Asymmetric synthesis of benzofuryl β-amino alcohols by the transfer hydrogenation of α-functionalized ketones

Article abstract of DOI:10.1016/j.tet.2017.05.059

The asymmetric transfer hydrogenation of representative benzofuryl α-sulfonyloxy ketones and N-protected α-amino ketones with an azeotropic mixture of formic acid/triethylamine, catalyzed by RhCl[(R,R)-TsDPEN](C₅Me₅), afforded the corresponding 1,2-diol monosulfonates and N-substituted β-amino alcohols in high yields and with enantioselectivities up to 99%. Transformation of the reduction products to the chiral benzofuryl β-amino alcohols possessing a primary amine group is also described.

Full text of DOI:10.1016/j.tet.2017.05.059

Tetrahedron xxx (2017) 1e15
Contents lists available at ScienceDirect
Tetrahedron
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Asymmetric synthesis of benzofuryl
b-amino alcohols by the transfer
hydrogenation of
a
-functionalized ketones
*
ꢀ
ꢀ
ꢀ
Agnieszka Tafelska-Kaczmarek , Marek P. Krzeminski, Marta Cwiklinska
ꢀ
ꢀ
Faculty of Chemistry, Nicolaus Copernicus University in Torun, 7 Gagarin St., Torun, Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
The asymmetric transfer hydrogenation of representative benzofuryl a-sulfonyloxy ketones and N-pro-
Received 10 March 2017
Received in revised form
30 April 2017
Accepted 15 May 2017
Available online xxx
tected
TsDPEN](C5Me5), afforded the corresponding 1,2-diol monosulfonates and N-substituted
hols in high yields and with enantioselectivities up to 99%. Transformation of the reduction products to
the chiral benzofuryl -amino alcohols possessing a primary amine group is also described.
© 2017 Elsevier Ltd. All rights reserved.
a
-amino ketones with an azeotropic mixture of formic acid/triethylamine, catalyzed by RhCl[(R,R)-
b
-amino alco-
b
Keywords:
Asymmetric synthesis
Transfer hydrogenation
Amino alcohols
Benzofuran
Amino ketones
1. Introduction
ketones,20e24 and many others have been developed.25e27 An
attractive method for -amino alcohol synthesis is the asymmetric
transfer hydrogenation of
-functionalized ketones.28e31 Asym-
metric transfer hydrogenation (ATH) is established as an excellent
reduction method due to its versatility, operational simplicity,
avoidance of explosive hydrogen gas, catalyst robustness, and high
stereoselectivity.32e35
b
Chiral amino alcohols represent useful structures in organic and
medicinal chemistry. -Amino alcohols are found in the structural
units of many building blocks, chiral auxiliaries, and ligands.1e5
Moreover, optically active -amino alcohols containing heteroaryl
moieties are of great importance as a key intermediates for the syn-
thesis of physiologically active compounds.6,7 Benzofuran is consid-
ered as an important structure due to its diverse biological profile.8
There have been many reports on the synthesis of benzofuran de-
rivatives because of their clinical importance.9,10 For example,
bufuralol (2-tert-butylamino-1-(7-ethylbenzofuran-2-yl)ethanol) isa
a
b
b
In our previous asymmetric syntheses of benzofuryl
alcohols, the transfer hydrogenation of
-halo ketones,36
ketones,37 and -dialkylamino ketones38 was a key step. Hereby,
the corresponding -amino alcohols possessing secondary and
b-amino
a
a-imino
a
b
tertiary amine groups were obtained.
potent non-selective
b-adrenergic receptor antagonist of comparable
In continuation of our earlier efforts toward the preparation of
potency to propranolol, an inhibitor of testosterone 6
b
-hydroxylase,
chiral benzofuryl
metric transfer hydrogenation of
amino ketones, -succinimido, and
b
-amino alcohols, we herein report the asym-
-sulfonyloxy, N-Cbz protected
-phthalimido ketones, and
-amino alcohols with primary
and commonly used marker of hepatic CYP 2D6 activity.11e15 1-(3-
Phenethylbenzofuran-2-yl)-2-propylaminoethanol, a propafenone
a
a-
a
a
analogue, shows antiarrhythmic activity with a lack of
b-adre-
further transformations to afford
and secondary amine groups.
b
noacceptor blocking activity.16
Various syntheses of enantiomerically pure
including: the aminohydroxylation of olefins,17 the reduction-
amination of
-halo ketones,5,18 the enzymatic resolution of
racemic -amino
-amino alcohols,19 catalytic reduction of
b-amino alcohols
2. Results and discussion
a
b
a
2.1. Asymmetric transfer hydrogenation of benzofuryl
ketones
a-sulfonyloxy
The
a-sulfonyloxy benzofuryl ketones 1e4 were readily pre-
* Corresponding author.
E-mail address: tafel@chem.umk.pl (A. Tafelska-Kaczmarek).
pared by sulfonyloxylation of the corresponding (benzofuran-2-yl)
http://dx.doi.org/10.1016/j.tet.2017.05.059
0040-4020/© 2017 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Tafelska-Kaczmarek A, et al., Asymmetric synthesis of benzofuryl
hydrogenation of -functionalized ketones, Tetrahedron (2017), http://dx.doi.org/10.1016/j.tet.2017.05.059
b-amino alcohols by the transfer
a

2
A. Tafelska-Kaczmarek et al. / Tetrahedron xxx (2017) 1e15
Table 1
Asymmetric transfer hydrogenation of benzofuryl a-sulfonyloxy ketones 1e4.
Ketone
R1
R2
R3
Alcohol
Yielda (%)
eeb (%)
1a
1b
1c
1d
1e
2a
2b
2c
3a
3b
3c
4a
4b
4c
4e
H
H
Me
Me
Ph(CH2)2
H
H
Me
H
H
Me
H
H
Me
Ph(CH2)2
H
Et
H
Me
H
H
Et
H
H
Et
H
H
4-Me-C6H4
4-Me-C6H4
4-Me-C6H4
4-Me-C6H4
4-Me-C6H4
4-Cl-C6H4
4-Cl-C6H4
4-Cl-C6H4
Ph
Ph
Ph
Me
Me
5a
5b
5c
5d
5e
6a
6b
6c
7a
7b
7c
8a
8b
8c
8e
92
93
96
89
95
84
93
96
99
93
93
95
93
93
96
97
90
92
87
93
98c
94c
90
97
94
92
99
95
93
93
Et
H
H
Me
Me
a
Isolated yield.
b
c
Determined by HPLC analysis on a chiral column (Daicel Chiralcel OD-H, 250 ꢁ 4.6 mm, 5
mm).
Separation was not possible. Assignments based on the ee of -azido alcohols 9 and 10, respectively.
b
ethanones with [hydroxy(tosyloxy)iodo]benzene (PhI(OH)OTs),39
[hydroxy(mesyloxy)iodo]benzene (PhI(OH)OMs),40 [hydroxy(4-
chloroben-zenesulfonyloxy)iodo]benzene (PhI(OH)OCs),39 and
[hydroxy(benzenesulfonyloxy)-iodo]benzene (PhI(OH)OSO2Ph).39
transfer hydrogenation of 1ꢀ4 was carried out with the formic acid/
triethylamine azeotrope (5:2), catalyzed by RhCl[(R,R)-
TsDPEN](C5Me5), in ethyl acetate at room temperature. All 1,2-diol
monosulfonates 5e8 were formed in very high yields (84e99%) and
with enantioselectivities over 90% (Table 1). Only one product, 2-
tosyloxy-1-(3,7-dimethylbenzofuran-2-yl)ethanol (5d), was ob-
tained with lower ee, 87%. There was no significant influence of the
sulfonyl group type on the yield and enantioselectivity of the
reduction. 2-Sulfonyloxy-1-(benzofuran-2-yl)ethanols (5e8)a
differing in the substituent of the sulfonyl group, were afforded
with excellent ee, 97e99%. Derivatives of 3-methylbenzofuran
(5e8)c were isolated with 90e93% ee, and 2-tosyloxy-1-(3-
The a-sulfonyloxylation reactions were carried out in acetonitrile
at reflux for 3 h,41 and products were separated in moderate to
good yields (45e79%). In general, the reaction products of ketones
with PhI(OH)OCs were formed with lower yields than in other cases
(see Experimental section). Moreover, in contrast to Lee and co-
workers,41 no problems with mesyloxylation and tosyloxylation of
1-(7-ethylbenzofuran-2-yl)ethanone were noticed; appropriate
products were obtained in 57% and 76% yields, respectively. The
Table 2
Asymmetric synthesis of benzofuryl b-amino alcohols.
No.
R1
R2
No.
Yielda (%)
ee (%)
No.
Yielda (%)
5a
5b
5c
5d
5e
6a
6b
8a
H
H
Me
Me
H
Et
H
Me
H
H
9
84
72
62
53
50
77
88
99
97b
90c
92c
87b
93b
98b
94c
99b
14
15
16
17
18
ed
ed
ed
99
97
96
79
71
e
10
11
12
13
9
Ph(CH2)2
H
H
H
Et
H
10
9
e
e
a
Isolated yield.
b
c
Determined by HPLC analysis on a chiral column (Daicel Chiralcel OD-H, 250 ꢁ 4.6 mm, 5
m
mm).
m).
Determined by HPLC analysis on a chiral column (Daicel Chiralcel OJ, 250 ꢁ 4.6 mm, 10
d
Not tested.
Please cite this article in press as: Tafelska-Kaczmarek A, et al., Asymmetric synthesis of benzofuryl
hydrogenation of -functionalized ketones, Tetrahedron (2017), http://dx.doi.org/10.1016/j.tet.2017.05.059
b-amino alcohols by the transfer
a

A. Tafelska-Kaczmarek et al. / Tetrahedron xxx (2017) 1e15
3
phenethylbenzofuran-2-yl)ethanol (5e) and 2-mesyloxy-1-(3-
phenethylbenzofuran-2-yl)ethanol (8e) with 93% ee. Minor differ-
ences in the reduction selectivity were found for the 7-
ethylbenzofuran derivatives (1e4)b; the products were obtained
with ee from 90 to 95%. In addition, we have no explanation, why 2-
tosyloxy-1-(7-ethylbenzofuran-2-yl)ethanol (5b) and 2-mesyloxy-
1-(7-ethylbenzofuran-2-yl)ethanol (8b) were formed with 90 and
95% ee, while (S)-5b and (S)-8b were reported as 95 and 97% ee,
respectively.41 It is noteworthy that Lee was unable to separate 2-
tosyloxy-1-(benzofuran-2-yl)ethanol (5a) by chiral HPLC,41
whereas we were successful. The enantioselectivity was deter-
mined to be 97% ee, using HPLC analysis on a Daicel Chiralcel OD-H
column. However, determination of the enantiomeric excess of 6a
and 6b was not possible, rather it was assigned based on HPLC
transformations.
b
-Sulfonyloxy alcohols were treated with an
excess of sodium azide in DMSO to give b-azido alcohols 9e13 in
good yields (50e99%). The results are summarized in Table 2.
The ee values were determined by HPLC analysis using Daicel
Chiralcel OD-H or OJ columns. The results indicate that no race-
mization occurred during the azidation reaction. Next, the obtained
b-azido alcohols were hydrogenated under 10 atm. pressure over
10% Pd/C to provide the benzofuryl -amino alcohols 14e18 in high
b
yields (71e99%). The exact enantiomeric excess of products could
not be determined by chiral HPLC, hence we assumed that ee values
were unchanged. The present work represents a convenient and
highly enantioselective method for the synthesis of the benzofuryl
b-amino alcohols in three steps from a-sulfonyloxy ketones.
separation of b-azido alcohols 9 and 10, prepared in the next step
2.2. Asymmetric transfer hydrogenation of benzofuryl N-Cbz
amino ketones
a-
(Table 2). The configuration of 1,2-diol monosulfonates 5e8 was
(R), as established by comparing the sign of rotation with known
(S)-5a, (S)-5b, and (S)-8b.41
We were interested to apply the optically active benzofuryl 1,2-
diol monosulfonates, obtained with high enantiomeric excesses, as
The enantioselective reduction of a-amino ketones is a one-step
transformation, which represents an attractive short synthetic
pathway, and is an objective of ongoing interest.45e48 The possi-
precursors for the synthesis of
aryl, heteroaryl, and alkyl -sulfonyloxy alcohols have been used to
obtain these target compounds,42,43 there has been no report of the
synthesis of chiral benzofuryl -amino alcohols in this manner. To
the best of our knowledge, no chiral benzofuryl -amino alcohols
b-amino alcohols. Although various
bility of free a-amino ketone reduction is limited due to their poor
b
availability and stability, because the primary and secondary amino
group reacts with the carbonyl group.49e51 However, their hydro-
chlorides are more stable and can be reduced, providing amino
groups which remain in the hydrochloride form under the reducing
b
b
possessing a primary amine group have been reported in the
literature. Furthermore, derivatives of 2-amino-1-(benzofuran-2-
yl)ethanol are an interesting group of compounds due to their
anti-obesity, hypoglycemic, anti-inflammatory, and platelet-
aggregation inhibiting activity.44 Thus, following the known
conditions.52,53 The benzofuryl
a-amino ketones, as their hydro-
chloride salts 27e30, were obtained in two steps from the appro-
priate a
-bromo ketones 19e22, following the reported procedure.54
The reaction of 19ꢀ22 with sodium diformylamide55 in acetonitrile
led to the stable N,N-diformylamino ketones 23e26 in quantitative
yields (Scheme 1). The formyl groups were easily removed by 5%
sequence:
b
-sulfonyloxy alcohol /
b-azido alcohol / b-amino
alcohol,43 the new benzofuryl
b
-amino alcohols were prepared. For
hydrochloric acid in ethanol to afford the corresponding a-amino
ketone hydrochlorides 27e30 in high yields.
this purpose, tosylates 5aꢀe, 4-chlorobenzenesulfonates 6a, 6b,
and mesylate 8a were selected for the aforementioned
Attempts at the transfer hydrogenation (HCOOH/Et3N 5:2 as a
Scheme 1. Synthesis of benzofuryl N-Cbz protected a-amino ketones 31e34.
Please cite this article in press as: Tafelska-Kaczmarek A, et al., Asymmetric synthesis of benzofuryl
hydrogenation of -functionalized ketones, Tetrahedron (2017), http://dx.doi.org/10.1016/j.tet.2017.05.059
b-amino alcohols by the transfer
a

4
A. Tafelska-Kaczmarek et al. / Tetrahedron xxx (2017) 1e15
Table 3
Asymmetric transfer hydrogenation of 31e34 and deprotection of 35e38.
No.
R1
R2
No.
Yielda (%)
eeb (%)
No.
Yielda (%)
31
32
33
34
H
H
Me
Me
H
Et
H
35
36
37
38
81
76
94
95
99
98
95
97
14
15
16
17
99
78
75
80
Me
a
Isolated yield.
b
Determined by HPLC analysis on a chiral column (Daicel Chiralcel OD-H, 250 ꢁ 4.6 mm, 5
mm).
hydrogen source, RhCl[(R,R)-TsDPEN](C5Me5) as catalyst, AcOEt as a
solvent) of the representative 2-amino-1-(benzofuran-2-yl)etha-
none hydrochloride (27) failed. We presume that the catalyst
containing an amine ligand undergoes deactivation by hydrogen
chloride from the amino ketone hydrochloride. On the other hand,
Wills and coworkers have reported the successful transfer hydro-
(76e95%), and excellent enantioselectivities (95e99%), as deter-
mined by chiral HPLC. Deprotection of the nitrogen group in 35ꢀ38,
under 8 atm. pressure of hydrogen over 10% Pd/C in methanol, gave
benzofuryl b-amino alcohols 14e17 in high yields. The (R) config-
uration of compounds 35e38 was assigned based on comparison of
the optical rotation signs of the final products 14e17 with those
obtained earlier (Table 2). As can be seen from Table 3, benzofuryl
genation of various N-Boc and N-Cbz protected
a-amino ke-
tones.28,29,56 Therefore, we decided to protect the benzofuryl
a-
N-Cbz protected a-amino ketones are excellent substrates for the
amino ketones prior to the reduction. Considering the possibility of
removing the protecting group under neutral conditions (the
benzofuryl derivatives are sensitive to strong acids), we chose the
benzyloxycarbonyl group (Cbz) for protection of the amine. The
reaction of the amino ketones hydrochlorides 27e30 with benzyl
chloroformate, in a mixture of 1,4-dioxane/water (1:1) at room
temperature, furnished benzyl (2-(benzofuran-2-yl)-2-oxoethyl)
carbamates 31e34 in high yields (Scheme 1). Next, 31e34 were
subjected to the transfer hydrogenation with formic acid/triethyl-
amine (5:2), catalyzed by RhCl[(R,R)-TsDPEN](C5Me5), in ethyl ac-
etate at room temperature (Table 3). The corresponding optically
asymmetric transfer hydrogenation, and hence benzofuryl
mary amino alcohols are obtained with high yields and ees.
b-pri-
2.3. Asymmetric transfer hydrogenation of benzofuryl
succinimido and -phthalimido ketones
a-
a
Succinimido and phthalimido ketones are alternative substrates
for the synthesis of amino alcohols with easily removable pro-
tecting groups. There are several examples in the literature of the
enantioselective catalytic reduction of various aromatic and
aliphatic substituted
a-phthalimido ketones under a high pressure
of hydrogen and with diphosphine catalysts.57e60 Very recently, Xu
active
b-amino alcohols 35e38 were obtained in high yields
Table 4
Asymmetric transfer hydrogenation of benzofuryl a-succinimido and a-phthalimido ketones 39e45.
No.
R1
R2
X
No.
Yielda (%)
ee (%)
39
40
41
42
H
H
Me
Me
H
Et
H
46
47
48
49
95
89
79
76
94b
91c
80c
79c
Me
43
44
45
H
H
Me
H
Et
H
50
51
52
98
76
92
91c
89c
84c
a
Isolated yield.
b
c
Determined by HPLC analysis on a chiral column (Daicel Chiralcel OD-H, 250 ꢁ 4.6 mm, 5
mm).
Determined by HPLC analysis on a chiral column (Daicel Chiralcel OJ, 250 ꢁ 4.6 mm, 10 m).
m
Please cite this article in press as: Tafelska-Kaczmarek A, et al., Asymmetric synthesis of benzofuryl
hydrogenation of -functionalized ketones, Tetrahedron (2017), http://dx.doi.org/10.1016/j.tet.2017.05.059
b-amino alcohols by the transfer
a

