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Table 1 Studies on the deprotection of tert-butanesulfinyl amine 1aa
the amines in good to excellent isolated yields, and a number of
functional groups were well tolerated. Delightfully, this method could
also be used for the deprotections of p-toluenesulfinyl units (Table 3,
substrates 1u and 1v).
In order to get some insights into this iodine catalyzed process, a
number of experiments with tert-butanesulfinyl amine 1b were carried
out. We firstly elaborated the amine salts (Scheme 3, also see ESI†)
obtained in the aqueous phase. Based on HRMS analysis (ESI-MS), the
salt was identified as compound 3b, a sulfate of amine 2b. It was
deduced that the sulfate ion might come from the oxidation of the
sulfinyl unit by iodine. Next, we carried out the reaction in deuterated
THF and D2O in a sealed tube. tert-Butanol (4b), di-tert-butyl thiosul-
fonate (5b) and di-tert-butyl thiosulfinate (6b) were identified (based on
Entry
Additives
Bases, solvents
Yields
1
2
3
4
5
6
7
8
KI, CuSO4
IBD, CuSO4
n-Bu4NBr
K2CO3, EtOH–H2O (1 : 1)
DMAP (0.2 eq.), EtOH
0%b
0%c
K2CO3, PhMe–H2O (2 : 1)
K2CO3, DMAP, THF–H2O
K2CO3 (3.0 eq.), THF–H2O
DMAP (3.0 eq.), THF–H2O
Na2CO3 (3.0 eq.), THF–H2O
K2CO3 (3.0 eq.), THF–H2O
Na2CO3 (3.0 eq.), acetone–H2O
Na2CO3 (3.0 eq.), MeCN–H2O
KHCO3 (6.0 eq.), THF–H2O
Na2CO3 (3.0 eq.), THF–H2O
0%d
I2 (0.5 eq.)
I2 (2.5 eq.)
I2 (2.5 eq.)
I2 (2.5 eq.)
I2 (2.5 eq.)
I2 (2.5 eq.)
I2 (2.5 eq.)
I2 (2.5 eq.)
I2 (2.5 eq.)
2: tracee, f
2: 14% f
2: 10% f
2: 27% f
2: 44%g
2: 21%g
2: 51%g
2: 53%g
2: 71%g
9
10
11
12
a
Yields represent isolated yields. Reactions were conducted at
0.25 mmol scale in designated solvents (5 mL) at 20 1C for 14 hours. NMR and ESI-MS analyses of the reaction mixture) in the reaction
b
c
K2CO3 (2.0 eq.), KI (2.0 eq.) and CuSO4 (0.2 eq.). IBD (2.0 eq.), CuSO4
system. These compounds might be the by-products obtained from
further oxidation of tert-butylsulfinic acid.6 Di-tert-butyl thiosulfonate
(5b) was isolated and fully characterized by NMR and HRMS. Deprotec-
tion of the p-toluenesulfinyl unit with compound 1y was also conducted
(Scheme 3), formation of p-toluenesulfate 3c was confirmed by NMR
d
e
(0.2 eq.). n-Bu4NBr (0.2 eq.), K2CO3 (2.0 eq.). K2CO3 (0.5 eq.), DMAP
(0.5 eq.). THF : H2O = 1 : 1. DMAP (0.2 eq.) was added, organic
solvents : H2O = 1 : 1.
f
g
In order to develop a general iodine mediated method for the and ESI-MS analyses. To make sure that tert-butanesulfonyl amine 1z
deprotection of both tert-butanesulfinyl and p-toluenesulfinyl units, was not involved as an intermediate in this deprotection process, a
tert-butanesulfinyl amine 1b was then prepared and used as a typical control experiment with 1z, obtained by oxidation of 1b with m-CPBA,
substrate for screening other possible reaction conditions. It was was also carried out. No deprotection of the tert-butanesulfonyl group
found that bases such as sodium carbonate or DMAP were not occurred under the identical reaction conditions (Scheme 3).
necessary for deprotection of compound 1b bearing a moiety less
Deprotection in the presence of excess sodium carbonate (3.0 eq.)
labile to acid hydrolysis. The reaction occurred efficiently in the was conducted to exclude the possible hydrolysis of acids (HI acid,
absence of bases and required only catalytic amounts of iodine which might be generated in the reaction process). Although more
(entry 5, 0.2 eq.). Although the reaction could be conducted at room iodine (2.5 eq.) was required, amine 2b was obtained in 81% yield
temperature (entry 5), elevating the reaction temperature (50 1C oil together with compound 7b (Scheme 4).7 It could be concluded that
bath, entry 9) could significantly shorten the reaction times. To the iodine, rather than acids generated in situ, plays the key role in this
best of our knowledge, this is the first example of iodine catalyzed deprotection process.
deprotection of a tert-butanesulfinyl amine, a complementary process
to the acid hydrolysis.
We next conducted the reaction in the presence of a stable oxyl
radical, 2,2,6,6-tetramethyl-1-oxylpiperidine (TEMPO),8 and found
With the optimal reaction conditions (Table 1, entry 12 for acid that the deprotections were significantly inhibited (Scheme 4). It
sensitive substrates; Table 2, entry 9 for regular substrates) in hand, was noteworthy that no reaction was observed upon treatment of tert-
we next conducted a number of deprotections, the results are butanesulfinyl amine 1b with n-Bu3SnH, a radical initiator. Based on
summarized in Table 3. The new deprotection procedures afforded collected evidence, a single electron transfer initiated pathway was
Table 2 Screening of optimal reaction conditions for the deprotection of tert-butanesulfinyl aminesa
Entry
Iodine, additive
Solvent, temperature
Time; yields
1
2
3
4
5
6
7
8
9
10
I2 (2.5 eq.), Na2CO3 (3.0 eq.), DMAP (0.2 eq.)
I2 (2 eq.), DMAP (0.2 eq.)
I2 (2 eq.), none
I2 (0.2 eq.), DMAP (0.1 eq.), CuSO4 (0.1 eq.)
I2 (0.2 eq.), none
I2 (0.2 eq.), none
I2 (0.2 eq.), none
I2 (0.2 eq.), none
I2 (0.2 eq.), none
None
THF/H2O, rt
THF/H2O, rt
THF/H2O, rt
THF/H2O, rt
16 h, 81%b
12 h, 95%b
12 h, 95%b
72 h, 87%b
72 h, 70%c
12 h, 69%d
12 h, 63%d
12 h, 82%d
12 h, 97%d
96 h, 0%d
THF/H2O, rt
MeCN/H2O, 50 1C
EtOH/H2O, 50 1C
Acetone/H2O, 50 1C
THF/H2O, 50 1C
THF/H2O, 50 1C
a
Yields represent isolated yields at 0.25 mmol scale of 1b, and the reactions could be conducted either under air or nitrogen in solvents (5 mL).
THF/H2O = 1/1. THF/H2O = 3/1. Organic solvents/H2O = 5/1.
b
c
d
6260 | Chem. Commun., 2014, 50, 6259--6262
This journal is ©The Royal Society of Chemistry 2014
Chen, Wen
