RuPHOX-Ru-Catalyzed Selective Asymmetric Hydrogenation of Exocyclic α,β-Unsaturated Pentanones

Article abstract of DOI:10.1021/acs.organomet.9b00366

A RuPHOX-Ru catalyzed selective asymmetric hydrogenation of exocyclic α,β-unsaturated ketones has been developed, furnishing the corresponding chiral exocyclic allylic alcohols in high yields and with up to >99.5percent ee. The reaction could be performed on a gram scale with a relatively low catalyst loading (up to 10000 S/C) without any loss in reaction activity and enantioselectivity. The resulting hydrogenated products could be easily transformed to several biologically active compounds with high asymmetric performance. The asymmetric protocol provides an efficient methodology for the synthesis of chiral exocyclic allylic alcohols.

Full text of DOI:10.1021/acs.organomet.9b00366

Article
pubs.acs.org/Organometallics
Cite This: Organometallics XXXX, XXX, XXX−XXX
RuPHOX-Ru-Catalyzed Selective Asymmetric Hydrogenation of
Exocyclic α,β-Unsaturated Pentanones
Jing Li,† Yue Zhu,† Yufei Lu,† Yanzhao Wang,‡ Yangang Liu,† Delong Liu,*,† and Wanbin Zhang*,†,‡
†Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Pharmacy, and ‡School of Chemistry and Chemical
Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, People’s Republic of China
S
* Supporting Information
ABSTRACT: A RuPHOX-Ru catalyzed selective asymmetric hydrogenation
of exocyclic α,β-unsaturated ketones has been developed, furnishing the
corresponding chiral exocyclic allylic alcohols in high yields and with up to
>99.5% ee. The reaction could be performed on a gram scale with a relatively
low catalyst loading (up to 10000 S/C) without any loss in reaction activity
and enantioselectivity. The resulting hydrogenated products could be easily
transformed to several biologically active compounds with high asymmetric performance. The asymmetric protocol provides an
efficient methodology for the synthesis of chiral exocyclic allylic alcohols.
hydrogenation of CO bonds in exocyclic α,β-unsaturated
INTRODUCTION
■
carbonyl compounds by using Ir complexes bearing chiral spiro
aminophosphine ligands with good to excellent results
(Scheme 1, middle).7a Just recently, we have developed a
novel planar chiral ferrocene phosphine-oxazoline ligand,
which has been successfully applied to the above reaction,
with the desired products being obtained in up to 98% yield
and 99% ee (Scheme 1, middle).7b It is obvious that the
asymmetric hydrogenation of CO double bonds of exocyclic
α,β-unsaturated ketones has received much less attention and
the substrate scope is somewhat limited. Therefore, the
exploration of efficient metal-catalyzed asymmetric hydro-
genation of the CO double bond of various exocyclic α,β-
unsaturated ketones remains worthy of further investigations.
We have previously developed a chiral phosphino-oxazoline
ligand, RuPHOX,8d which has shown promising asymmetric
catalytic behavior in several asymmetric reactions.8 In
particular, its Ru complex, RuPHOX-Ru,9a has been success-
fully applied in the asymmetric hydrogenation of many types of
substrates containing CC and/or CO double bonds.9 Just
recently, we have achieved an efficient RuPHOX-Ru-catalyzed
selective asymmetric hydrogenation of the CO double bond
of four-membered exo-α,β-unsaturated cyclobutanones.10 In a
continuation of our efforts concerning the synthesis of chiral
exocyclic allylic alcohols, we herein report the efficient and
mild RuPHOX-Ru catalyzed asymmetric hydrogenation of the
CO double bond of five-, six-, and seven-membered
exocyclic α,β-unsaturated ketones (Scheme 1, bottom).
Chiral allylic alcohols, particularly chiral cyclopentanols, are of
great importance in organic synthesis because they are found
not only in natural products but also in pharmaceuticals.1
Some typical examples include the following (Figure 1): 16β-
Figure 1. Chiral five-membered allylic alcohols and their derivatives.
m-carbamoylbenzyl-E2 (CC-156, A), identified as a promising
inhibitor of 17β-hydroxysteroid dehydrogenase type 1 (17β-
HSD1), which is involved in the conversion of estrone into
estradiol, the most potent estrogen in women;2 the propionic
acid derivative of chiral exocyclic allylic alcohol, the non-
steroidal anti-inflammatory drug loxoprofen (B);3 estradiol
(C), a female sex hormone that regulates many processes in
the body, which is used to treat menopause symptoms such as
hot flashes.4
The transition-metal-catalyzed asymmetric hydrogenation of
exocyclic α,β-unsaturated ketones is one of the most powerful
strategies for the synthesis of chiral exocyclic allylic alcohols,
due to its atom efficiency and minimal environmental impact.5
This protocol has been conducted using a diverse array of
chiral iridium-based catalysts,6 as exemplified by the
independent pioneering studies of Bolm, Hou, Ding, Qiu,
and our groups, who have developed Ir complexes bearing
chiral P,N-ligands for the efficient asymmetric hydrogenation
of the CC double bond of exocyclic α,β-unsaturated ketones
(Scheme 1, top). As a comparison, the asymmetric hydro-
genation of the CO double bond of such ketones is rare. In
2010, Zhou and co-workers realized an efficient asymmetric
Special Issue: Asymmetric Synthesis Enabled by Organometallic
Complexes
Received: May 31, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.organomet.9b00366
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
a
Scheme 1. Asymmetric Hydrogenation of Exocyclic α,β-
Table 1. Solvent and Hydrogen Pressure Screening
Unsaturated Ketones
b
c
entry
solvent
MeOH
EtOH
i-PrOH
CF3CH2OH
THF
H2 (bar)
conversion (%)
ee (%)
1
2
3
4
20
20
20
20
>99
>99
>99
NR
72
99.5
99
97
5
20
79
6
7
8
9
10
11
12
acetone
toluene
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
20
20
50
6
38
47
>99
>99
>99
70
89
96
99.5
99.5
99.5
97
2
balloon
balloon
balloon
d
45
28
76
92
e
13
a
Reaction conditions: 1a (0.30 mmol), (S,Sp)-RuPHOX-Ru (1.0 mol
%), and DBU (1.0 equiv) in a suitable solvent (2 mL) under a certain
b
1
hydrogen pressure at room temperature for 1 h. Determined by H
c
NMR. Determined by chiral HPLC analysis of 2a using an OD-H
column. The absolute configuration of 2a was determined according
d
to reported data.7a mono-RuPHOX/RuCl2(PPh3)3 = 1/1 (molar
e
ratio). RuPHOX/RuCl2(PPh3)3 = 1/1 (molar ratio).
aprotic solvents (entries 5−7). Next, the asymmetric hydro-
genation was carried out in MeOH under different hydrogen
pressures. To our delight, the hydrogenation pressure did not
affect the asymmetric behaviors and >99% conversions and
99.5% ees were obtained when the reactions were carried out
at either a high or low hydrogen pressure (entries 8−10). To
illustrate the role of the two Ru sites of the RuPHOX-Ru,
asymmetric hydrogenation was conducted under a hydrogen
balloon by using a catalytic system of RuPHOX-Ru, mono-
RuPHOX/Ru (molar ratio 1/1) or RuPHOX/Ru (molar ratio
1/1). The reaction catalyzed by mono-RuPHOX/Ru gave low
reaction activity as well as inferior enantioselectivity in
comparison with that using RuPHOX-Ru as a catalyst (entry
11 versus entry 12). Asymmetric hydrogenation with the last
catalytic system provided the desired product with more than
90% ee but in low conversion (entry 13). The results suggest
that the two Ru atoms of the RuPHOX-Ru act as catalytic
centers and are essential for the excellent catalytic behavior.
With the optimized reaction conditions in hand, exploration
of the hydrogenated substrate scope was commenced (Scheme
2). First, substrates with different lengths of carbon chains (n =
0−2) between the phenyl ring and CC double bonds were
investigated (1a−c). As shown in Scheme 2, 1a bearing the
shortest link (n = 0) provided the highest ee value (2a, 99.5%
ee). Next, substrates 1 bearing different substituted aryl rings
were investigated. Compounds 1 with different substituents at
the 2-position of the aryl rings were examined, and the desired
products were obtained in high yields and with 95−98% ees
(2d−i). Electronic properties had little effect on the reaction,
RESULTS AND DISCUSSION
■
Initially, the RuPHOX-Ru-catalyzed asymmetric hydrogena-
tion of (E)-2-benzylidenecyclopentan-1-one (1a) was carried
out under 20 bar of hydrogen pressure with 1 equiv of DBU as
a base in different solvents at room temperature for 1 h.11 As
shown in Table 1, MeOH was first used as a solvent with the
desired product (R,E)-2-benzylidenecyclopentan-1-ol (2a)
being obtained in quantitative conversion and 99.5% ee
(entry 1). The use of EtOH provided the same conversion but
a slightly lower enantioselectivity in comparison to that of
MeOH (entry 2). When i-PrOH was used as a solvent,
quantitative conversion and 97% ee were obtained (entry 3).
However, none of the desired product was formed when the
reaction was conducted in CF3CH2OH (entry 4). As a
comparison, aprotic solvents such as THF, acetone, and PhMe
were used. Good to excellent enantioselecitvities but inferior
activities were observed when the reaction was conducted in
B
DOI: 10.1021/acs.organomet.9b00366
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
a
substrates, varying from five-membered to seven-membered
alkyl rings (2a,af,ag).
Scheme 2. Exploration of Substrates
The asymmetric hydrogenation was conducted under 20 bar
of hydrogen pressure at 50 °C over 12 and 24 h, with the aim
of completing the reduction of both the CO and CC
double bonds (Scheme 3). It was found that the CC double
Scheme 3. Reduction of both CO and CC Double
Bonds
bond could be hydrogenated together with the CO double
bond to give the desired hydrogenated product 2a′. However,
the CC double bond could not be hydrogenated completely
and a mixture of 2a and fully hydrogenated product 2a′ was
obtained, even after 24 h. The results reveal that the CO and
CC double bonds can be hydrogenated together and the
CO double bond is more easily reduced in comparison with
that of the CC double bond in the current reaction.
