Solvent Solvent Solvent Solvent Solvent Solvent and substra and

Solvent and substrate effects on the stereoselective Heck
arylations of 3--cyclopentenol
cyclopentenol
Ricardo A
A. Angnes,† Juliana M
M. de Oliveira,† Vitor H. M. da Silva,‡ Bruno M. Servilha,‡
Ataualpa A. C. Braga‡ and Carlos Roque D
D.. Correia†*
†
Departamento de Química Orgânica, Universidade Estadual de Campinas, Cidade Universitária, Zeferino
Vaz, s/n, Campinas, SP, Brazil
‡
Departamento de Química Fundamental, Universidade de São Paulo, Lineu Prestes, 748, Bl. 05 sup. Sl.
0552 Butantã, São Paulo, SP, Brazil.
*[email protected]
[email protected]
[email protected]:
Keywords: Enantioselective catalysis, Heck-Matsuda,
Heck Matsuda, homogeneous
omogeneous catalysis
INTRODUCTI
INTRODUCTI
ODUCTION
ON
Recently, we have demonstrated the synthetic
potential of the enantioselective HeckHeck-Matsuda
Matsuda
desymmetrization strategy for the construction of
important arylated five
five-membered
membered carboc
carbocyclic
yclic
1
scaffolds in a straightforward and efficient manner.
As a drawback the reaction usually provided a
mixture of two Heck products, the allylic 4
4-aryl
aryl
cyclopentenol
cyclopentenols 3,
3 as major product,
product and its isomer,
isomer,
the 3--aryl
aryl cyclopentanones
cyclopentanone
4 as byproducts
(Scheme 1
1).
OH
Pre
eviou
us res
sult s
+
CONCLUSION
Heck-M
H
Matsud
da
condiictionss
R
+
ref.
f.2
1
2
R
R
3
4
20-70
0% yie
eld
89-9
99% ee
e
16-27%
1
% yie
eld
17-56
56% ee
e
R = ED
DG, EWG
E
Rec
cent impro
i
ov em
ment s
N 2BF
B 4
+
1
O
N 2BF
F4
OH
O
OH
predicted in silico to be even more pronounced in
toluene. These results prompted us to investigate
the use of toluene as the reaction solvent in order to
obtain the d
desired
esired aryl cyclopentenols 3 with high
enantioselectivity, while minimizing the formation of
the 33-aryl
aryl cyclopentanones byproducts.
Gratifyingly
Gratifyingly,, performing
performing the reaction in pure
toluene le
led
d to the 4
4-aryl
aryl cyclopentenols 3 as the
exclusive product although in rather low yield.
However, w
when
hen we used a binary mixture of toluene
containing a small fraction of methanol the 4-aryl
4 aryl
cyclopenteno
cyclopentenolss 3 were obtained as the exclusive
products in high yield
yields and enantiosselectivities
R
2
New
w HeckkMa
atsuda
cond
dictionss
3
R = EDG,
E
EWG
G
Aid
d of c
comp
putat ional
i
l stud
dy
O
OH
Both the role of the hydroxyl group in 3
3cyclopenten
cyclopenten-1--ol
ol and the reaction medium were
further clarified by this study.
The new insights allowed us to drasticly increase
selectivity of the arylation of 3
3-cyclopenten
cyclopenten
cyclopenten-1
1-ol
ol with
key modifications on the react
reaction
ion conditions.
ACKNOWLEDG
ACKNOWLEDGEMENTS
MENTS
R
Hig
gher yields
y
s;
H
Higherr ee;
Exclus
E
sive produ
p
uct!!!
We wish to thank FAPESP for the financial support
Scheme 1. Previous results and recent improvements
improvements.
REFERENCE
REFERENCES
S
1
RESULTS AND DISCUSSION
Angnes, R. A.; Oliveira, J. M.; Oliveira, C. C.; Martins, N. C.;
Correia, C. R. D. Chem. Eur. J. 2014,
2014, 20,, 13117
13117–
–13121
13121
In search for ways to obtain exclusively the desired
4-aryl
4 aryl cyclopentenol 3,, we
we performed transition
transition state
energy computational calculations for the migratory
insertion step - which is mainly responsible for the
stereochemical outcome of the reaction. It was
found that the hydroxyl group of the starting
cyclopentenol has a strong stabilizing effect when at
the endo position,
sition, putting this group closer to the
cationic palladium. This stabilizing effect was
16
6th Brazilian Meeting on Organic Synthesis – 16
6th BMOS – November 15--18,, 201
2015 - Búzios
Búzios,, Brazil