Ru-Catalyzed Chemo- And Enantioselective Hydrogenation of 2,4-Pentadien-1-ones: Synthesis of Chiral 2,4-Pentadien-1-ols

Article abstract of DOI:10.1021/acs.joc.9b02576

The asymmetric hydrogenation of 2,4-pentadien-1-ones has been achieved by using trans-RuCl₂[(R)-XylylSunPhos][(R)-Daipen] as a catalyst under basic conditions. This hydrogenation demonstrated exclusive C1-carbonyl selectivity, and thus the conjugated 2,4-diene motifs remained untouched, which provides a synthetically useful method for various chiral 2,4-pentadien-1-ols.

Full text of DOI:10.1021/acs.joc.9b02576

Subscriber access provided by University of Cincinnati Libraries
Article
Ru-Catalyzed Chemo- and Enantioselective Hydrogenation of
2,4-Pentadien-1-ones: Synthesis of Chiral 2,4-Pentadien-1-ols
Chengyang Li, Wenkui Lu, Bin Lu, Wanfang Li, Xiaomin Xie, and Zhaoguo Zhang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b02576 • Publication Date (Web): 18 Nov 2019
Downloaded from pubs.acs.org on November 18, 2019
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a service to the research community to expedite the dissemination
of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in
full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully
peer reviewed, but should not be considered the official version of record. They are citable by the
Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore,
the “Just Accepted” Web site may not include all articles that will be published in the journal. After
a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web
site and published as an ASAP article. Note that technical editing may introduce minor changes
to the manuscript text and/or graphics which could affect content, and all legal disclaimers and
ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or
consequences arising from the use of information contained in these “Just Accepted” manuscripts.
is published by the American Chemical Society. 1155 Sixteenth Street N.W.,
Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the
course of their duties.

Page 1 of 20
The Journal of Organic Chemistry
1
2
3
4
5
6
Ru-Catalyzed Chemo- and Enantioselective Hydrogenation of 2,4-Pentadien-1-
ones: Synthesis of Chiral 2,4-Pentadien-1-ols
7
8
9
Chengyang Li,† Wenkui Lu,† Bin Lu,† Wanfang Li,‡ Xiaomin Xie,† and Zhaoguo Zhang*,†,§
†Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Chemistry and Chemical
Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China
‡College of Science, University of Shanghai for Science and Technology, Shanghai 200093, China
§Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai
200032, China
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
zhaoguo@sjtu.edu.cn
ABSTRACT
The asymmetric hydrogenation of 2,4-pentadien-1-ones has been achieved by using trans-RuCl2[(R)-
XylylSunPhos][(R)-Daipen] as catalyst under basic conditions. This hydrogenation demonstrated
exclusive C1-carbonyl selectivity and thus the conjugated 2,4-diene motifs remained untouched, which
provides a synthetically useful method for various chiral 2,4-pentadien-1-ols.
INTRODUCTION
Over the past few decades, homogeneous catalytic asymmetric hydrogenation of porchiral ketones has
become a mature and powerful method for the synthesis of secondary chiral alcohols.1 In this field,
selective hydrogenation of carbonyl groups in unsaturated ketones has been considered difficult for a
long time (Scheme 1a). The two hydrogenation systems, Ir-DIOP2 and [Ir(BINAP)(COD)]BF4-
aminophosphine3 gave good chemoselectivities but with only moderate enantioselectivities. Since the
1990s, Noyori and co-workers has made a great progress by introducing novel and efficient Ru-
diphosphane-diamine bifunctional catalysts.1b,4 This significant discovery characterized excellent
compatibility of various functional groups and the reversion of the classical chemoseletivitity in the
hydrogenation of C=C and C≡C over C=O groups. Subsequently, Ru-diphosphane-diamine catalyzed
hydrogenation represents one of the most reliable approach to various types of valuable chiral allylic
alcohols.5 Besides, several other catalytic hydrogenation systems,6 kinetic resolution,7 enantioselective
aldehydevinylation,8 asymmetric transfer hydrogenation,9 and other asymmetric reduction of unsaturated
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 20
1
2
3
4
5
ketones10 have been developed for this purpose with high chemoselectivities and moderate to excellent
enantioselectivities.
6
7
Scheme 1. The Asymmetric Hydrogenation of Conjugated Ketones
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
However, the asymmetric hydrogenation of α,β-γ,δ-unsaturated ketones, which possessed multiple
unsaturated bonds conjugated carbonyl, is rarely explored. To the best of our knowledge, only the
hydrogenation of β-ionone which contains a low activity tetrasubstituted double bond, has been reported
(Scheme 1b).3,4b,4d,6e Furthermore, the polyene-conjugated chiral allyl alcohols are important units of a
number of natural compounds and biologically active molecules (Figure 1). On the other hand, these
motifs with conjugated polyenes could be further exploited through subsequent diverse transformations,
for example, they could serve as both dienes and dienophiles in Diels-Alder rection.11 Up to now, only a
few methods are available for the synthersis of chiral secondary polyenols, such as asymmetric
reduction,10a,10d,10f asymmetric addition,12 reductive coupling13 and (dynamic) kinetic resolution.14
Nevertheless, these synthetic methods suffered from limited scope of substrates, low efficiency and/or
poor enantioselectivity. Accordingly, the search for effective and highly selective approaches to
synthesize enantiomerically pure polyenols is still a significant and challenging work.
Figure 1. Selected Chiral 2,4-Pentadiene-1-ol Units in Drugs and Natural Products
Our group has been devoted to the Ru-catalyzed asymmetric hydrogenation of functionalized and
ACS Paragon Plus Environment

Page 3 of 20
The Journal of Organic Chemistry
1
2
3
4
5
simple ketones using SunPhos and its derivatives as chiral ligands.1j,15 As our continued interest, we
reported herein an efficient and selective synthetic approach for polyene-conjugated chiral allyl alcohol
through Ru-SunPhos-catalyzed asymmetric hydrogenation of α,β-γ,δ-unsaturated ketones.
6
7
8
9
RESULTS AND DISCUSSION
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Inspired by the fact that in 1998 Noyori et al. adopted the weak base K2CO3, instead of conventional
tBuOK, in the hydrogenation of some highly base sensitive unsaturated ketones with improvement of ee
values,4d we chose the easily available (3E,5E)-6-phenylhexa-3,5-dien-2-one (1a) as the model substrate,
and initially carried out the reaction in i-PrOH containing trans-RuCl2[(S)-SunPhos][(S)-Daipen] and
K2CO3 under 10 bar of H2 at 30 °C for 15 h. To our surprises, the corresponding chiral alcohol 2a was
obtained with nearly quantitative yield and 91.3% ee (Table 1, entry 1). Next, various chiral diphosphines
(shown in Figure 2) were also tested to explore the effect of the ligand structure on the reactivity and
enantioselectivity for the asymmetric hydrogenation of α,β-γ,δ-unsaturated ketones. The results are
showed in Table 1. Tol-SunPhos or DMM-SunPhos with matching configuration diamine-DAIPEN also
gave good enantioselectivities but slightly lower than that using Xylyl-SunPhos as the ligand (Table 1,
entries 1-4, 91.3%-95.6% ee). The matching/mismatching effect between diphosphine and diamine was
also included here. Mismatching ligands led to disappointed result (Table 1, entries 5, 77.0% ee, 35%
conv.). Employing other several commercially available diphosphine ligands, such as (S)-BINAP, (S)-
SEGPhos, (S)-C3-TunePhos and (S)-MeO-Biphep with matching (S)-DAIPEN resulted in good ee values
(Table 1, entries 6-9, 83.1%-92.9% ee). Overall, the diphosphine Xylyl-SunPhos was the ligand of choice
in terms of enantioselectivity.
Figure 2. Structures of bidentate ligands.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 20
1
2
3
4
5
6
7
8
9
Table 1. Effects of Ligands in Asymmetric Hydrogenation a
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
entry
cat
ee (%)b
-91.3
94.7
1
2
3
4c
5
6
7
8
9
trans-{RuCl2[(S)-DAIPEN][(S)-SunPhos]}
trans-{RuCl2[(R)-DAIPEN][(R)-Tol-SunPhos]}
trans-{RuCl2[(R)-DAIPEN][(R)-Xylyl-SunPhos]}
trans-{RuCl2[(S)-DAIPEN][(R)-Xylyl-SunPhos]}
trans-{RuCl2[(S)-DAIPEN][(S)-DMM-SunPhos]}
trans-{RuCl2[(S)-DAIPEN][(S)-BINAP]}
trans-{RuCl2[(S)-DAIPEN][(S)-MeO-Biphep]}
trans-{RuCl2[(S)-DAIPEN][(S)-SegPhos]}
trans-{RuCl2[(S)-DAIPEN][(S)-C3-TunePhos]}
95.6
77.0
-95.2
-83.1
-90.0
-89.6
-92.9
aUnless otherwise stated, all reactions were carried out with a substrate (0.25
mmol) in mL i-PrOH under 10 bar H2 at 30 °C for 15 h,
1
substrate/catalyst/K2CO3 = 100/1/10. All in full conversion. bDetermined by
HPLC on a Chiralpak IA-3 column. c35% conversion by 1H NMR..
Next, the effects of the solvent, reaction temperature, and hydrogen pressure were explored and the
results were depicted in Table 2. Both protic solvents (i-PrOH, MeOH, EtOH, i-BuOH and isoamyl
alcohol, Table 2, entries 1-5) and aprotic solvents (THF, DCM and toluene, Table 2, entries 5-7) were
tested, and it turned out that i-PrOH was the best choice for this hydrogenation. The enantioselectivity
of the hydrogenation was dramatically influenced by the reaction temperature. Increased the temperature
caused an obvious drop of enantiomeric excess (Table 2, entry 9, 50 °C, 87.3% ee). Unexpectedly, the
hydrogen pressures exhibited little effect on the reaction (Table 2, entry 10, 30 bar, 94.2% ee). Moreover,
the transfer hydrogenation process was also excluded by the result that 1a was fully recovered in the
absence of hydrogen (Table 2, entry 11).
Table 2. Optimization of Solvent, Temperature, and Pressurea
ACS Paragon Plus Environment

Page 5 of 20
The Journal of Organic Chemistry
1
2
3
4
conv.(%)b
ee (%)c
entry
solvent
P (bar)
5
6
7
8
i-PrOH
MeOH
10
10
10
10
10
10
> 99
90
95.6
92.4
93.4
92.3
94.9
--
1
2
9
EtOH
> 99
> 99
> 99
0
3
4
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
i-BuOH
Isoamyl alcohol
DCM
5
6
THF
10
10
10
30
0
0
0
--
--
7
8
Toluene
i-PrOH
i-PrOH
i-PrOH
9 d
10
11e
> 99
> 99
0
87.3
94.2
--
aUnless otherwise stated, all reactions were carried out using trans-
{RuCl2[(R)-DAIPEN][(R)-Xylyl-SunPhos]} as the catalyst with
substrate (43.0 mg, 0.25 mmol) in 1 mL solvent under 10 bar of H2 at
30 °C for 15 h, substrate/catalyst/K2CO3 = 100/1/10. bDetermined by
c
d
NMR. Determined by HPLC on a Chiralpak IA-3 column. Reaction
temperature 50 °C. eWithout H2.
Subsequently, we turned our attention to the effect of bases (Table 3). tBuOK, which was mostly used in
Ru/diphosphine/diamine hydrogenation systems, gave very poor enantioselectivity (Table 3, entry 2, 5.2%
ee). And it was investigated that the lack of enantioselectivity using tBuOK as base was not due to product
t
i
racemization. When we treat the product 2a in the presence of BuOK in PrOH, no racemization was
observed. Other potassium bases (KOH, K3PO4 and KOAc) other carbonates (Cs2CO3, Na2CO3) and
organic base (NEt3) led to lower enantioselectivities and/or activities than using K2CO3 as the base.
