J. Wang, H. Hou, Y. Hu et al.
Tetrahedron Letters 65 (2021) 152801
Table 1
Control experiment.
a,b
Entry
Variation from the reaction condition
Yieldc,d
1
2
3
4
5
6
7
8
9
none
no catalyst
93
trace
trace
trace
32
trace
53
no nBu
nBu NI instead of nBu
Catalytic amount of nBu
dark and 40 °C instead of sunlight and rt
AIBN instead of I
4
NBr
4
4
NBr
NBr
4
2
fluorescein instead of I
no base
2
66
–
Scheme 1. Organic molecules containing the amide moieties.
10
11
12
13
14
K
K
2
CO
PO
3
instead of KOH
instead of KOH
72
77
32
44
3
4
DMF instead of water
ethyl alcohol instead of water
5 W LED lamp instead of sunlight
81
a
1
(0.50 mmol), 2a (0.55 mmol), catalyst (20 mol%), base (2.0 eq), PTC (1.0 eq),
water (2.5 mL), sunlight, 2.5 h.
b
The temperature increases up to 40 °C.
HPLC yield by using benzimidazole as an internal standard.
Intriplicate.
c
d
careful evaluation of the reaction conditions, we found that a com-
bination of I (0.2 equiv) in the presence of KOH powder (2.0 equiv)
2
in aqueous under irradiation of sunlight for 2.5 h in the ambient
atmosphere gave the best yield for the desired product (Table 1,
entry 1). However, the reaction did not/little take place in the
absence of either the photocatalysts or without sunlight (Table 1,
entries 2 and 6). When the reaction was tested without the use
of nBu
matically to trace (Table 1, entries 3–4). At a catalytic amount of
nBu NBr (0.2 equiv), the reaction became sluggish, and the yield
of product decreased to 32% (Table 1, entry 5). It is worth noting
that using I was critical for achieving the high yield. Lower yields
4 4 4
NBr or nBu NI instead of nBu NBr, the yield dropped dra-
Fig. 1. Strategies for the synthesis of amides.
4
elementary I
2
is applied as both a visible light photocatalyst and a
2
p
Lewis acid, enabling the direct activation of alkyne C„C bonds
were observed when using AIBN (azobisisobutyronitrile) or fluo-
rescein as catalysts (Table 1, entries 7–8). After a screening of
selected bases, we found that bases had a significant effect on
the reaction efficiency and KOH was proved to be the most effec-
tive ones at facilitating transformation (Table 1, entries 9–11).
The control experiments indicated that water was crucial for this
reaction (Table 1, entries 12–13). Finally, the reaction still pro-
ceeded well under 5 W LED lamp instead of sunlight indicating
the sunlight was the best choice for this protocol (Table 1, entry
14).
for electrophilic cyclization reactions, one of the most important
reactions of alkynes [19]. Moreover, iodine has been shown to be
more low-cost and more in line with the concept of green
chemistry than several metal catalysts. Among the various
reactions mediated by visible light catalysis, the formation of
CAN bond and its subsequent transformation have drawn much
attention [20]. Such as Fu group reported a protocol for visible-
light-mediated copper-catalyzed N alkylation reactions of unacti-
vated secondary halides [20].
Recently, owing to the increasing environmental concerns,
chemical industries have been prompted to minimize the use of
toxic and hazardous solvents in chemical manufacture. It is
strongly recommended to replace technologies that pollute the
environment by benign alternatives. Thus, organic chemists are
turning their attention to developing clean, economical, and envi-
ronmentally safer methodologies. Water as reaction medium is
generally considered as cheap, safe, and environmentally benign
alternative to non-natural solvents [21].
We envisioned that photoredox catalysis with uniform light
penetration may activate amine through SET to enable radical
addition on acid to access amides. Inspired by these pioneering
works and our endeavors to develop environmentally friendly pro-
tocols, herein we report an environment friendly direct N-acylation
for amides from available acids and amines through visible-light-
In this work, we demonstrate that under visible light or sunlight
irradiation, a catalytic amount of I can realize the highly efficient
2
synthesis of amides. Encouraged by the above results, we further
applied this system to the N-acylation of acids and amines
(Table 2). Amines bearing a variety of functional groups, including
nitro, hydroxyl, halide and methoxyl of the anilines, nitrogen hete-
rocycle, amino acid groups and aliphatic amines were also success-
fully tolerated in the reaction. Electron-donating groups and
electron-withdrawing groups were reacted smoothly and afforded
the corresponding amides products in moderate to good yields. For
example, nitro, methoxyl of the aniline were affording desired
products in 88–95% yields (Table
2, 3c, 3e). The yields of chlorine products were 89% under the
present conditions (Table 2, 3d). Glycine, which could react with
acid, was also compatible (Table 2, 3n). The coupling of benzoic
acid with ammonia and propylamine yielded the respective N-ami-
dation products, benzamide and N-propylbenzamide in 90% and
82% isolated yields, respectively (Table 2, 3l, 3m). Moreover,
2
driven I catalysis at room temperature in aqueous.
To test the feasibility of this process for N-acylation, we selected
benzoic acid and aniline as the model substrate (Table 1). After
2