Cascade Reaction by Chemo- and Biocatalytic Approaches to Obtain Chiral Hydroxy Ketones and anti 1,3-Diols

Article abstract of DOI:10.1002/open.201800056

A chemo- and biocatalytic cascade approach was applied for the stereoselective synthesis of hydroxy ketones and the corresponding 1,3-diols. A new class of tridentate N,N,O ligands was used with copper(II) complexes for the asymmetric β-borylation of α,β-unsaturated compounds. The complex containing ligand L5 emerged as the best performer, and it gave the organoborane derivatives with good ee values. The corresponding keto–alcohol compounds were then bioreduced by yeasts. The biotransformation set up with Rhodotorula rubra allowed (R)-keto–alcohols and (S,S)-diols to be obtained with up to 99 % ee and up to 99 % de in favor of the anti enantiomers.

Full text of DOI:10.1002/open.201800056

DOI: 10.1002/open.201800056
Cascade Reaction by Chemo- and Biocatalytic Approaches
to Obtain Chiral Hydroxy Ketones and anti 1,3-Diols
Raffaella Gandolfi+,[a] Giorgio Facchetti+,[a] Michael S. Christodoulou,[a] Marco Fus›,[b]
Fiorella Meneghetti,[a] and Isabella Rimoldi*[a]
A chemo- and biocatalytic cascade approach was applied for
the stereoselective synthesis of hydroxy ketones and the corre-
sponding 1,3-diols. A new class of tridentate N,N,O ligands was
used with copper(II) complexes for the asymmetric b-boryla-
tion of a,b-unsaturated compounds. The complex containing
ligand L5 emerged as the best performer, and it gave the orga-
noborane derivatives with good ee values. The corresponding
keto–alcohol compounds were then bioreduced by yeasts. The
biotransformation set up with Rhodotorula rubra allowed (R)-
keto–alcohols and (S,S)-diols to be obtained with up to 99%ee
and up to 99%de in favor of the anti enantiomers.
1. Introduction
Asymmetric transition-metal catalysts and enzymes have
emerged as the most effective synthetic tools for the stereose-
lective preparation of many chiral compounds. The possibility
to exploit different catalytic approaches for enantio- and dia-
stereoselective catalysis is a challenging topic in chemical syn-
thesis, especially if control of multiple stereogenic centers is in-
volved.[1] Furthermore, the development of improved proce-
dures by means of using less expensive, easy-to-handle, and
more sustainable catalyst systems still remains an elusive goal.
Herein, we report a simple, inexpensive, and efficient cata-
lyst system for simultaneous 1,4-conjugate addition and reduc-
tion steps on a,b-unsaturated carbonyl compounds through
base-controlled transition-metal catalysis or/and by using
yeasts under mild conditions at room temperature. In our case,
a cascade reaction allowed the asymmetric synthesis of differ-
ently substituted diols through the formation of the corre-
sponding chiral keto–alcohols and diols by bioreduction. The
first step is based on enriched keto–alcohol formation through
CuII-catalyzed asymmetric boron conjugate addition to a,b-un-
saturated carbonyl compounds.[2] In contrast to popular proto-
cols involving the use of chiral CuI for the enantioselective b-
borylation of a,b-unsaturated acceptors, those involving the
use of chiral CuII catalysts have been investigated only recently.
In particular, the complexation of Schiff base bidentate li-
gands with copper has been shown to result in compounds
with interesting catalytic properties. On the other hand, orga-
noboranes are known as extremely useful and versatile syn-
thetic intermediates for organic synthesis[3] that can also dis-
play biological activities. Here, for 1,4-conjugate addition to
carbon–carbon double bonds, we used bis(pinacolato)diboron
[B2(pin)2], which is one of the most practical tools for the es-
tablishment of new CÀB bonds through transition-metal
catalysis.[4]
To enhance the catalytic performance of asymmetric catalyt-
ic boron conjugate addition, tripodal ligands,[5] based on the
tetrahydroquinoline or quinolone scaffold, were incorporated
into the CuII complexes. This successful combination led to
keto–alcohol derivatives in an enantiomerically enriched form.
A subsequent bioreduction step involving the use of different
whole cells allowed the reduction of the keto–alcohol sub-
strates to the corresponding enriched chiral diols,[1a,6] leaving
the other isomer unreacted (Scheme 1). The obtained sub-
strates are important building blocks in the synthesis of diverse
organic molecules that are versatile elements in the pharma-
ceutical field.[7]
[a] Prof. R. Gandolfi,+ Dr. G. Facchetti,+ Dr. M. S. Christodoulou,
Dr. F. Meneghetti, Dr. I. Rimoldi
Dipartimento di Scienze Farmaceutiche
Università degli Studi di Milano
Via Venezian 21, 20133 Milano (Italia)
E-mail: isabella.rimoldi@unimi.it
[b] Dr. M. Fus›
Scuola Normale Superiore
Piazza dei Cavalieri 7, 56126 Pisa (Italia)
[+] These authors contributed equally to this work
The ORCID identification number(s) for the author(s) of this article can
be found under:
https://doi.org/10.1002/open.201800056.
ꢀ 2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.
This is an open access article under the terms of the Creative Commons
Attribution-NonCommercial-NoDerivs License, which permits use and
distribution in any medium, provided the original work is properly cited,
the use is non-commercial and no modifications or adaptations are
made.
Scheme 1. Combining transition-metal catalysis with a biocatalytic approach
to obtain diols.
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2. Results and Discussion
Considering the use of Schiff bases and their corresponding re-
duced amines as ligands in copper complexes for the asym-
metric b-borylation of a,b-unsaturated carbonyl compounds,
the tridentate ligands were easily synthesized starting from 8-
aminoquinoline and its chiral derivatives by condensation with
salicylaldehyde in EtOH at room temperature for 5 h. Then, the
corresponding amines were obtained by reduction with NaBH4
in a mixture of THF/MeOH at 08C for 1 h (Scheme 2). Chiral 8-
aminotetrahydroquinolines were previously synthesized and
studied in our research group as ligands in metal complexes
and were used as catalysts in the asymmetric transfer hydroge-
nation (ATH) of different ketones with good results.[8]
Figure 1. ORTEP[9] view of the asymmetric unit with an arbitrary atom-num-
bering scheme (ellipsoids are drawn at 40% probability). H atoms are shown
as spheres of arbitrary radii.
substrate. Catalytic experiments showed that the best results
were obtained by using Et2O with 50 equivalents of MeOH at
room temperature (Table 1).
