Efficient asymmetric copper(I)-catalyzed henry reaction using chiral N-alkyl-C1-tetrahydro-1,1′-bisisoquinolines

Article abstract of DOI:10.1002/ejoc.201100579

A series of closely related chiral N-alkyl-C₁-tetrahydro-1, 1′-bisisoquinoline ligands only differing in the steric bulk of the alkyl groups has been examined in the asymmetric Henry reaction. A complex derived from the (R)-N-methyl-1′,2′,3′,4′

Full text of DOI:10.1002/ejoc.201100579

FULL PAPER
DOI: 10.1002/ejoc.201100579
Efficient Asymmetric Copper(I)-Catalyzed Henry Reaction Using Chiral
N-Alkyl-C1-tetrahydro-1,1Ј-bisisoquinolines
Yao Qiong ji,[a] Gao Qi,[a] and Zaher M. A. Judeh*[a]
Keywords: Asymmetric synthesis / C–C coupling / Copper / Diastereoselectivity / Nitroaldol reactions / Ligand design
A series of closely related chiral N-alkyl-C1-tetrahydro-1,1Ј-
bisisoquinoline ligands only differing in the steric bulk of the
alkyl groups has been examined in the asymmetric Henry
phatic aldehydes to give the expected nitroalcohol products
in high yields (up to 99%), excellent enantioselectivities (up
to 94%ee), and moderate diastereoselectivities (up to 1.6:1).
This catalyst system is very general, requires no additives for
activation, and is also simple in operation because no special
precautions are taken to exclude moisture or air from the re-
action flask.
reaction.
A complex derived from the (R)-N-methyl-
1Ј,2Ј,3Ј,4Ј-tetrahydro-1,1Ј-bisisoquinoline and copper(I) chlo-
ride proved to be a very efficient catalyst system that can
promote the reaction of a wide range of aromatic and ali-
tivity and reactivity. Because our major aim is to explore
the application of 1,1Ј-bisisoquinolines in various asymmet-
ric reactions, it was logical to methodically examine the ef-
fect of substituents at the sp3-N of (R)-1a.[2] We hypothe-
sized that elucidating the effect of carefully selected alkyl
substituents should facilitate the design of very effective li-
gands of type (R)-1a.
Introduction
We have been interested in the synthesis, chemistry, and
catalytic application of 1,1Ј-bisisoquinolines for several
years.[1] Recently, we disclosed a straightforward synthesis
of chiral C1-tetrahydro-1,1Ј-bisisoquinoline (R)-1a (Fig-
ure 1) and its derivatives with the intention of using them
as chiral ligands for various asymmetric reactions.[2,3] Based
on our DFT calculations[4] and X-ray crystallographic
analyses[2,3] we found that the two isoquinoline units are
structurally different: the ring containing the sp2-N atom
was found to be flat due to its aromatic nature, whereas the
ring containing the sp3-N atom was found to predominantly
assume a distorted boat conformation. We also found that
the size of the dihedral angle N1–C1–C1Ј–N1Ј (Figure 1) is
a function of the type (alkyl, acyl, sulfonyl) and the size
(bulkiness) of the substituent on the sp3-N.[2–4] This discov-
ery allows us to tune the bite-angle to a great extent. This
angle is understood to significantly affect the level of selec-
The Henry reaction is a powerful C–C bond-forming
protocol in organic synthesis. Its enantioselective version,
which provides enantioenriched nitroalcohol adducts, was
discovered by Shibasaki in 1992 using chiral heterobimetal-
lic catalysts.[5] The adducts can be transformed into many
valuable chiral building blocks such as nitro alkenes, amino
alcohols, amino acids, etc.[6] Various types of metal-cata-
lytic and organocatalytic systems have been developed for
this reaction. Most catalysts that have been developed use
copper[7] because of its excellent chelating properties to bi-
and poly-dentate ligands. Nevertheless, other metals such
as Zn,[8] Co,[9] Cr,[10] Pd,[11] and rare metals[5,11,12] have also
been examined with variable success. The majority of li-
gands developed, for example, bisoxazolines,[13] bisoxazol-
idines,[14] diamines,[15] (–)-sparteine,[16] sulfonyldiamines,[7c]
sulfonimidamides,[7a] aminopyridines,[17] tetrahydrosal-
ens,[18] and N,NЈ-dioxides,[7b] are nitrogen-based with a
variety of structural features that modulate their reactivity
and enantioselectivity. Limitations such as ligand complex-
ity, low substrate scope, high catalyst loading, and require-
ment for strict reaction conditions mandate the develop-
ment of more robust and efficient ligands.[15e]
Figure 1. C1-Tetrahydro-1,1Ј-bisisoquinoline (R)-1a and its chiral
N-alkyl derivatives (R)-1b–f.
[a] School of Chemical and Biomedical Engineering,
Nanyang Technological University,
Herein, we systematically explore the modular effects of
various alkyl substituents attached to the sp3-N of (R)-1a
on the reactivity and selectivity in the enantioselective
Henry reaction, with the ultimate aim of obtaining very ef-
fective ligands that can be applied to a range of asymmetric
reactions.
62 Nanyang Drive, N1.2 B1-14,
Singapore 637459, Singapore
Fax: +65-67947553
E-mail: zaher@ntu.edu.sg
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201100579.
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Eur. J. Org. Chem. 2011, 4892–4898

Efficient Asymmetric Copper(I)-Catalyzed Henry Reaction
reaction. Subsequently, screening of other copper sources
was accomplished using the most efficient ligand (R)-1b
(Table 1, Entries 7–11). The results obtained revealed that
CuI sources are superior to CuII sources in terms of both
yield and enantioselectivity (Table 1, Entries 2, 7, 8 vs. 9–
11). Both, CuCl and CuI gave similar results to those with
CuBr (Table 1, Entries 7 and 8 vs. Entry 2), indicating that
the counter anion had no prominent effect. Among the CuII
salts tested, Cu(OAc)2 gave the highest enantioselectivity
(65%ee). Considering that CuCl is cheaper and less toxic,
this metal salt was chosen as the copper source for further
studies.