A. Tafelska-Kaczmarek et al. / Tetrahedron xxx (2017) 1e15
5
and co-workers reported the first asymmetric transfer hydroge-
nation of -phthalimido ketones with the use of a chiral Ru(II)/
TsDPEN complex and HCOOH as hydrogen resource.30 On the other
hand, only one example of the catalytic reduction of an -succini-
mido ketone has been described.61 Therefore, we decided to pre-
pare the benzofuryl -succinimido and -phthalimido ketones, and
submit them to the asymmetric transfer hydrogenation. The ben-
zofuryl -succinimido ketones 39e42 were synthesized by the re-
action of -bromo ketones 19e22 with freshly prepared potassium
succinimide (see Experimental section).61 Similarly,
-phthalimido
spectrometer. Optical rotations were measured on an automatic
polarimeter, PolAAr 3000, Optical Activity Ltd. HPLC analyses were
performed on a Shimadzu LC-10AT chromatograph. IR analyses
were recorded on a Perkin Elmer Spectrum RX I spectrometer.
Melting points were determined in open glass capillaries and are
uncorrected. Elemental analyses were performed on, a Vario
MACRO CHN, ELEMENTAR Analysensysteme GmbH instrument.
a
a
a
a
a
a
4.2. Materials
a
ketones 43e45 were obtained in the reactions of 19ꢀ21 with
Silica Gel 60, Merck 230e400 mesh, was used for preparative
column chromatography. Analytical TLC was performed using
Merck TLC Silica gel 60 F254 0.2 mm aluminium plates. THF was
freshly distilled from sodium benzophenone ketyl. Acetonitrile was
distilled from calcium hydride. Methanol was dried over 4 Å mo-
lecular sieves. Benzyl chloroformate and potassium phthalimide
were commercial products. 1-(Benzofuran-2-yl)ethanone,63 1-(7-
ethylbenzofuran-2-yl)ethanone,64 1-(3-phenethylbenzofuran-2-
yl)ethanone,64 1-(benzofuran-2-yl)-2-bromoethanone,65 1-(3-
methylbenzofuran-2-yl)ethanone,66 2-bromo-1-(7-ethyl-benzo-
commercially available potassium phthalimide. Under our ATH
conditions (HCOOH/Et3N as
a hydrogen source, RhCl[(R,R)-
TsDPEN](C5Me5) as catalyst), the benzofuryl succinimido and
phthalimido ketones were reduced to yield alcohols 46e52 in high
yields and with good to high enantioselectivities (Table 4).
The transfer hydrogenation reactions were run at room tem-
perature in ethyl acetate. The substrates 39e45 were sufficiently
soluble in this solvent. However, longer reaction times were
required (72 h); the reaction progress was monitored by TLC
analysis. As shown in Table 4, the type of protecting group on ni-
trogen has no significant influence on enantioselectivity, in contrast
to the substituents on the benzofuran ring. 3-Methylbenzofuryl
ketones 41, 42, and 45 furnished the corresponding alcohols with
lowered ees (79e84%) in comparison to other products (89e94%).
The next step was deprotection of the succinimides and phthali-
furan-2-yl)ethanone,64
ethanone,66
2-bromo-1-(3-methylbenzofuran-2-yl)
[hydrox-
[hydroxy(to-syloxy)iodo]benzene,39
y(mesyloxy)iodo]benzene,40 [hydroxy(4-chlorobenzene-sulfony-
loxy)iodo]benzene,39
[hydroxy(benzenesulfonyloxy)iodo]benze
ne,39 RhCl[(R,R)-TsDPEN](C5Me5),38 sodium diformylamide,55 and
potassium succinimide61 were prepared according to the literature
procedures. 1-(3,7-Dimethylbenzofuran-2-yl)ethanone was pre-
pared from 3,7-dimethylbenzofuran and acetic anhydride; 2-
bromo-1-(3,7-dimethylbenzofuran-2-yl)ethanone from 1-(3,7-
dimethylbenzofuran-2-yl)ethanone and pyridinium tribromide,
according to the known protocols.64 The formic acid/triethylamine
(molar ratio 5:2) azeotrope was prepared by distillation of the
mixture.67
mides to obtain
b-amino alcohols with a primary amine group.
Removal of the succinic acid group was accomplished by treating
46e49 with 20% aqueous sodium hydroxide in refluxing ethanol,61
whilst phthalimides 50e51 were cleaved in the presence of hy-
drazine utilizing the classic Gabriel synthesis.62 The optical rotation
sign (þ) of the obtained primary
b-amino alcohols was the same as
that of 14ꢀ17 prepared in the previous methods, hence the R
configuration of compounds 46e52 was assigned.
The appropriate racemic compounds were also prepared and
used as standards for ee determination.
3. Conclusion
4.3. General procedure for
ketones
a-sulfonyloxylation of the benzofuryl
In conclusion, we have described the highly efficient and
enantioselective asymmetric transfer hydrogenation of benzofuryl
a
-functionalized ketones, catalyzed by RhCl[(R,R)-TsDPEN](C5Me5).
The obtained chiral benzofuryl 1,2-diol monosulfonates represent
useful substrates for three-step synthesis of -amino alcohols with
a primary amine group. Moreover, the 1,2-diol monosulfonates can
be used as key intermediates in the direct synthesis of important
To a solution of the corresponding benzofuryl ketone (7.5 mmol)
in acetonitrile (50 mL) was added PhI(OH)OSO2R (R ¼ 4-Me-C6H4,
4-Cl-C6H4, Ph, Me) (7.5 mmol) and stirred at reflux for 3 h. After
cooling to rt, the reaction mixture was concentrated in vacuo. The
residue was purified by column chromatography on silica gel or
crystallized from ethanol.
b
b
-
amino alcohols possessing a secondary amine group. For example,
(S)-2-mesyloxy-1-(7-ethylbenzofuran-2-yl)ethanol ((S)-8b) was
reacted with tert-butylamine in ethanol providing (S)-bufuralol in
4.3.1. 2-Tosyloxy-1-(benzofuran-2-yl)ethanone 1a41
99% ee.41 The simple deprotection of benzofuryl N-Cbz protected
b
-
Crystallized from ethanol, 1.75 g, 70% yield, mp 115e116 ꢂC. 1H
amino alcohols, obtained with 95e99% ee, led to
with an NH2 group. Furthermore, the chiral carbamate derivatives
b
-amino alcohols
NMR (400 MHz, CDCl3):
d
¼ 2.47 (s, 3H, CH3), 5.24 (s, 2H, CH2),
7.34e7.40 (m, 3H), 7.54 (td, J ¼ 8.4, 1.2 Hz, 1H), 7.58 (ddd, J ¼ 8.4, 1.5,
0.8 Hz, 1H), 7.66 (d, J ¼ 1.2 Hz, 1H), 7.75 (dt, J ¼ 7.6, 1.2 Hz, 1H),
of b-amino alcohols, in turn, can be used in the synthesis of opti-
cally active aziridines.28,29 Hence, our ongoing experiments are
focused on the synthesis of new chiral benzofuryl compounds
7.90e7.92 (m, 2H) ppm. 13C NMR (75 MHz, CDCl3):
d
¼ 21.7 (CH3),
69.7 (CH2), 112.4 (CH), 114.7 (CH), 123.6 (CH), 124.3 (CH), 126.6 (C),
128.2 (2xCH), 129.1 (CH), 129.9 (2xCH), 132.5 (C), 145.4 (C), 149.7
(C), 155.6 (C), 181.5 (CO) ppm. Anal. calcd for C17H14O5S: C, 61.81; H,
4.27. Found: C, 61.75; H, 4.25.
based on chiral b-amino alcohols.
4. Experimental
4.1. General
4.3.2. 2-Tosyloxy-1-(7-ethylbenzofuran-2-yl)ethanone 1b41,68
Crystallized from ethanol, 1.88 g, 76% yield, mp 69e70 ꢂC. 1H
Experiments with air and moisture sensitive materials were
carried out under a nitrogen atmosphere. Glassware was oven dried
for several hours, assembled hot, and cooled in a stream of nitro-
gen. 1H and 13C spectra were recorded on Varian Gemini 200,
Bruker AMX 300 MHz, Avance III 400 MHz, and Avance 700 MHz
spectrometers. MS spectra were recorded on an AMD 604
NMR (300 MHz, CDCl3):
d
¼ 1.35 (t, J ¼ 7.5 Hz, 3H, CH3), 2.45 (s, 3H,
CH3), 2.96 (q, J ¼ 7.5 Hz, 2H, CH2), 5.25 (s, 2H, CH2), 7.24e7.29 (m,
1H), 7.33e7.38 (m, 3H), 7.54 (d, J ¼ 7.5 Hz, 1H), 7.63 (s, 1H),7.89 (d,
J ¼ 8.1 Hz, 2H). 13C NMR (75 MHz, CDCl3):
¼ 13.9 (CH3), 21.7 (CH3),
d
22.6 (CH2), 69.6 (CH2), 115.0 (CH), 120.9 (CH), 124.5 (CH), 126.2 (C),
128.0 (CH), 128.2 (2xCH), 128.9 (C), 129.9 (2xCH), 132.6 (C), 145.4
Please cite this article in press as: Tafelska-Kaczmarek A, et al., Asymmetric synthesis of benzofuryl
hydrogenation of -functionalized ketones, Tetrahedron (2017), http://dx.doi.org/10.1016/j.tet.2017.05.059
b-amino alcohols by the transfer
a

6
A. Tafelska-Kaczmarek et al. / Tetrahedron xxx (2017) 1e15
(C), 149.5 (C), 154.4 (C), 181.4 (CO) ppm. Anal. calcd for C19H18O5S: C,
63.67; H, 5.06. Found: C, 63.82; H, 5.15.
CDCl3):
d
¼ 2.63 (s, 3H, CH3), 5.40 (s, 2H, CH2), 7.37 (ddd, J ¼ 8.4, 7.0,
1.4 Hz, 1H), 7.51 (dt, J ¼ 8.4, 0.7 Hz, 1H), 7.55 (ddd, J ¼ 8.4, 7.0, 1.4 Hz,
1H), 7.58 (dt, J ¼ 8.1, 2.1 Hz, 2H), 7.70 (ddd, J ¼ 8.4, 1.4, 0.7 Hz,
1H),8.00 (dt, J ¼ 8.4, 2.1 Hz, 2H) ppm. 13C NMR (175 MHz, CDCl3):
4.3.3. 2-Tosyloxy-1-(3-methylbenzofuran-2-yl)ethanone 1c
Crystallized from ethanol, 1.78 g, 75% yield, mp 126e127 ꢂC. 1H
d
¼ 10.3 (CH3), 71.2 (CH2), 113.2 (CH), 122.8 (CH), 124.8 (CH), 128.4
NMR (200 MHz, CDCl3):
d
¼ 2.45 (s, 3H, CH3), 2.59 (s, 3H, CH3), 5.31
(C), 129.7 (C), 130.2 (CH), 130.6 (4xCH), 135.6 (C), 141.8 (C), 146.3 (C),
155.3 (C), 183.6 (CO) ppm. IR, neat (cmꢀ1): 3094, 2923, 1690, 1374,
1011, 814. Anal. calcd for C17H13ClO5S: C, 55.97; H, 3.59. Found: C,
56.25; H, 3.35.
(s, 2H, CH2), 7.34e7.38 (m, 3H), 7.48e7.59 (m, 2H), 7.65 (d,
J ¼ 10.0 Hz, 1H), 7.90 (d, J ¼ 8.2 Hz, 2H) ppm. 13C NMR (75 MHz,
CDCl3):
d
¼ 9.2 (CH3), 21.6 (CH3), 69.9 (CH2), 112.2 (CH), 121.7 (CH),
123.6 (CH), 127.0 (C), 128.1 (2xCH), 128.7 (C), 129.0 (CH), 129.8
(2xCH), 132.9 (CH), 145.1(C), 145.4 (C), 154.2 (C), 182.7 (CO) ppm.
Anal. calcd for C18H16O5S: C, 62.78; H, 4.68. Found: C, 62.46; H, 4.79.
4.3.9. 2-Benzenesulfonyloxy-1-(benzofuran-2-yl)ethanone 3a
Purified by column chromatography on silica gel (hexane/ethyl
acetate, 8:2), 1.48 g, 63% yield, mp 112e115 ꢂC. 1H NMR (700 MHz,
4.3.4. 2-Tosyloxy-1-(3,7-dimethylbenzofuran-2-yl)ethanone 1d
Crystallized from ethanol, 1.87 g, 76% yield, mp 146e148 ꢂC. 1H
CDCl3):
d
¼ 5.30 (s, 2H, CH2), 7.38 (ddd, J ¼ 8.4, 7.0, 0.7 Hz, 1H), 7.55
(ddd, J ¼ 8.4, 7.0, 1.4 Hz, 1H), 7.59 (dq, J ¼ 8.4, 1.4 Hz, 1H), 7.60e7.63
(m, 2H), 7.68 (d, J ¼ 1.4 Hz, 1H), 7.71e7.73 (m, 1H), 7.76 (ddd, J ¼ 8.4,
1.4, 0.7 Hz, 1H), 8.04e8.06 (m, 2H) ppm. 13C NMR (175 MHz, CDCl3):
NMR (200 MHz, CDCl3):
d
¼ 2.45 (s, 3H, CH3), 2.51 (s, 3H, CH3), 2.57
(s, 3H, CH3), 5.34 (s, 2H, CH2), 7.18e7.39 (m, 4H), 7.48 (d, J ¼ 10.0 Hz,
1H), 7.90 (d, J ¼ 8.2 Hz, 2H) ppm. 13C NMR (50 MHz, CDCl3):
d
¼ 9.4
d
¼ 70.8 (CH2), 113.5 (CH), 115.7 (CH), 124.7 (CH), 125.4 (CH), 127.6
(CH3), 14.8 (CH3), 21.6 (CH3), 69.7 (CH2), 119.0 (CH), 122.5 (C), 123.8
(CH), 127.5 (C), 128.1 (2xCH), 128.3 (C), 129.6 (CH), 129.8 (2xCH),
133.1 (C), 145.0 (C), 145.4 (C), 153.5 (C), 182.7 (CO) ppm. Anal. calcd
for C19H18O5S: C, 63.67; H, 5.06. Found: C, 62.63; H, 5.16.
(C), 129.2 (2xCH), 130.2 (CH), 130.4 (2xCH), 135.3 (CH), 136.6 (C),
150.7 (C), 156.7 (C), 182.4 (CO) ppm. IR, neat (cmꢀ1): 2919, 1701,
1370, 1186, 919, 684. Anal. calcd for C16H12O5S: C, 60.75; H, 3.82.
Found: C, 60.53; H, 3.66.
4.3.5. 2-Tosyloxy-1-(3-phenethylbenzofuran-2-yl)ethanone 1e
Crystallized from ethanol, 1.92 g, 59% yield, mp 120e123 ꢂC. 1H
4.3.10. 2-Benzenesulfonyloxy-1-(7-ethylbenzofuran-2-yl)ethanone
3b
NMR (300 MHz, CDCl3):
d
¼ 2.44 (s, 3H, CH3), 2.88e2.93 (m, 2H),
Purified by column chromatography on silica gel (hexane/ethyl
3.31e3.36 (m, 2H), 5.31 (s, 2H, CH2), 7.16e7.30 (m, 6H), 7.35e7.38
(m, 2H), 7.48 (d, J ¼ 1.2 Hz, 1H), 7.49 (dd, J ¼ 3.3, 1.2 Hz, 1H), 7.54 (dt,
J ¼ 7.8, 0.9 Hz, 1H), 7.89e7.92 (m, 2H) ppm. 13C NMR (75 MHz,
acetate, 9:1), 1.01 g, 76% yield, mp 62e64 ꢂC. 1H NMR (700 MHz,
CDCl3):
d
¼ 1.38 (t, J ¼ 7.7 Hz, 3H, CH3), 2.99 (q, J ¼ 7.7 Hz, 2H, CH2),
5.32 (s, 2H, CH2), 7.29 (t, J ¼ 7.0 Hz, 1H), 7.36 (dq, J ¼ 7.7, 1.4 Hz, 1H),
7.57 (dd, J ¼ 7.7, 1.4 Hz, 1H), 7.59e7.62 (m, 2H), 7.65 (s, 1H), 7.71 (tt,
J ¼ 7.0, 0.7 Hz, 1H), 8.04e8.06 (m, 2H) ppm. 13C NMR (175 MHz,
CDCl3):
d
¼ 21.6 (CH3), 26.2 (CH2), 35.6 (CH2), 69.9 (CH2), 112.3 (CH),
121.8 (CH), 123.7 (CH), 126.2 (CH), 128.0 (C), 128.2 (2xCH), 128.4
(2xCH), 128.5 (2xCH), 128.9 (CH), 129.9 (2xCH), 130.9 (C), 132.9 (C),
140.9 (C), 145.1 (C), 145.3 (C), 154.3 (C), 182.5 (CO) ppm. Anal. calcd
for C25H22O5S: C, 69.11; H, 5.10. Found: C, 69.23; H, 5.36.
CDCl3):
d
¼ 14.9 (CH3), 23.6 (CH2), 70.7 (CH2), 116.0 (CH), 122.0 (CH),
125.6 (CH), 127.3 (C), 129.0 (CH), 129.2 (2xCH), 130.0 (C), 130.3
(2xCH),135.2 (CH), 136.7 (C), 150.5 (C), 155.5 (C), 182.3 (CO) ppm. IR,
neat (cmꢀ1): 2969, 1693, 1236, 1174, 923, 742. Anal. calcd for
4.3.6. 2-(4-Chlorobenzenesulfonyloxy)-1-(benzofuran-2-yl)
ethanone 2a
C18H16O5S: C, 62.78; H, 4.68. Found: C, 62.24; H, 4.36.
Purified by column chromatography on silica gel (hexane/ethyl
4.3.11. 2-Benzenesulfonyloxy-1-(3-methylbenzofuran-2-yl)
ethanone 3c
acetate, 7:3), 1.23 g, 48% yield, mp 103e105 ꢂC. 1H NMR (700 MHz,
CDCl3):
d
¼ 5.35 (s, 2H, CH2), 7.38 (ddd, J ¼ 7.7, 7.0, 0.7 Hz, 1H), 7.56
Purified by column chromatography on silica gel (hexane/ethyl
(td, J ¼ 7.0, 1.4 Hz, 1H), 7.58e7.61 (m, 3H), 7.67 (d, J ¼ 1.4 Hz, 1H),
acetate, 8:2), 1.72 g, 69% yield, mp 119e121 ꢂC. 1H NMR (700 MHz,
7.77 (ddd, J ¼ 7.7,1.4, 0.7 Hz,1H),7.98 (dt, J ¼ 9.1, 2.1 Hz, 2H) ppm. 13
C
CDCl3):
d
¼ 2.62 (s, 3H, CH3), 5.38 (s, 2H, CH2), 7.36 (ddd, J ¼ 7.7, 7.0,
NMR (175 MHz, CDCl3):
d
¼ 70.9 (CH2), 113.5 (CH), 115.6 (CH), 124.7
0.7 Hz,1H), 7.51 (dt, J ¼ 8.4, 0.7 Hz, 1H), 7.54 (ddd, J ¼ 8.4, 7.0, 1.4 Hz,
(CH), 125.4 (CH), 127.6 (C), 130.2 (CH), 130.6 (2xCH), 130.7 (2xCH),
135.3 (C), 142.0 (C), 150.7 (C), 156.7 (C), 182.3 (CO) ppm. IR, neat
(cmꢀ1): 3007, 1698, 1382, 1172, 749. Anal. calcd for C16H11ClO5S: C,
54.79; H, 3.16. Found: C, 54.75; H, 3.25.
1H), 7.60e7.63 (m, 2H), 7.69e7.72 (m, 2H), 8.06 (dt, J ¼ 9.8, 1.4 Hz,
2H) ppm. 13C NMR (175 MHz, CDCl3):
d
¼ 10.3 (CH3), 71.1 (CH2),
113.2 (CH), 122.7 (CH), 124.7 (CH), 128.2 (C), 129.1 (2xCH), 129.8 (C),
130.1 (CH), 130.3 (2xCH), 135.1 (CH), 137.0 (C), 146.4 (C), 155.3 (C),
183.7 (CO) ppm. IR, neat (cmꢀ1): 2923, 1695, 1356, 1172, 874, 740.
Anal. calcd for C17H14O5S: C, 61.81; H, 4.27. Found: C, 61.33; H, 4.47.
4.3.7. 2-(4-Chlorobenzenesulfonyloxy)-1-(7-ethylbenzofuran-2-yl)
ethanone 2b
Purified by column chromatography on silica gel (hexane/ethyl
4.3.12. 2-Mesyloxy-1-(benzofuran-2-yl)ethanone 4a
acetate, 9:1), 1.63 g, 56% yield, mp 82e85 ꢂC. 1H NMR (700 MHz,
Crystallized from ethanol, 1.51 g, 79% yield, mp 104e105 ꢂC. 1H
CDCl3):
d
¼ 1.39 (t, J ¼ 7.7 Hz, 3H, CH3), 3.00 (q, J ¼ 7.7 Hz, 2H, CH2),
NMR (400 MHz, CDCl3):
d
¼ 3.32 (s, 3H, CH3), 5.51 (s, 2H, CH2), 7.38
5.37 (s, 2H, CH2), 7.31 (t, J ¼ 6.3 Hz, 1H), 7.37 (dq, J ¼ 7.0, 0.7 Hz, 1H),
(ddd, J ¼ 8.0, 6.8, 1.2 Hz, 1H), 7.56 (td, J ¼ 8.4, 1.2 Hz, 1H), 7.61 (ddd,
J ¼ 8.4,1.5,1.2 Hz,1H), 7.67 (d, J ¼ 0.8 Hz,1H), 7.77 (dt, J ¼ 8.0, 0.8 Hz,
7.57e7.59 (m, 3H), 7.65 (s, 1H).7.99 (dt, J ¼ 9.1, 2.1 Hz, 2H) ppm. 13
C
NMR (175 MHz, CDCl3):
d
¼ 14.9 (CH3), 23.6 (CH2), 70.8 (CH2), 115.9
1H) ppm. 13C NMR (175 MHz, CDCl3):
d
¼ 38.8 (CH3), 69.5 (CH2),
(CH), 120.0 (CH), 125.6 (CH), 127.3 (C), 129.1 (CH), 130.0 (C), 130.6
(2xCH), 130.7 (2xCH), 135.3 (C), 141.9 (C), 150.4 (C), 155.5 (C), 182.2
(CO) ppm. IR, neat (cmꢀ1): 2967, 1700, 1356, 1172, 979, 767. Anal.
calcd for C18H15ClO5S: C, 57.07; H, 3.99. Found: C, 56.95; H, 3.65.
112.1 (CH), 113.9 (CH), 123.3 (CH), 124.1 (CH), 126.1 (C), 128.8 (CH),
149.2 (C), 155.4 (C), 182.1 (CO) ppm. IR, neat (cmꢀ1): 2949, 1682,
1339, 1115, 757. Anal. calcd for C11H10O5S: C, 51.96; H, 3.96. Found:
C, 51.73; H, 3.87.
4.3.8. 2-(4-Chlorobenzenesulfonyloxy)-1-(3-methylbenzofuran-2-
yl)ethanone 2c
4.3.13. 2-Mesyloxy-1-(7-ethylbenzofuran-2-yl)ethanone 4b41
Purified by column chromatography on silica gel (hexane/ethyl
acetate, 8:2), 1.58 g, 75% yield, mp 56e59 ꢂC. 1H NMR (700 MHz,
Purified by column chromatography on silica gel (hexane/ethyl
acetate, 9:1), 1.37 g, 50% yield, mp 106e108 ꢂC. 1H NMR (700 MHz,
CDCl3):
d
¼ 1.37 (t, J ¼ 7.7 Hz, 3H, CH3), 2.98 (q, J ¼ 7.7 Hz, 2H, CH2),
Please cite this article in press as: Tafelska-Kaczmarek A, et al., Asymmetric synthesis of benzofuryl
hydrogenation of -functionalized ketones, Tetrahedron (2017), http://dx.doi.org/10.1016/j.tet.2017.05.059
b-amino alcohols by the transfer
a

