On the Origin of Regioselectivity in Palladium-Catalyzed Oxidation of Glucosides

Article abstract of DOI:10.1002/ejoc.202001453

The palladium-catalyzed oxidation of glucopyranosides has been investigated using relativistic density functional theory (DFT) at ZORA-BLYP?D3(BJ)/TZ2P. The complete Gibbs free energy profiles for the oxidation of secondary hydroxy groups at C2, C3, and C

Full text of DOI:10.1002/ejoc.202001453

Communications
doi.org/10.1002/ejoc.202001453
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
On the Origin of Regioselectivity in Palladium-Catalyzed
Oxidation of Glucosides
[a, b]
[b]
[a]
[a]
Ieng Chim (Steven) Wan,
Trevor A. Hamlin, Niek N. H. M. Eisink, Nittert Marinus,
[c]
[c]
[c]
[a]
Casper de Boer, Christopher A. Vis, Jeroen D. C. Codée, Martin D. Witte,*
[a]
[b, d]
Adriaan J. Minnaard,* and F. Matthias Bickelhaupt*
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
[
1]
The palladium-catalyzed oxidation of glucopyranosides has
been investigated using relativistic density functional theory
saccharide units and coupling them together via glycosylation.
This synthetic approach is highly adaptable for various
oligosaccharides, but often contains numerous synthetic steps.
This is because carbohydrates contain multiple hydroxy (OH)
groups, which must first be selectively protected before
(DFT) at ZORA-BLYPÀ D3(BJ)/TZ2P. The complete Gibbs free
energy profiles for the oxidation of secondary hydroxy groups
at C2, C3, and C4 were computed for methyl β-glucoside and
methyl carba-β-glucoside. Both computations and oxidation
experiments on carba-glucosides demonstrate the crucial role
of the ring oxygen in the C3 regioselectivity observed during
the oxidation of glucosides. Analysis of the model systems for
oxidized methyl β-glucoside shows that the C3 oxidation
product is intrinsically favored in the presence of the ring
oxygen. Subsequent energy decomposition analysis (EDA) and
Hirschfeld charge analysis reveal the role of the ring oxygen: it
positively polarizes C1/C5 by inductive effects and disfavors any
subsequent buildup of positive charge at neighboring carbon
atoms, rendering C3 the most favored site for the β-hydride
elimination.
glycosylation can occur in
a
regio- and stereoselective
[1,2]
manner.
Site-selective (regioselective) reactions on (unpro-
tected) carbohydrates are, therefore, highly desired and are
often employed in the synthesis of functionalized carbohy-
drates. These reactions are well-developed to suit a variety of
monosaccharides with different stereochemical configuration
[
3]
and with controllable selectivity for the desired transformation
[
4,5]
[6]
and include, but are not limited to, acylation,
alkylation,
[7]
silylation, and oxidation. While the utility of acylation,
alkylation and silylation is clear in protecting-group chemistry,
[
8]
and acylation allows for limited subsequent modifications,
oxidation, on the other hand, allows further modifications such
[
9]
as epimerization, reductive amination, nucleophilic addition
[10]
and epoxidation without further protection. One of the most
well-studied oxidation reactions is the selective oxidation of
Carbohydrate chemistry remains a popular field of research due
to its importance in biology. Like other important bio-molecules
such as peptides, oligosaccharides are usually synthesized
chemically using a bottom-up approach, starting with mono-
[11]
pyranosides at C6 with TEMPO or transition metal catalysts
[12]
such as rhodium. This makes use of the inherent lack of steric
crowding of this primary hydroxy group. On the other hand,
regioselective oxidation of the secondary hydroxy groups is far
less common. Tin acetal mediated oxidation has been reported
to induce high regioselectivity in glycosides containing cis-
[
a] I. C. (Steven) Wan, Dr. N. N. H. M. Eisink, N. Marinus, Dr. M. D. Witte,
Prof. Dr. A. J. Minnaard
[
13]
Stratingh Institute for Chemistry,
University of Groningen
Nijenborgh 7, 9747 AG Groningen, The Netherlands
diols.