Scheme 2. Synthesis of ligands. Reagents and conditions: i) EtOH, RT, 5 h;
ii) NaBH4, THF/CH2Cl2, 08C, 1 h.
Table 1. Screening of the copper-catalyzed b-borylation of the standard
substrate.[a]
In the case of ligand L1, reduction to the corresponding
amine did not proceed in the presence of different amounts of
NaBH4 or by using Pd/C (1, 5, or 10% molar equivalents) under
a H2 atmosphere pressure, probably because of the extensive
double-bond conjugation of the substrate.
The copper(II)/L complexes, obtained by treating the ligand
with Cu(OAc)2 in EtOH for 3 h at room temperature, were com-
pletely characterized. Crystals of the copper complex bearing
ligand L1 suitable for X-ray structure analysis were obtained by
slow evaporation of a 33% water/acetone solution at room
temperature. The complex crystallized in the centrosymmetric
Entry
Ligand
Conversion[b] [%]
ee [%][c] (R)
1
2
3
4
5
L1
L2
L3
L4
L5
99.9
99.9
99.9
99.9
99.9
–
rac
12
21
45
¯
P1 space group, with five molecules of water and one mole-
cule of acetone, depicted as an ORTEP[9] view in Figure 1. The
complex is monomeric, and the central CuII atom is coordinat-
ed by two nitrogen donor atoms, one hydroxy oxygen atom,
and one oxygen atom from acetone in a square-planar ar-
rangement. The bond lengths and angles are within the ex-
pected ranges. Ligand L1 is nearly planar with a maximum de-
viation of 0.026(3) Š for the O1 atom. The crystal structure is
consolidated by an extensive network of water contacts, and
this leads to the formation of supramolecular chains running
along the a axis perpendicular to the ligands. In addition, weak
CpÀH···Owater intermolecular interactions contribute to stabilize
the crystal packing.
[a] All reactions were performed for 18 h by using the Cu complex
(5 mol%) in diethyl ether; c(substrate)final =28 mm, c(catalyst)final =1.4 mm.
[b] Conversion was determined by 1H NMR spectroscopy. [c] Data were
compared by taking the average of three independent experiments.
Enantiomeric excess was determined by HPLC with a chiral column (see
the Experimental Section).
The enantiomeric excess was evaluated directly on the orga-
noborane compounds by HPLC analysis. Assignment of the
configuration was achieved by comparison with the corre-
sponding b-hydroxy keto derivatives reported in the literature
after deprotecting the organoborane compounds with
NaBO3·H2O in THF/water for 1 h. Considering that the best re-
sults were obtained upon using L5 as the ligand (Table 1,
entry 5), the b-borylation reaction was extended under the
same reaction conditions to other a,b-unsaturated carbonyl
Catalytic asymmetric b-borylation was conducted starting
from different a,b-unsaturated carbonyl compounds. Different
reaction solvents (Et2O, MeOH, EtOH, toluene, water, dichloro-
methane, acetonitrile, and THF) were evaluated in the presence
of variable amounts of MeOH as a hydrogen donor (20– compounds (Table 2).
150 equiv.). With all catalysts, good yields were observed
within 18 h by using 1,3-diphenyl-2-propenone as a standard
For all the chalcone derivatives (Table 1, entries 5–12), the b-
borylation reaction products gave very appreciable outcomes
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Table 2. Asymmetric b-borylation with a copper catalyst bearing ligand
(S)-L5.[a]
Entry
R
R’
Conversion[b] [%]
ee[c] [%] (R)
1
2
3
4
5
6
7
8
H
CH3
CH3
CH3
CH3
99.9
94
63
12
15
21
–
45
4
13
11
37
7
30
50
51
21
15
3-Cl
4-Cl
4-NO2
H
H
H
H
H
H
H
–
Scheme 3. Proposed reaction mechanism.
C6H5
99.9
99.9
99.9
99.9
99.9
99.9
99.9
99.9
99.9
99.9
59
4-NCC6H4
4-F3CC6H4
4-ClC6H4
3-ClC6H4
4-CH3OC6H4
3-CH3OC6H4
2-CH3OC6H4
4-CH3C6H4
3-CH3C6H5
2-CH3C6H5
The data show that good results were obtained for the bio-
catalytic reduction upon using whole cells of Rhodotorula
rubra, Pichi etchellsii, Torulopsis magnoliae, and Torulopsis mo-
lischiana (Table 3, entries 1, 5, 11, and 12) as biocatalysts. As
good outcomes ensued by employing Rhodotorula rubra either
in the enantioselective reduction of the carbonyl moiety
(97%ee, 91%de, 23% yield; Table 3, entry 1) or in the biore-
duction of the hydroxy ketone substrate (65%ee), this yeast
seemed to be the best candidate as a biocatalyst in the reduc-
tion reaction of different racemic 3-hydroxy ketones, which
were eventually obtained by b-borylation and deprotection of
the substrates reported in Table 2 by using a copper catalyst
containing achiral ligand L1 (Table 4).
9
10
11
12
13
14
15
H
H
H
H
[a] All reactions were performed for 18 h by using the Cu complex
(5 mol%) in diethyl ether; c(substrate)final =28 mm, c(catalyst)final =1.4 mm.
[b] Conversion was determined by 1H NMR spectroscopy. [b] Data were
compared by taking the average of three independent experiments.
Enantiomeric excess was determined by HPLC with a chiral column (see
the Experimental Section).
Upon using methyl aryl hydroxy ketones, the results in
terms of stereoselectivity were modest both in the formation
of the diols and in the resolution of the hydroxy ketone com-
pounds (Table 4, entries 1–4). In the case of biaryl hydroxy ke-
tones, the best results were obtained with para-substituted
compounds in terms of molar conversion, whereas if the sub-
stituent was in the meta position, the yield decreased; the
product was undetectable for substrates with ortho substitu-
ents. This behavior could be correlated to a change in steric
hindrance of the substrate, as access to the active catalytic site
could become challenging if the substituents on the phenyl
ring were in a certain unfavorable position. The stereoselective
control observed with the yeast seemed to confirm this hy-
pothesis. In fact, the predominance of one configuration of the
enantiomers changed between the para- and meta-substituted
substrates: in the first case, the dominant (S,S)-diol underlined
that the yeast followed the Prelog rule, whereas in the pres-
ence of meta-substituted substrates, (R,R)-diols were formed
(ante-Prelog rule) (Table 4, entries 6–8, 10, and 13 vs. entries 9,
11, and 14). Excellent results in terms of stereoselectivity were
obtained with 4-H, 4-Cl, and 4-CH3 substituents for biocatalytic
ketone reduction (Table 4, entries 5, 8, and 13).
in terms of enantioselectivity, with the exception of 4-(4-nitro-
phenyl)but-3-en-2-one, for which the reaction did not proceed.
