Dynamic Kinetic Resolution for Construction of Three Transannular Stereocenters of Dihydrobenzofuranols

Article abstract of DOI:10.1021/acs.joc.8b01613

A handy and effective method was established to obtain the cis-2,3-dihydrobenzofuranols having three stereocenters, involving asymmetric transfer hydrogenation of benzofuranones via dynamic kinetic resolution. The general applicability of this method was examined with different benzofuran-3-(2H)-ones, and stereoselectivities of 85-99% ee and up to 98/2 dr were obtained.

Full text of DOI:10.1021/acs.joc.8b01613

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Note
Dynamic Kinetic Resolution for Construction of Three
Transannular Stereocenters of Dihydrobenzofuranols
Lizhen Fang, Fangfei Zhao, Shuyu Hu, Lili Han, Xiaojing Hu, Mingyong Wang, Qianqian Sun, and Huipan Wu
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b01613 • Publication Date (Web): 17 Sep 2018
Downloaded from http://pubs.acs.org on September 17, 2018
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The Journal of Organic Chemistry
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Dynamic Kinetic Resolution for Construction of Three
Transannular Stereocenters of Dihydrobenzofuranols
a,
a
a
a
b
c
a
a
1
1
1
1
1
1
1
1
1
1
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2
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0
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8
9
0
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0
Lizhen Fang, * Fangfei Zhao, Shuyu Hu, Lili Han, Xiaojing Hu, Mingyong Wang, Qianqian Sun, Huipan Wu
a
School of Pharmacy, Xinxiang Medical University, Xinxiang, Henan 453003, People’s Republic of China
b
The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453003, People’s Republic of China
School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, Henan 453003, People’s Republic of China
c
Supporting Information
3
a (0.5 mol %)
Ts
N
O
O
HO
O
HCOONa (5 equiv.)
Ph
Ph
R
R
3a =
Ru
Cl
CTAB (20 mol %)
CH OH, 65 ºC
N
3
O
OH
examples
H
2
7
R= CH , i-Pr, CH Ph, etc.
85-99% ee, dr >98:2, yield: 31-90%
3
2
ABSTRACT: A handy and effective method was established to obtain the cisꢀ2,3ꢀdihydrobenzofuranols having three stereocenters,
involving asymmetric transfer hydrogenation of benzofuranones via dynamic kinetic resolution. The general applicability of this
method was examined with different benzofuranꢀ3ꢀ(2H)ꢀones and stereoselectivities of 85%ꢀ99% ee and up to 98/2 dr were obꢀ
tained.
Multiple stereocenters are common and important in natuꢀ
In our investigation of the DKRꢀATH method for the prepꢀ
aration of dihydrobenzofuranols, we obtained a unique subꢀ
1
2
3
8
ral products, drugs and organic synthesis motifs. However,
it is challenging to construct these chiral motifs. Methods
which produce the desired multiple stereocenters in one step
are highly valuable for organic synthesis; for example, the
strate 1a and reduced it using the catalyst RuCl(pꢀ
cymene)[(R,R)ꢀTsDPEN] with the DKRꢀATH procedure. Unꢀ
expectedly, we obtained the products with a good selectivity
(Scheme 1). Chiral analysis showed that the reaction gave
only four products (Figure 1), and the main product with three
transannular cisꢀstereocenters was more than 99% ee after
purification. Their configurations were carefully determined
by xꢀray crystallography and comparison of the enantiomers
and racemates, respectively. We are very interested in this
result and continue to explore it.
4
5
pericyclic reaction and domino reactions. In recent years,
dynamic kinetic resolution through asymmetric transfer hyꢀ
6
drogenation (DKRꢀATH) has also been used as a potent
methodology to achieve various optically active compounds
7
with 1,2 or 1,3ꢀstereocenters. Up to this date, DKRꢀATH has
only been used to construct two stereocenters in a chiral comꢀ
pound, with the stereocenters close in space and on the same
side of a benzene ring. Construction of three stereocenters,
specifically the transannular stereocenters, by this method has
not been reported.
During our wide investigation of the chiral TsDPEN (Nꢀ(pꢀ
toluenesulfonyl)ꢀ1,2ꢀdiphenylethylenediamine)ꢀbased organꢀ
ometal complexes in the ATH reaction, two commercially
a
Scheme 1. DKRꢀATH of the Substrate 1a and xꢀray crystal structure of 2a
Ru-I (0.5 mol %)
HCOONa (5 equiv.)
O
O
O
OH
OH
OH
OH
HO
+
HO
O
CTAB (20 mol %)
CH Cl /H O, 25 ºC
OH
a (major)
OH
O
1a
2
2
2
2
2a′
Ts
O
O
Ph
Ph
N
OH
3a =
Ru
HO
+
HO
N
H
Cl
OH
OH
2
2a″
2
a″′
yield: 62%, 99% ee, and 91:9 dr
a
Displacement ellipsoids are drawn at the 40% probability level.
1
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a
Table 1. Optimization of Reaction of 1a
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
catalyst 3 (0.5 mol %)
HCOONa (5 equiv.)
Ts
O
O
Ph
Ph
N
OH
OH 3b =
Ru
O
PTC (20 mol %)
solvent, T, 12h
HO
N
Cl
O
H
2
OH
1
a
2a
b
entry
catalyst
solvent
temperature
yield of 2a
ee (%) of
dr (2a+2a'/
PTC
c
d
d
(
°C)
(%)
2a
2a"+2a‴)
1
3a
3b
3a
3a
3b
3a
3a
3a
3a
3a
3a
3a
CH Cl /H O 25
CTAB
CTAB
CTAB
CTAB
CTAB
none
62
9
99
99
99
99
90
99
99
99
99
99
99
99
91/9
85/15
95/5
98/2
88/12
95/5
96/4
95/5
96/4
94/6
97/3
94/6
2
2
2
2
CH Cl /H O 25
2 2 2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
3
MeOH
MeOH
25
65
45
63
32
10
43
63
62
34
53
26
4
5
CH Cl /H O 35
2 2 2
6
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
65
65
65
65
65
65
65
7
TAHS
DTAC
TTAC
TBAC
βꢀCD
8
9
10
1
1
a
1
2
TBAB
The reactions were run on a 1.0 mmol scale in a 25 mL sealed flask under the protection of argon. The solvent amount was 4 mL, and the
ratio of the coꢀsolvents was 1:1. Abbreviations: PTC, phase transfer catalyst; CTAB, cetyltrimethylammonium bromide; TAHS, tetrabuꢀ
tylammonium hydrogen sulfate; DTAC, dodecyltrimethylammonium chloride; TTAC, trimethyltetradecylammonium chloride; TBAC,
tetrabutylammonium chloride; βꢀCD, βꢀcyclodextrin; TBAB, tetrabutylammonium bromide. Isolated yield including the minor enantioꢀ
b
c
d
mer. Determined by HPLC analysis using a chiral column.
to the conventional CH Cl /H O solvent system, the polar
solvent MeOH obtained higher diastereomeric ratio (dr) values
Table 1, entries 2 and 3). In addition, the optimum temperaꢀ
ture and the phase transfer catalyst are crucial to achieving
high performance in the reactions.
2
2
2
(
With these optimized conditions in hand, we first wanted to
find out how varying the acetyl position at the benzene ring of
a influences the reaction for a transannular hydrogen transfer
1
system (Figure 2). So we designed the substrates 1 as in
Scheme 2. It should be noted that these commercially unavailꢀ
able substrates 1 were not easy to be obtained. Compounds 1
were prepared from the purchased starting materials 4a and
4c. A CꢀH activation method was carried out using the comꢀ
mercial compound 8 in order to prepare 4b (Scheme 2). The
substrate 1d proved too difficult to successfully prepare which
may be due to its extreme instability.
R3
1
R2
R1
1
1
1
1
a R =COCH
3
O
2
b R =COCH
3
OH
3
c R =COCH
3
Figure 1. HPLC analysisꢀspectra of the crude product of the
reaction of 1a . HPLC conditions: CHIRALPAK IA column;
nꢀhexane/iꢀPrOH=92/8; 280 nm; 0.5 mL⋅min ; 35˚C.
4
R4
O
d R =COCH
3
a
a
®
1
Remaining R groups = H
ꢀ
1
Figure 2. The designed substrates 1.
available organometallic complexes, 3a (RuCl(pꢀcymene)
[(R,R)ꢀTsDPEN]) and 3b (RuCl[(R,R)ꢀTsDPEN] (mesityꢀ
lene)), combined with different solvents, phase transfer cataꢀ
lysts, and reaction temperatures, were screened to compare
their catalytic properties. The highest selectivity and yield was
obtained under the conditions of entry 4 (Table 1). Compared
Next, we examined the reaction with compounds 1 under
the optimum conditions (Table 1, entry 4). Satisfactorily, all
the reactions could go smoothly with the compounds 1 (Table
2). Regardless of where the acetyl was located, all the subꢀ
strates gave high selectivities (Table 2, entries 1ꢀ3), but for 2b,
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Scheme 3. Preparation of Compounds 10
Table 2. DKRꢀATH of Compounds 1
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
d
entry
substrate
yield of 2 ee(%) of
dr
b
c
(%)
2
1
2
1a
1b
1c
63
>99
96
98/2
31
50
>99/1
>99/1
3
95
a
The reactions were run on a 1.0 mmol scale in a 25 mL sealed
b
flask under the protection of argon. Isolated yield including the
minor enantiomer. Determined by HPLC analysis using a chiral
column. The calculation method was the same as the model 2a.
c
d
a
Table 3. DKRꢀATH of compounds 10
Scheme 2. Preparation of Substrates 1
d
entry
substrate
yield of
ee(%)
of 16
dr
b
c
1
6 (%)
1
2
3
4
10a
10b
10c
10d
79
87
82
90
91
94
85
92
>99/1
>99/1
>99/1
>99/1
a
The reactions were run on a 1.0 mmol scale in a 25 mL sealed
b
flask under protection of argon. Isolated yield including the miꢀ
nor enantiomer. Determined by HPLC analysis using a chiral
column. The calculation method was the same as the model 2a.
c
d
the yield was modest with many byꢀproducts generated during
the reaction.