To gain a better understanding of the reaction mechanism,
we conducted deuterium labeling experiments by using D2
and/or CD3OD in place of H2 and/or CH3OH (Scheme 4).
Scheme 4. Deuterium Labeling Experiments
a
Reaction conditions: 1 (0.30 mmol), (S,Sp)-RuPHOX-Ru (1 mol
%), and DBU (1.0 equiv) in MeOH (2 mL) under 2 bar of hydrogen
pressure at room temperature for 1 h. Isolated yields. ees were
determined by chiral HPLC analysis of 2 using an OD-H, OJ-H, or
AS-H column. The absolute configurations of 2 were determined
according to reported data.7a
and excellent results were observed for all products. Similarly,
when election-donating or electron-withdrawing groups were
located at the 3-positions of the aryl rings, high yields and
excellent enantioselectivities were still obtained (2j−o).
Substrates bearing para substitutents on the phenyl rings also
provided excellent asymmetric catalytic behaviors (2p−v).
Replacing the electron-withdrawing substituent with an
electron-donating group, such as MeO or Me, also had no
effect on the reaction, with the desired products being
obtained in quantitative yields and up to 99% ee. When the
phenyl ring was replaced by naphthalene, high yields and
excellent enantioselectivities were also obtained (2w,x).
Pleasingly, this catalytic asymmetric hydrogenation system is
also amenable to heterocyclic substrates (2y,z). The aryl group
can be replaced by alkyl groups (Cy, n-Bu, i-Bu, and i-Pr) with
the desired products 2aa−ac being obtained in almost
quantitative yields and with up to 99.5% ee. In addition, a
substrate with a tetrasubstituted olefin unit was subjected to
the reaction and the desired product was obtained in 76% yield
and with 69% ee (2ae). Finally, the size of the alkyl ring was
examined in the reaction. We were pleased to find that
excellent results were obtained for all of the hydrogenated
When the reaction was performed under a H2 atmosphere in
CD3OD, 72% H was incorporated at the α-position of the
hydroxyl group (eq 1). However, none of the desired product
was observed if the above reaction was carried out in the
absence of H2 (eq 2). The results revealed that the reaction
proceeds via reduction by H2 rather than the reaction solvent
MeOH. Additionally, approximately 50% H at the α position
was deuterated when the reaction was carried out in CD3OD,
suggesting the presence of a keto−enol tautomerization
equilibrium during the reaction (eqs 1−3). It was found that
C
DOI: 10.1021/acs.organomet.9b00366
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
genation substrates were synthesized according to the reported
method.7a Column chromatography was performed using 100−200
mesh silica gel. Melting points were measured with an SGW X-4
micro melting point apparatus, and the thermometer was uncorrected.
1H NMR and 13C NMR spectra were recorded on Bruker Ascend 400
(400 and 100 MHz), Bruker Ascend 500 (500 and 125 MHz), and
Bruker Avance III600 spectrometers (600 and 151 MHz). 19F NMR
spectra were recorded on a Bruker Ascend 500 spectrometer (500 and
470 MHz). High-resolution mass spectra (HRMS) were obtained on
a Fourier-transform mass spectrometer at the Instrumental Analysis
Center of Shanghai Jiao Tong University. Enantioselectivity was
measured by high-performance liquid chromatography (HPLC) using
Daicel Chiralcel OD-H, OJ-H, and AS-H columns with n-hexane/i-
PrOH as eluent. GC analysis was performed using a Shimadzu GC-
2010 plus instrument with a chiral capillary column (β-dex-225 or β-
dex-120, 30 m × 250 μm × 0.25 μm).
General Procedure for Asymmetric Hydrogenation of
Exocyclic α,β-Unsaturated Ketones. In a nitrogen-filled glovebox,
a hydrogenation tube was charged with a stirring bar, 1 (0.3 mmol),
RuPHOX-Ru (5.2 mg, 1 mol %), and DBU (45.7 mg, 1.0 equiv),
followed by the addition of MeOH (2 mL) using a syringe. The
hydrogenation tube was then put into an autoclave. The system was
evacuated and filled with hydrogen three times. The autoclave was
then charged with hydrogen to 2 bar hydrogen pressure, and the
reaction mixture was stirred at room temperature for 1 h. After the
hydrogen was released, the reaction mixture was concentrated on a
rotary evaporator. The conversion of the substrate was determined by
1H NMR analysis of the above crude product. After purification via
no deuteration of the α-position H atom occurred when the
reaction was carried out with D2 in MeOH, illustrating that the
reaction process proceeds via an asymmetric hydrogenation of
the CO double bond of the ketone without including the
CC double bond of the enol equivalent (eq 4).
To examine the efficiency of the catalyst system, a gram-
scale hydrogenation of 1a (5.1 g) was carried out with a low
catalyst loading of 0.01 mol % (S/C = 10000) and with
modified reaction conditions of 30 bar of H2 at room
temperature for 72 h. To our delight, the desired product 2a
was obtained in quantitative yield without any loss in
enantioselectivity (Scheme 5). The CC double bond of 2a
Scheme 5. Gram-Scale Synthesis of 2a and Its
Transformations
column chromatography (SiO2, PE/EtOAc = 4/1), the ee value of the
pure product was determined by HPLC using Chiralcel OD-H, OJ-H,
and AS-H columns with n-hexane/i-PrOH as eluent.
(R,E)-2-Benzylidenecyclopentan-1-ol (2a).7b White solid (51.7
1
mg, 99%). Mp: 81−82 °C. H NMR (400 MHz, CDCl3): δ 7.38−
7.33 (m, 4H), 7.27−7.21 (m, 1H), 6.59 (q, J = 1.6 Hz, 1H), 4.59 (t, J
= 5.6 Hz, 1H), 2.76−2.69 (m, 1H), 2.62−2.54 (m, 1H), 2.26 (br s,
1H), 2.02−1.91 (m, 2H), 1.77−1.62 (m, 2H). 13C NMR (100 MHz,
CDCl3): δ 147.7, 137.8, 128.4, 128.3, 126.5, 123.5, 77.2, 34.7, 29.3,
22.5. HPLC (Chiralcel OD-H, n-hexane/i-PrOH 95/5, UV 254 nm,
flow rate 0.8 mL/min): tR1 = 19.0 min (major) and tR2 = 20.5 min
(minor), ee = 99.5%. [α]2D5 = −6.12 (c 0.40, CHCl3).
(R,E)-2-(2-Phenylethylidene)cyclopentan-1-ol (2b). Colorless oil
(53.7 mg, 95%). 1H NMR (400 MHz, CDCl3): δ 7.31−7.27 (m, 2H),
7.21−7.18 (m, 3H), 5.73 (t, J = 7.2 Hz, 1H), 4.47−4.39 (m, 1H),
3.37 (d, J = 7.2 Hz, 2H), 2.56−2.46 (m, 1H), 2.37−2.27 (m, 1H),
1.95−1.84 (m, 2H), 1.73−1.61 (m, 2H), 1.48 (br s, 1H). 13C NMR
(100 MHz, CDCl3): δ 146.7, 140.7, 128.4, 128.3, 125.9, 122.6, 75.5,
35.6, 35.6, 27.1, 21.9. IR (KBr) cm−1: 3430, 2957, 1716, 1451, 1176,
1025, 748, 698. HR-MS (ESI): m/z 171.1174, calcd for C13H16O [M
− OH]+ 171.1168. HPLC (Chiralcel OD-H, n-hexane/i-PrOH 80/20,
could be further reduced using Pd/C as a catalyst in THF,
affording the corresponding 3 in 99% yield, 2:1 dr, and 99% ee.
The CC double bond could also be oxidized by m-CPBA to
give the corresponding epoxidation product 4 in 83% yield
without any loss in enantioselectivity.12 4 was then hydro-
genated with H2 catalyzed by Pd/C and was further
transformed to its adjacent dihydroxyl product 5 (99% yield,
>99.5% ee). The hydroxyl group of 2a could also be acetylated
with Ac2O easily to give 6, which was then treated with
CH3MgBr, providing the alkylated product 7 in high yield and
99.5% ee (Scheme 5).13
UV 210 nm, flow rate 0.8 mL/min): tR1 = 6.4 min (minor) and tR2
=
CONCLUSION
■
7.2 min (major), ee = 93%. [α]2D5 = −16.06 (c 0.77, CHCl3).
In summary, we have developed an efficient RuPHOX-Ru-
catalyzed selective asymmetric hydrogenation of exocyclic α,β-
unsaturated ketones. Under the optimal reaction conditions,
the corresponding chiral exocyclic allylic alcohols were
obtained in almost quantitative yields and up to >99.5% ee.
The reaction could be performed on a gram scale with a
relatively low catalyst loading (up to 10000 S/C), and the
resulting products were transformed to several biologically
active compounds. The asymmetric protocol provides an
efficient methodology for the synthesis of chiral exocyclic
allylic alcohols.
(R,E)-2-(3-Phenylpropylidene)cyclopentan-1-ol (2c).14 Colorless
1
oil (58.3 mg, 96%). H NMR (400 MHz, CDCl3): δ 7.31−7.27 (m,
2H), 7.21−7.20 (m, 3H), 5.58 (t, J = 8.0 Hz, 1H), 4.41−4.34 (m,
1H), 2.70 (t, J = 7.6 Hz, 2H), 2.37−2.27 (m, 3H), 2.13−2.05 (m,
1H), 1.87−1.77 (m, 2H), 1.67−1.55 (m, 3H). 13C NMR (100 MHz,
CDCl3): δ 146.5, 142.0, 128.4, 128.2, 125.8, 123.1, 75.5, 35.5, 35.5,
31.2, 26.9, 21.9. HPLC (Chiralcel OJ-H, n-hexane/i-PrOH 90/10, UV
210 nm, flow rate 0.8 mL/min): tR1 = 7.9 min (major) and tR2 = 8.7
min (minor), ee = 92%. [α]2D5 = −17.66 (c 0.26, CHCl3).