Further optimization of the reaction conditions were
conducted by examining the effect of solvents using the (R)-
1b/CuCl catalyst system (Table 2). The solvents examined
showed similarly good enantioselectivities, affording 3a in
83–86%ee. However, iPrOH, THF, and (iPr)2O gave 3a in
much higher yields (89, 99, and 90%, respectively) com-
pared with CHCl3 and CH3CN (65 and 12%, respectively;
Table 2, Entries 1, 4, 5 vs. 2 and 3). Considering the yield
and ee, we selected (iPr)2O for further optimization. We be-
lieved that conducting the reaction at a lower temperature
would result in the reaction proceeding at an acceptable rate
with increased enantioselectivity. Indeed, when the reaction
was conducted at 0 °C, the enantioselectivity of 3a in-
creased from 86 to 91%ee while the yield decreased from
90 to 65% (Table 2, Entry 5 vs. 6). In an attempt to maxim-
ize both the yield and ee of 3a, a range of (R)-1b/CuCl
ratios and loadings were examined at 0 °C. Changing the
(R)-1b/CuCl ratio from 1:1 to 1:2 or 2:1 resulted in a slight
decrease in the enantioselectivity and a remarkable decrease
in the yield of 3a (Table 2, Entries 7 and 8). Using a 1:1
ratio of (R)-1b/CuCl, attempts to increase the catalyst load-
ing from 10 to 20 mol-% provided 3a in higher yield (90%)
but lower enantioselectivity (86%) (Table 2, Entry 6 vs. 9)
Results and Discussion
We envisioned that by introducing different alkyl substit-
uents at the sp3-N of (R)-1a (Figure 1), the steric hindrance
at the chelating centers can easily be modulated and the
effect of steric crowding can be delineated. Such insights are
extremely important in the design of an optimum catalyst.
Therefore, selected N-alkyl derivatives (R)-1b–f were syn-
thesized by reacting (R)-1a with the corresponding haloalk-
anes (see the Supporting Information).[2,3]
Initial studies were carried out to screen the selectivity
and reactivity of ligands (R)-1a–f (Figure 1) using a range
of copper sources under standard enantioselective Henry
reaction conditions. In a typical experiment, the ligand
(10 mol-%) and copper source (10 mol-%) were stirred in
tetrahydrofuran (THF) (1.5 mL) for 1 h followed by drop-
wise sequential addition of nitromethane (20 equiv.) and
benzaldehyde (0.2 mmol), and the reaction was allowed to
proceed for 20 h at room temperature. No special pre-
cautions were taken to exclude air or moisture. The results
are summarized in Table 1. Initially, CuBr was chosen as
the copper source for screening. The parent ligand (R)-1a,
bearing no substituent, gave product 3a in 94% yield and
68%ee (Table 1, Entry 1). Ligand (R)-1b, bearing the small-
est N-alkyl (N-CH3) substituent, proved to be the most ef-
ficient, giving product 3a in 98% yield and 83%ee (Table 1,
Entry 2). Ligands (R)-1c–e, bearing larger N-alkyl substitu-
ents, afforded the product in comparable yields to (R)-1b
but with lower ee (Table 1, Entries 3–5). Surprisingly, ligand
(R)-1f was found to be completely inactive (Table 1, En-
try 6). Presumably, complexation between the copper and
the nitrogen atoms of (R)-1f was not sufficient for effective
catalysis. From the results summarized in Table 1, it is evi-
dent that the steric bulk of the N-alkyl group contributes
significantly to the selectivity and reactivity in the Henry
Table 1. Screening of ligands (R)-1a–f and copper sources for the
asymmetric Henry reaction.
Table 2. Optimization of the reaction conditions using (R)-1b/CuCl
for the asymmetric Henry reaction.
Entry
Ligand
Cu salt
Yield [%][a]
ee [%][b]
Entry Solvent
T
[°C]
(R)-1b
CuCl
[mol-%] [mol-%]
Yield
[%][a]
ee
[%][b]
1
2
3
4
5
6
7
8
(R)-1a
(R)-1b
(R)-1c
(R)-1d
(R)-1e
(R)-1f
(R)-1b
(R)-1b
(R)-1b
(R)-1b
(R)-1b
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
CuCl
CuI
94
98
98
95
85
0
99
99
40
70
75
68
83
65
67
69
–
83
70
31
65
3
1[c]
2
3
iPrOH
CHCl3
CH3CN
THF
r.t.
r.t.
r.t.
r.t.
r.t.
0
0
0
0
0
10
10
10
10
10
10
10
10
20
5
10
10
10
10
10
10
5
20
20
5
89
65
12
99
90
65
35
18
90
20
85
83
86
83
86
91
82
63
86
80
4
5
6
(iPr)2O
(iPr)2O
(iPr)2O
(iPr)2O
(iPr)2O
(iPr)2O
7[c]
8[c]
9
9
10
11
CuCl2
Cu(OAc)2
Cu(OTf)2
10[c]
[a] Yield of isolated product. [b] Enantiomeric excess values were
determined by HPLC using a Chiralcel OD-H column. The abso-
lute configuration (R) was determined by comparison with the lit-
erature data.[13a]
[a] Yield of isolated product. [b] Enantiomeric excess values were
determined by HPLC using a Chiralcel OD-H column. The abso-
lute configuration (R) was determined by comparison with the lit-
erature data.[13a] [c] Reacted for 48 h.
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Z. M. A. Judeh et al.
FULL PAPER
whereas attempts to decrease the catalyst loading from 10 are generally better than those for the aromatic aldehydes
to 5 mol-% afforded 3a in lower ee (80%) and unreasonably due to their inherently higher reactivities, and reactions
low yield (20%), even after extending the reaction time for with the former substrates could therefore be accomplished
48 h (Table 2, Entry 10). Overall, the most effective condi- in a shorter time (Table 3, Entries 10–17 vs. 1–9). Moreover,
tions were found to be 10 mol-% (R)-1b/CuCl in a ratio of heteroaromatic 2-furaldehyde and conjugated trans-cinnam-
1:1 at 0 °C in (iPr)2O, which gave 3a with the highest ee aldehyde gave products 3r and 3s, respectively, in excellent
(91%) and acceptable yield (65%) (Table 2, Entry 6). It is yields and respectable enantioselectivities (Table 3, En-
worth noting that the reaction using ligand (R)-1b (20 mol- tries 18 and 19).
%) and Cu(OAc)2 (10 mol-%) gave 3a in 80% yield and
Encouraged by the excellent results obtained from ad-
70%ee. When (R)-1b was used to catalyze the reaction dition of nitromethane to various aldehydes (Table 3), we
without CuCl, racemic 3a was obtained in only 10% yield. decided to examine the catalytic activity of (R)-1b/CuCl in
The substrate scope of the reaction was then studied un- the more challenging and less explored diastereoselective
der the optimized conditions described in Table 2, Entry 6. Henry reaction. Thus, nitroethane was treated with several
Pleasingly, the reaction was found to be very general and aromatic and aliphatic aldehydes under our optimized con-
applicable to a variety of aromatic, heteroaromatic, and ali- ditions (Table 2, Entry 6) to give nitroaldol adducts 4a–g
phatic aldehydes (Table 3). Aromatic aldehydes gave the ex- (Table 4) in moderate diastereoselectivities (up to 1.6:1,
pected products 3a–i in moderate to excellent yields and anti/syn), and the anti product was obtained predominantly
excellent enantioselectivities, with ee values above 86%. The with ee values up to 90%.
position and electronic nature of the substituent on the aro-
matic ring seems to have no great bearing on the yields and
enantioselectivities of the products (Table 3, Entries 1–9).
