C O M M U N I C A T I O N S
lated product 1j (Table 3, entry 1). It is interesting that when
1-chloro-4-iodobenzene 4c was subjected to the reaction conditions,
it provided bis-arylation product 3j in 71% isolated yield (Table 3,
entry 3). 1-Bromo-4-iodobenzene 4b could bis-arylate smoothly
and generated the desired 3j in 68% yield (Table 3, entry 2). The
reactions of the meta-substituted chloro, bromo, and iodo-iodoben-
zene as the electrophiles (4f, 4e, and 4d in Table 3) were also
investigated. The corresponding bis-arylated products were isolated
under the standard conditions in 32%, 60%, and 79% yields,
respectively (Table 3, entries 4-6). The reactions of the ortho-
substituted 4g, 4h, and 4i generated bis-arylated 6 in 21%, 30%,
and 29% yields, as well as a significant reduction product biphenyl
(53%, 48%, and 40% respectively) due to the possible sterical
influence. It is worthy of note that no reactions were observed where
aryl chlorides (without the iodo-group) were employed as the
electrophiles, and less than 5% direct arylation with phenyl bromide
was identified.
Bunnett et al. had investigated the “nucleophilic” replacement
of two halogens in dihalobenzenes without the intermediacy of
monosubstitution products under irradiation.11 They proposed that
the radical anion intermediacy is the type utilizing an intermediate
I with higher reactivity.11 Radical trapping experiments and the
abnormal reactivities of dihalobenzenes in Table 3 induced us to
propose that the DMEDA-catalyzed direct arylation of benzene also
involved an aryl radical anion intermediate (Scheme 3). In fact, a
radical anion could be generated from vicinal diamines (such as
ethylenediamine, DMEDA, etc.) in the presence of KOtBu.12 It
could activate ArI to form the aryl radical anion intermediates.
Figure 1. (A) Reaction profile of the direct arylation of benzene with 1a.
(B) Distribution of bis-arylated 3j and monoarylated 1j with reaction time
during the reaction of 4a with benzene. (C) The reaction profiles (amount
of 1j or 4a and reaction time) of the direct arylations of benzene with 4a
and 1j, respectively. (D) The reaction profiles of the competitive reaction
of equal molar 1j and 4a with benzene (for more details, see Supporting
Information).
benzene in the presence of potassium tert-butoxide. The arylation
of unactivated benzene with aryl iodides, or aryl bromides and even
chlorides under the assistance of an iodo-group, could simply take
place at 80 °C. The new methodology presumably involves an aryl
radical anion as an intermediate. This finding offers an excellent
option toward establishing a new horizon for direct C-H/cross-
coupling reactions. The detailed kinetic and mechanistic studies
are currently undergoing in our laboratory, and will be reported in
due course.
Scheme 3. Speculated Intermediate of Reaction of Dihalobenzene
with Benzene
Acknowledgment. This work was supported by the NSFC of
China (20702040, 20832003, 20972118, and 20972119). We thank
Prof. Xinquan Hu’s proofreading and valuable discussion.
Supporting Information Available: Experimental procedures and
compound characterization data. This material is available free of charge
The reaction profile of the direct arylation of benzene with 1a
indicated the existence of an inductive period (Figure 1A). Further
monitoring of the product distribution within time intervals revealed
that the yield of bis-arylated product 3j increased with time, while
the monoarylated product 1j remained around 10% during the
reaction period (Figure 1B). The reaction profile in Figure 1C clearly
illustrated that the reactivity of 1j is less than that of 4a. A further
competitive experiment with equal molar amounts of 4a and 1j in
the presence of benzene was also carried out (Figure 1D). The
consumption of 4a is much faster than that of 1j. The formation of
3j was related to the consumption of 4a.
The above reaction profiles in Figure 1 unambiguously ruled out
path A but supported path B in Scheme 3. It also indicates that
intermediate I has a higher reactivity than 1j and 4a (X ) I).
According to the DFT calculations (see Supporting Information),
the C-I bond distance of intermediate I is 0.300 nm, which is 0.085
nm longer than that of 1j (0.215 nm) and 0.086 nm longer than
that of 4a (0.214 nm). These are consistent with the hypothesis in
Scheme 3. The C-Cl bond of the 4-chlorobiphenyl radical anion
was 0.266 nm, which is 0.090 nm longer than that of 4-chlorobi-
phenyl (0.176 nm). These calculation data could rationalize the
“abnormal” reactivities of dihalobenzenes in Table 3.
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In summary, we uncovered a conceptually different approach
toward biaryl syntheses by using an organomolecule (DMEDA) as
a catalyst to promote the direct C-H arylation of unactivated
9
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