Regioselective hydration of terminal alkynes catalyzed by a neutral gold(I) complex [(IPr)AuCl] and one-pot synthesis of optically active secondary alcohols from terminal alkynes by the combination of [(IPr)AuCl] and Cp?RhCl[(R, R)-TsDPEN]

Article abstract of DOI:10.1021/acs.joc.5b00164

A neutral gold(I) complex [(IPr)AuCl] (IPr = 1,3-bis(diisopropylphenyl)imidazol-2-ylidene) was found to be a highly effective catalyst for the hydration of terminal alkynes, including aromatic alkynes and aliphatic alkynes. The desired methyl ketones were obtained in high yields with complete regioselectivities. Furthermore, a series of optically active secondary alcohols could be obtained in high yield with good to excellent enatioselectivities via one-pot sequential hydration/asymmetric transfer hydrogenation (ATH) from terminal alkynes by the combination of of [(IPr)AuCl] and Cp?RhCl[(R,R)-TsDPEN] (Cp? = pentamethylcyclopentadienyl, TsDPEN = N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine). Notably, this research exhibited the potential of the direct use of neutral gold(I) complexes instead of cationic ones as catalysts for the activation of multiple bonds for organic synthesis.

Full text of DOI:10.1021/acs.joc.5b00164

Article
pubs.acs.org/joc
Regioselective Hydration of Terminal Alkynes Catalyzed by a Neutral
Gold(I) Complex [(IPr)AuCl] and One-Pot Synthesis of Optically Active
Secondary Alcohols from Terminal Alkynes by the Combination of
[(IPr)AuCl] and Cp*RhCl[(R,R)‑TsDPEN]
Feng Li,* Nana Wang, Lei Lu, and Guangjun Zhu
Key Laboratory for Soft Chemistry and Functional Materials, Ministry of Education, Nanjing University of Science & Technology,
Nanjing 210094, People’s Republic of China
S
* Supporting Information
ABSTRACT: A neutral gold(I) complex [(IPr)AuCl] (IPr = 1,3-
bis(diisopropylphenyl)imidazol-2-ylidene) was found to be a highly
effective catalyst for the hydration of terminal alkynes, including
aromatic alkynes and aliphatic alkynes. The desired methyl ketones were
obtained in high yields with complete regioselectivities. Furthermore, a
series of optically active secondary alcohols could be obtained in high
yield with good to excellent enatioselectivities via one-pot sequential
hydration/asymmetric transfer hydrogenation (ATH) from terminal
alkynes by the combination of of [(IPr)AuCl] and Cp*RhCl[(R,R)-
TsDPEN] (Cp* = pentamethylcyclopentadienyl, TsDPEN = N-(p-
toluenesulfonyl)-1,2-diphenylethylenediamine). Notably, this research
exhibited the potential of the direct use of neutral gold(I) complexes
instead of cationic ones as catalysts for the activation of multiple bonds
for organic synthesis.
silylium salt [(Tol)SiEt3][B(C6F5)4] to activate [(IPr)AuCl]
(Scheme 1, D),13 the use of Cu(OTf)2 to acivate [(PPh3)AuCl]
(Scheme 1, E),14 and the use of a Brønsted acid/Lewis acid to
[(PPh3)Au(Pht)] (Scheme 1, F).15 Despite these advances, the
direct use of a neutral gold(I) complex [Au(L)Cl] as an
efficient catalyst for the regioselective hydration of terminal
alkynes to methyl ketons is apparently highly desirable from
both synthetic and environmental points of view.
We have reported a series of catalytic transformations with
alcohols as electrophiles catalyzed by an iridium complex.16 We
also described the combination of cationic gold(I) and iridium
catalysts for the synthesis of α-alkylated ketones17a and α-
alkylated amides.17b As part of our continuing interest in this
field of research, we herein demonstrate the direct use of a
neutral gold(I) complex as a general and highly effective
catalyst for the regioselective hydration of terminal alkynes.
Furthermore, one-pot synthesis of optically active secondary
alcohols via hydration/asymmetric transfer hydrogenation
(ATH) from terminal alkynes by the combination of
[(IPr)AuCl] and Cp*RhCl[(R,R)-Tsdpen] (Cp* = pentam-
ethylcyclopentadienyl, Tsdpen = N-(p-toluenesulfonyl)-1,2-
diphenylethylenediamine) was demonstrated.
INTRODUCTION
■
The regioselective hydration of terminal alkynes to methyl
ketones represents one of the most important C−O bond-
forming reactions in organic synthesis because of the wide
availability of alkynyl substrates, the fundamental importance of
the carbonyl motif, and the complete atom efficiency of the
reaction.1 Traditionally, this transformation is performed in the
presence of a large amount of concentrated sulfuric acid
(typically ≥ stoichiometric amount) and/or highly toxic
mercury reagents.2 Over the past several decades, various
metal complexes such as Pt,3 Fe,4 Pd,5 Ir,6 Ag,7 Co,8 and Au9
have been developed as catalysts for such transformations.
Recently, cationic gold(I) species [Au(L)]+ (L = phosphine or
N-heterocyclic carbene) have emerged as one of the most
promising catalysts for the regioselective hydration of terminal
alkynes because of high reactivity and regioselectivity.9f−s
Generally, cationic gold(I) species were generated via reactions
of neutral gold(I) complexes [Au(L)Cl] with silver salts (AgX,
X = OTf, BF4, SbF6, NTf2, etc.) (Scheme 1, A). However, these
procedures have some drawbacks, such as high price and the
light sensitivity of silver salts. In addition, silver salts have
themselves also catalytic activities for the hydration of akynes.10
More recently, several silver salt-free protocols for the
generation of cationic gold(I) species have been developed,
including a protic acid (methanesulfonic acid) activation of
[Au(CH3)(PPh3)] complex (Scheme 1, B),11 a Brønsted acid
activation of [(IPr)Au(OH)] (Scheme 1, C),12 the use of the
Received: January 24, 2015
Published: March 10, 2015
© 2015 American Chemical Society
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corresponding products 2j−o were obtained in 89−96% yields
(Table 1, entries 9−14). Transformations of other arylalkynes,
such as 2-ethynylnaphthalene (1p) and 2-ethynylthiophene
(1q), also afforded the desired products 2p and 2q in 94% and
93% yields, respectively (Table 1, entries 15 and 16). In the
case of bisalkyne, such as 1,3-diethynylbenzene (1r) and 1,4-
diethynylbenzene (1s), the corresponding bisketones 2r and 2s
were isolated in 90% and 92% yields, respectively (Table 1,
entries 17 and 18). Aliphatic alkynes, such as 3,3-dimethyl-1-
butyne (1t), ethynylcyclopropane (1u), 1-hexyne (1v), 3-
butynol (1w), and propargyl acetate (1x), were proven to be
suitable substrates, and reactions gave the corresponding
products 2t−x in >99% NMR yields (Table 1, entries 19−
23). However, no reaction occurred when nonterminal alkyne
1,2-diphenylethyne (1y) was used as a substrate under the same
reaction conditions (Table 1, entry 24).
