Pd(II)/PhI(OAc)2 promoted direct cross coupling of glucals with aromatic acids

Article abstract of DOI:10.1016/j.carres.2018.03.002

A highly efficient oxidative C2-aroyloxylation of D-glucal with aromatic carboxylic acids has been achieved for the first time using 5 mol% Pd(OAc)₂ and 1 equiv of PhI(OAc)₂ to produce C2-aroyloxyglycals in good yields. The use of excess of PhI(OAc)₂ (2 equiv) provides C2-acyloxyglycal exclusively.

Full text of DOI:10.1016/j.carres.2018.03.002

Accepted Manuscript
Pd(II)/PhI(OAc) promoted direct cross coupling of glucals with aromatic acids
2
Zubeda Begum, G. Shankar, K. Sirisha, B.V. Subba Reddy
PII:
S0008-6215(18)30078-8
10.1016/j.carres.2018.03.002
CAR 7533
DOI:
Reference:
To appear in: Carbohydrate Research
Received Date: 6 February 2018
Revised Date: 4 March 2018
Accepted Date: 4 March 2018
Please cite this article as: Z. Begum, G. Shankar, K. Sirisha, B.V.S. Reddy, Pd(II)/PhI(OAc) promoted
2
direct cross coupling of glucals with aromatic acids, Carbohydrate Research (2018), doi: 10.1016/
j.carres.2018.03.002.
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Pd(II)/PhI(OAc) promoted direct cross
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coupling of glucals with aromatic acids
Zubeda Begum, G. Shankar, K. Sirisha, B. V. Subba Reddy

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Pd(II)/PhI(OAc) promoted direct cross
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coupling of glucals with aromatic acids
Zubeda Begum, G. Shankar, K. Sirisha, B. V. Subba Reddy

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Carbohydrate Research
journal homepage: www.elsevier.com
Pd(II)/PhI(OAc) promoted direct cross coupling of glucals with aromatic acids
2
a
a
b
a*
Zubeda Begum, G. Shankar, K. Sirisha, B. V. Subba Reddy
a
b
Centre for Semiochemicals, Centre for Nuclear Magnetic Resonance, CSIR-Indian Institute of Chemical Technology, Hyderabad –500 007,
India. E-mail: basireddy@iict.res.in; www.iictindia.org
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A highly efficient oxidative C2-aroyloxylation of D-glucal with aromatic
carboxylic acids has been achieved for the first time using 5 mol% Pd(OAc) and
2
1
equiv of PhI(OAc) to produce C2-aroyloxyglycals in good yields. The use of
2
excess of PhI(OAc) (2 equiv) provides C2-acyloxyglycal exclusively.
2
Available online
2
009 Elsevier Ltd. All rights reserved.
Keywords: C2-Aroyloxyglycals; C-H activation; D-
Glucal; Hypervalent iodonium reagent; Transition
metal catalysis
PhI(OAc) through an oxidative cross-coupling of glycals
with carboxylic acids (Scheme 1).
Introduction
2
Transition metal catalyzed modification of glycals is a
powerful tool to produce substituted glycals and glycosides.
[1]
In particular, the cross-coupling of glycals with activated
alkenes through a transition metal catalysis is a versatile
[2]
strategy to generate C-2 functionalized glycals. These C-2
substituted glycals are common intermediates for natural
[3,4]
products and other biological active molecules.
On the
other hand, 2-hydroxy-/2-acyloxyglycals are common
building blocks for the synthesis of O-glycosides, C-
Scheme 1. C2-aroyloxylation of 3,4,6-triacetyl-D-glucal
[5]
glycosides, S-glycosides and N-glycosides. Generally, these
[
6]
2
-acetoxy glycals are prepared from glycosyl bromides, or
Initially, we attempted the cross-coupling of 3,4,6-triacetyl-D-
glucal (1) with benzoic acid (2a) in the presence of 5 mol% of
[7]
from thioglycosides. Subsequently, alternative routes for 2-
[8]
hydroxyglycals have been developed.
Recently, C2-
Pd(OAc)
under diverse reaction conditions. The reaction was
2
acyloxyglycals are preapred from glucose pentaacetate in two
carried out with 1 equiv of benzoic acid and 1 equiv of
PhI(OAc) at 80 C. The desired product was obtained in 70%
2
[9]
o
steps using I /PMHS and excess of DBU. In addition, the
2
substrtae directed aroyloxylation of aromatic system has been
also reported using a transition metal catalysis. However,
there are no reports on the C2-aroyloxylation of glycals.
yield as a mixture of 3a and 4 in a 1:1 ratio (Table 1, entry a).
To improve the ratio, the reaction was performed again with 2
equiv of benzoic acid and 1 equiv of PhI(OAc) at the same
2
[10]
temperature. To our delight, the ratio of 3a and 4 was
Results and Discussion
increased to 3:1 (Table 1, entry b). To know the effect of
temperature, the above reaction was carried out at 100 C. A
slight increase in yield was observed (Table 1, entry c). The
best conversion and selectivity were achieved when the
o
Following our interest on transition metal catalyzed C-H bond
[11]
functionalization, we herein report a novel strategy for the
synthesis of C2 functionalized glycals using a catalytic
amount of Pd(OAc)2 and a stoichiometric amount of
reaction was conducted using 2 equiv of benzoic acid and 1.0
o
equiv of PhI(OAc) at 120 C (Table 1, entry d). A trace
2