Our group reported on the catalytic C3-selective
[14]
[15]
oxidation of glucopyranosides using Waymouth’s catalyst 2
E-mail: m.d.witte@rug.nl
and has studied this reaction intensively (Scheme 1).
Since the discovery that glucosides can be oxidized
selectively at the C3 position, this methodology has been used
a.j.minnaard@rug.nl
[b] I. C. (Steven) Wan, Dr. T. A. Hamlin, Prof. F. M. Bickelhaupt
Department of Theoretical Chemistry
Amsterdam Institute of Molecular and Life Sciences (AIMMS),
Institution Amsterdam Center for Multiscale Modeling (ACMM),
Vrije Universiteit Amsterdam
De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
E-mail: f.m.bickelhaupt@vu.nl
c] C. de Boer, C. A. Vis, Prof. Dr. J. D. C. Codée
Leiden Institute of Chemistry,
Leiden University
Einsteinweg 55, 2333 CC Leiden, The Netherlands
d] Prof. F. M. Bickelhaupt
[
[
Institute for Molecules and Materials (IMM),
Radboud University
Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands
Supporting information for this article is available on the WWW under
https://doi.org/10.1002/ejoc.202001453
©
2020 The Authors. European Journal of Organic Chemistry published by
Wiley-VCH GmbH. This is an open access article under the terms of the
Creative Commons Attribution License, which permits use, distribution and
reproduction in any medium, provided the original work is properly cited.
Scheme 1. C3-selective oxidation of methyl β-glucoside with Waymouth’s
catalyst.
Eur. J. Org. Chem. 2021, 632–636
632
© 2020 The Authors. European Journal of Organic Chemistry
published by Wiley-VCH GmbH

Communications
doi.org/10.1002/ejoc.202001453
for the oxidation of various other monosaccharides and
using a combination of synthetic experiments and computa-
tional chemistry.
We began our study by investigating the palladium-
catalyzed oxidation of carba-β-glucose and carba-1-deoxyglu-
cose, where the ring oxygen has been substituted by a
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
[16]
oligosaccharides. In parallel, a number of studies have been
carried out to investigate and challenge the C3-selectivity of the
[17a,b]
palladium catalyzed oxidation.
The effect of the following
factors on C3-selecitivity have been studied (Scheme 2): 1) steric
crowding, 2) the stereochemical configuration and substitution
pattern of the glycoside substrate, 3) the solvent, and 4) the
temperature (Scheme 2). A competition experiment between 1
and its C4-THP protected variant showed that steric hindrance
near C3 only results in decreased reactivity. However, it did not
methylene (CH ) group. These substrates were synthesized (see
2
Supporting Information for experimental methods and charac-
terization) and subjected to oxidation conditions using catalyst
2. Interestingly and in contrast to methyl β-glucoside, the
oxidations of the carba-glucose derivatives were unselective
and provided a nearly equal amount of C2, C3, and C4 oxidation
products (and C1 oxidation in the case of carba-β-glucose)
(Scheme 3). These experiments suggest that the ring oxygen
plays a significant role in the regioselective C3 oxidation of
methyl β-glucoside. To understand the influence of the ring
oxygen on the regioselectivity, we next turn to density func-
tional theory (DFT) calculations.
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
[
17b]
affect the site-selectivity.
Varying substitution patterns on
[14,17a,b]
the glycoside do not alter the site-selectivity for C3 either.
The apparent loss in regioselectivity in xylosides, galactosides
and mannosides is the result of subsequent oxidation reactions
on the keto-product, which leads to over-oxidation and
[17b]
rearrangement.
Switching the solvent from a water/
acetonitrile mixture to DMSO or trifluoroethanol affects the
reaction rate, but in all cases the oxidation of the C3 OH is
All calculations were carried out using the Amsterdam
[14,17a]
[18]
favored.
Lastly, elevated reaction temperature erodes
Density Functional (ADF) program with dispersion-corrected
selectivity and results in the formation of the C4-oxidized
relativistic density functional theory at ZORA-BLYPÀ D3(BJ)/
[17a]
[19]
product.