Secondly, we further examined the scope of the general apꢀ
plicability using benzofuranꢀ3ꢀ(2H)ꢀone analogues 10aꢀ10d
that having different alkyl groups and aromatic groups (benꢀ
zyl) at the 2ꢀposition (Figure 3). These substrates 10 were
prepared by different methods as shown in Scheme 3, and
were subsequently reduced under the standard conditions. All
the substrates were able to be reduced and afforded good selecꢀ
Figure 3. The designed substrates 10.
tivities (Table 3, entries 1ꢀ4). These results showed that this
method was applicable to obtaining a wide scope of chiral 2,3ꢀ
dihydrobenzofuranꢀ3ꢀols containing three stereocenters.
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8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
General Procedure for Preparation of Compounds 5 (5a
as a model). To a solution of 4a (388 mg, 2 mmol) in acetone
(
10 mL), K CO (966 mg, 7 mmol) and BrCH CO Me (367mg,
2
3
2
2
2
.4 mmol) were added. After stirring under reflux for 3 h, the
reaction mixture was concentrated under reduced pressure,
diluted with water and extracted with ethyl acetate. The organꢀ
ic layer was washed with brine, dried with Na SO , and conꢀ
2
4
centrated under reduced pressure. The residue was purified by
silica gel chromatography using petroleum ether /ethyl acetate
=
3/1 as eluent to give 5a (452 mg, 85%) as a white solid.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Methyl 5ꢀacetylꢀ2ꢀ(2ꢀmethoxyꢀ2ꢀoxoethoxy)benzoate (5a).
1
White solid, 85% yield; mp 108 ˚C; H NMR ( 400 MHz,
CDCl ): δ 7.87 ( d, J = 8.0 Hz, 1H ), 7.56 ( dd, J = 1.4 Hz, J
=
(
3
1
2
8.0 Hz, 1H ), 7.43 ( d, J = 1.4 Hz, 1H ), 4.77 ( s, 2H ), 3.91
13
s, 3H ), 3.79 ( s, 3H ), 2.59 ( s, 3H ); C NMR ( 100 MHz,
Figure 4. Proposed transition state (TS).
CDCl ): δ 197.2, 168.8, 166.0, 157.5, 140.9, 132.3, 125.5,
3
In our experiments, as an example as compound 1, we obꢀ
served that the carbonyl group at the furan ring was much
easier to be reduced than the acetyl group at the benzene ring,
and the intermediate compound was also obtained (see supꢀ
porting information). Based on other previously reported
1
21.9, 112.8, 66.4, 52.7, 52.6, 27.0; HRMS (ESI): calc. for
+
C H NaO [M+Na] : 289.0683; found: 289.0684.
13
14
6
Methyl 4ꢀacetylꢀ2ꢀ(2ꢀmethoxyꢀ2ꢀoxoethoxy)benzoate (5b).
1
White solid, 82% yield; mp 69 ˚C; H NMR ( 400 MHz,
CDCl ): δ 7.74 ( d, J = 8.0 Hz, 1H ), 7.47 ( dd, J = 1.2 Hz, J
8.0 Hz, 1H ), 7.34 ( d, J = 1.2 Hz, 1H ), 4.69 ( s, 2H ), 3.81
8a,9
3
1
2
work,
we proposed a mechanism for the transfer hydroꢀ
=
genation reaction of 1a through a catalytic cycle with two
different stages (1a as a model). In the first stage, the substrate
13
( s, 3H ), 3.69 ( s, 3H ), 2.49 ( s, 3H ); C NMR ( 100 MHz,
CDCl ): δ 196.9, 168.5, 165.7, 157.2, 140.7, 132.0, 125.2,
121.6, 112.6, 66.1, 52.4, 52.3, 26.7; HRMS (ESI): calc. for
C H NaO [M+Na] : 289.0683; found: 289.0684.
3
1
a bonds with the catalyst, in which there is energetically faꢀ
vored and disfavored configurations due to the steric hinꢀ
drance between 1a and the catalyst as shown in TS (Figure 4,
for the detailed explanation see supporting information). This
caused the furanone part of 1a to be reduced by a DKRꢀATH
process. In the second stage, the catalyst bonds to 1a in the
same configuration fixed from the first stage, and the acetoꢀ
phenone part of 1a is reduced via an ATH process. The absoꢀ
lute configurations of all products were assigned as for the
model compound 1a and rationalized using the Noyori/Ikariya
+
13 14
6
Methyl 3ꢀacetylꢀ2ꢀ(2ꢀmethoxyꢀ2ꢀoxoethoxy)benzoate (5c).
1
Yellow oil, 89% yield; H NMR ( 400 MHz, CD COCD ): δ
3
3
7
.95 ( dd, J = 1.8 Hz, J = 7.7 Hz, 1H ), 7.78 ( dd, J = 1.8 Hz,
1
2
1
J = 7.7 Hz, 1H ), 7.33 ( t, J = 7.7 Hz, 1H ), 4.71 ( s, 2H ), 3.89
2
13
1
0
(
s, 3H ), 3.71 ( s, 3H ), 2.63 ( s, 3H ); C NMR ( 100 MHz,
CD COCD ): δ 199.8, 169.5, 166.3, 157.3, 136.6, 135.4,
3
3
1
34.2, 126.3, 125.2, 72.8, 52.9, 52.1, 31.3; HRMS (ESI): calc.
+
for C H NaO [M+Na] : 289.0683; found: 289.0685.
(R,R)ꢀI catalyst.
13 14
6
General Procedure for Preparation of Compounds 6 ( 6a
In summary, we developed a handy and efficient method to
as a model ). A solution of 5a (266 mg, 1 mmol) in CH OH (2
mL) was added to a solution of Na (28.8 mg, 1.25 mmol) in
CH OH (4 mL). The reaction mixture was refluxed and stirred
for 2 h. The reaction mixture was concentrated under reduced
pressure. The residue was added water and adjusted pH = 3ꢀ4
with aqueous hydrochloric acid (1.0 N). The mixture was filꢀ
tered and dried to afford 6a (201 mg, 86%) as a white solid.
obtain the cisꢀ2,3ꢀdihydrobenzofuranes containing three stereꢀ
ocenters by the reduction of benzofuranones via DKRꢀATH.
This methodology is an efficient tool to construct the transanꢀ
nular multiple stereocenters of dihydrobenzofuranol motifs
with excellent stereoselectivities for organic synthesis.
3
3
EXPERIMENTAL SECTION
General Information. All commercial reagents were purꢀ
chased from SigmaꢀAldrich, AlfaꢀAesar, Acros and they were
used without further purification unless specified. The proꢀ
Methyl 5ꢀacetylꢀ3ꢀhydroxybenzofuranꢀ2ꢀcarboxylate (6a).
1
White solid, 86% yield; mp 190 ˚C; H NMR ( 400 MHz,
CD
Hz, J
3.35 ( br s, 1H ), 2.63 ( s, 3H ); C NMR ( 100 MHz,
CD SOCD ): δ 196.9, 159.4, 154.9, 147.6, 132.1, 128.5,
127.9, 123.5, 121.8, 112.5, 51.4, 26.8; HRMS (ESI): calc. for
SOCD
): δ 8.70 ( d, J = 1.6 Hz, 1H ), 8.07 ( dd, J = 1.6
3 1
3
1
13
gress of the reaction was monitored by TLC. H and C NMR
spectra were recorded on Bruker AVꢀ400 spectrometers operꢀ
2
= 8.8 Hz, 1H ), 7.66 ( d, J = 8.8 Hz, 1H ), 3.83 ( s, 3H ),
13
1
13
ating respectively at 400 MHz for H, and 100 MHz for C.
The peaks were internally referenced to TMS (0.00 ppm) or
residual undeuterated solvent signal. Peak multiplicities are
reported as follows: s = singlet, br s = broad singlet, d = douꢀ
blet, t = triplet, m = multiplet. The enantiomeric excess (ee)
was determined by HPLC analysis. HPLC data were obtained
3
3
+
C
H
10NaO
[M+Na] : 257.0420; found: 257.0424.
12
5
Methyl 6ꢀacetylꢀ3ꢀhydroxybenzofuranꢀ2ꢀcarboxylate (6b).
1
White solid, 75% yield; mp 162 ˚C; H NMR ( 400 MHz,
CD SOCD ): δ 11.05 ( s, 1H ), 8.15 ( s, 1H ), 7.98 ( d, J = 8.3
Hz, 1H ), 7.86 ( d, J = 8.3 Hz, 1H ), 3.85 ( s, 3H ), 2.64 ( s,
3
3
®
on a VARIAN HPLC system using DAICEL CHIRALPAK
13
IA column (25 cm) at 35 ˚C. The Melting points were deterꢀ
mined using WRSꢀ1B apparatus and are uncorrected. High
resolution mass spectra for new compounds were recorded on
a Bruker micro TOFꢀQ III spectrometer. Xꢀray crystallographꢀ
ic analyses were performed at the Xꢀray crystallography faciliꢀ
3
H ); C NMR ( 100 MHz, CD SOCD ): δ 197.4, 159.4,
3 3
1
52.2, 146.5, 136.8, 129.3, 125.3, 122.2, 121.3, 112.8, 51.5,
+
2
7.0; HRMS (ESI): calc. for C H NaO [M+Na] : 257.0420;
12
10
5
found: 257.0425.
