Highly enantioselective asymmetric reactions involving zinc ions promoted by chiral aziridine alcohols

Article abstract of DOI:10.1016/j.tetasy.2017.10.007

Enantiomerically pure, chiral secondary and tertiary aziridine alcohols (including the aziridine analogue of ProPhenol—AziPhenol) have proven to be highly effective catalysts for enantioselective asymmetric reactions in the presence of zinc ions, including arylation of aromatic aldehydes, epoxidation of chalcone and addition of diethylzinc to aldehydes, leading to the desired chiral products in high chemical yields (up to 90%) and with ee's up to 90%. A higher catalytic activity of Prophenol-type bis(aziridine alcohol) in the aforementioned asymmetric transformations has been demonstrated.

Full text of DOI:10.1016/j.tetasy.2017.10.007

Tetrahedron: Asymmetry xxx (2017) xxx–xxx
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Highly enantioselective asymmetric reactions involving zinc ions
promoted by chiral aziridine alcohols
⇑
´
´
Szymon Jarzynski, Greta Utecht, Stanisław Lesniak, Michał Rachwalski
´
´
Department of Organic and Applied Chemistry, University of Łódz, Tamka 12, 91-403 Łódz, Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
Enantiomerically pure, chiral secondary and tertiary aziridine alcohols (including the aziridine analogue
of ProPhenol—AziPhenol) have proven to be highly effective catalysts for enantioselective asymmetric
reactions in the presence of zinc ions, including arylation of aromatic aldehydes, epoxidation of chalcone
and addition of diethylzinc to aldehydes, leading to the desired chiral products in high chemical yields
(up to 90%) and with ee’s up to 90%. A higher catalytic activity of Prophenol-type bis(aziridine alcohol)
in the aforementioned asymmetric transformations has been demonstrated.
Received 16 September 2017
Accepted 9 October 2017
Available online xxxx
Ó 2017 Elsevier Ltd. All rights reserved.
1. Introduction
In order to continue our studies on stereocontrolled reactions
including the formation of carbon–carbon bonds,21–25 having
The enantioselective formation of carbon–carbon bonds is one
of the most essential strategies in modern organic chemistry.1,2
Among them, asymmetric reactions involving zinc cations consti-
tute current and extensively studied topics in synthetic organic
chemistry. Typical examples of zinc(II)-mediated stereocontrolled
transformations are asymmetric arylation of aldehydes3 and epox-
advantageous results in the asymmetric arylation of aldehydes
using secondary and tertiary aziridine alcohols3 we decided to syn-
thesize a novel ProPhenol-type ligand (AziPhenol) containing chi-
ral aziridine moieties and to compare its catalytic activity with
those exhibiting by the aforementioned simple aziridine alcohols.
Similar studies have been conducted using azetidine analogues of
ProPhenol ligands in Friedel–Crafts reaction.20 These analogues
exhibited much higher catalytic activity in comparison with those
found with simple chiral azetidine alcohols.20 First of all, we
decided to check the catalytic activity of all designed ligands in
the asymmetric epoxidation of chalcone.
idation of
a
,b-unsaturated carbonyl compounds (e.g. chalcone).4
Both processes are of great importance due to a high significance
of potential applications of their chiral products. Thus, diaryl-
methanols can act as precursors of many biologically and pharma-
cologically relevant compounds,3 e.g. (R)-orphenadrine and (R)-
neobenodine,5 (S)-cetirizine6 or (S)-BMS 1843947,8 (Fig. 1).
In turn, chiral epoxides are a structural part of many natural
products, fragrances (epoxides of carvone), pheromones ((+)-dis-
parlure) or alkaloids (scopolamine). Moreover, chiral epoxides find
applications in the synthesis of other natural products such as (ꢀ)-
Cleistenolide9 and cascarillic acid,10 and in many other asymmetric
transformations.11 Chiral epoxides are also present in many biolog-
ically relevant molecules such as Neocarzinostatin,12 Ovalicin13 or
Epothilones (Fig. 2).14,15
2. Results and discussion
2.1. Synthesis of the ligands
Chiral aziridine alcohols L1–L4 (Fig. 3) were synthesized as
described previously.26,27 AziPhenol ligand L5 was prepared via a
three-step synthetic route (Scheme 1).