(R,E)-2-(2-Fluorobenzylidene)cyclopentan-1-ol (2d). Colorless oil
(56.5 mg, 98%). 1H NMR (500 MHz, CDCl3): δ 7.44 (td, J = 8.0, 1.5
Hz, 1H), 7.24−7.19 (m, 1H), 7.13 (td, J = 7.5, 1.0 Hz, 1H), 7.08−
7.04 (m, 1H), 6.79−6.73 (m, 1H), 4.68−4.59 (m, 1H), 2.72−2.66
(m, 1H), 2.57−2.50 (m, 1H), 2.03−1.93 (m, 2H), 1.79−1.65 (m,
3H). 13C NMR (125 MHz, CDCl3): δ 160.1 (d, J = 246.75 Hz),
150.0, 129.1 (d, J = 2.875 Hz), 128.1 (d, J = 8.375 Hz), 125.5 (d, J =
12.625 Hz), 123.6 (d, J = 3.375 Hz), 115.4, 115.2 (d, J = 6.25 Hz),
77.0, 34.8, 29.1, 22.3. 19F NMR (470 MHz, CDCl3): δ −116.5. IR
(KBr) cm−1: 3354, 2961, 1485, 1455, 1095, 753. HR-MS (ESI): m/z
EXPERIMENTAL SECTION
■
General Remarks. All reactions were performed in flame-dried
glassware under an atmosphere of dry nitrogen, and the workup was
carried out in air, unless otherwise noted. Solvents were dried and
degassed by standard procedures. Commercially available reagents
were used without further purification. The asymmetric hydro-
D
DOI: 10.1021/acs.organomet.9b00366
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
215.0844, calcd for C12H13FO [M + Na]+ 215.0844. HPLC (Chiralcel
UV 254 nm, flow rate 0.5 mL/min): tR1 = 20.1 min (major) and tR2
22.1 min (minor), ee = 97%. [α]2D5 = −18.67 (c 0.39, CHCl3).
=
OD-H, n-hexane/i-PrOH 95/5, UV 254 nm, flow rate 0.8 mL/min):
t
R1 = 10.7 min (major) and tR2 = 12.8 min (minor), ee = 95%. [α]D25
=
(R,E)-2-(3-Chlorobenzylidene)cyclopentan-1-ol (2k).7b Colorless
1
−52.50 (c 0.63, CHCl3).
oil (62.0 mg, 99%). H NMR (400 MHz, CDCl3): δ 7.32 (s, 1H),
(R,E)-2-(2-Chlorobenzylidene)cyclopentan-1-ol (2e).7b Colorless
7.26−7.16 (m, 3H), 6.52−6.46 (m, 1H), 4.60−4.53 (m, 1H), 2.75−
2.66 (m, 1H), 2.58−2.52 (m, 1H), 2.02−1.92 (m, 2H), 1.77−1.59
(m, 3H). 13C NMR (100 MHz, CDCl3): δ 149.3, 139.5, 134.1, 129.5,
128.1, 126.5, 126.5, 122.2, 77.1, 34.8, 29.3, 22.3. HPLC (Chiralcel
OD-H, n-hexane/i-PrOH 80/20, UV 254 nm, flow rate 0.8 mL/min):
1
oil (61.4 mg, 98%). H NMR (400 MHz, CDCl3): δ 7.43−7.40 (m,
1H), 7.36 (dd, J = 7.6, 0.8 Hz, 1H), 7.24−7.20 (m, 1H), 7.15 (td, J =
7.6, 1.2 Hz, 1H), 6.82 (q, J = 1.6 Hz, 1H), 4.62 (t, J = 5.6 Hz, 1H),
2.67−2.59 (m, 1H), 2.51−2.43 (m, 1H), 2.02−1.88 (m, 2H), 1.80 (br
s, 1H), 1.75−1.62 (m, 2H). 13C NMR (100 MHz, CDCl3): δ 150.9,
135.6, 133.5, 129.4, 129.3, 127.8, 126.3, 120.0, 76.8, 34.7, 28.8, 22.3.
HPLC (Chiralcel OD-H, n-hexane/i-PrOH 80 20, UV 254 nm, flow
rate 0.8 mL/min): tR1 = 6.5 min (major) and tR2 = 7.8 min (minor),
ee = 98%. [α]2D5 = −31.66 (c 1.39, CHCl3).
(R,E)-2-(2-Bromobenzylidene)cyclopentan-1-ol (2f). Colorless oil
(74.4 mg, 98%). 1H NMR (400 MHz, CDCl3): δ 7.56 (d, J = 8.0 Hz,
1H), 7.40 (d, J = 8.0 Hz, 1H), 7.28−7.24 (m, 1H), 7.06 (td, J = 7.6,
1.2 Hz, 1H), 6.78−6.73 (m, 1H), 4.63 (t, J = 4.8 Hz, 1H), 2.65−2.56
(m, 1H), 2.48−2.40 (m, 1H), 2.03−1.87 (m, 3H), 1.72−1.63 (m,
2H). 13C NMR (100 MHz, CDCl3): δ 149.9, 137.3, 132.7, 129.4,
128.0, 126.9, 124.2, 122.6, 76.7, 34.7, 28.7, 22.2. IR (KBr) cm−1:
2965, 1716, 1465, 1436, 1024, 749. HR-MS (ESI): m/z 235.0116,
calcd for C12H13BrO [M − OH]+ 235.0117. HPLC (Chiralcel OD-H,
tR1 = 6.4 min (major) and tR2 = 6.9 min (minor), ee = 99%. [α]D25
−2.88 (c 0.50, CHCl3).
=
(R,E)-2-(3-Bromobenzylidene)cyclopentan-1-ol (2l). Colorless oil
(74.4 mg, 98%). 1H NMR (400 MHz, CDCl3): δ 7.50−7.46 (m, 1H),
7.32 (dt, J = 8.0, 1.6 Hz, 1H), 7.26−7.24 (m, 1H), 7.20−7.17 (m,
1H), 6. 49 (q, J = 1.6 Hz, 1H), 4.57 (t, J = 5.6 Hz, 1H), 2.74−2.65
(m, 1H), 2.61−2.51 (m, 1H), 2.04−1.91 (m, 2H), 1.77−1.70 (m,
2H), 1.67−1.57 (m, 1H). 13C NMR (100 MHz, CDCl3): δ 149.3,
139.8, 131.0, 129.7, 129.4, 126.9, 122.4, 122.1, 77.1, 34.8, 29.3, 22.3.
IR (KBr) cm−1: 3400, 2961, 1716, 1473, 1419, 783, 684. HR-MS
(ESI): m/z 235.0116, calcd for C12H13BrO [M − OH]+ 235.0117.
HPLC (Chiralcel OD-H, n-hexane/i-PrOH 95/5, UV 254 nm, flow
rate 1.0 mL/min): tR1 = 12.2 min (major) and tR2 = 14.0 min (minor),
ee = 97%. [α]2D5 = −3.91 (c 0.53, CHCl3).
n-hexane/i-PrOH 90/10, UV 230 nm, flow rate 0.8 mL/min): tR1
10.1 min (major) and tR2 = 14.1 min (minor), ee = 98%. [α]D25
−13.22 (c 0.56, CHCl3).
=
=
(R,E)-2-(3-(Trifluoromethyl)benzylidene)cyclopentan-1-ol (2m).
Colorless oil (71.2 mg, 98%). 1H NMR (400 MHz, CDCl3): δ
7.58−7.53 (m, 1H), 7.49−7.40 (m, 3H), 6.62−6.55 (m, 1H), 4.64−
4.55 (m, 1H), 2.79−2.68 (m, 1H), 2.60−2.55 (m, 1H), 2.00−1.97
(m, 2H), 1.87 (br s, 1H), 1.77−1.62 (m, 2H). 13C NMR (100 MHz,
CDCl3): δ 149.7, 138.4, 131.4, 128.7, 124.8 (q, J = 3.7 Hz), 123.0 (q,
J = 3.6 Hz), 122.8, 122.2, 77.1, 34.7, 29.2, 22.2. IR (KBr) cm−1: 2962,
1716, 1330, 804, 696. HR-MS (ESI): m/z 265.0085, calcd for
C13H13F3O [M − OH]+ 265.0086. HPLC (Chiralcel OD-H, n-
hexane/i-PrOH 99/1, UV 230 nm, flow rate 0.5 mL/min): tR1 = 35.2
min (major) and tR2 = 37.3 min (minor), ee = 97%. [α]2D5 = −3.58 (c
0.47, CHCl3).
(R,E)-2-(2-(Trifluoromethyl)benzylidene)cyclopentan-1-ol (2g).
1
Colorless oil (69.7 mg, 96%). H NMR (400 MHz, CDCl3): δ 7.63
(d, J = 8.0 Hz, 1H), 7.50−7.44 (m, 2H), 7.30 (t, J = 7.2 Hz, 1H), 6.82
(s, 1H), 4.63−4.55 (m, 1H), 2.59−2.53 (m, 1H), 2.42−2.33 (m, 1H),
2.02−1.95 (m, 1H), 1.91−1.85 (m, 1H), 1.79 (br s, 1H), 1.72−1.60
(m, 2H). 13C NMR (100 MHz, CDCl3): δ 150.7, 136.5, 131.3, 129.8,
127.9 (q, J = 32.1 Hz), 126.4, 125.7 (q, J = 5.6 Hz), 122.9, 119.7,
76.4, 34.7, 28.6, 22.1. 19F NMR (470 MHz, CDCl3): δ −60.184. IR
(KBr) cm−1: 3354, 2953, 1716, 1487, 1455, 1034, 768, 657. HR-MS
(ESI): m/z 265.0815, calcd for C13H13F3O [M + Na]+ 265.0811.
