Highly Enantioselective Ring-Opening of meso-Epoxides with O- and N-Nucleophiles Catalyzed by a Chiral Sc(III)/bipyridine Complex

Article abstract of DOI:10.1002/ejoc.202001493

The ring-opening of epoxides is a synthetically significant process widely applied in all kinds of chemistry. Herein, we report the catalytic and highly enantioselective variant of this reaction exploiting our recent endeavors to design and synthesize chi

Full text of DOI:10.1002/ejoc.202001493

Full Papers
doi.org/10.1002/ejoc.202001493
1
2
3
4
5
6
7
8
9
Highly Enantioselective Ring-Opening of meso-Epoxides
with O- and N-Nucleophiles Catalyzed by a Chiral
Sc(III)/bipyridine Complex
Štefan Malatinec,[a] Eva Bednářová,[a] Hiroki Tanaka,[a, b] and Martin Kotora*[a]
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
The ring-opening of epoxides is a synthetically significant
process widely applied in all kinds of chemistry. Herein, we
report the catalytic and highly enantioselective variant of this
reaction exploiting our recent endeavors to design and
synthesize chiral bipyridine type ligands. A Sc-complex with a
newly developed bipyridine ligand exhibited high reactivity and
stereocontrol in the desymmetrization of meso-epoxides with
various alcohols. The respective enantiomerically enriched 1,2-
alkoxyalcohols were obtained with e.r. values of up to 99.5:0.5
for various alcohols regardless of their nature (benzyl, alkyl,
cycloalkyl, allyl, propargyl, etc.). We attempted ring-opening of
meso-epoxides with anilines as well; however, it proceeded with
lower enantioselectivity and was strongly depended on the
electronic effect of substituents attached to the aromatic ring.
Introduction
Interestingly, alcohols and other oxygen nucleophiles have
been rarely used in catalytic enantioselective ring-opening of
meso-epoxides. There have been just a handful of examples
such as the addition of carboxylic acids providing 1,2-diol
monoesters and monoether in high yields and reasonable
enantioselectivities. Jacobsen et al.[22] utilized a cobalt(III) salen
complex as a chiral Lewis acid in the addition of carboxylic
acids to epoxides furnishing 1,2-diol monoesters in excellent
yields and moderate to high enantioselectivity (up to 93% ee).
As for organocatalytic procedures, List et al.[23] showed that a
chiral TRIP could catalyze enantioselective ring-opening of
meso-epoxides with benzoic acid (up to 92% ee). Shibasaki
et al.[24] reported a procedure relying on catalysis by a gallium-
lithium-BINOL complex, which allowed the addition of para-
methoxyphenol in good to excellent enantioselectivities (up to
96% ee).[25]
Desymmetrization is the modification of a molecule that results
in the loss of one or more symmetry elements and usually is
accompanied by the introduction of chirality. It is generally
carried out on achiral or meso-compounds[1] and represents a
powerful synthesis of chiral compounds because several stereo-
genic centers can be established concurrently.[2–6] However,
catalytic enantioselective desymmetrization of prochiral systems
is not an easy task, because it involves a symmetry breaking
operation, where two enantiotopic moieties must be
differentiated.[7–9]
In this respect, meso-epoxides are ideal substrates for
testing new chiral catalytic systems or new chiral ligands. The
meso-epoxides are inexpensive and readily available com-
pounds that after catalytic enantioselective ring-opening give
rise to enantiomerically enriched 1,2-difunctionalized building
blocks. An array of C, N, O, S, Se, and halogen nucleophiles can
be applied and synthesis of substances such as 1,2-cyanoalco-
hols, 1,2-azidoalcohols, 1,2-aminoalcohols, 1,2-diol monoesters
and monoethers, mercaptoalcohols, and 1,2-halohydrins[10–21]
have been achieved so far with good enantioselectivities. Chiral
Lewis acids or bases usually catalyze such processes, and during
the process, two enantiotopic carbon atoms of the epoxide
moiety are differentiated by SN2 nucleophilic attack at one of
the epoxide carbon atoms.
Early examples showed that different rare earth metal
triflates are highly active catalysts for the alcoholysis of
[26–28]
epoxides (Sc(OTf)3
and Yb(OTf)3[29]). These works provided a
good impetus for Schneider et al., who assessed the scope of
alcoholysis of meso-epoxides catalyzed by using a chiral
catalytic system composed of Sc(OTf)3 (10 mol%) and Bolm’s
ligand).[30,31]
1 (10 mol%) (Figure 1). Asymmetric induction
reached up to 99:1 e.r.[32,33] Interestingly, the only attempt in
this direction was a para-bromobenzyl alcohol reaction study
by Kobayashi et al.[34] Since then, this area has remained
dormant, and no significant progress has been reported. On the
[a] Š. Malatinec, Dr. E. Bednářová, H. Tanaka, Prof. Dr. M. Kotora
Department of Organic Chemistry
Chemistry, Faculty of Science, Charles University
Albertov 6, 128 43 Praha 2, Czech Republic
E-mail: kotora@natur.cuni.cz
[b] H. Tanaka
A visiting student from Research Institute for Interdisciplinary Science
Okayama University
3-1-1 Tsushimanaka, Kita-ku, Okayama 700-8530, Japan
Supporting information for this article is available on the WWW under
https://doi.org/10.1002/ejoc.202001493
Figure 1. Bolm’s ligands.
Eur. J. Org. Chem. 2021, 1249–1257
1249
© 2021 Wiley-VCH GmbH

Full Papers
doi.org/10.1002/ejoc.202001493
other hand, it should be also noted that the scope of the use of
Table 1. Influence of metal triflates on asymmetric induction.
1
2
3
rare earth metal salts as Lewis acids has been applied to many
reactions.[35–37]
Various metal salts in combinations of Bolm’s ligand 1 were
used to catalyze ring opening of meso-epoxides with various
amines in a similar manner. Among them are worth mentioning
system using Sc(OTf)3 or Sc(DS)3 (10 mol%) that provided
product with e.rs up to 97.5:2.5,[32,38,39] Zn(OTf)2 and Cu(OTf)2
(e.rs up to 95:5 and 90:10, respectively),[40] Fe(ClO4)2 (e.rs up to
97.5:2.5),[41] and In salts (e.rs up to 99:1).[42] Sc salts were also
used to catalyze opening of meso-epoxides with imines[43] and
benzotriazole[32] with e.rs up to 94:6 and 87:13, respectively.[44]
We have recently reported a synthesis of a Bolm’s ligand
analog (S,S)-2 possessing bicyclic ring systems (Figure 1).[45]
Screening of its potential applications as an chiral ligand in
various transition metal complex catalyzed reaction revealed
that the in situ formed scandium complex (Sc(OTf)3 (10 mol%)/
(S,S)-2 (10 mol%)) is a good catalyst for ring-opening of meso-
stilbene oxide 3 with para-methoxybenzyl alcohol 4a. A
preliminary screening turned out to give the respective
enantioenriched alkoxyalcohol 5a with e.r. of 98.5:1.5 under
mild reaction conditions. (5a was obtained with 97.5:2.5 e.r
when Bolm’s ligand (10 mol%) was used). Although the increase
in enantioselectivity could be considered rather marginal, this
result sparked our interest to evaluate its potential application
in the opening of meso-epoxides. We would like to demonstrate
in this work that the system composed of Sc(OTf)3/(S,S)-2 is a
suitable catalytic system for enantioselective ring-opening of
various meso-epoxides with a plethora of alcohols (O-nucleo-
philes) providing the corresponding 1,2-alkoxyalcohols in high
yields and excellent asymmetric induction.
4
5
6
7
8
9
Entry
M(OTf)n
Yield [%][a]
e.r
1
2
3
4
5
6
7
8
9
Sc(OTf)3
Y(OTf)3
90
99:1
94:6
15[b]
La(OTf)3
Sm(OTf)3
Tb(OTf)3
Ho(OTf)3
Yb(OTf)3
In(OTf)3
Bi(OTf)3
Fe(OTf)2
2[b]
73.5:26.5
71:29
77.5:22.5
91.5:8.5
96.5:3.5
92:8
23
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
15
6[b]
50[b]
15[b]
25[b]
5[b]
67:33
85.5:14.5
10
1
[a] Isolated yield unless otherwise mentioned. [b] H NMR yield.