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General Procedure for Preparation of Compounds 7 ( 7a
1H ), 4.49 ( s, 1H ), 2.72 ( s, 3H ), 1.43 ( s, 3H ), 1.27 ( s, 3H );
13
1
2
3
4
5
6
7
8
9
as a model ). A solution of 6a (234 mg, 1 mmol), LiOH H O
C NMR ( 100 MHz, CDCl ): δ 200.2, 195.0, 171.3, 138.8,
2
3
(168 mg, 4.0 mmol), DMSO (3 mL) and H O (2 mL) were
129.6, 123.8, 123.6, 122.6, 89.8, 72.7, 31.5, 26.0, 24.9; HRMS
2
+
stirred at 75 ˚C for 3 h. After being cooled to ambient temꢀ
perature, the mixture was added water and adjusted pH = 1ꢀ2
with aqueous hydrochloric acid (1.0 N). The mixture was filꢀ
tered and dried to give 7a (137 mg, 78%) as a pale yellow
solid.
(ESI): calc. for C H NaO [M+Na] : 257.0784; found:
13
14
4
257.0785.
Procedure for Preparation of Compounds 9. A 50 mL
Schlenkꢀtype tube (with a Teflon high pressure valve and side
arm) equipped with a magnetic stir bar was charged with
5
ꢀAcetylbenzofuranꢀ3(2H)ꢀone (7a). Pale yellow solid, 78%
Pd(OAc) (11.2 mg, 0.05 mmol) followed by 8 (0.5 mmol),
2
1
yield; mp 139ꢀ140 ˚C; H NMR ( 400 MHz, CDCl ): δ 8.27
benzoquinone (54.0 mg, 0.5 mmol), KOAc (98.0 mg, 1 mmol)
and N,Nꢀdimethylacetamide (1.5 mL). The reaction tube was
3
(
7
dd, J = 1.8 Hz, J = 8.8 Hz, 1H ), 8.22 ( d, J = 1.8 Hz, 1H ),
1
2
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
13
.18 ( d, J = 8.8 Hz, 1H ), 4.71 ( s, 2H ), 2.57 ( s, 3H );
C
evacuated and backꢀfilled with O (3 times, balloon). After the
2
NMR ( 100 MHz, CDCl ): δ 198.9, 196.0, 176.8, 138.0, 131.9,
reaction mixture was stirred at 115 ˚C for 24 h, it was allowed
to cool to ambient temperature. The reaction mixture was diꢀ
luted with ethyl acetate and water and then filtered through a
small pad of Celite. The filtrate was washed with aqueous HCl
(1.0 N, 5 mL) and brine (5 mL, twice). The organic phase was
3
1
25.6, 121.2, 114.3, 76.0, 26.6; HRMS (ESI): calc. for
+
C H NaO [M+Na] : 199.0366; found: 199.0368.
1
0
8
3
6
ꢀAcetylbenzofuranꢀ3(2H)ꢀone (7b). Pale yellow solid, 63%
1
yield; mp 120 ˚C; H NMR ( 400 MHz, CDCl ): δ 7.73 ( d, J
3
dried (Na SO ) and concentrated in vacuo. The residue was
=
8.0 Hz, 1H ), 7.66 ( s, 1H ), 7.63 ( d, J = 8.0 Hz, 1H ), 4.69
2
4
1
3
purified by silica gel flash column chromatography to give the
corresponding product 9.
( s, 2H ), 2.63 ( s, 3H ); C NMR ( 100 MHz, CDCl ): δ
3
199.6, 197.2, 174.0, 144.9, 124.6, 124.4, 121.9, 113.7, 75.6,
+
2
7.4; HRMS (ESI): calc. for C H NaO [M+Na] : 199.0366;
4ꢀAcetylꢀ2ꢀhydroxybenzoic acid (9). White solid, 51% yield;
10
8
3
1
found: 199.0371.
mp 201 ˚C; H NMR ( 400 MHz, CD OD ): δ 7.96 ( d, J = 7.3
3
13
Hz, 1H ), 7.52ꢀ7.40 ( m, 2H ), 2.59 ( s, 3H ); C NMR ( 100
7ꢀAcetylbenzofuranꢀ3(2H)ꢀone (7c). Pale yellow solid, 53%
1
MHz, CD OD ): δ 199.7, 172.9, 163.2, 144.0, 132.1, 119.4,
yield; mp 144 ˚C; H NMR ( 400 MHz, CDCl ): δ 8.18 ( dd,
3
3
–
1
1
18.1, 117.7, 27.1; HRMS (ESI): calc. for C H O [M–H] :
J = 1.5 Hz, J = 7.7 Hz, 1H ), 7.85 ( dd, J = 1.5 Hz, J = 7.7
9
7
4
1
2
1
2
79.0350; found: 179.0354.
Hz, 1H ), 7.17 ( t, J = 7.7 Hz, 1H ), 4.74 ( s, 2H ), 2.68 ( s,
1
3
3
1
H ); C NMR ( 100 MHz, CDCl ): δ 198.7, 195.2, 172.4,
Procedure for Preparation of Compounds 4b. To a soluꢀ
3
38.5, 129.4, 124.2, 123.0, 122.4, 75.1, 31.4; HRMS (ESI):
calc. for C H NaO [M+Na] : 199.0366; found: 199.0365.
tion of 9 (900 mg, 5 mmol) in CH OH (25 mL) was added
3
+
dropwise concentrated sulfuric acid (10 drops ). After stirring
under reflux for 12 h, the reaction mixture was concentrated
under reduced pressure, diluted with water and extracted with
ethyl acetate. The organic layer was washed with saturated
10
8
3
General Procedure for Preparation of Compounds 1 (1a
as a model). To a stirred solution of acetone (15 mL) and
basic alumina (816 mg, 8 mmol, 10 equiv.) was added dropꢀ
wise 7a (137 mg, 1 mmol), and the resulting mixture was
stirred at room temperature for about 30 min. The reaction
mixture was monitored by TLC (Thin Layer Chromatography)
analysis, and the reaction mixture was filtered and concentratꢀ
ed under reduced pressure when the substrate disappeared.
Then the residue was purified by silica gel chromatography
using petroleum ether /ethyl acetate = 2:1 as an eluent to give
aqueous NaHCO solution, and brine, and dried with Na SO ,
3
2
4
and concentrated under reduced pressure. The crude mixture
was purified by flash chromatography (petroleum ether /ethyl
acetate = 4/1) to afford 4b (970 mg, 93%) as a white solid.
Methyl 4ꢀacetylꢀ2ꢀhydroxybenzoate (4b). White solid, 93%
1
yield; mp 86 ˚C; H NMR ( 400 MHz, CDCl ): δ 10.74 ( s,
3
1H ), 7.88 ( d, J = 8.3 Hz, 1H ), 7.48 ( d, J = 1.6 Hz, 1H ), 7.40
( dd, J = 1.6 Hz, J = 8.3 Hz, 1H ), 3.95 ( s, 3H ), 2.57 ( s,
1
a (117 mg, 50%) as a pale yellow solid.
1
2
1
3
3
1
H ); C NMR ( 100 MHz, CDCl ): δ 197.6, 170.1, 161.7,
5
ꢀAcetylꢀ2ꢀ(2ꢀhydroxypropanꢀ2ꢀyl)benzofuranꢀ3(2H)ꢀone
3
1
42.8, 130.5, 118.4, 117.9, 115.8, 52.9, 27.1; HRMS (ESI):
(
1a). Pale yellow solid, 50% yield; mp 139 ˚C; H NMR
+
calc. for C H NaO [M+Na] : 217.0471; found: 217.0476.
(
400MHz, CDCl ): δ 8.28 ( d, J = 8.8 Hz, 1H ), 8.20 ( s, 1H ),
10 10
4
3
7
3
.20 ( d, J = 8.8 Hz, 1H ), 4.47 ( s, 1H ), 2.97 ( s, 1H ), 2.57 ( s,
H ), 1.35 ( s, 3H ), 1.26 ( s, 3H ); C NMR ( 100 MHz,
Procedure for Preparation of Compounds 13. To a soluꢀ
13
tion of 11 (830 mg, 5 mmol) in CH OH (25 mL) was added
3
CDCl ): δ 200.2, 196.0, 175.6, 138.4, 132.0, 125.8, 121.9,
dropwise concentrated sulfuric acid (10 drops). After stirring
under reflux for 12 h, the reaction mixture was concentrated
under reduced pressure, diluted with water and extracted with
ethyl acetate. The organic layer was washed with saturated
aqueous NaHCO solution, and brine, and dried with Na SO ,
3
1
14.0, 90.8, 72.7, 26.6, 25.6, 24.7; HRMS (ESI): calc. for
+
C H NaO [M+Na] : 257.0784; found: 257.0784.
1
3
14
4
6
ꢀAcetylꢀ2ꢀ(2ꢀhydroxypropanꢀ2ꢀyl)benzofuranꢀ3(2H)ꢀone
1
(
1b). Pale yellow solid, 47% yield; mp 84 ˚C; H NMR
3
2
4
and concentrated under reduced pressure. The crude mixture
was purified by flash chromatography (petroleum ether /ethyl
acetate = 4/1) to afford 12 (855 mg, 95%) as a colorless oil.
(
400MHz, CDCl ): δ 7.71 ( d, J = 8.0 Hz, 1H ), 7.67 ( s, 1H ),
3
7.62 ( d, J = 8.0 Hz, 1H ), 4.43 ( s, 1H ), 2.62 ( s, 3H ), 1.34 ( s,
1
3
3H ), 1.25 ( s, 3H ); C NMR ( 100 MHz, CDCl ): δ 200.9,
3
197.1, 172.9, 145.2, 125.0, 124.7, 122.0, 113.3, 90.3, 72.8,
K CO (276 mg, 2 mmol) and methyl 2ꢀbromopropionate
2
3
+
2
2
7.3, 25.6, 24.7; HRMS (ESI): calc. for C H NaO [M+Na] :
57.0784; found: 257.0783.