HPLC (Chiralcel OD-H, n-hexane/i-PrOH 95/5, UV 254 nm, flow
rate 0.8 mL/min): tR1 = 7.9 min (major) and tR2 = 8.6 min (minor),
ee = 96%. [α]2D5 = −19.09 (c 0.68, CHCl3).
(R,E)-2-(3-Methylbenzylidene)cyclopentan-1-ol (2n). Colorless oil
(54.8 mg, 97%). 1H NMR (400 MHz, CDCl3): δ 7.26−7.22 (m, 1H),
7.18−7.17 (m, 2H), 7.04 (d, J = 7.2 Hz, 1H), 6.58−6.52 (m, 1H),
4.62−4.53 (m, 1H), 2.75−2.69 (m, 1H), 2.60−2.51 (m, 1H), 2.36 (s,
3H), 2.02−1.91 (m, 3H), 1.78−1.61 (m, 2H). 13C NMR (100 MHz,
CDCl3): δ 147.5, 137.7, 137,7 129.2, 128.2, 127.3, 125.4, 123.6, 77.3,
34.8, 29.3, 22.5, 21.5. IR (KBr) cm−1: 2952, 1744, 1628, 910, 786,
695. HR-MS (ESI): m/z 171.1176, calcd for C13H16O [M − OH]+
171.1168. HPLC (Chiralcel OD-H, n-hexane/i-PrOH 95/5, UV 254
nm, flow rate 0.8 mL/min): tR1 = 12.8 min (major) and tR2 = 15.1 min
(minor), ee = 98%. [α]2D5 = −50.98 (c 0.64, CHCl3).
(R,E)-2-(2-Methylbenzylidene)cyclopentan-1-ol (2h).15 White
solid (54.8 mg, 97%). Mp: 72−73 °C. 1H NMR (400 MHz,
CDCl3): δ 7.32 (d, J = 7.6 Hz, 1H), 7.20−7.09 (m, 3H), 6.67 (s, 1H),
4.64−4.58 (m, 1H), 2.67−2.56 (m, 1H), 2.49−2.38 (m, 1H), 2.31 (s,
3H), 2.03−1.87 (m, 2H), 1.71−1.64 (m, 3H). 13C NMR (100 MHz,
CDCl3): δ 148.2, 136.5, 136.1,129.9, 127.9, 126.7, 125.5, 121.5, 76.7,
34.9, 28.7, 22.3, 19.9. HPLC (Chiralcel OD-H, n-hexane/i-PrOH 90/
10, UV 230 nm, flow rate 0.8 mL/min): tR1 = 9.5 min (major) and tR2
= 11.7 min (minor), ee = 98%. [α]2D5 = −14.26 (c 0.41, CHCl3).
(R,E)-2-(2-Methoxybenzylidene)cyclopentan-1-ol (2i).15 Colorless
(R,E)-2-(3-Methoxybenzylidene)cyclopentan-1-ol (2o).15 Color-
1
less oil (60.6 mg, 99%). H NMR (400 MHz, CDCl3): δ 7.25 (t, J =
8.0 Hz, 1H), 6.95 (d, J = 7.6 Hz, 1H), 6.90 (s, 1H), 6.77 (d, J = 8.0
Hz, 1H), 6.54 (s, 1H), 4.61−4.55 (m, 1H), 3.80 (s, 3H), 2.77−2.69
(m, 1H), 2.60−2.54 (m, 1H), 2.01−1.90 (m, 2H), 1.77−1.59 (m,
3H). 13C NMR (100 MHz, CDCl3): δ 159.4, 148.1, 139.1, 129.2,
123.5, 121.0, 113.8, 112.1, 77.3, 55.1, 34.8, 29.4, 22.4. HPLC
(Chiralcel OD-H, n-hexane/i-PrOH 90:/10, UV 230 nm, flow rate 0.8
mL/min): tR1 = 19.4 min (minor) and tR2 = 25.4 min (major), ee =
99%. [α]2D5 = −45.23 (c 0.59, CHCl3).
1
oil (60.1 mg, 98%). H NMR (400 MHz, CDCl3): δ 7.37 (d, J = 7.6
Hz, 1H), 7.20 (t, J = 7.6 Hz, 1H), 6.93 (t, J = 7.6 Hz, 1H), 6.87−6.85
(m, 2H), 4.65−4.58 (m, 1H), 3.83 (s, 3H), 2.72−2.64 (m, 1H),
2.54−2.45 (m, 1H), 1.99−1.89 (m, 2H), 1.76−1.60 (m, 3H). 13C
NMR (100 MHz, CDCl3): δ 156.7, 147.9, 128.7, 127.9, 126.5, 120.1,
117.8, 110.3, 77.1, 55.3, 34.7, 29.1, 22.5. HPLC (Chiralcel OD-H, n-
hexane/i-PrOH 80/20, UV 254 nm, flow rate 0.8 mL/min): tR1 = 9.2
min (major) and tR2 = 17.5 min (minor), ee = 98%. [α]2D5 = −56.45 (c
0.63, CHCl3).
(R,E)-2-(3-Fluorobenzylidene)cyclopentan-1-ol (2j). Colorless oil
(55.9 mg, 97%). 1H NMR (500 MHz, CDCl3): δ 7.30 (dd, J = 8.5, 2.0
Hz, 1H), 7.13 (d, J = 8.0 Hz, 1H), 7.08 (dt, J = 8.5, 2.0 Hz, 1H), 6.93
(dt, J = 8.5, 2.0 Hz, 1H), 6.56 (q, J = 1.5 Hz, 1H), 4.60 (t, J = 5.5 Hz,
1H), 2.76−2.69 (m, 1H), 2.62−2.55 (m, 1H), 2.03−1.95 (m, 2H),
1.79−1.71 (m, 1H), 1.70−1.62 (m, 1H). 13C NMR (125 MHz,
CDCl3): δ 163.7, 161.8, 149.0, 140.0 (d, J = 7.6 Hz), 129.6 (d, J = 8.3
Hz), 124.2 (d, J = 2.6 Hz), 122.5 (d, J = 2.5 Hz), 114.7 (d, J = 21.5
Hz), 113.3 (d, J = 21.2 Hz), 34.7, 29.3, 22.3. 19F NMR (470 MHz,
CDCl3): δ −113.4. IR (KBr) cm−1: 2961, 1716, 1589, 1488, 1253,
787, 686. HR-MS (ESI): m/z 175.0928, calcd for C12H13FO [M −
OH]+ 175.0918. HPLC (Chiralcel OD-H, n-hexane/i-PrOH 95/5,
(R,E)-2-(4-Fluorobenzylidene)cyclopentan-1-ol (2p).15 Yellow
solid (55.4 mg, 96%). Mp: 56−57 °C.1H NMR (500 MHz,
CDCl3): δ 7.32−7.28 (m, 2H), 7.04−6.99 (m, 2H), 6.53 (q, J =
1.5 Hz, 1H), 4.57 (t, J = 5.5 Hz, 1H), 2.69−2.49 (m, 3H), 2.00−1.91
(m, 2H), 1.76−1.61 (m, 2H). 13C NMR (125 MHz, CDCl3): δ 161.3
(d, J = 244.8 Hz), 147.1 (d, J = 2.125 Hz), 133.9 (d, J = 3.25 Hz),
129.8 (d, J = 7.875 Hz), 122.4, 115.1 (d, J = 21.25 Hz), 77.1, 34.7,
29.2, 22.4. 19F NMR (470 MHz, CDCl3): δ −115.3. HPLC (Chiralcel
OD-H, n-hexane/i-PrOH 95/5, UV 254 nm, flow rate 1.0 mL/min):
tR1 = 8.7 min (minor) and tR2 = 9.9 min (major), ee = 94%. [α]D25
−2.82 (c 0.28, CHCl3).
=
(R,E)-2-(4-Chlorobenzylidene)cyclopentan-1-ol (2q).7b White
solid (62.0 mg, 99%). Mp: 84−85 °C. 1H NMR (400 MHz,
CDCl3): δ 7.33−7.30 (m, 4H), 6.54 (q, J = 1.6 Hz, 1H), 4.60 (t, J =
E
DOI: 10.1021/acs.organomet.9b00366
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
5.2 Hz, 1H), 2.75−2.67 (m, 1H), 2.60−2.52 (m, 1H), 2.06−1.94 (m,
2H), 1.81−1.74 (m, 1H), 1.68−1.62 (m, 2H). 13C NMR (100 MHz,
CDCl3): δ 148.4, 136.2, 132.1, 129.5, 128.4, 122.4, 77.2, 34.8, 29.3,
22.4. HPLC (Chiralcel OD-H, n-hexane/i-PrOH 90/10, UV 254 nm,
flow rate 0.8 mL/min): tR1 = 7.8 min (minor) and tR2 = 8.6 min
(major), ee = 99%. [α]2D5 = −88.89 (c 0.58, CHCl3).
(R,E)-2-(Naphthalen-2-ylmethylene)cyclopentan-1-ol (2x).7b
White solid (65.9 mg, 98%). Mp: 95−96 °C. H NMR (500 MHz,
CDCl3): δ 7.84−7.81 (m, 4H), 7.54 (dd, J = 8.5, 2.0 Hz, 1H), 7.51−
7.46 (m, 2H), 6.76 (q, J = 1.5 Hz, 1H), 4.67 (t, J = 5.5 Hz, 1H),
2.90−2.83 (m, 1H), 2.75−2.68 (m, 1H), 2.08−1.98 (m, 2H), 1.83−
1.68 (m, 3H). 13C NMR (100 MHz, CDCl3): δ 148.3, 135.3, 133.4,
132.1, 128.0, 127.8, 127.5, 127.2, 126.7, 126.1, 125.7, 123.7, 77.4,
34.9, 29.5, 22.6. HPLC (Chiralcel OD-H, n-hexane/i-PrOH 90/10,
1
(R,E)-2-(4-Bromobenzylidene)cyclopentan-1-ol (2r).7a White
solid (74.4 mg, 98%). Mp: 84−85 °C. 1H NMR (400 MHz,
CDCl3): δ 7.42 (d, J = 8.0 Hz, 2H), 7.17 (d, J = 8.0 Hz, 2H), 6.47 (s,
1H), 4.58−4.51 (m, 1H), 2.70−2.62 (m, 1H), 2.52−2.43 (m, 1H),
2.02 (s, 1H), 1.97−1.88 (m, 2H), 1.75−1.54 (m, 2H). 13C NMR (100
MHz, CDCl3): δ 148.5, 136.6, 131.3, 129.8, 122.4, 120.2, 77.1, 34.7,
29.3, 22.3. HPLC (Chiralcel OD-H, n-hexane/i-PrOH 95/5, UV 230
nm, flow rate 0.8 mL/min): tR1 = 11.8 min (major) and tR2 = 13.4 min
(minor), ee = 98%. [α]2D5 = −152.81 (c 1.038, CHCl3).