Full conversion was instead generally observed upon using
chalcone derivatives as starting materials; it was observed that
if the substituent on the benzylic moiety was in the para posi-
tion, the enantioselectivity decreased and was close to a race-
mate, apart from the methyl group (51%ee; Table 2, entry 13).
Therefore, different substituents in the ortho and meta posi-
tions were evaluated, and the enantioselectivity increased for
the ÀCl and ÀOCH3 groups going from the para position to
the ortho position (Table 2, entries 8–12); on the other hand,
the enantiomeric excess decreased in the case of the ÀCH3
substituent (Table 2, entries 13–15). These data agree with the
proposed reaction mechanism, in that the substituent on the
benzylic moiety plays a pivotal role in the nucleophilic addition
step to form an O-enolate in terms of steric hindrance or elec-
tronic properties (Scheme 3).[4a,10]
With the aim to combine asymmetric chemocatalysis with
biocatalytic reactions, the ability of yeasts to reduce the car-
bonyl group of the resulting b-hydroxy keto derivatives selec-
tively by biotransformation was then evaluated. Racemic 3-hy-
droxy-1,3-diphenylpropan-1-one was synthesized through b-
borylation and deprotection by using a copper(II) complex
containing L1 as the ligand, and it was used as a standard sub-
strate for the screening of different biocatalysts.[11] All reactions
were performed in the presence of glucose (50 gLÀ1) as a co-
substrate with a substrate concentration of 2 gLÀ1 in phos-
phate buffer, and the biotransformation results were evaluated
after 48 h.
A cascade reaction was then set up taking into consideration
the good results obtained with the biocatalysis approach as re-
gards the molar conversion. Thus, compounds with or without
a substituent in the para position of the phenyl ring were eval-
uated. The cascade reaction involved first b-borylation/depro-
tection and then bioreduction. Although the enantioselectivity
of the first step (chemocatalysis) was modest, this was an indis-
pensable condition for bypassing the issue of negligible molar
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Table 3. Screening results for the bioreduction of 3-hydroxy-1,3-diphenylpropan-1-one by yeasts.
Entry
Yeast
ee[a] [%]
Diol conversion[b] [%]
ee[a] [%]
de[b] [%]
(R)-Hydroxy ketone
(S,S)-diol
Diols
1
2
3
4
5
6
7
8
Rhodotorula rubra MIM 147
Saccharomyces cerevisiae
Saccharomyces cerevisiae zeus
Pichia henricii CBS 5765
Pichia etchellsii MIM
Pichia pastoris CBS 2612
Pichia glucozyma CBS 5766
Pachysolen tannophylus CBS 4044
Kluyveromyces marxianus var. lactis CL69
Kluyveromyces marxianus CBS 1553
Torulopsis magnoliae MIM 42
Torulopsis molischiana CBS 837
Torulopsis castelli MIM 1705
Torulopsis pinus 207
65
2
4
rac
55
34
8
23
8
12
10
19
8
10
89
7
10
28
24
7
97
20
25
91 (anti)
92 (meso)
42 (meso)
66 (anti)
85 (anti)
97 (anti)
74 (anti)
74 (anti)
96 (anti)
78 (anti)
90 (anti)
91 (anti)
42 (meso)
58 (meso)
95 (anti)
91 (anti)
À84
99
70
56
29
87
93
74
82
36
5
9
24
16
74
67
39
8
10
11
12
13
14
15
16
11
8
9
À15
67
77
Sporobolomyces salmonicolor MIM
Lindnera fabiani CBS 5640
21
7
[a] The ee value was determined by HPLC with a chiral column (see the Experimental Section). [b] Molar conversion and de were calculated by 1H NMR
spectroscopy.
catalyzed by a complex bearing ligand L5 led to the organo-
Table 4. Biotransformation of different 3-hydroxy ketones with Rhodotor-
ula rubra.[a]
borane compound with the R configuration and variable enan-
tiomeric excess values (7–51%ee). Subsequently, the solvent
was removed in vacuo and NaBO3·H2O (3 equiv.) in THF/H2O
(1:3, 50 mg substrate/1 mL) was added. After 1 h, phosphate
buffer (0.1m, pH 7, 50 mL), glucose (50 gLÀ1), and Rhodotorula
rubra whole cells were added to the previous untreated solu-
tion to work with a final substrate concentration of 1 mgmLÀ1
for 48 h (Table 5).
Entry
R
R’
ee[b] [%]
ee[b] [%]
de[c] [%]
Hydroxy ketone
Diol
Diols
1
2
3
4
5
6
7
8
H
CH3
CH3
CH3
CH3
rac
70 (S)
47 (S)
10 (S)
65 (R)
88 (R)
85 (R)
75 (R)
44 (S)
44 (R)
53 (S)
–
55 (R,S)
84 (R,S)
22 (R,S)
43 (R,S)
97 (S,S)
rac
82 (S,S)
96 (S,S)
37 (R,R)
99 (S,S)
52 (R,R)
64 (anti)
29 (anti)
75 (anti)
46 (anti)
91 (anti)
61 (anti)
44 (anti)
98 (anti)
89 (anti)
93 (anti)
75 (anti)
From the data reported in Table 5, it was observed that in
the presence of electron-donating groups or hydrogen as a
substituent, (S,S)-diols were provided with high enantiomeric
excess values (Table 5, entries 1, 2, and 6). Excellent ee values
were also obtained for (R)-hydroxy ketones, although in the
3-Cl
4-Cl
4-NO2
H
H
H
H
H
H
H
C6H5
4-CNC6H4
4-CF3C6H4
4-ClC6H4
3-ClC6H4
4-CH3OC6H4
3-CH3OC6H4
2-CH3OC6H4
4-CH3C6H4
3-CH3C6H4
2-CH3C6H4
9
10
11
12
13
14
15
Table 5. Cascade reactions.
H
H
H
H
–
97 (S,S)
98 (R,R)
–
85 (anti)
95 (anti)
72 (R)
10 (S)
–
–
–
[a] Substrate concentration was 2 mgmLÀ1. [b] The ee value was deter-
mined by HPLC with a chiral column (see the Experimental Section).
