Pseudo enantiomeric mixed S/P ligands derived from carbohydrates for the 1,4-addition of phenyl boronic acid to cyclohexenone

Article abstract of DOI:10.1039/c5ra10181f

The application of phosphinite-thioglycosides and phosphine-thioglycosides ligands in Rh(i)-catalyzed 1,4-addition of phenylboronic acid to cyclohexenone is reported. Among the ligands tested, phosphinite-thioglycoside 3 and phosphine-thioglycoside 10, be

Full text of DOI:10.1039/c5ra10181f

View Article Online
View Journal
RSC Advances
This article can be cited before page numbers have been issued, to do this please use: V. Valdivia, N.
Bilbao Bustinza, J. F. Moya-López, C. M. Rosales Barrios, Á. Salvador, R. Recio, F. Inmaculada and N. Khiar,
RSC Adv., 2015, DOI: 10.1039/C5RA10181F.
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. This Accepted Manuscript will be replaced by the edited,
formatted and paginated article as soon as this is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the Ethical guidelines still
apply. In no event shall the Royal Society of Chemistry be held
responsible for any errors or omissions in this Accepted Manuscript
or any consequences arising from the use of any information it
contains.
www.rsc.org/advances

Please do not adjust margins
Page 1 of 9
RSC Advances
View Article Online
DOI: 10.1039/C5RA10181F
RSC Advances
ARTICLE
Pseudo Enantiomeric Mixed S/P Ligands Derived from
Carbohydrates for the 1,4-Addition of Phenyl Boronic Acid to
Cyclohexenone
Received 00th January 20xx,
Accepted 00th January 20xx
V. Valdivia,a,b N. Bilbao Bustinza,a J. F. Moya,a C. M. Rosales,a A. Salvador,a R. Recio,b I. Fernández,
DOI: 10.1039/x0xx00000x
*b and N. Khiar.*a
www.rsc.org/
The application of phosphinite-thioglycosides and phosphine-thioglycosides ligands in the Rh(I)-catalyzed 1,4-addition of
phenylboronic acid to cyclohexenone is reported. Among the ligands tested, phosphinite-thioglycoside 3 and phosphine-
thioglycoside 10, bearing a 1,2-cis arrangement of the two heteroatoms, have exhibited the best results in terms of
reactivity and enantioselectivity. Interestingly, ligands 3 and 10, both derived from a D-sugar are able to generate the
addition product of the phenylboronic acid to the cyclohexenone with opposite configuration, behaving thus as
enantiomers.
hydroxyl groups in different orientations and, compared to
other biomolecules, their chiral coding information capacity is
by far the most significant.7 However, usually both
enantiomers of a target compound are required, imposing the
Introduction
The synthesis of enantiopure compounds is a standing area of
interest, consequence of the significance of chirality in
medicine, fragrances, agriculture and material science.1 Among
all the different approximations developed so far,
enantioselective catalysis is the method of choice,2 as it
combines efficiency, versatility, atom economy, and suitability
for green chemistry.3 Enantioselective catalysis is usually
achieved by using a chiral organic ligand either alone4 or linked
to a transition metal.5 The difficulties to predict the structural
requirements of a ligand for generating an efficient catalyst,
explain the continuous need of new modular ligands with
different coordinating or activation modes. To develop such
ligands, the first step is the search of interesting scaffolds, and
sequentially appends the ligating group. Ideally, the scaffold
must be easily obtained in optically pure form, and equipped
with orthogonal functions which allow optimization of the
ligating groups individually. Among the different compounds
need to easily access to both enantiomeric ligands, which in
the case of carbohydrates is highly challenging. This drawback
has been solved by developing the concept of pseudo-
enantiomeric ligands, which consist in the use of D-sugars as
starting material for the synthesis of two structurally different
ligands, yet able to generate both enantiomers.8 Based on
these premises, and within our interest in the synthesis and
application of chiral sulfur compounds in organic9 and
organometallic asymmetric synthesis,10 we have developed
highly enantioselective pseudo enantiomeric mixed S/P ligands
for Pd-catalyzed allylic substitution,11 Rh(I)-catalyzed enamide
hydrogenation12 and hydrosilylation of prochiral ketones.13 In
the present work, we report our preliminary results directed
toward the development of two pseudo-enantiomeric ligands
I
and II for the Rh(I)-catalyzed 1,4 addition of phenyl boronic
acid to cyclohexenone, Figure 1.
which can be used in this task, carbohydrates hold
a
prominent role.6 Indeed, carbohydrates account for the 93% of
the renewable biomass on earth, are the cheapest
Results and Discussion
enantiopure compounds in the market, possess various Within C-C bond formation reactions, the Rh(I)-catalyzed
addition of boronic acids to activated ketones is one of the
most powerful approximations.14 Since the pioneering works
of Hayashi,15 and Miyaura16 a wide number of methodologies
have been successfully developed for this transformation and
very high levels of sophistication and efficiency have been
achieved so far. Among the most important contributions
recently developed, it is interesting to highlight the discovery
that C217 and C118 ligands with a chiral sulfinyl group (S-O) are
a.Asymmetric Synthesis and Functional Nanosystem Group, Instituto de
InvestigacionesQuímicas CSIC-Universidad de Sevilla
c/. Américo Vespucio, 49., Isla de la Cartuja, 41092 Seville, Spain.
E-mail: khiar@iiq.csic.es
b.Departamento de Química Orgánica y Farmacéutica.
Facultad de Farmacia, Universidad de Sevilla.
C/Profesor García González 2, 41012, Seville, Spain.
Electronic Supplementary Information (ESI) available: [Copies of 1H, 13C and 31
P
spectra of compounds 12-14
, 16-18, and HPLC chromatograms of 6 obtained with
ligand and 10. See DOI: 10.1039/x0xx00000x
3
This journal is © The Royal Society of Chemistry 20xx
RSC Advances., 2015, 00, 1-7 | 1
Please do not adjust margins

Please do not adjust margins
RSC Advances
Page 2 of 9
ARTICLE
Journal Name
View Article Online
DOI: 10.1039/C5RA10181F
Figure 1. General Structure of mixed S/P ligands used in the Rh-
Scheme 1. Use of phopshinite thioglycosides
1-3 as ligands in the Rh(I)-
catalyzed 1,4-addition of phenylboronic acid to cyclohexenone
catalysed 1,4-addition of phenyl boronic acid to cyclohexenone
4
.
able to generate efficient catalysts for this transformation.
alkylation, and in the Rh(I)-catalyzed hydrogenation of
enamides, led to significant increase in the
enantioselectivity. Indeed using ligand enabled the
production of the addition product with 67% yield and an
interesting 70% ee in favor of the (R) enantiomer.
