Paracyclophane-based carbene-copper catalyst tuned by transannular electronic effects for asymmetric boration

Article abstract of DOI:10.1039/c6ra14404g

A series of planar chiral carbene-copper complexes based on the [2.2]paracyclophane backbone with a pseudo-ortho substitution pattern have been synthesized and applied to asymmetric β-boration of α,β-unsaturated esters. As a result, transannular electronic effects of the substituent of the chiral catalyst have significant influence on the catalytic performance. A variety of chiral β-hydroxyl esters were obtained in excellent enantioselectivities (up to 97% ee) and yields (up to 99%).

Full text of DOI:10.1039/c6ra14404g

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[2.2]Paracyclophane-based carbene–copper
catalyst tuned by transannular electronic effects for
asymmetric boration†
Cite this: RSC Adv., 2016, 6, 75144
a
c
a
b
b
*
Jianqiang Chen, Wenzeng Duan, Zhen Chen, Manyuan Ma, Chun Song
a
*
and Yudao Ma
A series of planar chiral carbene–copper complexes based on the [2.2]paracyclophane backbone with
a pseudo-ortho substitution pattern have been synthesized and applied to asymmetric b-boration of a,b-
unsaturated esters. As a result, transannular electronic effects of the substituent of the chiral catalyst
have significant influence on the catalytic performance. A variety of chiral b-hydroxyl esters were
obtained in excellent enantioselectivities (up to 97% ee) and yields (up to 99%).
Received 3rd June 2016
Accepted 3rd August 2016
DOI: 10.1039/c6ra14404g
www.rsc.org/advances
can be remotely controlled by an electronic effect, represents
a challenging conceptual advance in modern asymmetric tran-
Introduction
sition metal catalysis.
Organoboranes are versatile synthetic intermediates for the
preparation of a wide range of organic molecules.1 Catalytic
boration of C]C bonds with diboron reagents is a promising
strategy for synthesis of organoboron derivatives.2 Aer the
seminal report of Miyaura and Suzuki,3 several catalysts for the
addition of diboron reagents to various unsaturated compounds
including asymmetric variants were developed.4 In particular,
copper-catalyzed b-boration of a,b-unsaturated carbonyl
compounds with diborons has become the most straightforward
approach to access structurally diverse carbonyl compounds
containing a C–B bond. The copper-catalyzed asymmetric b-
boration of a,b-unsaturated carbonyl compounds was rst re-
ported by Yun et al.5 Subsequently, carbene–copper catalysts for
Cyclophanes are a special group of aromatic compounds
which consist of two phenyl rings locked face-to-face by
aliphatic chains.8 The [2.2]paracyclophane core holds the two
rings together with a well-dened orientation and facilitates
strong through-space electronic interactions between the upper
and lower rings in addition to the through-bond interactions
normally associated with p-conjugated skeletons. Besides the
unique electronic properties, [2.2]paracyclophane backbone as
a planar chiral source has inspired great interest from
researchers in asymmetric catalysis.9 Recently, our group also
reported a series of planar chiral NHC precursors derived from
[2.2]paracyclophane and employed them in asymmetric transi-
tion metal catalysis.10 On the basis of current knowledge, we
anticipated that simple introduction of a range of substituents
in the pseudo-ortho position of the [2.2]paracyclophane back-
bone exhibiting different transannular electronic effects might
allow a rapid and effective ne-tuning of the electronic prop-
erties of the carbene center without change in the ligand's steric
properties. Beyond, we also intended to examine the effects of
such a modulation on the catalytic behavior of relevant
complex. Herein, we report that the catalytic performance of
[2.2]paracyclophane-based NHC–copper complexes in the
asymmetric boration can be controlled by the electronic tuning
of carbene ligands.
the enantioselective boration of a,b-unsaturated esters were
6
´
devised by Fernaandez and co-workers. Since then, catalysis
mediated by N-heterocyclic carbenes (NHCs) as well as their
metal complexes has been developed as one of the most efficient
methods for synthesis of organoboranes.7 However, in pioneer-
ing studies on the use of NHCs as chiral ligands, substantial
efforts was directed toward the control of their steric properties.
To date, the consequences of an electronic tuning of the chiral
carbene center on the catalytic performance of relevant
complexes has not been examined. The development of chiral
carbene–metal complexes, the catalytic performance of which
aDepartment of Chemistry, Shandong University, Shanda South Road No. 27, Jinan
250100, P. R. China. E-mail: ydma@sdu.edu.cn
bSchool of Pharmaceutical Sciences, West Wenhua Road No. 44, Jinan 250012, P. R.
Results and discussion
China. E-mail: chunsong@sdu.edu.cn
Planar chiral imidazolium salts based on the pseudo-ortho-
substituted [2.2]paracyclophane backbone were selected as the
precursors of a series of target ligands showing almost the same
steric hindrance (Fig. 1). We conceived that remote electronic
effects should provide a handle to control the reactivity of
cSchool of Chemistry and Chemical Engineering, Liaocheng University, Hunan Road
No. 1, Liaocheng 252000, P. R. China
† Electronic supplementary information (ESI) available: Experimental procedures,
full compound characterization, detailed spectral data and HPLC chromatograms
for products. See DOI: 10.1039/c6ra14404g
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Fig. 2 Comparison of the kinetics of the ligands in the Cu-catalyzed
asymmetric boration of ethyl cinnamate.
Fig. 1 Various planar chiral carbene precursor.
metal–NHC–based catalysts.11 Therefore, the energies of the
orbital occupied by the carbene lone pair of electrons (Es) and of
the lowest unoccupied orbital at the carbene center (Ep) were
determined by density functional theory (DFT) calculations at
the B3LYP/6-31G (d,p) level (Table 1). And a set of planar chiral
NHC–copper complexes was prepared and applied to the
asymmetric b-boration of a,b-unsaturated esters (Table 1). At 5
mol% catalyst loading in THF solvent at room temperature, all
of these catalysts facilitated addition of bis(pinacolato)diboron
(B2Pin2) to ethyl cinnamate, and aer oxidative workup, the
derived hydroxyl compound was isolated with signicant levels
of enantioenrichment (Table 1, entries 1–4). In line with our
expectations, these NHC–copper complexes showed strikingly
different behavior in the asymmetric boration. Thus, methoxyl-
substituted (RP)-L1-CuCl, which contains the strongest electron
donor of all ligands in Table 1 (Es ¼ ꢀ5.33), gave the boration
product 2c with 65% yield and 22% ee. By contrast, uorine-
substituted (SP)-L4-CuCl, which appears as the poorest elec-
tron donor of the whole series (Es ¼ ꢀ5.64), furnished 87% yield
and 80% ee. Furthermore, a comparative kinetic study of these
ligands shows that a slight difference in the substitution pattern
of the pseudo-ortho-substituted [2.2]paracyclophanyl NHC
dramatically alters the activity of the resulting copper catalyst
(Fig. 2). Based on these observations, we can conclude that, at
least in the present case, the transannular electronic effects of
the substituent on the pseudo-ortho-substituted [2.2]para-
cyclophanyl NHC has signicant inuence on the catalytic
performances. Moreover, NHC–copper complexes with more
electron decient ligands give higher yields and selectivities.