Table 3. Screening of Basea
entry
solvent
conv.(%)b
ee (%)c
K2CO3
tBuOK
KOH
> 99
> 99
> 99
> 99
95.6
5.2
1
2
3
4
8.3
K3PO4
12.7
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 20
1
2
3
4
5
6
7
8
9
Cs2CO3
Na2CO3
Et3N
> 99
48
66.3
5
6
95.3
--
0
0
7
8
--
KOAc
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
aUnless otherwise stated, all reactions were carried out
using trans-{RuCl2[(R)-DAIPEN][(R)-Xylyl-SunPhos]}
as the catalyst with substrate (43.0 mg, 0.25 mmol) in 1 mL
i-PrOH under 10 bar of H2 at 30 °C for 15 h,
b
substrate/catalyst/base = 100/1/10. Determined by NMR.
cDetermined by HPLC on a Chiralpak IA-3 column.
With the optimized conditions in hand, the scope of substrates was investigated and the results were
summarized in Scheme 2. A series of polyene-conjugated chiral allyl alcohols were synthesized with
perfect chemical selectivities, good to excellent ee values and wide functional group tolerance. The
model substrate 1a (R = Me) was hydrogenated in 99% yield and 95.6% ee. When the substrate with a
longer chain, the activity and enantioselectivity was still remained (R = n-Pr, 1b; 98% yield, 94.9% ee).
However, when the substrate 1c containing a bulkier isopropyl group was subjected to the reaction, the
corresponding product 2c was obtained in only 37.5% ee. Substituents on the conjugated diene motifs
had little influence on the selective hydrogenation reactions wherein the desired chiral alcohols 2d-f were
isolated with good enantioselectivities and high yields. When the substrates possessing meta-CF3 (1g) or
ortho-Me (1h) were subjected to this hydrogenation, the corresponding hydrogenation products 2g and
2h were obtained in 90.4% and 94.0% ee, respectively. Besides, a range of para-substituted substrates
delivered universally high enantiomeric excess, and halogen (1i-1k), methoxyl (1l) and dimethylamino
group (1m) were tolerated. Notably, the nitro group was also bearable in the reaction, affording the
product 2n in 93.3% ee, albeit in 62% conversion. Interestingly, compound 1o with conjugated triple and
double bonds was also hydrogenated in good chemo- and enantioselectivity. Moreover, under the
reaction conditions, substrate 1p and 1q both gave high yield and Enantioselectivity. In addition,
hydrogenation of heterocyclic compound 1r and 1s afforded the corresponding alcohols with good ee
values in full conversion.
With tarns-RuCl2[(R)-XylylSunPhos][(R)-Daipen]-K2CO3 as catalyst, hydrogenation of 1t afforded 2t
in full conversion but only 67.5% ee. The ortho-Cl compound 1u was attempted delivering desired
alcohol with excellent enantioselectivity (2u, 92.2% ee). This phenomenon is under further investigation
to find whether steric hindrance or electronic effect dominate the difference.
Scheme 2. Substrate Scopea
ACS Paragon Plus Environment

Page 7 of 20
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
aUnless otherwise stated, all reactions were carried out using trans-{RuCl2[(R)-DAIPEN][(R)-
Xylyl-SunPhos]} as the catalyst with a substrate (0.25 mmol) in 1 mL i-PrOH under 10 bar of
H2 at 30 °C for 15 h, substrate/catalyst/K2CO3 = 100/1/10. All in full conversion. The ee values
were determined by HPLC on a Chiralpak column. The absolute configurations of 2b-2s were
determined according to 2a. b62% conversion by 1H NMR.
Finally, to further evaluate the catalytic efficiency of this hydrogenation system, a gram scale
hydrogenation of 1a (7.5 mmol, 1.29 g) was carried out (S/C = 1000) under 30 bar of H2 at 30 oC for 48
h, and the chiral product (S,3E,5E)-6-phenylhexa-3,5-dien-2-ol (2a) could be obtained in 98% yield and
95.2% ee (Scheme 3).
Scheme 3. Gram-Scale Asymmetric Hydrogenation of 1a
CONCLUSION
In summary, we realized a general and practical selective hydrogenation of 2,4-pentadiene-1-ones to 2,4-
pentadiene-1-ols. The conjugated disubstituted C=C bonds remained untouched to afford a wide range
of enantiopure 1,3-dieneols. The bifunctional catalyst trans-{RuCl2[(R)-DAIPEN][(R)-Xylyl-SunPhos]}
showed high enantioselectivity (up to 98% ee) and reactivity (S/C up to 1000) for a wide range of 2,4-
pentadiene-1-ones under very mild conditions. Further applications of this protocol are currently under
investigation in our group.
EXPERIMENTAL SECTION
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 20
1
2
3
4
5
6
7
8
9
General Procedures. Unless those noted below, commercially available reagents purchased from
macklin chemical company were used throughout without further purification. EtOH and MeOH were
distilled from magnesium under nitrogen. iPrOH and DCM were dried over CaH2 under nitrogen. Toluene
and THF were freshly distilled from Na-benzophenone under nitrogen. Unless otherwise noted, all
reactions were performed using standard Schlenk techniques under an atmosphere of nitrogen. Oil bath
was used in all experiments for reactions that require heating. Flash column chromatography was
performed using 300-400 mesh silica gel. 1HNMR spectra were recorded at 500 MHz with TMS as an
internal standard. 13C{1H} NMR spectra were recorded at 125 MHz and referenced to the central peak
of 39.52 ppm for d6-DMSO or 77.00 ppm for CDCl3. Coupling constants (J) are reported in units (Hz)
and refer to apparent peak multiplications. Specific rotation [α]D were obtained in a 0.5 dm cell using the
D-line (589 nm) of a sodium lamp. HRMS data were measured on an ESI-TOF mass spectrometer. IR
data determinated from Perkin Elmer Spectrum 100 (KBr).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Typical Procedure for the Preparation of 1a, 1e, 1g-1n, 1q, 1r, 1s.
To a solution of the corresponding aldehyde (10 mmol) in acetone (10 mL) and H2O (10 mL) was added
dropwise 10 mL 5% NaOH aqueous solution slowly at room temperature; Upon completion of the
reaction (monitored by TLC), the pH value was adjusted to 6-7 with 10% HCl, and the resulting solution
was extracted with DCM (20 mL × 3). The combined organic phase was washed with saturated brine
before dried over anhydrous Na2SO4, and the concentration was conducted under vacuum. The crude
product was purified by flash column chromatography or recrystallized from DCM/ PE (petroleum ether).
Typical Procedure for the Preparation of 1b, 1t, 1u.
To a solution of the corresponding aldehyde (10 mmol) and ketone (11 mmol) in EtOH (10 mL) was
added dropwise 10 mL 5% NaOH aqueous solution slowly at room temperature; Upon completion of the
reaction (monitored by TLC), the pH value was adjusted to 6-7 with 10% HCl, and the resulting solution
was extracted with DCM (20 mL × 3). The combined organic phase was washed with saturated brine
before dried over anhydrous Na2SO4, and the concentration was conducted under vacuum. The crude
product was purified by flash column chromatography or recrystallized from DCM/ PE.
(3E,5E)-6-Phenylhexa-3,5-dien-2-one (1a):16 Recrystallized from DCM/ PE. Yellow solid: 1.41 g, 82%
yield; mp: 60–61 °C; 1H NMR (500 MHz, CDCl3): δ 7.48–7.46 (m, 2H), 7.38–7.26 (m, 4H), 6.97 –6.85
(m, 2H), 6.26 (d, J = 15.5 Hz, 1H), 2.31 (s, 3H).13C{1H} NMR (125 MHz, CDCl3): δ 198.3, 143.4, 141.2,
135.9, 130.4, 129.2, 128.8, 127.2, 126.6, 27.3.
(5E,7E)-8-Phenylocta-5,7-dien-4-one (1b):17 Recrystallized from DCM/ PE. Pale yellow solid: 0.41 g,
21% yield; mp: 41–43 °C; 1H NMR (500 MHz, CDCl3):δ 7.48–7.47 (m, 2H), 7.38–7.30 (m, 4H), 6.95
(d, J = 15.5 Hz, 1H), 6.88 (dd, J = 15.5 Hz, 10.5Hz, 1H), 6.29 (d, J = 15.5 Hz, 1H), 2.58 (t, J = 7.5 Hz,
2H), 1.73–1.65 (m, 2H), 0.97 (t, J = 7.5 Hz, 3H). 13C{1H} NMR (125 MHz, CDCl3): δ 200.6, 142.3,
141.1, 136.0, 129.7, 129.1, 128.8, 127.1, 126.7, 42.6, 17.8, 13.8.
(4E,6E)-2-Methyl-7-phenylhepta-4,6-dien-3-one (1c): Under nitrogen atmosphere, to a pre-cooled
solution of diisopropylamine (2.42 g, 12 mmol), THF (20 mL) was added n-butyl lithium solution
dropwisely (11 mmol, 2.4 M, 4.6 mL) at -20°C, and the resulting solution was stirred at -20°C for 0.5 h.
Then 3-methyl-2-butanone(0.86 g, 10 mmol) in 5 mL THF was added dropwisely, keeping the
temperature at -20°C, after the addition the mixture was stirred for another 0.5 h, then cinnamaldehyde
ACS Paragon Plus Environment

Page 9 of 20
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
(1.45 g, 11 mmol) in 5 mL THF added dropwise at -20°C. After completion of addition, the reaction was
stirred for 1 h, then quenched with 3 mL 10% HCl at -20°C. The mixture was extracted by ethyl acetate
(30 mL × 3).and the combined organic phase was washed by brine before dried using Na2SO4. Combined
organic phase was washed by brine before dried using Na2SO4.
After removing the solvents under vacuum, Ac2O (4 mL) and NaOAc (1 g) was added and the
resulting mixture was stirred over night at room temperature under nitrogen atmosphere. Then the
mixture was heated to 110°C for 10 minutes before ethanol (10 mL) was added at RT, then the mixture
was stirred for another 2h. Finally the mixture was filtered and the solvent was evaporated before it was
subjected to column separation.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Petroleum ether/ Ethyl acetate = 50/1 as the eluent. Then recrystallized from DCM/ PE. Pale yellow
solid: 1.34 g, 67% yield; mp: 59.4–61.0 °C; 1H NMR (500 MHz, CDCl3): δ 7.48–7.46 (m, 2H), 7.41–
7.29 (m, 4H), 6.97–6.87 (m, 2H), 6.37 (d, J = 15.0 Hz, 1H), 2.90–2.82 (m, 1H), 1.15 (d, J = 6.5 Hz, 6H).
13C{1H} NMR (125 MHz, CDCl3): δ 204.0, 142.4, 141.1, 136.1, 129.1, 128.8, 127.8, 127.1, 126.8, 39.1,
18.50. FT-IR (KBr, cm-1): 3553, 3479, 3417, 3239, 2976, 2966, 1681, 1639, 1615, 1590, 1464, 1450,
1385, 1456, 1285, 1227, 1184, 1124, 1084, 1051, 1022, 760, 707, 690, 617, 511, 475. HRMS-ESI (m/z):
(M + H)+ calcd. for C14H17O, 201.1279; found 201.1272.