Figure S23). The previous works showed that the optimal
catalyst and ligand load for Sc(OTf)3 and Bolm’s ligand 1 is
10 mol%.[33] Asymmetric induction started to drop below that
value and reaction times became too long (e.g., for 1 mol%
load, 86.5:13.5 e.r., five days (120 h)). To assess the optimal
reaction conditions in terms of yields, asymmetric induction,
and reaction time, we screened the course of the reaction of
meso-stilbene oxide 3 with para-methoxybenzyl alcohol 4a at
°
25 C in CH2Cl2 with several different Sc(OTf)3/(S,S)-2 loads
(Scheme 1). Initially, carrying out the reaction with the catalyst
load of 10 mol% provided 5a in 90% yield and 99:1 e.r. within
24 h. A decrease of the catalyst loading to 5 mol% gave almost
the same result regarding the yield and enantioselectivity, but
the reaction time was prolonged to 48 h. Its further lowering to
2 mol% led to a longer reaction time of 72 h, but the yield
(90%) and the enantioselectivity (98.5:1.5 e.r.) remained the
same.
Results and Discussion
Ring-opening with alcohols. Since other transition metal
triflates are known to be potent Lewis acids, enantioselective
ring opening of meso-stilbene oxide 3 with para-methoxybenzyl
alcohol 4a was tested with a combination of several metal
Lowering the catalyst amount to 1 mol% resulted in a
negligible decrease in enantioselectivity (within the limits of
experimental error) to only 98:2 e.r. However, the reaction time
was 120 h. We decided to carry out the subsequent reactions
with the 2 mol% load from a practical point of view.
°
triflates (10 mol%) and (S,S)-2 (10 mol%) at 25 C to assess yields
and asymmetric induction. The most important results are
summarized in Table 1. The best results in terms of yield and
enantioselectivity, 90% and 99:1 e.r., respectively, were
obtained with Sc(OTf)3 (Entry 1). High asymmetric induction of
96.5:3.5 e.r. was also observed with Yb(OTf)3, albeit the yield
was somewhat mediocre (50%) (Entry 7). The use of Y(OTf)3,
Ho(OTf)3, and In(OTf)3 gave the respective product with some-
what lower enantiomeric ratios of 94:6, 91.5:8.5, and 92:8,
respectively (Entries 2, 6, and 8). The application of La, Sm, Tb,
Bi, and Fe, triflates gave rather average asymmetric induction
(73.5:26.5, 71:29, 77.5:22.5, 67:33, and 85.5:14.5 e.r., Entries 3–
5, 9, and 10).
At the outset, we focused on assessment of the reaction of
meso-stilbene oxide
3 with respect to various alcohols
(Scheme 2). Reactions with para- and meta-methoxybenzyl
alcohols 4a and 4b proceeded with high enantiomer ratios of
99:1 (published value for 5a was 98.5:1.5 e.r.[32]). In the case of
ortho-methoxybenzyl alcohol 4c a small drop to 94:6 e.r. was
observed, probably due to steric hindrance. As for other para-
substituted benzyl alcohols, those bearing electron-donating
(Me) or -accepting groups (Br, COOMe, NO2, CF3) 4d, 4f–4i as
Regarding the triflates, the observed trend in asymmetric
induction follows the Lewis acidity (oxophility) scale based on
the work of Imamoto et al.[46] The obtained results clearly
demonstrated that Sc(OTf)3 is the compound with the highest
Lewis acidity followed by Yb, Y, and other triflates (see
Scheme 1. Effect of catalyst loading on enantioselectivity.
Eur. J. Org. Chem. 2021, 1249–1257
www.eurjoc.org
1250
© 2021 Wiley-VCH GmbH

Full Papers
doi.org/10.1002/ejoc.202001493
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
Scheme 2. Scope of the Sc(OTf)3/(S,S)-2-catalyzed alcoholysis of 3.
well as for unsubstituted benzyl alcohol 4e, the ring opening of
3 proceeded with excellent asymmetric induction giving highly
enantioenriched 5d–5i in the range of 96.5–99:3.5–1 e.rs
(published value for 5f was 93:7 e.r.[34]). Excellent enantiose-
lectivities of 98.5:1.5 and 98:2 e.rs were obtained for 5j (86%)
and 5k (63%) that were formed in the reactions of 1-
naphthalenemethanol 4j and 9-anthracenemethanol 4k. In the
and purification of cyclohexanol resulted in a very good isolated
yield of 5p as well as enantioselectivity (99.5:0.5 e.r.), albeit a
long reaction time of 23 days was required. Once again, it is
assumed that the low reaction rate could be result of steric
hindrance of the alcohol. The structure and (S,S) configuration
of 5p was confirmed by a single crystal X-ray diffraction analysis
(Figure 2). It should be also noted that a fresh batch of Sc(OTf)3
has been always dried prior to the use, a repetitive use of once
dried Sc(OTf)3 resulted in lower enantioselectivity along with
formation of aldehydes and ketones by acid catalyzed rear-
rangement of the starting epoxide 3 (see, Table S1).
°
latter case, heating of the reaction mixture to 40 C reduced the
reaction time to 3 days. It took 11 days to obtain 5k in 55%
°
yield (97.5:2.5), when the reaction was carried out at 25 C.
Presumably, the observed lower reactivity of 4k could be
attributed to steric hindrance exercised by the anthracene
moiety and its overall low solubility.
Besides, the epoxide ring-opening of meso-(4-chlorophenyl)
oxirane 6 with para-methoxybenzyl alcohol 4a (Scheme 3)
Interestingly, the reaction with 2-furfuryl alcohol 4l was
rather sluggish and gave 5l in only 92.5:7.5 e.r. Gratifyingly,
running the reaction in the presence of molecular sieves
resulted in the increased asymmetric induction of 98.5:1.5 e.r.,
but at the expense of a long reaction time (23 d). The ring-
opening with (thiophen-2-yl)methanol 4m proceeded under
standard reaction conditions with 98.5:1.5 e.r. The ring opening
with ferrocenemethanol 4n giving rise to 5n proceeded well
with 94.5:5.5 e.r. High enantioselectivities were also obtained
with representatives of aliphatic alcohols such as methanol,
cyclohexyl, allyl, and propargyl alcohols which gave the
respective products 5o–5r with e.rs of 96.5:3.5, 99.5:0.5,
97.5:2.5, and 99:1, respectively (published e.r. values for 5o,
5q, and 5r were 96:4, 97.5:2.5, and 95.5:4.5[32]). The case of
cyclohexanol deserves a detailed comment. Under the standard
reaction conditions the product was formed in low yield of 35%
(1H NMR) (e.r. was not determined). However, meticulous drying
Figure 2. The ORTEP plot of (S,S)-5p. Elipsoids are shown with 30%
probability.
Eur. J. Org. Chem. 2021, 1249–1257
www.eurjoc.org
1251
© 2021 Wiley-VCH GmbH

Full Papers
doi.org/10.1002/ejoc.202001493
Mechanistic considerations. Kobayashi et al.[47] and
1
2
3
4
5
6
7
8
9
Schneider et al.[33] have reported crystal structures of the
monomeric scandium (composed of ScBr3 and 1) and the
yttrium catalyst (composed of Y(OTf)3 and 1). The former had a
pentagonal-bipyramidal coordination geometry of the metal,
and it can be clearly seen that the bipyridine ligand is twisted
°
along the bipyridine axis (ff 20.8 for N1a-C1a-C1-N1). The latter
corresponded to the eight-coordinate yttrium-bipyridine com-
plex again, having the bipyridine rings slightly twisted along
Scheme 3. Reaction of meso-(4-chlorophenyl)oxirane 6 with para-meth-
oxybenzyl alcohol 4a catalyzed by the Sc(OTf)3/(S,S)-2 complex.
°
the bipyridine axis (ff 19.1 N1-C1-C6-N2) and coordinated to
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
the metal center in a tetradentate fashion.
The cyclopentane rings in ligand 2 impose considerable
steric hindrance that does not allow the pyridine rings to adopt
coplanar conformation. Instead, they are twisted with respect to
each other. Hence, the formation of monomeric complexes
such as those mentioned above would probably be difficult
because of the reactants’ expected inefficient orbital alignment.
Instead, it could promote the formation of complexes possess-
ing multiple metal centers. This effect was observed previously
by us in the case of cationic and neutral Cu/ bipyridine 2
provided the respective product 7 in 67% yield and 98.5:1.5 e.r.