With imidazolium salt (SP)-L4 as the optimal ligand, we
screened the reaction conditions to optimize the yield and
selectivity of the boration product. As shown in Table 2, strong
bases such as KOtBu and NaOtBu did not improve the yields and
enantioselectivities. Among the various nonprotic solvents
tested (THF, dioxane, DME, Et2O, CH2Cl2, CHCl3, DCE,
Table 2 Screening of the reaction conditionsa
Table 1 Investigation of transannular electronic effectsa
Entry
Solvent
T (ꢁC)
Base
Yieldb (%)
eec (%)
1
2
3
4
5
6
7
8
THF
THF
THF
Dioxane
DME
25
25
25
25
25
25
25
25
25
25
0
Cs2CO3
NaOtBu
KOtBu
87
74
85
84
80
83
87
73
87
85
57
83
<5
80
77
78
78
70
71
81
68
70
82
82
81
—
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Entry
Ligand
Yieldb (%)
eec (%)
Esd (eV)
Ep (eV)
Et2O
CH2Cl2
CHCl3
DCE
Toluene
Toluene
Toluene
THF
1
2
3
4
(RP)-L1
(SP)-L2
(RP)-L3
(SP)-L4
65
82
89
87
22 (R)
72 (S)
64 (R)
80 (S)
ꢀ5.33
ꢀ5.62
ꢀ5.57
ꢀ5.64
ꢀ0.64
ꢀ0.54
ꢀ0.68
ꢀ0.54
9
10
11d
12
13e
40
25
a
The reaction was carried out with ligand (5.0 mol%), Cu2O (2.5 mol%),
Cs2CO3 (5.0 mol%), (B2Pin2) (0.19 mmol), 1c (0.17 mmol) and MeOH
b
a
(0.34 mmol) in THF (0.5 mL) at room temperature. Yield of product
The reaction was carried out with (Sp)-L4 (5.0 mol%), Cu2O (2.5 mol%),
c
aer oxidated by NaBO3$4H2O. Determined by HPLC analysis using (B2Pin2) (0.19 mmol), 1c (0.17 mmol) and MeOH (0.34 mmol) in solvent
d
b
a chiral stationary phase (Chiralpak IA column). All calculations (0.5 mL).
Yield of product aer oxidated by NaBO3$4H2O.
Determined by HPLC analysis using a chiral stationary phase
d
c
were performed by using the DFT method with B3LYP function
e
implemented
in
Gaussian03
program
package.
Geometry (Chiralpak IA column). The reaction was carried out in 5 h. The
optimizations were performed using the 6–31 G (d,p) basis set.
reaction was performed with the in situ formed catalyst system.
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toluene), toluene was identied to afford the highest enantio-
selectivity (82% ee), so it was chosen as the optimal solvent
(Table 2, entries 4–10). Interestingly, reaction could be per-
formed at temperature between 0 ꢁC and 40 ꢁC with little
erosion of enantioselectivity, although the reaction rate drop-
Scheme 1 Asymmetric b-boration of 1f on a larger scale.
ꢁ
ped sharply at 0 C (Table 2, entries 11–12).
Under these optimized reaction conditions, we explored the
scope of b-boration with various a,b-unsaturated esters con-
taining diverse steric and electronic properties. The results were
summarized in Table 3. First, the reaction scope was probed by
changing the nature of the cinnamate partner. Methyl and
benzylic cinnamates led to slightly lower selectivities (Table 3,
entries 1–2). In contrast to our previously published results,10d
increasing the size of the ester moiety of the substrate had
a benecial impact on the overall selectivity (Table 3, entries 3–
6). Among the cinnamate partners screened, t-butyl cinnamate
gave the best enantioselectivity (95% ee). Inspired by the
exciting result, we continued to evaluate various b-substituted
unsaturated t-butyl esters in order to investigate the substituent
effect. It appears that substituents on the aromatic rings of the
a,b-unsaturated esters have little effect on the catalytic activity
and enantioselectivity (Table 3, entry 7–20), no matter whether
it is a electron-withdrawing substituent or a electron-donating
one. Besides, the substrate bearing a furyl ring proceeded
smoothly to give the desired product 2u in good yield (96%) and
enantiomeric excess (92% ee). Furthermore, the cyclohexyl-
substituted a,b-unsaturated ester was a suitable substrate
under the modied conditions, affording the boration product
in good yield (87%) and stereoselectivity (93% ee). However, iso-
propyl and tert-butyl substituted acrylates yielded the corre-
sponding products with 84% and 86% enantiomeric excesses,
respectively.
Table 3 Investigating the substrate scope of the reactiona
To further demonstrate the applicability of our catalytic
process, a larger scale reaction was attempted with only 0.5
mol% of (Sp)-L4 at room temperature. Under these conditions,
the reaction could also complete in half an hour and gave the
chiral b-hydroxyl esters 2f in 96% yield and 92% enantiose-
lectivity (Scheme 1). This result indicated that the catalysis
could also keep efficient with much less catalyst loadings (10%
of the amount used before) when the substrates were broadened
to a larger scale.
Entry
R1
R2
Yieldb (%)
eec (%)
1
2
3
4
5
6
7
8
Ph
Ph
Ph
Ph
Ph
Ph
Me
Bn
91 (2a)
90 (2b)
85 (2c)
87 (2d)
82 (2e)
86 (2f)
84 (2g)
84 (2h)
86 (2i)
99 (2j)
99 (2k)
97 (2l)
86 (2m)
83 (2n)
85 (2o)
91 (2p)
83 (2q)
88 (2r)
99 (2s)
94 (2t)
96 (2u)
87 (2v)
81 (2w)
85 (2x)
76 (S)d
80 (S)
82 (S)
87 (S)
70 (S)
95 (S)
93 (S)
90 (S)
97 (S)
91 (S)
92 (S)
93 (S)
90 (S)
94 (S)
95 (S)
90 (S)
95 (S)
95 (S)
91 (S)
95 (S)
92 (S)
93 (S)
84 (S)
86 (S)
Et
iPr
Conclusions
iBu
tBu
tBu
tBu
tBu
tBu
tBu
tBu
tBu
tBu
tBu
tBu
tBu
tBu
tBu
tBu
tBu
tBu
tBu
tBu
In conclusion, we synthesized a series of planar chiral imida-
zolium salts derived from the pseudo-ortho-substituted [2.2]
paracyclophane skeleton and evaluated their transannular
electronic effects and chiral discrimination ability based on
the Cu-catalyzed asymmetric b-boration of a,b-unsaturated
esters. Our efforts led to the development of the uorine-
substituted catalyst (Sp)-L4-CuCl, which exhibited an excep-
tionally high reactivity and enantioselectivity in the asym-
metric boration reaction by virtue of transannular electronic
effects. To the best of our knowledge, this is the rst successful
example of an electronic tuning of the chiral carbene center on
the catalytic performance of relevant complexes, which might
provide a new direction to the design of the chiral carbene
backbone.