(E)-2-((E)-3-Phenylallylidene)cyclobuta-1-one (1d):18 Petroleum ether/ Ethyl acetate = 100/1 as the
eluent. Pale yellow solid: 0.59 g, 32% yield; mp: 104.1–105.9 °C; 1H NMR (500 MHz, CDCl3): δ 7.49–
7.47 (m, 2H), 7.38–7.30 (m, 3H), 6.94 (d, J = 15.0 Hz, 1H), 6.84–6.72 (m, 2H), 3.03–2.99 (m, 2H), 2.80–
2.77 (m, 2H). 13C{1H} NMR (125 MHz, CDCl3): δ 199.2, 147.6, 142.5, 136.1, 129.2, 128.8, 127.2, 126.6,
123.4, 43.7, 20.8.
(3E,5E)-5-Methyl-6-phenylhexa-3,5-dien-2-one (1e):19 Recrystallized from DCM/ PE. Pale yellow
solid: 0.71 g, 38% yield; mp: 68.6–69.4 °C; 1H NMR (500 MHz, CDCl3): δ 7.40–7.28 (m, 6H), 6.89 (s,
1H), 6.26 (d, J = 16.0 Hz, 1H), 2.34 (s, 3H), 2.06 (d, J = 1.0 Hz, 3H). 13C{1H} NMR (125 MHz, CDCl3):
δ 198.6, 148.7, 139.7, 136.6, 134.4, 129.4, 128.3, 127.8, 126.7, 27.5, 13.7.
(3E,5Z)-5-Bromo-6-phenylhexa-3,5-dien-2-one (1f):20 Synthesized according to the literature.20
Petroleum ether/ Ethyl acetate = 20/1 as the eluent. Yellow solid: 1.05 g, 42% yield; mp: 38.4–39.1 °C;
1H NMR (500 MHz, DMSO): δ 7.83–7.81 (m, 3H), 7.60 (d, J = 15.0 Hz, 1H), 7.50–7.42 (m, 3H), 6.45
(d, J = 15.0 Hz, 1H), 2.34 (s, 1H). 13C{1H} NMR (125 MHz, DMSO): δ 197.4, 143.6, 140.3, 134.6, 130.7,
129.8, 129.7, 128.5, 120.1, 28.0.
(3E,5E)-6-(3-(Trifluoromethyl)phenyl)hexa-3,5-dien-2-one (1g): Petroleum ether/ Ethyl acetate =
50/1 as the eluent. Yellow oil: 1.35g, 56% yield; 1H NMR (500 MHz, CDCl3): δ 7.70 (s, 1H), 7.64–7.63
(m, 1H), 7.57–7.55 (m, 1H), 7.50–7.47 (m, 1H), 7.31–7.26 (m, 1H), 6.98–6.91 (m, 2H), 6.32 (d, J = 15.5
Hz, 1H), 2.33 (s, 3H). 13C{1H} NMR (125 MHz, CDCl3): δ 198.2, 142.4, 139.1, 136.7, 131.5, 131.3 (q,
J = 32.3 Hz), 130.1, 129.3, 128.3, 125.5 (q, J = 3.8 Hz), 123.8 (q, J = 270.8 Hz), 123.7 (q, J = 3.8 Hz),
27.50. 19F NMR (471 MHz, CDCl3): δ -62.9. FT-IR (KBr, cm-1): 3551, 3479, 3417, 3041, 1669, 1619,
1436, 1363, 1327, 1281, 1254, 1207, 1125, 1098, 1073, 996, 962, 914, 877, 795, 695, 664, 641, 597, 561,
520. HRMS-ESI (m/z): (M + H)+ calcd. for C13H12F3O, 241.0840; found 241.0832.
(3E,5E)-6-(o-Tolyl)hexa-3,5-dien-2-one (1h):19 Petroleum ether/ Ethyl acetate = 50/1 as the eluent.
Yellow oil: 1.41g, 76% yield; 1H NMR (500 MHz, CDCl3): δ 7.57–7.55 (m, 1H), 7.33 (dd, J = 15.5, 10.5
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 20
1
2
3
4
5
6
Hz, 1H), 7.24–7.17 (m, 4H), 6.81 (dd, J = 15.5, 11.0 Hz, 1H), 6.26 (d, J = 15.5 Hz, 1H), 2.40 (s, 3H),
2.33 (s, 3H). 13C{1H} NMR (125 MHz, CDCl3): δ 198.4, 143.7, 138.9, 136.6, 134.8, 130.7, 130.3, 129.0,
127.6, 126.3, 125.6, 27.4, 19.7.
7
8
9
(3E,5E)-6-(4-Chlorophenyl)hexa-3,5-dien-2-one (1i):16 Recrystallized from DCM/ PE. Yellow solid:
1.31 g, 63% yield; mp: 73.5–74.7 °C; 1H NMR (500 MHz, CDCl3): δ 7.41–7.39 (m, 2H), 7.35–7.32 (m,
2H), 7.29–7.24 (m, 1H), 6.92–6.82 (m, 2H), 6.27 (d, J = 16.0 Hz, 1H), 2.32 (s, 3H). 13C{1H} NMR (125
MHz, CDCl3): δ 198.3, 142.9, 139.7, 134.9, 134.4, 130.8, 129.1, 128.3, 127.2, 27.4.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(3E,5E)-6-(4-Bromophenyl)hexa-3,5-dien-2-one (1j):19 Recrystallized from DCM/ PE. Yellow solid:
1.97 g, 78% yield; mp: 100.7–102.5 °C; 1H NMR (500 MHz, CDCl3): δ 7.50–7.48 (m, 2H), 7.35–7.33
(m, 2H), 7.29–7.24 (m, 1H), 6.91–6.83 (m, 2H), 6.27 (d, J = 15.5 Hz, 1H), 2.32 (s, 3H). 13C{1H} NMR
(125 MHz, CDCl3): δ 198.3, 142.9, 139.7, 134.9, 132.0, 130.9, 128.6, 127.3, 123.2, 27.5.
(3E,5E)-6-(4-Fluorophenyl)hexa-3,5-dien-2-one (1k):14a Petroleum ether/ Ethyl acetate = 20/1 as the
eluent. Yellow oil: 1.70 g, 89% yield; 1H NMR (500 MHz, CDCl3): δ 7.47–7.43 (m, 2H), 7.30–7.24 (m,
1H), 7.08–7.03 (m, 2H), 6.91 (d, J = 15.5 Hz, 1H), 6.80 (dd, J = 15.5, 10.5 Hz, 1H), 6.25 (d, J = 15.5 Hz,
1H), 2.31 (s, 3H). 13C{1H} NMR (125 MHz, CDCl3): δ 198.3, 163.1 (d, J = 250.6 Hz), 143.1, 139.8,
132.2 (d, J = 3.5 Hz), 130.4 (d, J = 1.1 Hz), 128.9 (d, J = 8.1 Hz), 126.3 (d, J = 2.5 Hz), 115.8(d, J = 21.8
Hz), 27.4. 19F NMR (471 MHz, CDCl3): δ -111.2.
(3E,5E)-6-(4-Methoxyphenyl)hexa-3,5-dien-2-one (1l):14a Recrystallized from DCM/ PE. Yellow solid:
1
1.82g, 90% yield; mp: 103.9–104.8 °C; H NMR (500 MHz, CDCl3): δ 7.44–7.41 (m, 2H), 7.31–7.26
(m, 1H), 6.92–6.88 (m, 3H), 6.79–6.74 (m, 1H), 6.22 (d, J = 15.5 Hz, 1H), 3.84 (s, 3H), 2.31 (s, 3H).
13C{1H} NMR (125 MHz, CDCl3): δ 198.5, 160.6, 144.0, 141.1, 129.4, 128.8, 128.7, 124.5, 114.3, 55.4,
27.3.
(3E,5E)-6-(4-(Dimethylamino)phenyl)hexa-3,5-dien-2-one (1m): Recrystallized from DCM/ PE. Red
solid: 1.70g, 79% yield; mp: 131.1–132.4 °C; 1H NMR (500 MHz, CDCl3): δ 7.38–7.35 (m, 2H), 7.32–
7.27 (m, 1H), 6.88 (d, J = 15.5 Hz, 1H), 6.73–6.66 (m, 3H), 6.16 (d, J = 15.5 Hz, 1H), 3.01 (s, 6H), 2.29
(s, 3H). 13C{1H} NMR (125 MHz, CDCl3): δ 198.5, 151.1, 144.9, 142.2, 128.8, 127.9, 124.1, 122.1,
112.0, 40.2, 27.1. FT-IR (KBr, cm-1): 3554, 3478, 3416, 1639, 1619, 1385, 1365, 1258, 1156, 1085, 994,
669, 618, 476. HRMS-ESI (m/z): (M + H)+ calcd. for C14H18NO, 216.1388; found 216.1380.
(3E,5E)-6-(4-Nitrophenyl)hexa-3,5-dien-2-one (1n):16 Recrystallized from DCM/ PE. Brown solid:
1.70 g, 78% yield; mp: 115.6–116.3 °C; 1H NMR (500 MHz, CDCl3): δ 8.25–8.22 (m, 2H), 7.64–7.60
(m, 2H), 7.32–7.26 (m, 1H), 7.05–6.97 (m, 2H), 6.36 (d, J = 16.0 Hz, 1H), 2.35 (s, 3H). 13C{1H} NMR
(125 MHz, CDCl3): δ 198.1, 147.6, 142.1, 141.7, 138.0, 132.6, 130.8, 127.6, 124.2, 27.7.
(E)-6-Phenylhex-3-en-5-yn-2-one (1o):21 Synthesized according to the literature.21 Petroleum ether/
1
Ethyl acetate = 20:1 as the eluent. Yellow solid: 0.63 g, 37% yield; mp: 40.1–42.3 °C; H NMR (500
MHz, CDCl3): δ 7.50–7.48 (m, 2H), 7.40–7.34 (m, 3H), 6.84 (d, J = 16.0 Hz, 1H), 6.57 (d, J = 16.0 Hz,
1H), 2.31 (s, 3H). 13C{1H} NMR (125 MHz, CDCl3): δ 197.0, 137.7, 131.9, 129.4, 128.5, 123.8, 122.1,
99.6, 86.7, 27.6.
(3E,5E)-hepta-3,5-dien-2-one (1q): 17 Petroleum ether/ Ethyl acetate = 50:1 as the eluent. Pale yellow
oil: 0.53 g, 48% yield; 1H NMR (500 MHz, CDCl3): δ 7.13–7.07 (m, 1H), 6.24–6.17 (m, 2H), 6.05 (d, J
= 15.0 Hz, 1H), 2.26 (s, 3H), 1.88 (d, J = 5.0 Hz, 3H). 13C{1H} NMR (125 MHz, CDCl3): δ 198.7, 143.7,
ACS Paragon Plus Environment

Page 11 of 20
The Journal of Organic Chemistry
1
2
3
4
140.2, 130.1, 128.5, 27.0, 18.7.
(3E,5E)-6-(Furan-2-yl)hexa-3,5-dien-2-one (1r):14a Petroleum ether/ Ethyl acetate = 10/1 as the eluent.
Red solid: 1.18g, 73% yield; mp: 34.2–35.8°C; 1H NMR (500 MHz, CDCl3): δ 7.45 (d, J = 1.5 Hz, 1H),
7.22 (dd, J = 15.0, 10.5 Hz, 1H), 6.81–6.70 (m, 2H), 6.48–6.44 (m, 2H), 6.24 (d, J = 15.5 Hz, 1H), 2.30
(s, 3H). 13C{1H} NMR (125 MHz, CDCl3): δ 198.2, 152.1, 143.8, 142.9, 130.2, 127.6, 124.9, 112.2,
112.1, 27.4.
