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achieved on the synthesis of both types of essential molecular
scaffolds.[2f–i,3a,e,f,9,10] Nevertheless, the development of efficient
and straightforward methods in a simple operation and under
mild conditions is still fueled by the strong and growing aspi-
ration for such processes in most areas of chemical synthesis.
It is known that the status of cascade cyclization as a
powerful and ingenious strategy for the synthesis of cyclic
compounds is irreplaceable. Herein, iodocyclization shows
undeniable benefits in most cases, including being metal-free,
having mild conditions, having the potential for further exploi-
tation, and providing economies of time, labor, and cost,[11]
whereas Brønsted acids, as budget and green catalysts, have
emerged as valuable tools for the generation of carbo- and/or
heterocyclic skeletons with unmatched advantages.[12] Alkynols,
as interesting and important starting materials with two
mutual activated functional groups, have become star mole-
cules in synthetic methodology.[13] In the past few years, our
group has successfully developed a series of efficient methods
for the synthesis of carbo- and/or heterocyclic building blocks
through cascade iodocyclization[11] and Brønsted acid catalyzed
cyclization with various alkynols (or alkynones) as the starting
materials.[14] By taking into consideration our current interest in
new approaches to cyclic skeletons with atom economy, as
well as the continued advancement of green chemistry, we
designed an iodocyclization and a Brønsted acid catalyzed
cascade cyclization for the synthesis of 2H-chromene and 4-
chromanone derivatives by using various propynols as the sub-
strates (Scheme 1). Herein, different products derived from the
same starting materials are observed under diverse reaction
systems. Relative to the traditional strategies, our developed
reaction systems could be conveniently operated and avoid
inert-gas protection or toxic transition-metal catalysts, which
may open up a new potential application for these systems in
industrial production.
Results and Discussion
The initial exploration for the synthesis of 2H-chromenes was
started by employing compound 1a (0.1 mmol) as the model
substrate with iodine (2.0 equiv) in MeCN (2.0 mL) at 608C
(Table 1, entry 1). To our delight, our anticipated product, 3,4-
Table 1. Optimization of the iodocyclization for the synthesis of 2a[a]
Entry
Solvent
I2 [equiv]
T [8C]
Yield [%][b]
1
2
3
4
5
6
7
8
MeCN
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
1.2
1.0
1.2
60
60
60
60
60
60
60
RT
RT
RT
0
79
45
61
N.R.[d]
62
trace[e]
trace[f]
90
98
93
95
MeNO2
1,2-DCE[c]
toluene
THF
DMSO
1,4-dioxane
MeCN
MeCN
MeCN
MeCN
9
10
11
[a] Unless otherwise noted, all reactions were performed with 1a
(0.1 mmol) with I2 in anhydrous solvent (2.0 mL) under an air atmosphere
for 0.5 h. [b] Yields of isolated products. [c] 1,2-DCE: 1,2-dichloroethane.
[d] N.R.: no reaction. [e] 79% of 1-(2-hydroxyphenyl)-2-iodo-3,3-diphenyl-
prop-2-en-1-one was detected. [f] 71% of 1a was recovered.
diiodo-2,2-diphenyl-2H-chromene (2a), was isolated in 79%.
However, no better results were obtained after a brief survey
of various representative solvents (Table 1, entries 2–7).
Lowering of the temperature led to a higher yield of 90%
(Table 1 entry 8). We believe that the higher temperature was
advantageous to the generation of the iodo Meyer–Schuster
rearrangement by-product. Other adjustments indicated that
the most appropriate amount of iodine was 1.2 equivalents,
which gave 98% yield (Table 1, entries 8–10). Afterwards, 95%
yield of 2a was achieved at 08C due to the relatively lower
activity, as expected (Table 1, entry 11). Finally, the optimal
reaction conditions for producing 2a were affirmed as the use
of iodine (1.2 equiv) in MeCN (2.0 mL) at room temperature for
0.5 h (Table 1, entry 9; conditions A).
To verify our concept of the Brønsted acid catalyzed cascade
cyclization for the generation of 4-chromanones, p-TsOH
(10 mol%) was used as the catalyst to initiate a tentative
inquiry in a solution of 1a (0.1 mmol) and MeOH (2.0 mL) at
room temperature. Only 36% of 3a and 59% of 1-(2-hydroxy-
Scheme 1. Our previous work and new anticipation towards the synthesis of
2H-chromene and 4-chromanone derivatives. DDQ: 2,3-dichloro-5,6-dicyano-
1,4-benzoquinone; NIS: N-iodosuccinimide; p-TsOH: p-toluenesulfonic acid.
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Chem. Eur. J. 2015, 21, 1 – 9
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ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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