3
and furnished 2j in 70% yield (entry 9). Additionally, sensitive
aldehyde functionality in 1K remains unspoiled in reaction
medium and converted to desired sulphonylated 2K in excellent
yield (entry 10). Thus milder reaction conditions, protecting as
well as functional group tolerability and chemoselectivity
towards aryl TBDMS ethers makes this protocol noteworthy.
We planned intermolecular competition and cross-over
experiments for the assessment of reactivity order (Scheme 1).
An equimolar mixture of 1a and benzyl alcohol 3 when treated
with excess of NFSI/KF only former underwent sulfonylation
and produced 1b in 90% yield whereas the benzyl alcohol 3 was
fully recovered. Interestingly, the reaction of an equimolar
mixture of aryl TBDMS ether 1a and phenol
4 with
stoichiometric use of NFSI/KF provided mixture of sulfonylated
products 1b (20%) and 5 (70%). Thus, the order of reactivity for
sulfonylation is phenol > aryl TBDMS ethers > aliphatic
alcohols. Next, equimolar mixture of aryl TBDMS ether 1a and
phenol 4 when treated with stoichiometric NFSI and catalytic KF
furnished sulfonylated product 5 (70%), whereas aryl TBDMS
ether 1a was fully recovered. This methodology could be further
extended for sulfonylation of phenols with the use of catalytic KF
and work in this direction is underway.
Scheme 2. Plausible mechanism for interconversion of aryl TBDMS
ether to aryl benzene sulfonate.
Conclusions
In conclusion, we have developed an efficient protocol for the
direct interconversion of aryl TBDMS ethers to corresponding
benzene sulfonate esters by using NFSI/KF in DMF. The mild
conditions and neutral reaction medium well preserves sensitive
functionalities. The present methodology also validated for
exclusive chemoselectivity towards aryl TBDMS ethers. More
significantly, conventional operations, use of inexpensive
reagents and step economy would demonstrate the scope of this
method in total synthesis.
OSO2Ph
OTBDMS
OH
OH
NFSI (2.5 eq.)
KF (2.5 eq.)
+
+
DMF, RT, 6 h
F
F
(1:2)
Acknowledgments
3
(recovered)
3
1b
90%
1a
This research did not receive any specific grant from funding
agencies in the public, commercial, or not-for-profit sectors.
OTBDMS
OSO2Ph
OH
OSO2Ph
NFSI (1.2 eq)
KF (1.2 eq)
+
Supplementary data
+
DMF, RT, 6 h
(1:1)
F
1a
Electronic Supplementary Information (ESI) available: Copies of
1H and 13C NMR spectra for all compounds.
F
4
5 70%
1b 20%
OTBDMS
OTBDMS
+
OH
Experimental
OSO2Ph
NFSI (1.2 eq)
KF (0.1 eq)
+
General procedure for interconversion of aryl TBDMS ethers
to aryl benzene sulfonate esters
DMF, RT, 6 h
(1:1)
F
F
To a stirred solution of NFSI (1.2 mmol) in DMF (8 mL) was
added KF (1.2 mmol) at room temperature. After stirring for 5
minutes turbidity was observed. Then to the resulting turbid
solution was added aryl TBDMS ether (1 mmol) in DMF (2 mL)
and stirring continued at room temperature for specified time.
Next, water (30 mL) was added and reaction mass was extracted
with ethyl acetate (3×20 mL). The combined organic layer was
washed with water (50 mL), brine, dried (Na2SO4) and
concentrated under vacuum. The crude residue was purified on
silica gel column chromatography.
1a
4
5 70%
1a
(recovered)
Scheme 1. Crossover and competitive interconversion experiments.
In order to gain mechanistic insights, we attempted the isolation
of intermediates formed during course of reaction as shown in
Scheme 2. When equimolar mixture of NFSI and KF was stirred
in DMF at room temperature initially it form clear solution but
after 5 minute reaction mass becomes turbid (mass spectra shows
peak at m/z= 174 in negative mode). This suggests that existence
of
reversible
transient
potassium
salt
of
N-
fluorobenzenesulfonimide in reaction medium. Further addition
of 2N aqueous HCl to the reaction medium facilitates formation
of six member transient complex I (between NFSI, KF and HCl),
which leads to enforcement of equilibrium towards right hand
side by forming strong ionic bond in KCl. Thus, after workup we
References and notes
1
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7 and N-
fluorobenzenesulfonamide 8. The isolated reaction intermediates
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(between NFSI, KF and Aryl TBDMS ether) in case of
interconversion of aryl TBDMS ether to their benzene sulfonate.
The formation of strong Si-F bond in TBDMSF is the driving
force for shifting equilibrium towards aryl sulfonate formation.
2
3
(a) J. F. Bunnett, J. Y. Bassett, J. Am. Chem. Soc. 1959, 81, 2104-
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2N HCl
-KCl
+
PhSO2-NHF
PhSO2-F
8
7