Scheme 1. Advances in the Generation of Cationic Gold(I)
Species
It noteworthy that apart from the desired methyl ketones,
none of isomer byproducts (aldehydes) were observed in all
cases. Clearly, the hydration of terminal alkynes catalyzed by
[(IPr)AuCl] exhibited complete regioselectivities.
To demonstrate the practicality and safety of this protocol,
the hydration of alkyne on a multigram scale was investigated
(Scheme 3). In a sealed 250 mL Schlenk tube, the reaction of
1a (5.1 g, 50 mmol) was carried out in the presence of
[(IPr)AuCl] (0.2 mol %) in MeOH/H2O (2:1) at 110 °C for
12 h to give the product in 90% yield. This experiment is safe
under the present reaction conditions without safety
precautions.
A possible reacion mechansm is proposed to account for the
hydration of alkynes catalyzed by [(IPr)AuCl] (Scheme 4).
The initial step of the reaction involved the formation of
cationic species A by the dissociation of [(IPr)AuCl] in a polar
H2O/MeOH mixture.18 The resulting species A was coordi-
nated with an alkyne as a two-electron ligand to give species B.
Furthermore, species B underwent nucleophilic attack of water
to afford species C, which could be converted to species D via
keto−enol equilibrium. Finally, the reaction of species D and
H+ occurred to release methyl ketones as the product
accompanied by the regeneration of catalytic species A.
As shown in Figure 1, the addition of NaCl (10 mol %) has
obvious influence on the reaction rate. Apparently, the presence
of a large excess of chloride resulted in a left shift of equilibrium
in Scheme 5, and thus, the reaction rate for the hydration of 1a
is reduced. This result strongly supported the proposed
reaction mechanism in Scheme 4 where [(IPr)Au]+ is the
catalytic active species.
RESULTS AND DISCUSSION
■
Initially, the hydration of phenylacetylene (1a) was chosen as a
model reaction. The reaction of 1a was carried out in the
presence of [(IPr)AuCl] (IPr = 1,3-bis(diisopropylphenyl)-
imidazol-2-ylidene) (0.5 mol %) in MeOH/H2O (2:1) at 80 °C
for 6 h to afford acetophenone (2a) in 88% yield with complete
regioselectivity. It was observed that the product 2a could be
obtained in 99% yield when the temperature of reaction was
enhanced to 110 °C. When [(Ph3P)AuCl] was used as an
alternative catalyst under same reaction conditions, this
reaction gave the product 2a in 51% yield (Scheme 2).
Scheme 2. Hydration of Phenylacetylene (1a)
In recent years, one-pot syntheses have received great
attention as an alternative to traditional multistep synthetic
procedures for the rapid assembly of biologically active and
complex chiral molecules from simple substrates because they
minimize the use of chemicals, energy, and waste production.19
Herzon and co-workers demonstrated a one-pot syntheis of
racemic secondary alcohols involving cationic gold(I)-catalyzed
regioselective hydration of alkynes.9m Very recently, Lei, Sun,
and co-workers described the synthesis of optical active
secondary alcohols via one-pot sequential hydration/asymmet-
ric-transfer hydrogenation (ATH) from terminal alkynes
catalyzed by the combination of Salen−Co3+ catalyst and chiral
ruthenium catalyst.8b However, the addition of H2SO4 (2 mol
%) is necessary for the hydration of terminal alkynes. In
addition, the scope of reaction is also limited and Salen−Co3+
catalyst is not effective for the hydration of phenylacetylenes
bearing a serious electron-withdrawing group. As a result, we
Having established the optimized conditions, the hydration
of a variety of alkynes 1 was conducted, and the results are
shown in Table 1. Reactions of phenylacetylenes bearing one or
two halogen atoms, such as 3-fluoro (1b), 4-fluoro (1c), 4-
chloro (1d), 3-bromo (1e), and 4-bromo (1f), gave the
corresponding products 2b−f in 93−97% yields (Table 1,
entries 1−5). Phenylacetylenes bearing a serious electron-
withdrawing group, such as 4-nitro (1g), 4-(trifluoromethyl)
(1h), and 4-cyano (1i), could be converted to the desired
products 2g−i in 91%−94% yields, although relatively long
reaction time was required (Table 1, entries 6−8). When
phenylacetylenes bearing an electron-donating group, such as 3-
methyl (1j), 4-methyl (1k), 4-ethyl (1l), 4-propyl (1m), 4-
methoxy (1n), and 4-amino (1o), were used as substrates, the
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a
Table 1. Hydration of a Variety of Alkynes 1 to Methyl Ketones Catalyzed by [(IPr)AuCl]
a
b
c
Reaction conditions: 1 (1 mmol), [(IPr)AuCl] (0.5 mol %), MeOH (1 mL), H2O (0.5 mL), 110 °C, 6 h. [(IPr)AuCl] (1 mol %). [(IPr)AuCl] (1
d
e
1
mol %), 120 °C. 12 h. Determined by H NMR spectroscopy.
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As shown in Scheme 6, a series of Noyori−Ikariya catalysts
(0.3 mol %), including RuCl[(R,R)-TsDPEN](p-cymene),
Scheme 3. Hydration of Phenylacetylene (1a) on a
Multigram Scale
Scheme 6. One-Pot Synthesis of Optically Active 1-
Phenylethanol (3a) from Phenylacetylene (1a)
Scheme 4. Proposed Reaction Mechanism
Cp*IrCl[(R,R)-TsDPEN], and Cp*RhCl[(R,R)-TsDPEN],
were selected as a catalyst, and HCOONa (5 equiv) was
used as a hydrogen source for the asymmetric-transfer
hydrogenation (ATH) of acetophenone (2a), which resulted
from the regioselective hydration of phenylacetylene (1a)
catalyzed by [(IPr)AuCl]. Among them, Cp*RhCl[(R,R)-
TsDPEN] exhibited the highest reactivity and enatioselectivity,
and this cascade reaction afforded (R)-1-phenylethanol (3a) in
97% yield with 97% ee. When Cp*RhCl[(S,S)-TsDPEN] was
used as an alternative catalyst, the product (S)-1-phenylethanol
(4a) was obtained in 96% yield with 98% ee.