Nevertheless, the C3 product dominates in all cases.
TZ2P. When noted, solvent effects of DMSO were modelled
[20]
Despite these mechanistic studies, the pertinent C3-selectivity
has not been adequately explained. In this study, we show that
the endocyclic oxygen is essential for the observed selectivity
with COSMO. Experimentally, it was observed that the use of
solvents other than DMSO results in the same regioselectivity
[14,17a]
but with differing reaction rates.
Throughout this paper,
we focus on the electronic energies of the molecular systems.
The Gibbs free energies at 298.15 K and 1 atm were calculated
for the reactions as well, and trends in reactivity turned out to
be unchanged. All open-shell systems were treated with the
spin-unrestricted formalism at ZORA-(U)BLYPÀ D3(BJ)/TZ2P.
The reaction energies were computed for the oxidation of
β-glucoside 1 with catalyst 2 in the presence of benzoquinone
3
, leading to all possible products and hydroquinone 4
(
Scheme 4). Based on the experimental results and computa-
[15]
tions by Waymouth and coworkers,
we ruled out the
possibility of oxidation at C6 and focused on the difference
between the seemingly similar equatorial secondary alcohols at
C2, C3, and C4. There are thus three possible outcomes of the
oxidation: oxidation at C2, C3, C4, forming 5.2, 5.3 and 5.4,
respectively. When the reaction was carried out at room
Scheme 2. Mechanistic studies carried out by our group and Waymouth and
coworkers.
Scheme 3. Oxidation of carba-glucosides in DMSO using catalyst 2. Only 1
eq benzoquinone was used. All yields are NMR yields.
Eur. J. Org. Chem. 2021, 632–636
www.eurjoc.org
633
© 2020 The Authors. European Journal of Organic Chemistry published
by Wiley-VCH GmbH

Communications
doi.org/10.1002/ejoc.202001453
begins with the reversible formation of hydroxyalkoxide
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
reactant complexes S2-4 (see Supplementary Information for
detailed structures). The β-hydride elimination is initiated by
the isomerization of S to the agostic alkoxide S’. A four-
membered transition state was found for the β-hydride
elimination T to form the corresponding palladium-hydride
complex U. The energy differences between the different forms
of S have little influence on the selectivity of the reaction, in
line with the experimental observations; no significant rate
difference was observed for the oxidation of glucoside 1, 2-
deoxyglucoside and 4-deoxyglucoside, despite the absence of a
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
[
17b]
chelation equilibrium in the latter two substrates.
~
The
À 1
Scheme 4. Computed Gibbs free reaction energies (kcalmol ) for the
À 1
5 kcalmol difference between the resting state S of C3 and
formation of oxidized products 5.2-5.4 computed at COSMO(DMSO)-ZORA-
BLYPÀ D3(BJ)/TZ2P.
C2/C4 could be attributed to the enhanced hydrogen bonding
2
+
between the electron deficient Pd bound OÀ H on C4 and O
lone pair on C6, which does not exist in either the resting state
S of C2 or C4. In the case of the resting state S of C2, a
hydrogen bond is present between the OÀ H on C4 and O lone
pair on C6, but it is very weak due to the fact that the acidity of
the OÀ H proton on C4 is not enhanced by the coordination of
temperature, product 5.3 was the observed product (Scheme 1).
Our calculations found that formation of product 5.3 is the
À 1
most exergonic reaction (~G =À 15.3 kcalmol ), followed by
rxn
À 1
2+
5
.4 (~Grxn =À 15.0 kcalmol ), and then 5.2 (~G
=
O to Pd . Structure T is the rate-determining transition state
rxn
À 1
À 1
À 13.8 kcalmol ). The small ~~G (0.3 kcalmol ) between 5.3
(TS) in all three pathways. The barrier of the C3-oxidation
rxn
�
À 1
�
and 5.4 suggests that the formation of the experimentally
observed 5.3 is under kinetic control, in line with the report of
pathway has the lowest ~E (12.7 kcalmol ). This ~E is
�
significantly lower than for C2/C4 oxidation (~~E of
[17a]
À 1
À 1
�
Waymouth
was heated.
