Table 1. Optimization of the iodine cyclization of 1-phenylbut-2-yne-1,4-
Table 2. Synthesis of 3,4-diiododihydrofurans 2 from but-2-yne-1,4-diol de-
rivatives 1.[a]
diol, 1a.[a]
Entry
Solvent
I2 [equiv]
Time [h]
Yield [%][b]
1
2
3
4
5
6
7
8
9
CH2Cl2
CH2Cl2
CH2Cl2
dry CH2Cl2
DCE
DMF
MeOH
THF
1.2
1.5
2.0
2.0
2.0
2.0
2.0
2.0
2.0
12
8
4
12
6
12
12
12
12
62
95
99
2a, 99%[b] 2b, 96%
2c, 90%
2h, 82%
2d, 92%
2i, 93%
2e, 94%
2j, 92%
trace
90
nr[c]
nr[c]
41
2 f, 90%
2g, 70%[c]
CH3CN
72
[a] Conditions: 1a (0.3 mmol) and I2 in CH2Cl2 (3.0 mL), at room temper-
ature. [b] Isolated yield. [c] nr=no reaction.
2k, 92%
2p, 80%
2l, 87%[d]
2m, 83%[d]
2n, 82%[d]
2o, 83%[d]
2t, 82%[d]
2q, 75%
2r, 91%
2s, 88%
present to 1.5 equivalents, a 95% yield of 2a was obtained
after 8 h (Table 1, entry 2) and, on further increasing the
amount of I2 to 2.0 equivalents, an excellent yield of 2a was
obtained (up to 99%; Table 1, entry 3). The reaction was
also tested in dry CH2Cl2, in which case only trace amounts
of 2a were observed (Table 1, entry 4).
[a] All reactions were run under the following conditions, unless otherwise
indicated: 1 (0.30 mmol) and I2 (2.0 equiv) in CH2Cl2 (3 mL), at room tem-
perature. [b] Isolated yield. [c] 20% of the starting material was recovered.
[d] The reaction was carried out at 408C.
The reaction was also tested in other solvents. The use of
dichloroethene (DCE) gave an almost identical result, albeit
with a very slightly lower yield (Table 1, entry 5), whereas
DMF and MeOH proved to be ineffective and THF and
CH3CN were less effective (Table 1, entries 6–9). Thus, the
optimum reaction conditions employ 1.0 equivalent of 1a
and 2.0 equivalents of I2, in CH2Cl2, at room temperature.
With the optimized conditions in hand, various but-2-yne-
1,4-diol derivatives, 1a–t, were subjected to the above condi-
tions, as depicted in Table 2. Thus, the tandem carbon–het-
Table 3. Synthesis of 3,4-diiododihydropyrroles 2u–ac[b] from 4-amino-
but-2-yn-1-ol derivatives 1u–ac.[a]
2u, 86%
2v, 91%
2w, 87%
ACHTUNGTRENNUNGeroatom bond formation reactions of but-2-yne-1,4-diol de-
rivatives 1a–t proceeded smoothly to provide the corre-
sponding products 2a–t in moderate to excellent yields. The
reaction works well with aromatic R’ groups. Electron-rich
aryl groups showed better results than those with an elec-
tron-withdrawing group in this tandem reaction (e.g., 1a vs.
1g). Substrates 1h and 1i, with a styrene or heteroaromatic
R’ group, can also afford the desired products 2h and 2i in
83 and 93% yield, respectively. Interestingly, substrates like
1l–o, with aliphatic groups, can also gave the corresponding
3,4-diiodoheterocyclic compounds 2l–o in moderate yields.
Other substrates, like 1p–t, can also afford the correspond-
ing products 2p–t in moderate to excellent yield.
2x, 80%[c]
2y, 97%[c]
2z, 45%[c]
2aa, 85%[c]
2ab, 80%[c]
2ac, 70%[c]
[a] All reactions were run under the following conditions, unless other-
wise indicated: 1 (0.30 mmol) and I2 (3.0 equiv) in CH2Cl2 (3 mL), at
room temperature. [b] Isolated yield. [c] The reaction was carried out at
408C.
Furthermore, to expand the scope of this reaction, we also
investigated a range of 4-aminobut-2-yn-1-ol derivatives,
1u–ac. It was found that, under the optimized conditions,
substrates 1u–ac were transferred into 3,4-diiodo-dihydro-
pyrroles 2u–ac in moderate to excellent yields, as depicted
in Table 3. The molecular structure of the representative
product 2u was determined by X-ray crystallography
(Figure 1).[16] Substrates like 1x–ac, with aliphatic substitu-
ents, can also afford the desired spiro products in good
yield.
As we know, six-membered pyran rings are very impor-
tant in organic chemistry. Consequently, under the opti-
mized conditions, we also investigated the reaction of pent-
2-yne-1,5-diol derivative 1ad. Fortuitously, 4,5-diiodo-2,6-di-
6152
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2010, 16, 6151 – 6154