3
organocatalysis pathway.17 Though the metal-free Suzuki-
very broad with regard to both reacting partners. The boronic
acids containing electron donating substituent facilitates the
coupling thereby furnishing the desired products in good to
excellent yields. Similarly, the boronic acids with electron
withdrawing groups also reacted efficiently albeit giving slightly
lower yields. Easy access to halo boronic acids is worth
mentioning as they furnish the products with additional synthetic
handle for further synthetic manipulation. Similarly
electronically and structurally diverse benzoyl chlorides were
form to couple with phenyl boronic acids in good to better yields.
There was no appreciable change in reactivity observed in most
of the cases. Boronic acid derivatives of heterocycles such as
thiophene were smoothly transformed into desired product in
good yields. Thus the heteroaryl boronic acid (thiophene-3-
boronic acid) did couple with benzoyl chloride, 4-nitro-benzoyl
chloride and 4-methyl benzoyl chloride in good isolated yields
(80-82 % yields). The transformation was less sensitive to steric
effects as sterically hindered naphthyl boronic acid underwent
this coupling to give 92 % yield with benzoyl chloride, 90 %
yield with 4-nitro-benzoyl chloride and 87 % yield with 4-
methyl-benzoyl chloride.
Miyaura coupling occurs through base induced
protodeborylation18 type nucleophilic aromatic substitution
pathways.19 In this metal-free base induced Suzuki type cross-
coupling of acyl chlorides with arylboronic acids the mechanism
is unclear.
In this work, we developed an efficient, simple practical
route for the synthesis of dissymmetric ketones by transition
metal-free base induced cross-coupling reactions in toluene in
short reaction time under air. The method allows broad reaction
scope for the transformation of range of benzoyl chlorides and
aryl boronic acids. The protocol uses readily available reagents
and no additional ligand and additive were required with
moderate functional group tolerance. Additionally, the synthesis
can be performed under economically favorable conditions.
Experimental Section:
An oven-dried Schlenk flask, equipped with a magnetic
stir bar, septum and a condenser was charged with acyl chloride
(1.0 mmol), arylboronic acid (1.0 mmol), NaOH (4 mmol) and
toluene (5.0 mL). The flask was immersed in an oil bath and
stirred at 100 °C. Upon complete consumption of starting
materials as determined by GC analysis, the water (10.0 mL) was
added. The reaction mixture was extracted with diethyl ether (3 ×
5.0 mL). The combined organic layer was collected, dried over
anhydrous Na2SO4 and concentrated in vacuum to afford product
which was purified by silica gel column chromatography (eluent:
n-hexane/ethyl acetate = 9:1).
Table 3
The transition metal-free Suzuki type cross-coupling reaction of
various acyl chlorides and arylboronic acids.a
O
O
O
O
O
Acknowledgments
Cl
Br
We wish to express our appreciation to the Science and
Engineering Research Board, Department of Science and
Technology (SERB-DST), Government of India, New Delhi, for
supporting this work under the scheme of Start-Up research
grants for Young Scientists (SB/FT/CS-153/2013).
C1, 95 %
O
C2, 91 %
C3, 92 %
O
C5, 89 %
C4, 94 %
O
O
O
Cl
S
O2N
F
CN
Cl
C7, 85 %
C6, 88 %
C10, 95 %
O
C9, 92 %
C8, 82 %
O
O
O
References and notes
O2N
O2N
Cl
O2N
O2N
C14, 85 %
C13, 88 %
O
C12, 90 %
O
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C11, 94 %
O
O
Cl
S
O2N
CN
O2N
O2N
F
O2N
C16, 86 % Cl
O
C18, 92 %
C15, 89 %
O
C17, 81 %
O
2. (a) Magano J, Dunetz JR, Chem. Rev. 2011; 111: 2177; (b)
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O
Br
C19, 93 %
O
C20, 90 %
C21, 87 %
Cl
C22, 90 %
O
O
O
O
I
S
C26, 80 %
CN
Cl
Cl
C24, 94 %
O
C27, 92 %
O
C23, 93 %
C25, 85 %
O
O
O
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1898.
F
Cl
F
F
CN
F
F
C28, 90 %
C29, 90 %
C30, 94 %
C31, 91 %
C32, 93 %
Reaction conditions: acyl chlorides (1.0 mmol), arylboronic acids (1.0 mmol), NaOH (4.0 mmol),
Toluene (5.0 mL), at 100 °C. Isolated yields in 2 h after column chromatography.
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It has been known that the transition metal-free cross-coupling
occurred through the different pathways like radical type
homolytic aromatic substitution (HAS) reactions,12 radical cation
type hyperiodine-mediated oxidative coupling reactions,13
cationic type oxidative coupling reactions,14 electrophilic
aromatic substitution,15 aryne pathway,16 and the classical