(334 mg, 2 mmol) were added to a solution of 12 (360 mg, 2
mmol) in dry DMF (3 mL). After stirring at room temperature
for 12 h, the mixture was diluted with ethyl acetate (5 mL),
washed with 1 N HCl (5 mL), and dried (Na SO ). The organꢀ
13 14
4
7ꢀAcetylꢀ2ꢀ(2ꢀhydroxypropanꢀ2ꢀyl)benzofuranꢀ3(2H)ꢀone
1
(
1c). Pale yellow solid, 45% yield; mp 107 ˚C; H NMR
2
4
ic layer was then concentrated and the crude residue was puriꢀ
(
400MHz, CDCl ): δ 8.20 ( dd, J = 1.5 Hz, J = 7.6 Hz, 1H ),
3
1
2
7
.84 ( dd, J = 1.5 Hz, J = 7.6 Hz, 1H ), 7.18 ( t, J = 7.6 Hz,
1 2
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Page 6 of 9
1
fied by column chromatography using petroleum ether /ethyl
Pale yellow solid, 65% yield; mp 153 ˚C; H NMR ( 400 MHz,
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
acetate = 5:1 as eluent to give 13 (505 mg, 95%) as a colorless
oil.
CDCl ): δ 8.26 ( d, J = 1.3 Hz, 1H ), 8.23 ( dd, J = 1.3 Hz, J
3
1
2
= 8.7 Hz, 1H ), 7.21 ( d, J = 8.7 Hz, 1H ), 2.58 ( s, 3H ), 2.35
13
( s, 3H ), 2.10 ( s, 3H ); C NMR ( 100 MHz, CDCl ): δ
Methyl 5ꢀethylꢀ2ꢀ((1ꢀmethoxyꢀ1ꢀoxopropanꢀ2ꢀyl)oxy) benꢀ
3
1
1
1
96.4, 183.2, 167.1, 145.6, 136.3, 134.3, 132.1, 125.7, 123.5,
13.2, 26.7, 20.5, 17.8; HRMS (ESI): calc. for C H NaO
3
zoate (13). Colorless oil, 95% yield; H NMR ( 400 MHz,
CDCl ): δ 7.60 ( d, J = 2.3 Hz, 1H ), 7.20 ( dd, J = 2.3 Hz, J
13 12
3
1
2
+
[
M+Na] : 239.0679; found: 239.0680.
Procedure for Preparation of Compound 10b. To a soluꢀ
tion of Pd/C (10%) in CHCl (5 mL) and CH CH OH (5 mL),
=
8.4 Hz, 1H ), 6.78 ( d, J = 8.4 Hz, 1H ), 4.71 ( q, J =6.8 Hz,
1
1
(
H ), 3.86 ( s, 3H ), 3.72 ( s, 3H ), 2.57 ( q, J = 7.6 Hz, 2H ),
.62 ( d, J = 6.8 Hz, 3H ), 1.18 ( t, J = 7.6 Hz, 3H ); C NMR
13
3
3
2
100 MHz, CDCl ): δ 172.8, 166.9, 155.4, 137.9, 132.9,
15b (108 mg, 0.5 mmol) was added. The reaction was stirred
3
1
31.2, 121.6, 116.2, 75.1, 52.5, 52.2, 28.0, 18.8, 15.7; HRMS
at room temperature and backꢀfilled with H (3 times, balloon).
2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
+
(ESI): calc. for C H NaO [M+Na] : 289.1046; found:
After 20 min, the reaction mixture was filtered with 15 mL of
ethyl acetate and concentrated under reduced pressure. Then
the residue was purified by silica gel chromatography using
petroleum ether /ethyl acetate = 5:1 as an eluent to give 10b
(43 mg, 20%) as a colorless oil.
1
4
18
5
2
89.1045.
Procedure for Preparation of Compounds 14. K CO (69
2
3
mg, 0.5 mmol) was added to a solution of 13 (266 mg, 1 mmol)
in DMF (1.0 mL) and MeOH (0.5 mL). The mixture was heatꢀ
ed at 170 ˚C for 10 min under stirring and 300 W microwave
irradiation power. After cooling to ambient temperature, the
mixture was diluted with ethyl acetate (5 mL). The resulting
organic layer was washed with 1 N HCl (5 mL) and dried
5ꢀAcetylꢀ2ꢀisopropylbenzofuranꢀ3(2H)ꢀone (10b). Colorless
1
oil, 20% yield; H NMR ( 400 MHz, CDCl ): δ 8.26 ( dd, J =
3
1
1.8 Hz, J = 8.8 Hz, 1H ), 8.19 ( d, J = 1.8 Hz, 1H ), 7.16 ( d, J
2
= 8.8 Hz, 1H ), 4.50 ( d, J = 3.8 Hz, 1H ), 2.56 ( s, 3H ), 2.41ꢀ
2.31 ( m, 1H ), 1.13 ( d, J = 6.9 Hz, 3H ), 0.85 ( d, J = 6.9 Hz,
(
Na SO ). The organic layer was then concentrated and puriꢀ
2 4
13
fied by column chromatography using petroleum ether /ethyl
acetate = 70:1 as eluent to give 14 (82 mg, 47%) as a colorless
oil.
3H ); C NMR ( 100 MHz, CDCl ): δ 201.1, 196.1, 176.0,
3
138.0, 131.6, 125.7, 121.8, 113.9, 91.2, 31.2, 26.6, 18.9, 15.8;
+
HRMS (ESI): calc. for C H NaO [M+Na] : 241.0835; found:
13
14
3
2
41.0839.
5
ꢀEthylꢀ2ꢀmethylbenzofuranꢀ3(2H)ꢀone (14). Colorless oil,
1
4
2
7% yield; H NMR ( 400 MHz, CDCl ): δ 7.49ꢀ7.42 ( m,
Procedure for Preparation of Compound 15c. Benzaldeꢀ
3
H ), 7.02 ( dd, J = 1.0 Hz, J = 8.1 Hz, 1H ), 4.62 ( q, J = 7.2
hyde (127 mg, 1.2 mmol, 1.5equiv.) and basic alumina (816
mg, 8 mmol, 10 equiv.) were added to a solution of 7a (142
mg, 0.8 mmol) in CH Cl (10 mL). The resulting mixture was
1
2
Hz, 1H ), 2.65 ( q, J = 7.6 Hz, 2H ), 1.51 ( d, J = 7.2 Hz, 3H ),
13
1
2
1
1
.23 ( t, J = 7.6 Hz, 3H ); C NMR ( 100 MHz, CDCl ): δ
3
2
2
02.8, 171.2, 138.6, 138.1, 122.6, 120.4, 113.3, 82.2, 28.2,
6.5, 15.8; HRMS (ESI): calc. for C H NaO [M+Na] :
99.0730; found: 199.0731.
Procedure for Preparation of Compound 10a. To a soluꢀ
tion of CrO (800 mg, 9 mmol) in Ac O (3 mL) and AcOH
stirred at room temperature for about 2 h. The reaction mixture
was monitored by TLC analysis, and the reaction mixture was
filtered and concentrated under reduced pressure when the
substrate disappeared. Then the residue was purified by silica
+
1
1
12
2
gel chromatography using CH Cl /CH OH/(CH ) CO)
=
2
2
3
3 2
3
2
2
00/1/1) as an eluent to give 15c (126 mg, 60%) as a pale yelꢀ
(1.5 mL) was added dropwise a suspension of the 14 (176 mg,
1 mmol) in AcOH (1.5 mL) at 0 ˚C over 10 min. The reaction
mixture was stirred at 0 ˚C for 10 min, and poured into iceꢀ
low solid.
(Z)ꢀ5ꢀacetylꢀ2ꢀbenzylidenebenzofuranꢀ3(2H)ꢀone(15c). Pale
1
water (40 mL) and then was extracted with CHCl . The comꢀ
yellow solid, 60% yield; mp 192 ˚C; H NMR ( 400 MHz,
3
bined organic layer was washed with water, saturated aqueous
NaHCO solution, and brine, and dried over Na SO . The
CDCl ): δ 8.37 ( d, J = 1.7 Hz, 1H ), 8.34 ( dd, J = 1.9 Hz, J
3
1
2
= 8.7 Hz, 1H ), 7.93ꢀ7.89 ( m, 2H ), 7.50ꢀ7.38 ( m, 4H ),
3
2
4
13
crude mixture was purified by flash chromatography (petroleꢀ
um ether /ethyl acetate = 5/1) to afford 10a (67 mg, 35%) as a
colorless solid.
6.95( s, 1H ), 2.63( s, 3H ); C NMR ( 100 MHz, CDCl ): δ
3
196.2, 184.1, 168.7, 147.2, 137.1, 133.2, 132.0, 130.7, 129.2,
129.2, 126.0, 121.8, 114.9, 113.6, 26.8; HRMS (ESI): calc. for
+
C H NaO [M+Na] : 287.0679; found: 287.0682.
5
ꢀAcetylꢀ2ꢀmethylbenzofuranꢀ3(2H)ꢀone (10a). Colorless oil,
17 12
3
1
3
5% yield; H NMR ( 400 MHz, CDCl ): δ 8.29 ( dd, J = 1.9
Procedure for Preparation of Compound 10c. To a soluꢀ
3
1
Hz, J = 8.8 Hz, 1H ), 8.23 ( d, J = 1.9 Hz, 1H ), 7.15 ( d, J =
tion of Pd/C (10%) in CHCl (5 mL) and CH CH OH (5 mL),
2
3
3
2
8
.8 Hz, 1H ), 4.74 ( q, J = 7.2 Hz, 1H ), 2.58 ( s, 3H ), 1.55 ( d,
15c (106 mg, 0.4 mmol) was added. The reaction was stirred
13
J =7.2 Hz, 3H ); C NMR (100 MHz, CDCl ): δ 201.7, 196.1,
at room temperature and backꢀfilled with H (3 times, balloon).