To expend the scope of this one-pot sequential reaction, a
range of alkynes were investigated, and these results are
outlined in Table 2. Transformations of phenylacetylenes
bearing a halide atom (1b−f) afforded the corresponding
products 3b−f in 89−95% yields with 90−97% ee (Table 2,
entries 1−5). Furthermore, phenylacetylenes bearing a serious
electron-withdrawing group, such as nitro (1g), trifluoromethyl
(1h), and cyano (1i), could be converted to the desired
products 3g−i in 88−90% yields with 87−95% ee (Table 2,
entries 6−8). This catalytic system was also successfully applied
to phenylacetylenes bearing an electron-donating group, such
as methyl (1j,k), ethyl (1l), propyl (1m), methoxy (1n), and
amino (1o), affording the desired products 3j−o in 80−93%
yield with 93−98% ee, although a longer time (24 h) is
required (Table 2, entries 9−14). For 2-ethynylnaphthalene
(1p) and 2-ethynylthiophene (1q), reactions proceeded
smoothly to give the corresponding products 3p and 3q in
92% yield with 92% ee and in 91% yield with 98% ee,
respectively (Table 2, entries 15 and 16).
Figure 1. Time-Course of the Hydration of 1a. Reaction conditions
for black course are described in Scheme 2. The red course indicates
the addition of NaCl (10 mol %).
Scheme 5. Dissociation Equilibrium of [(IPr)AuCl]
CONCLUSION
■
In summary, we have demonstrated that a neutral gold(I)
complex [(IPr)AuCl] is a general and highly effective catalyst
for the regioselective hydration of terminal alkynes, including
aromatic alkynes and aliphatic alkynes. A series of methyl
are interested in exploring the combination of [(IPr)AuCl] and
Noyori−Ikariya catalysts20 for one-pot synthesis of optically
active secondary alcohols from terminal alkynes.
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Table 2. One-Pot Synthesis of Optically Active Alcohols from Terminal Alkynes 1 by the Combination of [(IPr)AuCl] and
a
Cp*RhCl[(R,R)-TsDPEN].
a
Reaction conditions: (1) 1a (1 mmol), [(IPr)AuCl] (0.5 mol %), MeOH (1 mL), H2O (0.5 mL), 110 °C, 6 h; (2) [Cp*RhCl[(R,R)-TsDPEN]
b
c
(0.3 mol %), HCOONa (5 equiv), H2O (1.5 mL), 30 °C, 5 h. Determined by chiral GC or HPLC analysis. In the first step, [(IPr)AuCl] (1 mol
%). In the first step, [(IPr)AuCl] (1 mol %), 120 °C; in the second step, [Cp*RhCl[(R,R)-TsDPEN] (1 mol %), 40 °C. In the first step,
[(IPr)AuCl] (1 mol %), 120 °C. f In the first step, 12 h.
d
e
ketones were obtained in high yields with complete
regioselectivities. Furthermore, a range of optically active
secondary alcohols could be obtained in high yields with
good to excellent enatioselectivities from terminal alkynes via a
one-pot sequential hydration/asymmetric-transfer hydrogena-
tion (ATH) by the combination of of [(IPr)AuCl] and
Cp*RhCl[(R,R)-TsDPEN]. Notably, this research exhibited
the potential of the direct use of neutral gold(I) complexes
instead of cationic ones as catalysts for the activation of of
multiple bonds for organic synthesis.
EXPERIMENTAL SECTION
■
Experimental Details. Melting points were measured on a
micromelting apparatus. 1H NMR spectra were recorded at 500
MHz. Chemical shifts are reported in delta (δ) units, parts per million
(ppm) downfield from tetramethylsilane or ppm relative to the center
of the singlet at 7.26 ppm for CDCl3. Coupling constants (J) are
reported in hertz (Hz), and the splitting patterns are designated as
follows: s, singlet; d, doublet; t, triplet; m, multiplet; b, broad. 13C{1H}
NMR spectra were recorded at 125 MHz with broadband 1H
decoupling. Chemical shifts are reported in δ, ppm relative to the
center of the triplet at 77.0 ppm for CDCl3. 19F NMR spectra were
recorded at 470 MHz. Analytical thin-layer chromatography (TLC)
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was carried out using 0.2 mm commercial silica gel plates. Optical
rotations were measured on a polarimeter. The enantiomeric excess of
the compounds was determined by chiral GC or HPLC using racemic
compounds as references.
1-(4-Propylphenyl)ethanone (2m):31 colorless oil; 89% yield (144
mg); 1H NMR (500 MHz, CDCl3) δ 7.88 (d, J = 7.9 Hz, 2H), 7.26 (d,
J = 7.9 Hz, 2H), 2.64 (t, J = 7.9 Hz, 2H), 2.58 (s, 3H), 1.66 (sext, J =
7.6 Hz, 2H), 0.94 (t, J = 7.5 Hz, 3H); 13C{1H} NMR (125 MHz,
CDCl3) δ 197.7, 148.4, 134.9, 128.5, 128.3, 37.9, 26.4, 24.1, 13.6.
1-(4-Methoxyphenyl)ethanone (2n):26 colorless oil; 92% yield
[(IPr)AuCl],21,22 RuCl[(R,R)-TsDPEN](p-cymene),23 Cp*IrCl-
[(R,R)-TsDPEN],24 Cp*RhCl[(R,R)-TsDPEN],25 and Cp*RhCl-
[(S,S)-TsDPEN]25 were synthesized according the previous reports.
General Procedure for Hydration of Alkynes Catalyzed by
[(IPr)AuCl] (Table 1). To a 25 mL Schlenk tube were added alkyne 1
(1 mmol), [(IPr)AuCl] (3.1 mg, 0.5 mol %), MeOH (1 mL), and H2O
(0.5 mL). The mixture was heated at 110 °C for 6 h and was then
allowed to cool to ambient temperature. The reaction was concetrated
in vacuo and purified by flash column chromatography with hexanes/
ethyl acetate to afford the corresponding product.
1
(138 mg); H NMR (500 MHz, CDCl3) δ 7.94 (d, J = 9.0 Hz, 2H),
6.93 (d, J = 8.6 Hz, 2H), 3.87 (s, 3H), 2.55 (s, 3H); 13C{1H} NMR
(125 MHz, CDCl3) δ 196.7, 163.4, 130.5, 130.2, 113.6, 55.4, 26.2.
1-(3-Aminophenyl)ethanone (2o):32 yellow solid; 90% yield (122
1
mg); mp 98−99 °C; H NMR (500 MHz, CDCl3) δ 7.33 (d, J = 7.5
Hz, 1H), 7.28−7.21 (m, 2H), 6.89−6.85 (m, 1H), 3.81 (br s, 2H),
2.56 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 198.5, 146.7, 138.1,
129.3, 119.6, 118.6, 113. 9, 26.5.