[c] The de was calculated by H NMR spectroscopy.
1
Entry
R
ee [%] ee [%] ee [%] ee [%]
(R)-b[a] (R)-c[b] (R)-c[c] (S,S)-d
de [%]
(anti)-d
Yield [%]
Diol
1
2
3
4
5
6
H
45
51
4
13
11
7
65
72
88
85
75
44
96
99
90
88
85
46
99 (S,S) 95 (anti) 96
99 (S,S) 98 (anti) 98
7 (S,S) 63 (anti) 78
83 (S,S) 46 (anti) 75
96 (S,S) 99 (anti) 98
99 (S,S) 94 (anti) 95
CH3
CN
CF3
Cl
conversion into diols as a consequence of a probable substrate
inhibition effect in the biotransformations. Different substrate
concentrations were examined to avoid this inhibition effect.
Furthermore, the biocatalytic reduction starting from the corre-
sponding diketones did not proceed in terms of product con-
version (5% yield) or stereoselectivity. The organoborylation
OCH3
[a] After catalytic b-borylation/deprotection. [b] After bioreduction by
yeast starting from racemic hydroxy ketone. [c] Cascade reaction.
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126.2, 121.3, 119.6, 118.7 118.1, 117.6 ppm; FTIR (NaCl): n=3468,
3368, 3050, 2917, 2894, 1661, 1617, 1372, 1150, 1114, 789 cmÀ1; MS
(ESI): m/z=249.27 [M+H]+.
case of the substrate with a para-OCH3 substituent, we believe
that the average ee value is due to steric hindrance generated
by the lone pair of electrons of the methoxy substituent in the
pocket of the yeast. Regarding the results obtained with elec-
tron-withdrawing substituents, only low enantiomeric excess
values were achieved in the reduction of (S,S)-diols and in the
resolution of (R)-hydroxy ketones (Table 5, entries 3–5). In this
case, it is conceivable that erosion of the biocatalyst per-
formance is a result of the low enantioselectivity of the chemo-
reaction.
(E)-2-{[(5,6,7,8-Tetrahydroquinolin-8-yl)imino]methyl}phenol (L2): S
isomer: [a]2D0 =À42.13 (c=1.1 in CHCl3); R isomer: [a]2D0 = +42.05
(c=0.7 in CHCl3); 1H NMR (300 MHz, CDCl3): d=8.63 (s, 1H), 8.39
(d, J=4.67 Hz, 1H), 7.43 (d, J=7.69 Hz, 1H), 7.32–7.24 (m, 2H),
7.12–7.08 (m, 1H), 6.97–6.83 (m, 2H), 4.56 (t, J=3.85 Hz, 1H), 2.94–
2.76 (m, 2H), 2.15–2.04 (m, 3H), 1.94–1.89 ppm (m, 1H); 13C NMR
(75 MHz, CDCl3): d=164.62, 161.32, 155.02, 147.72, 137.58, 132.81,
132.35, 131.92, 122.84, 119.27, 118.77, 117.07, 68.19, 31.30, 28.82,
18.84 ppm; FTIR (NaCl): n=3436, 3046, 2927, 1964, 1629, 1262,
1088, 1031, 803 cmÀ1
[M+Na]+.
;
MS (ESI): m/z=254.0 [M+H]+, 276.3
3. Conclusions
In conclusion, a cascade reaction combining transition-metal
complexes with biocatalysts was set up for the enantioselec-
tive synthesis of keto–alcohols and the corresponding 1,3-
diols. A new class of tridentate N,N,O pyridine-based ligands
was used for the first time in the b-borylation reaction with
copper(II) complexes to afford, in the case of ligand L5, keto–
alcohols in enriched form with up to 51%ee, which was crucial
for setting up the subsequent biotransformation. Rhodotorula
rubra, under optimized condition reactions, gave (S,S)-diols (up
to 99%ee), and the S enantiomer of the keto–alcohol was con-
sumed completely (up to 99%ee for the unreacted R enantio-
mer) with both excellent enantio- and diastereoselectivities.
(E)-2-{[(2-Methyl-5,6,7,8-tetrahydroquinolin-8-yl)imino]methyl}phe-
nol (L3): R isomer: [a]D20 =À53.4 (c=0.4 in CHCl3); S isomer: [a]2D0
+59.9 (c=0.5 in CHCl3); 1H NMR (300 MHz, CDCl3): d=13.60 (s,
1H), 8.60 (s, 1H), 7.33–7.25 (m, 3H), 7.04–6.84 (m, 3H), 4.56 (s, 1H),
2.88–2.63 (m, 2H), 2.24–2.04 (m, 3H), 1.94–1.87 ppm (m, 1H);
13C NMR (75 MHz, CDCl3): d=164.48, 161.43, 156.18, 153.95, 137.83,
132.26, 131.81, 129.50, 122.64, 119.37, 118.68, 117.10, 67.62, 31.31,
28.35, 24.34, 18.68 ppm; FTIR (NaCl): n=3056, 2930, 2864, 2733,
2665, 1731, 1627, 1472, 1416, 1081, 757 cmÀ1; MS (ESI): m/z=
267.21 [M+H]+.
=
General Procedure for the Synthesis of Ligands L4 and L5
The ligand (1 equiv.) was dissolved in MeOH/THF (1:1, 5 mL), and
the mixture was cooled to 08C. NaBH4 (0.5 equiv.) was added, and
the mixture was stirred at room temperature for 1 h. The solution
was quenched with saturated NH4Cl solution (4 mL) and was ex-
tracted with CH2Cl2 (3”8 mL). The combined organic layer was
dried (Na2SO4), and the solvent was evaporated. The obtained
product did not need further purification.
Experimental Section
Synthetic Procedures
General
1H NMR and 13C NMR spectra were recorded in CDCl3 by using a
Bruker DRX Avance (300 and 75 MHz) spectrometer equipped with
a nonreverse probe. Chemical shifts [ppm] are referenced to the re-
sidual solvent proton/carbon signal. Polarimetry analyses were per-
formed with a PerkinElmer 343 Plus equipped with Na/Hal lamp.