A. Tafelska-Kaczmarek et al. / Tetrahedron xxx (2017) 1e15
7
3.31 (s, 3H, CH3), 5.51 (s, 2H, CH2), 7.28 (t, J ¼ 7.7 Hz, 1H), 7.36 (dd,
½
a 2D0
ꢃ
¼ ꢀ33.1 (c 0.66, CHCl3); 94.67% ee. 1H NMR (400 MHz, CDCl3):
J ¼ 7.7, 0.7 Hz, 1H), 7.57 (dd, J ¼ 7.7, 0.7 Hz, 1H), 7.65 (s, 1H) ppm. 13
C
d
¼ 1.32 (t, J ¼ 7.6 Hz, 3H, CH3), 2.42 (s, 3H, CH3), 2.71 (d, J ¼ 5.4 Hz,
NMR (175 MHz, CDCl3):
d
¼ 13.6 (CH3), 22.3 (CH2), 38.8 (CH3), 69.5
1H, OH), 2.87 (q, J ¼ 7.6 Hz, 2H, CH2), 4.36 (dd, J ¼ 10.4, 6.8 Hz, 1H,
CH2), 4.44 (dd, J ¼ 10.4, 4.4 Hz, 1H, CH2), 5.13 (dd, J ¼ 9.9, 5.4 Hz, 1H,
CH), 6.70 (t, J ¼ 0.4 Hz, 1H), 7.24 (td, J ¼ 7.2, 1.2 Hz, 1H), 7.27e7.29
(m, 3H), 7.39 (ddd, J ¼ 8.0, 2.0, 0.8 Hz, 1H), 7.54 (ddd, J ¼ 7.6, 1.6,
0.8 Hz, 1H), 7.76 (dt, J ¼ 8.4, 2.0 Hz, 2H) ppm. 13C NMR (100 MHz,
(CH2), 114.3 (CH), 120.6 (CH), 124.3 (CH), 125.8 (C), 127.7 (CH), 128.6
(C), 148.9 (C), 154.2 (C), 182.1 (CO) ppm. IR, neat (cmꢀ1): 3023, 2931,
1685, 1305, 920, 765. Anal. calcd for C13H14O5S: C, 55.31; H, 5.00.
Found: C, 54.99; H, 4.67.
CDCl3):
d
¼ 14.0 (CH3), 21.6 (CH3), 22.7 (CH2), 66.7 (CH), 71.4 (CH2),
4.3.14. 2-Mesyloxy-1-(3-methylbenzofuran-2-yl)ethanone 4c
Purified by column chromatography on silica gel (hexane/ethyl
acetate, 7:3), 1.27 g, 62% yield, mp 108e111 ꢂC. 1H NMR (700 MHz,
104.9 (CH), 118.7 (CH), 123.2 (CH), 123.8 (CH), 127.3 (C), 127.7 (C),
127.9 (2xCH), 129.9 (2xCH), 132.5 (C), 145.1 (C), 153.4 (C), 153.6 (C)
ppm. IR, neat (cmꢀ1): 3500, 2963, 2931,1598,1455,1362,1290,1177,
983, 814. 748, 665. Anal. calcd for C19H20O5S: C, 63.32; H, 5.59.
Found: C, 63.19; H, 5.35.
CDCl3):
d
¼ 2.65 (s, 3H, CH3), 3.32 (s, 3H, CH3), 5.53 (s, 2H, CH2), 7.35
(ddd, J ¼ 7.7, 7.0, 1.4 Hz, 1H), 7.51 (dq, J ¼ 8.4, 0.7 Hz, 1H), 7.54 (ddd,
J ¼ 8.4, 7.0, 1.4 Hz, 1H), 7.69 (dq, J ¼ 7.7, 0.7 Hz, 1H) ppm. 13C NMR
(175 MHz, CDCl3):
d
¼ 8.9 (CH3), 38.9 (CH3), 70.2 (CH2), 111.9 (CH),
4.4.3. (R)-2-Tosyloxy-1-(3-methylbenzofuran-2-yl)ethanol 5c
121.4 (CH), 123.4 (CH), 127.1 (C), 128.3 (C), 128.9 (CH), 144.9 (C),
154.0 (C), 183.7 (CO) ppm. IR, neat (cmꢀ1): 3020, 2921, 1697, 1281,
960, 716. Anal. calcd for C12H12O5S: C, 53.72; H, 4.51. Found: C,
53.73; H, 4.67.
Yellow solid, 0.36 g, 96% yield, mp 58e60 ꢂC, ½a D25
¼ þ29.27 (c
ꢃ
1.52, CHCl3), 92% ee, determined by HPLC analysis, Daicel Chiralcel
OD-H column 250 ꢁ 4.6 mm, 5
0.6 mL/min, (S) 12.34 min, 3.78%, (R) 13.59 min, 96.22%. 1H NMR
(400 MHz, CDCl3):
mm, hexane/isopropanol 70:30, flow
d
¼ 2.24 (s, 3H, CH3), 2.42 (s, 3H, CH3), 2.54 (bs,
4.3.15. 2-Mesyloxy-1-(3-phenethylbenzofuran-2-yl)ethanone 4e
Crystallized from ethanol, 1.71 g, 64% yield, mp 99e102 ꢂC. 1H
1H, OH), 4.32 (dd, J ¼ 10.4, 4.8 Hz,1H, CH2), 4.45 (dd, J ¼ 10.4, 7.6 Hz,
1H, CH2), 5.17 (t, J ¼ 6.0 Hz, 1H, CH), 7.23e7.27 (m, 3H), 7.30 (td,
J ¼ 8.4, 1.2 Hz, 1H), 7.36 (ddd, J ¼ 8.0, 1.2, 0.8 Hz, 1H), 7.49 (ddd,
J ¼ 7.6, 1.2, 0.8 Hz, 1H), 7.74 (dt, J ¼ 8.4, 2.0 Hz, 2H) ppm. 13C NMR
NMR (700 MHz, CDCl3):
d
¼ 2.97e3.00 (m, 2H, CH2), 3.30 (s, 3H,
CH3), 3.40e3.42 (m, 2H, CH2), 5.50 (s, 2H, CH2), 7.19 (tt, J ¼ 7.0,
1.4 Hz, H), 7.21e7.22 (m, 2H), 7.25e7.27 (m, 2H), 7.30 (ddd, J ¼ 8.4,
5.6, 2.8 Hz, 1H), 7.51e7.52 (m, 2H), 7.56 (dt, J ¼ 7.7, 0.7 Hz, 1H) ppm.
(175 MHz, CDCl3):
d
¼ 7.4 (CH3), 21.3 (CH3), 64.3 (CH), 70.7 (CH2),
13C NMR (175 MHz, CDCl3):
d
¼ 25.9 (CH2), 35.3 (CH2), 38.9 (CH3),
110.8 (CH), 113.9 (C), 119.3 (CH), 122.2 (CH), 124.5 (CH), 127.5
(2xCH), 129.0 (C), 129.5 (2xCH), 132.0 (C), 144.7 (C), 147.5 (C), 153.6
(C) ppm. Anal. calcd for C18H18O5S: C, 62.41; H, 5.24. Found: C,
62.39; H, 5.26.
70.1 (CH2), 111.9 (CH), 121.5 (CH), 123.4 (CH), 125.9 (CH), 127.6 (C),
128.0 (2xCH), 128.1 (2xCH), 128.8 (CH), 130.8 (C), 140.5 (C), 144.8
(C), 154.1 (C), 183.4 (CO) ppm. IR, neat (cmꢀ1): 3018, 2950, 1681,
1571, 1125, 875, 696. Anal. calcd for C19H18O5S: C, 63.67; H, 5.06.
Found: C, 63.51; H, 5.00.
4.4.4. (R)-2-Tosyloxy-1-(3,7-dimethylbenzofuran-2-yl)ethanol 5d
Light yellow solid, 0.31 g, 89% yield, mp 64e66 ꢂC, ½a D25
¼ þ15.33
ꢃ
4.4. General procedure for the asymmetric transfer hydrogenation
(c 1.26, CHCl3), 87% ee, determined by HPLC analysis, Daicel Chir-
of benzofuryl
a-sulfonyloxy ketones
alcel OD-H column 250 ꢁ 4.6 mm, 5
flow 0.6 mL/min, (S) 10.87 min, 6.39%, (R) 11.80 min, 93.61%. 1H
NMR (300 MHz, CDCl3):
mm, hexane/isopropanol 70:30,
To a solution of
a-sulfonyloxy ketone (1 mmol) in ethyl acetate
d
¼ 1.89 (bs, 1H, OH), 2.21 (s, 3H, CH3), 2.38
(10 mL) was added RhCl[(R,R)-TsDPEN](C5Me5) (3.2 mg,
0.005 mmol) and HCOOH/Et3N (5:2, 0.3 mL), and the mixture was
stirred at rt for 24 h. The solvent was removed under reduced
pressure and the product isolated by column chromatography on
silica gel (hexane/ethyl acetate, 7:3).
(s, 3H, CH3), 2.41 (s, 3H, CH3), 4.31 (dd, J ¼ 10.2, 5.1 Hz, 1H, CH2),
4.45 (dd, J ¼ 10.2, 7.5 Hz, 1H, CH2), 5.14 (dd, J ¼ 7.5, 5.1 Hz, 1H, CH),
7.08 (ddd, J ¼ 7.2, 1.5, 0.9 Hz, 1H), 7.14 (t, J ¼ 7.2 Hz, 1H), 7.19e7.22
(m,1H), 7.29 (ddd, J ¼ 7.5,1.5, 0.6 Hz,1H), 7.70 (dt, J ¼ 8.4,1.8 Hz, 2H)
ppm. 13C NMR (75 MHz, CDCl3):
d
¼ 7.8 (CH3), 14.9 (CH3), 21.6 (CH3),
64.7 (CH), 71.1 (CH2), 114.5 (C), 117.0 (CH), 121.4 (C), 122.6 (CH),
125.8 (CH), 127.8 (2xCH), 128.9 (C), 129.7 (2xCH), 132.5 (C), 144.9
(C), 147.6 (C), 153.0 (C) ppm. Anal. calcd for C19H20O5S: C, 63.32; H,
5.59. Found: C, 62.98; H, 5.60.
4.4.1. (R)-2-Tosyloxy-1-(benzofuran-2-yl)ethanol 5a41
White solid, 0.31 g, 92% yield, mp 78e80 ꢂC, ½a D26
¼ þ33.50 (c
ꢃ
2.00, CHCl3), 97% ee, determined by HPLC analysis, Daicel Chiralcel
OD-H column 250 ꢁ 4.6 mm, 5
mm, hexane/isopropanol 70:30, flow
0.6 mL/min, (S) 14.50 min, 1.57%, (R) 15.40 min, 98.43%. Lit.41 for (S)-
5a ½a 2D7
ꢃ
¼ ꢀ28.98 (c 0.98, CHCl3). 1H NMR (300 MHz, CDCl3):
4.4.5. (R)-2-Tosyloxy-1-(3-phenethylbenzofuran-2-yl)ethanol 5e
d
¼ 2.42 (s, 3H, CH3), 2.60 (d, J ¼ 5.7 Hz, 1H, OH), 4.34 (dd J ¼ 10.5,
Light pink oil, 0.46 g, 95% yield, ½a D25
¼ þ18.71 (c 1.28, CHCl3),
ꢃ
6.9 Hz, 1H, CH2), 4.42 (dd, J ¼ 10.5, 3.9 Hz, 1H, CH2), 5.11 (ddd,
J ¼ 6.8, 4.0, 0.8 Hz, 1H, CH), 6.71 (d, J ¼ 0.4 Hz, 1H, CH), 7.22 (td,
J ¼ 7.2, 1.2 Hz, 1H), 7.24e7.31 (m, 3H), 7.38 (d, J ¼ 8.1 Hz, 1H),
7.52e7.55 (m, 1H), 7.75 (dt, J ¼ 8.4, 2.0 Hz, 2H) ppm. 13C NMR
93% ee, determined by HPLC analysis, Daicel Chiralcel OD-H column
250 ꢁ 4.6 mm, 5
(S) 34.04 min, 3.67%, (R) 42.85 min, 96.33%. 1H NMR (400 MHz,
CDCl3):
mm, hexane/isopropanol 90:10, flow 0.7 mL/min,
d
¼ 2.43 (s, 3H, CH3), 2.90e3.06 (m, 4H, 2xCH2), 2.96 (bs,1H,
(100 MHz, CDCl3):
d
¼ 21.7 (CH3), 66.7 (CH), 71.3 (CH2), 104.7 (CH),
OH), 3.98 (dd, J ¼ 10.4, 4.8 Hz,1H, CH2), 4.23 (dd, J ¼ 10.4, 7.6 Hz,1H,
CH2), 4.70 (dd, J ¼ 7.6, 4.8 Hz, 1H, CH), 7.01e7.03 (m, 2H), 7.15e7.20
(m, 1H), 7.22e7.29 (m, 5H), 7.32 (td, J ¼ 8.0, 1.6 Hz, 1H), 7.37 (ddd,
J ¼ 8.0, 2.0, 0.8 Hz, 1H), 7.56 (ddd, J ¼ 7.6, 1.2, 0.8 Hz, 1H), 7.71 (dt,
111.3 (CH), 121.3 (CH), 123.1 (CH), 124.6 (CH), 127.7 (C), 127.9 (2xCH),
129.9 (2xCH), 132.4 (C), 145.2 (C), 153.9 (C), 154.8 (C) ppm. IR, HCB
(cmꢀ1): 3513, 3461, 1563, 1339, 1173, 980, 851. 794, 655. Anal. calcd
for C17H16O5S: C, 61.43; H, 4.85. Found: C, 61.49; H, 4.77.
J ¼ 8.0, 2.0 Hz, 2H) ppm. 13C NMR (100 MHz, CDCl3):
¼ 21.6 (CH3),
d
25.6 (CH2), 35.6 (CH2), 64.3 (CH), 70.7 (CH2), 111.5 (CH), 117.4 (C),
119.7 (CH), 122.7 (CH), 124.9 (CH), 126.4 (CH), 127.9 (2xCH), 128.3
(C), 128.5 (2xCH), 128.8 (2xCH), 129.8 (2xCH), 132.6 (C), 141.2 (C),
144.9 (C), 149.1 (C), 154.3 (C) ppm. IR, neat (cmꢀ1): 3518 3028, 2926,
1598,1495,1455,1360,1252,1178, 983, 814. 750, 655. Anal. calcd for
4.4.2. (R)-2-Tosyloxy-1-(7-ethylbenzofuran-2-yl)ethanol 5b41,69
Yellow oil, 0.33 g, 93% yield, ½a D25
¼ þ31.42 (c 1.22, CHCl3), 90%
ꢃ
ee, determined by HPLC analysis, Daicel Chiralcel OD-H column
250 ꢁ 4.6 mm, 5
mm, hexane/isopropanol 70:30, flow 0.6 mL/min,
(S) 11.63 min, 5.13%, (R) 12.47 min, 94.87%. Lit.41 for (S)-5b
C
25H24O5S: C, 68.79; H, 5.54. Found: C, 68.50; H, 5.42.
Please cite this article in press as: Tafelska-Kaczmarek A, et al., Asymmetric synthesis of benzofuryl
hydrogenation of -functionalized ketones, Tetrahedron (2017), http://dx.doi.org/10.1016/j.tet.2017.05.059
b-amino alcohols by the transfer
a