In the first step, p-cresol was treated with formaldehyde in
aqueous NaOH solution affording the corresponding diol 2.18 To
the above diol, HBr in acetic acid was added at room temperature,
which gave compound 3 in 80% yield.18 Dibromide 3 was reacted
with aziridine alcohol 426 in dry DMF, in the presence of potassium
carbonate at 0 °C. Pure ligand L5 was obtained after purification via
column chromatography in 86% yield.
ProPhenol dinuclear ligands containing proline16–19 or aze-
tidine20 can form complexes with zinc ions facilitating various
asymmetric transformations such as direct aldol reactions,16,19
1,4-additions of diethyl phosphite to enones,17 nitroaldol (Henry)
reactions,18 or Friedel–Crafts alkylations of pyrrole with
chalcones.20
⇑
Corresponding author.
E-mail address: mrach14@wp.pl (M. Rachwalski).
https://doi.org/10.1016/j.tetasy.2017.10.007
0957-4166/Ó 2017 Elsevier Ltd. All rights reserved.
´
Please cite this article in press as: Jarzynski, S.; et al. Tetrahedron: Asymmetry (2017), https://doi.org/10.1016/j.tetasy.2017.10.007

´
S. Jarzynski et al. / Tetrahedron: Asymmetry xxx (2017) xxx–xxx
2
CO2H
O
NMe2
HO
N
N
O
HO2C
Me
(S)-BMS-184394
Cl
Cetirizine; Virlix; Cetryn; Zirtek;
2-Me: (R)-orphenandrine
4-Me: (R)-neobenodine
NMe2
O
O
N
PhSO3H
CO2H
N
N
Cl
Bepotastine besilate
Cl
Carbinoxamine
Figure 1. Diarylmethane-based drugs.
2.2. Asymmetric epoxidation of chalcone—screening of the
conditions and ligands
O
O
O
O
O
O
OH
The designed aziridine alcohol L5 was tested as a chiral ligand
in the asymmetric epoxidation of chalcone following the procedure
described by Ulukanli et al.4 (Scheme 2).17 The reactions were car-
ried out in various solvents and at 0 °C or 20 °C, respectively, in the
O
O
Ovalicin
OCH3
R
O
O
S
N
O
OH
H
O
O
OH
1. Ligand L5 (0.1 mmol)
2. Zn2Et (0.2 mmol)
3. CMHP (0.6 mmol)
O
O
O
O
N
H
OH
O
OH
O
OH
solvent
Epothilones
Neocarzinostatin
Scheme 2. Asymmetric epoxidation of chalcone catalyzed by ligand L5 under
various conditions.
Figure 2. Drugs containing a chiral epoxide.
Ph
Ph
Ph
Ph
OH
HO
Ph
CF3
N
OH
N
OH
Ph
Ph
Ph
Ph
CF3
OH
OH
N
N
H
OH
N
N
Trt
Trt
CH3
Trt
L1
L2
L3
L4
L5
Figure 3. Chiral aziridine alcohols L1–L5.
Ph
Ph
Ph
OH
HO
Ph
Ph
Ph
N
OH
N
OH
OH
OH OH
Br
OH
Br
OH
4
N
H
HBr, AcOH
rt
NaOH, HCHO
H2O, rt
K2CO3, DMF, rt
CH3
CH3
CH3
CH3
L5
2
3
1
Scheme 1. Synthesis of ProPhenol ligand L5.
´
Please cite this article in press as: Jarzynski, S.; et al. Tetrahedron: Asymmetry (2017), https://doi.org/10.1016/j.tetasy.2017.10.007

´
3
S. Jarzynski et al. / Tetrahedron: Asymmetry xxx (2017) xxx–xxx
Table 1
Asymmetric epoxidation of chalcone promoted by an AziPhenol system L5, under various conditions
Entry
Solvent
T [°C]
Yield [%]
ee [%]a
1
2
3
4
5
THF
20
20
20
20
0
73
81
78
88
93
50
27
60
76
97
CH2Cl2
Toluene
Et2O
Et2O
a
Determined by chiral HPLC using Chiralcel OD-H column.