3
2
175.3, 138.2, 131.8, 126.1, 120.5, 114.2, 83.5, 26.6, 16.5;
After 20 min, the reaction mixture was filtered with 15 mL of
ethyl acetate and concentrated under reduced pressure. Then
the residue was purified by silica gel chromatography using
petroleum ether /ethyl acetate = 5:1 as an eluent to give 10c
+
HRMS (ESI): calc. for C H NaO [M+Na] : 213.0522; found:
1
1
10
3
213.0522.
Procedure for Preparation of Compound 15b. To a
stirred solution of acetone (10 mL) and basic alumina (816 mg,
8 mmol, 10 equiv.) was added dropwise 7a (142 mg, 0.8 mmol)
and the resulting mixture was stirred at room temperature for
about 2 h. The reaction mixture was monitored by TLC analyꢀ
sis, and the reaction mixture was filtered and concentrated
under reduced pressure when the substrate disappeared. Then
the residue was purified by silica gel chromatography using
petroleum ether /ethyl acetate = 3:1 as an eluent to give 15b
(16 mg, 15%) as a colorless oil.
5ꢀAcetylꢀ2ꢀbenzylbenzofuranꢀ3(2H)ꢀone (10c). Colorless oil,
1
15% yield; H NMR ( 400 MHz, CDCl ): δ 8.25 ( dd, J = 1.9
3
1
Hz, J = 8.8 Hz, 1H ), 8.18 ( d, J = 1.7 Hz, 1H ), 7.29ꢀ7.19 ( m,
2
5H ), 7.14 ( d, J = 8.8 Hz, 1H ), 4.91 ( dd, J = 3.8 Hz, J = 8.0
1
2
Hz, 1H ), 3.38 ( dd, J = 3.8 Hz, J = 14.7 Hz, 1H ), 3.06 ( dd,
1
2
13
J = 8.0 Hz, J = 14.7 Hz, 1H ), 2.56 ( s, 3H ); C NMR ( 100
1
2
MHz, CDCl ): δ 200.2, 196.0, 175.4, 138.1, 135.4, 131.7,
3
(113 mg, 65%) as a pale yellow solid.
129.6, 128.7, 127.3, 125.8, 121.0, 114.0, 87.2, 37.4, 26.5;
5
ꢀAcetylꢀ2ꢀ(propanꢀ2ꢀylidene)benzofuranꢀ3(2H)ꢀone (15b).
6
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The Journal of Organic Chemistry
+
HRMS (ESI): calc. for C H NaO [M+Na] : 289.0835; found:
289.0833.
gel column chromatography (Petroleum ether /ethyl acetate =
2/1) afforded 2a (including the minor enantiomer). Other samꢀ
ples 2bꢀ2c were prepared as the same procedure.
1
7
14
3
1
2
3
4
5
6
7
8
9
Procedure for Preparation of Compound 15d. Furfural
(
115 mg, 1.2 mmol) and basic alumina (816 mg, 8 mmol)
(2R,3S)ꢀ5ꢀ((S)ꢀ1ꢀhydroxyethyl)ꢀ2ꢀ(2ꢀhydroxypropanꢀ2ꢀyl)ꢀ
were added to a solution of 7a (142 mg, 0.8 mmol) in CH Cl2
2,3ꢀdihydrobenzofuranꢀ3ꢀol (2a). White solid, 63% yield; mp
2
1
(10 mL). the resulting mixture was stirred at room temperature
for about 2 h. The reaction mixture was monitored by TLC
analysis, and the reaction mixture was filtered and concentratꢀ
ed under reduced pressure when the substrate disappeared.
Then the residue was purified by silica gel chromatography
using CH Cl /CH OH/(CH ) CO) = 200/1/1) as an eluent to
169ꢀ170 ˚C; 99% ee, 98/2 dr; H NMR ( 400 MHz, CD OD ):
3
δ 7.38 ( br s, 1H ), 7.24 ( dd, J = 1.7 Hz, J = 8.3 Hz, 1H ),
1
2
6.81 ( d, J = 8.3 Hz, 1H ), 5.28 ( d, J = 6.0 Hz, 1H ), 4.79 ( q, J
= 6.4 Hz, 1H ), 4.20 ( d, J = 6.0 Hz, 1H ), 3.34 ( s, 1H ), 1.48
1
3
( s, 3H ), 1.42 ( s, 3H ) 1.41 ( d, J = 6.4 Hz, 3H ); C NMR
( 100 MHz, CD OD ): δ 160.6, 140.4, 131.2, 129.0, 124.0,
2
2
3
3 2
3
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
give 15d (142 mg, 70%) as a pale yellow solid.
110.9, 91.4, 73.6, 73.4, 70.9, 27.3, 26.8, 25.8; HRMS ( ESI ):
+
calc. for C H NaO [M+Na] : 261.1097; found: 261.1097.
(
Z)ꢀ5ꢀacetylꢀ2ꢀ(furanꢀ2ꢀylmethylene)benzofuranꢀ3(2H)ꢀone
13 18
4
®
1
HPLC (DAICEL CHIRALPAK IA column, eluent: Hexꢀ
anes/iꢀPrOH =92/8, detector: 280 nm, flow rate: 0.5 mL/min,
(15d). Pale yellow solid, 70% yield; mp 194ꢀ195 ˚C; H NMR
(
=
400 MHz, CDCl ): δ 8.34 ( d, J = 1.7 Hz, 1H ), 8.31 ( dd, J1
3
35 ˚C ): t = 46.693 min.
1.7 Hz, J = 8.7 Hz, 1H ), 7.63 ( d, J = 1.7 Hz, 1H ), 7.37 ( d,
R
2
J = 8.7 Hz, 1H ), 7.14 ( d, J = 3.5 Hz, 1H ), 6.93 ( s, 1H ), 6.60
(
( 100 MHz, CDCl ): δ 196.2, 183.2, 168.2, 148.6, 146.2,
145.3, 136.8, 133.2, 125.8, 122.2, 118.5, 113.6, 113.5, 103.1,
(2R,3S)ꢀ6ꢀ((R)ꢀ1ꢀhydroxyethyl)ꢀ2ꢀ(2ꢀhydroxypropanꢀ2ꢀyl)ꢀ
13
dd, J = 1.7 Hz, J = 3.5 Hz, 1H ), 2.61 ( s, 3H ); C NMR
2,3ꢀdihydrobenzofuranꢀ3ꢀol (2b). White solid, 31% yield; mp
1
2
1
139ꢀ140 ˚C; 96% ee, >99/1 dr; H NMR ( 400 MHz, CD OD ):
3
3
δ 7.30 ( d, J = 7.6 Hz, 1H ), 6.94ꢀ6.90 ( m, 1H ), 6.89 ( s, 1H ),
5.27 ( d, J = 6.0 Hz, 1H ), 4.78 ( q, J = 6.5 Hz, 1H ), 4.20 ( d, J
= 6.0 Hz, 1H ), 1.48 ( s, 3H ), 1.43 ( s, 3H ), 1.40 ( d, J = 6.5
+
2
6.7; HRMS (ESI): calc. for C H NaO [M+Na] : 277.0471;
15 10
4
found: 277.0473.
13
Hz, 3H ); C NMR ( 100 MHz CD OD ): δ 161.6, 150.9,
Procedure for Preparation of Compound 10d. To a soluꢀ
3
1
2
30.1, 126.5, 119.4, 108.3, 91.5, 73.4, 73.4, 71.0, 27.3, 26.8,
tion of Pd/C (10% ) in CHCl (5 mL) and CH CH OH (5 mL),
1
at room temperature and backꢀfilled with H (3 times, balloon).
After 20 min, the reaction mixture was filtered with 15 mL of
ethyl acetate and concentrated under reduced pressure. Then
the residue was purified by silica gel chromatography using
petroleum ether /ethyl acetate = 5:1 as an eluent to give 10d
3
3
2
+
5.9; HRMS ( ESI ): calc. for C H NaO [M+Na] : 261.1097;
5d (102 mg, 0.4 mmol) was added. The reaction was stirred
13 18
4
®
found: 261.1097. HPLC (DAICEL CHIRALPAK IA column,
eluent: Hexanes/iꢀPrOH =92/8, detector: 280 nm, flow rate:
2
0
(
.5 mL/min, 35 ˚C ): t = 71.917 min (major), t = 67.444 min
R
R
minor).
(2R,3S)ꢀ7ꢀ((R)ꢀ1ꢀhydroxyethyl)ꢀ2ꢀ(2ꢀhydroxypropanꢀ2ꢀyl)ꢀ
2,3ꢀdihydrobenzofuranꢀ3ꢀol (2c). Colorless oil, 50% yield,
(17 mg, 17%) as a colorless oil.
1
9
(
5%ee, >99/1 dr; H NMR ( 400 MHz, CDCl ): δ 7.29ꢀ7.20
5
ꢀAcetylꢀ2ꢀ(furanꢀ2ꢀylmethyl)benzofuranꢀ3(2H)ꢀone (10d).