8
A. Tafelska-Kaczmarek et al. / Tetrahedron xxx (2017) 1e15
4.4.6. (R)-2-(4-Chlorobenzenesulfonyloxy)-1-(benzofuran-2-yl)
4.4.10. (R)-2-Benzenesulfonyloxy-1-(7-ethylbenzofuran-2-yl)
ethanol 6a
ethanol 7b
Light brown solid, 0.29 g, 84% yield, mp 58e61 ꢂC, ½a D27
ꢃ
¼ þ77.50
Light brown oil, 0.32 g, 93%, ½a D27
¼ þ57.50 (c 0.80, CHCl3), 94%
ꢃ
(c 0.80, CHCl3). 1H NMR (700 MHz, CDCl3):
d
¼ 2.64 (bs, 1H, OH),
ee, determined by HPLC analysis, Daicel Chiralcel OD-H column
4.41 (dd, J ¼ 10.5, 7.0 Hz, 1H, CH2), 4.47 (dd, J ¼ 10.5, 4.2 Hz, 1H,
CH2), 5.15 (ddd, J ¼ 6.3, 1.5, 0.7 Hz, 1H, CH), 6.74 (t, J ¼ 0.7 Hz, 1H),
7.27 (ddd, J ¼ 7.7, 7.0, 1.4 Hz, 1H), 7.32 (ddd, J ¼ 9.8, 7.7, 1.7 Hz, 1H),
7.40 (dq, J ¼ 8.4, 0.7 Hz, 1H), 7.44 (dt, J ¼ 8.4, 2.1 Hz, 2H), 7.56 (dq,
J ¼ 7.7, 0.7 Hz, 1H), 7.79 (dt, J ¼ 8.4, 0.9 Hz, 2H) ppm. 13C NMR
250 ꢁ 4.6 mm, 5
(S) 14.51 min, 2.85%, (R) 15.65 min, 97.15%. 1H NMR (700 MHz,
CDCl3):
mm, hexane/isopropanol 55:45, flow 0.4 mL/min,
d
¼ 1.33 (t, J ¼ 7.7 Hz, 3H, CH3), 2.62 (bs, 1H, OH), 2.88 (q,
J ¼ 7.7 Hz, 2H, CH2), 4.41 (dd, J ¼ 10.5, 6.3 Hz, 1H, CH2), 4.90 (dd,
J ¼ 10.5, 4.2 Hz, 1H, CH2), 5.16 (ddd, J ¼ 7.0, 4.2, 0.7 Hz, 1H, CH), 6.73
(d, J ¼ 0.7 Hz, 1H), 7.14 (dt, J ¼ 7.0, 0.7 Hz, 1H), 7.19 (t, J ¼ 7.0 Hz, 1H),
7.40 (dd, J ¼ 7.7,1.4 Hz,1H), 7.50e7.53 (m, 2H), 7.65 (tt, J ¼ 7.7, 1.4 Hz,
(175 MHz, CDCl3):
d
¼ 67.5 (CH), 72.6 (CH2), 105.9 (CH), 112.3 (CH),
122.3 (CH), 124.1 (CH), 125.8 (CH), 128.6 (C), 130.3 (2xCH), 130.6
(2xCH),134.9 (C), 141.7 (C), 154.9 (C), 155.8 (C) ppm. IR, neat (cmꢀ1):
3505, 3094, 1341, 1172, 942, 750. Anal. calcd for C16H13ClO5S: C,
54.47; H, 3.71. Found: C, 54.30; H, 3.62.
1H), 7.90e7.92 (m, 2H) ppm. 13C NMR (175 MHz, CDCl3):
d
¼ 15.0
(CH3), 23.7 (CH2), 67.7 (CH), 72.5 (CH2), 105.9 (CH), 119.8 (CH), 124.2
(CH), 124.8 (CH), 128.4 (C), 128.8 (C), 128.9 (2xCH), 130.3 (2xCH),
134.9 (CH),136.5 (C),154.5 (C),154.6 (C) ppm. IR, neat (cmꢀ1): 3500,
3063, 1357, 1175, 973, 748. Anal. calcd for C18H18O5S: C, 62.41; H,
5.24. Found: C, 62.18; H, 5.02.
4.4.7. (R)-2-(4-Chlorobenzenesulfonyloxy)-1-(7-ethylbenzofuran-
2-yl)ethanol 6b
Light brown solid, 0.36 g, 93% yield, mp 36e39 ꢂC, ½a D27
¼ þ67.27
ꢃ
4.4.11. (R)-2-Benzenesulfonyloxy-1-(3-methylbenzofuran-2-yl)
(c 1.10, CHCl3). 1H NMR (700 MHz, CDCl3):
d
¼ 1.33 (t, J ¼ 7.7 Hz, 3H,
ethanol 7c
Light brown oil, 0.31 g, 93%, ½a D27
¼ þ38.75 (c 0.80, CHCl3), 92%
ꢃ
CH3), 2.61 (bs, 1H, OH), 2.87 (q, J ¼ 7.7 Hz, 2H, CH2), 4.42 (dd,
J ¼ 10.5, 6.3 Hz, 1H, CH2), 4.49 (dd, J ¼ 10.5, 3.0 Hz, 1H, CH2), 5.15
(ddd, J ¼ 7.0, 4.2, 0.7 Hz, 1H, CH), 6.72 (d, J ¼ 0.7 Hz, 1H), 7.15 (dt,
J ¼ 7.7, 0.7 Hz, 1H), 7.20 (t, J ¼ 7.0 Hz, 1H), 7.40 (dd, J ¼ 7.7, 0.7 Hz,
1H), 7.42 (dt, J ¼ 8.4, 2.1 Hz, 1H), 7.79 (dt, J ¼ 8.4, 2.1 Hz, 2H) ppm.
ee, determined by HPLC analysis, Daicel Chiralcel OD-H column
250 ꢁ 4.6 mm, 5
(S) 16.72 min, 4.21%, (R) 18.41 min, 95.79%. 1H NMR (700 MHz,
CDCl3):
mm, hexane/isopropanol 55:45, flow 0.4 mL/min,
d
¼ 2.26 (s, 3H, CH3), 2.49 (bs, 1H, OH), 4.36 (dd, J ¼ 10.5,
13C NMR (175 MHz, CDCl3):
d
¼ 15.0 (CH3), 23.7 (CH2), 67.6 (CH),
4.9 Hz, 1H, CH2), 4.49 (dd, J ¼ 10.5, 7.0 Hz, 1H, CH2), 5.20 (dd, J ¼ 7.0,
4.9 Hz, 1H, CH), 7.27 (ddd, J ¼ 7.7, 7.0, 0.7 Hz, 1H), 7.32 (ddd, J ¼ 8.4,
7.0, 1.4 Hz, 1H), 7.38 (dt, J ¼ 7.7, 0.7 Hz, 1H), 7.49e7.52 (m, 3H), 7.63
(tt, J ¼ 7.0, 1.4 Hz, 1H), 7.88e7.90 (m, 2H) ppm. 13C NMR (175 MHz,
72.6 (CH2), 106.0 (CH), 119.7 (CH), 124.3 (CH), 124.9 (CH), 128.1 (C),
128.3 (C), 128.7 (C), 130.3 (2xCH), 130.6 (2xCH), 134.9 (C), 141.7 (C),
154.4 (C) ppm. IR, neat (cmꢀ1): 3487, 2966,1348,1113, 975, 827, 746.
Anal. calcd for C18H17ClO5S: C, 56.77; H, 4.50. Found: C, 56.67; H,
4.40.
CDCl3):
d
¼ 8.7 (CH3), 65.6 (CH), 72.3 (CH2), 112.2 (CH), 115.3 (C),
120.7 (CH), 123.6 (CH), 125.9 (CH), 128.8 (2xCH), 130.2 (2xCH), 130.4
(C), 134.9 (CH), 136.5 (C), 149.0 (C), 155.0 (C) ppm. IR, neat (cmꢀ1):
3518, 3064, 2922, 1359, 1185, 972, 744. Anal. calcd for C17H16O5S: C,
61.43; H, 4.85. Found: C, 61.40; H, 4.72.
4.4.8. (R)-2-(4-Chlorobenzenesulfonyloxy)-1-(3-
methylbenzofuran-2-yl)ethanol 6c
Yellow solid, 0.35 g, 96% yield, mp 65e68 ꢂC, ½a D27
¼ þ53.68 (c
ꢃ
4.4.12. (R)-2-Mesyloxy-1-(benzofuran-2-yl)ethanol 8a
1.90, CHCl3), 90% ee, determined by HPLC analysis, Daicel Chiralcel
Green oil, 0.24 g, 95% yield, ½a D24
¼ þ37.69 (c 1.30, CHCl3), 99% ee,
ꢃ
OD-H column 250 ꢁ 4.6 mm, 5
0.4 mL/min, (S) 17.83 min, 4.94%, (R) 19.12 min, 95.06%. 1H NMR
(700 MHz, CDCl3):
mm, hexane/isopropanol 55:45, flow
determined by HPLC analysis, Daicel Chiralcel OD-H column
250 ꢁ 4.6 mm, 5
(S) 68.92 min, 0.46%, (R) 72.39 min, 99.54%. 1H NMR (400 MHz,
CDCl3):
mm, hexane/isopropanol 90:10, flow 0.7 mL/min,
d
¼ 2.26 (s, 3H, CH3), 2.65 (bs, 1H, OH), 4.36 (dd,
J ¼ 10.5, 4.2 Hz, 1H, CH), 4.49 (dd, J ¼ 10.5, 7.0 Hz, 1H, CH), 5.19 (dd,
J ¼ 7.0, 4.9 Hz, 1H, CH), 7.28 (ddd, J ¼ 7.7, 7.0, 1.4 Hz, 1H), 7.34 (td,
J ¼ 7.0, 1.4 Hz, 1H), 7.36 (ddd, J ¼ 8.4, 1.4, 0.7 Hz, 1H), 7.41 (dt, J ¼ 9.1,
2.1 Hz, 2H), 7.51 (ddd, J ¼ 8.4, 1.4, 0.7 Hz.1H), 7.77 (dt, J ¼ 8.4, 2.1 Hz,
d
¼ 2.74 (d, J ¼ 5.2 Hz, 1H, OH), 3.09 (s, 3H, CH3), 4.60 (dd,
J ¼ 10.8, 7.2 Hz, 1H, CH2), 4.64 (dd, J ¼ 10.8, 3.6 Hz, 1H, CH2), 5.21
(dd, J ¼ 10.4, 4.4 Hz, 1H, CH), 6.81 (t, J ¼ 0.8 Hz, 1H), 7.26 (td, J ¼ 7.6,
1.2 Hz, 1H), 7.33 (ddd, J ¼ 8.4, 7.2, 1.6 Hz, 1H), 7.48 (ddd, J ¼ 8.4, 1.6,
1.2 Hz, 1H), 7.59 (ddd, J ¼ 7.6, 5.6, 0.8 Hz, 1H) ppm. 13C NMR
2H) ppm. 13C NMR (100 MHz, CDCl3):
d
¼ 8.7 (CH3), 65.5 (CH), 72.4
(CH2), 112.2 (CH), 115.4 (C), 120.7 (CH), 123.7 (CH), 126.1 (CH), 130.2
(2xCH), 130.3 (C), 130.5 (2xCH), 134.9 (C), 141.6 (C), 148.8 (C), 154.9
(C) ppm. IR, neat (cmꢀ1): 3518, 3096, 1356, 1181, 973, 742. Anal.
calcd for C17H15ClO5S: C, 55.67; H, 4.12. Found: C, 55.10; H, 3.80.
(100 MHz, CDCl3):
d
¼ 37.7 (CH3), 66.8 (CH), 71.1 (CH2), 104.8 (CH),
111.3 (CH), 121.4 (CH), 123.2 (CH), 124.8 (CH), 127.7 (C), 153.9 (C),
154.9 (C) ppm. IR, neat (cmꢀ1): 3391, 3114, 1342, 1170, 957, 774.
Anal. calcd for C11H12O5S: C, 51.55; H, 4.72. Found: C, 51.45; H, 4.71.
4.4.9. (R)-2-Benzenesulfonyloxy-1-(benzofuran-2-yl)ethanol 7a
4.4.13. (R)-2-Mesyloxy-1-(7-ethylbenzofuran-2-yl)ethanol 8b41
Light brown oil, 0.31 g, 99% yield, ½a D27
ꢃ
¼ þ24.00 (c 1.00, CHCl3),
Yellow oil, 0.26 g, 93% yield, ½a D26
¼ þ44.50 (c 2.00, CHCl3), 95%
ꢃ
97% ee, determined by HPLC analysis, Daicel Chiralcel OD-H column
ee, determined by HPLC analysis, Daicel Chiralcel OD-H column
250 ꢁ 4.6 mm, 5
(S) 17.30 min, 1.57%, (R) 18.21 min, 98.44%. 1H NMR (700 MHz,
CDCl3):
m
m, hexane/isopropanol 55:45, flow 0.4 mL/min,
250 ꢁ 4.6 mm, 5
mm, hexane/isopropanol 60:40, flow 0.7 mL/min,
(S) 14.92 min, 2.49%, (R) 16.90 min, 97.51%. Lit.41 for (S)-8b
d
¼ 2.89 (s, 1H, OH), 4.39 (dd, J ¼ 10.5, 7.0 Hz, 1H, CH2), 4.46
½
a 2D0
ꢃ
¼ ꢀ45.15 (c 1.11, CHCl3); 97.32% ee. 1H NMR (700 MHz, CDCl3):
(dd, J ¼ 10.5, 4.2 Hz, 1H, CH2), 5.14 (dd, J ¼ 7.0, 4.2 Hz, 1H, CH), 6.73
(t, J ¼ 0.7 Hz, 1H), 7.25 (ddd, J ¼ 8.4, 7.0, 0.7 Hz, 1H), 7.31 (ddd,
J ¼ 8.4, 7.0, 0.7 Hz, 1H), 7.41 (dq, J ¼ 8.4, 1.4 Hz, 1H), 7.51e7.52 (m,
2H), 7.56 (dq, J ¼ 7.7, 0.7 Hz, 1H), 7.63e7.66 (m, 1H), 7.89e7.91 (m,
d
¼ 1.34 (t, J ¼ 7.0 Hz, 3H, CH3), 2.75 (bs, 1H, OH), 2.92 (q, J ¼ 7.0 Hz,
2H, CH2), 3.07 (s, 3H, CH3), 4.58 (dd, J ¼ 11.2, 7.0 Hz, 1H, CH2), 4.62
(dd, J ¼ 11.2, 4.2 Hz, 1H, CH2), 5.20 (dd, J ¼ 5.6, 2.8 Hz, 1H, CH), 6.78
(s, 1H), 7.13 (dt, J ¼ 7.7, 0.7 Hz, 1H), 7.18 (t, J ¼ 7.0 Hz, 1H), 7.40 (dd,
2H) ppm. 13C NMR (175 MHz, CDCl3):
d
¼ 67.6 (CH), 72.4 (CH2),
J ¼ 7.0, 1.4 Hz, 1H) ppm. 13C NMR (175 MHz, CDCl3):
¼ 13.7 (CH3),
d
105.8 (CH), 112.3 (CH), 122.3 (CH), 124.1 (CH), 125.6 (CH), 128.7 (C),
128.9 (2xCH), 130.3 (2xCH), 135.0 (CH), 136.5 (C), 154.9 (C), 155.8 (C)
ppm. IR, neat (cmꢀ1): 3509, 3065, 1356, 1173, 972, 750. Anal. calcd
for C16H14O5S: C, 60.37; H, 4.43. Found: C, 59.98; H, 4.12.
22.4 (CH2), 37.3 (CH3), 66.5 (CH), 70.7 (CH2), 104.6 (CH), 118.4 (CH),
122.9 (CH), 123.6 (CH), 126.9 (C), 127.5 (C), 153.1 (C), 153.2 (C) ppm.
IR, neat (cmꢀ1): 3501, 3028, 1347, 1169, 958, 816, 746. Anal. calcd for
C13H16O5S: C, 54.92; H, 5.67. Found: C, 54.87; H, 5.60.
Please cite this article in press as: Tafelska-Kaczmarek A, et al., Asymmetric synthesis of benzofuryl
hydrogenation of -functionalized ketones, Tetrahedron (2017), http://dx.doi.org/10.1016/j.tet.2017.05.059
b-amino alcohols by the transfer
a

