Asymmetric organocatalytic oxy-Michael addition of alcohols to α,β-unsaturated aldehydes

Article abstract of DOI:10.1016/j.tet.2007.03.179

A 1,4-addition of alcohols to α,β-unsaturated aldehydes was found to be efficiently promoted by biphenyldiamine-based catalyst 3?without formation of the acetals. An asymmetric variant of this reaction has also been performed by designing a novel axially

Full text of DOI:10.1016/j.tet.2007.03.179

Tetrahedron 63 (2007) 8658–8664
Asymmetric organocatalytic oxy-Michael addition of
alcohols to a,b-unsaturated aldehydes
*
Taichi Kano, Youhei Tanaka and Keiji Maruoka
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto 606-8502, Japan
Received 7 March 2007; accepted 21 March 2007
Available online 19 April 2007
Abstract—A 1,4-addition of alcohols to a,b-unsaturated aldehydes was found to be efficiently promoted by biphenyldiamine-based catalyst
3 without formation of the acetals. An asymmetric variant of this reaction has also been performed by designing a novel axially chiral organo-
catalyst (R)-10c.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
addition of simple alcohols to a,b-unsaturated aldehydes;13
however, an asymmetric version of this process has re-
mained elusive despite its potential application in organic
synthesis. In this context, we are interested in the develop-
ment of a novel secondary amine-type chiral catalyst for the
1,4-addition reaction of alcohols to a,b-unsaturated alde-
hydes. Herein we report that the biaryldiamine-based orga-
nocatalyst can be utilized to realize the first asymmetric
oxy-Michael addition reaction of alcohols to a,b-unsatu-
rated aldehydes.
b-Hydroxy carbonyl compounds and their alkoxy analogues
serve as valuable building blocks and structural motifs in a
variety of natural products,1 and these compounds are usually
prepared by the aldol reaction2 and/or the subsequent alkyl-
ation of the resulting hydroxyl group. Alternatively, intermo-
lecular 1,4-addition of alcohols to a,b-unsaturated carbonyl
compounds also represents an attractive method for the direct
synthesis of b-alkoxy carbonyl compounds. Such oxy-
Michael additions of alcohols to a,b-unsaturated ketones or
esters have recently been effected by several catalysts such
as L-proline,3 PMe3,4 DBU,5 Tf2NH,6 and transition metal
complexes;7 however, the oxy-Michael addition of alcohols
to a,b-unsaturated aldehydes remains a challenge, mainly
because of the competitive acetal formation (Scheme 1).
2. Results and discussion
We first investigated the oxy-Michael addition reaction of
methanol to 2-heptenal using N-methylaniline (1) as a cata-
lyst since it has sufficient nucleophilicity to form the
iminium salts of a,b-unsaturated aldehydes as a reactive
intermediate, in addition to the ease of structural and elec-
tronical modifications. Thus, the oxy-Michael addition of
methanol to 2-heptenal was carried out in MeOH/H2O
(95:5) in the presence of 5 mol % of N-methylaniline (1)
or its derivatives, and the results are summarized in Table
1. In the absence of the catalyst, small amounts of acetal 5
were obtained (entry 1), and the reaction with N-methylani-
line (1) gave only trace amounts of the desired oxy-Michael
adduct 4 (entry 2). We then surveyed acidic additives to im-
prove the yield of the desired oxy-Michael adduct without
loss of the favorable chemoselectivity. The addition of HCl
cocatalyst accelerated both the oxy-Michael addition and the
acetalization (entry 3). Use of a weaker acid such as TFA
led to an increased ratio of oxy-Michael adduct 4 to acetal
5 (entry 4). Moreover, in the case of the weakly acidic
additive 2, the oxy-Michael addition occurred exclusively
to give 4 in moderate yield (entry 5), while 2 itself was
found not to catalyze the oxy-Michael addition (entry 6).
OR'
OR'
acetal formation
OR'
CHO
CHO
R
R
R
+
oxy-Michael addition
R'OH
Scheme 1.
