Handbook of Functionalized Organometallics Applications in S

3.2 Preparation and Reaction of Functionalized Aryl and Heteroaryl Boranes
However, aryl bromides substituted with electron-donating groups such as NMe 2
and OMe poorly undergo the palladium-acetate-catalyzed cross-coupling. This
modified procedure is advantageous compared to the original Miyaura synthesis
in ease of work-up, catalyst removal and low catalyst cost (Scheme 3.14).
O O
FG
Br
B
O
B
O
37
aorb
FG = 4-COMe; 3-CN; 4-NO 2; 2-Me und 4-CO 2Me
(a) Pd(OAc) 2 (3 mol %), KOAc, DMF, 80 ºC; (b) Pd/C (3 mol %)
Scheme 3.14 Ligandless palladium-catalyzed cross-coupling.
FG
O
B
O
70 - 90 %
Wang has synthesized boronic acids derived from nitrophenols such as 45 and
46 with possible use as a recognition and signalling unit for the construction of
polyboronic acid sensors [21]. Synthesis of boronic acid 45 involves cross-coupling
of 2-bromo-4-nitroanisole with 37 followed by hydrolysis of boronate ester and
deprotection of the methoxy group, whereas the dinitrophenyl boronic acid 46 is
prepared by nitration of 2-methoxyboronic acid and subsequent cleavage of the
methoxy ether with BBr 3. The resulting functionalized boronic acids are both
obtained in 90% yield (Scheme 3.15).
OMe
Br
NO 2
OMe
B(OH) 2
O O
B B
O
37
O
PdCl2(dppf), KOAc, DMSO
H2SO4, HNO3 -10ºC
O 2N
OMe O
B
O
NO 2
OMe
NO 2
Scheme 3.15 Synthesis of functionalized aryl boranes by palladium-catalyzed
cross-couplingor nitration.
B(OH) 2
1) NaIO4, 2 N HCl, 70 %
2) BBr3,CH2Cl2 BBr 3, CH 2Cl 2
O 2N
OH
NO 2
OH
NO 2
OH
B
OH
20 % 45: 90 %
50 % 46: 90%
Yamamoto has reported the synthesis of (4-boronylphenyl)alanine (BPA), used
clinically for treatment of malignant melanoma and brain tumors in neutron capture
therapy by Pd-catalyzed coupling of triflate 47 with the diboron derivative
48 [22]. The boronic ester 49 could be easily cleaved by hydrogenolysis to give
L-BPA 50 in 74% yield, whereas the corresponding pinacol ester yielded mixture
53
B(OH) 2