Most outstanding, the reaction proceeded smoothly with
Table 4. Diastereoselective Henry reaction of aldehydes with nitro-
ethane catalyzed by CuCl/(R)-1b.
straight chain (Table 3, Entries 10–14), branched (Table 3,
Entries 15 and 16), and cyclic aldehydes (Table 3, Entry 17)
to give products 3j–q in excellent enantioselectivities with
ee values ranging from 90–94% and with very good to ex-
cellent yields (70–99%). The yields for aliphatic aldehydes
Entry
R
Product Time
[h]
Yield anti/syn[b] ee
[%][a]
[%][c]
1
2
3
4
5
6
7
4-ClC6H4
2-FC6H4
4-MeC6H4
2-MeC6H4
2-MeOC6H4
iBu
4a
4b
4c
4d
4e
4f
48
48
48
48
72
48
48
70
75
65
60
71
50
70
1.4:1
1.6:1
1.6:1
1.4:1
1.4:1
1.1:1
1:1
61:82
68:86
80:88
72:88
76:91
90:84
82:80
Table 3. Enantioselective Henry reaction of various aldehydes with
nitromethane catalyzed by (R)-1b/CuCl.
nPr
4g
[a] Yield of isolated products. [b] Determined by 1H NMR analysis
and HPLC using Chiralcel OJ-H or Chiralpak AD-H columns.
[c] Enantiomeric excess values were determined by HPLC using
Chiralcel OJ-H or Chiralpak AD-H columns.[15g,20]
Entry
R
Product
Time
[h]
Yield
[%][a]
ee
[%][b]
1
2
3
4
5
6
7
8
Ph
4-FC6H4
4-ClC6H4
3-ClC6H4
4-MeC6H4
3-MeC6H4
2-MeC6H4
4-PhC6H4
2-MeOC6H4
Et
nPr
nBu
n-C5H11
n-C8H17
iPr
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
3r
3s
20
40
20
20
40
40
40
20
40
20
20
20
20
20
20
20
20
20
20
65
55
80
70
80
45
83
95
86
95
85
90
94
75
99
99
70
90
95
91
90
86
87
92
90
91
94
90
93
91
94
90
90
92
91
93
86
84
When (R)-1b and CuCl were mixed in a 1:1 ratio in
CH2Cl2 and the product analyzed by mass spectrometry,
molecular ion peaks at m/z 611 [molecular formula
C38H36CuN4 = 2ϫ (R)-1b + Cu] and at m/z 613 [molecular
formula C38H38CuN4 = 2ϫ (R)-1b + Cu + 2H+] were ob-
served, confirming the presence of a complex in a 2:1 ratio
of (R)-1b and CuCl. Accordingly, chelation of copper(I) to
(R)-1b is shown in Figure 2. The ligand acts as a base to
deprotonate the nitromethane to generate the active ni-
tronate nucleophile in the CuI transition state. The ni-
tronate group assumes an axial position, as shown in Fig-
ure 2. After taking into account the stereoelectronic consid-
erations and the observed absolute configuration of the
product, the Si-face of the carbonyl of benzaldehyde must
be favored for nucleophilic attack to give the corresponding
(R)-product.
9
10
11
12
13
14
15
16
17
18
19
iBu
cyclohexyl
2-fural
PhCH=CH
[a] Yield of isolated products. [b] Enantiomeric excess values were
determined by HPLC using Chiralcel OD-H, AD-H, or OJ-H col-
umns. The absolute configuration (R) was determined by compari-
son with the literature data.[7b,14b,19]
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Efficient Asymmetric Copper(I)-Catalyzed Henry Reaction
Figure 2. Proposed transition-state model for the asymmetric Henry reaction catalyzed by the (R)-1b/CuCl complex.
purity (98%ee) was determined by HPLC (Daicel Chiralcel OD-H
Conclusions
column; hexane/iPrOH, 98:2; 1.0 mL/min; 254 nm): tR = 4.98 [(S)-
1d], 5.42 [(R)-1d] min. [α]2D5 = +157.5 (c = 0.86, CH2Cl2). FTIR
We have demonstrated the pivotal role of the N-alkyl
substituents of C1-tetrahydro-1,1Ј-bisisoquinoline on the re- (KBr): νmax = 3402, 3052, 2965, 1623, 1585, 1560, 1496, 1452, 1342,
˜
1
1171, 1057, 826, 734, 648 cm–1. H NMR (300 MHz, CDCl3): δ =
activity and selectivity in the enantioselective Henry reac-
0.82 (d, J = 7.2 Hz, 3 H), 0.89 (d, J = 7.2 Hz, 3 H), 2.52–2.61 (m,
tion. (R)-N-Methyl-1Ј,2Ј,3Ј,4Ј-tetrahydro-1,1Ј-bisisoquinol-
2 H), 3.21–3.40 (d, J = 15.9 Hz, 1 H), 3.16–3.20 (m, 1 H), 3.22–
ine [(R)-1b] proved to be very efficient and general ligand
3.27 (m, 1 H), 5.47 (s, 1 H), 6.48 (d, J = 7.8 Hz, 1 H), 6.71 (t, J =
7.5 Hz, 1 H), 6.92 (t, J = 7.2 Hz, 1 H), 7.05 (d, J = 7.5 Hz, 1 H),
7.18 (t, J = 7.5 Hz, 1 H), 7.39 (t, J = 7.5 Hz, 1 H), 7.46 (d, J =
in the CuI-catalyzed asymmetric Henry reaction between
nitroalkanes and various aldehydes. The desired nitro-
alcohol products were obtained in high yields (up to 99%)
and good to excellent enantioselectivities (up to 94%ee)
using a broad range of aliphatic, aromatic, heteroaromatic,
and unsaturated aldehydes. We regard the moderate dia-
5.7 Hz, 1 H), 7.61 (d, J = 8.7 Hz, 1 H), 8.40 (d, J = 5.7 Hz, 1 H),
8.64 (d, J = 8.7 Hz, 1 H) ppm. 13C NMR (75.6 MHz, CDCl3): δ =
12.5, 21.3, 30.5, 41.5, 49.5, 70.7, 120.8, 125.7, 125.9, 126.0, 126.7,
126.8, 127.2, 127.8, 128.6, 129.7, 134.5, 137.3, 138.5, 141.0,
stereoselectivities obtained (up to 1.6:1) as a promising 162.8 ppm. HRMS (EI+): calcd. for C21H22N2 302.1861; found
303.1857 [M + 1].
starting point for further optimization. The operational
procedure using the present catalyst system is very simple
and does not require exclusion of air or moisture.