Acetophenone (2a):26 light yellow oil; 99% yield (119 mg); H
1
1-(Naphthalen-2-yl)ethanone (2p):27 white solid; 95% yield (161
NMR (500 MHz, CDCl3) δ 7.99−7.94 (m, 2H), 7.59−7.54 (m, 1H),
7.46 (t, J = 7.7 Hz, 2H), 2.61 (s, 3H); 13C{1H} NMR (125 MHz,
CDCl3) δ 198.0, 136.9, 133.0, 128.4, 128.1, 26.4.
1
mg); m.p 58−59 °C; H NMR (500 MHz, CDCl3) δ 8.47 (s, 1H),
8.04 (d, J = 8.8 Hz, 1H), 7.97 (d, J = 7.2 Hz, 1H), 7.89 (t, J = 8.0 Hz,
1H), 7.63−7.53 (m, 2H), 2.73 (s, 3H); 13C{1H} NMR (125 MHz,
CDCl3) δ 197.8, 135.3, 134.2, 132.3, 130.0, 129.3, 128.2, 128.2, 127.5,
126.5, 123.6, 26.4.
1-(3-Fluorophenyl)ethanone (2b):26 colorless oil; 97% yield (134
mg); 1H NMR (500 MHz, CDCl3) δ 7.74 (d, J = 7.1 Hz, 1H), 7.63 (d,
J = 8.9 Hz, 1H), 7.45 (q, J = 7.1 Hz, 1H), 7.30−7.24 (m, 1H), 2.60 (d,
J = 0.9 Hz, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 196.5, 162.6 (d,
JC−F = 245.7 Hz), 139.0 (d, JC−F = 5.8 Hz), 130.6 (d, JC−F = 7.5 Hz),
1-(Thiophene-2-yl)ethanone (2q):31 colorless oil; 93% yield (117
1
mg); HNMR (500 MHz, CDCl3) δ 7.71−7.69 (m, 1H), 7.64 (d, J =
4.8 Hz, 1H), 7.15−7.11 (m, 1H), 2.57 (d, J = 2.1 Hz), 13C{1H} NMR
(125 MHz, CDCl3) δ 190.4, 144.1, 133.5, 132.3, 127.8, 26.5.
123.9, 119.8 (d, JC−F = 22.0 Hz), 114.6 (d, JC−F = 22.6 Hz), 26.35; 19
NMR (470 MHz, CDCl3) δ −111.9.
F
1,3-Diacetylbenzene (2r):33 white solid; 90% yield (145 mg); H
1
1-(4-Fluorophenyl)ethanone (2c):27 colorless oil; 96% yield (133
mg); 1H NMR (500 MHz, CDCl3) δ 8.01−7.96 (m, 2H), 7.13 (t, J =
8.5 Hz, 2H), 2.59 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 196.4,
165.7 (d, JC−F = 252.5 Hz), 133.5, 130.9 (d, JC−F = 9.1 Hz), 115.6 (d,
JC−F = 22.2 Hz), 26.40; 19F NMR (470 MHz, CDCl3) δ −105.3.
1-(4-Chlorophenyl)ethanone (2d):28 colorless oil; 94% yield (145
mg); 1H NMR (500 MHz, CDCl3) δ 7.90 (dt, J = 8.5 and 2.2 Hz, 2H),
7.44 (dt, J = 8.6 and 2.1 Hz, 2H), 2.59 (s, 3H); 13C{1H} NMR (125
MHz, CDCl3) δ 196.7, 139.4, 135.3, 129.6, 128.8, 26.4.
NMR (500 MHz, CDCl3) δ 8.52 (s, 1H), 8.16 (dd, J = 1.3 and 7.8 Hz,
2H), 7.59 (t, J = 7.7 Hz, 1H), 2.67 (s, 3H); 13C{1H} NMR (125 MHz,
CDCl3) δ 197.2, 137.3, 132.4, 128.9, 127.9, 26.6.
1,4-Diacetylbenzene (2s):31 white solid; 92% yield (150 mg); H
1
NMR (500 MHz, CDCl3) δ 8.03 (s, 4H), 2.65 (s, 6H); 13C{1H} NMR
(125 MHz, CDCl3) δ 197.4, 140.0, 128.4, 26.8.
3,3-Dimethylbutan-2-one (2t):26 colorless oil; 1H NMR (500
MHz, CDCl3) δ 2.16−2.13 (m, 3H), 1.16−1.13 (m, 9H); 13C{1H}
NMR (125 MHz, CDCl3) δ 214.0, 44.1, 26.2, 24.5.
1-(3-Bromophenyl)ethanone (2e):28 colorless oil; 93% yield (186
mg); 1H NMR (500 MHz, CDCl3) δ 8.08 (s, 1H), 7.88 (d, J = 8.0 Hz,
1H), 769 (d, J = 8.0 Hz, 1H), 7.35 (t, J = 7.6 Hz, 1H), 2.59 (s, 3H);
13C{1H} NMR (125 MHz, CDCl3) δ 196.5, 138.7, 135.8, 131.3, 130.1,
126.8, 122.9, 26.5.
1-Cyclopropylethanone (2u):34 colorless oil; 1H NMR (500 MHz,
CDCl3) δ 2.25−2.23 (m, 3H), 1.98−1.91 (m, 1H), 1.05−1.00 (m,
2H), 0.92−0.86 (m, 2H); 13C{1H} NMR (125 MHz, CDCl3) δ 208.6,
29.8, 20.9, 10.4.
Hexan-2-one (2v):35 colorless oil; H NMR (500 MHz, CDCl3) δ
1
1-(4-Bromophenyl)ethanone (2f):27 yellow solid; 95% yield (189
mg); 1H NMR (500 MHz, CDCl3) δ 7.82 (dt, J = 8.6 and 2.1 Hz, 2H),
7.60 (dt, J = 8.6 and 2.1 Hz, 2H), 2.58 (s, 3H); 13C{1H} NMR (125
MHz, CDCl3) δ 196.8, 135.7, 131.7, 129.7, 128.1, 26.4.
2.43 (t, J = 7.7 Hz, 2H), 2.14 (s, 3H), 1.60−1.51 (m, 2H), 1.37−1.27
(m, 2H), 0.90 (td, J = 7.4 and 1.3 Hz, 3H); 13C{1H} NMR (125 MHz,
CDCl3) δ 209.3, 43.4, 29.7, 25.9, 22.2, 13.7.