Based on these preliminary results, we decided to apply other
ligands with a 1,2-cis disposition of both heteroatoms. At this
Surprisingly,
a
single type of ligands derived from
a
carbohydrates, entailing olefin/phosphinite coordinating
groups have been used in this transformation.19 Moreover; as
far as we know no example using mixed S/P ligand with a
prochiral thioether (S-R) group has been reported yet. In this
sense, one of the most important features in the sulfur-based
ligands derived from carbohydrates is that the sugar acts as a
chiral rely to the nascent stereogenic sulfur center upon
coordination to the metal. Consequently, an efficient control
of the stereochemical outcome in the coordination step will
lead to a well-defined chiral environment in a very close
3
6
point, it is worth of mention that while the synthesis of
-
mannothiolglycosides and -glucothioglycosides needed for
β
the synthesis of 1,2-trans diaxial and 1,2-trans diequatorial
mixed S/P ligands can be easily performed, the synthesis of the
corresponding 1,2-cis counterpart is more challenging. In order
to address this problem, and to evaluate the contribution of
the phosphinite moiety, and the ring size in the metallacycle
20
proximity to the coordination sphere of the metal. In our
previous works we have shown that this control may be
exerted, in the case of C2-symmetric bis-thioglycosides,21
through stereoelectronic factors, namely the exo-anomeric
effect, or through steric bias in the case of C1-symmetric
phosphinite thioglycosides.22 This stereocontrol coupled with
the higher trans effect of phosphorus vs sulfur23 led to the
intermediate on the catalytic performance of ligands
we have developed a method for the synthesis of
1
and
2,
β
-manno-
thioglycosides II, figure 1, with a biphenyl phosphine moiety at
C2.24 The approximation is based on the ring opening of an
allo-epoxide intermediate by biphenyl phosphinyl lithium.
Based on the modularity of the approximation, we decided to
apply it for the synthesis of a small library of ligands in order to
unravel the effect of sulfur and phosphorus substituents on
their catalytic behavior. Therefore, tert-Butyl and adamantyl
discovery, of ligands
1 and 2 derived from D-sugars galactose
and arabinose as excellent catalyst precursors for the synthesis
of L- and D-amino esters, scheme 1.12 Moreover, these ligands
have also shown interesting behavior in the Rh(I)-catlyzed
hydrosilylation of prochiral ketones.13
4,6-O-benzylidene-2,3-anhydro-1-thio-
and , prepared in four steps from glucose pentaacetate, were
used as starting materials, scheme 2.25
Addition of freshly prepared and titrated diphenylphosphinyl
lithium (PPh2H + BuLi) on a solution of epoxide dissolved in a
deoxygenated Et2O:DMF (1:1) mixture, afforded the desired
phosphine as a single diastereoisomer. To study the
β-D-allopyranosides,
7
In order to enhance the reaction scope of these ligands, we
8
assayed them in the model reaction of 2-cyclohexenone
4 and
phenylboronic acid . Employing Hayashi initial conditions in
5
the presence of 2.5 mol% of the rhodium precursor
[Rh(C2H4)Cl]2 and 5 mol% of ligand, the adduct was generally
obtained with good yields but with very low
7
9
enantioselectivities. The galactose derivative ligand
the addition compound with 70% yield and 9%
enantioselectivity in favor of the (S) enantiomer, while the
arabinose ligand led to the formation of in 75% yield and
1, led to
influence of the hydroxyl group on the position 3 of the sugar
on its catalytic behavior, the corresponding acetylated ligand
6
10 was synthesized by treatment of
9 with acetic anhydride in
2
6
pyridine Similarly, starting from epoxide 8, hydroxyphosphine
.
6% ee in favor of the (R) enantiomer, Scheme 1.
11 was obtained as a single diastereoisomer, which after
acetylation led to the fully protected ligand 12. Homo- and
heteronuclear NMR analyses indicate that the opening of the
epoxide takes place as predicted at the 2 position in accord
with the Fürst-Plattner rule (1,2-trans diaxial opening).26 Next,
different ligands with varied electronic and steric phosphine
moiety were synthesized by condensation of diarylphosphinyl
In our previous work on the Rh(I)-catalyzed hydrogenation of
enamides, we have shown that the relative disposition of the
coordinating sulfur and phosphorus atoms is extremely
important, being the 1,2-trans derivative the most favored.
Surprisingly, by using the galactose derivative with an
configuration at the anomeric center
3, which was neither
reactive nor enantioselective in Pd(0)-catalyzed allylic
2 | RSC Advances, 2015, 00, 1-7
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Page 3 of 9
RSC Advances
Journal Name
ARTICLE
View Article Online
DOI: 10.1039/C5RA10181F
Table 1. Rhodium-catalyzed 1,4-addition of the phenyl boronic acid 5 to
cyclohexenone 4 using chiral phosphine thioglycosides.a
b
c
c
Entry
Ligand
Yield
e.r.
e.e
(%)
%S/%R
(%)
1
85
87/23
64
Scheme 2. Synthesis of phosphine thioglycoside ligands by ring
opening of allo-epoxides with diarylylphosphinyl lithium
2
3
4
0
--
--
.
lithium on tert-butyl 4,6-O-benzylidene-2,3-anhydro-1-thio-β-
D-allopyranosides , Scheme 2.
The addition of bis-(para-methoxyphenyl)phosphinyl lithium to
the epoxide afforded the electron rich hydroxyphosphine
7
83
23
70/30
54/46
40
7
thioglycoside 13 with 62% yield, which after acetylation
afforded phosphine 14 with 66% yield. The use of the hindered
bis-(1,3,5-trimethylphenyl)phosphinyl lithium as nucleophile,
led to the opening product 17 with 76% yield, which gave
ligand 18 with 43% yield by acetylation. In the case of the
8
electronically
trifluorophenyl)phosphine,
deficient
phosphine,
the
bis-(1,3-bis-
corresponding
hydroxyphosphine 15, could not be isolated, but an in situ
acetylation led to the ligand 16 with 62% yield.
5
88
87/23
65
Once the ligands in hand, we assayed them in the model
reaction of 2-cyclohexenone
(Table 1), under the same conditions than for the phosphinite
thioglycosides 1-3
4 and phenyl boronic acid 5
.
As shown in Table 1, the enantioselectivity depends mainly on
the steric substituent of the sulfur and the phosphine.
Surprisingly, enhancing the steric hindrance of the sulfur
substituent from the tert-butyl to the adamantyl group has a
detrimental effect on the enantioselectivity. In this sense,
ligand 10 with the tert-butyl group led to the desired product
with 64% ee (Table 1, entry 1), while ligand 12 with the bulky
6
87
88/22
66
adamantyl group afforded compound
6 with a lower 40% ee
7
86
50/50
0
(Table 1, entry 3), eventhough both are equally reactive
affording the addition compound in good yields (85% and 83%
respectively). The protection of the hydroxyl group at the
position
enantioselectivity of the process. As a general trend, ligands
with free hydroxyl group generate unreactive and
3 is crucial, both for the reactivity and the
a
unselective catalysts compared with the acetylated
counterparts (compare entry 2 with 3 and 4 with 5). Ligand 14
with an electron rich phosphine moiety led to the desired
compound with an excellent 88% yield and a good 65%
enantioselectivity (Table 1, entry 5). Practically the same
results 88% yield and 65% ee were obtained with ligand 16
with an electron deficient phosphine group (Table 1, entry 6),
highlighting that the electronic factor are not determinant
a
All reactions were conducted using 5 mol% of the ligand together with 2.5 mol% of
b
[Rh(C2H4)Cl]2. Isolated yields of pure compound 6 after column chromatography
purification. Determined by chiral stationary phase HPLC with OD-H column: hexane:
iPrOH 98:2, flow 0.5 mL/min.
c
This journal is © The Royal Society of Chemistry 20xx
RSC Advances, 2015, 00, 1-7 | 3
Please do not adjust margins

Please do not adjust margins
RSC Advances
Page 4 of 9
ARTICLE
Journal Name
View Article Online
DOI: 10.1039/C5RA10181F
Scheme 3. Pseudo-enantiomeric behavior of ligands
3 and 10 in the
Rh-catalyzed 1,4-addition
in the reactivity of the ligands. At the contrary, enhancing the
steric hindrance of the phosphine has a detrimental effect on
the enantioselectivity, as shown by the result obtained by
Scheme 4. 1,4-addition of p-tolyl boronic acid 20 to cyclohexenone
and to 3-pentenone 19 using ligand 10
4
ligand 18 which affords compound
6 with 86% yield but in
racemic form (Table 1, entry 7).