2-MeC6H4
3-MeC6H4
4-MeC6H4
2-ClC6H4
3-ClC6H4
4-ClC6H4
2-MeOC6H4
3-MeOC6H4
4-MeOC6H4
2-CF3C6H4
3-CF3C6H4
4-CF3C6H4
1-Naphthyl
2-Naphthyl
2-Furyl
9
10
11
12
13
14
15
16
17
18
19
20
21
22e
23e
24e
Cyclohexyl
Isopropyl
tBu
Experimental
a
The reaction was carried out with (Sp)-L4 (5.0 mol%), Cu2O (2.5 mol%),
Imidazolium triates of (RP)-L1,10g (SP)-L2 (ref. 10f) and (RP)-L3
(ref. 10f) were synthesized following a reported procedure. The
Cs2CO3 (5.0 mol%), (B2Pin2) (0.165 mmol), substrate (0.15 mmol) and
b
MeOH (0.30 mmol) in toluene (0.5 mL) at room temperature. Yield
c
of product aer oxidated by NaBO3$4H2O. Determined by HPLC
analysis using a chiral stationary phase (Chiralpak IA or IB column). corresponding imidazolium chlorides were obtained easily by
d
The absolute conguration was established by comparison of the
anion exchange of their imidazolium triates analogue with an
e
optical rotation with literature values. The enantiomeric excess value
ion-exchange resin (chloride form) according the same method
as described by McQuade.12
was determined as benzoylated compound.
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Imidazolium chloride (RP)-L1
General procedure for the synthesis of imidazolium chloride
25
(SP)-L4
ꢁ
White solid: 126.4 mg, 65% yield, mp > 225 C (dec); [a]D
¼
ꢀ101.0 (c 0.4, CHCl3); 1H NMR (300 MHz, CDCl3) d 9.82 (s, 40% glyoxal (0.14 mL, 1.17 mmol) was added into the solution
1H), 8.34 (s, 2H), 7.09–6.95 (m, 2H), 6.87–6.75 (m, 2H), 6.72– of (Sp)-4-amino-12-uoro[2.2]paracyclophane (238.0 mg, 0.78
6.58 (m, 4H), 6.54–6.43 (m, 2H), 6.20–6.00 (m, 2H), 3.86 (s, mmol) in THF (1.0 mL) and the mixture stirred at room
6H), 3.42 (ddd, J ¼ 13.3, 9.2, 4.4 Hz, 2H), 3.36–3.20 (m, 4H), temperature for 4 h before a yellow precipitate separated out.
3.20–3.02 (m, 4H), 3.02–2.89 (m, 4H), 2.82 (ddd, J ¼ 13.4, 9.5, Aer completion of the reaction, as indicated by TLC, the yellow
5.5 Hz, 2H). 13C{1H}NMR (75 MHz, CDCl3) d 158.3, 142.7, precipitate diimine was ltered, dried and prepared for the next
142.2, 136.8, 135.9, 135.4, 134.7, 133.9, 132.3, 130.0, 128.2, step.
124.7, 123.4, 119.9, 60.2, 34.5, 33.7, 31.6, 30.3. HRMS (ESI-
To a suspension of AgOTf (200.5 mg, 0.78 mmol) in THF (1.0
TOF) m/z [M ꢀ Cl]+ calcd for C37H37N2O2 541.2855, found mL) was added chloromethyl pivalate (0.10 mL, 0.70 mmol) and
541.2858.
the resulting suspension was sealed and stirred for 30 min in
dark. Then the above diimine in CH2Cl2 (1.0 mL) was added and
the mixture continued to stir in the sealed tube in dark at 40 ꢁC
for another 24 h. When the reaction was over, the suspension
was ltered and solvent was removed under vacuum. The
residue was puried by chromatographed on silica gel (CH2Cl2/
ethanol ¼ 30/1) to give the imidazolium triate as a white solid.
The corresponding imidazolium chloride (SP)-L4 was obtained
easily by anion exchange of its imidazolium triate analogue
with an ion-exchange resin (chloride form) according the same
method as described by McQuade.12
Imidazolium chloride (SP)-L2
White solid: 60.7 mg, 62% yield, mp > 250 ꢁC (dec); [a]D25 ¼ +73.5
(c 0.4, CHCl3); 1H NMR (300 MHz, CDCl3) d 10.90 (s, 1H), 8.04 (s,
2H), 7.09 (d, J ¼ 6.5 Hz, 4H), 6.81–6.47 (m, 10H), 3.49–3.18 (m,
6H), 3.18–2.96 (m, 8H), 2.70 (dd, J ¼ 15.6, 6.6 Hz, 2H). 13C{1H}
NMR (75 MHz, CDCl3) d 143.5, 140.4, 140.3, 138.3, 137.4, 135.9,
135.3, 133.7, 133.2, 133.1, 131.8, 128.5, 127.1, 123.6, 35.0, 34.9,
34.6, 32.9. HRMS (ESI-TOF) m/z [M ꢀ Cl]+ calcd for C35H33N2
481.2644, found 481.2643.
Imidazolium chloride (SP)-L4
Imidazolium chloride (RP)-L3
White solid: 138.3 mg, 87% yield, mp > 250 ꢁC (dec); [a]D25
White solid: 203.0 mg, 78% yield, mp > 250 ꢁC; [a]D25 ¼ ꢀ88.7 (c
1
¼
0.5, CHCl3); H NMR (300 MHz, CDCl3) d 10.73 (s, 1H), 8.02 (s,
ꢀ57.5 (c 0.3, CHCl3); 1H NMR (300 MHz, CDCl3) d 11.21 (s, 1H), 2H), 7.21–7.01 (m, 2H), 7.00–6.77 (m, 2H), 6.76–6.66 (m, 2H),
8.38 (s, 2H), 7.24–7.17 (m, 2H), 6.93–6.84 (m, 2H), 6.77–6.66 (m, 6.66–6.44 (m, 4H), 6.27–5.95 (m, 2H), 3.68–3.07 (m, 10H), 3.01
6H), 6.65–6.57 (m, 2H), 3.64–3.44 (m, 4H), 3.31–3.13 (m, 6H), (ddd, J ¼ 12.8, 9.3, 3.4 Hz, 2H), 2.85 (dt, J ¼ 14.6, 5.5 Hz, 4H). 13
C
3.07–2.88 (m, 4H), 2.71–2.55 (m, 2H). 13C{1H}NMR (75 MHz, {1H}NMR (75 MHz, CDCl3) d 160.6 (d, 1JC–F ¼ 242.3 Hz), 143.7,
CDCl3) d 142.0, 141.5, 138.9, 138.0, 137.7, 135.9, 135.6, 133.4, 143.7, 143.7, 142.0, 137.6, 137.0, 137.0, 137.0, 136.3, 135.4,
133.3, 132.7, 132.3, 126.1, 122.7, 122.5, 35.5, 33.9, 32.9, 32.3. 135.4, 135.4, 134.1, 133.4, 129.4, 126.0, 125.8, 125.7, 123.5,
HRMS (ESI-TOF) m/z [M ꢀ Cl]+ calcd for C35H31Br2N2 639.0834, 123.3, 117.4, 117.4, 117.1, 117.1, 34.4, 33.5, 31.6, 29.0. HRMS
found 639.0833.