O
arylation using p-tolualdehyde, phenylboronic acid and diethylzinc
was performed in the presence of ligand L5 (Scheme 4).
Analyzing the results of the above transformation, the desired
diarylmethanol was obtained in 95% chemical yield and with 97%
enantiomeric excess. In the light of these values, it should be con-
cluded, that AziPhenol ligand L5 was the most active catalyst for
the asymmetric arylation of p-tolualdehyde using phenylboronic
acid and Et2Zn.
O
1. Ligand (0.1 mmol)
2. Zn2Et (0.2 mmol)
3. CMHP (0.6 mmol)
O
Et2O, 0 o
C
Scheme 3. Asymmetric epoxidation of chalcone catalyzed by aziridine alcohols L1–
L5.
presence of diethylzinc and using cumene hydroperoxide (CMHP)
as the epoxidising agent (Table 1).
2.5. Asymmetric addition of arylzinc systems generated from
phenylboronic acid and diethylzinc to aromatic aldehydes in
the presence of catalyst L5
Inspection of Table 1 clearly shows that the best solvent of this
asymmetric transformation is diethyl ether. Enantioselective epox-
idation of chalcone carried out in Et2O at 0 °C led to the formation
of the representative epoxide in 93% chemical yield and with very
high enantioselectivity (97% ee) (Table 1, entry 5).
Having the most active system L5 in hands, we decided to per-
form an enantioselective arylation reactions under the same condi-
tions, using other aromatic aldehydes as starting materials
(Scheme 5). The results are summarized in Table 3.
2.3. Asymmetric epoxidation of chalcone—screening of the
ligands
Having established the best results in terms of solvent and tem-
perature, further aziridine alcohols L1–L4 were investigated in the
same asymmetric process (Scheme 3). All the results (including
those for ligand L5) are collected in Table 2.
OH
B(OH)2
ZnEt
L5
Ligand
Et2Zn
Analysis of the results from Table 2 clearly evidences that all the
aziridine alcohols L1–L5 are efficient catalysts for the enantioselec-
tive epoxidation of chalcone, leading to the desired product in high
chemical yields and with high enantiomeric excess. The highest
enantioselectivity was achieved using an AziPhenol system L5.
toluene
CHO
60oC, 12h
Scheme 4. Asymmetric arylation of p-tolualdehyde catalyzed by L1–L5.
2.4. Asymmetric addition of arylzinc systems generated from
phenylboronic acid and diethylzinc to p-tolualdehyde catalyzed
by an AziPhenol system L5
OH
B(OH)2
ZnEt
Previously, we reported a successful asymmetric arylation of
aromatic aldehydes using aziridine alcohols L2–L4 (L1 had been
tested earlier by others).3 In the most efficient reaction, the corre-
sponding diarylmethanol was obtained in 89% yield and with 93%
of ee.3
L5
Ligand
Et2Zn
R
toluene
CHO
60oC, 12h
R
In order to compare the catalytic activity of AziPhenol L5 with
those exhibited by the aforementioned ligands L1–L4, asymmetric
Scheme 5. Addition of arylzinc system to aromatic aldehydes in the presence of
ligand L5.
Table 2
Asymmetric epoxidation of chalcone—screening of the ligands
Entry
Ligand
Product
ee [%]b
Abs. config.c
a
Yield [%]
[
a
]
D
1
2
3
4
5
L1
L2
L3
L4
L5
88
94
85
90
93
ꢀ176.4
ꢀ173.9
ꢀ172.8
ꢀ178.7
ꢀ179.2
86
82
80
91
97
(2R,3S)
(2R,3S)
(2R,3S)
(2R,3S)
(2R,3S)
a
b
c
In chloroform (c 0.3).
Determined by chiral HPLC using Chiralcel OD-H column.