(The published value for 7 was 96:4.[33]
)
Then ring-opening of aliphatic and cyclic epoxides such as
cis-2-butene oxide (8a), cyclohexene oxide (8b) and cis-cyclo-
octene oxide (8c) was tested with Sc(OTf)3 (2 mol%) and (S,S)-2
°
(2 mol%) at À 20 C. As far as the epoxide ring-opening of 8a
and 8b with para-methoxybenzyl alcohol 4a are concerned,
the reaction provided 9a and 9b in moderate enantioselectiv-
ities 76:24 and 65.5:34.5 e.r.) and 1H NMR yields of 40 and 70%
(Scheme 4). Enantioselectivity of the former is similar to the
published one (49% ee using Sc(OTf)3 (10 mol%), Bolm’s ligand
(R,R)-1 (10 mol%)[32]). However, for the latter, it was reduced by
almost 20%, the reported value is 52% ee using Sc(OTf)3
(10 mol%) and Bolm’s ligand (R,R)-1 (10 mol%).[32] (It should be
mentioned that we tried to carry out the reaction with Bolm’s
ligand as well but could not reach the reported value, the
product 9b was obtained in 34% ee). Surprisingly, the epoxide
ring opening of cis-cyclooctene oxide 8c did not proceed with
para-methoxybenzyl alcohol 4a at all. After many experiments
it was found that the reaction could be brought about in pure
complexes.[45] The twist in the ligand was ~20 in a dimeric
°
°
cationic Cu-complex. On the other hand, the twist of 90 was in
the latter. Therefore we assume that higher aggregates of
catalytically active species with a more rigid structure lead,
eventually, to higher asymmetric induction. Unfortunately, all
attempts to crystalize any Sc-complex were not met with
success. Also MS experiments in MeCN and MeOH did not
provide any evidence for the formation of polynuclear species,
only fragments assignable to a monomeric species were
detected.
An attempt to record the 1H NMR spectrum of the Sc/2
catalytic system and compare it with the spectrum of the Sc/1
one was carried out (Figure S24). The H NMR spectrum of the
1
°
MeOH (4o) at 70 C. Gratifyingly, enantioselectivity increased
Sc/1 catalytic system (turquoise line) indicates the formation of
a single structure from Sc(OTf)3 and 1 (red line). On the other
hand, mixing Sc(OTf)3 with 2 (yellow line) obviously did not
form a single structure as it is indicated by the presence of
more than one signal in the aromatic area (blue line). The
competitive complexation of ligands 1 and 2 with Sc(OTf)3 in
the ratio 1:1:1 revealed that probably both complexes are
formed, considering corresponding signals at 5.47 (for 1) and
5.29 (for 2). Hence, it is possible to conclude that there is not a
significant difference in their coordination capabilities.
Ring-opening with amines. With the above-obtained results
in hand, we decided to briefly screen reactions of cis-stilbene
oxide 3 with various anilines 10 bearing electron-donating and
-withdrawing groups catalyzed by the Sc/2 catalytic system.
First, the reaction with aniline (10b) was studied under different
catalyst loadings (see Table S7). It turned out that the highest
yield of the corresponding aminoalcohol 11b (90%) and
asymmetric induction (e.r. 99.5:05) was obtained by using
10 mol% catalyst‘s load within 2 days. Its reduction to 5 mol%
gave 11b in 72% yield and e.r. of 97.5:2.5 in 4 days (see also
Table 2, entry 3). Further lowering of the catalytic system to 2
and 1 mol% resulted in a decrease of yields, e.rs, and longer
reaction times were required. It was decided to use 5 mol%
load of the Sc/2 catalytic system for further experiments.
substantially to give alcohol 9c with 98:2 e.r. and in 85%
isolated yield. (For the details see Tables S2–S5 in the SI
section). An attempted reaction with cyclopentene oxide led to
a complex reaction mixture, in which the expected product was
not detected.
Scheme 4. Reaction of aliphatic meso-epoxides with 4a and 4o.
Eur. J. Org. Chem. 2021, 1249–1257
www.eurjoc.org
1252
© 2021 Wiley-VCH GmbH

Full Papers
doi.org/10.1002/ejoc.202001493
It is reasonable to presume that a somewhat larger differ-
Table 2. Aminolysis of 3 with various anilines 10.
1
2
3
4
5
6
7
8
9
ence in asymmetric induction in the Sc-catalyzed ring-opening
of 3 with anilines 10a–10c is caused by the difference in their
nucleophilicity.[48] Thus a high asymmetric induction is observed
with less nucleophilic 4-chloroaniline (10c), because efficient
catalysis is required to bring about the reaction. On the other
hand, the reaction with more nucleophilic 4-methoxyaniline
(10a) also proceeded through uncatalyzed ring-opening of 3,
diminishing enantioselectivity. The same trend is also observed
in the In-catalyzed process (Table 3).
°
Entry
Amine
T [ C]
Yield [%][a]
e.r.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
1
2
3
4
5
10a
10a
10b
10c
10d
22
0
45
80
72
53
78
93:7
84:16
99:1
98.5:1.5
98:2
22
22
22
Conclusion
In conclusion, we have reported substantially enhanced
enantioselective ring-opening of meso-epoxides with alcohols
catalyzed by Sc(OTf)3/Bolm’s ligand analog 2. The reactions
proceeded with a high level of stereocontrol giving rise to
highly enantioenriched products for a wide range of substrates
(alkyl, benzyl, allyl, and propargyl alcohols). The obtained e.rs
were up to 99:1 (the major stereoisomer was S,S). Moreover,
the reaction proceeded with a low catalyst load of just 2 mol%
within reasonable reaction times at ambient temperature
1
[a] H NMR yield.
The reaction with 4-methoxyaniline 10a provided product
11a in 45% yield and 93:7 e.r. (Entry 1). Since it has been
shown that higher enantioselectivity could be obtained at a
°
lower reaction temperature, we run a reaction at 0 C (Entry 2).
Albeit the reaction yield increased to 80%, enantioselectivity
dropped to 84:16. The reaction with 10b gave rise to amino-
alcohol 11b in a nice 72% yield and excellent e.r. of 99:1
(Entry 3). Analogically, the reactions with 4-chloroaniline 10c
and 1-aminonaphthalene 10d provided aminoalcohols 11c and
11d in 53 and 78% yields and superb e.rs of 98.5:1.5 and 98:2,
respectively (Entries 4 and 5). These values are higher than
those obtained with other catalytic systems.[30,34,40]
Also, reactions of 3 with anilines 10 under using indium-
(Schneider et al.[42]) and iron-based (Ollevier et al.[41]) catalytic
systems were carried out (Table 3). As far as the enantioselectiv-
ity is concerned, the In-based catalytic system followed the
trend observed for the Sc-catalyzed reactions. The lowest
asymmetric induction was observed with 10a (85.5:14:5,
Entry 1)), and the highest one was achieved for the reaction
with 10c (95.5:4.5, Entry 3). Catalysis of the reaction of 10a
with 3 with the Fe-system did not proceed efficiently, forming
°
(usually 25 C). The obtained e.rs are in most of the cases
considerably higher than those achieved under other catalytic
conditions (for comparison of various methods, see Table S6).
Thus, the results provide evidence that the stereoselectivity of
catalytic reactions could be enhanced by the judicious elabo-
ration of structural features of already known ligands. The
asymmetric induction is not influenced by the presence of
electron-donating or accepting groups in benzyl alcohols.
Screening of the reaction conditions with various metal salts
revealed that asymmetric induction could be correlated with
reasonable probability to Lewis acidity of the metal, at least in
the case of lanthanides and neighboring metals. Similar results
were also obtained for the ring-opening with amines, where
excellent e.rs were obtained in majority of the cases.
11a in only 10% yield (Entry 1). Surprisingly, a reaction with Experimental Section
10c gave 11c with low enantiopurity (82.5:17.5) as well
(Entry 6).
For experimental details, HPLC charts, copies of 1H and 13C NMR
spectra and other supplementary material, see the SI section.
General procedure for ring opening of epoxides: synthesis of 2-
hydroxyethers (a typical example). The respective oxide
(0.3 mmol) and alcohol (0.6 mmol) were added to a prestirred
(10 min) solution of Sc(OTf)3 (3 mg, 6 μmoL) and ligand (S,S)-2
(2.5 mg, 6 μmoL) in dry CH2Cl2 (1.5 mL) in a 4 mL vial. Then the
Table 3. Aminolysis of 3 with amines 10 catalyzed by In and Fe systems.
°
reaction mixture was stirred at 25 C for the appropriate period of
time, usually until 3 was fully consumed (disappearance of the
respective spot on TLC). Finally, the volatiles were removed under
reduced pressure. Column chromatography of the residue on silica
gel furnished the desired product. Racemic mixtures of products
were prepared by the same procedure using racemic Bolm’s ligand
1 and isolated by preparative TLC.