The most interesting feature that emerges from the analysis of
the results obtained with mixed ligand type II, is that without
exception all lead to the 6S enantiomer as major adduct.
Considering that phosphinites thioglycosides type I, tested at
the beginning of this study lead to the 6R isomer, one can
conclude that the two types of ligands, although structurally
different behave as pseudo-enantiomers, Scheme 3.
Experimental Section
General Methods
All reactions were run under an atmosphere of dry argon using
oven-dried glassware and freshly distilled and dried solvents.
THF and diethyl ether were distilled from sodium
benzophenone ketyl. Dichloromethane was distilled from
calcium hydride. TLC was performed on Silica Gel GF254
(Merck) with detection by charring with phosphomolybdic
acid/EtOH. For flash chromatography, silica Gel (Merck 230-
400 mesh) was used. Columns were eluted with positive air
pressure. Chromatographic eluents are given as volume to
volume ratios (v/v). NMR spectra were recorded with a Bruker
AMX500 (1H, 500 MHz) and Bruker Avance DRX500 (1H, 500
MHz) spectrometers. Chemical shifts are reported in ppm, and
coupling constants are reported in Hz. Routine spectra were
referenced to the residual proton or carbon signals of the
solvent. High-resolution mass spectra were recorded on a
Kratos MS-80RFA 241-MC apparatus. Optical rotations were
determined with a Perkin-Elmer 341 polarimeter. 1,2,3,4,6-
Next we studied the addition of other boronic acid to
cyclohexenone and to an acyclic
-unsaturated ketone,
Scheme 3. The use of p-tolyl boronic acid 20 as nucleophile
afforded the addition compound 21R in an excellent 98%
enantiomeric excess albeit with low yield, Scheme 3.
Surprisingly, the addition of p-tolyl boronic acid to the more
challenging 3-pentenone 19 afforded the desired 4-
phenylpentan-2-one 22S in 50% yield and an interesting 70%
ee.
Conclusions
In conclusion, we have reported the first application of mixed
S/P ligands with a prochiral thioether group in the Rh(I)-
catalyzed 1,4 addition of phenyl boronic acid to
cyclohexenone. The obtained results showed that, contrary to
Penta-O-acetyl-β-D-glucopyranose, was purchased from
the behavior of phosphinite thioglycosides
allylic substitution and Rh(I)-catalyzed hydrogenation of
enamides, the ligands with cis relationship of both
coordinating atoms are better catalyst precursors than those
with trans relationship. In the case of phosphine-
thioglycosides II ring opening of the allo-epoxide
I in Pd(0)-catalyzed
Aldrich.
a
General procedure for the incorporation of the phosphinite
moiety for the preparation of phosphinite-thioglycosides 1, 2
and 3.
a
,
a
intermediates, obtained in 4 steps from glucose pentaacetate,
with diarylphosphinyl lithium, allowed the preparation of
various ligands with a different substituent at sulfur, and with
diverse sterically and electronically phosphine moiety at C2.
To a solution of the monoalcohol (1.4 mmol) in 7 mL of dry and
deoxygented THF / NEt3 (1 / 1) solution, was added diphenyl
chlorophophine (276 L, 1.54 mmol) followed by a catalytic
amount of DMAP (30 mg). After 30 min, the suspension was
directly loaded on a short pad of silica and eluted with the
corresponding eluent previously deoxygenated. The
phosphinite thioglycosides are usually obtained as white solids
and immediately stored in a dry glove box.
Despite the structural dissimilarity of ligands
behave as pseudoenantiomers affording as major isomer (R)-
and (S)-3-phenylcyclohexanone respectively, in the Rh-
I and II, they
6
catalyzed addition of phenylboronic acid to cyclohexenone.
4 | RSC Advances, 2015, 00, 1-7
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Page 5 of 9
RSC Advances
Journal Name
ARTICLE
6-O-Acetyl-3,4-O-Isopropylidene-2-O-diphenylphosphinite-1-
thio- -D-galactopyranoside (1).
diphenylphosphinyl lithium solution (6 mL, 3.5 mVmiewolA)r.ticAleftOenrlin1e
h, NH4Cl (200 mg, 3.7 mmol) was added and stirring was
DOI: 10.1039/C5RA10181F
continued for 30 min more before evaporating the solvent.
o
1
White solid. m.p: 116-120 C.
20: +7.1 (c 1.05, CHCl3). H After coevaporation with toluene, the crude mixture was
D
RMN (500 MHz, CDCl3): δ 7.56-7.47 (m, 4H, PPh2), 7.34-7.29 purified by column chromatography (EtOAc : Hexanes, 1 : 6),
3
(m, 6H, PPh2), 4.51 (d, 1H, JH1-H2 = 9.5 Hz, H-1), 4.33-4.26 (m, affording the corresponding hydroxyphosphine-thioglycoside.
3
2
3H, H-3, H-4, H-6), 4.15 (dd, 1H, JH5-H6’ = 1.8 Hz, JH6-H6’ = 5.6
Hz, H-6’), 3.96-3.88 (m, 2H, H-2, H-5), 2.03 (s, 3H, OAc), 1.42 (s, tert-Butyl 4,6-O-benzylidene-2- deoxy-2-diphenylphosphino-
3H, O2CMe2), 1.29 (s, 3H, O2CMe2), 1.22 (s, 9H, SCMe3). 13C 1-thio- -D-altropyranoside (9).
RMN (125 MHz, CDCl3): δ 170.8 (COMe), 142.9 (d, JC-P= 18.4 Hz,
PPh2), 142.1 (d, JC-P= 15.2 Hz, PPh2), 131.3 (d, JC-P= 22.1 Hz, [ ]D20: + 13.9 (c. 0.6, CHCl3). 1H-NMR (500 MHz, CDCl3): δ 7.55-
PPh2), 130.5 (d, JC-P= 21.3Hz), 129.0 (d, JC-P= 32.5 Hz), 128.0 (d, 7.51 (m, 5H), 7.38-7.28 (m, 10H), 5.6 (dd, 3JH1-H2 = 3.4 and 3JH1-P
3
JC-P= 6.4 Hz), 127.9 (d, JC-P= 7.2 Hz), 110.5 (CMe2), 82.5 (C-1), = 24.4 Hz, 1H, H-1), 4.93 (s, 1H, CHPh), 4.22 (dd, JH6-H5 = 4.8,
3
3
83.1 (d, JC-P= 3.3 Hz, C-2), 80.6 (C-3), 73.6 (C-4, C-5), 63.9 (C-6), 3JH6-H6’ = 10.2 Hz, 1H, H-6), 3.90 (dt, JH5-H6,6’ = 4.9, JH5-H4 = 9.9
3
3
44.1 CMe3), 31.3 (CMe3), 27.7 (CMe2), 26.4 (CMe2), 20.8 (OAc). Hz, 1H, H-5), 3.5 (t, JH6’-H6 = JH6’-H5 = 10.2 Hz, 1H, H-6’), 3.08
31P RMN (121.4 MHz, CDCl3): δ 119.8. HRMS calc. For (m, 1H, H-4), 2.85 (m, 1H, H-2), 2.05 (bs, 1H, OH), 1.38 (s, 9H,
C27H35O6PSNa: 541.1792. Found: 541.1788 (-1.2 ppm).