4-Hydroxybutan-2-one (2w):36 colorless oil; H NMR (500 MHz,
1
1-(4-Nitrophenyl)ethanone (2g):29 yellow solid; 94% yield (156
mg); m.p 82−83 °C; 1H NMR (500 MHz, CDCl3) δ 8.32 (d, J = 9.3
Hz, 2H), 8.11 (d, J = 9.3 Hz, 2H), 2.68 (s, 3H); 13C{1H} NMR (125
MHz, CDCl3) δ 196.2, 150.3, 141.3, 129.2, 123.7, 26.9.
CDCl3) δ 3.84 (q, J = 4.9 Hz, 2H), 2.79 (br s, 1H), 2.73−2.67 (m,
2H), 2.21−2.18 (m, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 209.5,
57.6, 45.3, 30.4.
2-Oxopropyl acetate (2x):37 pale yellow oil; H NMR (500 MHz,
1
1-(4-(Trifluoromethyl)phenyl)ethanone (2h):30 yellow oil; 91%
CDCl3) δ 4.66 (s, 2H), 2.17 (s, 3H), 2.16 (s, 3H); 13C{1H} NMR
(125 MHz, CDCl3) δ 201.5, 170.1, 68.2, 25.9, 20.3.
1
yield (171 mg); H NMR (500 MHz, CDCl3) δ 8.06 (d, J = 8.3 Hz,
2H), 7.74 (d, J = 8.3 Hz, 2H), 2.65 (s, 3H); 13C{1H} NMR (125 MHz,
CDCl3) δ 196.7, 139.6, 134.2 (q, JC−F = 32.4 Hz), 128.5, 125.6 (d, JC−F
= 3.4 Hz), 123.5 (q, JC−F = 270.6 Hz), 26.41; 19F NMR (470 MHz,
CDCl3) δ −63.1.
Procedure for the Hydration of 1a on a Multigram Scale
(Scheme 3). To a 250 mL Schlenk tube were added alkyne 1a (5.1 g,
50 mmol), [(IPr)AuCl] (62 mg, 0.2 mol %), MeOH (20 mL), and
H2O (10 mL). The mixture was heated at 110 °C for 12 h and was
then allowed to cool to ambient temperature. The reaction mixture
was concetrated in vacuo and purified by flash column chromatog-
raphy with hexanes/ethyl acetate to afford the corresponding product
2a in 90% yield (5.371 g).
4-Acetylbenzonitrile (2i):31 white solid; 92% yield (133 mg); m.p
1
60−61 °C; H NMR (500 MHz, CDCl3) δ 8.05 (d, J = 8.2 Hz, 2H),
7.78 (d, J = 7.8 Hz, 2H), 2.65 (s, 3H); 13C{1H} NMR (125 MHz,
CDCl3) δ 196.4, 139.8, 132.4, 128.6, 117.8, 116.3, 26.7.
1-m-Tolylethanone (2j:.32 colorless oil; 96% yield (129 mg); H
1
Cascade Synthesis of Optically Active Secondary Alcohols
Catalyzed by the Combination of [(IPr)AuCl] and Cp*RhCl-
[(R,R)-TsDPEN] (Table 2). To a 25 mL Schlenk tube were added
alkyne 1 (1 mmol), [(IPr)AuCl] (3.1 mg, 0.5 mol %), MeOH (1 mL),
and H2O (0.5 mL). The mixture was heated at 110 °C for 6 h and was
then allowed to cool to ambient temperature. Cp*RhCl[(R,R)-
TsDPEN] (1.9 mg, 0.3 mol %), HCOONa (340 mg, 5 mmol, 5
equiv), and water (1.5 mL) were added, and the mixture was further
stirred at 30 °C for another 5 h. The reaction mixture was cooled to
ambient temperature, concentrated in vacuo, and purified by flash
column chromatography with hexanes/ethyl acetate to afford the
corresponding product.
NMR (500 MHz, CDCl3) δ 7.78−7.73 (m, 2H), 7.40−7.33 (m, 2H),
2.59 (s, 3H), 2.41 (s, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 198.3,
138.2, 137.1, 133.7, 128.7, 128.3, 125.5, 26.5, 21.2.
1-p-Tolylethanone (2k):32 colorless oil; 95% yield (127 mg); H
1
NMR (500 MHz, CDCl3) δ 7.85 (d, J = 8.1 Hz, 2H), 7.25 (d, J = 8.4
Hz, 2H), 2.57 (s, 3H), 2.40 (s, 3H, CH3); 13C{1H} NMR (125 MHz,
CDCl3) δ 197.6, 143.7, 134.5, 129.0, 128.2, 26.2, 21.4.
1-(4-Ethylphenyl)ethanone (2l):32 colorless oil; 93% yield (137
mg); 1H NMR (500 MHz, CDCl3) δ 7.88 (d, J = 8.5 Hz, 2H), 7.28 (d,
J = 8.5 Hz, 2H), 2.71 (q, J = 7.8 Hz, 2H), 2.58 (s, 3H), 1.25 (t, J = 7.6
Hz, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 197.8, 150.0, 134.9,
128.5, 128.0, 28.8, 26.4, 15.1.
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DOI: 10.1021/acs.joc.5b00164
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The Journal of Organic Chemistry
Article
(R)-1-Phenylethanol (3a):38 yellow oil; 97% yield (118 mg); [α]26
1.52 (d, J = 7.1 Hz, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 153.1,
147.1, 126.1, 123.7, 69.5, 25.5.
D
+72.4 (c 1, CHCl3, 97% ee) (lit.38 [α]23D +55.9 (c 0.78, CHCl3, 94.9%
1
ee); HNMR (500 MHz, CDCl3) δ 7.39−7.32 (m, 4H), 7.29−7.24
GC analysis: CP-Chirasil-DEX CB column (25 m × 0.32 mm);
carrier gas: N2; 30 psi; injector temp = 250 °C; detector temp (FID) =
300 °C; column temp = 170 °C; tR = 3.56 min, tS = 3.88 min.
(R)-1-(4-(Trifluoromethyl)phenyl)ethanol (3h):43 yellow oil; 88%
yield (167 mg); [α]26D +43.5 (c 1, CHCl3, 95% ee) (lit.43 [α]25D +35.0
(m, 1H), 4.88 (q, J = 5.0 Hz, 1H), 1.92 (br s, 1H), 1.49 (dd, J = 1.20
and 6.45 Hz, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 145.8, 128.3,
127.2, 125.3, 70.1, 25.0.