A. Tafelska-Kaczmarek et al. / Tetrahedron xxx (2017) 1e15
9
4.4.14. (R)-2-Mesyloxy-1-(3-methylbenzofuran-2-yl)ethanol 8c
(300 MHz, CDCl3):
d
¼ 1.35 (t, J ¼ 7.5 Hz, 3H, CH3), 2.62 (d, J ¼ 5.7 Hz,
Light green oil, 0.27 g, 93% yield, ½a D26
ꢃ
¼ þ22.00 (c 1.50, CHCl3),
1H, OH), 2.92 (q, J ¼ 7.5 Hz, 2H, CH2), 3.70 (dd, J ¼ 12.6, 4.5 Hz, 1H,
CH2), 3.76 (dd, J ¼ 12.6, 6.9 Hz, 1H, CH2), 5.04 (ddd, J ¼ 7.0, 4.5,
0.9 Hz, 1H, CH), 6.73 (d, J ¼ 0.6 Hz, 1H), 7.12 (ddd, J ¼ 7.2, 1.5, 0.6 Hz,
1H), 7.18 (t, J ¼ 7.5 Hz,1H), 7.40 (dd, J ¼ 7.5,1.5 Hz,1H) ppm. 13C NMR
93% ee, determined by HPLC analysis, Daicel Chiralcel OD-H column
250 ꢁ 4.6 mm, 5
(S) 16.44 min, 3.58%, (R) 19.49 min, 96.42%. 1H NMR (700 MHz,
CDCl3):
mm, hexane/isopropanol 55:45, flow 0.45 mL/min,
d
¼ 2.30 (s, 3H, CH3), 2.60 (bs,1H, OH), 3.06 (s, 3H, CH3), 4.47
(75 MHz, CDCl3):
d
¼ 14.1 (CH3), 22.7 (CH2), 55.1 (CH2), 67.8 (CH),
(dd, J ¼ 11.2, 4.2 Hz,1H, CH2), 4.67 (dd, J ¼ 11.2, 8.4 Hz,1H, CH2), 5.24
(dd, J ¼ 7.7, 4.2 Hz, 1H, CH),7.26 (td, J ¼ 7.7, 0.7 Hz, 1H), 7.32 (ddd,
J ¼ 8.4, 7.0, 1.4 Hz, 1H), 7.43 (dt, J ¼ 8.4, 0.7 Hz, 1H), 7.51 (dq, J ¼ 7.7,
104.2 (CH), 118.7 (CH), 123.2 (CH), 123.8 (CH), 127.4 (C), 127.8 (C),
153.4 (C), 155.3 (C) ppm. IR, neat (cmꢀ1): 3401, 2969, 2106, 1427,
1277, 1182, 1092, 820, 747.
0.7 Hz, 1H) ppm. 13C NMR (100 MHz, CDCl3):
d
¼ 7.8 (CH3), 37.7
(CH3), 64.9 (CH), 71.0 (CH2), 111.3 (CH), 114.4 (C), 119.8 (CH), 122.7
(CH), 125.1 (CH), 129.4 (C), 147.9 (C), 154.1 (C) ppm. IR, neat (cmꢀ1):
3502, 3028, 1346, 1081, 957, 745. Anal. calcd for C12H14O5S: C, 53.32;
H, 5.22. Found: C, 53.32; H, 5.25.
4.5.3. (R)-2-Azido-1-(3-methylbenzofuran-2-yl)ethanol 11
Prepared from 5c: yellow oil, 91 mg, 62% yield, ½a D25
¼ þ48.90 (c
ꢃ
0.73, CHCl3), 92% ee, determined by HPLC analysis, Daicel Chiralcel
OJ column 250 ꢁ 4.6 mm, 10
0.7 mL/min, (S) 26.05 min, 3.97%, (R) 28.34 min, 96.03%. 1H NMR
(300 MHz, CDCl3):
mm, hexane/isopropanol 90:10, flow
4.4.15. (R)-2-Mesyloxy-1-(3-phenetylbenzofuran-2-yl)ethanol 8e
d
¼ 2.29 (s, 3H, CH3), 2.30 (d, J ¼ 8.7 Hz, 1H, OH),
Yellow oil, 0.30 g, 96% yield, ½a D25
ꢃ
¼ þ12.50 (c 0.80, CHCl3), 93%
3.59 (dd, J ¼ 12.6, 4.8 Hz, 1H, CH2), 3.83 (dd, J ¼ 12.6, 7.8 Hz, 1H,
CH2), 5.07 (dd, J ¼ 7.8, 4.8 Hz, 1H, CH), 7.25 (td, J ¼ 7.2, 1.5 Hz, 1H),
7.31 (td, J ¼ 7.2, 1.5 Hz, 1H), 7.44 (ddd, J ¼ 8.1, 1.5, 0.9 Hz, 1H), 7.51
ee, determined by HPLC analysis, Daicel Chiralcel OD-H column
250 ꢁ 4.6 mm, 5
(R) 21.58 min, 96.34%, (S) 23.99 min, 3.66%. 1H NMR (400 MHz,
CDCl3):
mm, hexane/isopropanol 55:45, flow 0.45 mL/min,
(ddd, J ¼ 7.2, 1.5, 0.9 Hz, 1H) ppm. 13C NMR (75 MHz, CDCl3):
¼ 7.8
d
d
¼ 1.51 (d, J ¼ 4.0 Hz, 1H, OH), 2.96e3.12 (m, 4H, 2xCH2),
(CH3), 54.9 (CH2), 65.9 (CH), 111.2 (CH), 113.6 (C), 119.6 (CH), 122.6
(CH), 124.9 (CH), 129.5 (C), 149.4 (C), 154.0 (C) ppm.
3.01 (s, 3H, CH3), 4.05 (dd, J ¼ 10.8, 4.0 Hz, 1H, CH2), 4.42 (dd,
J ¼ 10.8, 8.0 Hz, 1H, CH2), 4.72 (dt, J ¼ 8.4, 4.0 Hz, 1H, CH), 7.00e7.04
(m, 2H), 7.21e7.30 (m, 3H), 7.32 (dd, J ¼ 7.6, 1.2 Hz, 1H), 7.36 (td,
J ¼ 7.6, 1.2 Hz, 1H), 7.46 (ddd, J ¼ 8.0, 1.2, 0.8 Hz, 1H), 7.62 (ddd,
4.5.4. (R)-2-Azido-1-(3,7-dimethylbenzofuran-2-yl)ethanol 12
Prepared from 5d: yellow oil, 83 mg, 53% yield, ½a D23
¼ þ44.30 (c
ꢃ
J ¼ 7.6, 1.6, 0.8 Hz, 1H) ppm. 13C NMR (100 MHz, CDCl3):
d
25.7
1.16, CHCl3), 87% ee, determined by HPLC analysis, Daicel Chiralcel
(CH2), 35.5 (CH3), 37.6 (CH2), 64.4 (CH), 70.7 (CH2), 111.6 (CH), 117.4
(C), 119.8 (CH), 122.8 (CH), 125.1 (CH), 126.5 (CH), 128.2 (C), 128.5
(2xCH), 128.9 (2xCH), 141.1 (C), 149.1 (C), 154.4 (C) ppm. IR, neat
(cmꢀ1): 3512, 3025, 2933, 1251, 1172, 961, 750. Anal. calcd for
OD-H column 250 ꢁ 4.6 mm, 5
0.7 mL/min, (S) 11.67 min, 6.29%, (R) 13.11 min, 93.71%. 1H NMR
(200 MHz, CDCl3):
mm, hexane/isopropanol 90:10, flow
d
¼ 2.20 (bs, 1H, OH), 2.28 (s, 3H, CH3), 2.51 (s,
3H, CH3), 3.60 (dd, J ¼ 12.6, 4.8 Hz, 1H, CH2), 3.85 (dd, J ¼ 12.6,
7.8 Hz, 1H, CH2), 5.06 (dd, J ¼ 7.8, 4.8 Hz, 1H, CH), 7.05e7.20 (m, 2H),
C
19H20O5S: C, 63.32; H, 5.59. Found: C, 63.21; H, 5.73.
7.32e7.38 (m, 1H) ppm. 13C NMR (50 MHz, CDCl3):
d
¼ 7.9 (CH3),
4.5. General procedure for the synthesis of benzofuryl
alcohols
b-azido
14.9 (CH3), 54.9 (CH2), 66.0 (CH), 113.9 (C), 117.0 (CH), 121.5 (C),
122.6 (CH), 125.8 (CH), 129.0 (C), 149.2 (C), 153.0 (C) ppm.
A mixture of benzofuryl 1,2-diol monosulfonate (0.68 mmol)
and sodium azide (0.88 mg, 1.36 mmol) in DMSO (5 mL) was heated
at 80 ꢂC for 2 h and then cooled to rt. To this was added water
(10 mL) and the mixture was extracted with ethyl acetate (3 ꢁ 7
mL). The combined extract was dried over anhydrous MgSO4,
filtered, and concentrated under reduced pressure. The residue was
purified by column chromatography on silica gel (hexane/ethyl
acetate/dichloromethane, 5:2:3).
4.5.5. (R)-2-Azido-1-(3-phenethylbenzofuran-2-yl)ethanol 13
Prepared from 5e: yellow oil, 0.10 g, 50% yield, ½a D26
¼ þ34.69 (c
ꢃ
1.03, CHCl3), 93% ee, determined by HPLC analysis, Daicel Chiralcel
OD-H column 250 ꢁ 4.6 mm, 5
0.7 mL/min, (S) 16.55 min, 3.48%, (R) 42.85 min, 96.52%. 1H NMR
(300 MHz, CDCl3):
mm, hexane/isopropanol 90:10, flow
d
¼ 1.47 (bs, 1H, OH), 2.93e3.10 (m, 5H, 3xCH2),
3.52 (dd, J ¼ 12.6, 8.1 Hz, 1H, CH2), 4.52 (dd, J ¼ 8.1, 4.8 Hz, 1H, CH),
6.97e7.01 (m, 2H), 7.21e7.30 (m, 4H), 7.33 (td, J ¼ 7.2, 1.5 Hz, 1H),
7.44e7.47 (m, 1H), 7.58e7.61 (m, 1H) ppm. 13C NMR (75 MHz,
4.5.1. (R)-2-Azido-1-(benzofuran-2-yl)ethanol 9
CDCl3):
d
¼ 25.6 (CH2), 35.4 (CH2), 54.2 (CH2), 65.4 (CH2), 111.5 (CH),
Prepared from 5a: light yellow solid, 0.12 g, 84% yield, mp
116.5 (C), 119.7 (CH), 122.7 (CH), 124.9 (CH), 126.4 (CH), 128.3 (C),
128.5 (2xCH), 128.9 (2xCH), 141.2 (C), 150.6 (C), 154.3 (C) ppm.
35e36 ꢂC, ½a 2D6
ꢃ
¼ þ90.50 (c 2.00, CHCl3), 97% ee, determined by
HPLC analysis, Daicel Chiralcel OD-H column 250 ꢁ 4.6 mm, 5
m
m,
hexane/isopropanol 95:5, flow 0.7 mL/min, (S) 33.89 min, 1.17%, (R)
4.6. General procedure for the synthesis of benzofuryl
alcohols from -azido alcohols
b-amino
36.56 min, 98.83%. 1H NMR (700 MHz, CDCl3):
d
¼ 2.54 (bs, 1H, OH),
b
3.75 (dd, J ¼ 12.6, 4.2 Hz, 1H, CH2), 3.80 (dd, J ¼ 12.6, 7.0 Hz, 1H,
CH2), 5.06 (ddd, J ¼ 7.0, 4.2, 0.7 Hz, 1H, CH), 6.78 (t, J ¼ 0.7 Hz, 1H),
7.27 (ddd, J ¼ 8.4, 7.0, 1.4 Hz, 1H), 7.33 (ddd, J ¼ 8.4, 7.0, 1.4 Hz, 1H),
A mixture of benzofuryl b-azido alcohol (0.5 mmol) and 10% Pd/
C (50 mg) in methanol (5 mL) was hydrogenated in an autoclave
under 10 atm. pressure for 3 h at rt. The reaction mixture was
filtered on a Celite pad and the filtrate was concentrated under
reduced pressure to give white solid products.
7.50 (dq, J ¼ 8.4, 0.7 Hz, 1H), 7.60 (dq, J ¼ 7.7, 0.7 Hz, 1H) ppm. 13
C
NMR (175 MHz, CDCl3):
d
¼ 56.0 (CH2), 68.7 (CH), 105.1 (CH), 112.3
(CH),122.3 (CH),124.1 (CH),125.6 (CH),128.9 (C),155.9 (C),156.8 (C)
ppm. IR neat (cmꢀ1): 3400, 2106, 1454, 1304, 1173, 1092, 812, 751.
Anal. calcd for C10H9O2N3: C, 59.11; H, 4.46; N, 20.68. Found: C,
58.96; H, 4.63; N, 20.37.
4.6.1. (R)-2-Amino-1-(benzofuran-2-yl)ethanol 14
88 mg, 99% yield, mp 128e132 ꢂC, ½a D25
¼ þ36.20 (c 1.13, MeOH).
ꢃ
1H NMR (300 MHz, DMSO-d6):
d
¼ 1.95 (bs, 2H, NH2), 2.79 (dd,
4.5.2. (R)-2-Azido-1-(7-ethylbenzofuran-2-yl)ethanol 10
J ¼ 13.2, 7.2 Hz, 1H, CH2N), 2.90 (dd, J ¼ 13.2, 4.8 Hz, 1H, CH2N), 4.57
(dd, J ¼ 6.9, 4.8 Hz, 1H, CH), 5.60 (bs, 1H, NH2), 6.72 (t, J ¼ 0.6 Hz,
1H), 7.19 (td, J ¼ 7.2, 1.5 Hz, 1H), 7.24 (td, J ¼ 7.2, 1.5 Hz, 1H), 7.51
(ddd, J ¼ 7.2, 1.5, 0.9 Hz, 1H), 7.57 (ddd, J ¼ 6.9, 2.1, 0.6 Hz, 1H) ppm.
Prepared from 5b: orange oil, 0.11 g, 72% yield, ½a D29
¼ þ67.65 (c
ꢃ
1.59, CHCl3), 90% ee, determined by HPLC analysis, Daicel Chiralcel
OJ column 250 ꢁ 4.6 mm, 10
mm, hexane/isopropanol 80:20, flow
0.7 mL/min, (S) 9.68 min, 5.06%, (R) 10.75 min, 94.94%. 1H NMR
13C NMR (75 MHz, DMSO-d6):
d
¼ 46.7 (CH2), 68.9 (CH), 102.4 (CH),
Please cite this article in press as: Tafelska-Kaczmarek A, et al., Asymmetric synthesis of benzofuryl
hydrogenation of -functionalized ketones, Tetrahedron (2017), http://dx.doi.org/10.1016/j.tet.2017.05.059
b
-amino alcohols by the transfer
a

10
A. Tafelska-Kaczmarek et al. / Tetrahedron xxx (2017) 1e15
110.9 (CH), 120.8 (CH), 122.6 (CH), 123.6 (CH), 128.0 (C), 153.9 (C),
160.1 (C) ppm. IR, KBr (cmꢀ1): 3341, 3059, 1606, 1454, 1256, 940,
809, 737. Anal. calcd for C10H11NO2: C, 67.78; H, 6.25; N, 7.90. Found:
C, 67.66; H, 6.27; N, 7.48
hexane/diethyl ether 1:1 to give a yellow solid.
4.7.1. 2-N,N-Diformylamino-1-(benzofuran-2-yl)ethanone 23
2.30 g, 99% yield, mp 122e123 ꢂC. 1H NMR (300 MHz, CDCl3):
d
¼ 5.11 (s, 2H, CH2), 7.35 (ddd, J ¼ 7.8, 6.9, 1.2 Hz, 1H), 7.53 (ddd,
4.6.2. (R)-2-Amino-1-(7-ethylbenzofuran-2-yl)ethanol 15
J ¼ 8.4, 6.9, 1.2 Hz, 1H), 7.60 (ddd, J ¼ 8.4, 1.8, 0.9 Hz, 1H), 7.63 (d,
J ¼ 0.9 Hz, 1H), 7.74 (ddd, J ¼ 7.8, 1.2, 0.9 Hz,1H), 9.05 (s, 2H, 2xCHO)
99 mg, 97% yield, mp 80e81 ꢂC, ½a D24
¼ þ32.53 (c 0.91, MeOH).
ꢃ
1H NMR (300 MHz, DMSO-d6):
d
¼ 1.26 (t, J ¼ 7.6 Hz, 3H, CH3), 1.65
ppm. 13C NMR (75 MHz, CDCl3):
d
¼ 44.7 (CH2), 112.5 (CH), 113.8
(bs, 2H, NH2), 2.78 (dd, J ¼ 12.6, 7.6 Hz, 1H CH2N), 2.84 (q, J ¼ 7.6 Hz,
2H, CH2), 2.90 (dd, J ¼ 12.6, 4.6 Hz, 1H, CH2N), 4.57 (dd, J ¼ 7.0,
4.8 Hz, 1H, CH), 5.57 (bs, 1H, OH), 6.68 (d, J ¼ 0.8 Hz, 1H), 7.06 (dd,
J ¼ 7.4, 0.8 Hz,1H,1H), 7.12 (t, J ¼ 7.2 Hz,1H), 7.38 (dd, J ¼ 7.0, 2.0 Hz,
(CH), 123.5 (CH), 124.3 (CH), 126.7 (C), 128.9 (CH), 150.5 (C), 155.7
(C), 163.1 (2xCHO), 181.4 (CO) ppm. Anal. calcd for C12H9NO4: C,
62.34; H, 3.92; N, 6.05. Found: C, 62.34; H, 4.01; N, 6.14.
1H) ppm. 13C NMR (75 MHz, DMSO-d6):
d
¼ 14.1 (CH3), 22.3 (CH2),
4.7.2. 2-N,N-Diformylamino-1-(7-ethylbenzofuran-2-yl)ethanone
46.9 (CH2), 69.0 (CH), 102.5 (CH), 118.4 (CH), 122.7 (CH), 122.8 (CH),
126.7 (C), 127.7 (C), 152.4 (C), 159.7 (C) ppm. IR, KBr (cmꢀ1): 3339,
2967, 1599, 1454, 1189, 1042, 995, 814, 740. Anal. calcd for
24
2.52 g, 98% yield, mp 106e107 ꢂC. 1H NMR (200 MHz, CDCl3):
d
¼ 1.37 (t, J ¼ 7.5 Hz, 3H, CH3), 3.00 (q, J ¼ 7.5 Hz, 2H, CH2), 5.13 (s,
C
12H15NO2: C, 70.22; H, 7.36; N, 6.82. Found: C, 70.35; H, 7.48; N,
2H, CH2), 7.27 (t, J ¼ 7.8 Hz, 1H), 7.35 (ddt, J ¼ 7.2 Hz, 1H), 7.56 (dd,
6.94
J ¼ 7.8, 1.5 Hz, 1H), 7.63 (s, 1H), 9.05 (s, 2H, 2xCHO) ppm. 13C NMR
(50 MHz, CDCl3):
d
¼ 13.9 (CH3), 22.6 (CH2), 44.6 (CH2), 114.1 (CH),
4.6.3. (R)-2-Amino-1-(3-methylbenzofuran-2-yl)ethanol 16
120.9 (CH), 124.4 (CH), 126.3 (C), 127.7 (CH), 128.9 (C), 150.1 (C),
154.4 (C), 163.4 (2xCHO), 184.5 (CO) ppm. Anal. calcd for
92 mg, 96% yield, mp 95e98 ꢂC, ½a D25
¼ þ14.14 (c 0.45, MeOH).
ꢃ
1H NMR (300 MHz, DMSO-d6):
d
¼ 1.68 (bs, 2H, NH2), 2.20 (s, 3H,
C14H13NO4: C, 64.86; H, 5.04; N, 5.40. Found: C, 64.58; H, 4.98; N,
5.27.
CH3), 2.79 (dd, J ¼ 12.6, 6.0 Hz, 1H, CH2), 2.88 (dd, J ¼ 12.6, 7.2 Hz,
1H, CH2), 4.65 (dd, J ¼ 7.2, 6.0 Hz, 1H, CH), 5.40 (bs, 1H, OH),
7.17e7.27 (m, 2H), 7.45e7.48 (m, 1H), 7.51e7.56 (m, 1H) ppm. 13C
4.7.3. 2-N,N-Diformylamino-1-(3-methylbenzofuran-2-yl)
ethanone 25
NMR (75 MHz, DMSO-d6):
d
¼ 7.5 (CH3), 46.6 (CH2), 67.4 (CH), 110.7
(CH), 111.1 (C), 119.2 (CH), 122.1 (CH), 123.8 (CH), 129.7 (C), 153.1 (C),
153.9 (C) ppm. IR, HCB (cmꢀ1): 3341, 2905, 1612, 1456, 1254, 1062,
740. Anal. calcd for C11H13NO2: C, 69.09; H, 6.85; N, 7.32. Found: C,
69.21; H, 6.80; N, 7.46.
2.48 g, 98% yield, mp 145e147 ꢂC. 1H NMR (200 MHz, CDCl3):
d
¼ 2.60 (s, 3H, CH3), 5.12 (s, 2H, CH2), 7.34 (dt, J ¼ 7.9, 3.7 Hz, 1H),
7.50e7.55 (m, 2H), 7.68 (dt, J ¼ 7.8, 1.0 Hz, 1H), 9.10 (s, 2H, 2xCHO)
ppm. 13C NMR (50 MHz, CDCl3):
d
¼ 9.4 (CH3), 45.5 (CH2), 112.2
(CH), 121.7 (CH), 123.6 (CH), 126.9 (C), 128.8 (C), 128.9 (CH), 146.1
(C), 154.4 (C), 163.3 (2xCHO), 182.9 (CO) ppm. IR, KBr (cmꢀ1): 3350,
2923, 1681, 1567, 1345, 1259, 1171, 983, 943, 852, 793, 655. Anal.
calcd for C13H11NO4: C, 63.67; H, 4.51; N, 5.71. Found: C, 63.58; H,
4.55; N, 5.77.
4.6.4. (R)-2-Amino-1-(3,7-dimethylbenzofuran-2-yl)ethanol 17
81 mg, 79% yield, mp 127e130 ꢂC, ½a D25
¼ þ13.03 (c 0.44, MeOH).
ꢃ
1H NMR (300 MHz, DMSO-d6):
d
¼ 1.43 (bs, 2H, NH2), 2.19 (s, 3H,
CH3), 2.41 (s, 3H, CH3), 2.81 (dd, J ¼ 12.9, 5.7 Hz, 1H, CH2), 2.90 (dd,
J ¼ 12.9, 7.2 Hz, 1H, CH2), 4.66 (dd, J ¼ 7.2, 5.7 Hz, 1H, CH), 5.42 (bs,
1H, OH), 7.05 (ddd, J ¼ 7.2,1.8, 0.9 Hz,1H), 7.10 (t, J ¼ 7.4 Hz,1H), 7.33
(ddd, J ¼ 7.2, 1.5, 0.6 Hz, 1H) ppm. 13C NMR (75 MHz, DMSO-d6):
4.7.4. 2-N,N-Diformylamino-1-(3,7-dimethylbenzofuran-2-yl)
ethanone 26
d
¼ 7.7 (CH3), 14.7 (CH3), 46.4 (CH2), 67.3 (CH), 111.3 (C), 116.7 (CH),
2.57 g, 99% yield, mp 104e108 ꢂC. 1H NMR (200 MHz, CDCl3):
120.3 (C), 122.2 (CH), 124.7 (CH), 129.3 (C), 152.0 (C), 153.5 (C) ppm.
IR, KBr, (cmꢀ1): 3277, 2922, 1586, 1451, 1258, 1035, 744. Anal. calcd
for C12H15NO2: C, 70.22; H, 7.36; N, 6.82. Found: C, 70.29; H, 7.58; N,
6.91.
d
¼ 2.55 (s, 3H, CH3), 2.59 (s, 3H, CH3), 5.15 (s, 2H, CH2), 7.24 (t,
J ¼ 7.2 Hz, 1H), 7.32 (ddd, J ¼ 7.2, 1.2, 0.9 Hz, 1H), 7.50 (ddd, J ¼ 7.8,
1.2, 0.6 Hz, 1H), 9.06 (s, 2H, 2xCHO) ppm. 13C NMR (50 MHz, CDCl3):
d
¼ 9.5 (CH3),14.8 (CH3), 45.4 (CH2),119.1 (CH),122.5 (C),123.7 (CH),
127.3 (C), 128.4 (C), 129.6 (CH), 146.0 (C), 153.5 (C), 163.4 (2xCHO),
182.2 (CO) ppm. Anal. calcd for C14H13NO4: C, 64.86; H, 5.04; N,
5.40. Found: C, 64.76; H, 5.09; N, 5.32.
4.6.5. (R)-2-Amino-1-(3-phenethylbenzofuran-2-yl)ethanol 18
100 mg, 71% yield, mp 107e109 ꢂC, ½a D23
¼ þ99.50 (c 0.81,
ꢃ
MeOH). 1H NMR (300 MHz, DMSO-d6):
d
¼ 1.65 (bs, 2H, NH2), 2.59
(dd, J ¼ 12.9, 5.1 Hz, 1H, CH2N), 2.79 (dd, J ¼ 12.9, 7.5 Hz, 1H, CH2N),
2.83e3.05 (m, 4H, 2xCH2), 4.56 (dd, J ¼ 7.2, 5.4 Hz, 1H, CH), 5.42 (bs,
1H, OH), 7.14e7.29 (m, 7H), 7.46e7.49 (m, 1H), 7.56e7.59 (m, 1H)
4.8. General procedure for the synthesis of benzofuryl
ketones hydrochlorides
a-amino
ppm. 13C NMR (75 MHz, DMSO-d6):
d
¼ 25.0 (CH2), 35.8 (CH2), 46.5
A mixture of benzofuryl N,N-diformylamino ketone 23e26
(10.0 mmol) and 5% HCl/EtOH (33 mL) was stirred at rt for 48 h. The
precipitate was filtered and crystallized from isopropanol to give
white solid products.
(CH2), 67.3 (CH), 110.9 (CH), 115.2 (CH), 119.5 (CH), 122.2 (CH), 123.8
(CH), 125.9 (CH), 128.2 (2xCH), 128.4 (2xCH), 128.8 (C), 141.5 (C),
153.2 (C), 154.2 (C) ppm. Anal. calcd for C18H19O2N: C, 76.84; H,
6.80; N, 4.98. Found: C, 76.48; H, 6.96; N, 4.92.
4.8.1. 2-Amino-1-(benzofuran-2-yl)ethanone hydrochloride 27
1.97 g, 94% yield, mp 211e212 ꢂC. 1H NMR (300 MHz, DMSO-d6):
4.7. General procedure for the synthesis of benzofuryl N,N-
diformylamino ketones
d
¼ 4.51 (s, 2H, CH2), 7.41 (ddd, J ¼ 7.8, 7.2, 0.9 Hz, 1H), 7.60 (ddd,
J ¼ 8.4, 7.2, 1.2 Hz, 1H), 7.77 (dd, J ¼ 8.4, 0.9 Hz, 1H), 7.89 (dd, J ¼ 7.8,
A mixture of the corresponding benzofuryl
a-bromo ketone
0.9 Hz, 1H), 8.12 (d, J ¼ 0.9 Hz, 1H), 8.53 (s, 3H, NH2xHCl) ppm. 13
C
19e22 (10.0 mmol) and sodium diformylamide (1.00 g, 10.5 mmol)
in acetonitrile (50 mL) was stirred at rt for 1.5 h and then heated at
70 ꢂC for 1 h. The hot mixture was filtered and the precipitated NaBr
was washed with hot acetonitrile (20 mL). The combined filtrates
were evaporated in vacuo and the product was crystallized from
NMR (75 MHz, DMSO-d6):
d
¼ 44.3 (CH2), 112.4 (CH), 115.9 (CH),
124.0 (CH), 124.4 (CH), 126.4 (C), 129.2 (CH), 149.5 (C), 155.1 (C),
183.2 (CO) ppm. IR, KBr (cmꢀ1): 3321, 3009, 1690, 1560, 1499, 1400,
991, 771. Anal. calcd for C10H10NO2Cl: C, 56.75; H, 4.76; N, 6.62.
Found: C, 56.58; H, 4.89; N, 6.87.
Please cite this article in press as: Tafelska-Kaczmarek A, et al., Asymmetric synthesis of benzofuryl
hydrogenation of -functionalized ketones, Tetrahedron (2017), http://dx.doi.org/10.1016/j.tet.2017.05.059
b-amino alcohols by the transfer
a