According to literature data.4
´
Please cite this article in press as: Jarzynski, S.; et al. Tetrahedron: Asymmetry (2017), https://doi.org/10.1016/j.tetasy.2017.10.007

´
S. Jarzynski et al. / Tetrahedron: Asymmetry xxx (2017) xxx–xxx
4
Table 3
Addition of arylzinc species to aromatic aldehydes promoted by ligand L5
Entry
R
Products
a
Yield [%]
[
a
]
D
ee [%]b
Abs. config.c
1
2
3
4
5
6
7
4-Me
4-OMe
4-NO2
4-CF3
4-Br
95
89
85
87
91
90
94
ꢀ4.4
97
92
91
93
91
98
93
(S)
(S)
(S)
(S)
(S)
(S)
(S)
ꢀ12.3
+48.4
+28.8
+17.1
+8.8
4-Cl
2-Me
ꢀ2.7
a
b
c
In chloroform (c 0.3).
Determined by chiral HPLC using Chiralcel OD, OD-H or AD-H columns.
Taken from the literature28,29 (on the basis of specific rotation signs and retention times in HPLC chromatograms).
O
3. Conclusions
OH
L5
Ligand
Et2Zn
Toluene, 24h
Ar
H
Ar
The newly synthesized bis(aziridine alcohol) L5 introduced into
a phenol system has proven to be very effective and versatile
ligand catalyzing asymmetric transformations involving zinc ions,
such as the enantioselective epoxidation of chalcone, arylation of
aromatic aldehydes using phenylboronic acid and diethylzinc addi-
tion to aromatic aldehydes. As described earlier, ProPhenol-type
ligands can spontaneously form chiral dinuclear metal complexes
with e.g. ZnEt2. Such formed complex posses both a Lewis acidic
site to activate an electrophile and a Brønsted basic site to depro-
tonate a pronucleophile.19 Moreover, this catalytic system exhib-
ited higher catalytic activity in comparison with those showed by
aziridine alcohols described earlier.3,27
Scheme 6. Enantioselective addition of diethylzinc to aromatic aldehydes cat-
alyzed by L5.
The results clearly indicate that aziridine alcohol L5 is a very
efficient chiral catalyst for the enantioselective addition of arylzinc
system to aromatic aldehydes, leading to the corresponding prod-
ucts in high chemical yields and also with high enantiomeric
excess values.
2.6. Asymmetric addition of diethylzinc to aromatic aldehydes
in the presence of ligand L5
4. Experimental
4.1. General
In our previous work, the enantioselective diethylzinc addition
to aromatic aldehydes in the presence of ligands of type L3, was
described.27 Using the most efficient system, the corresponding
chiral alcohol was formed in 97% yield and with 93% of ee.27
As in the case of the previous asymmetric reaction described
herein, we decided to confirm the catalytic activity of newly syn-
thesized AziPhenol ligand L5 with those exhibited by aziridine
alcohols reported previously.27 Moreover, anticipating its high cat-
alytic capacity, we also performed the asymmetric diethylzinc
addition to other aromatic aldehydes (Scheme 6). All the results
are collected in Table 4.
Inspection of Table 4 clearly evidences that aziridine alcohol L5
constructed on the AziPhenol platform exhibited the highest cat-
alytic activity in the asymmetric addition of diethylzinc to aro-
matic aldehydes, in comparison with previously studied chiral
aziridine alcohols.
Toluene, tetrahydrofuran and diethyl ether were distilled from
sodium benzophenone ketyl radical. Dichloromethane was dis-
tilled over calcium chloride. 1H, 13C and 19F NMR spectra were
recorded on a Bruker instrument at 600 MHz and 150 MHz, respec-
tively, with CDCl3 as solvent and TMS as internal standard. Data are
reported as s = singlet, d = doublet, t = triplet, q = quartet, m = mul-
tiplet, br. s = broad singlet. Optical rotations were measured on a
Anton Paar MCP500 polarimeter with a sodium lamp at room tem-
perature (c 0.3). Column chromatography was carried out using
Merck 60 silica gel. TLC was performed on Merck 60 F254 silica
gel plates. Visualization was accomplished with UV light (254
nm) or using iodine vapors. The enantiomeric excess (ee) values
were determined by chiral HPLC (Chiralcel AD-H, OD or OD-H
columns).
Table 4
Diethylzinc addition to aromatic aldehydes in the presence of ligand L5
Entry
Ar
Product
ee [%]b
Abs. config.c
a
Yield [%]
[a
]
D
1
2
3
4
Ph
97
92
91
86
ꢀ14.8
ꢀ13.7
ꢀ5.3
98
97
97
94
(S)
(S)
(S)
(S)
4-MePh
4-MeOPh
4-NCPh
ꢀ3.9
5
93
ꢀ4.6
98
(S)
a
b
c
In chloroform (c 0.3).