CMe3). 13C-NMR (125 MHz, CDCl3): δ 137.1, 136.9 (d, J=19.7
Hz), 135.8 (d, J = 10.9 Hz), 135.3 (d, J=21.9 Hz), 132.2 (d, J=18.3
Hz), 129.4 (d, J = 51.4 Hz), 128.7, 128.6, 128.5, 128.4, 128.3,
3,4-O-Isopropylidene-2-O-diphenylphosphinite-1-thio- -D-
arabinopyranoside (2).
2
128.2, 126.1, 101.8 (CHPh), 81.0 (d, JC-P = 14.5 Hz, C-1), 76.3
(C-4), 69.3 (C-6), 68.3 (C-5), 67.6 (C-3), 44.81 (d, 1JC-P = 22.3 Hz,
o
1
White solid. m.p: 119-125 C.
20: +5.8 (c 2.22, CHCl3). H- C-2), 31.6 (CMe3). 31P-NMR (121.4 MHz, CDCl3): δ -19.1.
D
NMR (500 MHz, CDCl3): δ 7.54–7.46 (m, 4H, PPh2), 7.33–7.29
3
(m, 6H, PPh2), 4.76 (d, JH1-H2 = 6.9 Hz, 1H), 4.28–4.26 (m, 1H, 1-Adamantyl
4,6-O-benzylidene-2-deoxy-2-
H-4), 4.22 (t, 3JH3-H2 = 5.7 Hz, 1H, H-3), 4.08 (dd, 3JH4-H5 = 4.8 Hz, diphenylphosphino-1-thio- -D-altropyranoside (11).
2JH5-H5’ = 12.7 Hz, H-5) 3.99–4.05 (m, 1H, H-2), 3.70 (dd, JH4-H5’
3
= 4.8 Hz, 2JH5-H5’ = 12.7 Hz, 1H, H-5’), 1.47 (s, 3H, O2CMe2), 1.30 1H-NMR (500 MHz, CDCl3): δ 7.54-7.50 (m, 4H), 7.38-7.35 (m,
(s, 3H, O2CMe2), 1.19 (s, 9H, SCMe3). 3C-NMR (125 MHz, 3H), 7.33-7.29 (m, 8H), 5.64 (dd, JH1-P = 24.6 and JH1-H2 = 3.2
1
3
3
CDCl3): δ 131.2 (d, JC-P = 22.1 Hz, PPh2), 130.5 (d, JC-P = 21.4 Hz, Hz, 1H, H-1), 4.91 (s, 1H, CHPh), 4.20 (dd, 3JH6-H5 = 4.8, 3JH6-H6’
=
PPh2), 129.1 (d, JC-P = 31.7 Hz, PPh2), 128.1 (d, JC-P = 5.9 Hz, 10.2 Hz, 1H, H-6), 3.85 (dt, 3JH5-H6,6’ = 4.9, 3JH5-H4 = 9.9 Hz, 1H, H-
3
3
PPh2), 128.0 (d, JC-P = 6.7 Hz, PPh2), 110.1 (CMe2), 84.5 (C-1), 5), 3.22 (t, JH6’-H6 = JH6’-H5 = 10.2 Hz, 1H, H-6’), 3.04-3.03 (m,
82.6 (d, JPC = 4.2 Hz, C-2), 80.3 (d, JPC = 19.2 Hz, C-3), 72.2 (C-4), 1H, H-4), 2.36 (m, 1H, H-2), 2.04-1.68 (m, 15H, Adam). 13C-
63.2 (C-5), 44.0 (CMe3), 31.3 (CMe3), 27.8 (CMe2), 26.3 (CMe2), NMR (125 MHz, CDCl3): δ 137.1, 135.4, 135.2, 132.1, 129.5,
17.2 (OAc). 31P-NMR (121.4 MHz, CDCl3): δ 118.6. Anal. Calcd. 129.1, 128.4, 128.4, 128.3, 128.2, 126.0 (12C), 101.7 (CHPh),
for C24H31O4PS: C, 64.55%, H, 7.00%. Found. C 64.94%, H 6.9%.
78.6 (d, 2JC-P = 14.5 Hz, C-1), 78.5, 76.2 (C-4), 69.3(C-6), 68.3 (C-
5), 67.5 (C-3), 47.0, 45.0 (d, 1JC-P = 22.3 Hz, C-2), 43.9, 36.3, 29.8
6-O-Acetyl-3,4-O-Isopropylidene-2-O-diphenylphosphinite-1-
(CMe3). 31P-NMR (202 MHz, CDCl3): δ -19.1. HRMS Calc.
for
thio- -D-galactopyranoside (3).
C35H39O4NaPSNa: 609.2204. Found: 609.2199 (-0.9 ppm).
o
1
White solid. m.p: 102-104 C.
20: +77.5 (c 1.65, CHCl3). H tert-Butyl
4,6-O-benzylidene-2-deoxy-2-di(p-
D
RMN (500 MHz, CDCl3): δ 7.57-7.50 (m, 4H, PPh2), 7.35-7.32 methoxy)phenylphosphine-1-thio- -D-altropyranoside (13).
3
(m, 6H, PPh2), 5.56 (d, 1H, JH1-H2 = 5.1 Hz, H-1), 4.70-4.67 (m,
o
1
1H, H-5), 4.34-4.11 (m, 5H, H6, H-6’, H-2, H-3, H-4), 2.02 (s, 3H, M.p: 104 C.
20: +6 (c 0.15, CHCl3). H-NMR: (500 MHz,
D
OAc), 1.41 (s, 3H, O2CMe2), 1,30 (s, 12 H, O2CMe2, SCMe3). 13C CDCl3): 7.48-7.44 (m, 4H), 7.32 (s, 5H), 6.92-6.87 (m, 4H),
3
3
RMN (75 MHz, CDCl3): δ 170.7 (COMe), 137.7(d, JC-P= 18.4 Hz, 5.58 (dd, JH1-H2 = 3.0 and JH1-P = 22.9 Hz, 1H, H-1), 5.08 (brs,
3
3
PPh2), 132.4 (d, JC-P= 15.2 Hz, PPh2), 131.1 (d, JC-P= 22.1 Hz, 1H, CHPh), 4.21(dd, JH6-H5 = 4.8, JH6-H6’ = 10.2 Hz, 1H, H-6),
PPh2), 130.8 (d, JC-P= 32.5 Hz), 130.6 (d, JC-P= 6.4 Hz), 129.5 (d, 4.15 (brs, 1H, H-3), 3.93 (dt, JH5-H6,6’ = 4.9, 3JH5-H4 = 9.9 Hz, 1H,
3
3
JC-P= 32.5 Hz), 128.1 (d, JC-P= 6.4 Hz), 110.5 (CMe2), 88.5 (C-1), H-5), 3.81 (s, 3H, OMe), 3.79 (s, 3H, OMe), 3.47 (t, JH6’-H6
=
88.4 (d, JC-P= 3.3 Hz, C-2), 80.4 (C-3), 80.1, 79.1, 74.0 (C-4), 73.7 3JH6’-H5 = 10.2 Hz, 1H, H-6’), 3.03-3.01 (m, 1H, H-2), 2.72 (dd,
(C-5), 63.7 (C-6), 38.7(CMe3), 27.8 (CMe2), 27.1 (CMe2), 26.4, 3JH4-H3 = 2.3, JH4-H5 = 9.6 Hz, 1H, H-4), 2.35 (brs, 1H, OH), 1.36
3
21.2 (OAc). 31P RMN (121.4 MHz, CDCl3): δ 117.5.