A. Tafelska-Kaczmarek et al. / Tetrahedron xxx (2017) 1e15
11
4.8.2. 2-Amino-1-(7-ethylbenzofuran-2-yl)ethanone hydrochloride
J ¼ 4.8 Hz, 2H, CH2N), 5.17 (s, 2H, CH2), 5.71 (bs, 1H, NH), 7.22e7.38
(m, 7H), 7.55 (dd, J ¼ 7.5, 1.2 Hz, 1H), 7.61 (s, 1H) ppm. 13C NMR
28
1.92 g, 81% yield, mp 198e200 ꢂC. 1H NMR (300 MHz, DMSO-d6):
(50 MHz, CDCl3):
d
¼ 14.0 (CH3), 22.7 (CH2), 47.8 (CH2), 67.1 (CH2),
d
¼ 1.30 (t, J ¼ 7.5 Hz, 3H, CH3), 2.92 (q, J ¼ 7.5 Hz, 2H, CH2), 4.51 (s,
113.8 (CH), 120.8 (CH), 124.4 (CH), 126.4 (C), 127.7 (CH), 128.1
(2xCH), 128.2 (CH), 128.5 (2xCH), 129.0 (C), 136.2 (C), 150.3 (C),
154.4 (C), 156.3 (CO), 185.5 (CO) ppm. IR, KBr (cmꢀ1): 3303, 2977,
1681, 1544, 1282, 1261, 1175, 987, 743. Anal. calcd for C20H19NO4: C,
71.20; H, 5.67; N, 4.15. Found: C, 71.36; H, 5.48; N, 4.23.
2H, CH2), 7.32 (t, J ¼ 7.4 Hz, 1H), 7.43 (dd, J ¼ 7.3, 0.9 Hz, 1H), 7.70
(dd, J ¼ 7.5, 0.9 Hz, 1H), 8.11 (s, 1H), 8.46 (s, 3H, NH2xHCl) ppm. 13
C
NMR (50 MHz, DMSO-d6):
d
¼ 13.9 (CH3), 22.1 (CH2), 44.2 (CH2),
116.2 (CH), 121.4 (CH), 124.6 (CH), 126.2 (C), 128.0 (C), 128.2 (CH),
149.2 (C), 153.8 (C), 183.1 (CO) ppm. IR, KBr (cmꢀ1): 3424, 2957,
1677, 1554, 1297, 1179, 917, 743. Anal. calcd for C12H14NO2Cl: C,
60.13; H, 5.88; N, 5.84. Found: C, 59.98; H, 5.89; N, 5.87.
4.9.3. Benzyl (2-(3-methylbenzofuran-2-yl)-2-oxoethyl)carbamate
33
0.52 g, 98% yield, mp 76e77 ꢂC. 1H NMR (700 MHz, CDCl3):
4.8.3. 2-Amino-1-(3-methylbenzofuran-2-yl)ethanone
hydrochloride 29
d
¼ 2.63 (s, 3H, CH3), 4.75 (d, J ¼ 4.8 Hz, 2H, CH2N), 5.17 (s, 2H, CH2),
5.71 (bs, 1H, NH), 7.30e7.40 (m, 6H), 7.50e7.53 (m, 2H), 7.67 (dt,
1.94 g, 86% yield, mp 217e218 ꢂC. 1H NMR (400 MHz, DMSO-d6):
J ¼ 7.8, 1.5 Hz, 1H) ppm. 13C NMR (175 MHz, CDCl3):
d
¼ 9.3 (CH3),
d
¼ 2.62 (s, 3H, CH3), 4.47 (s, 2H, CH2), 7.42 (ddd, J ¼ 8.0, 7.2, 0.8 Hz,
48.6 (CH2), 67.0 (CH2), 112.2 (CH), 121.6 (CH), 123.4 (CH), 126.2 (C),
128.0 (2xCH), 128.1 (CH), 128.5 (2xCH), 128.7 (CH), 128.9 (C), 136.3
(C), 146.1 (C), 154.3 (C), 156.2 (CO), 187.2 (CO) ppm. IR, KBr (cmꢀ1):
3331, 2939, 1679, 1625, 1570, 1185, 985, 741. Anal. calcd for
1H), 7.62 (ddd, J ¼ 8.4, 7.2,1.2 Hz,1H), 7.26 (d, J ¼ 8.4 Hz,1H), 7.90 (d,
J ¼ 8.0 Hz, 1H), 8.46 (s, 3H, NH2xHCl) ppm. 13C NMR (100 MHz,
DMSO-d6):
d
¼ 9.6 (CH3), 45.7 (CH2), 112.7 (CH), 122.8 (CH), 124.4
(CH), 126.7 (C), 128.8 (C), 129.9 (CH), 145.9 (C), 154.2 (C), 185.4 (CO)
ppm. IR, KBr (cmꢀ1): 3345, 2989, 1674, 1550, 1195, 969, 829, 761.
Anal. calcd for C11H12NO2Cl: C, 58.54; H, 5.36; N, 6.20. Found: C,
58.50; H, 5.49; N, 6.37.
C19H17NO4: C, 70.58; H, 5.30; N, 4.33. Found: C, 70.42; H, 5.38; N,
4.47.
4.9.4. Benzyl (2-(3,7-dimethylbenzofuran-2-yl)-2-oxoethyl)
carbamate 34
4.8.4. 2-Amino-1-(3,7-dimethylbenzofuran-2-yl)ethanone
hydrochloride 30
0.41 g, 61% yield, mp 85e89 ꢂC. 1H NMR (700 MHz, CDCl3):
¼ 2.54 (s, 3H, CH3), 2.61 (s, 3H, CH3), 4.74 (d, J ¼ 4.8 Hz, 2H, CH2N),
d
1.70 g, 71% yield, mp 188e192 ꢂC. 1H NMR (200 MHz, DMSO-d6):
5.17 (s, 2H, CH2), 5.76 (bs, 1H, NH), 7.22 (dd, J ¼ 7.5, 7.2 Hz, 1H),
d
¼ 2.51 (s, 3H, CH3), 2.59 (s, 3H, CH3), 4.48 (s, 2H, CH2), 7.30 (t,
J ¼ 7.5 Hz, 1H), 7.43 (d, J ¼ 7.5 Hz, 1H), 7.69 (d, J ¼ 7.5 Hz, 1H), 8.37 (s,
3H, NH2xHCl) ppm. 13C NMR (75 MHz, DMSO-d6):
7.25e7.45 (m, 6H), 7.49 (ddd, J ¼ 7.5, 1.2, 0.6 Hz, 1H) ppm. 13C NMR
(175 MHz, CDCl3):
d
¼ 9.5 (CH3), 14.8 (CH3), 48.5 (CH2), 66.9 (CH2),
d
¼ 9.3 (CH3),
118.9 (CH), 122.6 (C), 123.6 (CH), 126.6 (C), 126.9 (CH), 127.5 (CH),
128.1 (CH), 128.5 (2xCH), 129.4 (CH), 136.4 (C), 140.9 (C), 145.9 (C),
153.4 (C), 156.3 (CO), 187.2 (CO) ppm. IR, KBr (cmꢀ1): 3318, 3060,
2919, 1689, 1545, 1258, 1124, 1047, 965, 929, 776, 744, 698. Anal.
calcd for C20H19NO4: C, 71.20; H, 5.67; N, 4.15. Found: C, 71.07; H,
5.75; N, 4.30.
14.5 (CH3), 45.0 (CH2), 119.6 (CH), 121.9 (C), 123.9 (CH), 126.4 (C),
127.9 (C), 129.8 (CH), 145.3 (C), 152.8 (C), 184.8 (CO) ppm. IR, KBr,
(cmꢀ1): 3432, 2925, 1692, 1582, 1511, 1373, 1272, 1131, 932, 792, 751.
Anal. calcd for C12H14NO2Cl: C, 60.13; H, 5.88; N, 5.84. Found: C,
60.25; H, 5.71; N, 5.67.
4.9. General procedure for the synthesis of benzyl (2-(benzofuran-
2-yl)-2-oxoethyl)carbamates
4.10. Benzyl (R)-(2-(benzofuran-2-yl)-2-hydroxyethyl)carbamate
35
To a solution of benzofuryl
a
-amino ketone hydrochloride
Prepared by transfer hydrogenation of 31 (0.43 g, 1.4 mmol)
following the procedure described in 4.4: yellow solid, 0.35 g, 81%
27e30 (2.0 mmol) in 1,4-dioxane (8 mL) and water (8 mL) was
added benzyl chloroformate (0.72 g, 4.2 mmol) and the mixture
was stirred at rt for 3 h. The pH value of the reaction mixture was
maintained basic by the addition of sat. aq. NaHCO3. The resulting
mixture was extracted with ethyl acetate (3 ꢁ 10 mL), the organic
extracts were dried over anhydrous MgSO4, filtered, and concen-
trated under reduced pressure. The product was crystallized from
methanol to give yellow solid products.
yield, mp 107e108 ꢂC, ½a D20
¼ þ27.08 (c 4.98, CHCl3), 99% ee,
ꢃ
determined by HPLC analysis, Daicel Chiralcel OD-H column
250 ꢁ 4.6 mm, 5
(R) 15.44 min, 99.55%, (S) 17.44 min, 0.45%.
1H NMR (300 MHz, CDCl3):
mm, hexane/isopropanol 70:30, flow 0.6 mL/min,
d
¼ 3.16 (d, J ¼ 5.1 Hz, 1H, OH), 3.61
(ddd, J ¼ 14.3, 6.9, 5.6 Hz, 1H, CH2N), 3.80 (ddd, J ¼ 14.3, 6.7, 3.9 Hz,
1H, CH2N), 4.96e4.99 (m, 1H, CH), 5.12 (s, 2H, CH2), 5.18 (bs, 1H,
NH), 6.70 (s, 1H), 7.22 (td, J ¼ 7.2, 1.2, Hz, 1H), 7.25e7.40 (m, 6H),
7.44 (ddd, J ¼ 7.5, 1.2, 0.9 Hz, 1H), 7.54 (ddd, J ¼ 7.2, 1.2, 0.6 Hz, 1H)
4.9.1. Benzyl (2-(benzofuran-2-yl)-2-oxoethyl)carbamate 31
0.50 g, 81% yield, mp 93e95 ꢂC. 1H NMR (200 MHz, CDCl3):
ppm. 13C NMR (50 MHz, CDCl3):
d
¼ 45.6 (CH2), 67.1 (CH2), 68.0
d
¼ 4.73 (d, J ¼ 4.8 Hz, 2H, CH2N), 5.17 (s, 2H, CH2), 5.69 (bs, 1H, NH),
(CH), 103.7 (CH), 111.2 (CH), 121.1 (CH), 122.9 (CH), 124.3 (CH), 127.9
(C), 128.1 (CH), 128.2 (CH), 128.5 (3xCH), 136.1 (C), 154.8 (C), 156.6
(C), 157.3 (CO) ppm. IR, KBr (cmꢀ1): 3473, 3315, 3034, 2924, 1702,
1560, 1455, 1276, 1061, 742. Anal. calcd for C18H17NO4: C, 69.44; H,
5.50; N, 4.49. Found: C, 69.47; H, 5.56; N, 4.52. MS EI: m/z 311 (Mþ,
2), 91 (100), 147 (91), 77 (28), 79 (26), 65 (21), 176 (20), 131 (18), 89
(17), 51 (17), 203 (16),108 (15), 39 (15), 63 (14),160 (14), 92 (12),107
(12).
7.31e7.40 (m, 6H), 7.51 (ddd, J ¼ 8.2, 7.2, 1.2 Hz, 1H), 7.59 (ddd,
J ¼ 8.2, 1.8, 0.9 Hz, 1H), 7.61 (s, 1H), 7.73 (ddd, J ¼ 7.2, 1.8, 0.9 Hz, 1H)
ppm. 13C NMR (100 MHz, CDCl3):
d
¼ 47.9 (CH2), 67.2 (CH2), 112.5
(CH), 113.6 (CH), 123.5 (CH), 124.2 (CH), 126.7 (C), 128.1 (2xCH),
128.2 (CH), 128.6 (2xCH), 128.8 (CH), 136.3 (C), 150.6 (C), 155.7 (C),
156.3 (CO), 185.5 (CO) ppm. IR, KBr (cmꢀ1): 3338, 1685, 1560, 1289,
1258, 1177, 984, 735. Anal. calcd for C18H15NO4: C, 69.89; H, 4.88; N,
4.53. Found: C, 69.55; H, 4.50; N, 4.56.
4.11. Benzyl (R)-(2-(7-ethylbenzofuran-2-yl)-2-hydroxyethyl)
4.9.2. Benzyl (2-(7-ethylbenzofuran-2-yl)-2-oxoethyl)carbamate
carbamate 36
32
0.60 g, 90% yield, mp 81e82 ꢂC. 1H NMR (300 MHz, CDCl3):
Prepared by transfer hydrogenation of 32 (0.74 g, 2.2 mmol)
following the procedure described in 4.4: light yellow oil, 0.56 g,
d
¼ 1.36 (t, J ¼ 7.6 Hz, 3H, CH3), 2.98 (q, J ¼ 7.6 Hz, 2H, CH2), 4.75 (d,
Please cite this article in press as: Tafelska-Kaczmarek A, et al., Asymmetric synthesis of benzofuryl
hydrogenation of -functionalized ketones, Tetrahedron (2017), http://dx.doi.org/10.1016/j.tet.2017.05.059
b-amino alcohols by the transfer
a