MS analyses were performed by using a Thermo Finnigan (MA,
USA) LCQ Advantage system MS spectrometer with an electrospray
ionization source and an ion-trap mass analyzer. Mass spectra were
obtained by direct infusion of a sample solution in MeOH under
ionization (ESI+). Catalytic reactions were monitored by HPLC anal-
2-{[(5,6,7,8-Tetrahydroquinolin-8-yl)amino]methyl}phenol (L4):
S
isomer: [a]2D0 = +20 (c=0.1 in CHCl3); R isomer: [a]2D0 =À24.2 (c=
0.1 in CHCl3); 1H NMR (300 MHz, CDCl3): d=8.39 (d, J=3.96 Hz,
1H), 7.42 (d, J=7.62 Hz,1H), 7.18–7.03 (m, 3H), 6.84–6.76 (m, 2H),
4.14 (s, 2H), 3.86 (t, J=6.15 Hz, 1H), 2.89–2.63 (m, 2H), 2.22–2.15
(m, 1H), 2.02–1.73 (m, 3H),1.25 ppm (s, 1H); 13C NMR (75 MHz,
CDCl3): d=158.01, 155.95, 146.87, 137.24, 132.63, 128.68, 128.33,
123.61, 122.38, 119.05, 116,49, 57.99, 50.79, 28.55, 28.44,
19.74 ppm; FTIR (NaCl): n=3282, 2924, 1924, 1690, 1589, 1456,
1259, 1037, 754 cmÀ1; MS (ESI): m/z=256.1 [M+H]+.
ysis with
a Merck-Hitachi L-7100 equipped with Detector
UV6000LP and a chiral column (AD, OJ-H Chiralcel, Lux Cellulose-4,
Lux Cellulose-2 or Lux Amylose-2).
2-{[(2-Methyl-5,6,7,8-tetrahydroquinolin-8-yl)amino]methyl}phenol
(L5): S isomer: [a]D20 =À39.1 (c=0.6 in CHCl3); R isomer: [a]2D0 = +
32.9 (c=0.3 in CHCl3); 1H NMR (300 MHz, CDCl3): d=7.31 (d, J=
8.2 Hz, 1H), 7.13 (m, 1H) 6.96 (d, J=7.9 Hz, 2H) 6.83 (m, 2H) 4.14
(m, 3H) 2.47 (s, 4H) 1.86 ppm (m, 4H); 13C NMR (75 MHz, CDCl3):
d=155.7, 155.1, 137.5, 129.1, 128.9, 128.8, 128.0, 123.7, 121.9,
116.2, 57.9, 50.7, 28.7, 28.2, 20.4, 19.8 ppm; FTIR (NaCl) n=3281,
2925, 2858, 1597, 1499, 1471, 1258, 1091, 1035, 816 cmÀ1; MS (ESI):
m/z=269.15 [M+H]+.
General Procedure for the Synthesis of Ligands L1–L3
8-Aminoquinoline (1.2 equiv.) was dissolved in EtOH (10 mL), and
salicylaldehyde (1 equiv.) was added at room temperature. The
mixture was stirred for 5 h and then water (5 mL) was added. The
organic layer was extracted with CH2Cl2 (3”10 mL). Anhydrous
Na2SO4 was added, the mixture was filtered, and the solvent was
removed in vacuo. The obtained product did not need further
purification.
Synthesis of a,b-Unsaturated Ketones
(E)-2-[(Quinolin-8-ylimino)methyl]phenol (L1): 1H NMR (300 MHz,
CDCl3): d=8.99 (d, J=1.5 Hz, 1H), 8.95 (s, 1H) 8,76 (d, J=1.2 Hz,
1H) 8.17 (d, J=8.2 Hz, 1H) 8.06 (d, J=8.2 Hz, 1H) 7.71 (d, J=
8.0 Hz, 2H) 7.23–7.01 ppm (m, 4H); 13C NMR (75 MHz, CDCl3): d=
164.6, 162.1, 150.5, 145.5, 142.3, 135.9, 133.3, 132.4, 129.1, 126.5,
An aqueous solution of sodium hydroxide (30%, 25 mL) was slowly
added to a methanol solution (30 mL) of the appropriate aceto-
phenone (1 equiv.). The solution was cooled to room temperature,
and the appropriate benzaldehyde (1.2 equiv.) was added. The mix-
ture was stirred at room temperature overnight and was then
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poured into water (100 mL). The obtained solid was filtered,
washed with water until neutral pH, and recrystallized (ethanol).
The chemical structure was confirmed on the basis of previously
reported data.[12]
1-Phenyl-3-[4-(trifluoromethyl)phenyl]propane-1,3-diol:
1H NMR
(300 MHz, CDCl3): d=7.61–7.57 (m, 2H), 7.52–7.46 (m, 2H), 7.39–
7.25 (m, 5H), 5.29–5.05 (m, 2H, syn), 4.99–4.50 (m, 2H, anti), 2.22–
2.15 (m, 2H, anti), 2.05–1.88 ppm (m, 2H, syn); 13C NMR (75 MHz,
CDCl3): d=159.4, 143.8, 128.9, 128.6, 128.5, 127.9, 127.7, 125.9,
125.8, 125.6, 125.5, 125.3, 75.2 (anti), 74.2 (anti), 71.7 (syn), 71.1
(syn), 47.6 (anti), 46.4 (syn), 28.3 ppm; MS (ESI): m/z=319.0
[M+Na]+.
General Procedure for Asymmetric Boron Conjugate
Addition
1-(3-Chlorophenyl)-3-phenylpropane-1,3-diol: 1H NMR (300 MHz,
CDCl3): d=7.40–7.20 (m, 9H), 5.06–5.00 (m, 2H, syn), 4.99–4.95 (m,
2H, anti), 2.23–2.11 (m, 2H, anti), 1.99–1.92 ppm (m, 2H, syn);
13C NMR (75 MHz, CDCl3): d=146.3, 143.8, 134.4, 129.7, 128.6,
128.5, 127.9, 127.7, 127.5, 125.9, 125.8, 125.6, 125.5, 123.7, 123.7,
75.1 (anti), 74.2 (anti), 71.7 (syn), 71.1 (syn), 47.7 (anti), 46.3 (syn),
22.8 ppm; MS (ESI): m/z=285.8 [M+Na]+.
A mixture of Cu(OAc)2 (5% mol), chiral ligand L1–L5 (6% mol), and
B2(pin)2 (1.2 equiv.) in Et2O (7.5 mL) was stirred at room tempera-
ture for 1 h under a nitrogen atmosphere. A mixture of the a,b-un-
saturated carbonyl compound (1 equiv.) and MeOH (50 equiv.) in
Et2O (2.5 mL) was added, and the mixture was stirred at room tem-
perature for 15 h. The mixture was concentered in vacuo, the resi-
due was dissolved in THF/H2O (1.5:1, 4 mL), and NaBO3·H2O was
added. The mixture was stirred for 2 h and then filtered. The aque-
ous layer was extracted with EtOAc (2”5 mL), and the combined
organic layer was dried (Na2SO4). The solvent was evaporated, and
the enantiomeric excess of the product was checked by HPLC
analysis.