General Procedure for Asymmetric Henry Reaction: Ligand
(0.02 mmol, 10 mol-%) and CuCl (0.02 mmol, 10 mol-%) were
mixed in (iPr)2O (1.5 mL) and the mixture was stirred at room
temp. for 1 h, whereby a yellow solution was obtained. To the above
stirred solution, nitromethane/nitroethane (4 mmol, 20 equiv.) and
aldehyde (0.2 mmol) were added. The reaction mixture was then
stirred at the given temperature for the specified time (reaction
monitored by TLC). The β-nitroalcohol product was purified on
silica gel by flash column chromatography.
Experimental Section
General: All commercial chemicals were reagent grade unless other-
wise specified. Analytical thin layer chromatography (TLC) was
performed using F254 pre-coated silica gel plates (0.2 mm thick-
ness). Separation of products was achieved using column
chromatography on Silica Gel 60 (230–400 mesh). FTIR were re-
corded as thin films (KBr). NMR spectra were recorded at
300 MHz for 1H and at 75.6 MHz for 13C. Chemical shifts are given
in ppm relative to TMS (δ = 0 ppm) or solvent residual peaks
(CDCl3: 1H, δ = 7.26 ppm; 13C, δ = 75 ppm) as internal standards.
1H NMR multiplicities were designated as singlet (s), doublet (d),
doublet of doublet (dd), doublet of doublet of doublet (ddd), triplet
(t), triplet of doublet (td), quartet (q), pentet (p), multiplet (m),
and broad (br). HPLC separations were performed using Diacel
Chiralcel OD-H, OJ-H, and AD-H chiral columns.
(R)-1-Phenyl-2-nitroethanol [(R)-3a]: Prepared according to the ge-
neral procedure and purified by column chromatography (hexane/
EtOAc, 5:1) to give a colorless oil (65% yield). HPLC (Chiralcel
OD-H column; n-hex/IPA, 90:10; flow rate 0.8 mL/min; 215 nm):
tR = 18.21 (major enantiomer), 21.91 (minor enantiomer) min;
1
91%ee. H NMR (CDCl3): δ = 2.76 (br. s, 1 H), 4.39–4.56 (m, 2
H), 5.37 (dd, J = 9.3, 9.6 Hz, 1 H), 7.34–7.40 (m, 5 H) ppm. 13C
NMR: δ = 71.0, 81.3, 126.0, 129.0, 129.1, 138.2 ppm.
(R)-1-(4-Fluorophenyl)-2-nitroethanol [(R)-3b]: Prepared according
to the general procedure and purified by column chromatography
(hexane/EtOAc, 7:3) to give a colorless oil (55% yield). HPLC
(Chiralcel OD-H column; n-hex/IPA, 90:10; flow rate 0.8 mL/min;
215 nm): tR = 14.66 (major enantiomer), 17.23 (minor enanti-
omer) min; 90%ee. 1H NMR (CDCl3): δ = 2.89 (s, 1 H), 4.46–4.63
(m, 2 H), 5.47 (d, J = 7.5 Hz, 1 H), 7.07–7.13 (m, 2 H), 7.37–7.42
(m, 2 H) ppm. 13C NMR (CDCl3): δ = 70.3, 81.2, 115.9, 116.1,
116.3, 127.8, 134.0, 162.1, 164.1 ppm.
Preparation and Characterization of Ligands (R)-1a–f: (R)-
1Ј,2Ј,3Ј,4Ј-Tetrahydro-1,1Ј-bisisoquinoline (R)-1a and its deriva-
tives [(R)-1b, (R)-1c, (R)-1e, and (R)-1f] were prepared according
to our reported methods[1b,20] (see the Supporting Information).
For a typical procedure, the preparation of (R)-1d is described here.
Preparation of (R)-N-Isopropyl-1Ј,2Ј,3Ј,4Ј-tetrahydro-1,1Ј-bisiso-
quinoline [(R)-1d]: 2-Bromopropane (67.6 mg, 51.6 μL, 0.55 mmol)
was added to a solution of (R)-1Ј,2Ј,3Ј,4Ј-tetrahydro-1,1Ј-bisiso-
quinoline (R)-1a (130 mg, 0.5 mmol) in CH3CN (4 mL) in the pres-
ence of K2CO3 (138 mg, 1.0 mmol), and the mixture was heated at
reflux for 2 d (reaction monitored by TLC). The reaction mixture
was filtered and K2CO3 was washed with CH2Cl2 (2ϫ3 mL). The
combined filtrates were evaporated under reduced pressure and the
obtained gum was subjected to column chromatography purifica-
(R)-1-(4-Chlorophenyl)-2-nitroethanol [(R)-3c]: Prepared according
to the general procedure and purified by column chromatography
(hexane/EtOAc, 5:1) to give a colorless oil (85% yield). HPLC
(Chiralcel OD-H column; n-hex/IPA, 90:10; flow rate 1.0 mL/min;
215 nm): tR = 13.90 (major enantiomer), 17.70 (minor enantio-
1
mer) min; 86%ee. H NMR (CDCl3): δ = 2.89 (br. s, 1 H), 4.47–
4.62 (m, 2 H), 5.44–5.47 (m, 1 H), 7.34–7.40 (m, 4 H) ppm. 13C
tion to give (R)-1d as a white solid (84.6 mg, 56%). Enantiomeric NMR (CDCl3): δ = 70.3, 80.1, 127.3, 129.3, 134.9, 136.5 ppm.
Eur. J. Org. Chem. 2011, 4892–4898
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Z. M. A. Judeh et al.
(R)-1-(3-Chlorophenyl)-2-nitroethanol [(R)-3d]: Prepared according 2.57 (br. s, 1 H), 4.18–4.59 (m, 3 H) ppm. 13C NMR (CDCl3): δ =
FULL PAPER
to the general procedure and purified by column chromatography
(hexane/EtOAc, 5:1) to give a colorless oil (70% yield). HPLC
(Chiralcel OD-H column; n-hex/IPA, 90:10; flow rate 1.0 mL/min;
215 nm): tR = 13.6 (major enantiomer), 16.8 (minor enantio-
9.6, 26.9, 69.9, 80.4 ppm.