Entry
Ma)
In
Amine
R
Yield (%)b)
e.r.
85.5:14:5
1
2
10a
10b
10c
10a
10a
10c
OMe
H
Cl
OMe
H
Cl
85
80
80
10
55
16
In
88:12
95.5:4.5
ND
91.5:8.5
82.5:17.5
3
In
4c)
5
Fe
Fe
Fe
(1S,2S)-2-((4-Methoxybenzyl)oxy)-1,2-diphenylethan-1-ol (5a). Ac-
cording to the general procedure with p-methoxybenzyl alcohol 4a
(75 μl, 0.6 mmol) for 68 h. Column chromatography of the residue
on silica gel (5/1 hexanes/Et2O) furnished 82 mg (82%, 98% ee) of
6
[a] For In: X=10 and Y=10, for Fe: X=5 and Y=6. [b] 1H NMR yield. [c]
80% of 10a was still present in the reaction mixture. ND=Not Determined.
Eur. J. Org. Chem. 2021, 1249–1257
www.eurjoc.org
1253
© 2021 Wiley-VCH GmbH

Full Papers
doi.org/10.1002/ejoc.202001493
the title compound as colorless crystals. 1H-NMR (400 MHz, CDCl3) δ
91 h. Column chromatography of the residue on silica gel (5/1
hexanes/Et2O) furnished 80 mg of the title compound (88%, 98%
ee) as a colorless solid.1H NMR (400 MHz, CDCl3) δ 7.41–7.30 (m, 5H,
ArÀ H), 7.28–7.23 (m, 3H, ArÀ H), 7.21–7.15 (m, 3H, ArÀ H), 7.12–7.02
(m, 4H, ArÀ H), 4.75 (d, J=8.2 Hz, 1H, CH), 4.45 (d, J=11.5 Hz, 1H,
CH2), 4.37 (d, J=7.9 Hz, 1H, CH), 4.35 (d, J=11.2 Hz, 1H, CH2), 3.55
(br s, 1H, OH). 13C NMR (101 MHz, CDCl3) δ 139.28, 137.85, 137.68,
128.62, 128.29, 128.25, 128.09, 128.00, 127.96, 127.81, 127.40, 87.08,
78.74, 70.96. The recorded values were in agreement with the
published data.[49] Daicel Chiralpak IB, n-heptane/IPA 98/2, 1 mL/
min, 209 nm, 5e: tR,R =10.6, min tS,S =11.4 min.
1
2
3
4
5
6
7
8
9
7.26–7.20 (m, 5H, ArÀ H), 7.19–7.13 (m, 3H, ArÀ H), 7.10–6.99 (m, 4H,
ArÀ H), 6.92–6.86 (m, 2H, ArÀ H), 4,70 (d, J=8.3 Hz, 1H, CH), 4.47 (d,
J=11.0 Hz, 1H, CH2), 4.33 (d, J=8.3 Hz, 1H, CH), 4.27 (d, J=11.0 Hz,
1H, CH2), 3.83 (s, 3H, CH3), 3.53 (br s, 1H, OH). 13C NMR (100 MHz,
CDCl3) δ 159.51, 139.31, 137.81, 129.93, 129.78, 128.28, 128.20,
128.02, 127.94, 127.79, 127.41, 114.04, 86.77, 78.72, 70.63, 55.44.
The recorded values were in agreement with the published data.[33]
Daicel Chiralpak IB, n-heptane/IPA 95/5, 1 mL/min, 204 nm, tS,S
10.4 min tR,R =12.1 min.
=
(1S,2S)-2-((3-Methoxybenzyl)oxy)-1,2-diphenylethan-1-ol (5b). Ac-
cording to the general procedure with 3-methoxybenzyl alcohol 4b
(75 μl, 0.6 mmol) for 156 h. Column chromatography of the residue
on silica gel (5/1 hexanes/Et2O) furnished 86 mg (86%, 98% ee) of
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
(1S,2S)-2-((4-Bromobenzyl)oxy)-1,2-diphenylethan-1-ol (5f). Ac-
cording to the general procedure with 4-bromobenzyl alcohol 4f
(112 mg, 0.6 mmol) for 69 h. Column chromatography of the
residue on silica gel (5/1 hexanes/Et2O) furnished 90 mg (78%, 93%
1
the title compound as a colorless oil. H NMR (400 MHz, CDCl3) δ
1
7.31–7.13 (m, 7H, ArÀ H), 7.21–7.14 (m, 4H, ArÀ H), 6.92–6.83 (m, 3H,
ArÀ H), 4.74 (d, J=8.2 Hz, 1H, CH), 4.51 (d, J=11.6 Hz, 1H, CH2), 4.37
(d, J=8.2 Hz, 1H, CH), 4.32 (d, J=11.6 Hz, 1H, CH2), 3.82 (s, 3H, CH3),
3.52 (br s, 1H, OH). 13C NMR (101 MHz, CDCl3) δ 159.88, 139.46,
139.29, 137.66, 129.67, 128.31, 128.27, 128.02, 127.97, 127.83,
127.41, 120.28, 113.54, 113.47, 87.06, 78.73, 70.84, 55.38. IR νmax
3542, 3506, 3434, 3414, 3064, 3028, 2938, 2872, 2833, 1601, 1494,
1458, 1437, 1269, 1198, 1159, 1078, 1057, 1021, 961, 923, 851, 788,
767, 746, 695, 573 cmÀ 1. HRMS (ESI) m/z calculated for C22H23O3 (M
ee) of the title compound as colorless crystals. H NMR (400 MHz,
CDCl3) δ 7.51–7.45 (m, 2H, ArÀ H), 7.25–7.20 (m, 3H, ArÀ H), 7.19–7.12
(m, 5H, ArÀ H), 7.09–7.00 (m, 4H, ArÀ H), 4.74 (d, J=8.0 Hz, 1H, CH),
4.47 (d, J=11.7 Hz, 1H, CH2), 4.34 (d, J=8.0 Hz, 1H), 4.29 (d, J=
11.7 Hz, 1H, CH2), 3.40 (br s, 1H, OH). 13C NMR (100 MHz, CDCl3) δ
139.22, 137.46, 136.85, 131.71, 129.67, 128.37, 128.35, 128.00,
127.94, 127.87, 127.33, 121.87, 87.06, 78.65, 70.14. The recorded
values were in agreement with the published data.[34] Daicel
Chiralpak IB, n-heptane/IPA 98/2, 1 mL/min, 205 nm, tS,S =10.7 min,
+H) 335.1647; found 335.1646. [α]20D = +16.1 (CHCl3, 0.44 g/
t
R,R =12.0 min.
°
100 mL). Rf (5/1 hexanes/Et2O)=0.25. Daicel Chiralpak IB, n-
Methyl
4-(((1S,2S)-2-hydroxy-1,2-diphenylethoxy)methyl)
heptane/IPA 80/20, 1 mL/min, 205 nm, tR,R =7.8 min, tS,S =10.9 min.
benzoate (5g). According to the general procedure with methyl 4-
(hydroxymethyl)benzoate 4g (100 mg, 0.6 mmol) for 86 h. Column
chromatography of the residue on silica gel (2/1 hexanes/Et2O)
furnished 80 mg (76%, 95% ee) of the title compound as colorless
(1S,2S)-2-((2-Methoxybenzyl)oxy)-1,2-diphenylethan-1-ol (5c). Ac-
cording to the general procedure with 2-methoxybenzyl alcohol 4c
(80 μl, 0.6 mmol) for 116 h. Column chromatography of the residue
on silica gel (5/1 hexanes/Et2O) furnished 76 mg (76%, 88% ee) of
the title compound as colorless crystals. 1H NMR (400 MHz, CDCl3) δ
7.39–7.12 (m, 8H, ArÀ H), 7.09–7.00 (m, 4H, ArÀ H), 6.99–6.90 (m, 2H,
ArÀ H), 4.68 (d, J=8.5 Hz, 1H, CH), 4.54 (d, J=11.3 Hz, 1H, CH2), 4.47
(d, J=11.2 Hz, 1H, CH2), 4.34 (d, J=8.5 Hz, 1H, CH), 4.00 (br s, 1H,
OH), 3.87 (s, 3H, CH3). 13C NMR (101 MHz, CDCl3) δ 127.87, 139.35,
137.89, 129.96, 129.57, 128.11, 128.06, 127.97, 127.91, 127.75,
127.53, 126.08, 120.58, 110.58, 87.58, 78.88, 67.63, 55.43. Mp=88-
1
crystals. H NMR (400 MHz, CDCl3) δ 8.05–7.99 (m, 2H, ArÀ H), 7.40–
7.34 (m, 2H, ArÀ H), 7.30–7.14 (m, 6H, ArÀ H), 7.12–7.01 (m, 4H,
ArÀ H), 4.77 (d, J=8.7 Hz, 1H, CH), 4.57 (d, J=12.3 Hz, 1H, CH2), 4.40
(d, J=12.3 Hz, 1H, CH2), 4.37 (d, J=8.0 Hz, 1H, CH), 3.93 (s, 3H, CH3),
3.44 (br s, 1H, OH).13C NMR (101 MHz, CDCl3) δ 167.01, 143.08,
139.21, 137.38, 129.91, 129.69, 128.40, 128.02, 127.95, 127.90,
°
127.57, 127.35, 87.31, 78.69, 70.30, 52.28. Mp=94-95 C. IR (drift
KBr) νmax 3494, 3452, 3067, 3028, 2953, 2872, 1721, 1613, 1434,
89 C. IR (drift KBr) νmax 3405, 3064, 3028, 3001, 2965, 2941, 2899,
1284, 1198, 1174, 1105, 1023, 967, 914, 845, 758, 698, 576 cmÀ 1
.
