the catalytic dynamism of HFIP
facilitates the carbonylation of thiols. The whole reaction
procedure was pleasant and no work-up was required for the
rapid generation of thiolates in a high atom economical
fashion.
added to
a mixture of 4-nitrobenzoyl chloride and
benzenemethanethiol. To our delight, the reaction afforded
the thioester 3fd in >99% yield within seconds at room
temperature (Table 1, entry 1). Changing the loading of
fluoroalcohol had virtually no effect on the yield of thioester
in model reaction (entries 2 and 3). Excellent results were
obtained when HFIP was used as an additive in CH2Cl2
where the addition of 10, 30, or 50 mol% of HFIP furnished
Once the optimal conditions (Table 1, entry 3) was
established and identified the catalytic behavior of
hexafluoroisopropanol, the scope of this HFIP-catalyzed
thioesterification reaction was probed to a range of
substrates. With the optimized conditions in hand, different
−6), although a
the good amount of product (entries 4
qualitative decrease in rate was observed. Similar
experiments were carried out using strong hydrogen-bond
accepting solvents such as CH3CN and THF, which had a
deleterious effect in the thiocarbonyltion reaction31 (entries 7
and 8). The lower amount of 4-nitrobenzoyl chloride
surprisingly diminished the yield of the product (entry 9).
TFE did not work well for C–S bond formation and 3fd was
obtained in modest yield in 5 h (entry 10). The reaction
aryl thiols 1a–1e were evaluated for direct thiocarbonylation
reactions onto parent benzoyl chloride (2a). Delightedly,
aryl thiol 1a having electron-donating group at position 4
and thiophenol 1b were able to react with benzoyl chloride
to give the corresponding thioesters 3aa and 3ab in excellent
yields. Other aryl thiols 1c and 1d bearing electron-
withdrawing halo groups at position 4 of the aromatic ring,
when tested for this simple protocol, provided
proceeded slowly by employing
i-PrOH, the aliphatic analogue
of HFIP, possessing hydrogen bonding properties and product

3
thiocarbonylated products 3ac and 3ad in high yields.
Similarly, the reaction of bulky substrate 2-naphthalenethiol
also gave the corresponding product 3ae in excellent yield.
Encouraged by these results, benzoyl chlorides 2b and 2c
bearing electron-donating groups were next investigated to
product 3fe in excellent yield. Moreover, cyclohexylthiol
1g) was tested under aforementioned conditions and the
products 3ga 3gb 3gc and 3gd were obtained in high yield.
Ester functionalized thiol 1h worked well to yield the
products 3ha 3hb 3hc and 3hd. More importantly,
(
,
,
,
,
check the efficiency of HFIP. Thus thioester products 3ba
3bb 3bc 3be and 3ca 3ce were obtained in high to
excellent yields. Under these optimal conditions, 4-NO2
benzoyl chloride (2d) led to the formation of thioesters 3da
3dd in excellent to quantitative yields. Aryl alkyl thioesters
3ea 3ee were isolated in 78–85% yields from the ethanoyl
,
hydroxyl group-containing alkyl thioesters 1ic and 1id could
be synthesized in 68–75% yield when the reaction was
carried out by employing 2-mercaptoethanol (1i) as a
substrate for this novel transformation. Finally, the reactivity
of dichloroacetyl chloride (2f) was also examined in
acylation of thiols. Dichloroacetyl chloride was found to be
very reactive with different thiols. Interestingly, when
benzyl mercaptan (1f) was the nucleophile of choice, high
yield of 3ff was obtained within seconds.
,
,
–
–
–
chloride and a variety of thiophenols.