UV 230 nm, flow rate 0.8 mL/min): tR1 = 11.6 min (minor) and tR2
=
12.5 min (major), ee = 98%. [α]2D5 = −63.34 (c 0.70, CHCl3).
(R,E)-2-(Furan-2-ylmethylene)cyclopentan-1-ol (2y). Colorless oil
1
(48.8 mg, 99%). H NMR (400 MHz, CDCl3): δ 7.37 (s, 1H), 6.42
(d, J = 18.0 Hz, 2H), 6.23 (d, J = 2.8 Hz, 1H), 4.60−4.52 (m, 1H),
2.74−2.62 (m, 1H), 2.59−2.47 (m, 1H), 1.97−1.90 (m, 2H), 1.75−
1.59 (m, 3H). 13C NMR (100 MHz, CDCl3): δ 153.4, 146.2, 141.4,
112.2, 111.3, 108.1, 76.6, 35.4, 29.6, 22.1. IR (KBr) cm−1: 3439, 2958,
1715, 1600, 1362, 1261, 1019. HR-MS (ESI): m/z 147.0811, calcd for
C10H12O2 [M − OH]+ 147.0804. HPLC (Chiralcel AS-H, n-hexane/i-
PrOH 75/25, UV 210 nm, flow rate 0.8 mL/min): tR1 = 5.8 min
(minor) and tR2 = 6.6 min (major), ee = 98%. [α]2D5 = −55.28 (c 0.52,
CHCl3).
(R,E)-2-(4-(Trifluoromethyl)benzylidene)cyclopentan-1-ol (2s).15
1
Colorless oil (71.2 mg, 98%). H NMR (500 MHz, CDCl3): δ 7.59
(d, J = 8.5 Hz, 2H), 7.45 (d, J = 8.5 Hz, 2H), 6.62 (q, J = 1.5 Hz, 1H),
4.62 (t, J = 6.0 Hz, 1H), 2.77−2.70 (m, 1H), 2.65−2.57 (m, 1H),
2.09−1.96 (m, 2H), 1.79−1.71 (m, 1H), 1.69−1.62 (m, 1H). 13C
NMR (125 MHz, CDCl3): δ 150.4, 141.2 (q, J = 1.25 Hz), 128.4,
128.1, 125.2 (q, J = 3.75 Hz), 124.2 (q, J = 270.0 Hz), 122.3, 77.1,
34.8, 29.4, 22.2. 19F NMR (470 MHz, CDCl3): δ −62.4. HPLC
(Chiralcel AS-H, n-hexane/i-PrOH 90/10, UV 254 nm, flow rate 0.8
mL/min): tR1 = 7.9 min (minor) and tR2 = 9.9 min (major), ee = 98%.
[α]2D5 = −1.99 (c 0.32, CHCl3).
(R,E)-2-(Thiophen-2-ylmethylene)cyclopentan-1-ol (2z).15 Color-
less oil (53.5 mg, 99%). 1H NMR (400 MHz, CDCl3): δ 7.27 (d, J =
4.8 Hz, 1H), 7.03−6.95 (m, 2H), 6.80 (s, 1H), 4.63−4.54 (m, 1H),
2.69−2.62 (m, 1H), 2.53−2.47 (m, 1H), 2.05−1.92 (m, 2H), 1.81−
1.61 (m, 3H). 13C NMR (100 MHz, CDCl3): δ 145.8, 141.8, 127.0,
126.3, 125.1, 117.0, 76.8, 35.5, 29.7, 22.3. HPLC (Chiralcel AS-H, n-
hexane/i-PrOH 75/25, UV 210 nm, flow rate 0.8 mL/min): tR1 = 5.9
min (minor) and tR2 = 7.1 min (major), ee = 99.3%. [α]2D5 = −24.61
(c 0.25, CHCl3).
(R,E)-2-(4-Methylbenzylidene)cyclopentan-1-ol (2t).7b Colorless
1
oil (55.9 mg, 99%). H NMR (400 MHz, CDCl3): δ 7.25 (d, J = 6.8
Hz, 2H), 7.14 (d, J = 7.6 Hz, 2H), 6.54 (s, 1H), 4.60−4.55 (m, 1H),
2.74−2.68 (m, 1H), 2.58−2.51 (m, 1H), 2.34 (s, 3H), 2.00−1.89 (m,
2H), 1.78−1.69 (m, 1H), 1.66−1.62 (m, 2H). 13C NMR (100 MHz,
CDCl3): δ 146.7, 136.3, 134.9, 129.0, 128.3, 123.5, 77.3, 34.8, 29.3,
22.6, 21.1. HPLC (Chiralcel OD-H, n-hexane/i-PrOH 90/10, UV 254
nm, flow rate 0.8 mL/min): tR1 = 8.4 min (minor) and tR2 = 10.2 min
(major), ee = 99%. [α]2D5 = −17.58 (c 0.70, CHCl3).
(R,E)-2-(Cyclohexylmethylene)cyclopentan-1-ol (2aa).15 Color-
1
less oil (53.5 mg, 99%). H NMR (400 MHz, CDCl3): δ 5.35 (d, J
= 8.8 Hz, 1H), 4.38−4.29 (m, 1H), 2.38−2.33 (m, 1H), 2.23−2.13
(m, 1H), 2.06−1.98 (m, 1H), 1.85−1.75 (m, 2H), 1.69−1.59 (m,
7H), 1.45 (br s, 1H), 1.29−1.12 (m, 3H), 1.08−0.99 (m, 2H). 13C
NMR (100 MHz, CDCl3): δ 143.9, 130.1, 75.6, 38.4, 35.4, 32.7, 32.6,
26.7, 26.0, 25.9, 22.0. HPLC (Chiralcel OJ-H, n-hexane/i-PrOH 98/
2, UV 210 nm, flow rate 0.8 mL/min): tR1 = 5.8 min (major) and tR2
= 6.7 min (minor), ee = 99.98%. [α]2D5 = −288.68 (c 1.21, CHCl3).
(R,E)-2-Pentylidenecyclopentan-1-ol (2ab).16 Colorless oil (45.8
mg, 99%). 1H NMR (600 MHz, CDCl3): δ 5.52−5.48 (m, 1H),
4.35−4.33 (m, 1H), 2.34−2.33 (m, 1H), 2.16−2.15 (m, 1H), 2.00−
1.96 (m, 2H), 1.83−1.77 (m, 2H), 1.63−1.58 (m, 2H), 1.36−1.27
(m, 4H), 0.90−0.86 (m, 3H). 13C NMR (151 MHz, CDCl3): δ 145.3,
124.2, 75.2, 35.4, 31.4, 28.9, 26.8, 22.3, 21.8, 13.8. The enantiomeric
excess was determined by GC analysis using a chiral capillary column
(β-dex-120, 30 m × 250 μm × 0.25 μm), initially 90 °C, 1 °C/min:
tR1 = 42.5 min (major), ee >99.5%. [α]2D5 = −40.91 (c 1.01, CHCl3).
(R,E)-2-(3-Methylbutylidene)cyclopentan-1-ol (2ac). Colorless oil
(45.8 mg, 99%). 1H NMR (600 MHz, CDCl3): δ 5.55−5.54 (m, 1H),
4.37−4.34 (m, 1H), 2.33−2.32 (m, 1H), 2.16−2.14 (m, 1H), 1.88−
1.80 (m, 4H), 1.66−1.60 (m, 3H), 0.90−0.88 (m, 6H). 13C NMR
(151 MHz, CDCl3): δ 146.2, 122.9, 75.4, 38.5, 35.5, 28.5, 27.0, 22.3,
22.3, 21.9. IR (KBr) cm−1: 3362, 2955, 2869, 1601, 1464, 1383, 1365,
1090, 1023, 976. HR-MS (ESI): m/z 137.1326, calcd for C10H18O [M
− OH]+. 137.1336. The enantiomeric excess was determined by GC
analysis using a chiral capillary column (β-dex-120, 30 m × 250 μm ×
(R,E)-2-(4-Methoxybenzylidene)cyclopentan-1-ol (2u).7a White
solid (60.6 mg, 99%). Mp: 80−81 °C. 1H NMR (500 MHz,
CDCl3): δ 7.31 (d, J = 8.5 Hz, 2H), 6.90 (d, J = 9.0 Hz, 2H), 6.54 (q,
J = 1.5 Hz, 1H), 4.59 (t, J = 5.5 Hz, 1H), 3.82 (s, 3H), 2.74−2.67 (m,
1H), 2.58−2.52 (m, 1H), 2.03−1.90 (m, 3H), 1.79−1.72 (m, 1H),
1.69−1.63 (m, 1H). 13C NMR (125 MHz, CDCl3): δ 158.2, 145.4,
130.6, 129.6, 123.1, 113.7, 77.4, 55.2, 34.8, 29.2, 22.6. HPLC
(Chiralcel OD-H, n-hexane/i-PrOH 95/5, UV 230 nm, flow rate 0.8
mL/min): tR1 = 16.2 min (major) and tR2 = 18.0 min (minor), ee =
98%. [α]2D5 = −7.14 (c 0.59, CHCl3).
(R,E)-2-(4-(Trifluoromethoxy)benzylidene)cyclopentan-1-ol (2v).