(s, 9H, CMe3). 13C-NMR: (125 MHz, CDCl3): 160.9, 159.9,
137.1, 136.5, 136.3, 133.8, 133.6, 129.2, 128.2, 127.5, 127.1,
2
General procedure of the opening epoxide reaction.
126.0, 114.3, 114.2, 114.1, 114.0, 101.8 (CHPh), 80.9 (d, JC-P
=
14.5 Hz, C-1), 76.3 (C-4), 69.3 (C-6), 68.4 (C-5), 67.6 (C-3), 55.3,
1
To a solution of the corresponding epoxide (575mg, 1.8 mmol) 55.2, 45.5 (d, JC-P = 22.3 Hz, C-2), 44.7, 44.6, 31.5 (CMe3). 31P-
in a 1 : 1 mixture of THF : DMF (8 mL) at -10 ºC was added a NMR: (121.4 MHz, CDCl3): -19.1. Anal. Calc. for C31H37O6PS: C,
freshly prepared (P(Ar)2H + BuLi in THF) and titrated 0.6 M
This journal is © The Royal Society of Chemistry 20xx
RSC Advances, 2015, 00, 1-7 | 5
Please do not adjust margins

Please do not adjust margins
RSC Advances
Page 6 of 9
ARTICLE
Journal Name
65.48%; H, 6.56%; O, 16.88%; P, 5.45%; S, 5.64%. Found: C, 129.8, 128.9, 128.6, 128.5, 128.1, 126.0, (12C arom.), 101,6
View Article Online
64.80%, H, 6.67%, S, 5.65%.
(CHPh), 78.6 (d, 2JC-P = 14.5 Hz, C-1), 74.4 D(CO-I4: )1,07.1003.69/(CC5-R6A)1,06198.12F
(C-5), 68.2 (C-3), 47.0 (Adam.), 44,6 (d, JC-P = 22.3 Hz, C-2),
1
tert-Butyl
4,6-O-benzylidene-2-deoxy-2-di(2,4,6-trimethyl) 44.0, 36.2, 29.7 (Adam.), 21.2 (OAc). 31P-NMR (121.4 MHz,
phenylphosphine-1-thio- -D-altropyranoside (17).
CDCl3): -18.2. HRMS calc. for C37H41O5NaPSNa: 651.2310.
Found: 651.2331 (3.2 ppm.).
1H-NMR: (500 MHz, CDCl3): 7.33 (s, 5H), 7.05-6.77 (m, 4H),
3
3
5.52 (dd, JH1-H2 = 3.0 and JH1-P = 22.9 Hz, 1H, H-1), 5.14 (brs, tert-Butyl
3-O-acetyl-4,6-O-benzylidene-2-deoxy-2-di(p-
3
3
1H, CHPh), 4.26 (dd, JH6-H5 = 4.8, JH6-H6’ = 10.2 Hz, 1H, H-6), methoxy)phenylphosphine-1-thio- -D-altropyranoside (14).
4.14 (brs, 1H, H-3), 3.96 (dt, 3JH5-H6,6’ = 5, JH5-H4 = 10 Hz, 1H, H-
3
3
3
o
1
5), 3.60 (t, JH6’-H6 = JH6’-H5 = 10.2 Hz, 1H, H-6’), 2.99-3.01 (m, White solid. M.p: 94 C.
20: +5.71 (c 0.175, CHCl3). H-
D
1H, H-4), 2.85 (m, 1H, H-2), 2.24 (s, 8H), 2.22 (s, 3H), 2.16 (s, NMR: (400 MHz, CDCl3): 7.63-7.57 (m, 4H, arom.), 7.30 (s,
3
3H), 1.36 (s, 9H). 13C-NMR: (125 MHz, CDCl3): 160.9, 159.9, 5H, arom.), 6.92-6.87 (m, 4H, arom.), 5.43 (dd, JH1-H2 = 2.6 Hz,
137.1, 136.5, 136.3, 133.8, 133.6, 129.2, 128.2, 127.5, 127.1, 3JH1-P = 21.3 Hz, 1H, H-1), 5.31 (t, 3JH3-H2 = 3JH3-H4 = 2.5 Hz, 1H, H-
2
3
3
126.0, 114.3, 114.2, 114.1, 114.0, 101.7 (CHPh), 81.1 (d, JC-P
=
3), 5.09 (s, 1H, CHPh), 4.23 (dd, JH6-H5 = 4.8 Hz, JH6-H6’ = 10.4
3
3
3
14.5 Hz, C-1), 76.6 (C-4), 69.1 (C-6), 68.7 (C-5), 67.7 (C-3), 55.3, Hz, 1H, H-6), 4.95 (dt, JH5-H6 = JH5-H6’ = 4.9 Hz, JH5-H4 = 9.8 Hz,
55.2, 45.5 (d, JC-P = 22.3 Hz, C-2), 44.7, 44.6, 22.6, 21.9, 31.5 1H, H-5), 3.81 (s, 3H, OMe), 3.77 (s, 3H, OMe), 3.58 (t, 3JH6’-H6
=
1
(CMe3). 31P-NMR: (121.4 MHz, CDCl3): -28 ppm.
3JH6’-H5 = 10.3 Hz, 1H, H-6’), 3.13-3.10 (m, 2H, H-2 and H-4),
2.16 (s, 3H, OAc), 1.36 (s, 9H, CMe3). 13C-NMR: (125 MHz,
CDCl3): 170.1, 160.9, 160.12, 137.13, 136.8, 136.6, 134.4,
General procedure for the acetylation of the hydroxyl group.
134.1, 128.9, 128.1, 127.7, 127.6, 126.6, 126.4, 126.0, 114.3,
2
To
a
solution of the corresponding hydroxyphosphine- 114.2, 114.1, 101.7 (CHPh), 81.0 (d, JC-P = 14.5 Hz, C-1), 80.8,
thioglycoside (0.0924 mmol) in pyridine (0.25 ml) at r.t., was 74.5, 74.4 (C-4), 70.8 (C-6), 69.2 (C-5), 68.2(C-3), 55.2 (OMe),
added acetic anhydride (0.1386 mmol). After 2 hours, the 44.8 (d, 1JC-P = 22.3 Hz, C-2), 31.4 (CMe3), 21.2 (OAc). 31P-NMR:
solvent was evaporated to give the product as a white solid.