12
A. Tafelska-Kaczmarek et al. / Tetrahedron xxx (2017) 1e15
76% yield, ½a 2D0
ꢃ
¼ þ19.77 (c 10.62, CHCl3), 98% ee, determined by
m,
4.14. General procedure for deprotection of benzofuryl N-Cbz
protected -amino alcohols
HPLC analysis, Daicel Chiralcel OD-H column 250 ꢁ 4.6 mm, 5
m
b
hexane/isopropanol 70:30, flow 0.7 mL/min, (R) 9.69 min, 98.99%,
(S) 11.53 min, 1.01%.
A mixture of benzofuryl N-Cbz protected
b-amino alcohol
1H NMR (300 MHz, CDCl3):
d
¼ 1.32 (t, J ¼ 7.6 Hz, 3H, CH3), 2.90
35e38 (1.0 mmol) and 5% Pd/C (30 mg) in methanol (35 mL) was
hydrogenated in an autoclave under 8 atm. pressure for 24 h at rt.
The reaction mixture was filtered on a Celite pad and the filtrate
was concentrated under reduced pressure. The residue was purified
by column chromatography on silica gel (hexane/ethyl acetate/
dichloromethane/methanol, 6:4:1:0.5) to give white solid products.
(q, J ¼ 7.6 Hz, 2H, CH2), 3.39 (bs, 1H, OH), 3.58 (ddd, J ¼ 14.1, 6.8,
5.8 Hz, 1H, CH2N), 3.78 (ddd, J ¼ 14.1, 6.8, 4.0 Hz, 1H, CH2N), 4.97
(dd, J ¼ 6.8, 4.0 Hz, 1H, CH), 5.10 (s, 2H, CH2), 5.30 (bs, 1H, NH), 6.67
(s, 1H), 7.10 (ddt, J ¼ 7.5, 1.2, 0.6 Hz, 1H), 7.16 (t, J ¼ 7.5 Hz, 1H),
7.33e7.39 (m, 5H), 7.37 (dd, J ¼ 7.5, 1.5 Hz, 1H) ppm. 13C NMR
(50 MHz, CDCl3):
d
¼ 14.0 (CH3), 22.7 (CH2), 45.6 (CH2), 67.1 (CH2),
68.0 (CH), 103.8 (CH), 118.6 (CH), 123.0 (CH), 123.5 (CH), 127.5 (C),
127.7 (C),128.0 (CH),128.1 (2xCH),128.5 (2xCH),136.2 (C),153.4 (C),
156.3 (C), 157.3 (CO) ppm. IR, KBr (cmꢀ1): 3411, 2967, 2934, 1702,
1542, 1524, 1455, 1261, 747. Anal. calcd for C20H21NO4: C, 70.78; H,
6.23; N, 4.13. Found: C, 70.75; H, 6.24; N, 4.25. MS EI: m/z 339 (Mþ,
3), 175 (100), 91 (75), 79 (28), 77 (27), 231 (25), 159 (24), 188 (19),
108 (17), 115 (16), 51 (14), 204 (14), 65 (13), 176 (13), 107 (13), 131
(13), 187 (12), 39 (11).
4.14.1. (R)-2-Amino-1-(benzofuran-2-yl)ethanol 14
0.19 g, 99% yield, mp 129e133 ꢂC, ½a D28
¼ þ43.23 (c 2.23, MeOH).
ꢃ
1H and 13C NMR spectra were the same as described in 4.6.1.
4.14.2. (R)-2-Amino-1-(7-ethylbenzofuran-2-yl)ethanol 15
0.16 g, 78% yield, mp 85e86 ꢂC, ½a D27
¼ þ36.56 (c 10.75, MeOH).
ꢃ
1H and 13C NMR spectra were the same as described in 4.6.2.
4.14.3. (R)-2-Amino-1-(3-methylbenzofuran-2-yl)ethanol 16
0.08 g, 75% yield, mp 98e101 ꢂC, ½a D25
¼ þ14.56 (c 0.35, MeOH).
ꢃ
1H and 13C NMR spectra were the same as described in 4.6.3.
4.12. Benzyl (R)-(2-(3-methylbenzofuran-2-yl)-2-hydroxyethyl)
carbamate 37
4.14.4. (R)-2-Amino-1-(3,7-dimethylbenzofuran-2-yl)ethanol 17
0.16 g, 80% yield, mp 136e139 ꢂC, ½a D25
¼ þ14.26 (c 0.43, MeOH).
ꢃ
Prepared by transfer hydrogenation of 33 (0.53 g, 1.6 mmol)
following the procedure described in 4.4: light yellow solid, 0.50 g,
1H and 13C NMR spectra were the same as described in 4.6.4.
94% yield, mp 103e106 ꢂC, ½a D20
ꢃ
¼ ꢀ17.15 (c 2.91, CHCl3), 95% ee,
4.15. General procedure for the synthesis of benzofuryl
succinimido ketones
a-
determined by HPLC analysis, Daicel Chiralcel OD-H column
250 ꢁ 4.6 mm, 5
(R) 16.65 min, 97.30%, (S) 18.97 min, 2.70%. 1H NMR (200 MHz,
CDCl3):
mm, hexane/isopropanol 70:30, flow 0.6 mL/min,
The suspension of succinimide (0.93 g, 9.4 mmol) in THF (9 mL)
was stirred at 50 ꢂC until the succinimide was dissolved. In a
separate flask potassium tert-butoxide (1.12 g, 10.0 mmol) was
suspended in THF (7 mL) and the suspension sonicated for 10 min
to give a cloudy suspension which was added dropwise to the
stirred succinimide solution at such a rate that the temperature
remained below 20 ꢂC. After the addition was completed, the
mixture was sonicated for an additional 1 h. To this suspension was
d
¼ 2.24 (s, 3H, CH3), 2.68 (d, J ¼ 5.0 Hz, 1H, OH), 3.67 (t,
J ¼ 5.8 Hz, 2H, CH2N), 5.01e5.06 (m, 1H, CH), 5.12 (s, 2H, CH2), 5.17
(bs, 1H, NH), 7.19e7.50 (m, 9H) ppm. 13C NMR (175 MHz, CDCl3):
d
¼ 7.7 (CH3), 45.5 (CH2), 65.9 (CH), 67.0 (CH2), 111.1 (CH), 113.2 (C),
119.5 (CH), 122.4 (CH), 124.6 (CH), 128.1 (2xCH), 128.2 (CH), 128.5
(2xCH), 129.6 (C), 136.2 (C), 150.4 (C), 153.9 (C), 157.0 (CO) ppm. IR,
KBr (cmꢀ1): 3351, 3060, 2931, 1692, 1544, 1451, 1249, 1069, 1003,
749. Anal. calcd for C19H19NO4: C, 70.14; H, 5.88; N, 4.30. Found: C,
69.98; H, 5.77; N, 4.39. MS EI: m/z 325 (Mþ, 2), 161 (100), 91 (60), 77
(24), 79 (21), 174 (19), 105 (19), 159 (16), 65 (13), 51 (12), 131 (11),
162 (11), 115 (11), 103 (11).
added dropwise a solution of benzofuryl a-bromo ketone 19e22
(10.0 mmol) in DMF (11 mL) and the reaction mixture was stirred at
rt for 24 h. Water (90 mL) was added and the mixture was extracted
with dichloromethane (3 ꢁ 20 mL). The combined extracts were
dried over anhydrous MgSO4, filtered, and concentrated under
reduced pressure. The residue was purified by column chroma-
tography on silica gel (hexane/ethyl acetate/dichloromethane/
methanol, 5:3:1:0.5) and crystallized from ethanol to give white
solid products.
4.13. Benzyl (R)-(2-(3,7-dimethylbenzofuran-2-yl)-2-hydroxyethyl)
carbamate 38
Prepared by transfer hydrogenation of 34 (0.25 g, 0.7 mmol)
following the procedure described in 4.4: light yellow solid, 0.20 g,
4.15.1. 1-(2-(Benzofuran-2-yl)-2-oxoethyl)pyrrolidine-2,5-dione 39
1.04 g, 43% yield, mp 145e147 ꢂC. 1H NMR (300 MHz, CDCl3):
95% yield, mp 88e92 ꢂC, ½a D20
ꢃ
¼ ꢀ15.06 (c 3.34, CHCl3), 97% ee,
d
¼ 2.87 (s, 4H, 2xCH2), 4.96 (s, 2H, CH2), 7.33 (ddd, J ¼ 7.8, 6.9,
determined by HPLC analysis, Daicel Chiralcel OD-H column
0.9 Hz, 1H), 7.51 (td, J ¼ 7.2, 1.3 Hz, 1H), 7.58 (dt, J ¼ 9.3, 0.9 Hz, 1H),
250 ꢁ 4.6 mm, 5
(S) 10.50 min, 1.70%, (R) 18.32 min, 98.30%. 1H NMR (700 MHz,
CDCl3):
mm, hexane/isopropanol 60:40, flow 0.6 mL/min,
7.61 (d, J ¼ 0.9 Hz, 1H), 7.72 (ddd, J ¼ 7.8, 1.4, 0.9 Hz, 1H) ppm. 13
C
NMR (50 MHz, CDCl3):
d
¼ 28.3 (2xCH2), 44.6 (CH2), 112.5 (CH),
d
¼ 2.23 (s, 3H, CH3), 2.48 (s, 3H, CH3), 2.68 (d, J ¼ 3.3 Hz,1H,
113.6 (CH), 123.5 (CH), 124.2 (CH), 126.7 (C), 128.8 (CH), 150.6 (C),
155.7 (C), 176.5 (2xCO), 181.8 (CO) ppm. IR, neat (cmꢀ1): 3282, 2930,
1771, 1693, 1419, 1392, 1170, 1006, 758, 616. Anal. calcd for
OH), 3.61e3.64 (dd, J ¼ 13.8, 6.0 Hz, 1H, CH2N), 3.73 (dd, J ¼ 13.8,
7.5 Hz, 1H, CH2N), 5.05 (bs, 1H, CH), 5.12 (s, 2H, CH2), 5.19 (bs, 1H,
NH), 7.08 (ddt, J ¼ 7.5, 1.5, 0.6 Hz, 1H), 7.15 (t, J ¼ 7.5 Hz, 1H),
C14H11NO4: C, 65.39; H, 4.31; N, 5.44. Found: C, 65.09; H, 4.53; N,
7.27e7.40 (m, 6H) ppm. 13C NMR (175 MHz, CDCl3):
d
¼ 7.8 (CH3),
5.86.
14.9 (CH3), 45.6 (CH2), 65.9 (CH), 66.9 (CH2), 113.4 (C), 116.9 (CH),
121.3 (C), 122.5 (CH), 125.5 (CH), 126.9 (CH), 127.6 (C), 128.0 (CH),
128.1 (CH), 128.5 (2xCH), 129.1 (C), 136.3 (C), 150.2 (C), 152.9 (CO)
ppm. IR, KBr (cmꢀ1): 3370, 3259, 2922, 2851, 2342,1707,1656,1554,
1457, 1274. Anal. calcd for C20H21NO4: C, 70.78; H, 6.23; N, 4.13.
Found: C, 70.85; H, 6.31; N, 4.28.
4.15.2. 1-(2-(7-Ethylbenzofuran-2-yl)-2-oxoethyl)pyrrolidine-2,5-
dione 40
1.37 g, 51%, mp 146e147 ꢂC. 1H NMR (200 MHz, CDCl3):
d
¼ 1.38
(t, J ¼ 7.6 Hz, 3H, CH3), 2.88 (s, 4H, 2xCH2), 2.99 (q, J ¼ 7.6 Hz, 2H,
CH2), 4.99 (s, 2H, CH2), 7.23e7.37 (m, 2H), 7.56 (dd, J ¼ 7.4, 1.6 Hz,
Please cite this article in press as: Tafelska-Kaczmarek A, et al., Asymmetric synthesis of benzofuryl
hydrogenation of -functionalized ketones, Tetrahedron (2017), http://dx.doi.org/10.1016/j.tet.2017.05.059
b-amino alcohols by the transfer
a

A. Tafelska-Kaczmarek et al. / Tetrahedron xxx (2017) 1e15
13
1H), 7.61 (s, 1H) ppm. 13C NMR (75 MHz, CDCl3):
d
¼ 13.9 (CH3), 22.7
2938, 1775, 1714, 1681, 1416, 1391, 1155, 1009, 944, 754, 713. Anal.
calcd for C20H15NO4: C, 72.06; H, 4.53; N, 4.20. Found: C, 72.12; H,
4.48; N, 4.37.
(CH2), 28.3 (2xCH2), 44.7 (CH2), 113.9 (CH), 120.9 (CH), 124.4 (CH),
126.4 (C), 127.7 (CH), 128.9 (C), 150.4 (C), 154.5 (C), 176.5 (2xCO),
181.8 (CO) ppm. IR, neat (cmꢀ1): 3311, 2932, 1765, 1714, 1410, 1392,
1314, 1009, 720, 530. Anal. calcd for C16H15NO4: C, 67.36; H, 5.30; N,
4.91. Found: C, 66.97; H, 5.27; N, 5.15.
4.16.3. 2-(2-(3-Methylbenzofuran-2-yl)-2-oxoethyl)isoindoline-
1,3-dione 45
2.58 g, 81% yield, mp 210e212 ꢂC. 1H NMR (200 MHz, CDCl3):
4.15.3. 1-(2-(3-Methylbenzofuran-2-yl)-2-oxoethyl)pyrrolidine-
2,5-dione 41
d
¼ 2.60 (s, 3H, CH3), 5.16 (s, 2H, CH2), 7.34 (ddd, J ¼ 8.0, 7.2, 2.8 Hz,
1H), 7.53 (dd, J ¼ 2.6, 1.0 Hz, 1H), 7.55 (d, J ¼ 1.2 Hz, 1H), 7.69 (dt,
J ¼ 7.6, 1.0 Hz, 1H), 7.76 (dd, J ¼ 5.6, 3.0 Hz, 2H), 7.91 (dd, J ¼ 5.4,
1.40 g, 55% yield, mp 143e147 ꢂC. 1H NMR (300 MHz, CDCl3):
d
¼ 2.59 (s, 3H, CH3), 2.87 (s, 4H, 2xCH2), 4.98 (s, 2H, CH2), 7.34 (ddd,
3.2 Hz, 2H) ppm. 13C NMR (50 MHz, CDCl3):
d
¼ 9.3 (CH3), 44.9
J ¼ 7.8, 4.8, 3.3 Hz, 1H), 7.51 (dd, J ¼ 1.5, 0.9 Hz, 1H), 7.53 (d,
(CH2), 112.2 (CH), 121.7 (CH), 123.5 (2xCH), 126.7 (C), 126.8 (CH),
128.9 (C), 132.2 (C), 134.1 (2xCH), 146.2 (C), 154.4 (C), 167.9 (CO),
184.3 (2xCO) ppm. IR, neat (cmꢀ1): 3299, 2929, 1776, 1712, 1693,
1426, 1390, 1159, 1010, 947, 754, 712. Anal. calcd for C19H13NO4: C,
71.47; H, 4.10; N, 4.38. Found: C, 71.52; H, 4.29; N, 4.49.
J ¼ 1.2 Hz, 1H), 7.78 (dt, J ¼ 7.8, 0.9 Hz, 1H) ppm. 13C NMR (75 MHz,
CDCl3):
d
¼ 9.3 (CH3), 28.3 (2xCH2), 45.4 (CH2), 112.2 (CH), 121.7
(CH), 123.5 (CH), 126.8 (C), 128.9 (CH), 146.1 (C), 154.4 (C), 176.7
(2xCO), 183.5 (CO) ppm. IR, neat (cmꢀ1): 3267, 2944, 1768, 1680,
1410, 1391, 1171, 1010, 769. Anal. calcd for C15H13NO4: C, 66.41; H,
4.83; N, 5.16. Found: C, 66.62; H, 4.92; N, 5.04.
4.17. (R)-1-(2-(Benzofuran-2-yl)-2-hydroxyethyl)pyrrolidine-2,5-
dione 46
4.15.4. 1-(2-(3,7-Dimethylbenzofuran-2-yl)-2-oxoethyl)
pyrrolidine-2,5-dione 42
Prepared by transfer hydrogenation of 39 (0.26 g, 1.0 mmol)
following the procedure described in 4.4: white solid, 0.24 g, 95%
1.29 g, 48%, mp 172e175 ꢂC. 1H NMR (300 MHz, CDCl3):
d
¼ 2.55
(s, 3H, CH3), 2.59 (s, 3H, CH3), 2.88 (s, 4H, 2xCH2), 5.01 (s, 2H, CH2),
yield, mp 154e157 ꢂC, ½a D23
¼ þ26.47 (c 0.34, CHCl3), 94% ee,
ꢃ
7.21e7.23 (m, 1H), 7.31 (ddd, J ¼ 7.5, 1.5, 0.9 Hz, 1H), 7.50 (ddd,
determined by HPLC analysis, Daicel Chiralcel OD-H column
J ¼ 7.5,1.5, 0.9 Hz,1H) ppm. 13C NMR (50 MHz, CDCl3):
d
¼ 9.4 (CH3),
250 ꢁ 4.6 mm, 5
(S) 21.89 min, 3.11%, (R) 22.83 min, 96.88%. 1H NMR (300 MHz,
CDCl3):
mm, hexane/isopropanol 60:40, flow 0.5 mL/min,
14.8 (CH3), 28.3 (2xCH2), 45.4 (CH2), 119.1 (CH), 122.4 (C), 123.7
(CH), 127.2 (C), 128.4 (C), 129.5 (CH), 146.0 (C), 153.6 (C), 176.7
(2xCO), 183.4 (CO) ppm. IR, neat (cmꢀ1): 3276, 2942, 1769, 1682,
1418, 1392, 1171, 1005, 752, 642. Anal. calcd for C16H15NO4: C, 67.36;
H, 5.30; N, 4.91. Found: C, 67.41; H, 5.37; N, 4.78.
d
¼ 2.76 (s, 4H, 2xCH2), 3.07 (d, J ¼ 7.5 Hz, 1H, OH), 3.99 (dd,
J ¼ 14.1, 3.6 Hz, 1H, CH2N), 4.12 (dd, J ¼ 14.1, 8.7 Hz, 1H, CH2N), 5.10
(dd, J ¼ 8.4, 3.3 Hz, 1H, CH), 6.73 (t, J ¼ 0.9 Hz, 1H), 7.21 (td, J ¼ 7.2,
1.2 Hz, 1H), 7.28 (td, J ¼ 7.2, 1.5 Hz,1H), 7.45e7.49 (m, 1H), 7.55 (ddd,
J ¼ 7.2, 1.5, 0.6 Hz, 1H) ppm. 13C NMR (75 MHz, CDCl3):
d
¼ 28.1
4.16. General procedure for the synthesis of benzofuryl
phthalimido ketones
a-
(2xCH2), 43.7 (CH2), 66.5 (CH), 103.8 (CH), 111.3 (CH), 121.2 (CH),
122.9 (CH), 124.5 (CH), 127.8 (CH), 154.9 (C), 155.9 (C), 177.7 (2xCO)
ppm. IR, neat (cmꢀ1): 3331, 3270, 2926, 1776, 1715, 1683, 1415, 1391,
1157, 1012, 770, 743. Anal. calcd for C14H13NO4: C, 64.86; H, 5.05; N,
5.40. Found: C, 64.75; H, 5.16; N, 5.75.
To a solution of benzofuryl a-bromo ketone 19e21 (10.0 mmol)
in DMF (10 mL) was added potassium phthalimide (2.03 g,
11.0 mmol) and stirred at rt for 3 h. The reaction mixture was
poured into water (50 mL) and extracted with chloroform
(2 ꢁ 15 mL). The combined extracts were dried over anhydrous
MgSO4, filtered, and concentrated under reduced pressure. The
residue was crystallized from ethanol to give white solid products.
4.18. (R)-1-(2-(7-Ethylbenzofuran-2-yl)-2-hydroxyethyl)
pyrrolidine-2,5-dione 47
Prepared by transfer hydrogenation of 40 (0.28 g, 1.0 mmol)
following the procedure described in 4.4: white solid, 0.25 g, 89%
4.16.1. 2-(2-(Benzofuran-2-yl)-2-oxoethyl)isoindoline-1,3-dione 43
1.62 g, 53% yield, mp 201e203 ꢂC. 1H NMR (300 MHz, CDCl3):
yield, mp 152e154 ꢂC, ½a D25
¼ þ44.90 (c 1.25, CHCl3), 91% ee,
ꢃ
determined by HPLC analysis, Daicel Chiralcel OJ column
d
¼ 5.15 (s, 2H, CH2), 7.35 (dd, J ¼ 7.2, 0.9 Hz, 1H), 7.52 (dd, J ¼ 7.2,
250 ꢁ 4.6 mm, 10
(S) 51.81 min, 4.34%, (R) 55.64 min, 95.66%. 1H NMR (300 MHz,
CDCl3):
mm, hexane/isopropanol 90:10, flow 0.8 mL/min,
1.2 Hz, 1H), 7.61 (dd, J ¼ 8.4, 0.9 Hz, 1H), 7.64 (d, J ¼ 0.9 Hz, 1H), 7.54
(dt, J ¼ 8.1, 0.9 Hz, 1H), 7.76 (dd, J ¼ 5.4, 3.0 Hz, 2H), 7.91 (dd, J ¼ 5.7,
d
¼ 1.34 (t, J ¼ 7.5 Hz, 3H, CH3), 1.59 (bs, 1H, OH), 2.75 (s, 4H,
3.0 Hz, 2H) ppm. 13C NMR (75 MHz, CDCl3):
d
¼ 44.1 (CH2), 112.5
2xCH2), 2.93 (q, J ¼ 7.5 Hz, 2H, CH2), 3.97 (dd, J ¼ 14.1, 3.6 Hz, 1H,
CH2N), 4.15 (dd, J ¼ 14.1, 8.7 Hz, 1H, CH2N), 5.11 (dd, J ¼ 8.7, 3.6 Hz,
1H, CH), 6.72 (d, J ¼ 0.9 Hz, 1H), 7.11 (dd, J ¼ 7.5, 1.5 Hz, 1H), 7.16 (t,
J ¼ 7.5 Hz, 1H), 7.37 (dd, J ¼ 7.5, 1.5 Hz, 1H) ppm. 13C NMR (75 MHz,
(CH), 113.6 (CH), 123.5 (CH), 123.6 (2xCH), 124.2 (CH), 126.7 (C),
128.7 (CH), 132.1 (C), 134.1 (2xCH), 150.7 (C), 155.7 (C), 167.7 (CO),
182.6 (2xCO) ppm. IR, neat (cmꢀ1): 3315, 2936, 1774, 1710, 1683,
1415, 1392, 1160, 1100, 1003, 930, 753, 710. Anal. calcd for
C
4.60.
CDCl3):
d
¼ 14.1 (CH3), 22.7 (CH2), 28.1 (2xCH2), 43.7 (CH2), 66.6
18H11NO4: C, 70.82; H, 3.63; N, 4.58. Found: C, 70.96; H, 3.72; N,
(CH), 104.1 (CH), 118.7 (CH), 123.1 (CH), 123.7 (CH), 124.4 (C), 127.8
(C), 153.5 (C), 155.5 (C), 177.7 (2xCO) ppm. IR, neat (cmꢀ1): 3310,
3267, 2930, 1772, 1716, 1676, 1405, 1392, 1170, 1008, 755, 715. Anal.
calcd for C16H17NO4: C, 66.89; H, 5.96; N, 4.87. Found: C, 66.50; H,
5.76; N, 4.88.
4.16.2. 2-(2-(7-Ethylbenzofuran-2-yl)-2-oxoethyl)isoindoline-1,3-
dione 44
2.30 g, 69%, mp 184e185 ꢂC. 1H NMR (300 MHz, CDCl3):
d
¼ 1.38
(t, J ¼ 7.5 Hz, 3H, CH3). 2.99 (q, J ¼ 7.5 Hz, 2H, CH2), 5.16 (s, 2H, CH2),
7.27 (t, J ¼ 7.5 Hz, 1H), 7.34 (ddd, J ¼ 7.5, 1.5, 0.9 Hz, 1H), 7.56 (dd,
J ¼ 7.8, 1.5 Hz,1H), 7.64 (s, 1H), 7.76 (dd, J ¼ 5.4, 3.0 Hz, 2H), 7.91 (dd,
4.19. (R)-1-(2-Hydroxy-2-(3-methylbenzofuran-2-yl)ethyl)
pyrrolidine-2,5-dione 48
J ¼ 5.7, 3.0 Hz, 2H) ppm. 13C NMR (75 MHz, CDCl3):
d
¼ 13.9 (CH3),
Prepared by transfer hydrogenation of 41 (0.13 g, 0.5 mmol)
following the procedure described in 4.4: white solid, 0.11 g, 79%
22.7 (CH2), 44.2 (CH2), 113.9 (CH), 120.9 (CH), 123.6 (2xCH), 124.4
(CH), 126.4 (C), 127.7 (CH), 128.9 (C), 132.1 (C), 134.1 (2xCH), 150.4
(C), 154.5 (C), 167.7 (CO), 182.6 (2xCO) ppm. IR, neat (cmꢀ1): 3309,
yield, mp 150e151 ꢂC, ½a D32
¼ þ35.79 (c 0.95, CHCl3), 80% ee,
ꢃ
determined by HPLC analysis, Daicel Chiralcel OJ column
Please cite this article in press as: Tafelska-Kaczmarek A, et al., Asymmetric synthesis of benzofuryl
hydrogenation of -functionalized ketones, Tetrahedron (2017), http://dx.doi.org/10.1016/j.tet.2017.05.059
b-amino alcohols by the transfer
a