(R)-1-Nitropentan-2-ol [(R)-3k]: Prepared according to the general
procedure and purified by column chromatography (hexane/
EtOAc, 5:1) to give a yellow oil (85% yield). HPLC (Chiralcel AD-
1
mer) min; 87%ee. H NMR (CDCl3): δ = 2.96 (br. s, 1 H), 4.49–
H column; n-hex/IPA, 98:2; flow rate 1.0 mL/min; 215 nm): tR
=
4.63 (m, 2 H), 5.40 (m, 1 H), 7.26–7.73 (m, 4 H) ppm. 13C NMR
32.52 (major enantiomer), 54.01 (minor enantiomer) min; 91%ee.
1H NMR (CDCl3): δ = 0.98 (t, J = 6.9 Hz, 3 H), 1.50–1.59 (m, 4
H), 2.53 (br. s, 1 H), 4.35–4.46 (m, 3 H) ppm. 13C NMR (CDCl3):
δ = 13.7, 18.4, 35.8, 68.4, 80.7 ppm.
(CDCl3):
δ = 70.3, 81.0, 124.0, 126.2, 129.1, 130.3, 135.0,
140.0 ppm.
(R)-1-(4-Methylphenyl)-2-nitroethanol [(R)-3e]: Prepared according
to the general procedure and purified by column chromatography
(hexane/EtOAc, 8:1) to give a colorless oil (80% yield). HPLC
(Chiralcel OD-H column; n-hex/IPA, 90:10; flow rate 0.5 mL/min;
215 nm): tR = 26.50 (major enantiomer), 34.02 (minor enantio-
(R)-1-Nitrohexan-2-ol [(R)-3l]: Prepared according to the general
procedure and purified by column chromatography (hexane/
EtOAc, 5:1) to give a yellow oil (90% yield). HPLC (Chiralcel AD-
H column; n-hex/IPA, 98:2; flow 1.0 mL/min; 215 nm): tR = 24.29
(major enantiomer), 32.13 (minor enantiomer) min; 94%ee. 1H
NMR (CDCl3): δ = 0.94 (t, J = 6.9 Hz, 3 H), 1.34–1.61 (m, 6 H),
2.50 (br. s, 1 H), 4.31–4.49 (m, 3 H) ppm. 13C NMR (CDCl3): δ =
13.9, 22.4, 27.3, 33.4, 68.7, 80.6 ppm.
1
mer) min; 92%ee. H NMR (CDCl3): δ = 2.36 (s, 3 H), 2.48 (s, 1
H), 4.46–4.64 (m, 2 H), 5.40–5.46 (m, 1 H), 7.26–7.30 (m, 4
H) ppm. 13C NMR (CDCl3): δ = 21.2, 70.9, 81.3, 125.9, 129.7,
135.2, 139.0 ppm.
(R)-1-(3-Methylphenyl)-2-nitroethanol [(R)-3f]: Prepared according
to the general procedure and purified by column chromatography
(hexane/EtOAc, 5:1) to give a yellow oil (45% yield). HPLC (Chi-
ralcel OD-H column; n-hex/IPA, 90:10; flow rate 0.5 mL/min;
215 nm): tR = 22.91 (major enantiomer), 26.17 (minor enantio-
(R)-1-Nitroheptan-2-ol [(R)-3m]: Prepared according to the general
procedure and purified by column chromatography (hexane/
EtOAc, 5:1) to give a yellow oil (94% yield). HPLC (Chiralcel AD-
H column; n-hex/IPA, 98:2; flow 1.0 mL/min; 215 nm): tR = 23.81
(major enantiomer), 35.60 (minor enantiomer) min; 90%ee. 1H
NMR (CDCl3): δ = 0.84 (t, J = 6.9 Hz, 3 H), 1.15–1.53 (m, 8 H),
2.75 (br. s, 1 H), 4.24–4.40 (m, 3 H) ppm. 13C NMR (CDCl3): δ =
13.9, 22.5, 24.8, 31.5, 33.7, 68.7, 80.7 ppm.
1
mer) min; 90%ee. H NMR (CDCl3): δ = 2.38 (s, 3 H), 2.81 (s, 1
H), 4.50–4.65 (m, 2 H), 5.37–5.45 (m, 1 H), 7.23–7.32 (m, 4
H) ppm. 13C NMR (CDCl3): δ = 21.4, 71.1, 81.8, 123.0, 126.6,
128.9, 129.7, 138.0, 138.9 ppm.
(R)-1-Nitrodecan-2-ol [(R)-3n]: Prepared according to the general
procedure and purified by column chromatography (hexane/
EtOAc, 5:1) to give a yellow oil (75% yield). HPLC (Chiralcel AD-
(R)-1-(2-Methylphenyl)-2-nitroethanol [(R)-3g]: Prepared according
to the general procedure and purified by column chromatography
(hexane/EtOAc, 5:1) to give a colorless oil (83% yield). HPLC
(Chiralcel OD-H column; n-hex/IPA, 90:10; flow rate 0.5 mL/min;
215 nm): tR = 21.09 (major enantiomer), 31.46 (minor enantio-
H column; n-hex/IPA, 98:2; flow rate 1.0 mL/min; 215 nm): tR
=
20.15 (major enantiomer), 30.15 (minor enantiomer) min; 90%ee.
1H NMR (CDCl3): δ = 0.88 (t, J = 6.3 Hz, 3 H), 1.47–1.50 (m, 14
H), 2.49 (d, J = 4.5 Hz, 1 H), 4.34–4.47 (m, 3 H) ppm. 13C NMR
(CDCl3): δ = 14.1, 22.6, 25.2, 29.2, 29.3, 29.4, 31.8, 33.7, 68.7,
80.6 ppm.
1
mer) min; 91%ee. H NMR (CDCl3): δ = 2.40 (s, 3 H), 2.72 (d, J
= 3.6 Hz, 1 H), 4.42–4.60 (m, 2 H), 5.67–5.72 (m, 1 H), 7.25–7.31
(m, 3 H), 7.51–7.56 (m, 1 H) ppm. 13C NMR (CDCl3): δ = 18.9,
68.0, 80.2, 125.6, 126.8, 128.8, 130.9, 134.4, 136.2 ppm.