Table 2 HFIP–Catalyzed thioesterification using aryl thiolsa
HFIP
10 mol%
O
S
R2
S
Table 2 HFIP–Catalyzed thioesterification using aliphatic
thiolsa
R1
R1
R2
Cl
H
+
rt, <1 min
O
3aa-3ae
1a-1e
2a-2e
HFIP
10 mol%
O
S
R2
S
+
R1
R1
R2
Cl
H
S
S
S
S
rt, <1 min
O
3fa-3id
1f-1i
2a-2e
O
3ab, 95%
O
3ac, 92%
O
3ad (85%)
O
3aa, 95%
Cl
Br
O
S
O
O
S
S
S
S
S
S
OMe
(99%)
O
(98%)
(99%)
3fa
3fb
3fc
O
O
O
O
Cl
S
3ba (93%)
3bb (90%)
3bc (87%)
3ae (95%)
O
S
OMe
S
S
OMe
O
NO2
S
S
(97%)
3ga
(99%)
(95%)
3fd
3fe
O
O
O
NO2
OMe
3be (92%)
3ca (98%)
3cb (95%)
OMe
S
S
S
OMe
OMe
O
S
O
O
S
S
(98%)
MeO
(99%)
3gd
3gc
(95%)
3gb
O
O
O
Cl
Br
O
O
S
O
O
S
3cc (92%)
3cd (90%)
3ce (94%)
MeO
MeO
NO2
NO2
NO2
(95%)
(93%)
3ha
3hb
S
S
S
O
O
O
O
O
O
O
Cl
S
MeO
S
3da (99%)
3db (99%)
3dc (96%)
NO2
OMe
NO2
(98%)
3hd
(98%)
3hc
S
S
S
O
O
O
HO
HO
Cl
O
O
O
S
S
S
Br
Cl
3eb (81%)
Cl
(82%)
3ff
3dd (96%)
3ea (85%)
OMe
NO2
(68%)
3ic
(75%)
3id
S
S
S
aReaction conditions: Aliphatic thiol (0.5 mmol), acyl halide (0.6 mmol),
HFIP (0.05 mmol).
O
O
O
Br
3ed (78%)
3ee (83%)
3ec (81%)
aReaction conditions: Arylthiol (0.5 mmol), acyl halide (0.6 mmol), HFIP
(0.05 mmol).
Moreover, this elegant and green protocol for the
preparation of thioesters can be readily scaled up to prove
the catalytic efficacy of HFIP which can be recovered easily.
We then conducted the reaction of 4-bromothiophenol 1e
(5.0 mmol) with 4-NO2 benzoyl chloride 2d (6.0 mmol) in
the presence of HFIP (1.0 mmol) under the mild reaction
condition which afforded the thioester 3ed in 92% yield
(Scheme 2). Distillation of HFIP directly from the reaction
On the basis of promising results obtained in the case of
aryl thiols, we turned our attention towards aliphatic thiols
to broaden the scope of base and acid-free eco-friendly
protocol for the synthesis of thioesters (Table 3). Thus
HFIP–catalyzed thioesterification reaction onto benzene
methanethiol (1f) was examined. When parent benzoyl
chloride was employed, the product 3fa was isolated in 99%
yield. Subsequently,
a variety of benzoyl chlorides
possessing electron-donating groups (2b and 2c) and
electron-withdrawing group (2d) were successfully reacted
with compound 1f under the optimized conditions providing
thioesters 3fb, 3fc and 3fd in excellent to quantitative yield.
The use of ethanoyl chloride (2e) was also furnished the

4
Tetrahedron
5. Azuma, H.; Okano, K.; Tokuyama, H. Chem
6. Mehta, V. P.; Sharma, A.; Eycken, E. V. Org
7. Ueda, M.; Seki, K.; Imai, Y. Synthesis 1981, 99.
.
Lett
.
2011
,
40, 959.
Scheme 2 Gram-scale synthesis of thioester 3ed
.
.
Lett
.
2008
,
10, 1147.
pot afforded 80 microlitres of a fluorinated solvent. Notably,
the recovered solvent can be used for other occasions in
synthetic chemistry and be equally as good at catalyzing C–
S bond formation to synthesize thiolates as the store bought
material.
8. Fukuyama, T.; Lin, S. C.; Li, L. P.
7050.
J. Am. Chem. Soc. 1990, 112,
9. Yousif, N. M.; Pedersen, U.; Yde B.; Lawesson, S. O. Tetrahedron
1984 40, 2663.
,
10. Alvarez-Ibarra, C.; Mendoza, M.; Orellana, G.; Quiroga, M. L.
The plausible mechanism for HFIP catalyzed
thiocarbonylation between thiol and acyl halide is depicted
in Scheme 3. On the basis of previous reports for acyl halide
activation33 we contemplate that the addition of HFIP to acyl
Synthesis 1989, 560.
11. Steglich, W.; Hofle, G. Angew. Chem., Int. Ed. Engl. 1969
12. Vedejs, E.; Bennet, N. S.; Conn, L. M.; Diver, S. T.; Gingras, M.;
Lin, S.; Oliver, P. M.; Peterson, M. J. J. Org. Chem. 1993 58, 7286.