2
Carbohydrate Research
amount of desired product was formed in
A
t
C
he
C
a
E
bse
PT
nc
E
e
D
of MA11
N
H
U
},
S
a
C
lo
R
ngIP
with scalar coupling constant analysis have
T
PhI(OAc) (Table 1, entry e). On the other hand, in the
absence of PhCO H, the product 4 was formed exclusively
confirmed that the six-membered ring is in half-chair
conformation. The energy-minimized structure of 3k
adequately supports our NMR analysis (Figure 1).
2
2
(
Table 1, entry f). To know the effect of the solvent, the
reaction was performed in different solvents such as DMF,
,4-dioxane and toluene. These solvents failed to give the
1
required product (Table 1, entries, g-i). Furthermore, no
desired product was obtained in the absence of Pd(OAc)2
(
Table 1, entry j).
Table1. Optimization of reaction conditions
____________________________________________
_
Entry PhCO H PhI(OAc)2 Pd(OAc)2 Solvent Temp Ratio Yield
2
o
a
(
equiv) (equiv)
(mol%)
( C) (3/4) (%)
_
a
______________________________________________________
1.0
2.0
2.0
2.0
2.0
-
1.0
1.0
1.0
1.0
-
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
5.0
-
CH
3
CN
CN
CN
80
(50/50) (80)
b
c
d
e
f
CH
3
80
(75/25) (80)
(75/25) (85)
(98/2) (90)
(99/0) (10)
(0/99) (90)
CH
3
100
120
120
120
120
120
120
120
CH
3
CN
CH
3
CN
2.0
0.75
0.75
0.75
0.75
CH
3
CN
Figure 1. Characteristic NOEs and energy-minimized
structure of 3k
g
h
i
2.0
2.0
2.0
2.0
DMF
-
-
-
-
Table 2. Synthesis of C2-aroyloxy-glycals
Dioxane
Toluene
O
O
AcO
Pd(OAc)
2
(5 mol%)
AcO
AcO
O
-
-
+
ArCO
2
H
AcO
PhI(OAc)
2
(1 equiv)
O
Ar
O
1
OAc 2 (2 equiv)
3
OAc
j
CH
3
CN
-
-
_
_____________________________________________________________
O
O
O
AcO
AcO
O
AcO
AcO
O
O
AcO
AcO
Br
a
Yield refers to pure products after chromatography.
O
O
OAc
a, 87%
OAc
OAc
Cl
3
Inspired by these initial results, we extended this method to
different substrates bearing various substituents such as
halide, methyl, methoxy, trifluoromethyl and nitro groups on
the aromatic ring of the carboxylic acid (Table 2). This
method is compatible and quite successful with a wide range
of aromatic carboxylic acids. No dehalogenation was
observed in case of chloro-, bromo-, and fluoro- substituted
aromatic acids (Table 2, entries b,c,j,m,n & o). The
substituent present on the aromatic rind had shown some
effect on the conversion. Indeed, electron rich aromatic
carboxylic acids are found to be superior than electron
deficient counter parts. A sterically hindered 2-naphthoic acid
also gave the product in good yield (Table 2, entry l). The
structure of 3k was confirmed by the incisive NMR studies
and J-coupling analysis (Figure 1). From the one dimensional
3b, 90%
3c
,
89%
O
O
O
AcO
AcO
O
AcO
AcO
O
AcO
AcO
CF3
O
O
O
O
OAc
OAc
OAc
Me
NO2
3
d, 91%
3e
, 90%
3f
,78%
O
O
O
AcO
AcO
O
OMe
AcO
AcO
O
Me
AcO
AcO
O
O
O
O
OAc
OAc
OAc
MeO
OMe
OMe
3
g, 86%
3h, 89%
3i, 90%
Cl
O
O
O
AcO
AcO
O
O
AcO
O
AcO
AcO
O
AcO
O
O
OAc
OAc
OAc
F
OMe
3
j, 89%
3k, 80%
3l, 86%
NO
2
O
O
O
AcO
AcO
O
O
AcO
Br
O
Cl
AcO
AcO
O
F
1
AcO
O
O
H NMR data, the observed strong scalar coupling constants,
OAc
OAc
OAc
3o
Cl
3
J4-H/3-H/5-H = 4.7, clearly indicate that the 4-H protons are in
3m
, 86%
3n, 82%
, 84%
Br
axial position in the six-membered ring. 3-H and their
corresponding scalar coupling values J3-H/4-H = 4.3Hz,
respectively have suggested that 3H protons are in equatorial
position in the six membered ring. The characteristic NOE
correlations {5H-4H}, {4H-3H}, {4H-6H(a)}, and {10H-
O
AcO
AcO
O
O
3
OAc
Ph
3p, 90%
aAll products were characterzed by NMR, IR and mass spectroscopy.
bYield refers to pure products after chromatography.