(R)-3-Methyl-1-nitrobutan-2-ol [(R)-3o]: Prepared according to the
general procedure and purified by column chromatography (hex-
ane/EtOAc, 5:1) to give a yellow oil (99% yield). HPLC (Chiralcel
(R)-1-(4-Phenylphenyl)-2-nitroethanol [(R)-3h]: Prepared according
to the general procedure and purified by column chromatography
(hexane/EtOAc, 5:1) to give a pale-yellow crystalline solid (95%
yield). HPLC (Chiralcel OD-H column; n-hex/IPA, 85:15; flow rate
0.8 mL/min; 215 nm): tR = 19.44 (major enantiomer), 23.27 (minor
enantiomer) min; 94%ee. 1H NMR (CDCl3): δ = 2.88 (d, J =
3.3 Hz, 1 H), 4.36–4.69 (m, 2 H), 5.52 (d, J = 9.3 Hz, 1 H), 7.34–
7.64 (m, 9 H) ppm. 13C NMR (CDCl3): δ = 70.8, 81.2, 126.4, 127.1,
127.7, 127.8, 128.9, 137.0, 140.3, 142.0 ppm.
OD-H column; n-hex/IPA, 98:2; flow 0.5 mL/min; 215 nm): tR
=
40.22 (major enantiomer), 44.57 (minor enantiomer) min; 92%ee.
1H NMR (CDCl3): δ = 0.70–0.78 (m, 6 H), 1.66–1.81 (m, 1 H),
2.58 (br. s, 1 H), 4.05 (m, 1 H), 4.30–4.44 (m, 2 H) ppm. 13C NMR
(CDCl3): δ = 17.4, 18.4, 31.8, 73.4, 79.3 ppm.
(R)-4-Methyl-1-nitropentan-2-ol [(R)-3p]: Prepared according to the
general procedure and purified by column chromatography (hex-
ane/EtOAc, 5:1) to give a yellow oil (99% yield). HPLC (Chiralcel
(R)-1-(2-Methoxyphenyl)-2-nitroethanol [(R)-3i]: Prepared accord-
ing to the general procedure and purified by column chromatog-
raphy (hexane/EtOAc, 9:1) to give a yellow oil (86% yield). HPLC
(Chiralcel OD-H column; n-hex/IPA, 90:10; flow rate 1.0 mL/min;
215 nm): tR = 10.78 (major enantiomer), 12.55 (minor enantio-
AD-H column; n-hex/IPA, 95:5; flow 0.5 mL/min; 215 nm): tR
=
20.56 (major enantiomer), 29.13 (minor enantiomer) min; 91%ee.
1H NMR (CDCl3): δ = 0.85–0.91 (m, 6 H), 1.12–1.20 (m, 1 H),
1.39–1.49 (m, 1 H), 1.72–1.81 (m, 1 H), 2.53 (br. s, 1 H), 4.27–4.37
(m, 3 H) ppm. 13C NMR (CDCl3): δ = 21.8, 23.2, 24.3, 42.4, 67.0,
81.0 ppm.
1
mer) min; 90%ee. H NMR (CDCl3): δ = 3.24 (d, J = 6 Hz, 1 H),
3.90 (s, 3 H), 4.55–4.69 (m, 2 H), 5.62–5.68 (m, 1 H), 6.93 (d, J =
8.1 Hz, 1 H), 7.03 (t, J = 7.5 Hz, 1 H), 7.35 (t, J = 8.1 Hz, 1 H),
7.46 (d, J = 7.5 Hz, 1 H) ppm. 13C NMR (CDCl3): δ = 55.4, 67.8,
79.9, 110.6, 121.2, 126.0, 127.2, 129.8, 156.0 ppm.
(R)-1-Cyclohexyl-2-nitroethanol [(R)-3q]: Prepared according to the
general procedure and purified by column chromatography (hex-
ane/EtOAc, 5:1) to give a yellow oil (70% yield). HPLC (Chiralcel
(R)-1-Nitrobutan-2-ol [(R)-3j]: Prepared according to the general
procedure and purified by column chromatography (hexane/
EtOAc, 5:1) to give a yellow oil (95% yield). HPLC (Chiralcel AD-
AD-H column; n-hex/IPA, 98:2; flow 0.6 mL/min; 215 nm): tR =
48.60 (major enantiomer), 51.90 (minor enantiomer) min; 93%ee.
1H NMR (CDCl3): δ = 1.00–1.23 (m, 5 H), 1.42–1.54 (m, 1 H),
1.60–1.70 (m, 2 H), 1.72–1.78 (m, 3 H), 2.38 (d, J = 5.1 Hz, 1 H),
4.02–4.04 (m, 1 H), 4.36–4.44 (m, 2 H) ppm. 13C NMR (CDCl3):
δ = 25.9, 28.0, 28.8, 41.4, 72.8, 79.3 ppm.
H column; n-hex/IPA, 98:2; flow rate 1.0 mL/min; 215 nm): tR
=
49.70(major enantiomer), 84.59 (minor enantiomer) min; 93%ee.
1H NMR (CDCl3): δ = 0.94–0.98 (m, 3 H), 1.46–1.61 (m, 2 H),
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© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 4892–4898

Efficient Asymmetric Copper(I)-Catalyzed Henry Reaction
(R)-1-(2-Furyl)-2-nitroethanol [(R)-3r]: Prepared according to the
general procedure and purified by column chromatography (hex-
ane/EtOAc, 5:1) to give a yellow oil (90% yield). HPLC (Chiralcel
OJ-H column; n-hex/IPA, 90:10; flow rate 1.0 mL/min; 215 nm): tR
129.4, 135.4, 138.4; δ (syn isomer) = 16.5, 29.7, 76.2, 88.5, 126.8,
129.7, 133.4, 139.2 ppm.
2-Nitro-1-o-tolylpropan-1-ol (4d): Prepared according to the general
procedure and purified by column chromatography (hexane/
EtOAc, 5:1) to give a yellow oil (60% yield). Diastereomeric ratios
=
22.16 (major enantiomer), 26.73 (minor enantiomer) min;
1
86%ee. H NMR (CDCl3): δ = 2.90 (br. s, 1 H), 4.63–4.84 (m, 2
H), 5.40–5.50 (m, 1 H), 6.38–6.40 (m, 2 H), 7.40–4.41 (m, 1
H) ppm. 13C NMR (CDCl3): δ = 64.9, 78.4, 108.2, 100.7, 143.2,
150.7 ppm.
