Organic Letters
Letter
a
Scheme 1. Natural Products and Synthesis Strategies of Aryl
S/Se-Glycosides
Table 1. Optimization of the Reaction Conditions
b
entry
deviation from the standard conditions A
yield (%)
1
2
3
4
5
6
7
8
none
82
48
64
72
49
54
72
0
CuCl as the additive
CuBr as the additive
CuI as the additive
CuTC as the additive
Cs2CO3 instead of K3PO4
K2CO3 instead of K3PO4
no K3PO4
9
no Pd(TFA)2
5% Pd(TFA)2
35% norbornene
0
75
72
10
11
entry
b
deviation from the standard conditions B
yield (%)
12
13
14
15
16
17
18
19
20
21
none
81
65
48
0
0
45
0
0
76
70
TFP instead of P(p-ClC6H4)3
PPh3 instead of P(p-ClC6H4)3
DMF instead of DCP
1,4-dioxane instead of DCP
DCE instead of DCP
no Pd(MeCN)2Cl2
no K2CO3
5% Pd(MeCN)2Cl2
35% 5-norbornene-2-carbonitrile
methylbenzoylselenoglycoside to obtain aryl Se-glycosides has
not been realized.11 (3) The synthesis strategy of aryl S/Se-
glycosides has not been reported in Pd/NBE chemistry. Herein
we report our efforts toward a two-component Catellani-type
reaction of 1-thiosugars/1-selenoglycosides with (hetero)aryl
iodides to construct aryl thio/selenoglycosides.
a
Reaction conditions A: 1a (0.2 mmol, 2 equiv), 2a (0.1 mmol, 1
The standard conditions for the optimization of the two
processes were carried out with 1-iodonaphthalene 1a as the
substrate (Table 1). Inspired by Lanny S. Liebeskind and Jiri
Srogl (Liebeskind−Srogl coupling reaction) and other
researchers,15b,19 we sought to discover whether the CuI salt
may act as an additive to activate the C(O)−S bond. After
careful screening of CuI salts, the optimal conditions were not
achieved by adding the CuI salts (entries 2−5). We speculated
that the C(O)−S bond is probably easier to cleave due to the
special structure of the carbohydrates, and it did not require
CuI salt activation. Cs2CO3 was used as base to obtain the
desired product in moderate yield (entry 6), whereas K2CO3
improved the yield to 72% (entry 7). Next, we attempted the
introduction of aryl Se-glycoside 5a with β-p-methylbenzoylse-
lenoglycoside 3a. P(p-ClC6H4)3 was proved to be an optimal
ligand (entries 13 and 14). Of the solvents examined, a polar
solvent (entry 15) could not deliver the desired product, and
1,3-dichloropropane (DCP) was the best choice (entries 16
and 17). Control experiments indicated the crucial role of the
catalyst and base (entries 8 and 9 and entries 18 and 19). In
addition, Pd 5% and norbornene 35% reduced the yields
(entries 10 and 11 and entries 20 and 21).
equiv), 100 °C, 17 h, Ar. Reaction conditions B: 1a (0.2 mmol, 2
b
equiv), 3a (0.1 mmol, 1 equiv), 95 °C, 16 h, Ar. Isolated yields.
addition to glucose, reactions of other thiosugars 2 including
galactose 2d, 2e, xylose 2f, arabinose 2g, and mannose 3o
produced the desired aryl S-glycosides in 89, 51, 83, 84, and
65% yields, respectively. Notably, this reaction showed good
compatibility for dithiosaccharides and gave the target
products 4h and 4i in 82 and 80% yields, respectively. Further
studies about the effect of aryl iodides with different
substituent groups were carried out, and mono- and di-
methyl-substituted aryl iodides provided the aryl thioglycosides
(4k−4m) in excellent yields. Relative to the yield of 4a, the
lower yield of 4n was probably due to the hindrance effect. At
the same time, 7-methoxy, 4-bromo iodobenzene, and 1-
iodopyrene could afford excellent yields (4o−4q). Under the
optimized reaction conditions B, we expanded the scope of the
reaction substrates by employing cost-effective and convenient
β-p-methylbenzoylselenoglycosides 3 with aryl iodides 1 as
substrates. As shown in Scheme 2b, OAc-, OPiv-, or OBz-
protected selenopyranosides, including glucose (5a, 5b),
galactose (5f, 5g), and xylose 5h, gave the desired aryl Se-
glycosides in good yields. The product 5a was characterized by
Delightfully, benzyl (Bn, 5c) and tert-butyldiphenylsilyl
(TBDPS, 5d)-protected selenoglucoses were well tolerated.
A variety of substituted β-thiosugars 2 with aryl iodides 1
could successfully give the corresponding aryl S-glycosides in
moderate to good yields with exclusive β-selectivity under
standard conditions A (Scheme 2a). Glucose-bearing sub-
stituent groups such as acetyl (Ac, 4a), pivaloyl (Piv, 4b), and
benzyl (Bn, 4c) were well tolerated in this approach. In
5642
Org. Lett. 2021, 23, 5641−5646