1-(4-Methoxyphenyl)-3-phenylpropane-1,3-diol: 1H NMR (300 MHz,
CDCl3): d=7.39–7.23 (m, 7H), 6.86 (dd, J=8.72 Hz, 2H), 5.02–4.96
(m, 2H, syn), 4.93–4.90 (m, 2H, anti), 3.80 (s, 3H), 2.22–2.13 (m, 2H,
anti), 1.97–1.91 ppm (m, 2H, syn); 13C NMR (75 MHz, CDCl3): d=
144.2, 136.4, 136.3, 128.6, 128.5, 127.6, 127.4, 126.9, 126.8, 125.7,
125.6, 114.0, 113.9, 74.9 (anti), 74.6 (anti), 71.7 (syn), 71.3 (syn), 55.3,
47.7 (anti), 46.5 (syn), 29.6 ppm; MS (ESI): m/z=282.0 [M+Na]+.
The 1H NMR and 13C NMR spectra of 4-hydroxy-4-phenylbutan-2-
one, 4-(3-chlorophenyl)-4-hydroxybutan-2-one, 4-(4-chlorophenyl)-
4-hydroxybutan-2-one, 4-(4-nitrophenyl)-4-hydroxybutan-2-one, 3-
hydroxy-1,3-diphenylpropan-1-one, 3-hydroxy-3-phenyl-1-(p-tolyl)-
propan-1-one, 3-(4-chlorophenyl)-3-hydroxy-1-phenylpropan-1-one,
3-(3-chlorophenyl)-3-hydroxy-1-phenylpropan-1-one, 3-hydroxy-1-
(4-methoxyphenyl)-3-phenylpropan-1-one, 4-(3-hydroxy-3-phenyl-
propanoyl)benzonitrile, 3-hydroxy-1-(4- trifluoromethyl phenyl)-3-
phenylpropan-1-one, 3-hydroxy-1-(2-methoxyphenyl)-3-phenylpro-
1-(3-Methoxyphenyl)-3-phenylpropane-1,3-diol: 1H NMR (300 MHz,
CDCl3): d=7.40–7.18 (m, 5H), 7.0–6.79 (m, 2H), 5.30–4.68 (m, 2H),
3.81 (s, 3H), 2.21–2.15 (m, 2H, anti), 2.05–1.89 ppm (m, 2H, syn);
13C NMR (75 MHz, CDCl3): d=159.8, 145.9, 144.1, 129.6, 128.3,
127.7, 127.4, 125.7, 125.6, 117.8, 113.2, 112.8, 111.1, 75.0 (syn), 74.9
(syn), 71.7 (anti), 71.6 (anti), 55.2, 47.7 (syn), 46.4 ppm (anti); MS
(ESI): m/z=282.0 [M+Na]+.
pan-1-one,
3-hydroxy-1-(3-methylphenyl)-3-phenylpropan-1-one,
1-(2-Methoxyphenyl)-3-phenylpropane-1,3-diol: 1H NMR (300 MHz,
CDCl3): d=7.39–7.17 (m, 5H), 6.90 (d, J=7.5 Hz, 2H), 5.01–4.95(m,
2H, syn+anti), 3.80 (s, 3H), 3.51 (brs, 1H), 2.22–2.12(m, 2H, anti),
1.98–1.89 ppm (m, 2H, syn); 13C NMR (75 MHz, CDCl3): d=159.1,
144.2, 136.4, 128.5, 128.4, 127.7, 127.6, 126.6, 126.5, 125.2, 125.1,
113.8, 74.9 (syn), 74.6 (syn), 71.7 (anti), 71.3 (anti), 55.3, 47.7 (syn),
46.5 ppm (anti); MS (ESI): m/z=259.0 [M+H]+·
and 3-hydroxy-1-(2-methylphenyl)-3-phenylpropan-1-one corre-
spond to those reported in the literature.[4d,13]
3-Hydroxy-1-(3-methoxyphenyl)-3-phenylpropan-1-one:
1H NMR
(300 MHz, CDCl3): d=7.58–7.25 (m, 8H), 7.12 (d, J=8.2 Hz, 1H),
5.35–5.31 (m, 1H), 3.87 (s, 3H), 3.37–3.34 ppm (m, 2H); 13C NMR
(75 MHz, CDCl3): d=159.8, 144.8, 143.0, 137.9, 129.7, 128.5, 127.6,
125.7, 120.8, 120.1, 112.3, 55.4, 47.5, 24.5 ppm; MS (ESI): m/z=
279.1 [M+Na]+.
1
1-Phenyl-3-(m-tolyl)propane-1,3-diol: H NMR (300 MHz, CDCl3): d=
7.40–7.05 (m, 7H), 4.96–4.90 (m, 2H), 2.35 (s, 3H), 2.16–2.11 ppm
(m, 2H); 13C NMR (75 MHz, CDCl3): d=144.5, 144.3, 138.0, 128.4,
128.3, 127.5, 127.2, 126.2, 126.3, 125.6, 122.6, 74.8, 71.4, 46.6,
24.8 ppm; MS (ESI): m/z=243.9 [M+Na]+.
General Procedure for the Biotransformation
The biotransformation screening was performed in 10 mL screw-
capped test tubes by resuspending the yeast cells in 0.1m phos-
phate buffer (pH 7, 5 mL) containing glucose (50 gLÀ1) and adding
substrate (2 gLÀ1) dissolved in DMSO (1%). The mixtures were
magnetically stirred at 288C for 48 h. The mixtures were extracted
with diethyl ether (2”5 mL), dried (Na2SO4), and concentrated in
vacuo.
1
1-Phenyl-3-(o-tolyl)propane-1,3-diol: H NMR (300 MHz, CDCl3): d=
7.56 (d, J=7.2 Hz, 2H), 7.40–7.21 (m, 5H), 5.23–5.16 (m, 2H, syn),
5.08–5.03 (m, 2H, anti), 2.31 (s, 3H), 2.17–2.07 (m, 2H, anti), 1.98–
1.91 ppm (m, 2H, syn); 13C NMR (75 MHz, CDCl3): d=144.2, 142.1,
133.9, 130.4, 128.4, 127.7, 127.4, 127.3, 126.4, 125.3, 125.5, 125.1,
75.2 (anti), 71.9 (syn), 71.4 (anti), 68.2 (syn), 46.5 (anti), 45.1 (syn),
18.9 (anti), 18.6 ppm (syn); MS (ESI): m/z=243.8 [M+H]+.