GC analysis: CP-Chirasil-DEX CB column (25 m × 0.32 mm);
carrier gas: N2; flow rate 2 mL/min; injector temp = 230 °C; detector
temp (FID) = 280 °C; column temp: 1 min at 70 °C, heating at 20
°C/min to 130 °C, keeping at 130 °C for 5 min; tR = 6.60 min, tS =
6.86 min
1
(c 0.3, CHCl3, 91% ee); H NMR (500 MHz, CDCl3) δ 7.60 (d, J =
8.4 Hz, 2H), 7.48 (d, J = 8.3 Hz, 2H), 4.96 (q, J = 9.8 Hz, 1H), 2.05
(br s, 1H), 1.50 (d, J = 6.4 Hz, 3H); 13C{1H} NMR (125 MHz,
CDCl3) δ 149.7, 129.5 (q, JC−F = 32.4 Hz), 124.1 (q, JC−F = 270.4 Hz),
125.6, 125.3 (d, JC−F = 3.5 Hz), 69.6, 25.1; 19F NMR (470 MHz,
CDCl3) δ −62.4.
(R)-1-(3-Fluorophenyl)ethanol (3b):39 light yellow oil; 95% yield
(133 mg); [α]26D +49.7 (c 1, CHCl3, 97% ee) (lit.39 [α]20D +42.4 (c 1,
CHCl3, 96% ee); 1H NMR (500 MHz, CDCl3) δ 7.33−7.28 (m, 1H),
7.15−7.08 (m, 2H), 6.95 (m, 1H), 4.94−4.87 (m, 1H), 1.85 (d, J = 3.4
Hz, 1H), 1.49 (d, J = 6.5 Hz, 3H); 13C{1H} NMR (125 MHz, CDCl3)
GC analysis: CP-Chirasil-DEX CB column (25 m × 0.32 mm);
carrier gas: N2; 7 psi; injector temp = 250 °C; detector temp (FID) =
300 °C; column temp: 1 min at 70 °C, heating at 20 °C/min to 170
°C, keeping at 170 °C for 6 min; tR = 6.75 min, tS = 6.91 min.
(R)-4-(1-Hydroxyethyl)benzonitrile (3i):44 yellow oil; 90% yield
(133 mg); [α]26 +52.78 (c 1, CHCl3, 92% ee) (lit.44 [α]20 +77.1 (c
δ 162.9 (d, JC−F = 244.3 Hz), 148.5 (d, JC−F = 6.7 Hz), 129.9 (d, JC−F
=
7.7 Hz), 120.9 (d, JC−F = 2.8 Hz), 114.2 (d, JC−F = 20.8 Hz), 112.3 (d,
JC−F = 21.8 Hz), 69.7, 25.2; 19F NMR (470 MHz, CDCl3) δ −112.9.
GC analysis: CP-Chirasil-DEX CB column (25 m × 0.32 mm);
carrier gas: N2; flow rate 2 mL/min; injector temp = 250 °C; detector
temp (FID) = 300 °C; column temp: 1 min at 70 °C, heating at 20
°C/min to 140 °C, keeping at 140 °C for 9 min; tR = 6.26 min, tS =
6.49 min.
D
D
1
0.7, CHCl3, 92% ee); H NMR (500 MHz, CDCl3) δ 7.66−7.60 (m,
2H), 7.49 (d, J = 7.8 Hz, 2H), 5.00−4.94 (m, 1H), 2.18 (br s, 1H),
1.49 (d, J = 6.6 Hz, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 151.1,
132.3, 126.0, 118.8, 111.0, 69.6.
GC analysis: CP-Chirasil-DEX CB column (25 m × 0.32 mm);
carrier gas: N2; 30 psi; injector temp = 250 °C; detector temp (FID) =
300 °C; column temp = 170 °C; tR = 2.14 min, tS = 2.33 min.
(R)-1-(4-Fluorophenyl)ethanol (3c):38 light yellow oil; 93% yield
(130 mg); [α]26 +66.4 (c 1, CHCl3, 95% ee) (lit.38 [α]23 +43.1 (c
D
D
(R)-1-m-Tolylethanol (3j):39 yellow oil; 93% yield (126 mg); [α]26
1
0.73, CHCl3, 92.3% ee); H NMR (500 MHz, CDCl3) δ 7.36−7.32
(m, 2H), 7.02 (t, J = 8.7 Hz, 2H), 4.88 (q, J = 6.3 Hz, 1H), 1.89 (br s,
1H), 1.47 (d, J = 6.5 Hz, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ
D
+56.0 (c 1, CHCl3, 97% ee) (lit.39 [α]20D +64.2 (c 1, CHCl3, 97% ee);
1H NMR (500 MHz, CDCl3) δ 7.26−7.22 (m, 1H), 7.19 (s, 1H),
7.18−7.14 (d, J = 7.9 Hz, 1H), 7.10−7.07 (d, J = 7.4 Hz, 1H), 4.85 (q,
J = 6.4 Hz, 1H), 2.36 (s, 3H), 1.86 (br s, 1H), 1.48 (d, J = 6.6 Hz, 3H);
13C{1H} NMR (125 MHz, CDCl3) δ 145.8, 138.1, 128.4, 128.2, 126.1,
122.4, 70.4, 25.1, 21.4.
162.0 (d, JC−F = 244.0 Hz), 141.8 (d, JC−F = 2.6 Hz), 127.0 (d, JC−F
=
7.5 Hz), 115.1 (d, JC−F = 20.9 Hz), 69.6, 25.2; 19F NMR (470 MHz,
CDCl3) δ −115.3.
GC analysis: CP-Chirasil-DEX CB column (25 m × 0.32 mm);
carrier gas: N2; flow rate 2 mL/min; injector temp = 230 °C; detector
temp (FID) = 280 °C; column temp: 1 min at 70 °C, heating at 20
°C/min to 130 °C, keeping at 130 °C for 5 min; tR = 7.18 min, tS =
7.61 min.
GC analysis: CP-Chirasil-DEX CB column (25 m × 0.32 mm);
carrier gas: N2; flow rate 2 mL/min; injector temp = 250 °C; detector
temp (FID) = 300 °C; column temp: 1 min at 70 °C, heating at 20
°C/min to 140 °C, keeping at 140 °C for 9 min; tR = 6.88 min, tS =
7.06 min.
(R)-1-(4-Chlorophenyl)ethanol (3d):40 light yellow oil; 94% yield
(146 mg); [α]26 +56.4 (c 1, CHCl3, 95% ee) (lit.40 [α]21 +41.3 (c
(R)-1-p-Tolylethanol (3k):38 yellow oil; 91% yield (124 mg); [α]26
D
D
D
1.1, Et2O, 91% ee); 1H NMR (500 MHz, CDCl3) δ 7.31 (s, 4H), 4.88
(q, J = 6.4 Hz, 1H), 1.83 (br s, 1H), 1.47 (d, J = 6.6 Hz, 3H); 13C{1H}
NMR (125 MHz, CDCl3) δ 144.2, 132.9, 128.5, 126.7, 69.6, 25.2.