3
1
m, 2H ), 6.88 ( t, J = 7.4 Hz, 1H ), 5.21 ( d, J = 6.0 Hz, 1H ),
Colorless oil, 17% yield; H NMR ( 400 MHz, CDCl ): δ 8.26
(
7.26 ( d, J = 1.8 Hz, 1H ), 7.15 ( d, J = 8.8 Hz, 1H ), 6.24 ( dd,
J = 1.9 Hz, J = 3.0 Hz, 1H ), 6.13 ( d, J = 3.0 Hz, 1H ), 4.92
( dd, J = 4.0 Hz, J = 7.7 Hz, 1H ), 3.39 ( dd, J = 4.0 Hz, J =
1
(
1
8
2
3
5.04 ( q, J = 6.5 Hz, 1H ), 4.08 ( d, J = 6.0 Hz, 1H ), 1.49ꢀ1.44
dd, J = 1.8 Hz, J = 8.8 Hz, 1H ), 8.21 ( d, J = 1.9 Hz, 1H ),
1 2
13
(
1
2
m, 6H ), 1.42 ( s, 3H ); C NMR ( 100 MHz, CDCl ): δ
3
56.7, 129.6, 128.0, 126.9, 124.6, 121.5, 89.2, 73.0, 72.7, 64.2,
8.0, 26.0, 22.0; HRMS ( ESI ): calc. for C H NaO
1
2
13 18
4
1
2
1
2
+
[
M+Na] : 261.1097; found: 261.1095. HPLC (DAICEL
CHIRALPAK IA column, eluent: Hexanes/iꢀPrOH =92/8,
5.8 Hz, 1H ), 3.11 ( dd, J = 7.7 Hz, J = 15.8 Hz, 1H ), 2.57
1
2
®
13
s, 3H ); C NMR ( 100 MHz, CDCl ): δ 199.8, 196.0, 175.5,
3
detector: 280 nm, flow rate: 0.5 mL/min, 35 ˚C): t = 32.640
49.5, 142.2, 138.2, 131.9, 125.9, 120.8, 114.2, 110.6, 108.1,
R
+
min (major), t = 29.140 min (minor).
5.0, 30.2, 26.6; HRMS (ESI): calc. for C H NaO [M+Na] :
R
1
5
12
4
79.0628; found: 279.0629.
General Procedure for Preparation of Compound 16. 1.0
mmol 10, 5.0 mmol sodium formate, 5.0 µmol catalyst 3a and
Optimization of Reaction Conditions for DKRꢀATH of
a. 1.0 mmol 1a, 5.0 mmol sodium formate, 5.0 µmol catalyst
0
.2 mmol CTAB were added into 4 mL CH OH and the mixꢀ
1
3
ture was stirred at 65 ˚C under an atmosphere of argon for 12
h. During that time, the reaction was monitored constantly by
TLC analysis. After completion of the reaction, 5 mL Saturatꢀ
ed sodium chloride solution was added to the mixture, which
was extracted by CH Cl (3 × 5.0 mL). The combined organic
and 0.2 mmol PTC were added into 4 mL CH OH and the
3
mixture was stirred at 65 ˚C under argon for 12 h. During that
time, the reaction was monitored constantly by TLC. After
completion of the reaction, 5 mL Saturated sodium chloride
solution was added to the mixture, which was extracted by
CH Cl (3 × 5.0 mL). The combined organic layer was dehyꢀ
drated with anhydrous Na SO and concentrated under reꢀ
duced pressure. Purification of the residue by silica gel colꢀ
umn chromatography.
2
2
layer was dehydrated with anhydrous Na SO and concentratꢀ
2
4
2
2
ed under reduced pressure. Purification of the residue by silica
gel column chromatography (Petroleum ether /ethyl acetate =
/1) afforded 16 (including the minor enantiomer).
2
4
2
(2S,3S)ꢀ5ꢀ((R)ꢀ1ꢀhydroxyethyl)ꢀ2ꢀmethylꢀ2,3ꢀdihydroꢀbenzo
General Procedure for Preparation of Compounds 2. 1.0
mmol 1a, 5.0 mmol sodium formate, 5.0 µmol catalyst 3a and
0
ture was stirred at 65 ˚C under an atmosphere of argon for 12
h. During that time, the reaction was monitored constantly by
TLC analysis. After completion of the reaction, 5 mL Saturatꢀ
ed sodium chloride solution was added to the mixture, which
was extracted by CH Cl (3 × 5.0 mL). The combined organic
furanꢀ3ꢀol (16a). White solid, 79% yield; mp 92ꢀ93 ˚C; 91%
1
ee, >99/1 dr; H NMR ( 400 MHz, CD OD, 3.1:1 mixture of
.2 mmol CTAB were added into 4 mL CH OH and the mixꢀ
3
3
rotamers ): δ 7.40 ( br s, 1H ), 7.22 ( dd, J = 1.8 Hz, J = 8.3
1
2
Hz, 1H ), 6.72 ( d, J = 8.3 Hz, 1H ), 4.98 ( d, J = 6.0 Hz, 1H ),
.78 ( q, J = 6.5 Hz, 1H ), 4.61ꢀ4.52 ( m, 1H ), 1.45 ( d, J = 6.5
Hz, 3H ), 1.41 ( d, J = 6.5 Hz, 0.73H ), 1.41 ( d, J = 6.5 Hz,
4
13
2.26H ); C NMR ( 100 MHz, CD OD, mixture of rotamers ):
3
2
2
δ 160.7, 160.4, 140.2, 140.2, 130.9, 130.9, 129.0, 128.9, 124.5,
layer was dehydrated with anhydrous Na SO and concentratꢀ
ed under reduced pressure. Purification of the residue by silica
2
4
7
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 9
1
24.3, 110.7, 110.7, 88.6, 84.9, 79.3, 73.6, 70.9, 70.8, 25.8,
afforded the racemic 2a. Other racemic samples 2bꢀ2c and
16aꢀ16d were prepared as the same procedure.
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
25.8, 19.6, 14.1; HRMS ( ESI ): calc. for C H NaO
[M+Na] : 217.0835; found: 217.0836. HPLC (DAICEL
CHIRALPAK IA column, eluent: Hexanes/iꢀPrOH =85/15,
detector: 280 nm, flow rate: 0.5 mL/min, 35 ˚C): t = 16.421
1
1
14
3
+
®
R
ASSOCIATED CONTENT
Supporting Information
min (major), t = 17.479 min (minor).
R
(2S,3S)ꢀ5ꢀ((R)ꢀ1ꢀhydroxyethyl)ꢀ2ꢀisopropylꢀ2,3ꢀdihydroꢀben
1
13
H NMR and C NMR spectra, HPLC chromatograms, Xꢀray
zofuranꢀ3ꢀol (16b). White solid, 87% yield; mp: 105ꢀ106 ˚C;
9
of rotamers ): δ 7.40 ( d, J = 1.7 Hz, 1H ), 7.22 ( dd, J = 1.7
Hz, J = 8.3 Hz, 1H ), 6.75 ( d, J = 8.3 Hz, 1H ), 4.99 ( d, J =
1
data (PDF), Xꢀray crystallographic data for 2a (CIF)
4% ee, >99/1 dr; H NMR ( 400 MHz, CD OD, 3:1 mixture
3
1
AUTHOR INFORMATION
Corresponding Author
2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
5
.4 Hz, 1H ), 4.78 ( q, J = 6.5 Hz, 1H ), 3.87 ( dd, J = 5.4 Hz,
1
J2 = 10.2 Hz, 1H ), 2.31ꢀ2.17 ( m, 1H ), 1.41 ( d, J = 6.5 Hz,
0
3
major rotamer ): δ 160.9, 140.3, 131.7, 129.1, 124.4, 110.9,
94.7, 72.6, 71.1, 28.8, 26.0, 20.6, 19.9; HRMS ( ESI ): calc.
for C H NaO [M+Na] : 245.1148; found: 245.1149. HPLC
*Eꢀmail: 2002flz@163.com
.72H ), 1.41 ( d, J = 6.5 Hz, 2.16H ), 1.17 ( d, J = 6.6 Hz,
ORCID:
Lizhen Fang: 0000ꢀ0001ꢀ8594ꢀ4710
Notes
13
H ), 1.09 ( d, J = 6.6 Hz, 3H ); C NMR ( 100 MHz, CD OD,
3
The authors declare no competing financial interests.
+
13
18
3
®
(DAICEL CHIRALPAK IA column, eluent: Hexanes/iꢀPrOH
=
2
92/8, detector: 280 nm, flow rate: 0.5 mL/min, 35 ˚C): t =
ACKNOWLEDGMENT
R
5.972 min (major), t = 30.824 min (minor).
R
This project was sponsored by the National Natural Science
Foundation of China (No. 81172952), the program for Sciꢀ
ence&Technology Innovation Talents in Universities of Heꢀnan
Province (17HASTIT043), the support project for the Discipliꢀ
nary group of Psychology and Neuroscience, Xinxiang Medical
University. (2016PNꢀKFKTꢀ15).