°
2872, 2839, 1607, 1586, 1497, 1455, 1395, 1287, 1245, 1201, 1177,
HRMS (ESI) m/z calculated for C23H22O4Na (M+Na) 385.14103; found
1126, 1093, 1060, 1033, 934 851 776, 755, 701, 656, 626, 558 cmÀ 1
.
385.14041. [α]20D = +14.1 (CHCl3, 0.39 g/100 mL). Rf (5/1 hexanes/
°
HRMS (ESI) m/z calculated for C22H22O3Na (M+Na) 357.14612; found
Et2O)=0.1. Daicel Chiralpak IB, n-heptane/IPA 98/2, 1 mL/min,
204 nm, tS,S =28.8 min, tR,R =33.5 min.
357.14555. [α]20D = +25.6 (CHCl3, 0.39 g/100 mL). Rf (5/1 hexanes/
°
Et2O)=0.3. Daicel Chiralpak IB, n-heptane/IPA 80/20, 1 mL/min,
192 nm, tS,S =6.8 min tR,R =8.7 min.
(1S,2S)-2-((4-Nitrobenzyl)oxy)-1,2-diphenylethan-1-ol (5h). Ac-
cording to the general procedure with 4-nitrobenzyl alcohol 4h
(92 mg, 0.6 mmol) for 69 h. Column chromatography of the residue
on silica gel (5/1 hexanes/Et2O) furnished 81 mg (75%, 98% ee) of
the title compound as colorless crystals. 1H NMR (400 MHz, CDCl3) δ
8.25–8.16 (m, 2H, ArÀ H), 7.50–7.42 (m, 2H, ArÀ H), 7.32–7.14 (m, 6H,
ArÀ H), 7.11–7.01 (m, 4H, ArÀ H), 4.81 (d, J=7.8 Hz, 1H, CH), 4.61 (d,
J=12.8 Hz, 1H, CH2), 4.47 (d, J=12.8 Hz, 1H, CH2), 4.40 (d, J=7.8 Hz,
1H, CH), 3.34 (br s, 1H, OH). 13C NMR (101 MHz, CDCl3) δ 147.59,
145.43, 139.14, 137.13, 128.58, 128.53, 128.10, 128.09, 128.03,
(1S,2S)-2-((4-Methylbenzyl)oxy)-1,2-diphenylethan-1-ol (5d). Ac-
cording to the general procedure with 4-methylbenzyl alcohol 4d
(74 mg, 0.6 mmol) for 72 h. Column chromatography of the residue
on silica gel (5/1 hexanes/Et2O) furnished 84 mg (88%, 98% ee) of
the title compound as colorless crystals. 1H NMR (400 MHz, CDCl3) δ
7.29–7.12 (m, 10H, ArÀ H), 7.10–6.99 (m, 4H, ArÀ H), 4.77 (d, J=
8.0 Hz, 1H, CH), 4.49 (d, J=11.2 Hz, 1H, CH2), 4.35 (d, J=8.2 Hz, 1H,
CH), 4.30 (d, J=11.2 Hz, 1H, CH2), 3.54 (br s, 1H, OH), 2.37 (s, 3H,
CH3). 13C NMR (101 MHz, CDCl3) δ 139.30, 137.80, 137.77, 134.80,
129.33, 128.28, 128.25, 128.21, 128.02, 127.95, 127.80, 127.43, 86.96,
°
127.89, 127.27, 123.83, 87.58, 78.62, 69.72. Mp=76-77 C. IR (drift
KBr) νmax 3542, 3452, 3114, 3064, 3034, 2872, 1607, 1524, 1494,
4152, 1344, 1317, 1296, 1263, 1251, 1087, 1063, 1042, 1013, 920,
860, 770, 737, 701 cmÀ 1. HRMS (ESI) m/z calculated for C21H20NO4 (M
°
78.76, 70.85, 21.36. Mp=71-72 C. IR (drift KBr) νmax 3560, 3088,
3031, 2953, 2914, 1866, 1622, 1458, 1395, 1344, 1320, 1260, 1201,
1180, 1081, 1060, 1033, 1021, 1003, 946, 917, 857, 812, 764, 698,
656, 612, 597, 492 cmÀ 1. HRMS (ESI) m/z calculated for C22H23O3Na
+H) 350.1392; found 350.1389. [α]20D = +5.1 (MeOH, 0.39 g/
°
100 ml). Rf (5/1 hexanes/Et2O)=0.21. Daicel Chiralpak IB, n-heptane/
IPA 96/4, 1 mL/min, 206 nm, tS,S =27.3 min, tR,R =35.9 min.
(M+Na) 341.15120; found 341.15063. [α]20D = +23.4 (CHCl3,
°
0.32 g/100 mL). Rf (5/1 hexanes/Et2O)=0.53. Daicel Chiralpak IB, n-
heptane/IPA 98/2, 1 mL/min, 209 nm, tS,S =10.5 min, tR,R =11.8 min.
(1S,2S)-1,2-Diphenyl-2-((4-(trifluoromethyl)benzyl)oxy)ethan-1-ol
(5i). According to the general procedure with 4-(trifluoromethyl)
benzyl alcohol 4i (83 μl, 0.6 mmol) for 116 h. Column chromatog-
raphy of the residue on silica gel (5/1 hexanes/Et2O) furnished
(1S,2S)-2-(Benzyloxy)-1,2-diphenylethan-1-ol (5e). According to
the general procedure with benzyl alcohol 4e (62 μl, 0.6 mmol) for
Eur. J. Org. Chem. 2021, 1249–1257
www.eurjoc.org
1254
© 2021 Wiley-VCH GmbH

Full Papers
doi.org/10.1002/ejoc.202001493
96 mg (86%, 98% ee) of the title compound as colorless crystals. 1H
127.95, 127.83, 127.46, 110.42, 109.76, 86.71, 78.61, 62.84. IR (drift
KBr) νmax 3569, 3539, 3512, 3461, 3431, 3372, 3064, 3028, 2923,
2893, 2866, 1601, 1497, 1455, 1260, 1228, 1198, 1153, 1069, 1021,
984, 949, 923, 890, 851, 815, 752, 701, 647, 576 cmÀ 1. HRMS (ESI) m/
1
2
3
4
5
6
7
8
9
NMR (400 MHz, CDCl3) δ 7.64–7.56 (m, 2H, ArÀ H), 7.45–7.37 (m, 2H,
ArÀ H), 7.30–7.14 (m, 6H, ArÀ H), 7.12–7.00 (m, 4H, ArÀ H), 4.78 (d, J=
8.0 Hz, 1H, CH), 4.57 (d, J=12.3 Hz, 1H, CH2), 4.41 (d, J=12.3 Hz, 1H,
CH2), 4.39 (d, J=8.0 Hz, 1H, CH), 3.39 (br s, 1H, OH). 19F NMR
(376 MHz, CDCl3) δ À 62.52. 13C NMR (151 MHz, CDCl3) δ 141.94,
z calculated for C19H19O3 (M+H) 295.1335; found 295.1334. [α]20
=
D
°
+45.7 (CHCl3, 0.35 g/100 mL). Rf (5/1 hexanes/EtOAc)=0.2. Daicel
2
139.19, 137.35, 130.12 (q, JC-F=32.5 Hz), 128.46, 128.43, 128.05,
Chiralpak IB, n-heptane/IPA 80/20, 1 mL/min, 209 nm, 5l: tS,S
=
3
1
127.94, 127.33, 125.55 (q, JC-F =3.5 Hz), 124.26 (q, JC-F =272.0 Hz),
5.3 min, tR,R =6.4 min.