In the field of organocatalysis, 1,4-addition reactions of het-
eroatom nucleophiles such as thiols,8 amides,9 carbamates,10
and triazoles11 to a,b-unsaturated aldehydes have been
performed by iminium catalysis, and only a few reports
have been made on organocatalytic conjugate addition of
oxygen nucleophiles to a,b-unsaturated aldehydes.12 Re-
cently we also reported the organocatalytic oxy-Michael
Keywords: Oxy-Michael addition; a,b-Unsaturated aldehyde; Organocata-
lyst; Iminium catalysis.
* Corresponding author. Tel./fax: +81 75 753 4041; e-mail: maruoka@
kuchem.kyoto-u.ac.jp
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.03.179

T. Kano et al. / Tetrahedron 63 (2007) 8658–8664
8659
Table 2. Oxy-Michael addition of alcohols to a,b-unsaturated aldehydes
catalyzed by biphenyldiamine-based catalyst 3a
NHMe
NHTf
R1
5 mol% 3
R2OH/H2O
R1
CHO
NHMe
NHTf
CHO
R2
OR2
1
2
3
Entry
R1
Time (h)
Yieldb,c (%)
1
2
3
4
5
6
7
Bu
Pr
BnCH2
i-Pr
t-Bu
Ph
Bu
Bu
Bu
Bu
Me
Me
Me
Me
Me
Me
Et
Et
Pr
Pr
10
8
87
83
80
72
41
<5
63
81
61
72
<5
72
64
Based on these results, we then prepared the biphenyl-
diamine-based catalyst 3, which has both secondary amine
and acidic moieties in the molecule, and consequently, the
reaction using 3 was found to proceed smoothly to give
oxy-Michael adduct 4 in good yield (entry 7). It should be
noted that the present reaction was significantly retarded
without adding H2O, probably due to deceleration of the imi-
nium hydrolysis step in the catalytic cycle (entry 8).
10
10
36
24
23
22
24
24
24
40
24
8d
9d
10e
11e
12e
13e
Bu
Bu
Bu
i-Pr
Allyl
Bn
Table 1. Oxy-Michael addition of methanol to 2-heptenal with aromatic
amine-based catalystsa
a
Unless otherwise noted, the reaction of an a,b-unsaturated aldehyde
(0.25 mmol) was carried out in the presence of 5 mol % of 3 in an alcohol
(950 mL) and H2O (50 mL) at 0 ꢀC.
Isolated yield.
Acetal was not detected.
Bu
Bu
OMe
OMe
5 mol% cat
MeOH/H2O
Bu
CHO
+
CHO
OMe
4
b
c
d
e
5
Entry
Catalyst
Time (h)
Yieldb (%)
Alcohol (970 mL) and H2O (30 mL).
Alcohol (990 mL) and H2O (10 mL).
4
5
The proposed catalytic cycle is outlined in Scheme 2. This
organocatalytic oxy-Michael addition reaction can be ex-
plained by iminium activation of a,b-unsaturated aldehydes
by catalyst A. The first step is the formation of the iminium
ion intermediate D with the assistance of acidic sulfonamide
moiety via B and C. An alcohol then reacts as a nucleophile
with this intermediate D to give the enamine intermediate E,
whichis followed by hydrolysisto yieldthedesired b-alkoxy-
aldehyde with regeneration of catalyst A. While we have not
conducted a detailed study, the sulfonamide moiety might
also activate the alcohol in the conjugate addition step
(D to E).
1
2
3
4
5
6
7
8f
—
1
10
10
4
0
5
23
42
51
0
4
0
29
15
0
10
0
1+HClc
1+TFAd
4
1+2e
10
10
10
10
2
3
3
87
25
0
a
Unless otherwise noted, the reaction of 2-heptenal (0.25 mmol) was car-
ried out in the presence of 5 mol % of the catalyst in MeOH (950 mL) and
H2O (50 mL) at 0 ꢀC.