14
A. Tafelska-Kaczmarek et al. / Tetrahedron xxx (2017) 1e15
250 ꢁ 4.6 mm, 10
m
m, hexane/isopropanol 85:15, flow 0.8 mL/min,
(bs, 1H, OH), 2.87 (q, J ¼ 7.5 Hz, 2H, CH2), 4.17 (dd, J ¼ 14.4, 4.2 Hz,
1H, CH2N), 4.27 (dd, J ¼ 14.4, 8.1 Hz, 1H, CH2N), 5.21 (dd, J ¼ 8.1,
4.2 Hz, 1H, CH), 6.74 (t, J ¼ 0.6 Hz, 1H), 7.08e7.16 (m, 2H), 7.36 (dd,
J ¼ 7.5, 1.5 Hz, 1H), 7.72 (dd, J ¼ 5.7, 3.0 Hz, 2H), 7.86 (dd, J ¼ 5.4,
(S) 47.35 min, 10.10%, (R) 56.30 min, 89.90%. 1H NMR (200 MHz,
CDCl3):
d
¼ 2.27 (s, 3H, CH3), 2.76 (s, 4H, 2xCH2), 2.80 (d, J ¼ 8.0 Hz,
1H, OH), 3.83 (dd, J ¼ 14.0, 3.6 Hz, 1H, CH2N), 4.27 (dd, J ¼ 14.0,
9.4 Hz, 1H, CH2N), 5.15 (ddd, J ¼ 9.2, 7.8, 3.6 Hz, 1H, CH), 7.23 (td,
J ¼ 6.0, 1.6 Hz, 1H), 7.29 (td, J ¼ 6.6, 1.6 Hz, 1H), 7.41e7,51 (m, 2H)
3.0 Hz, 2H) ppm. 13C NMR (50 MHz, CDCl3):
d
¼ 14.0 (CH3), 22.7
(CH2), 43.1 (CH2), 67.0 (CH), 104.1 (CH), 118.6 (CH), 123.0 (CH), 123.5
(2xCH), 123.6 (CH), 127.5 (C), 127.8 (C), 131.9 (C), 134.2 (2xCH), 155.7
(C), 168.6 (2xCO) ppm. IR, neat (cmꢀ1): 3345, 2937, 1777, 1715, 1695,
1392, 1283, 1076, 1003, 944, 754, 713, 529. Anal. calcd for
ppm. 13C NMR (75 MHz, CDCl3):
d
¼ 1.0 (CH3), 7.7 (CH3). 28.2
(2xCH2), 43.5 (CH2), 64.3 (CH), 111.2 (CH), 113.1 (C), 119.6 (CH), 122.4
(CH), 124.7 (CH), 129.5 (C), 149.7 (C), 154.0 (C), 177.6 (2xCO) ppm. IR,
neat (cmꢀ1): 3326, 3266, 2935, 1777, 1716, 1684, 1418, 1392, 1318,
1170, 1011, 772, 756. Anal. calcd for C15H15NO4: C, 65.92; H, 5.53; N,
5.12. Found: C, 65.64; H, 5.66; N, 5.19.
C20H17NO4: C, 71.63; H, 5.11; N, 4.18. Found: C, 71.42; H, 5.27; N,
4.19.
4.23. (R)-2-(2-Hydroxy-2-(3-methylbenzofuran-2-yl)ethyl)
4.20. (R)-1-(2-(3,7-Dimethylbenzofuran-2-yl)-2-hydroxyethyl)
isoindoline-1,3-dione 52
pyrrolidine-2,5-dione 49
Prepared by transfer hydrogenation of 45 (51 mg, 0.16 mmol)
following the procedure described in 4.4: white solid, 47 mg, 92%
Prepared by transfer hydrogenation of 42 (0.14 g, 0.5 mmol)
following the procedure described in 4.4: white solid, 0.11 g, 76%
yield, mp 130e133 ꢂC, ½a D25
¼ þ25.15 (c 0.55, CHCl3), 84% ee,
ꢃ
yield, mp 175e177 ꢂC, ½a D25
ꢃ
¼ þ36.49 (c 0.64, CHCl3), 79% ee,
determined by HPLC analysis, Daicel Chiralcel OJ column
determined by HPLC analysis, Daicel Chiralcel OJ column
250 ꢁ 4.6 mm, 10
(S) 46.95 min, 8.20%, (R) 63.66 min, 91.80%. 1H NMR (300 MHz,
CDCl3):
mm, hexane/isopropanol 90:10, flow 0.8 mL/min,
250 ꢁ 4.6 mm, 10
(S) 35.40 min, 10.59%, (R) 41.61 min, 89.41%. 1H NMR (300 MHz,
CDCl3):
mm, hexane/isopropanol 90:10, flow 0.8 mL/min,
d
¼ 1.58 (bs, 1H, OH), 2.26 (s, 3H, CH3), 4.03 (dd, J ¼ 14.1,
d
¼ 2.26 (s, 3H, CH3), 2.50 (d, J ¼ 7.5, 1H, OH), 2.51 (s, 3H,
3.9 Hz, 1H, CH2N), 4.36 (dd, J ¼ 14.1, 9.0 Hz, 1H, CH2N), 5.24 (dd,
J ¼ 9.0, 4.2 Hz, 1H, CH), 7.23 (td, J ¼ 7.2, 1.2 Hz, 1H), 7.29 (td, J ¼ 7.2,
1.5 Hz,1H), 7.42e7.49 (m, 2H), 7.72 (dd, J ¼ 5.4, 3.0 Hz, 2H), 7.87 (dd,
CH3), 2.77 (s, 4H, 2xCH2), 3.82 (dd, J ¼ 14.1, 3.6 Hz, 1H, CH2N), 4.25
(dd, J ¼ 14.1, 9.6 Hz, 1H, CH2N), 5.16 (dd, J ¼ 9.6, 3.6 Hz, 1H, CH), 7.09
(ddd, J ¼ 7.5, 1.5, 0.6 Hz, 1H), 7.14 (t, J ¼ 7.2 Hz, 1H), 7.31 (ddd, J ¼ 7.5,
J ¼ 5.4, 3.0 Hz, 2H) ppm. 13C NMR (175 MHz, CDCl3):
d
¼ 8.8 (CH3),
1.5, 0.6 Hz, 1H) ppm. 13C NMR (75 MHz, CDCl3):
d
¼ 7.8 (CH3), 14.9
43.8 (CH2), 65.9 (CH), 112.2 (CH), 120.6 (CH), 123.5 (CH), 124.5
(2xCH),124.7 (C), 125.7 (CH), 132.9 (C), 135.1 (2xCH),135.3 (C),150.8
(C), 155.1 (C), 169.6 (2xCO) ppm. IR, neat (cmꢀ1): 3327, 2938, 1776,
1714, 1700, 1412, 1009, 947, 757, 714. Anal. calcd for C19H15NO4: C,
71.02; H, 4.71; N, 4.36. Found: C, 70.86; H, 4.55; N, 4.44.
(CH3). 28.1 (2xCH2), 43.5 (CH2), 64.3 (CH),113.3 (C),116.9 (CH), 121.4
(C), 122.5 (CH), 125.6 (CH), 128.9 (C), 149.4 (C), 153.0 (C), 177.6
(2xCO) ppm. IR, neat (cmꢀ1): 3320, 3287, 2933, 1776, 1710, 1686,
1415,1390,1165, 1004, 753, 712. Anal. calcd for C16H17NO4: C, 66.89;
H, 5.96; N, 4.87. Found: C, 66.35; H, 6.16; N, 4.89.
4.24. General procedure for deprotection of the succinimides
4.21. (R)-2-(2-(Benzofuran-2-yl)-2-hydroxyethyl)isoindoline-1,3-
dione 50
A mixture of the corresponding benzofuryl succinimido alcohol
46e49 (0.50 mmol) and 20% aqueous sodium hydroxide (2.4 mL) in
95% ethanol (15 mL) was stirred at reflux for 24 h. After cooling to
rt, the precipitate was filtered off and the reaction mixture was
concentrated in vacuo. The residue was refluxed with MTBE (8 mL)
and methylene chloride (4 mL) for 1 h. Next, the reaction mixture
was filtered on a Celite pad and the filtrate decolored by stirring
with Norit for 2 h. After filtration the solvents were removed under
reduced pressure to give white solid products.
Prepared by transfer hydrogenation of 43 (50 mg, 0.16 mmol)
following the procedure described in 4.4: white solid, 48 mg, 98%
yield, mp 158e160 ꢂC, ½a D23
¼ þ28.74 (c 0.42, CHCl3), 91% ee,
ꢃ
determined by HPLC analysis, Daicel Chiralcel OJ column
250 ꢁ 4.6 mm, 10
(S) 35.67 min, 4.62%, (R) 40.90 min, 95.38%. 1H NMR (300 MHz,
CDCl3):
mm, hexane/isopropanol 80:20, flow 0.7 mL/min,
d
¼ 3.05 (d, J ¼ 6.9 Hz, 1H, OH), 4.18 (dd, J ¼ 14.4, 4.2 Hz, 1H,
CH2N), 4.27 (dd, J ¼ 14.4, 8.1 Hz, 1H, CH2N), 5.19 (tdd, J ¼ 7.6, 4.2,
1.2 Hz, 1H, CH), 6.76 (t, J ¼ 0.9 Hz, 1H), 7.21 (td, J ¼ 7.2, 1.2 Hz, 1H),
7.28 (td, J ¼ 7.2, 1.5 Hz, 1H), 7.46 (ddd, J ¼ 8.4, 1.5, 0.9 Hz, 1H), 7.54
(ddd, J ¼ 7.8, 1.5, 0.9 Hz, 1H), 7.74 (dd, J ¼ 5.7, 3.0 Hz, 2H), 7.87 (dd,
4.24.1. (R)-2-Amino-1-(benzofuran-2-yl)ethanol 14
59 mg, 67% yield, mp 126e127 ꢂC; ½a D25
¼ þ34.48 (c 0.93,
ꢃ
MeOH). 1H and 13C NMR spectra were the same as described in 4.6.1.
J ¼ 5.4, 3.0 Hz, 2H) ppm. 13C NMR (75 MHz, CDCl3):
d
¼ 42.9 (CH2),
67.0 (CH), 103.9 (CH), 111.3 (CH), 121.2 (CH), 122.9 (CH), 123.6
(2xCH), 124.4 (CH), 127.8 (C), 131.8 (C), 134.2 (2xCH), 154.9 (C), 155.9
(C), 168.7 (2xCO) ppm. IR, neat (cmꢀ1): 3333, 2933, 1774, 1713, 1698,
1392, 1252, 1067, 1004, 942, 757, 708, 529. Anal. calcd for
4.24.2. (R)-2-Amino-1-(7-ethylbenzofuran-2-yl)ethanol 15
82 mg, 80% yield, mp 83e85 ꢂC; ½a D25
¼ þ32.84 (c 0.70, MeOH).
ꢃ
1H and 13C NMR spectra were the same as described in 4.6.2.
C
4.69.
18H13NO4: C, 70.35; H, 4.26; N, 4.56. Found: C, 70.26; H, 4.35; N,
4.24.3. (R)-2-Amino-1-(3-methylbenzofuran-2-yl)ethanol 16
79 mg, 83% yield, mp 84e86 ꢂC; ½a D25
¼ þ11.04 (c 0.52, MeOH).
ꢃ
1H and 13C NMR spectra were the same as described in 4.6.3.
4.22. (R)-2-(2-(7-Ethylbenzofuran-2-yl)-2-hydroxyethyl)
isoindoline-1,3-dione 51
4.24.4. (R)-2-Amino-1-(3,7-dimethylbenzofuran-2-yl)ethanol 17
80 mg, 78% yield, mp 120e123 ꢂC; ½a D23
¼ þ11.24 (c 0.30, MeOH).
ꢃ
Prepared by transfer hydrogenation of 44 (50 mg, 0.15 mmol)
following the procedure described in 4.4: white solid, 38 mg, 76%
1H and 13C NMR spectra were the same as described in 4.6.4.
yield, ½a 2D3
ꢃ
¼ þ33.15 (c 0.83, CHCl3), 89% ee, determined by HPLC
4.25. General procedure for deprotection of the phthalimides
analysis, Daicel Chiralcel OJ column 250 ꢁ 4.6 mm, 10
m
m, hexane/
isopropanol 90:10, flow 0.7 mL/min, (S) 40.16 min, 5.43%, (R)
A mixture of the corresponding benzofuryl phthalimido alcohol
50e52 (0.30 mmol) and hydrazine hydrate (22.5 mg, 0.45 mmol) in
95% ethanol (5 mL) was stirred at reflux for 5 h. After addition of
44.30 min, 94.57%.
1H NMR (300 MHz, CDCl3):
d
¼ 1.28 (t, J ¼ 7.5 Hz, 3H, CH3), 1.59
Please cite this article in press as: Tafelska-Kaczmarek A, et al., Asymmetric synthesis of benzofuryl
hydrogenation of -functionalized ketones, Tetrahedron (2017), http://dx.doi.org/10.1016/j.tet.2017.05.059
b-amino alcohols by the transfer
a

A. Tafelska-Kaczmarek et al. / Tetrahedron xxx (2017) 1e15
5876e5878.
15
concd. HCl (0.04 mL) the resulting mixture was again refluxed for
1 h. After cooling to rt, the precipitate was filtered off and the
filtrate was evaporated in vacuo. The residue was dissolved in water
(8 mL) and aqueous potassium hydroxide (5 mL) was added. The
mixture was extracted with dichloromethane (2 ꢁ 10 mL). The
combined extracts were dried over anhydrous MgSO4, filtered, and
concentrated under reduced pressure to give white solid products.
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4.25.1. (R)-2-Amino-1-(benzofuran-2-yl)ethanol 14
27 mg, 50% yield, mp 125e126 ꢂC; ½a D25
¼ þ33.20 (c 0.55,
ꢃ
MeOH). 1H and 13C NMR spectra were the same as described in 4.6.1.
4.25.2. (R)-2-Amino-1-(7-ethylbenzofuran-2-yl)ethanol 15
27 mg, 44% yield, mp 82e84 ꢂC; ½a D25
¼ þ31.00 (c 0.84, MeOH).
ꢃ
1H and 13C NMR spectra were the same as described in 4.6.2.
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J Org Chem. 2005;70(23):
4.25.3. (R)-2-Amino-1-(3-methylbenzofuran-2-yl)ethanol 16
9424e9429.
28 mg, 48% yield, mp 90e93 ꢂC; ½a D25
¼ þ12.62 (c 0.47, MeOH).
ꢃ
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Pietrasiak Katarzyna, Kozakiewicz Anna, Zaidlewicz Marek. Tetrahedron Asym.
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Acknowledgment
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The authors thank the Department of Chemistry, Nicolaus
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Supplementary data related to this article can be found at http://
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Please cite this article in press as: Tafelska-Kaczmarek A, et al., Asymmetric synthesis of benzofuryl
hydrogenation of -functionalized ketones, Tetrahedron (2017), http://dx.doi.org/10.1016/j.tet.2017.05.059
b-amino alcohols by the transfer
a