(121.4 MHz, CDCl3): -22.3.
tert-Butyl
3-O-acetyl-4,6-O-benzylidene-2-deoxy- terc-Butyl 3-O-acetyl-4,6-O-benzylidene-2-deoxy-2-bis[(3,5
diphenylphosphine-1-thio- -D-altropyranoside (10).
bis(trifluoromethyl)phenyl]phosphine-1-thio- -D-
altropyranoside (16).
o
White solid. m.p: 141-143 C.
20: -29.32 (c. 0.25, CHCl3),
D
1H-NMR: (500 MHz, CDCl3) δ 7.68-7.64 (m, 5H, arom.), 7.42- 1H-NMR: (500 MHz, CDCl3): 8.17 (dd, J = 6.8 and 27.5 Hz, 4H),
7.34 (m, 10H, arom.), 5.45 (dd, 3JH1-H2 = 2.6 Hz, JH1-P = 21.3 Hz, 7.92 (d, 28.2 Hz, 2H), 7.33 (s, 5H), 5.50 (dd, JH1-H2 = 2.6 Hz,
3
3
1H, H-1), 5.37 (t, JH3-H2 = JH3-H4 = 2.5 Hz, 1H, H-3), 4.95 (s, 1H, 3JH1-P = 21.3 Hz, 1H, H-1), 5.29 (s, 1H, CHPh), 5.0 (s, 1H, H-3),
3
3
CHPh), 4.20 (dd, 3JH6-H5 = 4.8 Hz, 3JH6-H6’ = 10.4 Hz, 1H, H-6), 3.90 4.31 (dd, JH6-H5 = 4.8 Hz, JH6-H6’ = 10.4 Hz, 1H, H-6), 4.09 (dt,
3
3
(dt, JH5-H6 = JH5-H6’ = 4.9 Hz, JH5-H4 = 9.8 Hz, 1H, H-5), 3.57 (t, 3JH5-H6 = 3JH5-H6’ = 4.9 Hz, 3JH5-H4 = 9.8 Hz, 1H, H-5), 3.67 (t, 3JH6’-H6
3
3
3
3JH6’-H6 = JH6’-H5 = 10.3 Hz, 1H, H-6’), 3.14-3.12 (m, 1H, H-2) = 3JH6’-H5 = 10.3 Hz, 1H, H-6’), 3.55 (dd, 3JH4-H3 = 2.3, 3JH4-H5 = 9.6
3
2.89-2.86 (m, 1H, H-4), 2.15 (s, 3H, OAc), 1.38 (s, 9H, t-Bu). 13C- Hz, 1H, H-4), 3.39 (s, 1H, H-2), 2.19 (s, 3H, OAc), 1.31 (s, 9H,
NMR: (125 MHz, CDCl3) 170 (COAc), 137.18, 135.59, 132.79, CMe3). 13C-NMR: (125 MHz, CDCl3):
170.0, 137.7, 136.6,
129.88, 128.97, 128.70, 128.61, 128.56, 128.26, 125.98 (Ph), 134.9, 133.5, 129.7, 129.3, 128.9, 128.3, 126.0, 124.4, 123.9,
101.64 (CHPh), 81.05 (d, 2JC-P = 14.5 Hz, C-1), 71.47 (C-4), 70.57 121.9, 102.3 (CHPh), 79.7 (d, 2JC-P = 14.5 Hz, C-1), 78.2, 74.6 (C-
1
1
(C-6), 69.25 (C-5), 68.35 (C-3), 44.56 (d, JC-P = 22.3 Hz, C-2), 4), 70.0 (C-6), 69.0 (C-5), 68.4 (C-3), 44.9 (d, JC-P = 22.3 Hz, C-
31.46 (CMe3), 21.21 (OAc). 31P-NMR (121.4 MHz, CDCl3) δ -18 2), 31.2 (CMe3), 21.0 (OAc). 31P-NMR: (121.4 MHz, CDCl3):
ppm. Anal. Calcd. for C31H35O5PS: C, 67.62%; H, 6.41%. Found: 17.0. HRMS calc. for C35H31O5F12PSNa: 845.1314. Found:
-
C, 67.20%, H, 6.19%.
845.1330 (-1.97 ppm.).
Adamantyl
3-O-acetyl-4,6-O-benzylidene-2-deoxy- tert-Butyl 3-O-acetyl-4,6-O-benzylidene-2-deoxy-2-di(2,4,6-
diphenylphosphine-1-thio- -D-altropyranoside (12).
trimethyl)phenylphosphine-1-thio- -D-altropyranoside (18).
1H-NMR (500 MHz, CDCl3): δ 7.66-7.63 (m, 4H, arom.), 7.37- 1H-NMR: (400 MHz, CDCl3): 7.29 (s, 5H), 6.96-6.67 (m, 4H),
3
3
7.29 (m, 6H, arom.), 7.28-7.25 (m ,5H, arom.), 5.50 (dd, 1H, 5.33 (dd, JH1-H2 = 2.6 Hz, JH1-P = 21.3 Hz, 1H, H-1), 5.10 (s, 1H,
3
3JH1-P = 22.9, Hz, JH1-H2 = 2.6 Hz, H-1), 5.36-5.35 (m, 1H, H-3), CHPh), 5.08 (s, 1H), 4.37 (s, 1H, H-3), 4.29 (dd, 3JH6-H5 = 4.8 Hz,
3
3
3
3
4.93 (s, 1H, CHPh), 4.19 (dd, JH6-H5 = 4.8 Hz, JH6-H6’ = 10.4 Hz, 3JH6-H6’ = 10.4 Hz, 1H, H-6), 3.94 (dt, JH5-H6 = JH5-H6’ = 4.9 Hz,
1H, H-6), 3.92 (dt, JH5-H6 = JH5-H6’ = 4.9 Hz, JH5-H4 = 9.8 Hz, 1H, 3JH5-H4 = 9.8 Hz, 1H, H-5), 3.69 (t, JH6’-H6 = JH6’-H5 = 10.3 Hz, 1H,
3
3
3
3
3
H-5), 3.44 (t, 3JH6’-H6 = 3JH6’-H5 = 10.3 Hz, 1H, H-6’), 3.09-3.07 (m, H-6’), 3.15 (dd, JH4-H3 = 2.3, JH4-H5 = 9.6 Hz, 1H, H-4), 2.92 (s,
3
3
3
3
1H, H-2), 2.83 (dd, JH4-H3 = 2.3, JH4-H5 = 9.6 Hz, 1H, H-4), 2.14 3H), 2.71 (s, 3H), 2.35 (s, 3H), 2.21(s, 6H), 2.14 (s, 3H), 2.10 (s,
(s, 3H, OAc), 2.03-1.64 (m, 15H, Adam.). 13C-NMR (125 MHz, 3H), 1.37 (s, 9H, CMe3). 13C-NMR: (125 MHz, CDCl3): 170.0,
2
CDCl3): δ 170.0 (OCOCH3), 137.2, 135.7, 135.6, 132.7, 132.6, 137.2, 128.9, 128.1, 126.0, 101.7 (CHPh), 81.6 (d, JC-P = 14.5
6 | RSC Advances, 2015, 00, 1-7
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Page 7 of 9
RSC Advances
Journal Name
ARTICLE
Hz, C-1), 75.0 (C-4), 71.5(C-6), 69.5 (C-5), 68.0 (C-4), 42.4 (d, 1JC- and Innovation of the University of Seville (CITIUS) for the use
View Article Online
DOI: 10.1039/C5RA10181F
P = 22.3 Hz, C-2), 31.4 (CMe3), 21.2, 20.9 (OAc), 20.5. 31P-NMR: NMR facilities.