(2S,3S)ꢀ2ꢀbenzylꢀ5ꢀ((R)ꢀ1ꢀhydroxyethyl)ꢀ2,3ꢀdihydroꢀbenzo
furanꢀ3ꢀol (16c). Colorless oil, 82% yield, 85% ee, >99/1 dr;
1
H NMR ( 400 MHz, CD OD, 3:1 mixture of rotamers ): δ
3
7
7
1
4
3
.42 ( d, J = 1.6 Hz, 1H ), 7.40ꢀ7.37 ( m, 1H ), 7.37 ( s, 1H ),
.33ꢀ7.27 ( m, 2H ), 7.25ꢀ7.18 ( m, 2H ), 6.74 ( d, J = 8.3 Hz,
H ), 5.02 ( d, J = 5.8 Hz, 1H ), 4.78 ( q, J = 6.5 Hz, 1H ),
.63ꢀ4.55 ( m, 1H ), 3.21 ( dd, J = 5.4 Hz, J = 14.3 Hz, 1H ),
1
2
REFERENCES
.09 ( dd, J = 8.6 Hz, J = 14.3 Hz, 1H ), 1.41 ( d, J = 6.5 Hz,
1
2
1
3
0.74H ), 1.41 ( d, J = 6.5 Hz, 2.22H ); C NMR ( 100 MHz,
CD OD, major rotamer ): δ 159.2, 139.0, 138.8, 129.7, 129.2,
128.1, 127.6, 126.1, 123.0, 109.5, 88.2, 71.7, 69.5, 34.5, 24.5;
HRMS ( ESI ): calc. for C H NaO [M+Na] : 293.1148;
found: 293.1146. HPLC (DAICEL CHIRALPAK IA column,
eluent: Hexanes/iꢀPrOH =90/10, detector: 280 nm, flow rate:
0
(1) (a) Cardullo, N.; Pulvirenti, L.; Spatafora, C.; Musso, N.;
Barresi, V.; Condorelli, D. F.; Tringali, C. Dihydrobenzofuran Neoꢀ
lignanamides: LaccaseꢀMediated Biomimetic Synthesis and Antiproꢀ
liferative Activity. J. Nat. Prod. 2016, 79, 2122ꢀ2134. (b) Liu, Q.ꢀB.;
Huang, X.ꢀX.; Bai, M.; Chang, X.ꢀB.; Yan, X.ꢀJ.; Zhu, T.; Zhao, W.;
Peng, Y.; Song, S.ꢀJ. Antioxidant and Antiꢀinflammatory Active Diꢀ
hydrobenzofuran Neolignans from the Seeds of Prunus tomentosa. J.
Agric. Food Chem. 2014, 62, 7796ꢀ7803. (c) Yamaguchi, S.; Muro,
S.; Kobayashi, M.; Miyazawa, M.; Hirai, Y. Absolute Structures of
Some Naturally Occurring Isopropenyldihydrobenzofuꢀrans, Remirol,
Remiridiol, Angenomalin, and Isoangenomalin. J. Org. Chem. 2003,
68, 6274ꢀ6278. (d) Masi, M.; Cimmino, A.; Boari, A.; Tuzi, A.; Zonꢀ
no, M. C.; Baroncelli, R.; Vurro, M.; Evidente, A. Colletochlorins E
and F, New Phytotoxic Tetrasubstituted Pyranꢀ2ꢀone and Dihydroꢀ
benzofuran, Isolated from Colletotrichum higginsianum with Potenꢀ
tial Herbicidal Activity. J. Agric. Food Chem. 2017, 65, 1124ꢀ1130.
(e) Ward, R. S. Lignans, Neolignans, and Related Compounds. Nat.
Prod. Rep. 1993, 10, 1ꢀ28. (f) Tshitenge, D. T.; Feineis, D.; Awale,
S.; Bringmann, G. Gardenifolins A−H, Scalemic Neolignans from
Gardenia ternifolia: Chiral Resolution, Configurational Assignment,
and Cytotoxic Activities against the HeLa Cancer Cell Line. J. Nat.
Prod. 2017, 80, 1604ꢀ1614.
(2) (a) Apers, S.; Paper, D.; Bürgermeister, J.; Baranikova, S.;
Dick, S. V.; Lemière, G.; Vlietinck, A.; Pieters, L. Antiangiogenic
Activity of Synthetic Dihydrobenzofuran Lignans. J. Nat. Prod. 2002,
65, 718ꢀ720. (b) Bose, J. S.; Gangan, V.; Prakash, R.; Jain, S. K.;
Manna, S. K. A Dihydrobenzofuran Lignan Induces Cell Death by
Modulating Mitochondrial Pathway and G2/M Cell Cycle Arrest. J.
Med. Chem. 2009, 52, 3184ꢀ3190. (c) O'Malley, S. J.; Tan, K. L.;
Watzke, A.; Bergman, R. G.; Ellman, J. A. Total Synthesis of (+)ꢀ
Lithospermic Acid by Asymmetric Intramolecular Alkylation via
Catalytic CꢀH Bond Activation. J. Am. Chem. Soc. 2005, 127, 13496ꢀ
13497. (d) Pieters, L.; Dyck, S. V.; Gao, M.; Bai, R. l.; Hamel, E.;
Vlietinck, A.; Lemière, G. Synthesis and Biological Evaluation of
Dihydrobenzofuran Lignans and Related Compounds as Potential
Antitumor Agents that Inhibit Tubulin Polymerization. J. Med. Chem.
3
+
17 18
3
®
.5 mL/min, 35 ˚C): t = 32.286 min (major), t = 40.577 min
R
R
(minor).
(2S,3S)ꢀ2ꢀ(furanꢀ2ꢀylmethyl)ꢀ5ꢀ((R)ꢀ1ꢀhydroxyethyl)ꢀ2,3ꢀdiꢀ
hydrobenzofuranꢀ3ꢀol (16d). Colorless oil, 90% yield, 92%
ee, >99/1 dr; H NMR ( 400 MHz, CD OD, 3:1 mixture of
rotamers ): δ 7.43ꢀ7.38 ( m, 2H ), 7.23 ( dd, J = 1.9 Hz, J =
8
6
Hz, 1H ), 4.72ꢀ4.66 ( m, 1H ), 3.22 ( dd, J = 5.6 Hz, J = 15.6
Hz, 1H ), 3.13 ( dd, J = 8.4 Hz, J = 15.6 Hz, 1H ), 1.41 ( d, J
= 6.5 Hz, 0.76H ), 1.41 ( d, J = 6.5 Hz, 2.28H ); C NMR
(
1
3
1
2
.3 Hz, 1H ), 6.75 ( d, J = 8.3 Hz, 1H ), 6.35ꢀ6.33 ( m, 1H ),
.23ꢀ6.20 ( m, 1H ), 5.07 ( d, J = 5.8 Hz, 1H ), 4.78 ( q, J = 6.5
1
2
1
2
13
100 MHz, CD OD, major rotamer ): δ 158.9, 152.4, 141.1,
3
1
6
39.0, 129.3, 127.5, 122.9, 110.0, 109.3, 106.2, 85.1, 71.5,
9.3, 27.1, 24.3; HRMS ( ESI ): calc. for C H NaO
1
5
16
4
+
[
M+Na] : 283.0941; found: 283.0941. HPLC (DAICEL
®
CHIRALPAK IA column, eluent: Hexanes/iꢀPrOH =85/15,
detector: 280 nm, flow rate: 0.5 mL/min, 35 ˚C): t = 21.590
min (major), t = 24.028 min (minor).
R
R
General Procedure for Preparation of Racemic Comꢀ
pounds 2. To a solution of 1a (117 mg, 0.5 mmol) in MeOH
(2 mL) at 0°C was added NaBH (37.8 mg, 1 mmol) in batchꢀ
4
es. The resulting mixture was stirred under for 2 h and then
quenched with aq 1N HCl. After concentration, the mixture
was extracted with ethyl acetate. The organic layer was colꢀ
lected, dried over Na SO , filtered, and concentrated under
reduced pressure. Purification of the residue by silica gel colꢀ
umn chromatography (Petroleum ether /ethyl acetate = 2/1)
2
4
8
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The Journal of Organic Chemistry
1
999, 42, 5475ꢀ5481. (e) Ghosh, A. K.; Cheng, X.; Zhou, B. Enantiꢀ
oselective Total Synthesis of (+)ꢀLithospermic Acid. Org. Lett. 2012,
4, 5046ꢀ5049.
3) (a) Enders, D.; Fronert, J.; Bisschops, T.; Boeck, F. Asymmetric
(7) (a) Ros, A.; Magriz, A.; Dietrich, H.; Fernández, R.; Alvarez,
E.; Lassaletta, J. M. Enantioselective Synthesis of Vicinal Halohyꢀ
drins via Dynamic Kinetic Resolution. Org. Lett. 2006, 8, 127ꢀ130.
(b) Cheng, T.ꢀY.; Ye, Q.ꢀQ.; Zhao, Q.ꢀK.; Liu, G.ꢀH. Dynamic Kinetꢀ
ic Resolution of Phthalides via Asymmetric Transfer Hydrogenation:
1
2
3
4
5
6
7
8
9
1
(
total synthesis of smyrindiol employing an organocatalytic aldol key
step. Beilstein J. Org. Chem. 2012, 8, 1112ꢀ1117. (b) Kesava Reddy,
N.; Vijaykumar, B.V.D ; Chandrasekhar, S. Formal Synthesis of Anꢀ
tiplatelet Drug, Beraprost. Org. Lett. 2012, 14, 299ꢀ301. (c) Natori,Y.;
Tsutsui, H.; Sato, N.; Nakamura, S.; Nambu, H.; Shiro, M.; Hashimoꢀ
to, S. Asymmetric Synthesis of Neolignans (ꢀ)ꢀepiꢀConocarpan and
A
Strategy Constructs 1,3ꢀDistereocentered 3ꢀ(2ꢀHydroxyꢀ2 arꢀ
ylethyl)isobenzofuranꢀ1(3H)ꢀone. Org. Lett. 2015, 17, 4972ꢀ4975. (c)
Vyas, V. K.; Bhanage, B. M. Kinetic Resolution Driven Diastereoꢀ
and Enantioselective Synthesis of cisꢀβꢀHeteroaryl Amino Cycloalkaꢀ
nols by RutheniumꢀCatalyzed Asymmetric Transfer Hydrogenation.
Org. Lett. 2016, 18, 6436ꢀ6439. (d) Xiong, Z.ꢀC.; Pei, C.ꢀF.; Xue, P.;
Lv, H.; Zhang, X.ꢀM. Highly enantioselective transfer hydrogenation
of racemic αꢀsubstituted βꢀketo sulfonamides via dynamic kinetic
resolution. Chem. Commun. 2018, 54, 3883ꢀ3886. (e) Ashley, E. R.;
Sherer, E. C.; Pio, B.; Orr, R. K.; Ruck, R. T. RutheniumꢀCatalyzed
Dynamic Kinetic Resolution Asymmetric Transfer Hydrogenation of
#ꢀChromanones by an EliminationꢀInduced Racemization Mechanism.