1
(anti/syn, 1.4:1) were determined by H NMR and HPLC. HPLC
(Chiralpak AD-H column; n-hex/IPA, 95:5; 1.0 mL/min; 210 nm):
tR = 10.17 [antiminor (1S,2R)], 11.38 [antimajor (1R,2S)], 13.82
[synminor (1S,2S)], 16.94 [synmajor (1R,2R)] min. anti/syn = 72%/
1
(R,E)-1-Nitro-4-phenyl-3-buten-2-ol [(R,E)-3s]: Prepared according
to the general procedure and purified by column chromatography
(hexane/EtOAc, 5:1) to give a yellow oil (95% yield). HPLC (Chi-
ralcel OD-H column; n-hex/IPA, 90:10; flow rate 0.8 mL/min;
215 nm): tR = 55.63 (minor enantiomer), 62.71 (major enantio-
mer) min; 84%ee. 1H NMR (CDCl3): δ = 2.68 (d, J = 3.9 Hz, 1
H), 4.51–4.61 (m, 2 H), 5.06–5.12 (m, 1 H), 6.15 (dd, J = 6.3,
15.9 Hz, 1 H), 6.79 (d, J = 15 Hz, 1 H), 7.30–7.46 (m, 5 H) ppm.
13C NMR (CDCl3): δ = 69.6, 79.9, 124.9, 126.7, 128.6, 128.8, 133.7,
135.5 ppm.
88%ee. H NMR (300 MHz, CDCl3): δ (anti isomer) = 1.43 (d, J
= 6.9 Hz, 3 H), 2.29 (s, 3 H), 2.58 (s, 1 H), 4.54–4.57 (m, 1 H), 5.54
(s, 1 H), 7.08–7.19 (m, 3 H), 7.46 (d, J = 7.2 Hz, 1 H); δ (syn
isomer) = 1.22 (d, J = 6.9 Hz, 3 H), 2.36 (s, 3 H), 2.48 (s, 1 H),
4.77–4.80 (m, 1 H), 5.27–5.30 (m, 1 H), 7.08–7.19 (m, 3 H), 7.29–
7.32 (m, 1 H) ppm. 13C NMR (75.6 MHz, CDCl3): δ (anti isomer)
= 11.5, 18.9, 70.9, 85.4, 126.0, 126.4, 128.4, 130.8, 134.3, 136.7; δ
(syn isomer) = 16.1, 19.6, 72.2, 88.8, 126.5, 126.8, 128.8, 131.0,
135.9, 136.6 ppm.
1-(2-Methoxyphenyl)-2-nitropropan-1-ol (4e): Prepared according to
the general procedure and purified by column chromatography
(hexane/EtOAc, 8:1) to give a yellow oil (71% yield). Dia-
stereomeric ratios (anti/syn, 1.4:1) were determined by 1H NMR
and HPLC. HPLC (Chiralpak OJ-H column; n-hex/IPA, 95:5;
0.6 mL/min; 210 nm): tR = 43.95 [antiminor (1S,2R)], 48.44 [antimajor
(1R,2S)], 56.62 [synminor (1S,2S)], 60.12 [synmajor (1R,2R)] min.
1-(4-Chlorophenyl)-2-nitropropan-1-ol (4a): Prepared according to
the general procedure and purified by column chromatography
(hexane/EtOAc, 5:1) to give a yellow oil (70% yield). Dia-
stereomeric ratios (anti/syn, 1.4:1) were determined by 1H NMR
and HPLC. HPLC (Chiralpak AD-H column; n-hex/IPA, 95:5;
1.0 mL/min; 210 nm); tR = 13.90 [antiminor (1S,2R)], 14.94 [antimajor
(1R,2S)], 19.90 [synminor (1S,2S)], 22.14 [synmajor (1R,2R)] min.
1
anti/syn = 76%/91%ee. H NMR (300 MHz, CDCl3): δ (anti iso-
1
anti/syn = 61%/82%ee. H NMR (300 MHz, CDCl3): δ (anti iso-
mer) = 1.39 (d, J = 6.9 Hz, 3 H), 3.07 (br. s, 1 H), 3.79 (s, 3 H),
4.79–4.86 (m, 1 H), 5.46 (s, 1 H), 6.80–6.94 (m, 2 H), 7.18–7.35 (m,
2 H); δ (syn isomer) = 1.25 (d, J = 6.9 Hz, 3 H), 3.27 (d, J = 3 Hz,
1 H), 3.83 (s, 3 H), 4.89–4.94 (m, 1 H), 5.04–5.06 (m, 1 H), 6.80–
6.94 (m, 2 H), 7.18–7.35 (m, 2 H) ppm. 13C NMR (75.6 MHz,
CDCl3): δ (anti isomer) = 12.6, 55.4, 70.8, 85.1, 110.4, 121.0, 126.3,
127.6, 129.5, 155.8; δ (syn isomer) = 16.6, 55.5, 74.1, 87.7, 111.0,
121.2, 125.9, 129.0, 130.1, 156.8 ppm.
mer) = 1.42 (d, J = 6.0 Hz, 3 H), 2.72 (s, 1 H), 4.60–4.68 (m, 1 H),
5.32 (br. s, 1 H), 7.20–7.30 (m, 4 H); δ (syn isomer) = 1.26 (d, J =
6.0 Hz, 3 H), 2.62 (s, 1 H), 4.60–4.68 (m, 1 H), 4.98 (d, J = 8.1 Hz,
1 H), 7.20–7.30 (m, 4 H) ppm. 13C NMR (75.6 MHz, CDCl3): δ
(anti isomer) = 12.0, 73.2, 87.2, 127.4, 129.0, 134.4, 136.9; δ (syn
isomer) = 16.4, 75.5, 88.2, 128.3, 129.2, 135.1, 136.8 ppm.
1-(2-Fluorophenyl)-2-nitropropan-1-ol (4b): Prepared according to
the general procedure and purified by column chromatography
(hexane/EtOAc, 5:1) to give a yellow oil (75% yield). Dia-
stereomeric ratios (anti/syn, 1.6:1) were determined by 1H NMR
and HPLC. HPLC (Chiralpak AD-H column; n-hex/IPA, 95:5;
1.0 mL/min; 210 nm): tR = 15.01 [antiminor (1S,2R)], 17.82 [antimajor
(1R,2S)], 22.26 [synminor (1S,2S)], 26.33 [synmajor (1R,2R)] min.