(121.4 MHz, CDCl3):
-27.5. HRMS calc. for C37H48O5PS:
635.2942. Found: 635.2955 (-1.93 ppm.).
Notes and references
General Procedure for the 1,4-Addition of Boronic acids to
activated ketones
1
(a) I. Agranat, H. Caner, J. Caldwell, Nat. Rev. Drug Discover.
2002, , 753A. (b) M. Rouhi, Chem. Eng. News, 2004, 82, 47.
(c) H.-J Federsel, Nat. Rev. Drug Discover, 2005, , 753. (d) G.
1
4
Miglierini, Chimia Oggi, 2005, 23, S3, (e) H. Murakami. Top.
Curr. Chem., 2006, 269, 273.
(a) Comprehensive Asymmetric Catalysis, Vol. I-III; E. N.
Jacobsen, A. Pfaltz, H. Yamamoto, Springer: Berlin, 1999. (b)
E. Meggers, Chem. Eur. J., 2010, 16, 752. (c) Assymmetric
Synthesis-The Essentials, M. Christmann, S. Brässe, Eds.;
Wiley-VCH: Weinheim, 2008.
A mixture of ligand 10 (0.03 mmol, 5 mol %) and [Rh(C2H4)Cl]2
(6.0 mg, 0.015 mmol, 2.5 mol %) was stirred for 0.5 h in 1.2 mL
of degassed toluene. Arylboronic acid (1.2 mmol) was added
over the catalyst and sequentially the the activated ketone (0.6
mmol) and an aqueous solution of KOH (120 μL, 2.5 M). The
reaction was followed by TLC, stopped at 24h, the crude
reaction mixtures were purified by column chromatography.
2
3
4
(a) Y. Uozomi, Synlett, 2010, 1988. (b) P. J. Walsh, H. M. Li, C.
A. De Parrodi, Chem. Rev., 2007, 107, 2503. (c) J. Mlynarski, J.
Paradowska, Chem. Soc. Rev., 2008, 37, 1502.
(a) C. Grondal, M. Jeanty, D. Enders, Nat. Chem., 2010, 2,
(S)-3-Phenylcyclohexanone (6).
167. (b) A. Dondoni, A. Massi, Angew. Chem. Int. Ed. Engl.,
2008, 47, 167. (c) A. G. Doyle, E. N. Jacobsen, Chem. Rev.,
2007, 107, 5596. (b) S. Mukherjee, J. W. Yang, S. Hoffmann,
B. List, Chem Rev., 2007, 107, 5471.
(a) B. Trost, Proc. Natl. Acad. Sci. USA., 2004, 101, 5348. (b)
R. Noyori, M. Kitamura, T. Ohkuma, Proc. Natl. Acad. Sci.
USA., 2004, 101, 5356. (c) T. P. Yoon, E. N. Jacobsen, Science,
2003, 299, 1691.
(a) Carbohydrates: Tools for stereoselective synthesis. Ed.
M.M.K. Boysen Wiley-VCH, 2013. (b) S. Castillon, C. Claver, Y.
Diaz, Chem. Soc. Rev., 2005, 34, 702. (b) M. Diéguez, O.
Pàmies, A. Ruiz, Y. Diaz, S. Castillon, C. Claver, Coord. Chem.
Rev., 2004, 248, 1759.
(a) R. A. Laine In: Glycosciences: status and perspectives. H.-
J. Gabius, S. Gabius, Eds. Chapman & Hall, London, 1997, pp
1–14.
Colorless oil. [α]D20: +11.2° (c 0.9, CHCl3). HPLC: 64%, Chiralcel
OD-H column (n-hexane/2-propanol, 90/10), 0.5 mL/min; tR =
1
19.5 min (S-isomer), 22.4 min (R-isomer). H-NMR (400 MHz,
5
6
CDCl3): δ 7.33−7.36 (m, 2H), 7.21−7.26 (m, 3H), 3.05−2.95 (m,
1H), 2.37−2.59 (m, 4H), 2.07−2.16 (m, 2H), 1.80−1.89 (m, 2H).
13C-NMR (100 MHz, CDCl3): δ 210.9, 144.3, 128.6, 126.6, 126.5,
48.9, 44.7, 41.1, 32.7, 25.5. HRMS calc. for C12H15O: 175.1113.
Found: 175.1117 (-2.34 ppm.).
(S)-3-( p-Tolyl)cyclohexanone (21)
7
20
Colorless oil. [α]D = +21.3 (c. 0.5, CH2Cl2). HPLC: 98 % ee,
Chiralcel® AS-H column (n-hexane/2-propanol, 60/40, 0.6
mL/min); tR: 12.6 min. (R-isomer), 14.8 min. (S-isomer). 1H
NMR (400 MHz, CDCl3): δ 7.10-7.01 (m, 4H), 2.93-2.84 (m, 1H),
2.51-2.29 (m, 4H), 2.22 (s, 3H), 2.08-1.96 (m, 2H), 1.82-1.64 (m,
2H). ppm. 13C NMR (125 MHz, CDCl3): δ 211.0, 141.4, 136.2,
129.3 (CH x 2), 126.4 (CH x 2), 49.0, 44.3, 41.1, 32.8, 25.5, 20.9.
HRMS calc. for C13H17O: 189.1628. Found: 189.1274 (-2.96
ppm.).
8
9
V. Benessere, M. Lega, F. Ruffo, J. Organometal. Chem.,
2014, 771, 105-114.
(a) Fernández, A. Alcudia, B. Gori, V. Valdivia, M. V. García, N.
Khiar, Org. Biomol. Chem., 2010, 8, 4388.
10 (a) V. Valdivia, I. Fernández, N. Khiar, Org. Biomol. Chem.,
2014, 12, 1211. (b) N. Khiar, C. S. Araújo, B. Suárez, I.
Fernández. Eur. J. Org. Chem., 2006. 1685.
11 N. Khiar, B. Suárez, V. Valdivia, I. Fernández, Synlett, 2005,
2963.
12 N. Khiar, R. Navas, B. Suarez, E. Alvarez, I. Fernandez. Org.
Lett., 2008, 10, 3697.
13 N. Khiar. M. Pernía Leal, R. Navas, J. F. Moya, M. V. García
Pérez, I. Fernández, Org. Biomol. Chem., 2012, 10, 355.
14 (a) P. Tian, H.-Q. Dong, H.-Q.; G.-Q. Lin, ACS Catal., 2012, 2,
(R)-4-(p-Tolyl)pentan-2-one (22).
