Chemistry Letters Vol.37, No.1 (2008)
29
Table 3. Addition reaction using various aldehydesa
e) H. Taguchi, K. Ghoroku, M. Tadaki, A. Tsubouchi, T.
1) R1CHO (2.5 equiv.)
TASF (5 mol %), MS 4A (dry)
O
O
X
X
O
O
X
X
THF, -78 °C − rt, Time
HO
OH
3
4
1a was prepared by the oxidation of the known (Z)-3-iodo-3-
trimethylsilylpropenol 10 with PCC/CeliteÒ in 86–90% yield.
For the synthesis of 10, see: a) K. D. Kim, P. A. Magriotis,
R3Si
SiR3
2) TBAF (1 M in THF)
3
0 °C, 10 min
R1
7
R1
Entry
R3Si
X
Time/h
16
R1
Ph
Yield/%b
1
2
3
4
5
6
7
8
9
TMS
TMS
TMS
TMS
TMS
TMS
TMS
TMS
TMS
TBS
TBS
I
I
I
I
I
I
I
65
50
78
37
54
77
57
75
64
21
16
16
16
16
16
16
16
14
14
16
11
4-MeOC6H4
(Z)-t-Bu(Cl)C=C
(E)-PhC=C
(E)-n-PrC=C
PhCꢃC
Propionitrile (10 mL) was added to TiI4 (2222 mg, 4.0 mmol)
at ambient temperature under an argon atmosphere. The solu-
tion was stirred for 10 min, and a propionitrile (10 mL) solution
of 1a (508.2 mg, 2.0 mmol) was added at ꢂ88 ꢁC during 2 h.
After being stirred at ꢂ88 to ꢂ20 ꢁC for 16.5 h, the reaction
was quenched with saturated aqueous NaHCO3, 10% aqueous
NaHSO3, and triethylamine. The whole mixture was filtered
through a Celite pad and extracted with ethyl acetate. The com-
bined organic extracts were dried over anhydrous Na2SO4 and
concentrated in vacuo. Purification on preparative silica gel
TLC (2:1 n-hexane/ethyl acetate as an eluent) gave 2a
cyclo-C6H11
4-ClC6H4
Ph
Br
Br
I
10
11
4-ClC6H4
Ph
I
aReaction was carried out according to the typical procedure (Ref. 8).
bIsolated yield as a mixture of diastereomers.
O
O
O
O
I
I
I
I
HO
OH
O
O
MnO2
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
6
1
CH2Cl2
0 °C − rt, 16 h
8
78%
(383.7 mg, 75%) as a colorless oil. dl:meso = 92:8. H NMR
Pinacol Phenylboronate (6.0 equiv.)
Pd(PPh3)4 (5 mol %)
(500 MHz, CDCl3): ꢂ 0.19 (s, 18H), 2.45 (brs, 0.16H), 2.58
(brs, 1.84H), 4.50–4.54 (m, 1.84H), 4.68–4.70 (m, 0.16H),
6.23–6.27 (m, 0.16H), 6.32–6.35 (m, 1.84H). 13C NMR
(126 MHz, CDCl3): ꢂ ꢂ1:7, 79.6, 116.9, 143.9.
O
O
Ph
Ph
O
O
K2CO3 (5.0 equiv.)
DME / H2O, 90 °C, 16 h
4-ClC6H4
4-ClC6H4
53%
9
5
Scheme 2. Functional group transformations.
the presence of 5 mol % of the fluoride source (Entries 7–9).
Under the optimized conditions a variety of aldehydes were
subjected to the addition reaction (Table 3).
6
7
a) E. Nakamura, T. Murofushi, M. Shimizu, I. Kuwajima,
J. Sakata, I. Kuwajima, E. Nakamura, M. Shimizu, J. Am.
Under an argon atmosphere to a suspension of TASF (0.5 mg,
0.004 mmol) in THF (1.0 mL) in the presence of molecular
sieves 4A (300 mg) was added a mixture of benzaldehyde
(8.9 mg, 0.084 mmol) and 3 (18.4 mg, 0.033 mmol) in THF
(2.0 mL) at ꢂ78 ꢁC, and with stirring the mixture was allowed
to stand at rt for 16 h. The mixture was cooled to 0 ꢁC, and a
THF solution of TBAF (0.07 mL, 0.07 mmol, 1 M solution)
was added to it. After being stirred for 10 min at 0 ꢁC, the
whole mixture was quenched by adding water and sat. aqueous
NH4Cl. After a usual work-up, the crude product was purified
on preparative silica gel TLC (3:1 n-hexane/ethyl acetate as an
eluent) to give 7 (R1 ¼ Ph) as a mixture of diastereomers
(13.4 mg, 65%). Rf ¼ 0:33 (n-hexane/ethyl acetate = 3:1).
1H NMR (500 MHz, CDCl3): ꢂ 1.50 (s, 3H), 1.50 (s, 3H),
2.32–2.37 (m, 2H), 4.64–4.70 (m, 2H), 5.08–5.11 (m, 1H),
5.16–5.19 (m, 1H), 6.32–6.37 (m, 1H), 6.40–6.44 (m, 1H),
7.25–7.38 (m, 10H). 13C NMR (126 MHz, CDCl3): ꢂ 26.9,
80.0, 80.0, 80.3, 80.4, 83.5, 83.6, 83.6, 110.5, 117.2, 117.4,
117.9, 126.8, 126.8, 127.0, 127.0, 128.2, 128.2, 128.3, 128.5,
131.7, 131.9, 132,0, 139.7, 139.8, 139.8.
The reaction proceeded well with aromatic aldehydes
(Entries 1 and 2). Although use of cinnamaldehyde gave the
adduct in moderate yield, those of chlorovinyl, phenylethynyl,
and aliphatic aldehydes recorded better yields (Entries 3–7).
The use of dibromo derivative as substrate gave essentially the
same results as in the case with the diiodinated starting material
(Entries 8 and 9). The bis-TBS derivative was not as reactive as
its TMS counterpart (Entries 10 and 11). The products were
obtained after desilylation with TBAF in the work-up process.
For further C–C bond-forming reaction with the adduct, we
carried out the following Suzuki coupling reaction.
The adduct was first oxidized with MnO2 to give the dike-
tone 8, which was treated with pinacol phenylboronate in the
presence of Pd0 to give the diphenylated product 9 in moderate
yield, making a useful addition to the synthesis of this class of
compounds (Scheme 2).9
8
In conclusion, we have shown that (Z)-3-iodo-3-trimethyl-
silylpropenal (1a) is an excellent substrate for the dl-selective
pinacol coupling under the influence of TiI4. The trimethyliodo-
vinyl moiety of the coupling product was in turn efficiently
utilized for the C–C bond-forming reactions.
References and Notes
1
a) J. Yoshida, K. Tamao, T. Kakui, M. Kumada, Tetrahedron
1317. d) K. Itami, T. Nokami, Y. Ishimura, K. Mitsudo, T.
2
9
a) A. G. M. Barrett, W. W. Doubleday, K. Kasdorf, G. J.