Chemistry Reference
In-Depth Information
F
R
OH
KHF
2
R
B
K
B
F
OH
F
2.214
2.215
Scheme 2.74
1. Py.BH
3
, I
2
2. KHF
2
, MeOH
BF
3
K
2.216
2.217
Scheme 2.75
N
Pd(OAc)
2
, RuPhos,
Na
2
CO
3
+
N
N
H
KF
3
B
N
Cl
H
2.218
2.220
2.219
Scheme 2.76
Another solution is to employ trifluoroborate salts
2.215
, which can be prepared from the boronic acid
by treatment with potassium hydrogen fluoride (Scheme 2.74). They can also be prepared from alkyl bo-
ranes in a similar way (Scheme 2.75).
82
These stable salts can be efficiently employed in Suzuki coupling
reactions (Scheme 2.76).
83
One application is in the synthesis of the unusual amino acid, trityrosine
2.226
(Scheme 2.77).
84
In this synthesis an aryl diiodide
2.222
was coupled with a trifluoroborate salt
2.224
that
had been formed by Miyaura borylation of iodide
2.223
followed by KHF
2
treatment. Global debenzylation
of coupling product
2.225
gave the product
2.226
. Another example of the use of a trifluoroborate salt can be
found in Scheme 2.88.
The installation of a vinyl group by Suzuki coupling presents a particular problem because vinyl boronic
acid is unstable, readily undergoing polymerization. In a study of vinylation in order to make a polymer
precursor, the vinyl trifluoroborate salt was found to be effective, giving the cleanest product
2.228
ona72g
scale (Scheme 2.78).
85
2.6.1 Alkenyl Borane Coupling Reactions
Alkenyl boranes are most commonly prepared by the
cis
-hydroboration of alkynes using catechol borane
(Scheme 2.79). The resulting catechol boranes may be directly coupled, or hydrolysed to the boronic acid,
prior to coupling.
This method was employed in the stereospecific construction of a silyl diene in a synthesis of chlorotri-
cholide (Scheme 2.80). The boronic acid partner
2.233
was prepared by hydroboration and hydrolysis. The
vinyl iodide was
2.235
prepared by hydroalumination-iodination. The silyl group was included in order to
boost stereoselectivity in the later Diels-Alder reaction, but also served to facilitate the synthesis of the vinyl
iodide coupling partner.
86
The Suzuki coupling yielded the diene
2.236
with retention of the stereochemistry
of both alkenes. Thallium hydroxide was employed as the Lewis base. Thallium-containing Lewis bases have
been found to be advantageous in a number of cases, but the toxicity of thallium is a serious concern.
Similarly, Suzuki coupling of a vinyl boronic acid was employed for formation of a diene
2.238
in a
synthesis of dictyostatin (Scheme 2.81).
87