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(3E,5E)-6-(3-(4-Fluorophenyl)-1-isopropyl-1H-indol-2-yl)hexa-3,5-dien-2-one (1s): Petroleum
ether/ Ethyl acetate = 10/1 as the eluent. Yellow solid: 1.18g, 37% yield; mp: 104.3–105.7 °C; 1H NMR
(500 MHz, CDCl3): δ 7.56–7.50 (m, 2H), 7.41–7.37 (m, 2H), 7.25–7.19 (m, 2H), 7.17–7.12 (m, 2H),
7.11–7.07 (m, 1H), 7.03 (d, J = 15.5 Hz, 1H), 6.38 (dd, J = 16.0, 11.5 Hz, 1H), 6.06 (d, J = 15.5 Hz, 1H),
4.94–4.86 (m, 1H), 2.27 (s, 3H), 1.70 (d, J = 7.0 Hz, 6H). 13C{1H} NMR (125 MHz, CDCl3): δ 198.1,
161.7 (d, J = 246.5 Hz), 143.0, 136.2, 132.4, 131.8 (d, J = 7.9 Hz), 130.8 (d, J = 3.3 Hz), 130.7, 130.1,
129.8, 128.4, 123.1, 120.1, 120.0, 118.2, 115.6 (d, J = 21.4 Hz), 111.9, 47.9, 27.7, 21.8. 19F NMR (471
MHz, CDCl3): δ -115.6. FT-IR (KBr, cm-1): 3555, 3479, 3417, 1663, 1639, 1609, 1525, 1358, 1343, 1225,
1156, 1142, 999, 749, 669, 618, 566, 476. HRMS-ESI (m/z): (M + H)+ calcd. for C23H23FNO, 348.1764;
found 348.1766.
(2E,4E)-1,5-Diphenylpenta-2,4-dien-1-one (1t):22 Recrystallized from EtOH. Yellow solid: 1.61 g, 69%
yield; mp: 93.8–94.8 °C; 1H NMR (500 MHz, CDCl3): δ 7.99–7.97 (m, 2H), 7.63–7.56 (m, 2H), 7.52–
7.48 (m, 4H), 7.39–7.31 (m, 3H), 7.10 (d, J = 15.0 Hz, 1H), 7.07–7.00 (m, 2H). 13C{1H} NMR (125
MHz, CDCl3): δ 190.4, 144.8, 141.9, 138.2, 136.1, 132.6, 129.2, 128.8, 128.5, 128.3, 127.3, 126.9, 125.4.
(2E,4E)-1-(2-Chlorophenyl)-5-phenylpenta-2,4-dien-1-one (1u):23 Recrystallized from DCM/ PE.
Yellow solid: 1.32 g, 49% yield; mp: 66.6–68.3 °C; 1H NMR (500 MHz, CDCl3): δ 7.48–7.31 (m, 9H),
7.22 (dd, J = 15.5, 9.5 Hz, 1H), 7.01–6.92 (m, 2H), 6.67 (d, J = 15.5 Hz, 1H). 13C{1H} NMR (125 MHz,
CDCl3): δ 193.9, 146.4, 142.5, 139.2, 135.9, 131.19, 131.18, 130.2, 129.6, 129.4, 129.2, 128.9, 127.4,
126.8, 126.6.
Typical Procedure for the Asymmetric Hydrogenation.
To a 25 mL Schlenk tube were placed (R)-Xylyl-SunPhos (17.2 mg, 22 μmol) and[RuCl2(benzene)]2 (5.0
mg, 10 μmol), the tube was evacuated and purged with nitrogen three times before addition of freshly
distilled and freeze-thaw degassed DMF (2 mL). The resulting mixture was heated at 100 °C for 10 min
before it was cooled to room temperature, and then (R)-Daipen (7.5 mg, 24 μmol) in DMF (1 mL) was
added. The tube was heated to 40 °C for 4 h before the solvent was removed to give a brownish yellow
i
solid. The catalyst was dissolved in freeze-thaw degassed PrOH (8 mL), and then the solution was
equally charged into eight vials which contained 0.25 mmol of substrates, K2CO3 (3.5 mg, 0.025 mmol).
Then the vials were transferred into a 300 mL autoclave. The autoclave was purged three times with H2,
and the required pressure of H2 was set under specified reaction conditions. After cooling to ambient
temperature and hydrogen was released carefully, the autoclaves were opened and the solvent was
evaporated. The residue was filtered through a short pad of silica gel column, and the enantiomeric excess
was directly determined by HPLC. The crude product was further purified by flash column
chromatography on silica gel to provide the pure compound.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 20
1
2
3
4
5
6
7
8
9
(S,3E,5E)-6-Phenylhexa-3,5-dien-2-ol (2a):14a White solid: 43.1 mg, 99% yield; mp: 70.5–71.8 °C; 1H
NMR (500 MHz, CDCl3):δ 7.39–7.37 (m, 2H), 7.32–7.29 (m, 2H), 7.23–7.20 (m, 1H), 6.75 (dd, J = 16.0,
10.5 Hz, 1H), 6.54 (d, J = 15.5 Hz, 1H), 6.37 (dd, J = 15.5, 10.5 Hz, 1H), 5.86 (dd, J = 15.5, 6.5 Hz, 1H),
4.43–4.38 (m, 1H), 1.32 (d, J = 6.5 Hz, 3H). 13C{1H} NMR (125 MHz, CDCl3): δ 137.6, 137.1, 132.6,
129.8, 128.6, 128.2, 127.5, 126.3, 68.5, 23.3. HPLC (Chiralcel IA-3 column, hexane/i-PrOH = 95/5, 1.0
mL/min, 254 nm): t1 = 10.7 min, t2 = 11.6 min. [α]2D5 = – 16.5 (c = 0.46 in CHCl3) for (S)-enantiomer
with 95.6% ee. (Lit.10d [α]D24 = + 17.73 (c=2.82 in CHCl3) for (R)-enantiomer with 90% ee.)
(S,5E,7E)-8-Phenylocta-5,7-dien-4-ol (2b):24 White solid: 49.5 mg, 98% yield; mp: 44.9–46.0 °C; 1H
NMR (500 MHz, CDCl3): δ 7.38–7.37 (m, 2H), 7.31–7.28 (m, 2H), 7.23–7.19 (m, 1H), 6.75 (dd, J =
15.5, 10.5 Hz, 1H), 6.53 (d, J = 15.5 Hz, 1H), 6.36 (dd, J = 15.5, 10.5 Hz, 1H), 5.81 (dd, J = 15.5, 7.0
Hz, 1H), 4.22–4.17 (m, 1H), 1.62–1.36 (m, 4H), 0.94 (t, J = 7.0 Hz, 3H). 13C{1H} NMR (125 MHz,
CDCl3): δ 137.1, 136.8, 132.5, 130.5, 128.5, 128.3, 127.5, 126.3, 72.4, 39.4, 18.6, 14.0. HPLC (Chiralcel
IA-3 column, hexane/i-PrOH = 90/10, 0.6 mL/min, 254 nm): t1 = 11.4 min, t2 = 12.5 min. [α]2D5 = – 1.7
(c = 0.23 in CHCl3) for (S)-enantiomer with 94.9% ee.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
(S,4E,6E)-2-Methyl-7-phenylhepta-4,6-dien-3-ol (2c):14c Pale yellow oil: 49.6 mg, 98% yield; H
NMR (500 MHz, CDCl3):δ 7.39–7.37 (m, 2H), 7.31–7.28 (m, 2H), 7.23–7.20 (m, 1H), 6.77 (dd, J = 15.5,
10.5 Hz, 1H), 6.53 (d, J = 16.0 Hz, 1H), 6.37 (dd, J = 15.0, 10.5 Hz, 1H), 5.82 (dd, J = 15.0, 7.0 Hz, 1H),
3.95–3.93 (t, J = 6.5 Hz, 1H), 1.81–1.73 (m, 1H), 0.96 (d, J = 7.0 Hz, 3H), 0.92 (d, J = 7.0 Hz, 3H).
13C{1H} NMR (125 MHz, CDCl3): δ 137.1, 135.0, 132.4, 131.5, 128.5, 128.3, 127.5, 126.3, 77.7, 34.0,
18.2, 18.0. HPLC (Chiralcel IA-3 column, hexane/i-PrOH = 90/10, 0.6 mL/min, 280 nm): t1 = 11.9 min,
t2 = 12.5 min. [α]2D5 = + 5.2 (c = 0.58 in CHCl3) for (S)-enantiomer with 37.5% ee. ( Lit.14c [α]D20 = + 0.9
(c= 1.89 in CHCl3) for (S)-enantiomer with 39.6% ee.)
(E)-2-((E)-3-Phenylallylidene)cyclobutan-1-ol (2d): White solid: 45.0 mg, 97% yield; mp: 99.4–
1
101.5 °C; H NMR (500 MHz, CDCl3): δ 7.39–7.38 (m, 2H), 7.31–7.28 (m, 2H), 7.22–7.19 (m, 1H),
6.73 (dd, J = 16.0, 11.0 Hz, 1H), 6.50 (d, J = 15.5 Hz, 1H), 6.25–6.21 (m, 1H), 4.80–4.76 (m, 1H), 2.74–
2.66 (m, 1H), 2.45–2.37 (m, 2H), 2.15 (brs, 1H), 1.91–1.82 (m, 1H). 13C{1H} NMR (125 MHz, CDCl3):
δ 149.5, 137.5, 131.3, 128.5, 127.3, 126.2, 124.4, 120.2, 71.7, 30.3, 22.5. HPLC (Chiralcel IA-3 column,
hexane/i-PrOH = 90/10, 0.6 mL/min, 254 nm): t1 = 11.4 min, t2 = 13.3 min. [α]2D5 = – 30.8 (c = 0.35 in
CHCl3) for (S)-enantiomer with 98.8% ee. FT-IR (KBr, cm-1): 3554, 3478, 3417, 1639, 1619, 967, 669,
618, 477. HRMS-ESI (m/z): (M + H – H2O)+ calcd. for C13H13, 169.1017; found 169.1010.
(S,3E,5E)-5-Methyl-6-phenylhexa-3,5-dien-2-ol (2e): Colorless oil: 45.6 mg, 97% yield; 1H NMR (500
MHz, CDCl3): δ 7.35–7.32 (m, 2H), 7.29–7.27 (m, 2H), 7.24–7.20 (m, 1H), 6.52 (s, 1H), 6.40 (d, J =
15.5 Hz, 1H), 5.82 (dd, J = 16.0, 7.0 Hz, 1H), 4.47–4.41 (m, 1H), 1.99 (d, J = 1.0 Hz, 3H), 1.34 (d, J =
6.0 Hz, 3H). 13C{1H} NMR (125 MHz, CDCl3): δ 137.7, 135.0, 134.8, 132.8, 131.6, 129.1, 128.1, 126.6,
69.0, 23.5, 13.9. HPLC (Chiralcel OJ-H column, hexane/i-PrOH = 90/10, 0.9 mL/min, 280 nm): t1 = 9.3
min, t2 = 10.9 min. [α]2D5 = – 9.7 (c = 0.39 in CHCl3) for (S)-enantiomer with 92.4% ee. FT-IR (KBr, cm-
1): 3400, 3081, 3023, 2972, 2923, 1638, 1598, 1491, 1445, 1385, 1367, 1303, 1145, 1058, 1013, 965,
947, 917, 861, 847, 824, 748, 699, 509. HRMS-ESI (m/z): (M + H – H2O)+ calcd. for C13H15, 171.1174;
found 171.1167.