GC analysis: CP-Chirasil-DEX CB column (25 m × 0.32 mm);
carrier gas: N2; flow rate 2 mL/min; injector temp = 250 °C; detector
temp (FID) = 300 °C; column temp: 1 min at 70 °C, heating at 20
°C/min to 140 °C, keeping at 140 °C for 9 min; tR = 10.32 min, tS =
11.10 min.
+56.0 (c 1, CHCl3, 96% ee) (lit.38 [α]23D +52.2 (c 0.96, CHCl3, 93.7%
1
ee); H NMR (500 MHz, CDCl3) δ 7.28−7.24 (d, J = 7.8 Hz, 2H),
7.18−7.14 (d, J = 8.2 Hz, 2H), 4.86 (m, 1H), 2.34 (s, 3H), 1.83 (br s,
1H), 1.47 (d, J = 6.5, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 142.9,
137.1, 129.1, 125.3, 70.2, 25.1, 21.1;
GC analysis: CP-Chirasil-DEX CB column (25 m × 0.32 mm);
carrier gas: N2; flow rate 2 mL/min; injector temp = 250 °C; detector
temp (FID) = 300 °C; column temp: 1 min at 70 °C, heating at 20
°C/min to 140 °C, keeping at 140 °C for 9 min; tR = 6.64 min, tS =
6.90 min.
(R)-1-(3-Bromophenyl)ethanol (3e):41 yellow oil; 89% yield (178
mg); [α]26 +46.75 (c 1, CHCl3, 89% ee) (lit.41 [α]D +45.0 (c 1,
D
1
(R)-1-(4-Ethylphenyl)ethanol (3l):45 yellow oil; 90% yield (135
mg); [α]26 +47.5 (c 1, CHCl3, 97% ee) (lit.45 [α]23 +32.6 (c 0.62,
CHCl3, 96% ee); H NMR (500 MHz, CDCl3) δ 7.52 (s, 1H), 7.39
(d, J = 7.8 Hz, 1H), 7.27 (d, J = 7.8 Hz, 1H), 7.20 (t, J = 7.9 Hz, 1H),
4.84 (q, J = 6.3 Hz, 1H), 2.11 (br s, 1H), 1.47 (d, J = 6.4 Hz, 3H);
13C{1H} NMR (125 MHz, CDCl3) δ 148.1, 130.4, 130.1, 128.5, 124.0,
122.6, 69.7, 25.2.
D
D
CHCl3, 97% ee); 1H NMR (500 MHz, CDCl3) δ 7.29 (d, J = 7.7 Hz,
2H), 7.18 (d, J = 7.7 Hz, 2H), 4.86 (q, J = 7.2 Hz, 1H), 2.64 (q, J = 7.7
Hz, 2H), 1.85 (d, J = 19.1 Hz, 1H), 1.48 (d, J = 7.0 Hz, 3H), 1.23 (t, J
= 7.8 Hz, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 143.5, 143.1,
128.0, 125.4, 70.3, 28.5, 25.0, 15.6;
HPLC analysis: Chiralpak IA column, UV detection at 254 nm, flow
1.0 mL/min, n-hexane/i-PrOH = 96:4, tR = 7.84 min, tS = 8.31 min.
(R)-1-(4-Bromophenyl)ethanol (3f):42 colorless oil; 94% yield (188
mg); [α]26 +49.2 (c 1, CHCl3, 96% ee) (lit.42 [α]20 +36.0 (c 1.7,
GC analysis: CP-Chirasil-DEX CB column (25 m × 0.32 mm);
carrier gas: N2; flow rate 2 mL/min; injector temp = 250 °C; detector
temp (FID) = 300 °C; column temp: 1 min at 70 °C, heating at 20
°C/min to 140 °C, keeping at 140 °C for 9 min; tR = 8.16 min, tS =
8.47 min.
D
D
CH2Cl2, 95% ee); 1H NMR (500 MHz, CDCl3) δ 7.47 (d, J = 8.3 Hz,
2H), 7.25 (d, J = 8.6 Hz, 2H), 4.86 (q, J = 7.2 Hz, 1H), 1.85 (s, 1H),
1.47 (d, J = 6.9 Hz, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 144.8,
131.6, 127.1, 121.2, 69.8, 25.2.
(R)-1-(4-Propylphenyl)ethanol (3m):46 Yellow oil; 87% yield (143
mg); [α]26 +47.9 (c 1, CHCl3, 98% ee) (lit.46 [α]20 +33.2 (c 2.2,
GC analysis: CP-Chirasil-DEX CB column (25 m × 0.32 mm);
carrier gas: N2; 15 psi; injector temp = 250 °C; detector temp (FID) =
300 °C; column temp: 1 min at 70 °C, heating at 20 °C/min to 170
°C, keeping at 170 °C for 6 min; tR = 7.06 min, tS = 7.20 min.
(R)-1-(4-Nitrophenyl)ethanol (3g):38 yellow oil; 90% yield (151
mg); [α]26 +26.3 (c 1, CHCl3, 87% ee), (lit.38 [α]23 +35.1 (c 1.46,
D
D
MeOH, 93% ee); 1H NMR (500 MHz, CDCl3) δ 7.28 (d, J = 7.6 Hz,
2H), 7.16 (d, J = 8.1 Hz, 2H), 4.87 (q, J = 6.8 Hz, 1H), 2.57 (t, J = 7.7
Hz, 2H), 1.79 (br s, 1H), 1.68−1.58 (m, 2H), 1.49 (d, J = 6.1 Hz, 3H),
0.94 (t, J = 7.3 Hz, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 143.0,
142.0, 128.6, 125.3, 70.3, 37.7, 25.0, 24.6, 13.8.
D
D
CHCl3, 88.4% ee); 1H NMR (500 MHz, CDCl3) δ 8.19 (d, J = 8.5 Hz,
2H), 7.54 (d, J = 8.6 Hz, 2H), 5.06−4.99 (m, 1H), 2.20 (br s, 1H),
GC analysis: CP-Chirasil-DEX CB column (25 m × 0.32 mm);
carrier gas: N2; flow rate 2 mL/min; injector temp = 250 °C; detector
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DOI: 10.1021/acs.joc.5b00164
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The Journal of Organic Chemistry
Article
temp (FID) = 300 °C; column temp: 1 min at 70 °C, heating at 20
°C/min to 140 °C, keeping at 140 °C for 9 min; tR = 10.40 min, tS =
10.90 min.
(2) (a) Kutscheroff, M. Chem. Ber. 1881, 14, 1540−1542.