Determined by chiral HPLC using Chiralcel OD, OD-H or AD-H columns.
According to literature data.30,31
´
Please cite this article in press as: Jarzynski, S.; et al. Tetrahedron: Asymmetry (2017), https://doi.org/10.1016/j.tetasy.2017.10.007

´
5
S. Jarzynski et al. / Tetrahedron: Asymmetry xxx (2017) xxx–xxx
4.2. Synthesis of the ligands
over anhydrous Na2SO4, filtered and the solvents were evaporated
in vacuo. The crude mixture was purified by column chromatogra-
phy (silica gel, hexane with ethyl acetate in gradient) to afford the
corresponding diarylmethanols. Their spectroscopic data are in full
agreement with literature.3,28,29 Chemical yield, specific rotation
and enantiomeric excess values are collected in Table 3. HPLC con-
ditions along with copies of HPLC chromatograms for the arylation
products are included in the Supporting Information.
Aziridine alcohols L1–L4 were synthesized according to the pro-
tocols described previously.26,27 Compounds 2 and 3 were obtained
according to literature data.18
4.2.1. Synthesis of AziPhenol ligand L5
In a round-bottomed flask, aziridine alcohol 426 (2 mmol),
K2CO3 (8 mmol) and dry DMF (5 mL) were mixed at 0 °C. The mix-
ture was stirred for 15 min under argon followed by the addition of
dibromide 3 (1 mmol). The ice bath was removed after the addition
and the resulting solution was allowed to stir at room temperature
for 12 h. Water was added in order to quench the reaction, which
was extracted with Et2O (3 ꢁ 10 mL) and the combined organic
layers were dried over anhydrous MgSO4, filtered and the solvents
were evaporated in vacuo. The crude mixture was purified by col-
umn chromatography (silica gel, hexane/ethyl acetate in gradient)
to afford the corresponding product L5.
4.5. Asymmetric addition of diethylzinc to aldehydes—general
procedure
Chiral ligand L5 (0.1 mmol) was placed in a dried Schlenk tube
under a nitrogen atmosphere. Freshly distilled toluene (10 mL) was
then added followed by Et2Zn solution (1.0 M in hexane, 3 mmol).
The resulting solution was cooled to 0 °C and stirred for approxi-
mately 15 min. The aldehyde (1 mmol) was added and the mixture
was stirred at room temperature overnight. The reaction was
quenched with saturated ammonium chloride solution, layers
were separated and the aqueous phase was extracted with diethyl
ether (4 ꢁ 10 mL). The combined organic layers were washed with
brine (10 mL) and dried over anhydrous MgSO4 and the solvents
were evaporated in vacuo. The crude compound was purified by
flash chromatography (hexane with ethyl acetate in gradient) to
give the final products. Their spectroscopic data are in full agree-
ment with literature.27,30,31 Chemical yield, specific rotation and
enantiomeric excess values are collected in Table 4. HPLC condi-
tions along with copies of HPLC chromatograms for the Et2Zn addi-
tion products are included in the Supporting Information.
4.2.1.1. ((2S,20S)-1,10-((2-Hydroxy-5-methyl-1,3-phenylene)bis
(methylene))bis(aziridine-2,1-diyl))bis(diphenylmethanol)
L5.