1
(S,3E,5Z)-5-Bromo-6-phenylhexa-3,5-dien-2-ol (2f): Yellow oil: 59.2 mg, 94% yield; H NMR (500
ACS Paragon Plus Environment

Page 13 of 20
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
MHz, CDCl3): δ 7.67–7.65 (m, 2H), 7.38–7.34 (m, 2H), 7.32–7.28 (m, 1H), 6.96 (s, 1H), 6.43 (d, J =
15.0 Hz, 1H), 6.27 (dd, J = 14.5, 5.5 Hz, 1H), 4.55–4.49 (m, 1H), 1.36 (d, J = 6.5 Hz, 3H). 13C{1H} NMR
(125 MHz, CDCl3): δ 138.9, 135.6, 131.9, 129.8, 129.4, 128.2, 128.1, 122.6, 67.9, 23.5. HPLC (Chiralcel
IA-3 column, hexane/i-PrOH = 90/10, 0.6 mL/min, 280 nm): t1 = 12.0 min, t2 = 12.9 min. [α]2D5 = + 1.0
(c = 0.39 in CHCl3) for (S)-enantiomer with 91.1% ee. FT-IR (KBr, cm-1): 3434, 2920, 2849, 1645, 1446,
1384, 1265, 1066, 954, 751, 696. HRMS-ESI (m/z): (M + H – H2O)+ calcd. for C12H12Br, 235.0122; found
235.0123.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(S,3E,5E)-6-(3-(Trifluoromethyl)phenyl)hexa-3,5-dien-2-ol (2g): Yellow oil: 60.2 mg, 99% yield; 1H
NMR (500 MHz, CDCl3):δ 7.61 (s, 1H), 7.54 (d, J = 7.5 Hz, 1H), 7.47–7.40 (m, 2H), 6.81 (dd, J = 16.0,
10.5 Hz, 1H), 6.55 (d, J = 16.0 Hz, 1H), 6.39 (dd, J = 15.5, 10.5 Hz, 1H), 5.93 (dd, J = 15.5, 6.5 Hz, 1H),
4.46–4.41 (m, 1H), 1.34 (d, J = 6.0 Hz, 3H). 13C{1H} NMR (125 MHz, CDCl3): δ 139.1, 137.9, 131.0 (q,
J = 31.9 Hz), 130.9, 130.0, 129.3 (d, J = 0.9 Hz), 129.1, 129.0, 124.1 (q, J = 270.8 Hz), 123.9 (q, J = 3.6
Hz), 122.9 (q, J = 3.8 Hz), 68.4, 23.3. 19F NMR (471 MHz, CDCl3): δ -62.8. HPLC (Chiralcel IA-3
column, hexane/i-PrOH = 99/1, 0.9 mL/min, 280 nm): t1 = 17.8 min, t2 = 18.7 min. [α]2D5 = + 12.6 (c =
0.35 in CHCl3) for (S)-enantiomer with 90.4% ee. FT-IR (KBr, cm-1): 3400, 2974, 2929, 1620, 1448,
1384, 1331, 1204, 1165, 1125, 1096, 1072, 987, 946, 906, 791, 696, 663. HRMS-ESI (m/z): (M + H –
H2O)+ calcd. for C13H12F3, 225.0891; found 225.0883.
1
(S,3E,5E)-6-(o-Tolyl)hexa-3,5-dien-2-ol (2h): Yellow oil: 45.3 mg, 96% yield; H NMR (500 MHz,
CDCl3): δ 7.48–7.46 (m, 1H), 7.18–7.13 (m, 3H), 6.77 (d, J = 15.5 Hz, 1H), 6.66 (dd, J = 15.5, 10.5 Hz,
1H), 6.41 (dd, J = 15.0, 10.0 Hz, 1H), 5.86 (dd, J = 15.0, 6.0 Hz, 1H), 4.44–4.39 (m, 1H), 2.34 (s, 3H),
1.33 (d, J = 6.5 Hz, 3H). 13C{1H} NMR (125 MHz, CDCl3): δ 137.4, 136.0, 135.5, 130.4, 130.3, 130.1,
129.3, 127.4, 126.1, 125.1, 68.5, 23.3, 19.8. HPLC (Chiralcel IA-3 column, hexane/i-PrOH = 99/1, 0.6
mL/min, 280 nm): t1 = 39.4 min, t2 = 41.7 min. [α]2D5 = – 11.5 (c = 0.33 in CHCl3) for (S)-enantiomer
with 94.0% ee. FT-IR (KBr, cm-1): 3411, 3023, 2972, 2927, 1644, 1615, 1600, 1485, 1462, 1383, 1294,
1135, 1099, 1057, 989, 945, 866, 748, 715. HRMS-ESI (m/z): (M + H – H2O)+ calcd. for C13H15, 171.1174;
found 171.1167.
(S,3E,5E)-6-(4-Chlorophenyl)hexa-3,5-dien-2-ol (2i):25 White solid: 50.1 mg, 96% yield; mp: 84.5–
85.7 °C; 1H NMR (500 MHz, CDCl3): δ 7.32–7.26 (m, 4H), 6.72 (dd, J = 16.0, 10.5 Hz, 1H), 6.49 (d, J
= 16.0 Hz, 1H), 6.36 (dd, J = 15.0, 10.5 Hz, 1H), 5.88 (dd, J = 15.5, 6.5 Hz, 1H), 4.45–4.40 (m, 1H),
1.33 (d, J = 6.5 Hz, 3H). 13C{1H} NMR (125 MHz, CDCl3): δ 138.2, 135.6, 133.1, 131.3, 129.4, 128.81,
128.76, 127.5, 68.5, 23.3. HPLC (Chiralcel IA-3 column, hexane/i-PrOH = 95/5, 0.9 mL/min, 280 nm):
t1 = 14.1 min, t2 = 15.8 min. [α]2D5 = + 0.6 (c = 0.36 in CHCl3) for (S)-enantiomer with 93.0% ee.
(S,3E,5E)-6-(4-Bromophenyl)hexa-3,5-dien-2-ol (2j): White solid: 62.0 mg, 98% yield; mp: 90.1-
91.0 °C; 1H NMR (500 MHz, CDCl3): δ 7.44–7.41 (m, 2H), 7.26–7.23 (m, 2H), 6.73 (dd, J = 15.5, 10.5
Hz, 1H), 6.47 (d, J = 15.5 Hz, 1H), 6.35 (dd, J = 15.0, 10.5 Hz, 1H), 5.88 (dd, J = 15.0, 6.0 Hz, 1H),
4.44–4.39 (m, 1H), 1.32 (d, J = 6.5 Hz, 3H). 13C{1H} NMR (125 MHz, CDCl3): δ 138.4, 136.1, 131.7,
131.3, 129.4, 128.9, 127.8, 121.2, 68.4, 23.3. HPLC (Chiralcel IA-3 column, hexane/i-PrOH = 90/10,
0.6 mL/min, 280 nm): t1 = 13.9 min, t2 = 15.2 min. [α]2D5 = – 15.8 (c = 0.43 in CHCl3) for (S)-enantiomer
with 94.4% ee. FT-IR (KBr, cm-1): 3555, 3478, 3417, 1639, 1619, 994, 669, 618, 480. HRMS-ESI (m/z):
(M + H – H2O)+ calcd. for C12H12Br, 235.0122; found 235.0114.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 20
1
2
3
4
5
6
7
8
9
(S,3E,5E)-6-(4-Fluorophenyl)hexa-3,5-dien-2-ol (2k):14a Pale yellow solid: 46.7 mg, 97% yield; mp:
96.2–97.1 °C; 1H NMR (500 MHz, CDCl3): δ 7.35–7.31 (m, 2H), 7.01–6.97 (m, 2H), 6.65 (dd, J = 16.0,
10.5 Hz, 1H), 6.49 (d, J = 15.5 Hz, 1H), 6.34 (dd, J = 15.5, 10.5 Hz, 1H), 5.85 (dd, J = 15.5, 6.5 Hz, 1H),
4.43–4.38 (m, 1H), 1.32 (d, J = 6.5 Hz, 3H). 13C{1H} NMR (125 MHz, CDCl3): δ 162.2 (d, J = 245.6 H),
137.7 (d, J = 0.8 Hz), 133.3 (d, J = 3.3 Hz), 131.3, 129.5, 128.0 (d, J = 2.4 Hz), 127.8 (d, J = 7.8 Hz),
115.5 (d, J = 21.5 Hz), 68.4, 23.3. 19F NMR (471 MHz, CDCl3): δ -114.2. HPLC (Chiralcel IA-3 column,
hexane/i-PrOH = 95/5, 0.9 mL/min, 280 nm): t1 = 13.4 min, t2 = 14.9 min. [α]2D5 = – 18.0 (c = 0.40 in
CHCl3) for (S)-enantiomer with 95.5% ee.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(S,3E,5E)-6-(4-Methoxyphenyl)hexa-3,5-dien-2-ol (2l):14a Pale yellow solid: 50.2 mg, 98% yield; mp:
1
122.2–124.8 °C; H NMR (500 MHz, CDCl3): δ 7.33–7.30 (m, 2H), 6.86–6.83 (m, 2H), 6.62 (dd, J =
15.5, 10.5 Hz, 1H), 6.49 (d, J = 15.5 Hz, 1H), 6.34 (dd, J = 15.5, 10.5 Hz, 1H), 5.80 (dd, J = 15.0, 6.5
Hz, 1H), 4.42–4.37 (m, 1H), 3.80 (s, 3H), 1.31 (d, J = 6.5 Hz, 3H). 13C{1H} NMR (125 MHz, CDCl3): δ
159.2, 136.5, 132.2, 130.0, 129.9, 127.5, 126.2, 114.0, 68.6, 55.2, 23.3. HPLC (Chiralcel IA-3 column,
hexane/i-PrOH = 90/10, 0.6 mL/min, 280 nm): t1 = 16.6 min, t2 = 18.2 min. [α]2D5 = – 26.2 (c = 0.29 in
CHCl3) for (S)-enantiomer with 95.3% ee.
(S,3E,5E)-6-(4-(Dimethylamino)phenyl)hexa-3,5-dien-2-ol (2m): Red solid: 52.7mg, 97% yield; mp:
67.2–70.1 °C; 1H NMR (500 MHz, CDCl3): δ 7.29–7.27 (m, 2H), 6.67–6.65 (m, 2H), 6.57 (dd, J = 15.5,
10.5 Hz, 1H), 6.47 (d, J = 15.5 Hz, 1H), 6.33 (dd, J = 15.5, 10.5 Hz, 1H), 5.75 (dd, J = 15.0, 6.5 Hz, 1H),
4.40–4.35 (m,, 1H), 2.95 (s, 6H), 1.30 (d, J = 6.5 Hz, 3H). 13C{1H} NMR (125 MHz, CDCl3): δ 150.0,
135.1, 133.0, 130.6, 127.4, 125.6, 124.1, 112.4, 68.8, 40.4, 23.3. HPLC (Chiralcel IA-3 column, hexane/i-
PrOH = 90/10, 0.6 mL/min, 290 nm): t1 = 16.6 min, t2 = 19.5 min. [α]2D5 = – 30.7 (c = 0.52 in CHCl3) for
(S)-enantiomer with 94.0% ee. FT-IR (KBr, cm-1): 3434, 2969, 2873, 1610, 1522, 1442, 1384, 1357,
1228, 1190, 1156, 1128, 1060, 984, 941, 870, 825, 798, 669, 527. HRMS-ESI (m/z): (M + H – H2O)+
calcd. for C14H18N, 200.1439; found 200.1433.