1
Colorless oil (75.1 mg, 98%). H NMR (500 MHz, CDCl3): δ 7.38
(d, J = 8.5 Hz, 2H), 7.20 (d, J = 8.5 Hz, 2H), 6.58 (q, J = 2.0 Hz, 1H),
4.61 (t, J = 5.5 Hz, 1H), 2.76−2.69 (m, 1H), 2.62−2.55 (m, 1H),
2.04−1.96 (m, 2H), 1.81−1.72 (m, 1H), 1.69−1.65 (m, 1H). 13C
NMR (100 MHz, CDCl3): δ 148.6, 147.5 (q, J = 1.8 Hz), 136.4,
129.5, 122.1, 120.7, 120.4 (q, J = 255.6 Hz), 77.2, 34.8, 29.2, 22.3. 19F
NMR (470 MHz, CDCl3): δ −57.8. IR (KBr) cm−1: 2891, 2637,
1507, 1362, 1261, 825. HR-MS (ESI): m/z 241.0839, calcd for
C13H13F3O2 [M − OH]+ 241.0835. HPLC (Chiralcel AS-H, n-
hexane/i-PrOH 90/10, UV 254 nm, flow rate 0.8 mL/min): tR1 = 7.3
min (minor) and tR2 = 11.3 min (major), ee = 97%. [α]2D5 = −35.92 (c
0.35, CHCl3).
0.25 μm), initially 90 °C, 1 °C/min: tR1 = 37.5 min (major) and tR2
=
(R,E)-2-(Naphthalen-1-ylmethylene)cyclopentan-1-ol (2w).15
40.6 min (minor), ee = 98%. [α]2D5 = −22.54 (c 0.99, CHCl3).
White solid (65.3 mg, 97%). Mp: 92−93 °C. H NMR (500 MHz,
(R,E)-2-(2-Methylpropylidene)cyclopentan-1-ol (2ad).14 Color-
1
1
CDCl3): δ 8.16−8.13 (m, 1H), 7.92−7.89 (m, 1H), 7.82−7.79 (m,
1H), 7.56−7.53 (m, 2H), 7.51 (s, 1H), 7.50 (d, J = 1.5 Hz, 1H), 7.24
(q, J = 2.0 Hz, 1H), 4.77 (t, J = 6.0 Hz, 1H), 2.68−2.62 (m, 1H),
2.51−2.44 (m, 1H), 2.29 (br s, 1H), 2.12−2.05 (m, 1H), 1.97−1.90
(m, 1H), 1.80−1.66 (m, 2H). 13C NMR (125 MHz, CDCl3): δ 149.8,
134.7, 133.6, 131.7, 128.5, 127.2, 125.8, 125.8, 125.7, 125.3, 124.4,
120.6, 76.5, 35.1, 28.8, 22.2. HPLC (Chiralcel OD-H, n-hexane/i-
PrOH 98/2, UV 254 nm, flow rate 0.5 mL/min): tR1 = 111.3 min
(minor) and tR2 = 117.9 min (major), ee = 96%. [α]2D5 = −29.54 (c
0.83, CHCl3).
less oil (40.0 mg, 95%). H NMR (600 MHz, CDCl3): δ 5.28−5.26
(m, 1H), 4.26−4.25 (m, 1H), 2.31−2.26 (m, 2H), 2.12−2.09 (m,
1H), 1.76−1.70 (m, 2H), 1.54−1.51 (m, 2H), 0.88 (d, J = 7.2 Hz,
6H). 13C NMR (151 MHz, CDCl3): δ 143.0, 131.2, 75.2, 35.3, 28.6,
26.5, 22.6, 22.5, 21.9. The enantiomeric excess was determined by GC
analysis using a chiral capillary column (β-dex-120, 30 m × 250 μm ×
0.25 μm), initially 90 °C, 1 °C/min: tR1 = 22.1 min (major) and tR2
=
24.4 min (minor), ee = 85%. [α]2D5 = −15.57 (c 0.34, CHCl3).
(R)-2-(Diphenylmethylene)cyclopentan-1-ol (2ae). Colorless oil
(57.1 mg, 76%). 1H NMR (600 MHz, CDCl3): δ 7.42−7.40 (m, 4H),
F
DOI: 10.1021/acs.organomet.9b00366
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
7.38−7.36 (m, 2H), 7.34−7.32 (m, 1H), 7.31−7.27 (m, 3H), 4.82 (t,
J = 4.8 Hz, 1H), 2.75−2.69 (m, 1H), 2.49−2.44 (m, 1H), 2.04−1.95
(m, 2H), 1.87−1.82 (m, 2H), 1.73−1.66 (m, 1H). 13C NMR (151
MHz, CDCl3): δ 144.7, 142.5, 141.8, 137.4, 129.1, 128.9, 128.5,
128.1, 127.0, 126.7, 73.3, 35.3, 31.3, 23.0. IR (KBr) cm−1: 3420, 2957,
1646, 1596, 1489, 1442, 765, 700. HR-MS (ESI): m/z 233.1328,
calcd for C18H18O [M − OH]+ 233.1336. HPLC (Chiralcel OJ-H, n-
hexane/i-PrOH 95/5, UV 254 nm, flow rate 0.8 mL/min): tR1 = 11.1
min (major) and tR2 = 12.7 min (minor), ee = 69%. [α]2D5 = −31.72 (c
1.19, CHCl3).
temperature for 3 h. After the hydrogen was released and the mixture
filtered carefully, the solution was concentrated in vaccuo to remove
solvent, affording 5 as a white solid (179.1 mg, 99%, >99.5% ee). Mp:
1
72−73 °C. H NMR (400 MHz, CDCl3): δ 7.33−7.29 (m, 2H),
7.26−7.23 (m, 3H), 3.86 (q, J = 6.8 Hz, 1H), 2.85−2.78 (m, 2H),
2.22 (s, 1H), 2.03−1.95 (m, 1H), 1.89 (d, J = 5.2 Hz, 1H), 1.87−1.74
(m, 1H), 1.71−1.61 (m, 3H), 1.54−1.44 (m, 1H). 13C NMR (100
MHz, CDCl3): δ 137.5, 130.0, 128.4, 126.6, 79.8, 77.0, 44.6, 35.6,
31.4, 18.9. HPLC (Chiralcel OD-H, n-hexane/i-PrOH 95/5, UV 220
nm, flow rate 0.8 mL/min): tR1 = 14.9 min (major), ee >99.5%. [α]D25
= −4.29 (c 0.41, CHCl3).
(R,E)-2-Benzylidenecyclohexan-1-ol (2af).7b White solid (54.8
(R,E)-2-Benzylidenecyclopentyl Acetate (6).13 Et3N (2.2
mmol) and 4-dimethylaminopyridine (DMAP, cat.) was added to a
stirred solution of 2a (350.0 mg, 2.0 mmol) in DCM (10 mL),
followed by the addition of acetic anhydride (2.4 mmol) at 0 °C. The
reaction mixture was stirred until the disappearance of 2a. The
reaction mixture was diluted with water, and the aqueous phase was
extracted with DCM (10 mL × 3). The combined organic phase was
washed with saturated aqueous NaHCO3 (10 mL × 3) and brine (10
mL × 3) and dried with anhydrous Na2SO4. Then the solvent was
evaporated to provide a crude product, which was then purified by
column chromatography (SiO2, PE/EA 20/1) to afford pure 6 as a
colorless oil (393.4 mg, 90%). 1H NMR (400 MHz, CDCl3): δ 7.38−
7.32 (m, 4H), 7.24−7.20 (m, 1H), 6.63 (q, J = 1.2 Hz, 1H), 5.68−
5.66 (m, 1H), 2.78−2.70 (m, 1H), 2.61−2.53 (m, 1H), 2.09 (s, 3H),
2.03−1.90 (m, 2H), 1.84−1.72 (m, 2H). 13C NMR (100 MHz,
CDCl3): δ 170.8, 142.8, 137.4, 128.6, 128.2, 126.8, 126.4, 79.1, 32.2,
29.6, 23.4, 21.4.
1
mg, 97%). Mp: 51−52 °C. H NMR (400 MHz, CDCl3): δ 7.34−
7.30 (m, 2H), 7.22−7.19 (m, 3H), 6.54−6.50 (m, 1H), 4.25−4.22
(m, 1H), 2.75−2.69 (m, 1H), 2.15−2.08 (m, 1H), 2.03−1.97 (m,
1H), 1.90−1.82 (m, 1H), 1.69−1.43 (m, 5H). 13C NMR (100 MHz,
CDCl3): δ 144.3, 137.6, 128.9, 128.0, 126.2, 120.7, 109.9, 73.7, 36.5,
27.3, 26.9, 23.1. HPLC (Chiralcel OD-H, n-hexane/i-PrOH 90/10,
UV 254 nm, flow rate 0.8 mL/min): tR1 = 8.0 min (major) and tR2
=
9.7 min (minor), ee = 96%. [α]2D5 = +37.89 (c 0.56, CHCl3).
(R,E)-2-Benzylidenecycloheptan-1-ol (2ag).7a Colorless oil (58.8
mg, 97%). 1H NMR (500 MHz, CDCl3): δ 7.35−7.20 (m, 5H), 6.57
(s, 1H), 4.40−4.36 (m, 1H), 2.49−2.40 (m, 2H), 2.14−2.08 (m, 1H),
1.87−1.80 (m, 1H), 1.76−1.67 (m, 4H), 1.64−1.46 (m, 2H), 1.43−
1.32 (m, 1H). 13C NMR (125 MHz, CDCl3): δ 146.3, 137.4, 128.5,
128.1, 126.7, 126.3, 76.9, 36.5, 29.0, 28.0, 26.5, 23.8. HPLC (Chiralcel
OD-H, n-hexane/i-PrOH 90/10, UV 210 nm, flow rate 0.8 mL/min):
tR1 = 7.6 min (major) and tR2 = 9.2 min (minor), ee = 97%. [α]D25
−117.55 (c 0.47, CHCl3).