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(R)-1-(4-Methoxyphenyl)ethanol (3n):40 yellow oil; 84% yield (127
mg); [α]26 +51.8 (c 1, CHCl3, 98% ee) (lit.40 [α]25 +53.5 (c 1.7,
D
D
CHCl3, 94% ee); 1H NMR (500 MHz, CDCl3) δ 7.31 (d, J = 8.7 Hz,
2H), 6.90 (d, J = 8.8 Hz, 2H), 4.85 (q, J = 6.5 Hz, 1H), 3.82 (s, 3H),
2.15 (br s, 1H), 1.49 (d, J = 6.3 Hz, 3H); 13C{1H} NMR (125 MHz,
CDCl3) δ 158.9, 138.0, 126.6, 113.8, 69.8, 55.2, 24.9;
(3) (a) Hiscox, W.; Jennings, P. W. Organometallics 1990, 9, 1997−
1999. (b) Jennings, P. W.; Hartman, J. W.; Hiscox, W. C. Inorg. Chim.
Acta 1994, 222, 317−322. (c) Francisco, L. W.; Moreno, D. A.;
Atwood, J. D. Organometallics 2001, 20, 4237−4245.
GC analysis: CP-Chirasil-DEX CB column (25 m × 0.32 mm);
carrier gas: N2; flow rate 2 mL/min; injector temp = 250 °C; detector
temp (FID) = 300 °C; column temp: 1 min at 70 °C, heating at 20
°C/min to 140 °C, keeping at 140 °C for 9 min; tR = 10.20 min, tS =
10.60 min.
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Guo, H. Org. Lett. 2014, 16, 948−951.
(R)-1-(3-Aminophenyl)ethanol (3o):47 brown oil; 80% yield (110
mg); mp 64−65 °C; [α]26D +45.7 (c 1.2, CHCl3, 93% ee) (lit.47 [α]25
D
+45.6 (c 1.2, CHCl3, 95% ee); 1H NMR (500 MHz, CDCl3) δ 7.11 (t,
J = 7.8 Hz, 1H), 6.72 (d, J = 7.3 Hz, 1H), 6.66 (s, 1H), 6.56 (d, J = 8.3
Hz, 1H), 4.75 (q, J = 9.8 Hz, 1H), 3.67 (s, 2H), 2.43 (br s, 1H), 1.43
(d, J = 6.8 Hz, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ 147.2, 129.4,
115.6, 114.2, 112.0, 70.4, 25.0.
(6) Hirabayashi, T.; Okimoto, Y.; Saito, A.; Morita, M.; Sakaguchi, S.;
Ishii, Y. Tetrahedron 2006, 62, 2231−2234.
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2012, 48, 434−436. (b) Venkateswara, K. T.; Prasad, P. S. S.; Lingaiah,
N. Green Chem. 2012, 14, 1507−1514.
HPLC analysis: Chiralpak IA column, UV detection at 254 nm, flow
1.0 mL/min, hexane/EtOH = 90:10, tR = 15.35 min, tS = 16.72 min.
(R)-1-(Naphthalen-2-yl)ethanol (3p):38 white solid; 92% yield (159
mg); mp 69−70 °C; [α]26 +53.7 (c 1, CHCl3, 92% ee) (lit.38 [α]23
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L.; Xiang, J.; He, W. J. Org. Chem. 2013, 78, 9190−9195. (r) Xie, L.;
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2668−2671. (s) Xu, Y.; Hu, X.; Shao, J.; Yang, G.; Wu, Y.; Zhang, Z.
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D
D
+46.7 (c 1.04, CHCl3, 92% ee); 1H NMR (500 MHz, CDCl3) δ 7.86−
7.80 (m, 4H), 7.52−7.44 (m, 3H), 5.06 (q, J = 6.9 Hz, 1H), 1.95 (br s,
1H), 1.58 (d, J = 5.8 Hz, 3H); 13C{1H} NMR (125 MHz, CDCl3) δ
143.2, 133.3, 132.8, 128.2, 127.9, 127.6, 126.1, 125.7, 123.8, 123.7,
70.4, 25.1.
HPLC analysis: Chiralpak IA column, UV detection at 254 nm, flow
1.0 mL/min, n-hexane/EtOH = 98:2, tR = 14.63 min, tS = 15.61 min.
(R)-1-(Thiophene-2-yl)ethanol (3q):38 yellow oil; 91% yield (116
mg); [α]26 +39.9 (c 1, CHCl3, 98% ee) (lit.38 [α]23 +20.4 (c 0.56,
D
D
1
CHCl3, 94.7% ee); H NMR (500 MHz, CDCl3) δ 7.23 (dd, J = 1.6
and 1.5 Hz, 1H), 6.99−6.95 (m, 2H), 5.12 (q, J = 6.4 Hz, 1H), 2.10
(br s, 1H), 1.60 (d, J = 6.4 Hz, 3H); 13C{1H} NMR (125 MHz,
CDCl3) δ 149.8, 126.4, 124.1, 123.0, 65.8, 25.0.
GC analysis: CP-Chirasil-DEX CB column (25 m × 0.32 mm);
carrier gas: N2; 7 psi; injector temp = 250 °C; detector temp (FID) =
300 °C; column temp: 1 min at 70 °C, heating at 20 °C/min to 170
°C, keeping at 170 °C for 6 min; tR = 6.33 min, tS = 6.41 min.
ASSOCIATED CONTENT
■
S
* Supporting Information
1H NMR, 13C NMR, and 19F NMR spectra of products; chiral
GC and HPLC chromatograms of chiral products. This
material is available free of charge via the Internet at http://
pubs.acs.org.
(10) Mathieu, B. T. T.; Andre, M.; Alain, W. Chem. Commun. 2012,
48, 434−436.
(11) (a) Teles, J. H.; Brode, S.; Chabanas, M. Angew. Chem., Int. Ed.
1998, 37, 1415−1418. (b) Mizushima, E.; Sato, K.; Hayashi, T.;
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AUTHOR INFORMATION
■
Corresponding Author
*E-mail: fengli@njust.edu.cn.
Notes
The authors declare no competing financial interest.
(12) (a) Gaillard, S.; Bosson, J.; Ramon, R. S.; Nun, P.; Slawin, A. M.
Z.; Nolan, S. P. Chem.Eur. J. 2010, 16, 13729−13740. (b) Gomez-
Suarez, A.; Oonishi, Y.; Meiries, S.; Nolan, S. P. Organometallics 2013,
32, 1106−1111.
ACKNOWLEDGMENTS
■
This work was supported by the National Natural Science
Foundation of China (No. 21272115).
(13) Lavallo, V.; Frey, G. D.; Kousar, S.; Donnadieu, B.; Bertrand, G.
Proc. Nat. Acad. Sci. U.S.A. 2007, 104, 13569−13573.
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