(ESI-TOF) m/z [M ꢀ Cl]+ calcd for C35H31F2N2 517.2450, found
517.2449.
General procedure for the synthesis of (Sp)-4-amino-12-uoro
[2.2]paracyclophane
General procedure for the copper-catalyzed b-boration of a,b-
unsaturated esters
(Sp)-4-Amino-12-uoro[2.2]paracyclophane was synthesized
following a reported procedure13 using the known enantiomer
(Sp)-4-bromo-12-uoro[2.2]paracyclophane14 as the starting
material.
Imidazolium chloride (SP)-L4 (4.15 mg, 7.5 ꢂ 10ꢀ3 mmol),
Cu2O (0.54 mg, 3.75 ꢂ 10ꢀ3 mmol) were added to 1.0 mL
anhydrous CH2Cl2 in an oven dried Schlenk ask under an
argon atmosphere. The mixture was stirred at 40 C for 72 h
before solvent was evaporated under argon at 60 C and 0.5
ꢁ
ꢁ
(Sp)-4-Amino-12-uoro[2.2]paracyclophane ((Sp)-3)
mL anhydrous toluene was added at room temperature.
White solid: 347.5 mg, 88% yield, mp 178–180 ꢁC; [a]D25
¼
Cs2CO3 (2.44 mg, 7.5 ꢂ 10ꢀ3 mmol) and bis(pinacolato)
ꢀ167.7 (c 0.13, CH2Cl2); 1H NMR (300 MHz, CDCl3) d 6.49–6.34 diboron (41.9 mg, 0.165 mmol) were added consecutively.
(m, 2H), 6.34–6.28 (m, 1H), 6.27–6.19 (m, 1H), 6.17–6.02 (m, The mixture was stirred at room temperature for 10 minutes
1H), 5.82–5.70 (m, 1H), 3.73–3.52 (m, 1H), 3.40–3.19 (m, 1H), before a,b-unsaturated esters (0.15 mmol) and MeOH (13.0
3.06–2.94 (m, 3H), 2.94–2.86 (m, 1H), 2.86–2.72 (m, 2H), 2.72– mL, 0.30 mmol) were added simultaneously. Aer being stir-
0.44 (m, 2H). 13C{1H}NMR (75 MHz, CDCl3) d 160.6 (d, 1JC–F
¼
red for 0.5 h, the solvent was removed under vacuum and the
237.8 Hz), 145.1, 141.6, 141.5, 140.1, 134.9, 134.8, 134.7, 128.8, crude product was subjected to the oxidation with sodium
128.8, 124.5, 124.2, 123.5, 123.4, 121.4, 119.8, 119.5, 34.6, 34.5, peroxoborate (115.4 mg, 5.0 eq.) in THF (1.0 mL) and H2O (1.0
30.8, 26.1, 26.0. HRMS (ESI-TOF) m/z [M + H]+ calcd for mL) at room temperature for 3 h. The reaction mixture was
C
16H17FN 242.1345, found 242.1345.
concentrated in vacuum and the residue was puried by
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column chromatography on silica gel (n-hexane/ethyl acetate
¼ 30/1–10/1), giving the corresponding alcohol 2.
(S)-tert-Butyl 3-hydroxy-3-phenylpropanoate 2f
Colorless oil: 36.7 mg, 86% yield, 95% ee, [a]2D5 ¼ ꢀ40.7 (c 0.30,
CHCl3); [lit.15a [a]D24 ꢀ 37.7 (c 1.20, CHCl3) for 88% ee (S)]. HPLC
(Chiralpak IA column, n-hexane/iPrOH 75 : 1, 220 nm, 1.0 mL
minꢀ1), retention time: 22.9 min (minor), 25.0 min (major); 1H
NMR (300 MHz, CDCl3) d 7.54–7.11 (m, 5H), 5.04 (dd, J ¼ 8.3, 4.6
Hz, 1H), 3.53 (s, 1H), 2.79–2.49 (m, 2H), 1.42 (s, 9H). 13C{1H}
NMR (75 MHz, CDCl3) d 172.2, 142.9, 128.8, 128.0, 126.0, 81.9,
70.7, 44.6, 28.4.
(S)-Methyl 3-hydroxy-3-phenylpropanoate 2a
Colorless oil: 24.6 mg, 91% yield, 76% ee, [a]2D5 ¼ ꢀ23.7 (c 0.17,
CHCl3); [lit.15a [a]D16 ꢀ 52.9 (c 1.00, CHCl3) for 95% ee (S)]. HPLC
(Chiralpak IA column, n-hexane/iPrOH 75 : 1, 220 nm, 1.0 mL
minꢀ1), retention time: 45.4 min (minor), 50.5 min (major); 1H
NMR (300 MHz, CDCl3) d 7.50–7.27 (m, 5H), 5.15 (dd, J ¼ 8.5, 4.3
Hz, 1H), 3.73 (s, 3H), 3.18 (s, 1H), 2.88–2.65 (m, 2H). 13C{1H}
NMR (75 MHz, CDCl3) d 172.9, 142.5, 128.7, 127.9, 125.7, 70.4,
52.0, 43.2, 29.8.
(S)-tert-Butyl 3-hydroxy-3-(2-methylphenyl)propanoate (2g)
Colorless oil 29.7 mg, 84% yield, 93% ee, [a]2D5 ¼ ꢀ56.6 (c 0.2,
CHCl3); HPLC (Chiralpak IA column, n-hexane/iPrOH 200 : 1,
220 nm, 1.0 mL minꢀ1), retention time: 50.9 min (major), 60.8
(S)-Benzyl 3-hydroxy-3-phenylpropanoate 2b
1
Colorless oil: 34.6 mg, 90% yield, 80% ee, [a]2D5 ¼ ꢀ17.6 (c 0.15,
CHCl3); [lit.15a [a]D26 ꢀ 34.8 (c 1.12, CHCl3) for 91% ee (S)]. HPLC
(Chiralpak IA column, n-hexane/EtOH 50 : 1, 220 nm, 1.0 mL
minꢀ1), retention time: 41.9 min (minor), 54.5 min (major); 1H
NMR (300 MHz, CDCl3) d 7.53–7.22 (m, 10H), 5.14 (s, 3H), 3.23
(d, J ¼ 2.4 Hz, 1H), 2.92–2.67 (m, 2H). 13C{1H}NMR (75 MHz,
CDCl3) d 172.2, 142.5, 135.6, 128.7, 128.6, 128.6, 128.4, 128.4,
128.3, 128.2, 127.9, 127.8, 125.9, 125.7, 83.0, 72.9, 70.4, 66.7,
66.4, 44.0, 43.4, 24.6, 24.5.
min (minor); H NMR (300 MHz, CDCl3) d 7.55–7.44 (m, 1H),
7.25–7.08 (m, 3H), 5.30 (dd, J ¼ 8.1, 4.6 Hz, 1H), 3.33 (s, 1H),
2.77–2.49 (m, 2H), 2.35 (s, 3H), 1.47 (s, 9H). 13C{1H}NMR (75
MHz, CDCl3) d 172.1, 140.5, 134.3, 130.4, 127.5, 126.3, 125.3,
81.5, 67.1, 43.0, 28.1, 19.0. HRMS (ESI-TOF) m/z [M + Na]+ calcd
for C14H20NaO3 259.1310, found 259.1300.