Isolated yield.
HCl (5 mol %).
TFA (5 mol %).
2 (5 mol %).
b
c
d
e
f
R
Without H2O.
Me
N
Under optimized conditions, we then investigated the scope
of the oxy-Michael addition between various a,b-unsatu-
rated aldehydes and alcohols, and the representative results
are summarized in Table 2. a,b-Unsaturated aldehydes,
which have a primary alkyl or a secondary alkyl group at
the b-position, were proved to be suitable substrates in the
oxy-Michael addition of methanol (entries 1–4). The reac-
tion of the sterically hindered tert-butyl-substituted analogue
resulted in low yield of the product (entry 5). Cinnamalde-
hyde was unreactive (entry 6). In addition, catalyst 3 was
also effective for the oxy-Michael addition of ethanol, prop-
anol, allyl alcohol, and benzyl alcohol, giving the corre-
sponding oxy-Michael adducts in moderate to good yields
(entries 8, 10, 12, and 13). Unfortunately, however, this
system was not suitable for secondary alcohol such as iso-
propanol (entry 11). Since benzyl and allyl groups can be
easily removed from the products, both oxy-Michael adducts
of benzyl and allyl alcohols serve as synthetic equivalents to
aldol products. In each case, the addition of a proper amount
of H2O to the alcohol solvent is necessary to attain good
chemical yields (entry 7 vs 8 and entry 9 vs 10). It should
be noted that all the reactions proceeded without acetal
formation.
R
H
H
Me
O
N
N
N
H
OHC
OH
H
Tf
B
R
Tf
C
Me
NH
R'OH
-H2O
H
N
Me
Tf
N
N
A
OHC
R'O
R
H2O
Me
H
Tf
OR'
N
R
D
R
NH
Tf
OR'
E
Scheme 2. Proposed mechanism for the oxy-Michael addition of alcohols to
a,b-unsaturated aldehydes.
We then turned our attention to the development of the
asymmetric oxy-Michael addition reaction, and enantiopure

8660
T. Kano et al. / Tetrahedron 63 (2007) 8658–8664
Table 4. Asymmetric oxy-Michael addition of alcohol to a,b-unsaturated
aldehydes catalyzed by (R)-10ca
catalysts of type (R)-10 were selected as axially chiral biphe-
nyldiamine derivatives and prepared as follows (Scheme 3).
Careful bromination of octahydrobinaphthyldiamine (R)-6
with NBS yielded (R)-7, which was treated with arylboronic
acids under standard Suzuki–Miyaura coupling conditions
to give (R)-8b and (R)-8c. Trifluoromethanesulfonylation
of diamines (R)-6, (R)-8b, and (R)-8c followed by methyl-
ation with MeOTf afforded (R)-10a–c, respectively.
R1
1 mol% (R)-10c
R2OH/H2O/toluene
*
R1
CHO
CHO
OR2
Entry
R1
R2
Time (h)
Yieldb (%)
eec (%)
1
2
3
Bu
Pr
BnCH2
Bu
Bu
Me
Me
Me
Et
48
48
48
24
48
65
66
83
55
60
51
46
53
48
16
4d,e
5d,f
Br
Ar
Allyl
NH2
NH2
a
NH2
NH2
NH2
NH2
a
b
The reaction of a,b-unsaturated aldehyde (0.25 mmol) was carried out in
the presence of 1 mol % of (R)-10c in MeOH (950 mL), H2O (50 mL), and
toluene (100 mL) at 0 ꢀC.
b
c
d
e
f
Br
Ar
Isolated yield.
(R)-6
(R)-7
(R)-8b:
Ar = Ph
Determined by GC analysis using chiral capillary column.
Use of 5 mol % of catalyst (R)-10c.
EtOH (970 mL) and H2O (30 mL).
t
(R)-8c: Ar = 4- Bu-C6H4
c
c
Allyl alcohol (990 mL) and H2O (10 mL).