1
The H NMR and 13C NMR spectra of 1-phenylbutane-1,3-diol, 1-(3-
chlorophenyl)butane-1,3-diol, 1-(4-chlorophenyl)butane-1,3-diol, 1-
(4-nitrophenyl)butane-1,3-diol, 1,3-diphenyl-1,3-propanediol, ben-
zoyl(4’-methylbenzoyl)methane, and benzoyl(4’-chlorobenzoyl)me-
thane correspond to those reported in the literature.[1a,b,14]
Analytical Conditions
4-(1,3-Dihydroxy-3-phenylpropyl)benzonitrile: 1H NMR (300 MHz,
CDCl3): d=7.65–7.61 (m, 2H), 7.48 (d, J=7.4 Hz, 2H), 7.46–7.28 (m,
5H), 5.12–5.03 (m, 2H, syn), 4.98–4.94 (m, 2H, anti), 2.20–2.05 (m,
2H, anti), 1.97–1.91 ppm (m, 2H, syn); 13C NMR (75 MHz, CDCl3): d=
149.5, 143.6, 132.3, 128.7, 128.6, 128.1, 127.8, 126.3, 126.3, 126.0,
125.6, 125.4, 118.8, 111.2, 75.4 (anti), 74.0 (anti), 71.8 (syn), 70.9
(syn), 47.5 (anti), 46.3 (syn), 29.6, 25.3 ppm; MS (ESI): m/z=276.4
[M+Na]+.
1
The products were analyzed by H NMR spectroscopy to determi-
nate the molar conversion, whereas the diastereomeric and enan-
tiomeric excess values were evaluated by HPLC analysis.
4-Hydroxy-4-phenylbutan-2-one: S isomer: tR =21 min, R isomer:
tR =18.7 min; 1-phenylbutane-1,3-diol: (anti form) S,R isomer: tR =
16 min, R,S isomer: tR =17 min, (syn form) R,R isomer: tR =19.7 min,
S,S isomer: tR =21 min; column: Lux cellulose-4, eluent: 2-propa-
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nol/hexane=5:95, flow=0.9 mLminÀ1, l=216 nm; data recorded
prior to TLC separation.
68 min; column: Lux amylose-2, eluent: ethanol/hexane=5:95,
flow=1.0 mLminÀ1, l=220 nm.
4-(3-Chlorophenyl)-4-hydroxybutan-2-one: S isomer: tR =15 min, R
isomer: tR =19 min; 1-(3-chlorophenyl)butane-1,3-diol: (anti form)
S,R isomer: tR =11 min, R,S isomer: tR =15 min, (syn form) R,R
isomer: tR =11.5 min, S,S isomer: tR =13 min; column: Lux amylose-
3-Hydroxy-1-(2-methoxyphenyl)-3-phenylpropan-1-one: S isomer:
tR =12 min, R isomer: tR =19 min; column: AD CHIRALCEL, eluent:
2-propanol/hexane=10:90, flow=1.0 mLminÀ1, l=220 nm.
3-Hydroxy-3-phenyl-1-(p-tolyl)propan-1-one:
R
isomer:
tR =
2, eluent: 2-propanol/hexane=15:85, flow=0.5 mLminÀ1
, l=
13.5 min, S isomer: tR =20.5 min; benzoyl-(4’-methylbenzoyl)me-
thane: (anti form) S,S isomer: tR =11 min, R,R isomer: tR =17 min,
(syn form) S,R isomer: tR =16 min, R,S isomer: tR =10 min; column:
216 nm.
4-(4-Chlorophenyl)-4-hydroxybutan-2-one: S isomer: tR =18 min, R
isomer: tR =20 min; 1-(4-chlorophenyl)butane-1,3-diol: (anti form)
S,R isomer: tR =14 min, R,S isomer: tR =24 min, (syn form) R,R
isomer: tR =13.5 min, S,S isomer: tR =26 min; column: Lux amylose-
Lux
cellulose-4,
eluent:
ethanol/hexane=10:90,
flow=
1.0 mLminÀ1, l=216 nm.
3-Hydroxy-1-(3-methylphenyl)-3-phenylpropan-1-one:
S
isomer:
2, eluent: 2-propanol/hexane=5:95, flow=1.0 mLminÀ1
,
l=
tR =14 min, R isomer: tR =11 min; 1-phenyl-3-(m-tolyl)propane-1,3-
diol: (anti form) S,S isomer: tR =6 min, R,R isomer: tR =10 min, (syn
form) S,R isomer: tR =21 min, R,S isomer: tR =24 min; column: Lux
216 nm.
4-(4-Nitrophenyl)-4-hydroxybutan-2-one: S isomer: tR =72 min, R
isomer: tR =65 min; 4-(4-nitrophenyl)butane-1,3-diol: (anti form) S,R
isomer: tR =33 min, R,S isomer: tR =35 min, (syn form) R,R isomer:
tR =37 min, S,S isomer: tR =40 min; column: OJ-H Chiralcel, eluent:
ethanol/hexane=5:95, flow=1.0 mLminÀ1, l=254 nm.
cellulose-2, eluent: 2-propanol/hexane=10:90, flow=0.8 mLminÀ1
l=220 nm.
,
3-Hydroxy-1-(2-methylphenyl)-3-phenylpropan-1-one:
S
isomer:
tR =12 min,
R isomer: tR =13.5 min; column: AD CHIRALCEL,
3-Hydroxy-1,3-diphenylpropan-1-one:
S
isomer: tR =24 min,
R
eluent: 2-propanol/hexane=8:92, flow=1.0 mLminÀ1, l=220 nm.
isomer: tR =41 min; 1,3-diphenyl-1,3-propanediol: meso form: tR =
13 min, R,R isomer: tR =15.5 min, S,S isomer: tR =18 min; column:
Cascade Reaction Procedure
Lux
amylose-2,
eluent:
ethanol/hexane=10:90,
flow=
1.0 mLminÀ1, l=216 nm.