°
87.36, 78.68, 70.13. Mp=75-76 C. IR (drift KBr) νmax 3524, 3402,
(1S,2S)-1,2-Diphenyl-2-(thiophen-2-ylmethoxy)ethan-1-ol
(5m).
3088, 3064, 3034, 2884, 1616, 1458, 1425, 1395, 1326, 1201, 1168,
According to the general procedure with thiophenyl-2-ylmethanol
4m (57 μl, 0.6 mmol) for 114 h. Column chromatography of the
residue on silica gel (20/1 hexanes/EtOAc) furnished 79 mg (85%,
97% ee) of the title compound as colorless crystals. .1H NMR
(400 MHz, CDCl3) δ 7.33 (dd, J=5.1, 1.2 Hz, 1H, ArÀ H), 7.28–7.21 (m,
3H, ArÀ H, ), 7.19–7.11 (m, 3H, ArÀ H), 7.09–6.98 (m, 5H, ArÀ H), 6.95-
6.93 (m, 1H, ArÀ H), 4.70-4.66 (m, 2H, CH+CH2), 4.52 (d, J=12.2 Hz,
1H, CH2), 4.38 (d, J=8.3 Hz, 1H, CH), 3.47 (br s, 1H, OH). 13C NMR
(101 MHz, CDCl3) δ 140.49, 139.16, 137.35, 128.34, 128.06, 127.96,
127.84, 127.44, 126.87, 126.79, 126.27, 86.60, 78.60, 65.27. Mp=61-
1123, 1087, 1069, 1021, 911, 857, 821, 776, 755, 701, 665, 576 cmÀ 1
.
HRMS (ESI) m/z calculated for C22H19F3O2Na (M+Na) 395.12294;
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
found 395.12225. [α]20D = +7.6 (CHCl3, 0.395 g/100 ml). Rf (5/1
°
hexanes/Et2O)=0.35. Daicel Chiralpak IB, n-heptane/IPA 95/5, 1 mL/
min, 208 nm, tS,S =9.2 min, tR,R =10.8 min.
(1S,2S)-2-(Naphthalen-1-ylmethoxy)-1,2-diphenylethan-1-ol (5j).
According to the general procedure with naphthalen-1-ylmethanol
4j (95 mg, 0.6 mmol) for 107 h. Column chromatography of the
residue on silica gel (5/1 hexanes/Et2O) furnished 94 mg (88%, 97%
1
°
ee) of the title compound as colorless crystals. H NMR (400 MHz,
62 C. IR (drift KBr) νmax 3530, 3106, 3058, 3031, 2938, 2887, 2860,
CDCl3) δ 8.09–8.01 (m, 1H, ArÀ H), 7.93–7.82 (m, 2H, ArÀ H), 7.59–7.49
(m, 2H, ArÀ H), 7.48–7.40 (m, 2H, ArÀ H), 7.31–7.24 (m, 3H, ArÀ H),
7.20–7.10 (m, 5H, ArÀ H), 7.05–6.98 (m, 2H, ArÀ H), 4.99 (d, J=
11.5 Hz, 1H, CH2), 4.78 (d, J=11.5 Hz, 1H, CH2), 4.74 (d, J=8.3 Hz,
1H, CH), 4.45 (d, J=8.2 Hz, 1H, CH), 3.42 (br s, 1H). 13C NMR
(101 MHz, CDCl3) δ 139.26, 137.70, 133.95, 133.32, 131.95, 129.09,
128.85, 128.35, 128.34, 128.11, 127.95, 127.80, 127.39, 127.07,
1957, 1882, 1817, 1491, 1452, 1932, 1335, 1269, 1222, 1198, 1177,
1069, 1045, 1021, 994, 920, 860, 824, 776, 755, 704, 656, 632, 612,
555, 540, 480, 462 cmÀ 1. HRMS (ESI) m/z calculated for C19H19O2S
311.1106 (M+H); found 311.1113. [α]20D = +46.7 (CHCl3, 0.54 g/
°
100 mL). Rf (10/1 hexanes/EtOAc)=0.2. Daicel Chiralpak IB, n-
heptane/IPA 80/20, 1 mL/min, 207 nm, tS,S =5.7 min, tR,R =7.1 min.
(1S,2S)-1,2-Diphenyl-2-(ferrocenylmethoxy)ethan-1-ol (5n). Ac-
cording to the general procedure with ferrocenyl methanol 4n
(135 mg, 0.6 mmol) for 11 days. Column chromatography of the
residue on silica gel (5/1 hexanes/Et2O) furnished 35 mg (27%, 89%
ee) of the title compound as orange crystals. 1H NMR (400 MHz,
CDCl3) δ 7.25–7.12 (m, 6H, ArÀ H), 7.07–6.95 (m, 4H, ArÀ H), 4.62 (d,
J=8.3 Hz, 1H, CH), 4.30 (d, J=8.2 Hz, 1H, CH), 4.29 (d, J=11.2 Hz,
1H, FcCH2), 4.25–4.17 (m, 4H, Cp) 4.14 (d, J=11.2 Hz, 1H, FcCH2),
4.10 (s, 5H, Cp), 3.53 (br s, 1H, OH). 13C NMR (101 MHz, CDCl3) δ
139.28, 137.91, 128.22, 128.14, 127.98, 127.93, 127.78, 127.45, 86.79,
°
126.62, 126.03, 125.36, 123.87, 87.35, 78.67, 69.42. Mp=73-74 C. IR
(drift KBr) νmax 3554, 3476, 3440, 3064, 3028, 2881, 1598, 1515, 1488,
1452, 1392, 1257, 1231, 1201, 1171, 1090, 1066, 1042, 1021, 917,
857, 800, 767, 701, 564, 555 cmÀ 1. HRMS (ESI) m/z calculated for
C25H22O2Na (M+Na) 377.15120; found 377.15095. [α]20D = +53.1
(CHCl3, 0.32 g/100 mL). Rf (5/1 hexanes/Et2O)=0.33. Daicel Chiralpak
IB, n-heptane/IPA 80/20, 1 mL/min, 224 nm, tR,R =11.2 min, tS,S
=
13.3 min.
(1S,2S)-2-(Anthracen-9-ylmethoxy)-1,2-diphenylethan-1-ol (5k).
According to the general procedure with 9-antharecenemethanol
°
83.32, 78.71, 69.53, 69.19, 68.94, 68.66, 67.38. Mp=108-109 C. IR
°
4k (125 mg, 0.6 mmol) at 40 C for 69 hours. Column chromatog-
(drift KBr) νmax 3560, 3545, 3464, 3446, 3091, 3064, 3028, 2926, 2866,
1658, 1604, 1449, 1413, 1237, 1201, 1108, 1072, 1021, 1003, 923,
824, 770, 698, 576, 504 cmÀ 1. HRMS (ESI) m/z calculated for
raphy of the residue on silica gel (5/1 hexanes/Et2O) furnished
76 mg (63%, 96% ee) of the title compound as yellowish crystals.
1H NMR (400 MHz, CDCl3) δ 8.50 (s, 1H, ArÀ H), 8.19–8.13 (m, 2H,
ArÀ H), 8.07–8.01 (m, 2H, ArÀ H), 7.55–7.45 (m, 4H, ArÀ H), 7.38–7.30
(m, 3H, ArÀ H), 7.23–7.11 (m, 5H, ArÀ H), 7.03–6.98 (m, 2H, ArÀ H),
5.46 (d, J=11.2 Hz, 1H, CH2), 5.34 (d, J=11.1 Hz, 1H, CH2), 4.69 (d,
J=8.2 Hz, 1H, CH), 4.52 (d, J=8.2 Hz, 1H, CH), 3.37 (br s, 1H, OH).
13C NMR (101 MHz, CDCl3) δ 139.18, 138.04, 131.59, 131.18, 129.27,
128.87, 128.51, 128.42, 128.26, 128.19, 127.95, 127.78, 127.37,
C25H25FeO2 (M+Na) 435.10179; found 435.10152. [α]20D = +52.1
(CHCl3, 0.48 g/100 mL). Rf (5/1 hexanes/EtOAc)=0.2. Daicel Chir-
alpak IB, n-heptane/IPA 90/10, 1 mL/min, 206 nm, tS,S =9.1 min,
°
t
R,R =25.1 min.