Ar
Ar
(100 mL) was added to dissolve the catalyst, and conse-
quently, moderate yield was achieved at the expense of the
reaction rate and enantioselectivity (entry 5).
NH2
NHTf
NHMe
NHTf
NH2
NHTf
d
d
Ar
Ar = H
Ar
We then applied our system to several a,b-unsaturated
aldehydes and alcohols and the results are shown in Table
4. Using 1 mol % of (R)-10c, the oxy-Michael addition of
methanol to a,b-unsaturated aldehydes having a primary
alkyl substituent at the b-position proceeded slowly to give
the corresponding adducts with moderate enantioselectivity
(entries 1–3). In the case of ethanol and allyl alcohol, cata-
lyst (R)-10c was dissolved in the alcohol/H2O mixed-solvent
system without using toluene (entries 4 and 5). Unfortu-
nately, however, the reaction with allyl alcohol resulted in
low enantioselectivity (entry 5).
(R)-9a
(R)-10a:
(R)-10b:
(R)-9b:
Ar = Ph
t
(R)-9c: Ar = 4- Bu-C6H4
Ar = Ph
t
(R)-10c: Ar = 4- Bu-C6H4
Scheme 3. Reagents and conditions: (a) NBS, THF, 0 ꢀC; (b) ArB(OH)2,
i
Pd(OAc)2, PPh3, Ba(OH)2$8H2O, DME, H2O, 80 ꢀC; (c)Tf2O, Pr2NEt,
DMAP, CH2Cl2, 0 ꢀC to rt; (d) MeOTf, CH3CN, 80 ꢀC.
With these new axially chiral organocatalysts, the oxy-
Michael addition reaction of methanol to 2-heptenal was
performed, and the results are summarized in Table 3.
Attempted use of (R)-10a resulted in formation of the oxy-
Michael adduct 4 with low enantioselectivity (entry 1);
however, introduction of phenyl group at 3,30-positions of
octahydrobinaphthyl moiety enhanced the enantioselectivity
(entry 2). Using the sterically more congested catalyst (R)-
10c, the oxy-Michael adduct 4 was obtained with 68% ee
albeit in low yield (entry 3). This low reactivity can be attrib-
uted to the low solubility of the catalyst (R)-10c in the
MeOH/H2O mixed-solvent system, and even 1 mol % of
(R)-10c was not completely dissolved in it, giving a similar
result (entry 4). Thus a minimum amount of toluene
3. Conclusion
In summary, we have developed oxy-Michael addition of
alcohols to a,b-unsaturated aldehydes catalyzed by biphe-
nyldiamine-based catalyst 3. Furthermore, using newly
designed axially chiral organocatalyst (R)-10c, the asym-
metric variant of this process has also been performed.
Our efforts will be directed toward improving the efficiency
of this and related catalyst systems. Further work aimed at
the elucidation of the mechanism is also in progress.
Table 3. Asymmetric oxy-Michael addition of MeOH to 2-heptenal cata-
lyzed by (R)-10a
Bu
5 mol% cat
MeOH/H2O
*
4. Experimental
4.1. General information
Bu
CHO
CHO
OMe
4
Entry
Catalyst
Time (h)
Yieldb (%)
eec (%)
Infrared (IR) spectra were recorded on a Shimadzu
IRPrestige-21 spectrometer. H NMR spectra were mea-
1
1
2
3
(R)-10a
(R)-10b
(R)-10c
(R)-10c
(R)-10c
20
14
14
24
48
80
46
36
29
65
2
37
68
68
51
sured on a JEOL JNM-FX400 (400 MHz) spectrometer.
Chemical shifts were reported in parts per million from tet-
ramethylsilane as an internal standard. Data were reported as
follows: chemical shift, integration, multiplicity (s¼singlet,
d¼doublet, t¼triplet, q¼quartet, m¼multiplet, br¼broad,
andapp¼apparent), couplingconstants(Hz), andassignment.