Yield 86%, Colorless solid; m.p. 141–143 °C, [a]
23 = +19.6
D
(c 0.3, CHCl3); 1H NMR (600 MHz, CDCl3) d: 1.47 (br s, 1H), 1.47
(d, 2H, JH,H = 6.0 Hz), 2.01 (d, 2H, JH,H = 3.0 Hz), 2.12 (s, 3H), 2.48
(dd, 2H, JH,H = 3.0 Hz, JH,H = 6.0 Hz), 3.09 (s, 2H), 3.37 (d, 2H, JH,H
= 13.5 Hz), 3.63 (d, 2H, JH,H = 13.5 Hz), 6.72 (s. 2H), 7.07–7.18 (m,
9H), 7.21–7.23 (m, 4H), 7.27–7.31 (m, 7H); 13C NMR (151 MHz,
CDCl3): d 20.5 (CH3), 30.7 (CH azir), 46.8 (CH azir), 59.8 (CH2),
74.8 (Cq), 123.8 (Cq ar), 126.3 (Car), 126.4 (Car), 127.0 (Car), 127.1
(Car), 128.0 (Car), 128.0 (Car), 128.2 (Cq ar) 128.6 (Car), 144.8 (Cqar),
146.7 (Cq ar), 152.0 (Cq ar) ppm; HRMS (ESI-TOF): m/z [M + H]+ calcd
for C39H39N2O3: 583.2968, found 583.2961. Copies of NMR spectra
of compound L5 are included in the Supporting Information.
Acknowledgement
Financial support by the National Science Centre (NCN), Poland,
Grant Preludium No. 2014/15/N/ST5/02897 for S. J. is gratefully
acknowledged.
4.3. Enantioselective epoxidation of chalcone—general
procedure4
A. Supplementary data
Aziridine alcohol L1–L5 (0.1 mmol) and anhydrous Et2O (4 mL)
were placed in a round-bottomed flask under nitrogen atmosphere.
After cooling to 0 °C, Et2Zn (0.2 mmol, 1 M solution in toluene) was
added whilst stirring. Chalcone (0.5 mmol) and CMHP (0.6 mmol,
80% solution in cumene) were added and the mixture was stirred
at 0 °C for 12 h. The reaction was quenched with aqueous saturated
NaHCO3 and extracted with Et2O. The organic layer was washed
with aqueous Na2CO3 and brine. The combined organic layers were
dried over MgSO4, and the solvent was evaporated in vacuo. The
residue was purified by column chromatography (silica gel, hexane
with ethyl acetate in gradient) to afford the appropriate chiral
epoxide. Its spectroscopic data are in full agreement with litera-
ture.4 Chemical yield, optical rotation and enantiomeric excess val-
ues are collected in Tables 1 and 2. HPLC conditions along with
copies of HPLC chromatograms for the epoxidation products are
included in the Supporting Information.
Supplementary data associated with this article can be found, in
the online version, at https://doi.org/10.1016/j.tetasy.2017.10.007.
References
1. Pellissier, H. Tetrahedron 2007, 63, 9267–9331.
2. Gaunt, M. J.; Johansson, C. C. C.; McNally, A.; Vo, N. T. Drug Discovery Today
2007, 12, 8–27.
3. Wujkowska, Z.; Jarzyn´ ski, S.; Pieczonka, A. M.; Les´niak, S.; Rachwalski, M.
Tetrahedron: Asymmetry 2016, 27, 1238–1244.
4. Karakaya, I.; Karabuga, S.; Mart, M.; Altundas, R.; Ulukanli, S. Synthesis 2016, 48,
1719–1726.
5. Meguro, K.; Aizawa, M.; Sohoda, T.; Kawamatsu, Y.; Nagaoka, N. Chem. Pharm.
Bull. 1985, 33, 3787–3797.
6. Devalia, J. L.; De Vos, C.; Hanotte, F.; Baltes, E. Allergy 2001, 56, 50–57.
7. Thacher, S. M.; Vasudevan, J.; Chandraratna, R. A. S. Curr. Pharm. Des. 2000, 6,
25–58.
8. Klaholz, B. P.; Mitschler, A.; Moras, D. J. Mol. Biol. 2000, 302, 155–170.
9. Schmidt, B.; Kunz, O.; Biernat, A. J. Org. Chem. 2010, 75, 2389–2394.
10. Kumar, P.; Dubey, A.; Harbindu, A. Org. Biomol. Chem. 2012, 10, 6987–6994.
11. Meninno, S.; Lattanzi, A. Chem. Eur. J. 2016, 22, 3632–3642.
12. Myers, A. G.; Liang, J.; Hammond, M.; Harrington, P. M.; Wu, Y.; Kuo, E. Y. J. Am.
Chem. Soc. 1998, 120, 5319–5320.