(S)-tert-Butyl 3-hydroxy-3-(3-methylphenyl)propanoate (2h)
Colorless oil: 29.7 mg, 84% yield, 90% ee, [a]2D5 ¼ ꢀ57.0 (c 0.15,
CHCl3); HPLC (Chiralpak IA column, n-hexane/iPrOH 100 : 1,
220 nm, 1.0 mL minꢀ1), retention time: 28.5 min (minor), 32.7
(S)-Ethyl 3-hydroxy-3-phenylpropanoate 2c
1
Colorless oil: 24.8 mg, 85% yield, 82% ee, [a]2D5 ¼ ꢀ35.4 (c 0.30,
CHCl3); [lit.15a [a]D26 ꢀ 46.5 (c 1.04, CHCl3) for 97% ee (S)]. HPLC
(Chiralpak IA column, n-hexane/iPrOH 100 : 1, 220 nm, 1.0 mL
minꢀ1), retention time: 46.4 min (minor), 49.5 min (major); 1H
NMR (300 MHz, CDCl3) d 7.53–7.21 (m, 5H), 5.13 (dd, J ¼ 8.4, 4.5
Hz, 1H), 4.18 (q, J ¼ 7.1 Hz, 2H), 3.29 (s, 1H), 2.87–2.62 (m, 2H),
1.26 (t, J ¼ 7.1 Hz, 3H). 13C{1H}NMR (75 MHz, CDCl3) d 172.4,
142.5, 128.6, 127.8, 125.7, 70.3, 60.9, 43.3, 14.2.
min (major); H NMR (300 MHz, CDCl3) d 7.25–7.12 (m, 3H),
7.09 (d, J ¼ 7.4 Hz, 1H), 5.05 (dd, J ¼ 8.1, 4.6 Hz, 1H), 3.39 (s,
1H), 2.75–2.53 (m, 2H), 2.35 (s, 3H), 1.45 (s, 9H). 13C{1H}NMR
(75 MHz, CDCl3) d 172.0, 142.5, 138.1, 128.4, 128.4, 126.4, 122.8,
81.5, 70.4, 44.3, 28.1, 21.4. HRMS (ESI-TOF) m/z [M + Na]+ calcd
for C14H20NaO3 259.1310, found 259.1308.
(S)-tert-Butyl 3-hydroxy-3-(4-methylphenyl)propanoate (2i)
Colorless oil: 30.3 mg, 86% yield, 97% ee, [a]2D5 ¼ ꢀ33.8 (c 0.2,
CHCl3); HPLC (Chiralpak IA column, n-hexane/iPrOH 100 : 1,
220 nm, 1.0 mL minꢀ1), retention time: 42.0 min (minor), 45.2
(S)-Isopropyl 3-hydroxy-3-phenylpropanoate 2d
Colorless oil: 27.2 mg, 87% yield, 87% ee, [a]2D5 ¼ ꢀ31.3 (c 0.20,
CHCl3); [lit.15a [a]D24 ꢀ 39.6 (c 0.94, CHCl3) for 92% ee (S)]. HPLC
(Chiralpak IA column, n-hexane/EtOH 50 : 1, 220 nm, 1.0 mL
minꢀ1), retention time: 19.9 min (minor), 21.6 min (major); 1H
NMR (300 MHz, CDCl3) d 7.58–7.22 (m, 5H), 5.26–4.98 (m, 2H),
1
min (major); H NMR (300 MHz, CDCl3) d 7.27 (s, 1H), 7.24 (s,
1H), 7.15 (d, J ¼ 7.9 Hz, 2H), 5.05 (dd, J ¼ 8.4, 4.4 Hz, 1H), 3.34
(s, 1H), 2.82–2.51 (m, 2H), 2.34 (s, 3H), 1.45 (s, 9H). 13C{1H}NMR
(75 MHz, CDCl3) d 172.0, 139.7, 137.3, 129.1, 125.7, 81.45, 70.3,
44.3, 28.1, 21.1. HRMS (ESI-TOF) m/z [M + Na]+ calcd for
3.34 (s, 1H), 2.83–2.60 (m, 2H), 1.24 (dd, J ¼ 6.3, 1.6 Hz, 6H). 13
C
{1H}NMR (75 MHz, CDCl3) d 172.0, 142.5, 128.5, 127.8, 125.7,
C
14H20NaO3 259.1310, found 259.1310.
70.3, 68.4, 43.6, 21.8.
(S)-tert-Butyl 3-hydroxy-3-(2-chlorophenyl)propanoate (2j)
Colorless oil: 38.1 mg, 99% yield, 91% ee, [a]2D5 ¼ ꢀ45.0 (c 0.2,
(S)-iso-Butyl 3-hydroxy-3-phenylpropanoate 2e
Colorless oil: 27.3 mg, 82% yield, 70% ee, [a]2D5 ¼ ꢀ33.6 (c 0.25, CHCl3); HPLC (Chiralpak IA column, n-hexane/iPrOH 75 : 1, 220
CHCl3); [lit.10d [a]D25 ꢀ 40.5 (c 0.1, CHCl3) for 96% ee (S)]. HPLC nm, 1.0 mL minꢀ1), retention time: 14.8 min (major), 15.9 min
1
(Chiralpak IA column, n-hexane/EtOH 50 : 1, 220 nm, 0.5 mL (minor); H NMR (300 MHz, CDCl3) d 7.68–7.55 (m, 1H), 7.38–
minꢀ1), retention time: 38.0 min (minor), 41.8 min (major); 1H 7.27 (m, 2H), 7.25–7.15 (m, 1H), 5.44 (dd, J ¼ 9.5, 2.7 Hz, 1H),
NMR (300 MHz, CDCl3) d 7.48–7.08 (m, 5H), 5.04 (dd, J ¼ 8.4, 4.5 3.72 (s, 1H), 2.78 (dd, J ¼ 16.6, 2.8 Hz, 1H), 2.51 (dd, J ¼ 16.6, 9.5
Hz, 1H), 3.81 (d, J ¼ 6.7 Hz, 2H), 3.29 (s, 1H), 2.80–2.52 (m, 2H), Hz, 1H), 1.47 (s, 9H). 13C{1H}NMR (75 MHz, CDCl3) d 172.0,
1.83 (dp, J ¼ 13.4, 6.7 Hz, 1H), 0.83 (d, J ¼ 6.7 Hz, 6H). 13C{1H} 140.0, 131.4, 129.3, 128.6, 127.1, 81.7, 67.2, 42.3, 28.1. HRMS
NMR (75 MHz, CDCl3) d 172.5, 142.5, 128.6, 127.8, 125.7, 71.0, (ESI-TOF) m/z [M + Na]+ calcd for C13H17ClNaO3 279.0764, found
70.3, 43.3, 27.7, 19.0.