(S,3E,5E)-6-(4-Nitrophenyl)hexa-3,5-dien-2-ol (2n): Yellow solid: 31.8 mg, 58% yield; mp: 58.9–
61.5 °C; 1H NMR (500 MHz, CDCl3): δ 8.19–8.16 (m, 2H), 7.52–7.49 (m, 2H), 6.91 (dd, J = 15.5, 10.5
Hz, 1H), 6.59 (d, J = 15.5 Hz, 1H), 6.42 (dd, J = 15.5, 10.5 Hz, 1H), 6.02 (dd, J = 15.5, 6.0 Hz, 1H),
4.48–4.45 (m, 1H), 1.35 (d, J = 6.5 Hz, 3H). 13C{1H} NMR (125 MHz, CDCl3): δ 146.7, 143.7, 141.0,
132.8, 130.0, 128.7, 126.7, 124.1, 68.3, 23.3. HPLC (Chiralcel IA-3 column, hexane/i-PrOH = 90/10,
0.6 mL/min, 254 nm): t1 = 31.6 min, t2 = 35.7 min. [α]2D5 = + 22.2 (c = 0.45 in CHCl3) for (S)-enantiomer
with 93.3% ee. FT-IR (KBr, cm-1): 3400, 2972, 2925, 1616, 1592, 1513, 1341, 1181, 1109, 1057, 990,
853, 825, 747, 691. HRMS-ESI (m/z): (M + H – H2O)+ calcd. for C12H12NO2, 202.0868; found 202.0860.
1
(S,E)-6-Phenylhex-3-en-5-yn-2-ol (2o):25 Colorless oil: 41.3 mg, 96% yield; H NMR (500 MHz,
CDCl3): δ 7.44–7.41 (m, 2H), 7.32–7.29 (m, 3H), 6.27 (dd, J = 16.0, 5.5 Hz, 1H), 5.92 (dd, J = 15.5, 1.5
Hz, 1H), 4.44–4.39(m, 1H), 1.33 (d, J = 6.5 Hz, 3H). 13C{1H} NMR (125 MHz, CDCl3): δ 146.6, 131.5,
128.3, 128.2, 123.2, 109.2, 90.1, 87.2, 68.3, 23.0. HPLC (Chiralcel OJ-H column, hexane/i-PrOH = 95/5,
0.9 mL/min, 280 nm): t1 = 31.5 min, t2 = 33.1 min. [α]2D5 = + 3.5 (c = 0.34 in CHCl3) for (S)-enantiomer
with 90.3% ee.
1
(S,E)-6-Methylhepta-3,5-dien-2-ol (2p): Colorless oil: 31.1 mg, 99% yield; H NMR (500 MHz,
CDCl3): δ 6.41 (dd, J = 15.0, 11.0 Hz, 1H), 5.81 (d, J = 11.5 Hz, 1H), 5.60 (dd, J = 15.0, 7.0 Hz, 1H),
ACS Paragon Plus Environment

Page 15 of 20
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
4.39–4.34 (m, 1H), 1.78 (s, 3H), 1.76 (s, 3H), 1.29 (d, J = 6.5 Hz, 3H). 13C{1H} NMR (125 MHz, CDCl3):
δ 136.1, 134.2, 126.3, 124.2, 68.9, 26.0, 23.4, 18.3. HPLC (Chiralcel AS-H column, hexane/i-PrOH =
99/1, 0.9 mL/min, 254 nm): t1 = 7.7 min, t2 = 8.2 min. [α]2D5 = + 6.8 (c = 1.53 in CHCl3) for (S)-
enantiomer with 90.7% ee. FT-IR (KBr, cm-1): 3548, 3475, 3417, 2978, 2934, 1637, 1619, 1457, 1385,
1260, 1147, 1084, 618, 476. HRMS-ESI (m/z): (M + H – H2O)+ calcd. for C8H13, 109.1017; found
109.1011.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(S,3E,5E)-hepta-3,5-dien-2-ol (2q):14a Colorless oil: 27.2 mg, 97% yield; 1H NMR (500 MHz, CDCl3):
δ 6.16 (dd, J = 15.5, 10.5 Hz, 1H), 6.06–6.00 (m, 1H), 5.74–5.67 (m, 1H), 5.60 (dd, J = 15.0, 6.5 Hz,
1H), 4.31–4.29 (m, 1H), 1.83 (s, 1H), 1.75 (dd, J = 6.5, 1.0 Hz, 1H), 1.27 (d, J = 6.5 Hz, 3H). 13C{1H}
NMR (125 MHz, CDCl3): δ 134.4, 130.7, 129.85, 129.81, 68.5, 23.3, 18.0. HPLC (Chiralcel OD-H
column, hexane/i-PrOH = 99/1, 0.6 mL/min, 210 nm): t1 = 8.2 min, t2 = 8.8 min. [α]2D4 = + 1.6 (c = 0.50
in CHCl3) for (S)-enantiomer with 93.3% ee.
1
(S,3E,5E)-6-(Furan-2-yl)hexa-3,5-dien-2-ol (2r):14a Yellow oil: 38.9 mg, 95% yield; H NMR (500
MHz, CDCl3): δ 7.35 (d, J = 1.5 Hz, 1H), 6.66 (dd, J = 15.5, 11.0 Hz, 1H), 6.38–6.25 (m, 4H), 5.84 (dd,
J = 15.5, 6.5 Hz, 1H), 4.41–4.36 (m, 1H), 2.11 (brs, 1H), 1.30 (d, J = 6.5 Hz, 3H). 13C{1H} NMR (125
MHz, CDCl3): δ 152.9, 142.1, 137.8, 129.2, 126.8, 120.1, 111.5, 108.3, 68.4, 23.2. HPLC (Chiralcel IA-
3 column, hexane/i-PrOH = 95/5, 0.6 mL/min, 280 nm): t1 = 17.2 min, t2 = 18.8 min. [α]2D5 = – 15.2 (c =
0.58 in CHCl3) for (S)-enantiomer with 95.4% ee.
(S,3E,5E)-6-(3-(4-Fluorophenyl)-1-isopropyl-1H-indol-2-yl)hexa-3,5-dien-2-ol (2s): Yellow solid:
1
85.4 mg, 98% yield; mp: 43.8–45.7 °C; H NMR (500 MHz, CDCl3): δ 7.55–7.52 (m, 2H), 7.43–7.39
(m, 2H), 7.21–7.17 (m, 1H), 7.14–7.06 (m, 3H), 6.58 (d, J = 15.5 Hz, 1H), 6.36–6.23 (m, 2H), 5.68 (dd,
J = 15.0, 6.5 Hz, 1H), 4.92–4.84 (m, 1H), 4.41–4.37 (m, 1H), 1.67 (d, J = 7.0 Hz, 6H), 1.54 (d, J = 3.5
Hz, 1H), 1.30 (d, J = 6.5 Hz, 3H). 13C{1H} NMR (125 MHz, CDCl3): δ 161.4 (d, J = 243.3 Hz), 138.1,
135.5, 134.0, 133.7, 131.7 (d, J = 7.8 Hz), 131.4 (d, J = 3.3 Hz), 129.5, 128.4, 121.9, 121.5, 119.7, 119.4,
115.3 (d, J = 21.1 Hz), 115.2, 111.7, 68.3, 47.6, 23.4, 21.6.19F NMR (471 MHz, CDCl3): δ -116.6. HPLC
(Chiralcel IA-3 column, hexane/i-PrOH = 95/5, 0.9 mL/min, 280 nm): t1 = 9.0 min, t2 = 9.8 min. [α]D25
=
– 0.2 (c = 0.99 in CHCl3) for (S)-enantiomer with 91.1% ee. FT-IR (KBr, cm-1): 3551, 3478, 3417, 1640,
1619, 1385, 1222, 1157, 669, 650, 618. HRMS-ESI (m/z): (M + H)+ calcd. for C23H25FNO, 350.1920;
found 350.1924.
1
(2E,4E)-1,5-Diphenylpenta-2,4-dien-1-ol (2t):26 White oil: 57.8 mg, 98% yield; H NMR (500 MHz,
CDCl3): δ 7.40–7.34 (m, 6H), 7.31–7.27 (m, 3H), 7.23–7.20 (m, 1H), 6.76 (dd, J = 15.5, 10.5 Hz, 1H),
6.56 (d, J = 15.5 Hz, 1H), 6.45 (dd, J = 15.0, 10.5 Hz, 1H), 5.98 (dd, J = 15.0, 6.5 Hz, 1H), 5.29 (d, J =
6.5 Hz, 1H), 2.13 (brs, 1H). 13C{1H} NMR (125 MHz, CDCl3): δ 142.7, 137.0, 135.5, 133.2, 130.9, 128.6,
128.0, 127.7, 127.6, 126.4, 126.3, 74.8. HPLC (Chiralcel IA-3 column, hexane/i-PrOH = 90/10, 0.6
mL/min, 254 nm): t1 = 16.5 min, t2 = 18.7 min. [α]2D5 = – 13.7 (c = 0.48 in CHCl3) with 67.5% ee.
(2E,4E)-1-(2-Chlorophenyl)-5-phenyl-1l3-penta-2,4-dien-1-ol (2u): Yellow solid: 64.9 mg, 96% yield;
mp: 78.4–79.9 °C; 1H NMR (500 MHz, CDCl3): δ 7.60–7.58 (m, 1H), 7.38–7.35 (m, 3H), 7.32–7.28 (m,
3H), 7.24–7.20 (m, 2H), 6.77 (dd, J = 15.5, 10.5 Hz, 1H), 6.58 (d, J = 15.5 Hz, 1H), 6.51 (dd, J = 15.5,
10.5 Hz, 1H), 5.96 (dd, J = 15.5, 6.5 Hz, 1H), 5.75–5.73 (m, 1H), 2.16 (d, J = 4.0 Hz, 1H). 13C{1H} NMR
(125 MHz, CDCl3): δ 140.1, 137.0, 133.5, 133.4, 132.2, 131.4, 129.5, 128.7, 128.6, 128.0, 127.63, 127.57,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 16 of 20
1
2
3
4
5
6
7
8
9
127.2, 126.4, 71.1. HPLC (Chiralcel IA-3 column, hexane/i-PrOH = 98/2, 0.9 mL/min, 280 nm): t1 =
42.2 min, t2 = 45.7 min. [α]2D5 = + 75.6 (c = 0.46 in CHCl3) with 92.2% ee. FT-IR (KBr, cm-1): 3369,
3024, 1469, 1449, 1436, 1390, 1328, 1276, 1208, 1191, 1122, 1074, 1042, 1023, 993, 947, 785, 754, 738,
693, 660. HRMS-ESI (m/z): (M + H – H2O)+ calcd. for C17H14Cl, 253.0779; found 253.0788.
Typical Procedure for the Gram-Scale Asymmetric Hydrogenation.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Under a nitrogen atmosphere, the substrate 1a (1.29 g, 7.5 mmol), the trans-{RuCl2[(R)-DAIPEN][(R)-
Xylyl-SunPhos]} catalyst (9.5 mg, 7.5 μmol), K2CO3 (210 mg, 1.5 mmol) was dissolved in freeze-thaw
degassed i-PrOH (8 mL) in a 30 mL vial, Then the container was transferred into a 125 mL autoclave.
The autoclave was purged three times with H2, and the specified reaction conditions (30 bar H2, 30 oC,
48 h) was set. After careful release of hydrogen, the autoclaves were opened and the solvent was
evaporated. The residue was purified by flash column chromatography (PE/EA=10/1 as the eluent) to
provide chiral product 2a as white solid (1.28 g, 98% yield, 95.2% ee).