, 8, 981.
,
chloride
2 may result in the formation of protosolvated
13. Pansare, S. V.; Malusare, M. G.; Rai, A. N. Synth. Commun. 2000
30, 2587.
,
cation due to the strong H-bonding with the oxygen atom of
acyl halide. Further, nucleophilic attack of sulfur from thiol
14. Nakae, Y.; Kusaki, I.; Sato, T. Synlett 2001, 1584.
15. Ishihara, K.; Kubota, M.; Kurihara, H.; Yamamoto, H. J. Org. Chem.
1996, 61, 4560.
1
onto protosolvated cation can take place. This transition
16. Iqbal J.; Srivastava, R. R. J. Org. Chem. 1992, 57, 2001.
17. Ishihara, K.; Kobuta, M.; Yamamoto, H. Synlett 1996, 265.
18. Orita, A.; Tanahashi, C.; Kakuda, A.; Otera, J. J. Org. Chem. 2001, 66,
8926.
state could be stabilized by high polarizing and low
nucleophilic HFIP to afford the corresponding thioester 3.
19. Procopiou, P. A.; Baugh, S. P. D.; Flack, S. S.; Inglis, G. G. A. J. Org.
Chem. 1998, 63, 2342.
20. Sarvanan P.; Singh, V. K. Tetrahedron Lett. 1999, 40, 2611
21. Chakraborti, A. K.; Gulhane, R. Tetrahedron Lett. 2003, 44, 6749.
22. Massah, A. R.; Kalbasi, R. J.; Toghiani, M.; Hojati, B.; Adibnejad, M.
Eur. J. Chem. 2012, 9, 2501.
23. Prajapti, S. K.; Nagarsenkar, A.; Babu, B. N. Tetrahedron Lett. 2014, 55,
1784.
24. Kumar, P.; Pandey, R. K.; Bodas, M. S.; Dagade, S. P.; Dongare, M. K.;
Ramaswamy, A. V. J. Mol. Catal. A: Chem. 2002, 181, 207.
25. Xi, Z.; Hao, W.; Wang, P.; Cai, M. Molecules 2009, 14, 352.
26. (a) Tasadaque, S.; Shah, A.; Mohammed, K. M.; Heinrich, A. M.;
Voelter, W. Tetrahedron Lett. 2002, 43, 8281; (b) Basu, B.; Paul, S.;
Nanda, A. K. Green Chem. 2010, 12, 767.
Scheme 3 Plausible reaction mechanism
27. (a) Wu, W.-Y.; Wang, J.-C.; Tsai, F.-Y. Green Chem. 2009
(b) Raj, M.; Singh, V. K. Chem. Commun 2009, 6687; (c) Gu, Y.
Green Chem. 2012 14, 2091; (d) Kommi, D. N.; Jadhavar, P. S.;
Kumar, D.; Chakraborti, A. K. Green Chem 2013 15, 798; (e) Paul,
S.; M. M.; Islam, S. k. M. RSC Adv 2015 , 42193; (f) Weisner, N.;
Khaledi, M. G. Green Chem 2016 18, 681.
28. (a) Tian, Y.; Xu, X.; Zhang, L.; Qu, J. Org. Lett
Champagne, P. A.; Benhassine, Y.; Desroches J.; Paquin, J.-F.
Angew. Chem., Int. Ed 2014 53 13835; (c) Acharya, A.;
Anumandla, D.; Jeffrey, C. S. J. Am. Chem. Soc 2015 137, 14858;
(d) Poto, M. C. D.; Hughes, R. P.; Wu, J. J. Am. Chem. Soc
137, 14861; (e) Anumandla, D.; Acharya, A.; Jeffrey, C. S. Org. Lett
2016
Lett
Carson, C. R. J. Am. Chem. Soc
Koster A. K.; Jeffrey, C. S. Tetrahedron Lett
, 11, 326;
This work reveals that HFIP is particularly pertinent catalyst
for the synthesis of thioesters. The reaction is assumed to proceed
through in situ generated protosolvated cation intermediates from
substrate acyl halides. Direct use of HFIP as catalyst allows the
S-carbonylation of thiols in green, clean and atom economical
fashion, favouring over the other tedious and traditional
protocols. Thus metal-, base- and acid-free, novel protocol also
greatly expanded the scope of thiols and acyl halides that are
compatible for the expeditious synthesis of thioesters in good to
quantitative yields. Further, the development of simple, efficient
and eco-friendly novel synthetic protocols employing HFIP
under progress in our laboratory.