ACS Catal. 2017, 7, 1446−1451. (f) Jeran, M.; Cotman, A. E.; Stephꢀ
an, M.; Mohar, B. Stereopure Functionalized Benzosultams via Ruꢀ
thenium(II)ꢀCatalyzed Dynamic Kinetic Resolution−Asymmetric
Transfer Hydrogenation. Org. Lett. 2017, 19, 2042−2045. (g) Zheng,
D.ꢀS.; Zhao, Q.ꢀK.; Hu, X.ꢀY.; Cheng, T.ꢀY.; Liu, G.ꢀH.; Wang, W. A
dynamic kinetic asymmetric transfer hydrogenationꢀcyclization tanꢀ
dem reaction: An easy access to chiral 3,4ꢀdihydroꢀ2Hꢀpyranꢀ
carbonitriles. Chem. Commun. 2017, 53, 6113−6116. (h) Hu, X.ꢀY.;
Zhang, K.; Chang, F.ꢀW.; Liu, R.; Liu, G.ꢀH.; Cheng, T.ꢀY. A substiꢀ
tution/dynamic kinetic resolution – Asymmetric transfer hydrogenaꢀ
tion tandem process for preparation of stereocenters βꢀhydroxy sulꢀ
fones. Molecular Catalysis, 2018, 452, 271ꢀ276.
(
+)ꢀConocarpan via Rh(II)ꢀCatalyzed CꢀH Insertion Process and Reꢀ
vision of the Absolute Configuration of (ꢀ)ꢀepiꢀConocarpan. J. Org.
Chem. 2009, 74, 4418ꢀ4421. (d) Wang, D.ꢀH.; Yu, J.ꢀQ. Highly Conꢀ
vergent Total Synthesis of (+)ꢀLithospermic. Acid via a LateꢀStage
Intermolecular CꢀH Olefination. J. Am. Chem. Soc. 2011, 133, 5767ꢀ
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
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769.
(4) (a) Kagan, H. B.; Riant, O. Catalytic Asymmetric DielsꢀAlder
Reactions. Chem. Rev. 1992, 92, 1007ꢀ1019. (b) Diels, O.; Alder, K.
Synthesen in der hydroaromatischen Reihe. J. Liebigs Ann. der Chem.
1
928, 460, 98ꢀ122. (c) Nicolaou, K. C.; Snyder, S. A.; Montagnon, T.;
Vassilikogiannakis, G. The Diels ꢀ Alder Reaction in Total Synthesis.
Angew. Chem. Int. Ed. 2002, 41, 1668ꢀ1698. (d) Namboothiri, I. N.
N.; Ganesh, M.; Mobin, S. M.; Cojocaru, M. A Stereoselective and
AtomꢀEfficient Approach to Multifunctionalized Fiveꢀ and Sixꢀ
Membered Rings via a Novel MichaelꢀInitiated Intramolecular Dielsꢀ
Alder Furan Reaction. J. Org. Chem. 2005, 70, 2235ꢀ2243. (e) Lee,
H. Y.; Kim, H. Y.; Tae, H.; Kim, B. G.; Lee, J. OneꢀPot Threeꢀ
Component Tandem Metathesis/DielsꢀAlder Reaction. Org. Lett.
2003, 5, 3439ꢀ3442. (f) Yu, S.ꢀY.; Zhang, H.; Gao, Y.; Mo, L.; Wang,
S.ꢀZ.; Yao, Z.ꢀJ. Asymmetric Cascade Annulation Based on Enantiꢀ
oselective OxaꢀDielsꢀAlder Cycloaddition of in Situ Generated Isoꢀ
(8) (a) Fang, L.ꢀZ.; Liu, S.ꢀS.; Han, L.ꢀL.; Li, H.ꢀH.; Zhao, F.ꢀF.
Ruthenium ꢀCatalyzed Synthesis of cisꢀ2,3ꢀDihydrobenzofuranꢀ3ꢀols
by Aqueous Transfer Hydrogenation via Dynamic Kinetic Resolution.
Organometallics 2017, 36, 1217ꢀ1219. (b) Fang, L.ꢀZ.; Lyu, Q.ꢀH.;
Lu, C.ꢀJ.; Li, H.ꢀH.; Liu, S.ꢀS.; Han, L.ꢀL. Synthesis of Chiral Dihyꢀ
drobenzofurans and Phthalides by Asymmetric Transfer Hydrogenaꢀ
tion via Dynamic Kinetic Resolution:A Strategy for Total Synthesis
of Daldinins A, B, and C and Concentricolide. Adv. Synth. Catal.
2016, 358, 3196ꢀ3200.
chromenyliums by Cooperative Binary Catalysis of Pd(OAc)
Trip. J. Am. Chem. Soc. 2013, 135, 11402ꢀ11407.
(5) (a) Pellissier, H. Recent Developments in Asymmetric Organoꢀ
catalytic Domino Reactions. Adv. Synth. Catal. 2012, 354, 237ꢀ294.
b) Poulin, J.; GriséꢀBard, C. M.; Barriault, L. Pericyclic domino
2
and (S)
‑
(
reactions: concise approaches to natural carbocyclic frameworks.
Chem. Soc. Rev. 2009, 38, 3092ꢀ3101. (c) Enders, D.; Grondal, C.;
Hüttl, M. R. Asymmetric Organocatalytic Domino Reactions. Angew.
Chem. Int. Ed. 2007, 46, 1570ꢀ1581. (d) Guo, H.ꢀC.; Ma, J.ꢀA. Cataꢀ
lytic Asymmetric Tandem Transformations Triggered by Conjugate
Additions. Angew. Chem. Int. Ed. 2006, 45, 354ꢀ366. (e) Tietze, L. F.;
Beifuss, U. Sequential Transformations in Organic Chemistry: A
Synthetic Strategy with a Future. Angew. Chem. Int. Ed. 1993, 32,
131ꢀ163. (f) Xie, P.ꢀZ.; Wang, L.ꢀY.; Yang, L.ꢀH.; Li, E.ꢀQ.; Ma, J.ꢀ
Z.; Huang,Y.; Chen, R.ꢀY. Domino Reaction for the Chemoꢀ and
Stereoselective Synthesis of transꢀ2,3ꢀDihydrobenzofurans from Nꢀ
Thiophosphinyl Imines and Sulfur Ylides. J. Org. Chem. 2011, 76,
(9) (a) Sandoval, C. A.; Bie, F.; Matsuoka, A.; Yamaguchi, Y.;
Naka, H.; Li, Y.ꢀH.; Kato, K.; Utsumi, N.; Tsutsumi, K.; Ohkuma, T.;
6
Murata, K.; Noyori, R. Chiral η ꢀArene/NꢀTosylethylenediamineꢀ
Ruthenium(II) Complexes: Solution Behavior and Catalytic Activity
for Asymmetric Hydrogenation. Chem. Asian J. 2010, 5, 806ꢀ816. (b)
Li, F.; Wang, N.ꢀN.; Lu, L.; Zhu, G.ꢀJ. Regioselective Hydration of
Terminal Alkynes Catalyzed by
a Neutral Gold(I) Complex
[(IPr)AuCl] and OneꢀPot Synthesis of Optically Active Secondary
Alcohols from Terminal Alkynes by the Combination of [(IPr)AuCl]
and Cp*RhCl[(R,R)‑TsDPEN]. J. Org. Chem. 2015, 80, 3538ꢀ3546.
7
699ꢀ7705.
(c) Kišić, A.; Stephan, M.; Mohara, B. ansaꢀRuthenium(II) Complexꢀ
6
(6) (a) Pellissier, H. Recent developments in dynamic kinetic resoꢀ
es of DPENꢀSO
2
N(Me) (CH
2
)
n
(η ꢀaryl) Conjugate Ligands for
lution. Tetrahedron 2008, 64, 1563ꢀ1601. (b) Ros, A.; Magriz, A.;
Dietrich, H.; Lassaletta, J. M.; Fernández, R. Enantioselective Synꢀ
thesis of cisꢀαꢀSubstituted Cycloalkanols and transꢀꢀCycloalkyl
Amines Thereof. Tetrahedron 2007, 63, 6755ꢀ6763. (c) Noyori, R.;
Hashiguchi, S. Asymmetric Transfer Hydrogenation Catalyzed by
Chiral Ruthenium Complexes. Acc. Chem. Res. 1997, 30, 97ꢀ102. (d)
Echeverria, P. G.; Ayad, T.; Phansavath, P.; RatovelomananaꢀVidal,
V. Recent Developments in Asymmetric Hydrogenation and Transfer
Hydrogenation of Ketones and Imines through Dynamic Kinetic Resꢀ
olution. Synthesis 2016, 48, 2523ꢀ2539.
Asymmetric Transfer Hydrogenation of Aryl Ketones. Adv. Synth.
Catal. 2014, 356, 3193ꢀ3198.
(10) (a) Noyori, R.; Yamakawa, M.; Hashiguchi, S. MetalꢀLigand
Bifunctional Catalysis: A Nonclassical Mechanism for Asymmetric
Hydrogen Transfer between Alcohols and Carbonyl Compounds. J.
Org. Chem. 2001, 66, 7931ꢀ7944. (b) Dub, P. A.; Gordon, J. C. The
mechanism of enantioselective ketone reduction with Noyori and
NoyoriꢀIkariya bifunctional catalysts. Dalton Trans. 2016, 45, 6756–
6781.
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