SUPPORTING INFORMATION
The Supporting Information is available free of charge on the ACS Publications website.
NMR spectra for compounds 1-2 (PDF)
HPLC data for racemic and chiral compounds 2 (PDF)
ACKNOWLEDGMENT
We thank the National Natural Science Foundation of China for the financial support.
REFERENCES
[1] For selected reviews: (a) Noyori, R.; Takaya, H. BINAP: an efficient chiral element for asymmetric
catalysis. Acc. Chem. Res. 1990, 23, 345-350; (b) Noyori, R.; Ohkuma, T. Asymmetric Catalysis by
Architectural and Functional Molecular Engineering: Practical Chemo- and Stereoselective
Hydrogenation of Ketones. Angew. Chem. Int. Ed. 2001, 40, 40-73; (c) Tang, W.; Zhang, X. New Chiral
Phosphorus Ligands for Enantioselective Hydrogenation. Chem. Rev. 2003, 103, 3029-3070; (d) Wu, J.;
Chan, A. S. C. P-Phos:ꢀ A Family of Versatile and Effective Atropisomeric Dipyridylphosphine Ligands
in Asymmetric Catalysis. Acc. Chem. Res. 2006, 39, 711-720; (e) Zhang, W.; Chi, Y.; Zhang, X.
Developing Chiral Ligands for Asymmetric Hydrogenation. Acc. Chem. Res. 2007, 40, 1278-1290; (f)
Xie, J.-H.; Zhou, Q.-L. Chiral Diphosphine and Monodentate Phosphorus Ligands on a Spiro Scaffold
for Transition-Metal-Catalyzed Asymmetric Reactions. Acc. Chem. Res. 2008, 41, 581-593; (g) Ager, D.
J.; de Vries, A. H. M.; de Vries, J. G. Asymmetric homogeneous hydrogenations at scale. Chem. Soc. Rev.
2012, 41, 3340-3380; (h) Li, Y.-Y.; Yu, S.-L.; Shen, W.-Y.; Gao, J.-X. Iron-, Cobalt-, and Nickel-
Catalyzed Asymmetric Transfer Hydrogenation and Asymmetric Hydrogenation of Ketones. Acc. Chem.
Res. 2015, 48, 2587-2598; (i) Morris, R. H. Exploiting Metal–Ligand Bifunctional Reactions in the
Design of Iron Asymmetric Hydrogenation Catalysts. Acc. Chem. Res. 2015, 48, 1494-1502; (j) Li, W.;
Lu, B.; Zhang, Z. A Decennary Journey towards the Efficient Asymmetric Hydrogenation of Highly
Functionalized Ketones. Chem. Rec. 2016, 16, 2506-2520; (k) Ohkuma, T.; Arai, N. Advancement in
Catalytic Asymmetric Hydrogenation of Ketones and Imines, and Development of Asymmetric
Isomerization of Allylic Alcohols. Chem. Rec. 2016, 16, 2801-2819; (l) Zhang, Z.; Butt, N. A.; Zhou, M.;
Liu, D.; Zhang, W. Asymmetric Transfer and Pressure Hydrogenation with Earth-Abundant Transition
Metal Catalysts. Chin. J. Chem . 2018, 36, 443-454.
[2] Spogliarich, R.; Vidotto, S.; Farnetti, E.; Graziani, M.; Gulati, N. V. Highly selective catalytic
hydrogenation of cyclic enones. Tetrahedron: Asymmetry 1992, 3, 1001-1002.
ACS Paragon Plus Environment

Page 17 of 20
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
[3] Mashima, K.; Akutagawa, T.; Zhang, X.; Takaya, H.; Taketomi, T.; Kumobayashi, H.; Akutagawa, S.
Chemoselective asymmetric hydrogenation of α,β-unsaturated carbonyl compounds to allylic alcohols
catalysed by [Ir(binap)(cod)]BF4-aminophosphine. J. Organomet. Chem. 1992, 428, 213-222.
[4] (a) Ohkuma, T.; Ooka, H.; Hashiguchi, S.; Ikariya, T.; Noyori, R. Practical Enantioselective
Hydrogenation of Aromatic Ketones. J. Am. Chem. Soc. 1995, 117, 2675-2676; (b) Ohkuma, T.; Ooka,
H.; Ikariya, T.; Noyori, R. Preferential hydrogenation of aldehydes and ketones. J. Am. Chem. Soc. 1995,
117, 10417-10418; (c) Doucet, H.; Ohkuma, T.; Murata, K.; Yokozawa, T.; Kozawa, M.; Katayama, E.;
England, A. F.; Ikariya, T.; Noyori, R. trans-[RuCl2(phosphane)2(1,2-diamine)] and Chiral trans-
[RuCl2(diphosphane)(1,2-diamine)]: Shelf-Stable Precatalysts for the Rapid, Productive, and
Stereoselective Hydrogenation of Ketones. Angew. Chem. Int. Ed. 1998, 37, 1703-1707; (d) Ohkuma, T.;
Koizumi, M.; Doucet, H.; Pham, T.; Kozawa, M.; Murata, K.; Katayama, E.; Yokozawa, T.; Ikariya, T.;
Noyori, R. Asymmetric Hydrogenation of Alkenyl, Cyclopropyl, and Aryl Ketones.
RuCl2(xylbinap)(1,2-diamine) as a Precatalyst Exhibiting a Wide Scope. J. Am. Chem. Soc. 1998, 120,
13529-13530; (e) Ohkuma, T.; Koizumi, M.; Muñiz, K.; Hilt, G.; Kabuto, C.; Noyori, R. trans-RuH(η1-
BH4)(binap)(1,2-diamine): a catalyst for asymmetric hydrogenation of simple ketones under base-free
conditions[J]. J. Am. Chem. Soc. 2002, 124, 6508-6509; (f) Arai, N.; Azuma, K.; Nii, N.; Ohkuma, T.
Highly Enantioselective Hydrogenation of Aryl Vinyl Ketones to Allylic Alcohols Catalyzed by the Tol-
Binap/Dmapen Ruthenium(II) Complex. Angew. Chem. Int. Ed. 2008, 47, 7457-7460; (g) Arai, N.;
Suzuki, K.; Sugizaki, S.; Sorimachi, H.; Ohkuma, T. Asymmetric Hydrogenation of Aromatic, Aliphatic,
and α,β-Unsaturated Acyl Silanes Catalyzed by Tol-binap/Pica Ruthenium(II) Complexes: Practical
Synthesis of Optically Active α-Hydroxysilanes. Angew. Chem. Int. Ed. 2008, 47, 1770-1773; (h)
Sandoval, C. A.; Li, Y.; Ding, K.; Noyori, R. The Hydrogenation/Transfer Hydrogenation Network in
Asymmetric Reduction of Ketones Catalyzed by [RuCl2(binap)(pica)] Complexes. Chem. Asian J. 2008,
3, 1801-1810;
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
[5] (a) Burk, M. J.; Hems, W.; Herzberg, D.; Malan, C.; Zanotti-Gerosa, A. A Catalyst for Efficient and
Highly Enantioselective Hydrogenation of Aromatic, Heteroaromatic, and α,β-Unsaturated Ketones. Org.
Lett. 2000, 2, 4173-4176; (b) Abdur-Rashid, K.; Lough, A. J.; Morris, R. H.
RuHCl(diphosphine)(diamine):ꢀ Catalyst Precursors for the Stereoselective Hydrogenation of Ketones
and Imines1. Organometallics 2001, 20, 1047-1049; (c) Wu, J.; Ji, J.-X.; Guo, R.; Yeung, C.-H.; Chan,
A. S. C. Chiral [RuCl2(dipyridylphosphane)(1,2-diamine)] Catalysts: Applications in Asymmetric
Hydrogenation of a Wide Range of Simple Ketones. Chem. Eur. J. 2003, 9, 2963-2968; (d) Xie, J.-H.;
Wang, L.-X.; Fu, Y.; Zhu, S.-F.; Fan, B.-M.; Duan, H.-F.; Zhou, Q.-L. Synthesis of Spiro Diphosphines
and Their Application in Asymmetric Hydrogenation of Ketones. J. Am. Chem. Soc. 2003, 125, 4404-
4405; (e) Li, W.; Sun, X.; Zhou, L.; Hou, G.; Yu, S.; Zhang, X. Highly Efficient and Highly
Enantioselective Asymmetric Hydrogenation of Ketones with TunesPhos/1,2-Diamine−Ruthenium(II)
Complexes. J. Org. Chem. 2009, 74, 1397-1399; (f) Chen, X.; Zhou, H.; Zhang, K.; Li, J.; Huang, H.
Highly Enantioselective Hydrogenation of Steric Hindrance Enones Catalyzed by Ru Complexes with
Chiral Diamine and Achiral Phosphane. Org. Lett. 2014, 16, 3912-3915;
[6] (a) Genêt, J. P.; Pinel, C.; Ratovelomanana-Vidal, V.; Mallart, S.; Pfister, X.; Bischoff, L.; De Andrade,
M. C. C.; Darses, S.; Galopin, C.; Laffitte, J. A. Enantioselective hydrogenation reactions with a full set
of preformed and prepared in situ chiral diphosphine-ruthenium (II) catalysts. Tetrahedron: Asymmetry
1994, 5, 675-690; (b) Xie, J.-B.; Xie, J.-H.; Liu, X.-Y.; Kong, W.-L.; Li, S.; Zhou, Q.-L. Highly
Enantioselective Hydrogenation of α-Arylmethylene Cycloalkanones Catalyzed by Iridium Complexes
of Chiral Spiro Aminophosphine Ligands[J]. J. Am. Chem. Soc. 2010, 132, 4538-4539; (c) Ma, X.; Li,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 18 of 20
1
2
3
4
5
6
7
8
9
W.; Li, X.; Tao, X.; Fan, W.; Xie, X.; Ayad, T.; Ratovelomanana-Vidal, V.; Zhang, Z. Ru-catalyzed highly
chemo- and enantioselective hydrogenation of γ-halo-γ,δ-unsaturated-β-keto esters under neutral
conditions[J]. Chem. Commun. 2012, 48, 5352-5354; (d) Lu, S.-M.; Gao, Q.; Li, J.; Liu, Y.; Li, C. A
robust Ru-PNNP catalyst system for the asymmetric hydrogenation of α,β-unsaturated ketones to allylic
alcohol. Tetrahedron Lett. 2013, 54, 7013-7016; (e) Patchett, R.; Magpantay, I.; Saudan, L.; Schotes, C.;
Mezzetti, A.; Santoro, F. Asymmetric Hydrogenation of Ketones with H2 and Ruthenium Catalysts
Containing Chiral Tetradentate S2N2 Ligands. Angew. Chem. Int. Ed. 2013, 52, 10352-10355; (f) Wang,
Y.; Yang, G.; Xie, F.; Zhang, W. A Ferrocene-Based NH-Free Phosphine-Oxazoline Ligand for Iridium-
Catalyzed Asymmetric Hydrogenation of Ketones. Org. Lett. 2018, 20, 6135-6139; (g) Li, J.; Lu, Y.; Zhu,
Y.; Nie, Y.; Shen, J.; Liu, Y.; Liu, D.; Zhang, W. Selective Asymmetric Hydrogenation of Four-Membered
Exo-α,β-Unsaturated Cyclobutanones Using RuPHOX–Ru as a Catalyst. Org. Lett. 2019, 21, 4331-4335;
[7] (a) Martin, V. S.; Woodard, S. S.; Katsuki, T.; Yamada, Y.; Ikeda, M.; Sharpless, K. B. Kinetic
resolution of racemic allylic alcohols by enantioselective epoxidation. A route to substances of absolute
enantiomeric purity?. J. Am. Chem. Soc. 1981, 103, 6237-6240; (b) Vedejs, E.; Jure, M. Efficiency in
Nonenzymatic Kinetic Resolution. Angew. Chem. Int. Ed. 2005, 44, 3974-4001; (c) Pellissier, H.
