Y. Xiao et al.
CarbohydrateResearch469(2018)10–13
Table 2
triethylamine and diisopropyl ethylamine (DIPEA) completely hindered
the oxidation reaction, consequently, only trace amount of sulfoxide
was obtained (entry 2, 3). Changing the base to pyridine or lutidine still
inhibited the reaction and 50–60% yields were obtained (entry 4, 5).
Interestingly, when 0.2 equiv of DTBMP was added as base, the yield
was increased to 93% yield without observing any de-protection of the
benzylidene group (entry 6). Inorganic base such as Na2CO3 seemed
inefficient in increasing the yield (entry 7). This condition was also
capable of oxidating other OPTB glycosides containing acid sensitive
functional groups, all reactions proceeded, smoothly to generate the
desired sulfoxides in excellent yields (Scheme 3). The disaccharide
OPTB glycosides 3q was oxidized to 4q perfectly under the optimum
condition.
Optimization of reaction conditions with bases.
Entry
Base (0.2 equiv)
Yield
1
2
3
4
5
6
7
\
TEA
82%
trace
trace
52%
60%
93%
85%
DIPEA
Pyridine
Lutidine
DTBMP
Na2CO3
Kochi et al. have proposed that a nitrosonium electron donor-ac-
ceptor (EDA) complex was formed between nitrogen oxide and thioe-
ther, which played a pivotal role in the nitrogen oxide mediated sulfide
oxidation reactions [11]. This complex was observed at low tempera-
ture by optical absorption detection. In our experiments, the EDA
complex was indeed observed even increasing the temperature to room
temperature (Fig. 1a). Interestingly, when TBAB was involved, a clear
bathochromic displacement was observed, indicating the formation of a
new EDA complex, possibly a ternary complex involved sulfide, NOBF4
and TBAB, which might account for the high efficiency of the present
oxidation reaction [13]. With respect to the base effect, apparently, all
of the tested organic bases affected the formation of the ternary EDA
complex as evidenced by the hypsochromic shifts (Fig. 1b). Among
these bases, TEA and DIPEA made the system significantly hypso-
chromic shift while DTBMP was less shift. These observations were
identical with the reaction efficiency of different bases. However, the
rational was unclear in this stage.
3. Conclusions
Scheme 3. Oxidation of OPTB glycosides containing acid labile groups.
In conclusion, we have successfully applied nitrogen oxide mediated
sulfoxidation to transform latent OPTB glycosides to active OPSB gly-
cosides. This method involved NOBF4 as catalyst, TBAB as additive and
O2 as terminal oxidant. In case of the acid sensitive substrates, catalytic
amount of DTBMP was able to neutralize the acidity without affecting
the oxidation efficiency. The method not only features the advantage of
high efficiency, wide applicability and allowance for large scale
synthesis, but also meets many aspects of green chemistry's require-
ment, such as non-metal and catalytic amount of reagents involved and
O2 used as terminal oxidant, high atom-economy, easy manipulation
and purification processes.
worth noting that all of the reactions were very clean thus a simple
wash of the reaction mixture with water followed by concentration
afforded the desired products in good purity. When necessary, passing
the crude mixture through a short plug of silica gel provided perfect
purity of the products.
However, when subjected the reaction condition to OPTB glycoside
3l possessing acid labile benzylidene group, a slightly lower yield was
obtained due to the partially de-protection of the benzylidene group
caused by the weak acidity of reaction system (Table 2, Entry 1). We
then considered adding base to neutralize the acidity. Unfortunately,
Fig. 1. Optical absorption spectra. (a) bathochromic shift of the catalytic reaction system; (b) hypsochromic shifts in presence of various organic bases.
DTBMP = 2,6-Di-tert-butyl-4-methylpyridine; DIPEA = N,N-Diisoopropylethylamine; TEA = Triethylamine.
12