The reaction mechanism proposed by Waymouth and co-
whereby 5.4 was formed only when the reaction
2.9 kcalmol and 2.0 kcalmol , respectively). The ~G follows
�
the same trend as the ~E . Calculations in DMSO (See
Supplementary Information for details) show the same trend in
[15]
�
workers
identifies the β-hydride elimination from a palla-
selectivity (~G : C3<C4<C2). In agreement with the previously
dium-alkoxide species to a palladium-hydride species forming
the carbonyl to be the rate determining step. The computed
activation barriers and reaction energies for this step of the
catalytic cycle associated with the formation of the oxidized
products 5.2, 5.3, and 5.4 are provided in Table 1. The reaction
reported experimental results, this indicates that solvation has
[14,17a]
little influence on the regioselectivity.
The electronic energies for the key structures of the
mechanistic steps S!S’!T!U in the oxidation of carba-
glucoside 1a were also computed (Table 1). Carba-glucoside 1a
has the same molecular structure as β-glucoside 1, except that
the ring oxygen in 1 is replaced by a methylene (CH ) group. In
2
Table 1. Electronic energies (~E) and [Gibbs free energies (~G)] (in
kcalmol ) of key intermediates and transition states in the β-hydride
elimination of 1 and 1a by the palladium-neocuproine complex relative to
the most stable reactant complex S3 computed at ZORA-BLYPÀ D3(BJ)/
TZ2P. The C3 pathway is depicted below.
contrast to the results obtained for 1, in the case of 1a all three
À 1
�
À 1
~
E values are within 1.5 kcalmol . Thus, the regioselectivity in
the oxidation reaction disappears when moving from 1 to 1a,
in line with our experimental observations shown in Scheme 3.
From these results, it becomes clear that the ring oxygen
has an influence on the regioselective oxidation of 1. The
correlation between the reactivity and the stability of the
resulting oxidized products (5.1, 5.2, and 5.3) prompted us to
next analyze model pyran systems 10a/b, 11a/b, 12a/b, and
1
3a/b (Scheme 5). These systems were judiciously selected with
the aim to minimize any complicating features such as intra-
molecular hydrogen bonding and to allow for the underlying
physics to be revealed. Furthermore, these model pyrans are
ideal probes to establish the relationship between the carbonyl
group that is formed during the reaction and the oxygen in the
ring.
As we can see, each isoelectronic structure has a thermody-
namic preference for the C3-keto structures (10a–13a) regard-
less of the substituents on the ring. Interestingly, the ring-
opened structures (14a/b) again show a clear energetic
preference for 14a, the linear chain C3-keto analog of 10a, over
1
Pathway
S
S’
T
U
C2
C3
C4
5.3 [5.3]
0.0 [0.0]
5.3 [5.8]
9.4 [7.9]
9.1 [7.2]
11.5 [9.2]
15.6 [11.7]
12.7 [9.1]
14.7 [10.7]
9.3 [6.2]
5.0 [1.9]
9.7 [5.9]
1
a
Pathway
S
S’
T
U
C2
C3
C4
6.4 [6.8]
0.0 [0.0]
6.5 [5.9]
11.0 [8.9]
10.2 [8.9]
12.3 [10.5]
14.9 [11.6]
13.8 [10.8]
14.5 [11.1]
7.6 [6.0]
5.0 [2.6]
6.9 [3.7]
Eur. J. Org. Chem. 2021, 632–636
www.eurjoc.org
634
© 2020 The Authors. European Journal of Organic Chemistry published
by Wiley-VCH GmbH

Communications
doi.org/10.1002/ejoc.202001453
interactions (~E ) that account for, among others, HOMO-
LUMO interactions. The corresponding energy decomposition
analysis (EDA) results are presented in Table 2.
Since 10a’ and 10b’ are regioisomers comprised of the
same molecular fragments M and N, the thermodynamic
preference for 10a’ over 10b’ should be reflected in the ~Eint
between the two fragments. Indeed, we see that the ~Eint
oi
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
slightly favors 10a’ over 10b’ (Table 2). By examining the
contributions towards ~E , the electrostatic interaction ~V
int
elstat
is the most significant contributor for a favorable ~Eint for 10a’.
