Carbon–Carbon Bond Forming by Ball Milling - Ball Milling Towards Green Synthesis: Applications, Projects, Challenges - page 36

(Scheme 2.2). 9 The influence of the base and milling auxiliary was studied in
this work. Additionally, the ratio of DABCO and phenylacetylene was varied.
A minimum of 1.5 equiv. base was necessary to reach high conversion.
Beside substituted phenylacetylene long-chained alkynes were successfully
tested in the coupling (45-92% yield). Furthermore, 2-iodothiophene was
converted under these conditions and double Sonogashira reactions were
also possible.
The coupling of phenylacetylene and 4-iodoanisole accomplished in a
planetary ball mill (Pulverisette 7, Fritsch GmbH) led to 57% isolated yield
after 20 min milling. 10 As the addition of Cu caused lower selectivity, it was
possible to dispense with this co-catalyst. Beside Pd(OAc) 2 , PdCl 2 and
[Pd(PPh 3 ) 4 ] were tested successfully in this reaction.

2.2.2 Suzuki-Miyaura Cross-coupling
The cross-coupling of 2-bromonaphthalene (Scheme 2.3) gave moderate
yields (21-53%) for different bases after 30 min milling in a planetary ball
mill (Pulverisette 7, Fritsch GmbH). 11 Best results were obtained in the
presence of K 2 CO 3 and 2 equiv. of phenylboronic acid. Various aryl halides
were tested in this reaction, giving 0-96% analytical yield in 30-50 min
under an air atmosphere.
This work was re-considered by G´lvez et al. in analyzing the results with
chemometric methods, like multi-linear regression or linear discriminant an-
alysis. 12 By means of the regression equations and the Moran autocorrelation
indices it was possible to predict the influence of electron-withdrawing
or -donating groups and reaction time. The calculations were very close to
the experimental results; consequently, time and costs can be saved.
In 2003 investigations of the reaction of 4-bromotoluene and phe-
nylboronic acid revealed that Pd(OAc) 2 is a better catalyst than PdCl 2 and
NEt 3 a significantly better base than Na 2 CO 3 (Scheme 2.4). 13 After grinding

5 mol% Pd(OAc) 2
1.25 equiv. DABCO
SiO 2
PBM
800 min -1 , 20 min

I

+

R 1 R 2

R 1

R 2

R 1 = H, 2-CH 3 , 4-CH 3 , 2-OCH 3 , 4-OCH 3 , 4-Ac
R 2 = H, 4-CH 3 , 4-OCH 3 , 4-F

Scheme 2.2 Copper-free Sonogashira cross-coupling with DABCO as base.

5 mol% Pd(PPh 3 ) 4
3 equiv. K 2 CO 3
NaCl
PBM
800 min -1 , 30 min

Br

B(OH) 2

+

Scheme 2.3 Suzuki cross-coupling of phenylboronic acid with 2-bromonaphthalene.