Y. Liang et al. / Chinese Chemical Letters 23 (2012) 777–780
779
Table 1 (Continued )
Entry
Substrate 1 (Z:E)
Product
Yield (%)b
92
Cl
H
H
H
13
14
15
16
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
Br
Br
Br
1m ( 99:1)
1n (>99:1)
1o (18:1)
Cl
3m
3n
3o
Br
73
89
89
Br
F
F
NO2
H
CO2Et
Br
NO2
3p
1p (10:1)
1q (2:1)
CO2Et
17
71
H
O
O
CO2Et
3q
Br
a
General reaction procedure: a mixture of 0.2 mmol of ethyl a-bromocinnamates 1 and 0.6 mmol of TBAF (1.5 mol/l in THF) in 1 ml of DMF was
stirred at 60–80 8C for 22 h. The reaction mixture was then cooled to the room temperature, and the product was extracted with EtOAc (15 ml Â2).
The combined organic layer was washed with brine (20 ml Â3) and dried with anhydrous Na2SO4. The solvent was removed under reduced pressure,
and the residual was treated with silica gel chromatography to give product 2 or 3.
b
Isolated yield.
c
The reaction time was 30 h. Besides 2b. There were 11% of recovered 1b and 7% of elimination product alkyne.
dominant. Unsubstituted compound 1a was converted to b-fluoroethylcinnamate 2a in yield of 89% under the reaction
conditions. Compounds 1b–1g, which incorporated a substituent at the para- or meta-position of the phenyl ring
reacted in the same way, giving rise to the corresponding fluorination products 2b–2g. The ratio of E to Z configuration
in the reactants did not have obvious influence on the result. It is noteworthy that compounds 2 were obtained
exclusively in Z-configuration [9]. This result is comparable to that concerning the mono-hydrofluorination of
electrophilic alkynes by using the CsF–H2O–DMF system, in which case a Z:E stereoselectivity of 95:5 was observed
for the formation of compound 2a [7]. However, when compound 1h was subjected to the reaction conditions, only
elimination product 3h was obtained after reaction.
On the other hand, when the substituents were at the ortho-position of the phenyl ring, as in the cases of 1i–1p, the
reaction products were exclusively alkynes 3 (Table 1, entries 9–16). As aforementioned, TBAF can act as base to
effect the elimination reaction of bromoalkenes [5]. The formation of 3h–3p is consistent with this reaction pattern.
However, the reaction of 1a–1g gave a different result. We believed that compounds 2 resulted from the
hydrofluorination of 3. This mechanism is supported by the observation that during the course of the reaction of 1b,
elimination product 3b formed firstly, but disappeared at the end of reaction time. In addition, control experiment
showed that 3a can be converted to 2a by treatment with TBAF.
It is interesting to see that the nature and position of the substituent played a critical role in determining the final
reaction consequence. In the absence of the ortho-substituent, compound 2 was formed exclusively in its Z
configuration, whereas in the presence of it, the formation of compound 2 became largely disfavored, and 3 was
obtained exclusively. These results indicate that in the present cases, the addition of HF to the electrophilic triple bond
is greatly influenced by the steric effect. We believe that the trajectory of fluoride attack on the triple bond falls in the
plane of phenyl ring and triple bond to keep the conjugated system, and a substituent at the ortho-position would
render the reaction much unfavorable (Scheme 1). By contrast, the elimination of HBr from 1 is not sensitive to the
position of substituent. The only exception to this scenario is ethyl 2-bromo-3-(4-methoxyphenyl) acrylate (2h), in
which case the product was 3h rather than the fluorination product. The reason why 1h failed to be transformed to the
corresponding 2h is probably due to the strong electron-donating methoxy group renders the triple bond unreactive
Liang, Yan