Colorless oil. [ ]D20= - 15.4 (c 0.3, CHCl3). HPLC: 70 % ee,
Chiralcel AS-H column (n-hexane/2-propanol, 98:2, 1 mL/min);
tR: 11.2 min (major), 12.9 min (minor). 1H NMR (500 MHz,
CDCl3): δ 7.14-7.12 (m, 4H), 3.32-3.28 (m, 1H), 2.80-2.60 (m,
2H), 2.34 (s, 3H), 2.09 (s, 3H), 1.28 (d, J = 6.5 Hz, 3H) ppm. 13C
NMR (125 MHz, CDCl3): δ 208.02, 143.20, 135.84, 129.27,
126.68, 52.16, 35.15, 30.60, 22.18, 21.03. HRMS calc. for
C12H16ONa: 199.1093. Found: 199.1089 (-2.32 ppm.).
95. (b) H. J. Edwards, J. D. Hargrave, S. D. Penrose, C. G.
Frost, Chem. Soc. Rev., 2010, 39, 2093. (c) N. Miyaura,
Organoboranes in Synthesis, American Chemical Society,
Washington, 2001, 94. (d) T. Hayashi, K. Yamasaki, Chem.
Rev., 2003, 103, 2829.
15 (a) Y. Takaya, M. Ogasawara, T. Hayashi, Tetrahedron Lett.,
1999, 40, 6957. (b) T. Hayashi, M. Takahashi, M. Takaya, M.
Ogasawara, J. Am. Chem. Soc., 2002, 124, 5052. (c) A. Kina, I.
Iwamura, T. Hayashi, J. Am. Chem. Soc., 2006, 128, 3904. (d)
A. Kina, T. Yasuhara, T. Nishimura, H. Iwamura, T. Hayashi,
Acknowledgements
Financial support was provided by the Andalusian Ministry of
Economy, Science and Innovation (P11-FQM-8046), the PAIDI
Program from the Andalusian Government (FQM-102 and
FQM-313), the Spanish Ministry of Economy and
Competitiveness (CTQ2013-49066-C2-1-R to and CTQ2013-
49066-C2-1-R. We thank the Centre of Research Technology
Chem. Asian J., 2006, 1, 707.
16 (a) M. Sakai, H. Hayashi, N. Miyaura, Organometallics, 1997,
16, 4229. (b) Y. Takaya, M. Ogasawara, T. Hayashi, M. Sakai,
N. Miyaura, J. Am. Chem. Soc., 1998, 120, 5579.
17 [17](a) N. Khiar, A. Salvador, V. Valdívia, A. Chelouan, A.
Alcudia, E. Álvarez, I. Fernández. J.Org. Chem., 2013, 78
,
6510 (a) J. Bürgi, R. Mariz, M. Gatti, E. Drinkel, X. Luan, S.
Blumentritt, A. Linden, R. Dorta, Angew. Chem. Int. Ed.,
This journal is © The Royal Society of Chemistry 20xx
RSC Advances, 2015, 00, 1-7 | 7
Please do not adjust margins

Please do not adjust margins
RSC Advances
Page 8 of 9
ARTICLE
Journal Name
2009, 48, 2768. (b) R. Mariz, A. Poater, M. Gatti, E. Drinkel, J.
View Article Online
DOI: 10.1039/C5RA10181F
J. Bürgi, X. J. Luan, S. Blumentritt, A. Linden, L. Cavallo, R.
Dorta,. Chem. Eur. J., 2010, 16, 14335. (c) A. Poater, F.
Ragone, R. Mariz, R. Dorta, L. Cavallo, Chem. Eur. J., 2010, 16
14348.
,
18 (a) F. Lang, D. Li, J. Chen, J. Chen, L. Li, L. Cun, J. Zhu, J. Deng,
J. Liao. Adv. Synth. Catal., 2010, 352, 843. (b) Thaler, T.; Guo,
L.-N.; Steib, A. K.; Raducan, A. K. M.; Karaghiosoff, K.; Mayer,
P.; Knochel, P. Org. Lett., 2011, 13, 3182; (c) Feng, X.; Wang,
Y.; Wei, B.; Yang, J.;Du, H. Org. Lett., 2011, 13, 3300; (d)
Chen, G.; Gui, J., Li, L.; Liao, L. Angew. Chem. Int. Ed. Engl.,
2011, 50, 7681; (e) Feng, X.; Wei, B.; Yang, J.; Du, H. Org.
Biomol. Chem., 2011, 9, 5927; (f) F. Xue, X. Li, B. Wan, J. Org.
Chem., 2011, 76, 7256; (g) Y. Wang, X. Feng, H. Du, Org. Lett.,
2011, 13, 4954. (h) Chen, Q.-A.; Dong, X.; Chen, M.-W.;
Wang, D.-S.; Zhou, Y.-G.; LI, Y.-X. Org. Lett., 2010, 12, 1928.
(i) Chen, J.; Chen, J.; Lang, F.; Zhang, X.; Cun, L.; Zhu, J.; Deng,
J.; Liao, J. J. Am. Chem. Soc., 2010, 132, 4552. For an
excellent review see: Y. Li, M.-H. Xu, Chem. Commun., 2014,
50, 3771.
19 (a) T. Minuth, M. M. K. Boysen, Org. Lett., 2009, 11, 4212. (b)
H. Grugel, F. Albrecht, T. Minuth, M. M. K. Boysen, Org. Lett.,
2012, 14, 3780. (c) H. Grugel, F. Albrecht, T. Minuth, M. M. K.
Boysen, Org. Lett., 2009, 14, 3780. (d) H. Grugel, F. Albrecht,
M. M. K. Boysen, Adv. Synth. Catal., 2014, 356, 3289.
20 (a) D. A. Evans, K. R. Campos, J. S. Tedrow, F. E. Michael, M.
R. Gagne, J. Am Chem Soc., 2000, 122, 7905. (b) D. A. Evans,
F. E. Michael, J. S. Tedrow, K. R. Campos, J. Am. Chem. Soc.,
2003, 125, 3538.
21 (a) N. Khiar, C. S. Araújo, B. Suárez, E. Álvarez, I. Fernández,
Chem. Commun., 2004, 44. (b) N. Khiar, C. S. Araújo, B.
Suárez, I. Fernández, Eur. J. Org. Chem., 2006, 1685.
22 N. Khiar, B. Suárez, V. Valdivia, I. Fernández, Synlett, 2005,
2963.
23 E. Abel, S.K. Bhargava, K. G. Orrell, Prog. Inorg. Chem., 1984,
32, 1. (b) E. Abel, J. Dormer, D. Ellis, K. G. Orrell, V. Sik, M. B.
Hursthouse, M. A. Mazid, J. Chem. Soc. Dalton Trans., 1992,
1073.
24 N. Khiar, R. Navas, E. Alvarez, I. Fernandez, Arkivoc,
2008, 8, 211.
25 J. F. Moya, E. Elhalem, E. Álvarez, I. Frenández, N. Khiar. Org.
Biomol. Chem., 2015, 13, 1904.
26 A. Fürst, P. A. Plattner, Helv. Chim. Acta, 1949, 32, 275.
8 | RSC Advances, 2015, 00, 1-7
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 9 of 9
RSC Advances
View Article Online
DOI: 10.1039/C5RA10181F
TOC
Mixed S/P ligands derived from carbohydrates are good
catalyst precursors for the Rh(I)-catalyzed 1,4-addition
of phenylboronic acid to cyclohexenone. Interestingly,
ligands 3 and 10, both derived from D-sugar are able to
generate the addition product of the phenylboronic acid
to the cyclohexenone with opposite configuration,
behaving thus as enantiomers.