5-Methyl-2-nitrohexan-3-ol (4f): Prepared according to the general
procedure and purified by column chromatography (hexane/
EtOAc, 5:1) to give a clear oil (50% yield). Diastereomeric ratios
1
(anti/syn, 1.1:1) were determined by H NMR and HPLC. HPLC
(Chiralpak AD-H column; n-hex/IPA, 98:2; 0.8 mL/min; 220 nm):
tR = 19.50 [antiminor (1S,2R)], 20.89 [antimajor (1R,2S)], 25.21
[synmajor (1R,2R)], 27.26 [synminor (1S,2S)] min. anti/syn = 90%/
1
anti/syn = 68%/86%ee. H NMR (300 MHz, CDCl3): δ (anti iso-
mer) = 1.41 (d, J = 6.9 Hz, 3 H), 2.82 (d, J = 6.9 Hz, 1 H), 4.72–
4.78 (m, 1 H), 5.66 (s, 1 H), 7.03–7.19 (m, 1 H), 7.28–7.57 (m, 3
H); δ (syn isomer) = 1.37 (d, J = 6.9 Hz, 3 H), 2.60 (s, 1 H), 4.72–
4.78 (m, 1 H), 5.43–5.45 (m, 1 H), 7.03–7.19 (m, 1 H), 7.28–7.57
(m, 3 H) ppm. 13C NMR (75.6 MHz, CDCl3): δ (anti isomer) =
11.9, 68.3, 85.2, 115.4, 124.6, 125.4, 127.8, 130.1, 157.5; δ (syn iso-
1
84%ee. H NMR (300 MHz, CDCl3): δ (anti isomer) = 0.86–0.91
(m, 6 H), 1.15–1.23 (m, 1 H), 1.48 (d, J = 6.6 Hz, 3 H), 1.76–1.80
(m, 2 H), 2.28 (br. s, 1 H), 4.20 (d, J = 6.6 Hz, 1 H), 4.40–4.46 (m,
1 H); δ (syn isomer) = 0.86–0.91 (m, 6 H), 1.06–1.14 (m, 1 H),
1.30–1.39 (m, 2 H), 1.49 (d, J = 6.9 Hz, 3 H), 2.28 (br. s, 1 H),
3.86–3.90 (m, 1 H), 4.40–4.46 (m, 1 H) ppm. 13C NMR (75.6 MHz,
CDCl3): δ (anti isomer) = 16.3, 21.7, 23.6, 24.3, 42.0, 71.2, 86.7; δ
(syn isomer) = 12.4, 21.4, 23.3, 24.5, 41.8, 70.2, 88.2 ppm.
mer)
= 16.2, 70.0, 87.9, 115.8, 125.0, 125.6, 128.3, 130.6,
160.8 ppm.
2-Nitro-1-p-tolylpropan-1-ol (4c): Prepared according to the general
procedure and purified by column chromatography (hexane/
EtOAc, 5:1) to give a yellow oil (65% yield). Diastereomeric ratios
2-Nitrohexan-3-ol (4g): Prepared according to the general pro-
cedure and purified by column chromatography (hexane/EtOAc,
5:1) to give a clear oil (70% yield). Diastereomeric ratios (anti/syn,
1
(anti/syn, 1.6:1) were determined by H NMR and HPLC. HPLC
1
(Chiralpak AD-H column; n-hex/IPA, 95:5; 1.0 mL/min; 210 nm):
1:1) were determined by H NMR and HPLC. HPLC (Chiralpak
tR = 12.72 [antiminor (1S,2R)], 14.03 [antimajor (1R,2S)], 19.13 AD-H column; n-hex/IPA, 98:2; 0.8 mL/min; 220 nm): tR = 23.65
[synminor (1S,2S)], 22.78 [synmajor (1R,2R)] min. anti/syn = 80%/ [antiminor (1S,2R)], 25.23 [antimajor (1R,2S)], 29.27 [synmajor
88%ee. H NMR (300 MHz, CDCl3): δ (anti isomer) = 1.51 (d, J (1R,2R)], 32.55 [synminor (1S,2S)] min. anti/syn = 82%/80%ee. 1H
= 6.9 Hz, 3 H), 2.36 (s, 3 H), 2.62 (br. s, 1 H), 4.67–4.81 (m, 1 H), NMR (300 MHz, CDCl3): δ (anti isomer) = 0.87–0.92 (m, 5 H),
1
5.34 (d, J = 3 Hz, 1 H), 7.21–7.28 (m, 4 H); δ (syn isomer) = 1.37 1.34–1.40 (m, 2 H), 1.46 (d, J = 6.9 Hz, 3 H), 2.13 (br. s, 1 H),
(d, J = 6.9 Hz, 3 H), 2.36 (s, 3 H), 2.47 (br. s, 1 H), 4.67–4.81 (m, 4.12–4.15 (m, 1 H), 4.42–4.50 (m, 1 H); δ (syn isomer) = 0.87–0.92
1 H), 5.06 (d, J = 8.1 Hz, 1 H), 7.21–7.28 (m, 4 H) ppm. 13C NMR
(75.6 MHz, CDCl3): δ (anti isomer) = 12.3, 21.1, 73.9, 87.5, 125.9,
(m, 5 H), 1.34–1.40 (m, 2 H), 1.49 (d, J = 6.9 Hz, 3 H), 2.22 (br.
s, 1 H), 3.75–3.85 (m, 1 H), 4.42–4.50 (m, 1 H) ppm. 13C NMR
Eur. J. Org. Chem. 2011, 4892–4898
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4897

Z. M. A. Judeh et al.
FULL PAPER
[10] For Cr, see: a) A. S. Zulauf, M. Mellah, E. Schulz, J. Org.
Chem. 2009, 74, 2242–2245; b) R. Kowalczyk, P. Kwiatkowski,
J. Skarzewski, J. Jurczak, J. Org. Chem. 2009, 74, 753–756.
[11] For Pd, see: S. Handa, K. Nagawa, Y. Sohtome, S. Matsunaga,
M. Shibasaki, Angew. Chem. 2008, 120, 3274; Angew. Chem.
Int. Ed. 2008, 47, 3230–3233.
(75.6 MHz, CDCl3): δ (anti isomer) = 13.8, 16.3, 18.4, 35.1, 72.7,
86.4; δ (syn isomer) = 12.4, 13.9, 19.0, 29.7, 71.8, 87.7 ppm.
Supporting Information (see footnote on the first page of this arti-
cle): NMR spectra, HRMS, and HPLC traces.
[12] a) T. Arai, Y. M. A. Yamada, N. Yamamoto, H. Sasai, M. Shi-
basaki, Chem. Eur. J. 1996, 2, 1368–1372; b) H. Sasai, T. Toku-
naga, S. Watanabe, T. Suzuki, N. Itoh, M. Shibasaki, J. Org.
Chem. 1995, 60, 7388–7389.
Acknowledgments
[13] a) D. A. Evans, D. Seidel, M. Rueping, H. W. Lam, J. T. Shaw,
C. W. Downey, J. Am. Chem. Soc. 2003, 125, 12692–12693; b)
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We are grateful to the Nanyang Technological University for finan-
cial support (RG27/07), and also appreciate scholarship support
for Y. Q. J. from the China Scholarship Council.
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Received: April 25, 2011
Published Online: July 14, 2011
4898
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Eur. J. Org. Chem. 2011, 4892–4898