(1S,2S)-2-Methoxy-1,2-diphenylethan-1-ol (5o). According to the
general procedure with methanol 4o (25 μl, 0.6 mmol) for 86 h.
Column chromatography of the residue on silica gel (5/1 hexanes/
Et2O) furnished 59 mg (87%, 93% ee) of the title compound as
colorless crystals. 1H NMR (400 MHz, CDCl3) δ 7.24–7.12 (m, 6H,
ArÀ H), 7.07–6.96 (m, 4H, ArÀ H), 4.66 (d, J=8.3 Hz, 1H, CH), 4.13 (d,
J=8.3 Hz, 1H, CH), 3.52 (br s, 1H, OH), 3.31 (s, 3H, CH3). 13C NMR
(101 MHz, CDCl3) δ 139.32, 137.54, 128.19, 128.15, 127.97, 127.90,
127.83, 127.43, 89.35, 78.81, 57.05. Rf (5/1 hexanes/Et2O)=0.2. The
recorded values were in agreement with the published data.[33]
°
126.61, 125.19, 124.14, 87.81, 78.66, 63.41. Mp=143-144 C. IR (drift
KBr) νmax 3509, 3458, 3058, 3031, 2887, 2863, 162, 1452, 1335, 1254,
1234, 1201, 1177, 1156, 1081, 1066, 1048, 1018, 1003, 985, 884, 848,
767, 734, 698, 585, 555 cmÀ 1. HRMS (ESI) m/z calculated for C29H24O2
(M+H) 404.1776; found 404.1771. [α]20D = +101.6 (CHCl3, 0.31 g/
°
100 mL). Rf (5/1 hexanes/Et2O)=0.2. Daicel Chiralpak IB, n-heptane/
IPA 50/50, 1 mL/min, 255 nm, 5k: tS,S =5.3 min, tR,R =13.6 min.
(1S,2S)-1,2-Diphenyl-2-(furan-2-ylmethoxy)ethan-1-ol (5l). Accord-
ing to the general procedure with furfuryl alcohol 4l (52 μl,
0.6 mmol) for 23 days. Reaction carried out with powdered MS 4 Å
(30 mg) and furnished desired alcohol 5 l in 75% 1H NMR yield with
97% ee. The product was isolated by preparative TLC for HPLC
analysis. 1H NMR (400 MHz, CDCl3) δ 7.44 (dd, J=1.8, 0.8 Hz, 1H,
ArÀ H), 7.25–7.11 (m, 6H, ArÀ H), 7.08–6.97 (m, 4H, ArÀ H), 6.45 (dd,
J=3.3, 0.75 Hz, 1H, ArÀ H), 6.26 (d, J=3.3 Hz, 1H, ArÀ H), 4.69 (d, J=
8.3 Hz, 1H, CH), 4.50 (d, J=12.7 Hz, 1H, CH2), 4.31 (d, J=8.4 Hz, 1H,
CH), 4.28 (d, J=12.7 Hz, 1H, CH2), 3.52 (s, 1H, OH). 13C NMR
(101 MHz, CDCl3) δ 151.33, 143.19, 139.16, 137.34, 128.27, 128.04,
Daicel Chiralpak IB, n-heptane/IPA 90/10, 1 mL/min, 208 nm, tS,S
6.2 min, tR,R =6.8 min.
=
(1S,2S)-2-(Cyclohexyloxy)-1,2-diphenylethan-1-ol (5p). According
to the general procedure with cyclohexanol 4p (60 μl, 0.6 mmol)
for 23 d in the presence of powdered MS 4 Å. Column chromatog-
raphy of the residue on silica gel (20/1 hexanes/Et2O) furnished
74 mg (83%, 99% ee) of the title compound as colorless crystals. 1H
NMR (400 MHz, CDCl3) δ 7.22–7.13 (m, 6H, ArÀ H), 7.07–6.98 (m, 4H,
ArÀ H), 4.59 (d, J=8.1 Hz, 1H, CH), 4.35 (d, J=8.1 Hz, 1H, CH), 3.60
(br s, 1H, OH), 3.32–3.23 (m, 1H, CH), 1.80–1.60 (m, 3H, CH2), 1.52–
Eur. J. Org. Chem. 2021, 1249–1257
www.eurjoc.org
1255
© 2021 Wiley-VCH GmbH

Full Papers
doi.org/10.1002/ejoc.202001493
1.08 (m, 7H, CH2). 13C NMR (101 MHz, CDCl3) δ 139.57, 139.05,
128.01, 127.91, 127.86, 127.85, 127.74, 127.44, 84.70, 78.80, 75.72,
[1] R. W. Hoffmann, Angew. Chem. Int. Ed. 2003, 42, 1096–1109; Angew.
1
2
3
4
5
6
7
8
9
Chem. 2003, 115, 1128–1142.
[2] T. Rovis, in New Frontiers in Asymmetric Catalysis, ed. K. Mikami, M.
Lautens, Wiley, Hoboken, NJ, 2007, pp. 275–311.
[3] M. C. Willis, J. Chem. Soc. Perkin Trans. 1 1999, 1765–1784.
[4] R. S. Ward, Chem. Soc. Rev. 1990, 19, 1–19.
[5] Berkessel, H. Groger, in Asymmetric Organocatalysis, Wiley-VCH,
°
33.67, 31.50, 25.83, 24.21, 24.03. Mp=55-56 C. IR (drift KBr) νmax
3524, 3061, 3031, 3029, 2887, 2860, 1491, 1449, 1389, 1320, 1260,
1225, 1195, 1084, 1069, 1024, 961, 911, 890, 851, 776, 749, 701, 662,
573 cmÀ 1. HRMS (ESI) m/z calculated for C20H25O2 (M+H) 297.1855;
found 297.1856. [α]20D =11.5 (CHCl3, 0.31 g/100 mL). Rf (5/1 hex-
°
Weinheim, 2005, Chpt. 13.
anes/EtOAc)=0.3. Daicel Chiralpak IB, n-heptane/IPA 90/10, 1 mL/
min, 208 nm, tS,S =4.5 min, tR,R =5.0 min.
[6] K. Mikami, A. Yoshida, J. Synth. Org. Chem. Jpn. 2002, 60, 732–739.
[7] E. García-Urdiales, I. Alfonso, V. Gotor, Chem. Rev. 2005, 105, 313–354.
[8] A. Borissov, T. Q. Davies, S. R. Ellis, T. A. Fleming, M. S. W. Richardson,
D. J. Dixon, Chem. Soc. Rev. 2016, 45, 5474–5540.
[9] X.-P. Zeng, Z.-Y. Cao, Y.-H. Wang, F. Zhou, J. Zhou, Chem. Rev. 2016, 116,
7330–7396.
(1S,2S)-2-(Allyloxy)-1,2-diphenylethan-1-ol (5q). According to the
general procedure with allyl alcohol 4q (41 μl, 0.6 mmol) for 86 h.
Column chromatography of the residue on silica gel (5/1 hexanes/
Et2O) furnished 65 mg (86%, 95% ee) of the title compound as
colorless crystals. 1H NMR (400 MHz, CDCl3) δ 7.24–7.12 (m, 6H,
ArÀ H), 7.07–6.96 (m, 4H, ArÀ H), 5.99–5.84 (m, 1H, CH), 5.32–5.10 (m,
2H,=CH2), 4.69 (d, J=8.4 Hz, 1H, CH), 4.30 (d, J=8.3 Hz, 1H, CH),
4.00 (app ddt, J=12.6, 5.1, 1.3 Hz, 1H, CH2), 3.85 (app ddt, J=12.6,
6.1, 1.3 Hz 1H, CH2), 3.54 (br s, 1H, OH). 13C NMR (101 MHz, CDCl3) δ
139.29, 137.72, 134.45, 128.20, 128.16, 127.97, 127.92, 127.84,
127.45, 117.46, 86.91, 78.74, 69.90. Rf (5/1 hexanes/Et2O)=0.3. The
recorded values were in agreement with the published data.[33]
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
[10] D. M. Hodgson, A. R. Gibbs, G. P. Lee, Tetrahedron 1996, 52, 14361–
14374.
[11] E. N. Jacobsen, M. H. Wu, in Ring Opening of Epoxides and Related
Reactions, ed. Eric N. Jacobsen, Andreas Pfaltz, Hisashi Yamamoto,
Comprehensive Asymmetric Catalysis, 1999, Vol. 3, pp. 1309–1326.
[12] P.-A. Wang, Beilstein J. Org. Chem. 2013, 9, 1677–1695.
[13] C. Wang, L. Luo, H. Yamamoto, Acc. Chem. Res. 2016, 49, 193–204.