.
,
.
,
.
, 5
.
,
.
2016, 18, 268; (b)
.
,
,
.
,
.
2015
,
.
,
18, 476; (f) Anumandla. D.; Littlefield, R.; Jeffrey, C. S. Org.
2014 16, 5112; (g) Jeffrey, C. S.; Barnes, K. L.; Eickhoff, J. A.;
2011 133, 7688; (h). Barnes, K. L.;
2014 55, 4690; (i)
.
,
.
,
.
,
Acharya, A.; Eickhoff, J. A.; Jeffrey C. S. Synthesis 2013, 1825; (j)
Acharya, A.; Eickhoff, J. A.; Chen, K.; Catalano, V. J.; Jeffrey, C. S.
Acknowledgment
Org.Chem. Front
29. Liu, J.; Wang, L.; Wang, X.; Xu, L.; Hao, Z.; Xiao, J. Org. Biomol.
Chem 2016 14, 11510.
30. (a) Li, G-X.; Jin, Q. Chem. Commun
Baeza, A.; Nájera, C. Org Chem
Q.; Schwertz, G.; Chessé, M;. Hazra, C. K.; Wencel-Delord, J.;
Colober, F. Chem. Eur 2016 22, 1735; (d) Weisnera, N.; Khaled,
M. G. Green Chem 2016 18, 681.
31. (a) Enthaler, S.; Weidauer, M. Catal
J. S.; Reddy, B. V. S.; Reddy, P. M. K.; Dash U.; Gupta, M. K.
Mol Catal Chem 2007 271, 266; (c) Berkessel, A.; Adrio, J. A.;
Huttenhain, D.; Neudorfl, J. M. J. Am. Chem. Soc 2006 128, 8421.
32. (a) Zhang, C.; Rao, Y. Org Lett 2015 17, 4456; (b) Motiwala, H. F.;
. 2016, 3, 330.
P.S. thanks UGC for a research fellowship.
.
,
Supplementary Material
.
2010
,
46, 2653; (b) Trillo, P.;
J
.
.
.
2012
, 77, 7344; (c) Dherbassy,
1H NMR and 13C NMR data and copies of spectra of all products
are available.
.
J
.
,
.
,
.
Lett. 2012, 142, 168; (b) Yadav,
References and notes
J
.
.
.
A
:
.
,
1. Staunton, J.; Weissman, K. J. Nat. Prod. Rep
.
2001
,
18, 380.
.
,
2. Bjorn, H. T.; Ben, F. L.; Adriaan, M. J. Chem
.
Commun. 2007, 5,
.
.
,
489.
Charaschanya, M.; Day, V. W.; Aubé, J.
1593.
J
.
Org
.
Chem
.
2016
, 81,
3. (a) Fuwa, H.; Nakajima, M.; Shi, J.; Takeda, Y.; Saito, T.; Sasaki, M.
Org Lett 2011 13, 1106; (b) Wang, B.; Huang, P. H.; Chen, C. S.;
Forsyth, C. J. J. Org. Chem 2011 76, 1140.
4. Tokuyama, H.; Yokoshima, S.; Yamashita, T.; Fukuyama, T.
Tetrahedron Lett 1998 39, 3189.
.
.
,
33. Motiwala, H. F.; Vekariya, R. H.; Aubé, J. Org
.
Lett
.
2015
, 17, 5484.
.
,
.
,

5
Highlights
Ms. Title:
Harnessing the catalytic behaviour
of 1,1,1,3,3,3-hexafluoro-2-propanol
(HFIP): An expeditious synthesis of
thioesters
•
•
•
Acid-, base- and metal-free and expeditious
synthesis of thioesters is unravelled.
Novel HFIP-catalyzed synthesis of thioesters in
excellent yields is reported.
Proceeds under aerobic conditions at room
temperature with wide substrate scope.
No additional reagent/solvent, no workup
required in this clean method.
•
•
Reuse of HFIP, high atom economy, gram-
scale synthesis are noteworthy.