279.0732.
75148 | RSC Adv., 2016, 6, 75144–75151
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HRMS (ESI-TOF) m/z [M + Na]+ calcd for C14H20NaO4 275.1259,
(S)-tert-Butyl 3-hydroxy-3-(3-chlorophenyl)propanoate (2k)
found 275.1257.
Colorless oil: 38.2 mg, 99% yield, 92% ee, [a]2D5 ¼ ꢀ16.0 (c 0.2,
CHCl3); HPLC (Chiralpak IA column, n-hexane/iPrOH 100 : 1,
220 nm, 0.5 mL minꢀ1), retention time: 26.5 min (minor), 41.3
(S)-tert-Butyl 3-hydroxy-3-(2-triuoromethylphenyl)
propanoate (2p)
1
min (major); H NMR (300 MHz, CDCl3) d 7.39 (d, J ¼ 2.0 Hz,
1H), 7.27–7.18 (m, 3H), 5.05 (t, J ¼ 6.3 Hz, 1H), 3.57 (s, 1H), 2.63
(d, J ¼ 6.2 Hz, 2H), 1.45 (s, 9H). 13C{1H}NMR (75 MHz, CDCl3)
d 171.7, 144.6, 134.4, 129.7, 127.8, 126.0, 123.8, 81.8, 69.7, 44.0,
28.1. HRMS (ESI-TOF) m/z [M + Na]+ calcd for C13H17ClNaO3
279.0764, found 279.0758.
Colorless oil: 39.6 mg, 91% yield, 90% ee, [a]2D5 ¼ ꢀ57.6 (c 0.2,
CHCl3); HPLC (Chiralpak IA column, n-hexane/iPrOH 75 : 1, 254
nm, 1.0 mL minꢀ1), retention time: 13.4 min (major), 16.0 min
1
(minor); H NMR (300 MHz, CDCl3) d 7.93–7.76 (m, 1H), 7.75–
7.50 (m, 2H), 7.48–7.32 (m, 1H), 5.49 (dd, J ¼ 8.9, 2.1 Hz, 1H),
3.68 (s, 1H), 2.80–2.43 (m, 2H), 1.48 (s, 9H). 13C{1H}NMR (75
MHz, CDCl3) d 171.8, 141.5, 132.3, 127.7, 125.6, 125.5, 125.4,
124.3 (q, 1JC–F ¼ 272.3 Hz), 81.8, 66.0, 44.3, 28.1. HRMS (ESI-
TOF) m/z [M + Na]+ calcd for C14H17F3NaO3 313.1027, found
313.1022.
(S)-tert-Butyl 3-hydroxy-3-(4-chlorophenyl)propanoate (2l)
White solid: 37.3 mg, 97% yield, 93% ee, [a]2D5 ¼ ꢀ48.8 (c 0.2,
CHCl3); [lit.15b [a]D20 + 13.8 (c 0.18, CHCl3) for 98% ee (R)]. Mp 48–
i
ꢁ
50 C; HPLC (Chiralpak IA column, n-hexane/ PrOH 30 : 1, 220
nm, 1.0 mL minꢀ1), retention time: 15.4 min (major), 16.3 min
1
(minor); H NMR (300 MHz, CDCl3) d 7.54–7.28 (m, 4H), 5.19–
(S)-tert-Butyl 3-hydroxy-3-(3-triuoromethylphenyl)
propanoate (2q)
4.96 (m, 1H), 3.57 (s, 1H), 2.76–2.49 (m, 2H), 1.45 (s, 9H). 13C
{1H}NMR (75 MHz, CDCl3) d 171.8, 141.1, 133.3, 128.6, 127.1,
81.8, 69.7, 44.1, 28.1. HRMS (ESI-TOF) m/z [M + Na]+ calcd for
Colorless oil: 36.1 mg, 83% yield, 95% ee, [a]2D5 ¼ ꢀ47.4 (c 0.15,
CHCl3); HPLC (Chiralpak IA column, n-hexane/EtOH 100 : 1,
220 nm, 1.0 mL minꢀ1), retention time: 13.0 min (minor), 13.9
min (major); 1H NMR (300 MHz, CDCl3) d 7.66 (s, 1H), 7.60–7.51
(m, 2H), 7.51–7.43 (m, 1H), 5.14 (t, J ¼ 6.3 Hz, 1H), 3.70 (s, 1H),
2.76–2.57 (m, 2H), 1.45 (s, 9H). 13C{1H}NMR (75 MHz, CDCl3)
d 171.7, 143.5, 129.1, 128.9, 124.5, 124.4, 124.1 (q, 1JC–F ¼ 270.8
Hz), 122.6, 122.5, 82.0, 69.8, 44.0, 28.0. HRMS (ESI-TOF) m/z [M
+ Na]+ calcd for C14H17F3NaO3 313.1027, found 313.1059.
C
13H17ClNaO3 279.0764, found 279.0763.
(S)-tert-Butyl 3-hydroxy-3-(2-methoxyphenyl)propanoate (2m)
White solid: 32.3 mg, 86% yield, 90% ee, [a]2D5 ¼ ꢀ30.3 (c 0.15,
CHCl3); mp 57–58 ꢁC; HPLC (Chiralpak IA column, n-hex-
ane/iPrOH 100 : 1, 220 nm, 1.0 mL minꢀ1), retention time: 31.9
min (major), 33.6 min (minor); 1H NMR (300 MHz, CDCl3)
d 7.55–7.34 (m, 1H), 7.31–7.18 (m, 1H), 7.10–6.91 (m, 1H), 6.90–
6.77 (m, 1H), 5.31 (dd, J ¼ 9.0, 3.7 Hz, 1H), 3.85 (s, 3H), 3.55 (s,
1H), 2.82–2.52 (m, 2H), 1.45 (s, 9H). 13C{1H}NMR (75 MHz,
CDCl3) d 172.1, 156.1, 130.6, 128.5, 126.7, 120.7, 110.3, 81.1,
66.6, 55.3, 42.7, 28.1. HRMS (ESI-TOF) m/z [M + Na]+ calcd for
(S)-tert-Butyl 3-hydroxy-3-(4-triuoromethylphenyl)
propanoate (2r)
White solid: 38.3 mg, 88% yield, 95% ee, [a]2D5 ¼ ꢀ50.0 (c 0.15,
CHCl3); mp 50–51 ꢁC; HPLC (Chiralpak IA column, n-hex-
ane/iPrOH 100 : 1, 220 nm, 1.0 mL minꢀ1), retention time: 28.3
min (major), 30.2 min (minor); 1H NMR (300 MHz, CDCl3) d 7.61
(d, J ¼ 8.2 Hz, 2H), 7.50 (d, J ¼ 8.1 Hz, 2H), 5.21–5.07 (m, 1H),
3.66 (s, 1H), 2.91–2.45 (m, 2H), 1.46 (s, 9H). 13C{1H}NMR (75
MHz, CDCl3) d 171.7, 146.5, 130.0, 126.0, 125.5, 125.4, 125.4,
125.3, 124.1 (q, 1JC–F ¼ 270.0 Hz), 82.0, 69.7, 44.0, 28.0. HRMS
(ESI-TOF) m/z [M + Na]+ calcd for C14H17F3NaO3 313.1027, found
313.1014.