[14] C. Wang, Synthesis 2017, 49, 5307–5319.
[15] M. Nonn, A. M. Remete, F. Fülöp, L. Kiss, Tetrahedron 2017, 73, 5461–
5483.
[16] H. Fernández-Pérez, P. Etayo, J. R. Lao, J. L. Núñez-Rico, A. Vidal-Ferran,
Chem. Commun. 2013, 49, 10666–10675.
[17] H. Pellissier, H. Clavier, Chem. Rev. 2014, 114, 2775–2823.
[18] P. Chauhan, S. Mahajan, D. Enders, Chem. Rev. 2014, 114, 8807–8864.
[19] M. Pinesci, Synlett 2014, 25, 1817–1826.
[20] S. Meninno, A. Lattanzi, Chem. Eur. J. 2016, 22, 3632–3642.
[21] M. B. Marakalala, E. M. Mmutlane, H. H. Kinfe, Beilstein J. Org. Chem.
2018, 14, 1668–1692.
[22] E. N. Jacobsen, F. Kakiuchi, R. G. Konsler, J. F. Larrow, M. Tokunaga,
Tetrahedron Lett. 1997, 38, 773–776.
[23] M. R. Monaco, S. Prévost, B. List, Angew. Chem. Int. Ed. 2014, 53, 8142–
8145; Angew. Chem. 2014, 126, 8280–8283.
Daicel Chiralpak IB, n-heptane/IPA 90/10, 1 mL/min, 207 nm, tS,S
5.3 min, tR,R =5.8 min.
=
(1S,2S)-1,2-Diphenyl-2-(prop-2-yn-1-yloxy)ethan-1-ol (5r). Accord-
ing to the general procedure with propargyl alcohol 4r (35 μl,
0.6 mmol) for 96 h. Column chromatography of the residue on silica
gel (5/1 hexanes/Et2O) furnished 65 mg (81%, 98% ee) of the title
1
compound as a colorless oil. H NMR (400 MHz, CDCl3) δ 7.25–7.12
(m, 6H, ArÀ H), 7.10–6.98 (m, 4H, ArÀ H), 4.73 (d, J=8.4 Hz, 1H, CH),
4.51 (d, J=8.4 Hz, 1H, CH), 4.22 (dd, J=15.7, 2.3 Hz 1H, CH2), 3.95
(dd, J=15.7, 2.2 Hz 1H, CH2), 3.45 (s, 1H, OH), 2.46 (t, J=2.2 Hz, 1H,
�CH). 13C NMR (101 MHz, CDCl3) δ 139.08, 136.61, 128.46, 128.32,
128.11, 127.99, 127.91, 127.47, 86.30, 79.41, 78.39, 75.04, 56.14. Rf
(5/1 hexanes/Et2O)=0.2. The recorded values were in agreement
with the published data.[33] Daicel Chiralpak IB, n-heptane/IPA
90/10, 1 mL/min, 208 nm, tS,S =7.3 min, tR,R =8.4 min.
[24] S. Matsunaga, J. Das, J. Roels, E. M. Vogl, N. Yamamoto, T. Iida, K.
Yamaguchi, M. Shibasaki, J. Am. Chem. Soc. 2000, 122, 2252–2260.
[25] Recently lanthanide-based coordination polymers could serve as
resuable lanthanide-based catalysts for opening of epoxides. G. Kumar,
G. Kumar, R. Gupta, RSC Adv. 2016, 6, 21352–21361.
[26] S. Kobayashi, Eur. J. Org. Chem. 1999, 15–27.
[27] B. M. Choudary, K. Jyothi, S. Madhi, M. L. Kantam, Synlett 2004, 231–234.
[28] A. Berkessel, E. Ashkenazi, M. R. M. Andreae, Appl. Catal. A: General
2003, 254, 27–34.
[29] P. R. Likhar, M. P. Kumar, A. K. Bandyopadhyay, Synlett 2001, 836–838.
[30] Recently lanthanide-based coordination polymers could serve as
resuable lanthanide-based catalysts for opening of epoxides. G. Kumar,
G. Kumar, R. Gupta, RSC Adv. 2016, 6, 21352–21361. C. Bolm, M.
Zehnder, D. Bur, Angew. Chem. Int. Ed. Engl. 1990, 29, 205–207.
[31] C. Bolm, M. Ewald, M. Felder, G. Schlingloff, Chem. Ber. 1992, 125, 1169–
1190.
[32] C. Schneider, A. R. Sreekanth, E. Mai, Angew. Chem. Int. Ed. 2004, 43,
5691–5694; Angew. Chem. 2004, 116, 5809–5812.
[33] A. Tschöp, A. Marx, A. R. Sreekanth, C. Schneider, Eur. J. Org. Chem.
2007, 2318–2327.
[34] M. Boudou, C. Ogawa, S. Kobayashi, Adv. Synth. Catal. 2006, 348, 2585–
2589.
[35] H. Pellissier, Coord. Chem. Rev. 2017, 336, 96–151.
[36] H. Pellissier, Coord. Chem. Rev. 2016, 313, 1–37.
[37] H. Pellissier, Coord. Chem. Rev. 2016, 324, 16–38.
[38] E. Mai, C. Schneider, Chem. Eur. J. 2007, 13, 2729–2741.
[39] A. Azoulay, K. Manabe, S. Kobayashi, Org. Lett. 2005, 11, 4596–4595.
[40] M. Kokubo, T. Naito, S. Kobayashi, Tetrahedron 2010, 66, 1111–1118.
[41] B. Plancq, T. Ollevier, Chem. Commun. 2012, 48, 3806–3808. For a
related reports see: a) S. Lauzon, H. Keipour, V. Gandon, T. Ollevier, Org.
Lett. 2017, 19, 6324–6327; b) M. Li, V. Carreras, A. Jalba, T. Ollevier, Org.
Lett. 2018, 20, 995–998; c) B. Planq, T. Ollevier, Aust. J. Chem. 2012, 65,
1564–1572.
Supporting Information (see footnote on the first page of this
article): For characterization of other compounds, see the SI.
Deposition Number 2015559 (for 5p) contains the supplementary
crystallographic data for this paper. These data are provided free of
charge by the joint Cambridge Crystallographic Data Centre and
Fachinformationszentrum Karlsruhe Access Structures service
www.ccdc.cam.ac.uk/structures.
Acknowledgements
The authors gratefully acknowledge financial support from the
Czech Science Foundation (grant No. 17-07707S). The authors
would like to express gratitude for measurements of ESI-MS to Dr.
Martin Štícha and for X-ray structure analysis to Dr. Ivana
Císařová (Charles University).
Conflict of Interest
The authors declare no conflict of interest.
[42] E. Mai, C. Schneider, Synlett 2007, 2136–2138.
[43] E. Mai, C. Schneider, Arkivoc 2008, (xvi) 216–222.
[44] For review on the use of Bolm’s ligand, see: Kotora E. Bednařová, Š.
Malatinec, M. Kotora, Molecules 2020, 25, 958.
[45] E. Bednářová, M. Dračínský, Š. Malatinec, I. Císařová, F. Lamaty, M.
Kotora, Adv. Synth. Catal. 2018, 360, 2869–2878.
Keywords: Chiral ligands · Desymmetrization · Enantioselective
reaction · Epoxides · Lewis acid
Eur. J. Org. Chem. 2021, 1249–1257
www.eurjoc.org
1256
© 2021 Wiley-VCH GmbH

Full Papers
doi.org/10.1002/ejoc.202001493
[46] The Lewis acidity scale was based on competitive dissociation of
[49] S. Superchi, M. Conturi, C. Rosini, Tetrahedron 1998, 54, 11247–11254.
1
2
3
4
5
lanthanoid(iii) compound observed by tandem mass spectrometry. a) H.
Tsuruta, K. Yamaguchi, T. Imamoto, Chem. Commun. 1999, 1703–1704;
b) H. Tsuruta, K. Yamaguchi, T. Imamoto, Tetrahedron 2003, 59, 10419–
10438.
[47] S. Ishikawa, T. Hamada, K. Manabe, S. Kobayashi, J. Am. Chem. Soc. 2004,
126, 12236–12237.
[48] F. Brotzel, Y. C. Chu, H. Mayr, J. Org. Chem. 2007, 72, 3679–3688.
Manuscript received: November 13, 2020
Revised manuscript received: January 1, 2021
Accepted manuscript online: January 16, 2021
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
Eur. J. Org. Chem. 2021, 1249–1257
www.eurjoc.org
1257
© 2021 Wiley-VCH GmbH