=
(S,E)-((2-Methylcyclopentylidene)methyl)benzene (7).13 In a
50 mL two-neck round-bottom flask was placed MeMgBr (2.5 equiv),
and CuCl (20 mol %) was added quickly when the reaction mixture
was cooled to 0 °C. Fifteen minutes later, compound 6 (1.0 mmol, 1.0
equiv) in dry THF was added dropwise. The reaction mixture was
quenched by 2 M HCl after 6 h and extracted with DCM (10 mL ×
3). The combined organic layer was dried over Na2SO4 and
evaporated in vacuo. The residue was purified by column
chromatography (SiO2, 100% hexane) to give the corresponding
product 7 (144.6 mg, 84%, 99.5% ee) as a colorless oil. 1H NMR (400
MHz, CDCl3): δ 7.36−7.33 (m, 4H), 7.21−7.17 (m, 1H), 6.28 (q, J =
2.0 Hz, 1H), 2.73−2.58 (m, 3H), 1.99−1.91 (m, 1H), 1.90−1.84 (m,
1H), 1.73−1.62 (m, 1H), 1.33−1.22 (m, 1H), 1.23 (q, J = 6.8 Hz,
3H). 13C NMR (100 MHz, CDCl3): δ 151.6, 138.9, 128.1, 128.0,
125.6, 120.1, 40.9, 34.6, 31.5, 24.7, 19.4. The enantiomeric excess
(99.5% ee) was determined by GC analysis using a chiral capillary
column (β-dex-225, 30 m × 250 μm × 0.25 μm), initially 90 °C, 1
°C/min: tR1 = 55.4 min (minor) and tR2 = 56.1 min (major), ee =
99.5%. [α]2D5 = −10.07 (c 1.01, CHCl3).
Transformation of 2a: (1R,2R)-2-Benzylcyclopentan-1-ol
(3).17 A hydrogenation tube was charged with a stirring bar, 2a
(0.6 mmol, 104.5 mg) and Pd/C (10 mol %), followed by the
addition of THF (5 mL) using a syringe. The hydrogenation tube was
then put into an autoclave. The system was evacuated and filled with
hydrogen 3 times. The autoclave was then charged with hydrogen to
10 bar hydrogen pressure, and the reaction mixture was stirred at
room temperature for 2 h. After releasing the hydrogen and filtered
carefully, the solution was concentrated in vaccuo to remove solvent,
affording 3 as colorless oil (104.7 mg, 99%, 99.0% ee). dr (2:1) was
determined by 1H NMR analysis of 3. 1H NMR (400 MHz, CDCl3):
δ 7.31−7.17 (m, 5H), 4.13−4.05 (m, 1H), 2.88−2.83 (m, 1H), 2.71−
2.66 (m, 1H), 2.06−1.96 (m, 1H), 1.88−1.79 (m, 2H), 1.74−1.62
(m, 2H), 1.60−1.46 (m, 2H), 1.36 (br s, 1H); 13C NMR (100 MHz,
CDCl3): δ 141.8, 128.7, 128.3, 125.7, 74.3, 47.6, 35.4, 34.8, 28.7, 21.8;
HPLC (Chiralcel OD-H, n-hexane/i-PrOH 99:1, UV 220 nm, flow
rate 0.8 mL/min), tR1 = 16.7 min (major), tR1 = 31.1 min (minor), ee
= 99.0%; [α]2D5 = −326.89 (c 2.26, CHCl3).
(2S,3S,4R)-2-Phenyl-1-oxaspiro[2.4]heptan-4-ol (4).18,19 m-
CPBA (6.0 mmol) was added to a stirred solution of 2a (418.1 mg,
2.4 mmol) in DCM (10 mL) at 0 °C, and the reaction was quenched
with saturated aqueous Na2S2O3 at 0 °C over 1 h. The resulting
mixture was extracted with DCM (10 mL × 3). The combined
organic phase was washed with saturated aqueous NaHCO3 and brine
and dried with anhydrous Na2SO4. Then the solvent was evaporated
to provide the crude product, which was then purified by column
chromatography (SiO2, PE/EA 20/1) to afford pure 4 as a white solid
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.organo-
met.9b00366.
■
S
Synthesis of hydrogenated substrates and NMR spectra
and HPLC data of both hydrogenated substrates and
products (PDF)
1
(377.1 mg, 83%, 99.4% ee). Mp: 62−63 °C. H NMR (400 MHz,
CDCl3): δ 7.36−7.25 (m, 5H), 4.07 (s, 1H), 4.05 (q, J = 6.8 Hz, 1H),
2.49−2.33 (m, 1H), 2.06−2.01 (m, 1H), 1.92−1.84 (m, 1H), 1.83−
1.66 (m, 2H), 1.64−1.57 (m, 1H). 13C NMR (100 MHz, CDCl3): δ
135.8, 128.2, 127.8, 126.1, 72.3, 72.3, 61.7, 33.9, 25.6, 19.4. HPLC
(Chiralcel OD-H, n-hexane/i-PrOH 90/10, UV 220 nm, flow rate 0.8
mL/min): tR1 = 8.6 min (major), tR1 = 10.0 min (minor), ee = 99.4%.
[α]2D5 = −60.96 (c 0.49, CHCl3).
Accession Codes
CCDC 1918858 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
via www.ccdc.cam.ac.uk/data_request/cif, or by emailing
data_request@ccdc.cam.ac.uk, or by contacting The Cam-
bridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
(1R,2R)-1-Benzylcyclopentane-1,2-diol (5).20 A hydrogenation
tube was charged with a stirring bar, 4 (0.9 mmol, 190.2 mg), and Pd/
C (10 mol %), followed by the addition of THF/MeOH (10 mL/5
mL) using a syringe. The hydrogenation tube was then put into an
autoclave. The system was evacuated and filled with hydrogen three
times. The autoclave was then charged with hydrogen to 10 bar
hydrogen pressure, and the reaction mixture was stirred at room
AUTHOR INFORMATION
Corresponding Authors
*E-mail for D.L.: dlliu@sjtu.edu.cn.
■
G
DOI: 10.1021/acs.organomet.9b00366
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
with Earth-abundant Transition Metal Catalysts. Chin. J. Chem. 2018,
36, 443−454.
*E-mail for W.Z.: wanbin@sjtu.edu.cn.
ORCID
(6) (a) Lu, S.-M.; Bolm, C. Highly Enantioselective Synthesis of
Optically Active Ketones by Iridium-catalyzed Asymmetric Hydro-
genation. Angew. Chem., Int. Ed. 2008, 47, 8920−8923. (b) Lu, W.-J.;
Chen, Y.-W.; Hou, X.-L. Iridium-catalyzed Highly Enantioselective
Hydrogenation of the C = C Bond of α,β-Unsaturated Ketones.
Angew. Chem., Int. Ed. 2008, 47, 10133−10136. (c) Tian, F.; Yao, D.;
Liu, Y.; Xie, F.; Zhang, W. Iridium-catalyzed Highly Enantioselective
Hydrogenation of Exocyclic α,β-Unsaturated Carbonyl Compounds.
Adv. Synth. Catal. 2010, 352, 1841−1845. (d) Li, Q.; Wan, P.; He, Y.;
Zhou, Y.; Li, L.; Chen, B.; Duan, K.; Cao, R.; Zhou, Z.; Qiu, L.
Enantioselective Hydrogenation of the Double Bond of Exocyclic α,β-
Unsaturated Carbonyl Compounds Catalyzed by Iridium/H8-BINOL
Derived Phosphine-oxazoline Complexes. Asian J. Org. Chem. 2014, 3,
774−783. (e) Liu, X.; Han, Z.; Wang, Z.; Ding, K. SpinPhox/
iridium(I)-catalyzed Asymmetric Hydrogenation of Cyclic α-
Alkylidene Carbonyl Compounds. Angew. Chem., Int. Ed. 2014, 53,
1978−1982.
(7) (a) 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. Am. Chem. Soc. 2010, 132, 4538−4539.
(b) 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.
(8) (a) For planar chiral RuPHOX ligands, see reviews: Zhang, W.;
Liu, D. In Chiral Ferrocenes in Asymmetric Catalysis: Synthesis and
Applications; Dai, L.-X., Hou, X.-L., Eds.; VCH: Weinheim, Germany,
2010; Chapter 14, pp 175. (b) Butt, N. A.; Liu, D.; Zhang, W. The
Design and Synthesis of Planar Chiral Ligands and Their Application
to Asymmetric Catalysis. Synlett 2014, 25, 615−630. (c) Butt, N. A.;
Zhang, W. Transition Metal-catalyzed Allylic Substitution Reactions
with Unactivated Allylic Substrates. Chem. Soc. Rev. 2015, 44, 7929−
7967. See selected papers: (d) Liu, D.; Xie, F.; Zhang, W. The
Synthesis of Novel C2-Symmetric P, N-Chelation Ruthenocene
Ligands and Their Application in Palladium-Catalyzed Asymmetric
Allylic Substitution. Tetrahedron Lett. 2007, 48, 585−588. (e) Huo,
X.; He, R.; Fu, J.; Zhang, J.; Yang, G.; Zhang, W. Stereoselective and
Site-specific Allylic Alkylation of Amino Acids and Small Peptides via
a Pd/Cu Dual Catalysis. J. Am. Chem. Soc. 2017, 139, 9819−9822.
(f) Huo, X.; Fu, J.; He, X.; Chen, J.; Xie, F.; Zhang, W. Highly
Enantioselective Access to α-Substituted α-Amino Acids and α-
Amino Amides. Chem. Commun. 2018, 54, 599−602.