3
ACCEPTED MANU[2
S
]
C
E.
R
Boyd, R. V. H. Jones, P. Quayle, A. J. Waring,
I
P
T
Tetrahedron Lett. 47 (2006) 7983-7986.
The use of 2 equiv of PhI(OAc) , the product 4 was formed
2
[
3] (a) D. Ellis, S. E. Norman, H. M. I. Osborn,
Tetrahedron 64 (2008) 2832-2854. (b) P. A. Colinas,
R. D. Bravo, Carbohydr. Res. 342 (2007) 2297-2302.
exclusively in 90% yield. In this case, PhI(OAc) acts as an
2
oxidant as well as the source of acetoxy group (Scheme 2).
(
1
c) R. Saeeng, M. Isobe, Org. Lett., 7 (2005) 1585-
588. (d) M. Hayashi, S. Nakayama, H. Kawabata,
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Scheme 2. C2-acyloxylation of 3,4,6-triacetyl-D-glucal
(
The structure of 4 was confirmed by comparing its spectral
data with the data reported in the literature.
[3i]
4
Conclusion
3
Chem. 54 (1989) 2103-2112. (f) S. Hanessian, A. M.
Faucher, S. Lerger, Tetrahedron 46 (1990) 231-243.
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E. Norman, H. M. I. Osborn, Tetrahedron, 64 (2008)
In summary, a novel strategy has been developed
for the synthesis C2 functionalized glycals through
an oxidative cross coupling of glucal with aromatic
carboxylic acids. These C2-acyloxyglycals are
useful building blocks for the synthesis of
biologically active natural products. This method is
simple, exquisitely selective and works with a
diverse range of aromatic acids, which makes it an
attractive strategy.
[
2
832-2854. (d) P. A. Colinas, R. D. Bravo,
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Supporting Information
3
231. (i) U. E. Udodong, B. Fraser-Reid, J. Org.
1
13
Characterization data and copies of H & C NMR
spectra of products 3a-p and 4 are provided in the
supporting information.
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Faucher, S. Lérger, Tetrahedron 46 (1990) 231-243.
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Yarlagadda, B. Sridhar, Org. Lett.
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Highlights
•
•
•
•
First report on aroyloxylation of glycals at C2 position.
C2-acyloxyglycals are useful chiral building blocks.
It is compatible with various functional groups.
This method works with a diverse range of acids.