Catalytic Non-Enzymatic Kinetic Resolution. Adv. Synth. Catal. 2011, 353, 1613-1666.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
[8] (a) Wipf, P.; Kendall, C. Novel Applications of Alkenyl Zirconocenes. Chem. Eur. J. 2002, 8, 1778-
1784; (b) Wipf, P.; Nunes, R. L. Selective carbon–carbon bond formations with alkenylzirconocenes.
Tetrahedron 2004, 60, 1269-1279; (c) Skucas, E.; Ngai, M.-Y.; Komanduri, V.; Krische, M. J.
Enantiomerically Enriched Allylic Alcohols and Allylic Amines via C–C Bond-Forming Hydrogenation:
Asymmetric Carbonyl and Imine Vinylation. Acc. Chem. Res. 2007, 40, 1394-1401.
[9] (a) Matsumura, K.; Hashiguchi, S.; Ikariya, T.; Noyori, R. Asymmetric Transfer Hydrogenation of
α,ꢀβ-Acetylenic Ketones. J. Am. Chem. Soc. 1997, 119, 8738-8739; (b) Noyori, R.; Hashiguchi, S.
Asymmetric Transfer Hydrogenation Catalyzed by Chiral Ruthenium Complexes. Acc. Chem. Res. 1997,
30, 97-102; (c) Iura, Y.; Sugahara, T.; Ogasawara, K. Oxidative resolution of 2-cyclopentenols by the
asymmetric hydrogen transfer protocol. Tetrahedron Lett. 1999, 40, 5735-5738; (d) Ikariya, T.; Blacker,
A. J. Asymmetric Transfer Hydrogenation of Ketones with Bifunctional Transition Metal-Based
Molecular Catalysts. Acc. Chem. Res. 2007, 40, 1300-1308; (e) Bizet, V.; Pannecoucke, X.; Renaud, J.-
L.; Cahard, D. Ruthenium-Catalyzed Redox Isomerization of Trifluoromethylated Allylic Alcohols:
Mechanistic Evidence for an Enantiospecific Pathway. Angew. Chem. Int. Ed. 2012, 51, 6467-6470; (f)
Liu, S.; Cui, P.; Wang, J.; Zhou, H.; Liu, Q.; Lv, J. Asymmetric transfer hydrogenation of cycloalkyl vinyl
ketones to allylic alcohols catalyzed by ruthenium amido complexes. Org. Biomol. Chem. 2019, 17, 264-
267; (g) Touge, T.; Sakaguchi, K.; Tamaki, N.; Nara, H.; Yokozawa, T.; Matsumura, K.; Kayaki, Y.
Multiple Absolute Stereocontrol in Cascade Lactone Formation via Dynamic Kinetic Resolution Driven
by the Asymmetric Transfer Hydrogenation of Keto Acids with Oxo-Tethered Ruthenium Catalysts. J.
Am. Chem. Soc. 2019, 141, 16354
[10] (a) Noyori, R.; Tomino, I.; Tanimoto, Y.; Nishizawa, M. Asymmetric synthesis via axially
dissymmetric molecules. 6. Rational designing of efficient chiral reducing agents. Highly
enantioselective reduction of aromatic ketones by binaphthol-modified lithium aluminum hydride
reagents. J. Am. Chem. Soc. 1984, 106, 6709-6716; (b) Brown, H. C.; Ramachandran, P. V. Asymmetric
reduction with chiral organoboranes based on .alpha.-pinene. Acc. Chem. Res. 1992, 25, 16-24; (c) Corey,
E. J.; Helal, C. J. Reduction of Carbonyl Compounds with Chiral Oxazaborolidine Catalysts: A New
Paradigm for Enantioselective Catalysis and a Powerful New Synthetic Method. Angew. Chem. Int. Ed.
1998, 37, 1986-2012; (d) He, P.; Liu, X.; Zheng, H.; Li, W.; Lin, L.; Feng, X. Asymmetric 1,2-Reduction
ACS Paragon Plus Environment

Page 19 of 20
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
of Enones with Potassium Borohydride Catalyzed by Chiral N,N′-Dioxide–Scandium(III) Complexes.
Org. Lett. 2012, 14, 5134-5137; (e) Chen, F.; Zhang, Y.; Yu, L.; Zhu, S. Enantioselective NiH/Pmrox-
Catalyzed 1,2-Reduction of α,β-Unsaturated Ketones. Angew. Chem. Int. Ed. 2017, 56, 2022-2025. (f)
Szewczyk, M.; Bezłada, A.; Mlynarski, J. Zinc-Catalyzed Enantioselective Hydrosilylation of Ketones
and Imines under Solvent-Free Conditions. ChemCatChem. 2016, 8, 3575-3579.
[11] (a) Eberle, M. K.; Weber, H. P. The regio- and stereoselectivity of intramolecular Diels-Alder
reactions of fumarates: An unusual rearrangement-cyclization. J. Org. Chem. 1988, 53, 231-235; (b)
Adam, W.; Glaeser, J.; Peters, K.; Prein, M. Highly Like-Selective [4 + 2] Cycloadditions of Chiral
Dienols: The Importance of 1,3-Allylic Strain in the Hydroxy-Directed Stereocontrol. J. Am. Chem. Soc.
1995, 117, 9190-9193; (c) Carreño, M. C.; García-Cerrada, S.; Urbano, A.; Di Vitta, C. Studies of
Diastereoselectivity in Diels−Alder Reactions of Enantiopure (SS)-2-(p-Tolylsulfinyl)-1,4-
naphthoquinone and Chiral Racemic Acyclic Dienes. J. Org. Chem. 2000, 65, 4355-4363.
[12] Li, H.; Walsh, P. J. Catalytic Asymmetric Vinylation and Dienylation of Ketones[J]. J. Am. Chem.
Soc. 2005, 127, 8355-8361.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
[13] (a) Kong, J. R.; Krische, M. J. Catalytic Carbonyl Z-Dienylation via Multicomponent Reductive
Coupling of Acetylene to Aldehydes and α-Ketoesters Mediated by Hydrogen:ꢀ Carbonyl Insertion into
Cationic Rhodacyclopentadienes. J. Am. Chem. Soc. 2006, 128, 16040-16041; (b) Kong, J.-R.; Ngai, M.-
Y.; Krische, M. J. Highly Enantioselective Direct Reductive Coupling of Conjugated Alkynes and α-
Ketoesters via Rhodium-Catalyzed Asymmetric Hydrogenation. J. Am. Chem. Soc. 2006, 128, 718-719.
[14] (a) Basak, S.; Kazmaier, U. Palladium-Catalyzed Dienylations of Chelated Enolates. Eur. J. Org.
Chem. 2008, 2008, 4169-4177; (b) Akai, S.; Hanada, R.; Fujiwara, N.; Kita, Y.; Egi, M. One-Pot
Synthesis of Optically Active Allyl Esters via Lipase−Vanadium Combo Catalysis. Org. Lett. 2010, 12,
4900-4903; (c) Yan, L.; Xu, J.-K.; Huang, C.-F.; He, Z.-Y.; Xu, Y.-N.; Tian, S.-K. Kinetic Resolution of
Racemic Allylic Alcohols by Catalytic Asymmetric Substitution of the OH Group with Monosubstituted
Hydrazines. Chem. Eur. J. 2016, 22, 13041-13045.
[15] Xie, X.; Lu, B.; Li, W.; Zhang, Z. Coordination determined chemo- and enantioselectivities in
asymmetric hydrogenation of multi-functionalized ketones. Coord. Chem. Rev. 2018, 355, 39-53.
[16] Gao, Z.; Fletcher, S. P. Construction of β to carbonyl stereogenic centres by asymmetric 1,4-addition
of alkylzirconocenes to dienones and ynenones. Chem. Commun. 2018, 54, 3601-3604.
[17] Lemhadri, M.; Battace, A.; Berthiol, F.; Zair, T.; Doucet, H.; Santelli, M. Palladium-Tetraphosphine
Complex Catalysed Heck Reaction of Vinyl Bromides with Alkenes: A Powerful Access to Conjugated
Dienes. Synthesis 2008, 1142-1152.
[18] Yu, L.; Wu, Y.; Cao, H.; Zhang, X.; Shi, X.; Luan, J.; Chen, T.; Pan, Y.; Xu, Q. Facile synthesis of
2-methylenecyclobutanones via Ca(OH)2-catalyzed direct condensation of cyclobutanone with
aldehydes and (PhSe)2-catalyzed Baeyer–Villiger oxidation to 4-methylenebutanolides. Green Chem.
2014, 16, 287-293.
[19] Wu, X.; Xie, F.; Ling, Z.; Tang, L.; Zhang, W. Regio- and Enantioselective Copper-Catalyzed 1,4-
Conjugate Addition of Trimethylaluminium to Linear α,β,γ,δ-Unsaturated Alkyl Ketones. Adv. Synth.
Catal. 2016, 358, 2510-2518.
[20] Poladura, B.; Martínez-Castañeda, Á.; Rodríguez-Solla, H.; Llavona, R.; Concellón, C.; del Amo,
V. General Metal-Free Baeyer–Villiger-Type Synthesis of Vinyl Acetates. Org. Lett. 2013, 15, 2810-2813.
[21] Hack, D.; Chauhan, P.; Deckers, K.; Hermann, G. N.; Mertens, L.; Raabe, G.; Enders, D. Combining
Silver Catalysis and Organocatalysis: A Sequential Michael Addition/Hydroalkoxylation One-Pot
Approach to Annulated Coumarins. Org. Lett. 2014, 16, 5188-5191.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 20 of 20
1
2
3
4
5
6
[22] Gao, P.-S.; Zhang, K.; Yang, M.-M.; Xu, S.; Sun, H.-M.; Zhang, J.-L.; Gao, Z.-W.; Zhang, W.-Q.;
Xu, L.-W. A robust multifunctional ligand-controlled palladium-catalyzed carbonylation reaction in
water. Chem. Commun. 2018, 54, 5074-5077.
7
8
9
[23] Wang, Z. S.; Chen, L. Z.; Zhou, H. P.; Liu, X. H.; Chen, F. H. Diarylpentadienone derivatives
(curcumin analogues): Synthesis and anti-inflammatory activity. Bioorg. Med. Chem. Lett. 2017, 27,
1803-1807.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
[24] Gallagher, W. P.; Terstiege, I.; Maleczka, R. E. Stille Couplings Catalytic in Tin:ꢀ The “Sn−O”
Approach. J. Am. Chem. Soc. 2001, 123, 3194-3204.
[25] Li, P.-F.; Wang, H.-L.; Qu, J. 1,n-Rearrangement of Allylic Alcohols Promoted by Hot Water:
Application to the Synthesis of Navenone B, a Polyene Natural Product. J. Org. Chem. 2014, 79, 3955-
3962.
[26] Gallagher, W. P.; Maleczka, R. E. Stille Reactions Catalytic in Tin:ꢀ A “Sn−F” Route for
Intermolecular and Intramolecular Couplings. J. Org. Chem. 2005, 70, 841-846.
ACS Paragon Plus Environment