To understand the trend in ~Velstat, we analyzed the Hirschfeld
charges of the terminal carbons of each fragment (Scheme 6b).
Carbonyl carbon 1 on fragment M is the most positively
polarized carbon in the fragment, while carbon 1’ on fragment
N is more negatively polarized compared to carbon 3’. The
positively polarized carbonyl atom therefore interacts favorably
with the (strongly) negatively polarized alkyl carbon during
bond formation, which explains the thermodynamic preference
for 10a’ over 10b’. Generalizing this result, we argue that the
build-up of positive charge is disfavored when the neighboring
carbon is the α-carbon of the ring oxygen (in the case of
compound 1, C1 and C5, Scheme 7) Therefore, the oxidation is
disfavored at C2/C4 relative to C3 because of the positive
charge build-up during the formation of the carbonyl (i.e. β-
hydride elimination).
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
Scheme 5. Relative electronic energies (~E, in kcalmolÀ 1) of isoelectronic C2-
and C3-ketoglucosides analogs. Note that, in every case, the C3-ketogluco-
side analogs (red) are more stable than the corresponding C2-ketoglucoside
analogs (blue).
its regioisomer 14b. From this, it can be concluded that the C3
preference retains in both cyclic and acyclic systems.
The results in Scheme 5 suggest that the effect of the ring
oxygen is inductive, i.e., the ring oxygen disfavors proximal
carbonyl groups (as in 10b). In order to gain further insights
into the relationship between the ring oxygen and the stability
of the oxidized product, we focused our analysis on model
systems 10a’ and 10b’ that have been optimized with a mirror
plane (σ ) in the C and C point group, respectively. The
In summary, we have computationally analyzed the mecha-
nism of the C3 selective palladium-catalyzed oxidation reaction
of methyl β-glucoside. Experimentally it was shown that the
oxidation of methyl β-glucoside was regioselective for C3,
whereas the same conditions for the oxidation of carba-β-
glucoside (in which the ring oxygen is replaced with a meth-
h
2v
s
bonding mechanism of the planar model systems 10a’ and 10b’
were analyzed using our energy decomposition analysis
[21]
(
EDA) method. The EDA decomposes the ~Eint between the
À 1
two fragments M and N (Scheme 6a) into three physically
meaningful energy terms: classical electrostatic interaction
Table 2. Energy decomposition analysis (in kcalmol ) of structures 10a’
and 10b’ computed at ZORA-(U)BLYPÀ D3(BJ)/TZ2P.
~E )[
a]
(
~Velstat), steric (Pauli) repulsion (~EPauli) which, in general, arises
EDA term
10a’
10b’
Difference (~
x
from two-center four-electron repulsions between the closed-
shell orbitals of both fragments, and stabilizing orbital
~
Eint
À 190.1
À 288.7
475.0
À 370.5
À 189.9
À 287.5
473.3
À 369.9
À 0.2
À 1.2
+1.7
À 0.6
~Velstat
~
EPauli
~Eoi
[
a] The difference is calculated as ~~E
x
=~E
x
(10a’)À ~E
x
(10b’), where ~E
x
is the EDA term (~E ~Velstat, ~EPauli, ~E ). A negative value for ~~Ex
int,
oi
corresponds to an EDA term that favors the C3 oxidation product.
Scheme 6. a) EDA fragmentation scheme. 10a’ and 10b’ are artificially planar
analogs of 10a and 10b, respectively and possess a mirror plane (σ ). 10a’
h
s
and 10b’ were fully optimized and analyzed in C2v and C symmetry,
respectively. b) Hirschfeld charges (milli a.u.) of carbons with singly occupied
orbitals on fragments M and N.
Scheme 7. Inductive effect of the ring oxygen on the selectivity of the β-
hydride elimination.