A mixture of Cu(OAc)2 (5% mol), chiral ligand L5 (6% mol), and
B2(pin)2 (1.2 equiv.) in Et2O (7.5 mL) was stirred at room tempera-
ture for 1 h under a nitrogen atmosphere. A mixture of the a,b-un-
saturated ketone (1 equiv.) and MeOH (50 equiv.) in Et2O (2.5 mL)
was added, and the mixtures was stirred at room temperature for
15 h. The mixture was concentrated in vacuo, the residue was dis-
solved in THF/H2O (1:3, 50 mg substrate/1 mL), and NaBO3·H2O
(5 equiv.) was added. The mixture was stirred for 1 h. Rhodotorula
rubra was then added to 0.1m phosphate buffer (pH 7, 50 mL) con-
taining glucose (50 gLÀ1) to work at a final substrate concentration
of 1 mgmLÀ1. The mixture was magnetically stirred at 288C for
48 h. The mixture was extracted with diethyl ether (2”5 mL), dried
(Na2SO4), and concentrated in vacuo.
4-(3-Hydroxy-3-phenylpropanoyl)benzonitrile: R isomer: tR =36 min,
S isomer: tR =46 min; 4-(1,3-dihydroxy-3-phenylpropyl)benzonitrile:
(anti form) S,S isomer: tR =17 min, R,R isomer: tR =19 min, (syn
form) S,R isomer: tR =8.8 min, R,S isomer: tR =9.6 min; column: Lux
cellulose-4, eluent: 2-propanol/hexane=3:97, flow=1.0 mLminÀ1
l=216 nm.
,
3-Hydroxy-1-(4-trifluoromethylphenyl)-3-phenylpropan-1-one:
R
isomer: tR =25.4 min, S isomer: tR =37.5 min; 1-phenyl-3-[4-(trifluor-
omethyl)phenyl]propane-1,3-diol: (anti form) S,S isomer: tR =
30 min, R,R isomer: tR =34.5 min; (syn form) S,R isomer: tR =49 min,
R,S isomer: tR =51 min; column: Lux cellulose-4, eluent: 2-propa-
nol/hexane=3:97, flow=1.0 mLminÀ1, l=216 nm.
3-(4-Chlorophenyl)-3-hydroxy-1-phenylpropan-1-one: S isomer: tR =
37 min, R isomer: tR =42 min; benzoyl-(4’-chlorobenzoyl)methane:
(anti form) S,S isomer: tR =34 min, R,R isomer: tR =21 min, (syn
form) R,S isomer: tR =18 min, S,R isomer: tR =23.5 min; column: Lux
amylose-2, eluent: ethanol/hexane=5:95, flow=1.0 mLminÀ1, l=
220 nm.
Material and Methods
Microorganisms: Culture Conditions
Strains from official collections or from our collection were routine-
ly maintained on a malt extract (8 gLÀ1 agar 15 gLÀ1, pH 5.5). To
obtain cells for the biocatalytic activity tests, the microorganisms
were grown on solid medium at 288C for 72 h, and then, they
were cultured in 1000 mL Erlenmeyer flasks containing the
medium (100 mL, OD530nm mLÀ1 =0.1 at t0). The microorganisms
were incubated at 288C for 48 h on a reciprocal shaker (100 rpm).
The yeasts were grown on malt extract with 5 gLÀ1 Difco yeast ex-
tract, pH 5.6. Fresh cells from submerged cultures were centrifuged
(4000”g for 15 min at 48C) and washed with tap water before
using. The cells used in the screening biotransformations were
concentrated in a ratio of 1:2.
3-(3-Chlorophenyl)-3-hydroxy-1-phenylpropan-1-one: R isomer: tR =
22 min, S isomer: tR =29 min; 1-(3-chlorophenyl)-3-phenylpropane-
1,3-diol: (anti form) S,S isomer: tR =36 min, R,R isomer: tR =41 min,
(syn form) R,S isomer: tR =62 min, S,R isomer: tR =54 min; column:
Lux cellulose-4, eluent: 2-propanol/hexane=3:97, flow=
1.0 mLminÀ1, l=216 nm.
3-Hydroxy-1-(4-methoxyphenyl)-3-phenylpropan-1-one:
R isomer:
tR =76 min, S isomer: tR =88 min; 1-(4-methoxyphenyl)-3-phenyl-
propane-1,3-diol: (anti form) S,S isomer: tR =46 min, R,R isomer:
tR =50 min, (syn-form) S,R isomer: tR =58 min, R,S isomer: tR =
69 min; column: Lux amylose-2, eluent: 2-propanol/hexane=
10:90, flow=0.8 mLminÀ1, l=220 nm.
Crystallography
Diffraction data for the crystal of complex/L1[19] were collected by
means of a Enraf–Nonius CAD4 four circle diffractometer working
at ambient temperature with graphite-monochromated MoKa X-ra-
diation (l=0.7107 Š). X-ray diffraction data in the 2q range of 4 to
608 and in the (hkl) range Æh,Æk,+l were collected by using a
3-Hydroxy-1-(3-methoxyphenyl)-3-phenylpropan-1-one:
S isomer:
tR =57 min, R isomer: tR =102 min; 1-(3-methoxyphenyl)-3-phenyl-
propane-1,3-diol: (anti form) S,S isomer: tR =43 min, R,R isomer:
tR =48 min, (syn-form) S,R isomer: tR =64 min, R,S isomer: tR =
ChemistryOpen 2018, 7, 393 –400
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ꢀ 2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

2017, 129, 16268–16272; b) Y. Nakamura, H. Egami, K. Matsumoto, T.
Uchida, T. Katsuki, Tetrahedron 2007, 63, 6383–6387.
[7] J. A. Burkhard, G. Wuitschik, M. Rogers-Evans, K. Müller, E. M. Carreira,
Angew. Chem. Int. Ed. 2010, 49, 9052–9067; Angew. Chem. 2010, 122,
9236–9251.
profiled w-scan mode with scan angles of (1.2+0.35tan q)8 and
prescan speed of 4.128minÀ1. Accurate unit-cell parameters were
obtained by a least-squares fit of the 2q values for 25 reflections in
the 2q range of 30 to 408. Data reductions (including intensity in-
tegration, background, Lorentz, and polarization corrections) were
performed with the WinGX package.[15] Absorption effects were
evaluated with the psi-scan method,[16] and absorption correction
was applied to the data (min/max transmission factors were 0.808/
0.924). The structure was solved by direct methods (SIR-97)[17] and
were completed by iterative cycles of full-matrix least-squares re-
[8] a) I. Rimoldi, G. Facchetti, E. Cesarotti, M. Pellizzoni, M. Fuse, D. Zerla,
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