(9) (a) Wang, J.; Liu, D.; Liu, Y.; Zhang, W. Asymmetric
Hydrogenation of β-Amino Ketones with the Bimetallic Complex
RuPHOX-Ru as the Chiral Catalyst. Org. Biomol. Chem. 2013, 11,
3855−3861. (b) Wang, Y.; Wang, J.; Liu, D.; Zhang, W. Synthesis of
Chiral γ-Amino Alcohols via a RuPHOX-Ru Catalyzed Asymmetric
Hydrogenation of β-Imide Ketones. Youji Huaxue 2014, 34, 1766−
1772. (c) Wang, J.; Wang, Y.; Liu, D.; Zhang, W. Asymmetric
Hydrogenation of β-Secondary Amino Ketones Catalyzed by a
Ruthenocenyl Phosphino-oxazoline-ruthenium Complex (RuPHOX-
Ru): the Synthesis of γ-Secondary Amino Alcohols. Adv. Synth. Catal.
2015, 357, 3262−3272. (d) Li, J.; Shen, J.; Xia, C.; Wang, Y.; Liu, D.;
Zhang, W. Asymmetric Hydrogenation of α-Substituted Acrylic Acids
Catalyzed by a Ruthenocenyl Phosphino-oxazoline-ruthenium Com-
plex. Org. Lett. 2016, 18, 2122−2125. (e) Guo, H.; Li, J.; Liu, D.;
Zhang, W. The Synthesis of Chiral α-Aryl α-Hydroxyl Carboxylic
Acids via RuPHOX-Ru Catalyzed Asymmetric Hydrogenation. Adv.
Synth. Catal. 2017, 359, 3665−3673. (f) Ma, Y.; Li, J.; Ye, J.; Liu, D.;
Zhang, W. Synthesis of Chiral Chromanols via a RuPHOX-Ru
Catalyzed Asymmetric Hydrogenation of Chromones. Chem.
Commun. 2018, 54, 13571−13574. (g) Li, J.; Ma, Y.; Lu, Y.; Liu,
Y.; Liu, D.; Zhang, W. Synthesis of Chiral γ-Lactones via a RuPHOX-
Ru Catalyzed Asymmetric Hydrogenation of γ-Keto Acids. Adv. Synth.
Catal. 2019, 361, 1146−1153. (h) Lu, Y.; Li, J.; Zhu, Y.; Shen, J.; Liu,
D.; Zhang, W. Synthesis of Chiral γ-Lactones via a RuPHOX-Ru
Delong Liu: 0000-0003-2190-1644
Wanbin Zhang: 0000-0002-4788-4195
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was partially supported by the National Natural
Science Foundation of China (Nos. 21672142, 21620102003,
and 21831005), Shanghai Municipal Education Commission
(No. 201701070002E00030). We also thank the Instrumental
Analysis Center of Shanghai Jiao Tong University.
REFERENCES
■
(1) (a) Johnson, R. A.; Sharpless, K. B. In Catalytic Asymmetric
Synthesis; Ojima, I., Ed.; Wiley-VCH: Weinheim, 2000; Chapter 6A.
(b) Katsuki, T. In Comprehensive Asymmetric Catalysis; Jacobsen, E.
N., Pfaltz, A., Yamamoto, H., Eds.; Springer: Berlin, 1999; Vol. 2, p
621. (c) Tsuji, J. Palladium Reagents and Catalysis; VCH: Chichester,
1997; Chapter 4.
(2) Maltais, R.; Trottier, A.; Delhomme, A.; Barbeau, X.; Lague, P.;
̈
Poirier, D. Identification of Fused 16β,17β-Oxazinone-estradiol
Derivatives as a New Family of Non-estrogenic 17β-Hydroxysteroid
Dehydrogenase Type 1 Inhibitors. Eur. J. Med. Chem. 2015, 93, 470−
480.
(3) Naruto, S.; Terada, A. Optical Resolution and Determination of
Absolute Configuration of ( )-2-[4-(2-Oxocyclopentylmethyl)-
phenyl]propionic Acids. Chem. Pharm. Bull. 1983, 31, 4286−4294.
(4) Liehr, G. Is Estradiola Enotoxic Mutagenic Carcinogen? Endocr.
Rev. 2000, 21, 40−54.
(5) (a) For reviews, see: Takaya, H.; Ohta, T.; Noyori, R. In
Catalytic Asymmetric Synthesis; Ojima, I., Ed.; Wiley-VCH: New York,
1993; p 1. (b) Noyori, R. Asymmetric Catalysis in Organic Synthesis;
Wiley: New York, 1994; Chapter 2. (c) Ohkuma, T.; Noyori, R. In
Transition Metals for Organic Synthesis: Building Blocks and Fine
Chemicals; Beller, M., Bolm, C., Eds.; Wiley-VCH: Weinheim, 1998;
Vol. 2, p 25. (d) Comprehensive Asymmetric Catalysis; Jacobsen, E. N.,
Pfaltz, A., Yamamoto, H., Eds.; Springer: Berlin, 1999. (e) Knowles,
W. S. Asymmetric Hydrogenations (Nobel Lecture). Angew. Chem.,
Int. Ed. 2002, 41, 1998−2007. (f) Noyori, R. Asymmetric Catalysis:
Science and Opportunities (Nobel Lecture). Angew. Chem., Int. Ed.
2002, 41, 2008−2022. (g) Tang, W.; Zhang, X. New Chiral
Phosphorus Ligands for Enantioselective Hydrogenation. Chem. Rev.
2003, 103, 3029−3070. (h) Xie, J.-H.; Zhu, S.-F.; Zhou, Q.-L.
Transition Metal-catalyzed Enantioselective Hydrogenation of
Enamines and Imines. Chem. Rev. 2011, 111, 1713−1760. (i) Xie,
J.-H.; Zhu, S.-F.; Zhou, Q.-L. Recent Advances in Transition Metal-
catalyzed Enantioselective Hydrogenation of Unprotected Enamines.
Chem. Soc. Rev. 2012, 41, 4126−4139. (j) Chen, Q.-A.; Ye, Z.-S.;
Duan, Y.; Zhou, Y.-G. Homogeneous Palladium-catalyzed Asym-
metric Hydrogenation. Chem. Soc. Rev. 2013, 42, 497−511. (k) Etayo,
P.; Vidal-Ferran, A. Rhodium-catalysed Asymmetric Hydrogenation as
a Valuable Synthetic Tool for the Preparation of Chiral Drugs. Chem.
Soc. Rev. 2013, 42, 728−754. (l) Verendel, J. J.; Pamies, O.; Dieguez,
M.; Andersson, P. G. Asymmetric Hydrogenation of Olefins Using
Chiral Crabtree-type Catalysts: Scope and Limitations. Chem. Rev.
2014, 114, 2130−2169. (m) Wang, Y.; Zhang, Z.; Zhang, W. The
Study on the Asymmetric Hydrogenation of Cyclic Dehydroamino
Acids and Their Derivatives. Youji Huaxue 2015, 35, 528−538.
(n) Yuan, Q.; Zhang, W. The Applications of Phosphoramidite
Ligands in Ir-Catalyzed Asymmetric Hydrogenation Reactions. Youji
Huaxue 2016, 36, 274−282. (o) Zhang, Z.; Butt, N.; Zhang, W.
Asymmetric Hydrogenation of Non-aromatic Cyclic Substrates. Chem.
Rev. 2016, 116, 14769−14827. (p) Zhang, Z.; Butt, N.; Zhou, M.;
Liu, D.; Zhang, W. Asymmetric Transfer and Pressure Hydrogenation
̀
́
H
DOI: 10.1021/acs.organomet.9b00366
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Catalyzed Asymmetric Hydrogenation of Aroylacrylic Acids. Tetrahe-
dron 2019, 75, 3643−3649.
(10) 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.
(11) The effect of different bases and the amount of DBU on the
reaction was examined. See the Supporting Information for details.
(12) Zheng, X.; Guo, R.; Zhang, G.; Zhang, D. Rhodium(I)-
catalyzed Asymmetric [4 + 2] Cycloaddition Reactions of 2-
Alkylenecyclobutanols with Cyclic Enones through C-C Bond
Cleavage: Efficient Access to Trans-bicyclic Compounds. Chem. Sci.
2018, 9, 1873−1877.
́
̈
(13) Warner, M. C.; Nagendiran, A.; Bogar, K.; Backvall, J.-E.
Enantioselective Route to Ketones and Lactones from Exocyclic
Allylic Alcohols via Metal and Enzyme Catalysis. Org. Lett. 2012, 14,
5094−5097.
(14) Feng, C.; Kobayashi, Y. Installation of a Chiral Side Chain to a
2-Alkylidene-1-cycloalkan-1-ol Unit by Using Allylic Substitution. Eur.
J. Org. Chem. 2013, 2013, 6666−6676.
(15) Liu, T.-L.; Wu, J.; Zhao, Y. Divergent Reactivities in
Fluoronation of Allylic Alcohols: Synthesis of Z-Fluoroalkenes via
Carbon-carbon Bond Cleavage. Chem. Sci. 2017, 8, 3885−3890.
(16) Oblinger, E.; Montgomery, J. A New Stereoselective Method
for the Preparation of Allylic Alcohols. J. Am. Chem. Soc. 1997, 119,
9065−9066.
(17) Kim, J. Y.; Kin, H. D.; Seo, M. J.; Kim, H. R.; No, Z.; Ha, D.-C.;
Lee, G. H. Reduction of Ketones to Corresponding Alcohols with
Magnesium Metal in Absolute Alcohols. Tetrahedron Lett. 2006, 47,
9−12.
(18) House, H. O.; Wasson, R. L. The Rearrangement of α,β-Epoxy
Ketones. IV. The Synthesis of Cyclic β-Diketones. J. Am. Chem. Soc.
1956, 78, 4394−4400.
(19) CCDC 1918858 (4) contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via www.ccdc.
cam.ac.uk/data_request/cif.
(20) Melis, N.; Luridiana, A.; Guillot, R.; Secci, F.; Frongia, A.;
Boddaert, T.; Aitken, D. J. Stereoselective and Regioselective Pinacol-
type Rearrangement of a Fused Bicyclic Oxetanol Scaffold. Eur. J. Org.
Chem. 2017, 2017, 5896−5902.
I
DOI: 10.1021/acs.organomet.9b00366
Organometallics XXXX, XXX, XXX−XXX