Eur. J. Org. Chem. 2021, 632–636
www.eurjoc.org
635
© 2020 The Authors. European Journal of Organic Chemistry published
by Wiley-VCH GmbH

Communications
doi.org/10.1002/ejoc.202001453
ylene (CH ) group) were unselective. These findings indicate
that the ring oxygen plays a crucial role in the regioselective C3
[8] a) M. Yanagi, Y. Ueda, R. Ninomiya, A. Imayoshi, T. Furuta, K. Mishiro, T.
Kawabata, Org. Lett. 2019, 21, 5006–5009; b) S. W. Baldwin, S. A. Haut, J.
Org. Chem. 1975, 40, 3885–3887.
2
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
oxidation. DFT studies verify that the β-hydride elimination of
methyl β-glucoside at C3 has both the lowest activation barrier
and is most exergonic compared to that at C2 or C4. These
reactivity differences between C2, C3, and C4 vanish when the
ring oxygen is removed in the case of carba-β-glucoside. Our
bonding analyses on model methyl β-glucosides reveal that the
predominant factor for the thermodynamic C3 preference
originates from the unfavorable electrostatic interaction be-
tween the positively polarized α-carbon of the ring oxygen and
the carbonyl carbon during β-hydride elimination. We envisage
that the newly identified intramolecular electrostatic repulsion
can serve as a general guideline for other molecules involving
the creation of a ketone in a six-membered ring, in which an
electronegative heteroatom is present.
[
9] J. Zhang, N. N. H. M. Eisink, M. D. Witte, A. J. Minnaard, J. Org. Chem.
2019, 84, 516–525.
[
10] N. Marinus, N. Tahiri, M. Duca, L. M. C. Marc Mouthaan, S. Bianca, M.
van den Noort, B. Poolman, M. D. Witte, A. J. Minnaard, Org. Lett. 2020,
22, 5622–5626.
[11] M. T. C. Walvoort, D. Sail, G. A. van der Marel, J. D. C. Codée, in
Carbohydrate Chemistry: Proven Synthetic Methods, Vol. 1, (Eds.: P.
Kováč), CRC Press, 2016, pp. 99–105.
12] M. Trincado, K. Kühlein, H. Grützmacher, Chem. Eur. J. 2011, 17, 11905–
11913.
13] a) Y. Tsuda, M. Hanajima, N. Matsuhira, Y. Okuno, K. Kanemitsu, Chem.
Pharm. Bull. (Tokyo) 1989, 37, 2344–2350; b) H.-M. Liu, Y. Sato, Y. Tsuda,
Chem. Pharm. Bull. (Tokyo) 1993, 41, 491–501; c) W. Muramatsu, Org.
Lett. 2014, 16, 4846–4849.
14] M. Jäger, M. Hartmann, J. G. De Vries, A. J. Minnaard, Angew. Chem. Int.
Ed. 2013, 52, 7809–7812; Angew. Chem. 2013, 125, 7963–7966.
15] K. Chung, S. M. Banik, A. G. De Crisci, D. M. Pearson, T. R. Blake, J. V.
Olsson, A. J. Ingram, R. N. Zare, R. N. Waymouth, J. Am. Chem. Soc. 2013,
[
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
[
[
[
135, 7593–7602.
[16] a) V. R. Jumde, N. N. H. M. Eisink, M. D. Witte, A. J. Minnaard, J. Org.
Chem. 2016, 81, 11439–11443; b) N. N. H. M. Eisink, J. Lohse, M. D. Witte,
A. J. Minnaard, Org. Biomol. Chem. 2016, 14, 4859–4864; c) J. Zhang,
N. N. H. M. Eisink, Martin D. Witte, Adriaan J. Minnaard, J. Org. Chem.
2019, 84, 516–525.
17] a) K. Chung, R. M. Waymouth, ACS Catal. 2016, 6, 4653–4659;
b) N. N. H. M. Eisink, M. D. Witte, A. J. Minnaard, ACS Catal. 2017, 7,
Acknowledgements
We thank the Netherlands Organization for Scientific Research
[
(NWO) for financial support.
1438–1445.
