reactions. In particular, halogen-promoted F-C alkylation of
R,â-unsaturated carbonyl compounds, especially of cin-
namate and chalcon would provide R-halo-â,â-diarylcarbonyl
compounds, which could be transformed into various useful
organic compounds by replacing the halogen with a series
of nucleophiles. More interestingly, â,â-diarylcarbonyl com-
pounds are important structural motifs found in many natural
products and a number of pharmaceuticals.6 Different
electron-rich arenes smoothly underwent NBS-promoted F-C
alkylation with a number of cinnamates and chalcones at 15
°C and produced R-bromo-â,â-diarylcarbonyl compounds in
high yields (Table 3).
Sm(OTf)3 was found to be an efficient catalyst for the
halogen-promoted F-C alkylation with alkenes including R,â-
unsaturated carbonyl compounds and provided anti-1,2-
haloarylated products in moderate to good yields. It seems
that Sm(OTf)3 activates NBS by chelation to facilitate the
formation of halonium ions from alkenes and the subsequent
reactions with arenes led to the formation of F-C alkylated
products along with regenaration of Sm(III) catalyst. Thus
a plausible mechanism has been proposed for Sm(OTf)3-
catalyzed halogen-promoted F-C alkylation reactions (Scheme
3). However, further investigations are warranted to support
this proposal.
Table 3. Sm(OTf)3-Catalyzed Halogen-Promoted F-C
Alkylation with R,â-Unsaturated Carbonyl Compoundsa
time
(h)
yieldb
(%)
entry
ArH 1
Ar′
R3
OMe
1
2
3
4
5
6
7
8
9
1c
1d
1e
1d
1e
1d
1d
1e
1d
1e
4-MeOC6H4
4-MeOC6H4
4-MeOC6H4
3,4-MeOC6H3
3,4-MeOC6H3
2-furyl
3,4-MeOC6H3
3,4-MeOC6H3
4-MeOC6H4
4-MeOC6H4
12
77
OMe
OMe
OMe
OMe
OMe
C6H5
C6H5
2-MeOC6H4
2-MeOC6H4
12
12
12
12
1
3.5
3.5
4
91
80c
85
76c
51
79
71c
90
10
4
90c
a Sm(OTf)3 (0.05 equiv)-catalyzed F-C alkylation was performed with
1.0 equiv of alkene, 1.2 equiv of arene, 1.2 equiv of NBS in CH3CN at 15
°C. b Isolated yields of 5 after column chromatography. c 10-15% of
trimethoxy bromobenzene was obtained.
electron-rich alkenes, e.g., p-methoxy-â-methylstyrene and
p-methoxy-â-propylstyrene, were carried out at -20 °C to
afford clean F-C alkylated products. Improved yields were
obtained when styrenes were used in excess (entries 5 and
6). Reactions of toluene and anisole with alkenes exclusively
produced para-substituted adduct. No ortho-regioisomer was
Scheme 3. Proposed Mechanism for Sm(OTf)3-Catalyzed
Halogen-Promoted F-C Alkylation
1
detected from the H NMR of the crude reaction mixture.
Reactions of anisole, 1,2-dimethoxybenzene, and 1,2,3-
trimethoxybenzene with 1,2-dihydronaphthalene produced
1-aryl-2-halotetralins in good yields (entries 7-9). The other
regioisomer 2-bromo-1-(3,4,5-trimethoxyphenyl)-1,2,3,4-tetra-
hydronaphthalene from 1,2,3-trimethoxybenzene was not
detected. It is to be noted that 1-aryl-2-halotetralins could
be key intermediates for the synthesis of many biologically
important compounds5 by replacing the halogen atom with
suitable nucleophiles.
R,â-Unsaturated carbonyl compounds represent a syntheti-
cally useful class of substrates for various alkene addition
We have developed a highly regio-, stereo-, and chemo-
selective halogen-promoted Friedel-Crafts alkylation of
aromatic compounds with alkenes using inexpensive and
easily available NBS or I2 as a halogen source. These
reactions are catalyzed by Lewis acids, in particular metal
triflates. Among these, Sm(OTf)3 was found be the best
catalyst. Electron-rich arenes smoothly underwent chemo-
selective halogen-promoted F-C alkylation with a variety of
alkenes. This method was also found to be very effective
with R,â-unsaturated carbonyl compounds such as
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