C
14H20NaO4 275.1259, found 275.1257.
(S)-tert-Butyl 3-hydroxy-3-(3-methoxyphenyl)propanoate (2n)
Colorless oil: 31.1 mg, 83% yield, 94% ee, [a]2D5 ¼ ꢀ53.2 (c 0.15,
CHCl3); HPLC (Chiralpak IB column, n-hexane/iPrOH 75 : 1, 220
nm, 1.0 mL minꢀ1), retention time: 18.3 min (major), 20.5 min
(minor); 1H NMR (300 MHz, CDCl3) d 7.32–7.16 (m, 1H), 6.94 (d,
J ¼ 7.6 Hz, 2H), 6.86–6.72 (m, 1H), 5.06 (dd, J ¼ 7.4, 5.3 Hz, 1H),
3.81 (s, 3H), 3.43 (s, 1H), 2.79–2.49 (m, 2H), 1.47 (d, J ¼ 7.1 Hz,
9H). 13C{1H}NMR (75 MHz, CDCl3) d 171.9, 159.8, 144.3, 129.5,
118.0, 113.3, 111.1, 81.6, 70.3, 55.2, 44.2, 28.1. HRMS (ESI-TOF)
m/z [M + Na]+ calcd for C14H20NaO4 275.1259, found 275.1259.
(S)-tert-Butyl 3-hydroxy-3-(naphthalen-1-yl)propanoate (2s)
Colorless oil: 40.4 mg, 99% yield, 91% ee, [a]2D5 ¼ ꢀ46.7 (c 0.2,
CHCl3); [lit.15c [a]2D4 + 28.2 (c 2.20, EtOH) for 94% ee (R)]. HPLC
(Chiralpak IA column, n-hexane/iPrOH 50 : 1, 254 nm, 1.0 mL
(S)-tert-Butyl 3-hydroxy-3-(4-methoxyphenyl)propanoate (2o)
Colorless oil: 32.1 mg, 85% yield, 95% ee, [a]2D5 ¼ ꢀ50.9 (c 0.18, minꢀ1), retention time: 22.9 min (major), 26.2 min (minor); 1H
CHCl3); [lit.15b [a]D20 + 28.0 (c 0.15, CHCl3) for 97% ee (R)]. HPLC NMR (300 MHz, CDCl3) d 8.17–8.01 (m, 1H), 7.93–7.84 (m, 1H),
(Chiralpak IA column, n-hexane/EtOH 100 : 1, 220 nm, 1.0 mL 7.83–7.74 (m, 1H), 7.74–7.65 (m, 1H), 7.59–7.42 (m, 3H), 5.87
minꢀ1), retention time: 40.3 min (major), 44.5 min (minor); 1H (dd, J ¼ 9.2, 3.3 Hz, 1H), 3.51 (s, 1H), 2.80 (qd, J ¼ 16.6, 6.3 Hz,
NMR (300 MHz, CDCl3) d 7.34–7.24 (m, 2H), 7.00–6.80 (m, 2H), 2H), 1.49 (s, 9H). 13C{1H}NMR (75 MHz, CDCl3) d 172.2, 138.1,
5.03 (dd, J ¼ 8.7, 4.1 Hz, 1H), 3.80 (s, 3H), 3.35 (s, 1H), 2.64 (dd, J 133.8, 130.1, 129.0, 128.2, 126.2, 125.5, 125.5, 123.0, 122.9, 81.6,
¼ 8.6, 6.4 Hz, 2H), 1.45 (s, 9H). 13C{1H}NMR (75 MHz, CDCl3) 67.4, 43.6, 28.1. HRMS (ESI-TOF) m/z [M + Na]+ calcd for
d 171.9, 159.1, 134.8, 127.0, 113.8, 81.4, 70.0, 55.3, 44.3, 28.1.
C17H20NaO3 295.1310, found 295.1305.
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(S)-tert-Butyl 3-hydroxy-3-(naphthalen-2-yl)propanoate (2t)
(S)-tert-Butyl 3-hydroxy-4-methylpentanoate (2w)
White solid: 38.4 mg, 94% yield, 95% ee, [a]2D5 ¼ ꢀ53.6 (c 0.15, Colorless oil: 22.9 mg, 81% yield, 84% ee, HPLC (benzoylated,
CHCl3); [lit.15d [a]D20 ꢀ 36.9 (c 0.42, CHCl3) for 96% ee (S)]. Mp 65– Chiralpak IA column, n-hexane/iPrOH 75 : 1, 220 nm, 1.0 mL
i
66 C; HPLC (Chiralpak IA column, n-hexane/ PrOH 30 : 1, 220 minꢀ1), retention time: 7.1 min (minor), 17.2 min (major);
ꢁ
nm, 1.0 mL minꢀ1), retention time: 21.2 min (major), 22.3 min [a]D25 ¼ ꢀ37.5 (c 0.2, CHCl3); [lit.15e [a]D25 + 35.0 (c 1.1, CHCl3) for
1
1
(minor); H NMR (300 MHz, CDCl3) d 8.02–7.67 (m, 4H), 7.63– 95% ee (R)]. H NMR (300 MHz, CDCl3) d 3.73 (s, 1H), 3.07 (s,
7.33 (m, 3H), 5.36–5.15 (m, 1H), 3.54 (s, 1H), 2.85–2.58 (m, 2H), 1H), 2.37 (qd, J ¼ 16.2, 6.2 Hz, 2H), 1.82–1.61 (m, 1H), 1.47 (s,
1.46 (s, 9H). 13C{1H}NMR (75 MHz, CDCl3) d 171.9, 140.0, 133.3, 9H), 0.93 (dd, J ¼ 8.6, 6.9 Hz, 6H). 13C{1H}NMR (75 MHz, CDCl3)
133.0, 128.3, 128.0, 127.7, 126.2, 125.9, 124.5, 123.9, 81.6, 70.5, d 173.0, 81.2, 72.8, 39.4, 33.1, 28.1, 18.3, 17.8. HRMS (ESI-TOF)
44.2, 28.1. HRMS (ESI-TOF) m/z [M + Na]+ calcd for C17H20NaO3 m/z [M + Na]+ calcd for C10H20NaO3 211.1310, found 211.1303.
295.1310, found 295.1299.