[18] a) G. Te Velde, F. M. Bickelhaupt, E. J. Baerends, C. Fonseca Guerra,
S. J. A. van Gisbergen, J. G. Snijders, T. Ziegler, J. Comput. Chem. 2001,
22, 931–967; b) C. Fonseca Guerra, J. G. Snijders, G. Te Velde, E. J.
Baerends, Theor. Chem. Acc. 1998, 99, 391–403; c) ADF2017.113, SCM
Theoretical Chemistry, Vrije Universiteit: Amsterdam (Netherlands).
http://www.scm.com.
Conflict of Interest
The authors declare no conflict of interest.
[
19] For ZORA: a) E. van Lenthe, E. J. Baerends, J. G. Snijders, J. Chem. Phys.
1
993, 99, 4597–4610; b) E. van Lenthe, E. J. Baerends, J. G. Snijders, J.
Keywords: Carbohydrates · Density functional calculations ·
Energy decomposition analysis · Oxidation · Regioselectivity
Chem. Phys. 1994, 101, 9783–9792; for BLYP:; c) A. D. Becke, J. Chem.
Phys. 1986, 84, 4524; d) A. D. Becke, Phys. Rev. A 1988, 38, 3098–3100;
for D3(BJ):; e) S. Grimme, J. Antony, S. Ehrlich, S. Krieg, J. Chem. Phys.
2
010, 132, 154104; f) A. D. Becke, E. R. Johnson, J. Chem. Phys. 2005, 123,
154101; for TZ2P:; g) E. van Lenthe, E. J. Baerends, J. Comput. Chem.
2003, 24, 1142–1156.
[
1] a) A. E. Christina, L. J. van den Bos, H. S. Overkleeft, G. A. nan der Marel,
J. D. C. Codée, J. Org. Chem. 2011, 76, 1692–1706; b) S. J. Danishefsky,
Y.-K. Shue, M. N. Chang, C.-H. Wong, Acc. Chem. Res. 2015, 48, 643–652;
c) P. Nagorny, B. Fasching, X. Li, G. Chen, B. Aussedat, S. J. Danishefsky,
J. Am. Chem. Soc., 2009, 131, 5792–5799.
[
[
20] a) A. Klamt, G. Schüürmann, J. Chem. Soc. Perkin Trans. 2 1993, 799–805;
b) A. Klamt, J. Phys. Chem. 1995, 99, 2224–2235; c) A. Klamt, V. Jonas, J.
Chem. Phys. 1996, 105, 9972–9981; d) C. C. Pye, T. Ziegler, Theor. Chem.
Acc. 1999, 101, 396–408.
21] a) F. M. Bickelhaupt, E. J. Baerends, in Rev. Comput. Chem. (Eds.: K. B.
Lipkowitz, D. B. Boyd), Wiley, Hoboken, 2000, pp. 1–86; b) R. van Meer,
O. V. Gritsenko, E. J. Baerends, J. Chem. Theory Comput. 2014, 10, 4432–
4441.
[2] J. Guo, X.-S. Ye, Molecules, 2010, 15, 7235–7265.
[3] a) V. Dimakos, M. S. Taylor, Chem. Rev. 2018, 118, 11457–11517; b) M.
Jäger, A. J. Minnaard, Chem. Commun. 2016, 52, 656–664.
[
4] Y. Ueda, T. Kawabata in Organocatalytic Site-Selective Acylation of
Carbohydrates and Polyol Compounds, Topics in Current Chemistry, Vol.
372, Springer International Publishing, 2016, pp. 203–231.
[
5] J. Lawandi, S. Rocheleau, N. Moitessier, Tetrahedron, 2016, 72, 6283–
6
319.
[
6] T. Ogawa, M. Matsui, Carbohydr. Res. 1978, 62, C1–C4.
Manuscript received: November 5, 2020
Revised manuscript received: December 17, 2020
Accepted manuscript online: December 18, 2020
[7] R. S. Mancini, J. B. Lee, M. S. Taylor, Org. Biomol. Chem. 2017, 15, 132–
43.
1
Eur. J. Org. Chem. 2021, 632–636
www.eurjoc.org
636
© 2020 The Authors. European Journal of Organic Chemistry published
by Wiley-VCH GmbH