Communication
a
Table 1. Optimization of reaction conditions.
substituted 3-bromopyridine (product 14), were demonstrated
to be competent coupling partners in this reaction. However,
3-bromopyridine derivatives with no substitution at C2 are
susceptible to a Cu-catalyzed cine-substitution, as demon-
[20]
strated in previous studies.
[17]
A proposed pathway from intermediate 2 to product 3 is
shown in Scheme 4a. An allylic transmetallation is likely to
occur via transition state 16 to generate allylÀ Pd complex
[21]
1
7. Due to the steric bulk of QPhos, it is likely that rapid
reductive elimination of 17 occurs prior to isomerization via π-
allyl intermediates that might lead to the minor isomer (e.g.,
[19]
4
). In comparison to our previously reported arylboration of
isoprene, use of QPhos-ligated Pd results in selective 1,4-
[13e]
arylboration.
As shown in Scheme 4b, a 1,4-transmetalation
pathway is unlikely to occur due to unfavorable steric
interactions. Instead, the transmetallation likely occurs through
transition state 19, and ultimately product following a rapid
reductive elimination.
In order to highlight the scalability of the difunctionaliza-
tion, a gram scale reaction was performed to generate 1.10 g
of 5 (Scheme 5). To exhibit the utility of the boronic ester unit,
conversion of the CÀ B bond to various groups was inves-
tigated. Mild oxidation of 5 using sodium perborate provided
homoallylic alcohol 20. Additionally, CÀ C bond formation
a
b
See the ESI for experimental details. Yields were determined by
1
H NMR analysis of the crude reaction mixture with an internal
c
standard. Product 4 was obtained as a 1:1 mixture of E:Z isomers.
d
Reaction run with NaOt-Bu instead of KOt-Bu.
arylboration product depending on transmetalation and reduc-
tive elimination pathways and rates.
We began our investigation by probing the reactivity and
selectivity of the arylboration of butadiene with various
ligands on Pd (Table 1). Poor reactivity was observed in
entries 1–2; however, use of PtBu -ligated Pd precatalyst led
3
to product formation but with low yield and selectivity
(entry 3). High yield and selectivity for the 1,2-arylboration
product were observed when the exceptionally large QPhos
[19]
was used as the ligand for Pd. We next explored whether
changing the ligand on Cu would improve the reaction. While
related NHCÀ CuCl complexes behaved similarly to
IMesÀ CuCl (entry 5), phosphineÀ Cu complexes did not
function well (entries 6–7). Additionally, we found that
selectivity for the 1,2-arylboration product was improved
when NaOtÀ Bu was used in place of KOtÀ Bu; however, the
yield was considerably lower (entry 8). Finally, attempted
reaction with the corresponding arylchloride, iodide and
triflate did not lead to product formation.
With an optimized set of conditions in hand, we probed the
scope of this transformation (Scheme 3). The 1,2-arylboration
of butadiene was found to proceed with arylbromides bearing
electron-withdrawing groups, providing products 5 and 6 in
high yield and selectivity. Products incorporating arenes with
electron-donating groups were also produced in good yield (7–
8
, 10). The reaction was shown to be tolerant of functional
Scheme 3. Substrate scope. See the ESI for experimental details.
Yields are for the isolated purified product. Yields in parentheses
groups such as esters and amides (6, 11–12). Additionally,
sterically demanding substituents did not inhibit reactivity as
shown by the synthesis of 8–10 in good yield. Finally, select
heteroaryl bromides, 3-bromothiophene (product 13) and a
1
were determined by H NMR analysis of the reaction mixture with an
a
b
internal standard. Isolated as a 9:1 mixture of regioisomers.
Isolated as an 8:1 mixture of regioisomers.
Isr. J. Chem. 2019, 59, 1–5
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2
��
These are not the final page numbers!
Bergmann, Allison M.