(S)-1-(tert-Butoxy)-4-methyl-1-oxopentan-3-yl benzoate (2w0)
Colorless oil: 52.6 mg, 84% yield; [a]2D5 ¼ ꢀ24.5 (c 0.18, CHCl3);
(S)-tert-Butyl 3-hydroxy-3-(furan-2-yl)propanoate (2u)
1H NMR (300 MHz, CDCl3) d 8.21–7.92 (m, 2H), 7.61–7.50 (m,
Colorless oil: 30.7 mg, 96% yield, 92% ee, [a]2D5 ¼ ꢀ22.5 (c 0.2,
1H), 7.49–7.35 (m, 2H), 5.38 (dt, J ¼ 8.2, 5.2 Hz, 1H), 2.74–2.51
(m, 2H), 2.15–1.94 (m, 1H), 1.35 (s, 9H), 1.00 (dd, J ¼ 6.8, 3.4 Hz,
6H). 13C{1H}NMR (75 MHz, CDCl3) d 167.0, 165.8, 132.8, 130.5,
129.6, 128.3, 80.8, 75.4, 38.1, 31.7, 27.9, 18.3, 17.7. HRMS (ESI-
TOF) m/z [M + Na]+ calcd for C17H24NaO4 315.1572, found
315.1572.
CHCl3); [lit.15e [a]D25 + 22.2 (c 1.5, CHCl3) for 90% ee (R)]. HPLC
(Chiralpak IA column, n-hexane/iPrOH 25 : 1, 220 nm, 0.5 mL
minꢀ1), retention time: 28.5 min (major), 31.1 min (minor); 1H
NMR (300 MHz, CDCl3) d 7.37 (dd, J ¼ 1.8, 0.8 Hz, 1H), 6.33 (dd,
J ¼ 3.2, 1.8 Hz, 1H), 6.27 (d, J ¼ 3.2 Hz, 1H), 5.08 (dd, J ¼ 7.7, 4.5
Hz, 1H), 3.40 (s, 1H), 2.92–2.68 (m, 2H), 1.46 (s, 9H). 13C{1H}
NMR (75 MHz, CDCl3) d 171.4, 154.9, 142.1, 110.2, 106.2, 81.7,
64.3, 40.7, 28.1. HRMS (ESI-TOF) m/z [M + Na]+ calcd for
(S)-tert-Butyl 3-hydroxy-4,4-dimethylpentanoate (2x)
Colorless oil: 34.3 mg, 85% yield, 86% ee, [a]2D5 ¼ ꢀ33.3 (c 0.15,
CHCl3); HPLC (benzoylated, Chiralpak IA column, n-hex-
ane/iPrOH 50 : 1, 220 nm, 1.0 mL minꢀ1), retention time: 6.0
min (minor), 9.7 min (major).
C
11H16NaO4 235.0946, found 235.0934.
(S)-tert-Butyl 3-cyclohexyl-3-hydroxypropanoate (2v)
Colorless oil: 29.7 mg, 87% yield, 93% ee, [a]2D5 ¼ ꢀ43.2 (c 0.2,
CHCl3); [lit.15e [a]D25 + 26.8 (c 1.1, CHCl3) for 92% ee (R)]. HPLC
(benzoylated, Chiralpak IA column, n-hexane/iPrOH 75 : 1, 220
nm, 1.0 mL minꢀ1), retention time: 8.0 min (minor), 31.0 min
(major); 1H NMR (300 MHz, CDCl3) d 3.73 (ddd, J ¼ 9.1, 6.0, 3.0
Hz, 1H), 3.00 (s, 1H), 2.57–2.23 (m, 2H), 1.96–1.81 (m, 1H), 1.81–
1.71 (m, 2H), 1.71–1.60 (m, 2H), 1.47 (s, 9H), 1.42–1.28 (m, 2H),
1.23–1.13 (m, 2H), 1.13–0.96 (m, 2H). 13C{1H}NMR (75 MHz,
CDCl3) d 173.1, 81.2, 72.2, 43.0, 39.5, 28.8, 28.3, 28.1, 26.5, 26.2,
26.1, 23.0. HRMS (ESI-TOF) m/z [M + Na]+ calcd for C13H24NaO3
251.1623, found 251.1615.
(S)-1-(tert-Butoxy)-4,4-dimethyl-1-oxopentan-3-yl benzoate
(2x0)
Colorless oil: 32.2 mg, 88% yield; [a]2D5 ¼ ꢀ20.8 (c 0.12, CHCl3);
1H NMR (300 MHz, CDCl3) d 8.10–8.00 (m, 2H), 7.59–7.50 (m,
1H), 7.49–7.38 (m, 2H), 5.40 (dd, J ¼ 9.3, 3.9 Hz, 1H), 2.58 (qd, J
¼ 15.0, 6.6 Hz, 2H), 1.32 (s, 9H), 1.00 (s, 9H). 13C{1H}NMR (75
MHz, CDCl3) d 170.3, 165.7, 132.7, 130.6, 129.6, 128.3, 80.9,
37.4, 34.9, 27.8, 25.9. HRMS (ESI-TOF) m/z [M + Na]+ calcd for
C
18H26NaO4 329.1729, found 329.1732.
Acknowledgements
The synthesis of (S)-3-(tert-butoxy)-1-cyclohexyl-3-oxopropyl
benzoate (2v0)
Financial support from the National Natural Science Founda-
tion of China (Grant No. 21372144 and 81473085) and Depart-
ment of Science and Technology of Shandong Province is
gratefully acknowledged.
To the oxidized product (0.19 mmol) in dichloromethane (1.0
mL) were added pyridine (75.2 mg, 0.95 mmol) and benzoyl
chloride (53.6 mg, 0.38 mmol). Aer the reaction mixture was
stirred for 1 h at 0 ꢁC, the resulting mixture was quenched with
1.0 mL of water. The obtained organic layer was dried over
anhydrous Na2SO4. Aer removal of solvent, the residue was
puried by preparative TLC (n-hexane/ethyl acetate ¼ 25/1) to
afford benzoylated product as a colorless oil: 47.0 mg, 74%
yield; [a]2D5 ¼ ꢀ54.6 (c 0.13, CHCl3); 1H NMR (300 MHz, CDCl3)
d 8.17–7.96 (m, 2H), 7.60–7.50 (m, 1H), 7.49–7.36 (m, 2H), 5.45–
5.31 (m, 1H), 2.75–2.52 (m, 2H), 1.97–1.53 (m, 7H), 1.35 (s, 9H),
1.23–1.06 (m, 4H). 13C{1H}NMR (75 MHz, CDCl3) d 170.1, 165.8,
132.8, 130.5, 129.6, 128.3, 80.8, 75.0, 41.6, 38.3, 28.8, 28.2, 27.9,
26.3, 26.0, 26.0. HRMS (ESI-TOF) m/z [M + Na]+ calcd for
Notes and references
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20H28NaO4 355.1885, found 355.1878.
75150 | RSC Adv., 2016, 6, 75144–75151
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