4.4. Asymmetric arylation of aldehydes with phenylboronic acid
in the presence of diethyl zinc—general procedure
13. Corey, E. J.; Dittami, J. P. J. Am. Chem. Soc. 1985, 107, 256–257.
14. Zhu, B.; Panek, J. S. Org. Lett. 2000, 2, 2575–2578.
Diethylzinc (2.5 mmol, 1 M solution in toluene) was added to a
solution of phenylboronic acid (0.5 mmol) in toluene (1.5 mL)
under nitrogen atmosphere. After stirring at 60 °C for 15 min, the
mixture was cooled to ambient temperature and the solution of
ligand L5 (10 mol%) in toluene (1 mL) was added. Reaction was
cooled to 0 °C and aldehyde (0.5 mmol) was added. After stirring
for 24 h, the mixture was quenched by 15 mL of saturated, aqueous
solution of NH4Cl and the aqueous phase was extracted with
diethyl ether (3 ꢁ 10 mL). The combined organic layers were dried
15. Wang, J.; Sun, B.-F.; Cui, K.; Lin, G.-Q. Org. Lett. 2012, 14, 6354–6357.
16. Trost, B. M.; Miege, F. J. Am. Chem. Soc. 2014, 136, 3016–3019.
17. Zhao, D.; Yuan, Y.; Chan, A. S. C.; Wang, R. Chem. Eur. J. 2009, 15, 2738–2741.
18. Trost, B. M.; Yeh, V. S. C.; Ito, H.; Bremeyer, N. Org. Lett. 2002, 4, 2621–2623.
19. Trost, B. M.; Bartlett, M. J. Acc. Chem. Res. 2015, 48, 688–701.
20. Hua, Y.-Z.; Han, X.-W.; Yang, X.-C.; Song, X.; Wang, M.-C.; Chang, J.-B. J. Org.
Chem. 2014, 79, 11690–11699.
21. Rachwalski, M.; Leenders, T.; Kaczmarczyk, S.; Kiełbasin´ ski, P.; Les´niak, S.;
Rutjes, F. P. J. T. Org. Biomol. Chem. 2013, 11, 4207–4213.
´
Please cite this article in press as: Jarzynski, S.; et al. Tetrahedron: Asymmetry (2017), https://doi.org/10.1016/j.tetasy.2017.10.007

´
S. Jarzynski et al. / Tetrahedron: Asymmetry xxx (2017) xxx–xxx
6
22. Les´niak, S.; Rachwalski, M.; Jarzyn´ ski, S.; Obijalska, E. Tetrahedron: Asymmetry
2013, 24, 1336–1340.
27. Jarzyn´ ski, S.; Les´niak, S.; Pieczonka, A. M.; Rachwalski, M. Tetrahedron:
Asymmetry 2015, 26, 35–40.
23. Rachwalski, M. Tetrahedron: Asymmetry 2014, 25, 219–223.
24. Rachwalski, M.; Kaczmarczyk, S.; Les´niak, S.; Kiełbasin´ ski, P. ChemCatChem
2014, 6, 873–875.
28. Karthikeyan, J.; Jeganmohan, M.; Cheng, C.-H. Chem. Eur. J. 2010, 16, 8989–
8992.
29. Yamamoto, Y.; Kurihara, K.; Miyaura, N. Angew. Chem., Int. Ed. 2009, 48, 4414–
25. Rachwalski, M.; Jarzyn´ ski, S.; Les´niak, S. Tetrahedron: Asymmetry 2013, 24,
4416.
1117–1119.
30. Zhao, W.-X.; Liu, G.-J.; Wang, J.; Li, F.; Liu, L. Tetrahedron: Asymmetry 2016, 27,
1139–1144.
31. Lombardo, M.; Chiarucci, M.; Trombini, C. Chem. Eur. J. 2008, 14, 11288–11291.
26. Willems, J. G. H.; Hersmis, M. C.; de Gelder, R.; Smits, J. M. M.; Hammink, J. B.;
Dommerholt, F. J.; Thijs, L.; Zwanenburg, B. J. Chem. Soc., Perkin Trans. 1 1997,
963–968.
´
Please cite this article in press as: Jarzynski, S.; et al. Tetrahedron: Asymmetry (2017), https://doi.org/10.1016/j.tetasy.2017.10.007