13C NMR spectra were recorded on a JEOL JNM-FX400
(100 MHz) spectrometer with complete proton decoupling.
Chemical shifts were reported in parts per million from the
4d
5d,e
a
The reaction of 2-heptenal (0.25 mmol) was carried out in the presence of
5 mol % of the catalyst in MeOH (950 mL) and H2O (50 mL) at 0 ꢀC.
Isolated yield.
Determined by GC analysis using chiral capillary column.
Use of 1 mol % of the catalyst.
Toluene (100 mL) was added.
b
c
d
e

T. Kano et al. / Tetrahedron 63 (2007) 8658–8664
8661
residual solvent as an internal standard. Analytical gas–liquid
phase chromatography (GLC) was performed on Shimadzu
GC-14B instruments equipped with a flame ionization detec-
tor using an Astec Chiraldex B-DM (30 mꢁ0.25 mm) col-
umn or a GL Science Chirasil-DEX CB (25 mꢁ0.25 mm)
column. The high-resolution mass spectra (HRMS) were
performed on a Bruker microTOF. Optical rotations were
measured on a JASCO DIP-1000 digital polarimeter. For
thin layer chromatography (TLC) analysis throughout this
4.2.3. (R)-2,20-Diamino-3,30-diphenyl-5,50,6,60,7,70,8,80-
octahydro-1,10-binaphthyl (R)-8b. A mixture of (R)-7
(216 mg, 0.48 mmol), Pd(OAc)2 (10.8 mg, 0.048 mmol),
PPh3 (50.3 mg, 0.192 mmol), Ba(OH)2$8H2O (606 mg,
1.92 mmol), and phenylboronic acid (176 mg, 1.44 mmol)
in degassed DME (5 mL) and H2O (500 mL) was refluxed
overnight. After cooling to room temperature, the resulting
mixture was poured into water and extracted with ethyl ace-
tate. The combined organic layers were washed with brine,
dried over Na2SO4, and concentrated. The residue was puri-
fied by flash column chromatography on silica gel (hexane/
diethyl ether¼25:1 as an eluent) to afford (R)-8b (88 mg,
work, Merck precoated TLC plates (silica gel 60 GF254
,
0.25 mm) were used. The products were purified by flash col-
umn chromatography on silica gel 60 (Merck 1.09386.9025,
230–400 mesh). In experiments requiring dry solvents,
tetrahydrofuran (THF) was purchased from Kanto Chemical
Co. Inc. as ‘Dehydrated’. a,b-Unsaturated aldehydes
were distilled and stored under an argon atmosphere at
ꢂ17 ꢀC. Other simple chemicals were purchased and used
as such.
1
0.20 mmol, 41% yield): [a]2D4 ꢂ28.2 (c 1.0, CHCl3); H
NMR (400 MHz, CDCl3) d 7.49 (4H, d, J¼7.6 Hz, Ar-H),
7.41 (4H, dd, J¼7.6, 7.6 Hz, Ar-H), 7.30 (2H, t, J¼7.6 Hz,
Ar-H), 6.91 (2H, s, Ar-H), 3.53 (4H, br s, NH2), 2.76 (4H,
t, J¼6.0 Hz, ArCH2), 2.33–2.42 (2H, m, ArCHH), 2.22–2.31
(2H, m, ArCHH), 1.65–1.80 (8H, m, CH2CH2CH2CH2); 13
C
NMR (100 MHz, CDCl3) d 140.1, 138.8, 135.6, 130.3,
129.2, 128.6, 127.3, 126.8, 125.6, 122.3, 29.3, 27.0, 23.5,
23.3; IR (neat) 3468, 3374, 2926, 2855, 2342, 2237, 1605,
1589, 1458, 1435, 908, 775, 731, 702, 648 cmꢂ1; HRMS
(ESI-TOF) calcd for C32H33N2: 445.2638 ([M+H]+); found:
445.2640 ([M+H]+).
4.2. Synthesis and characterization of 3 and (R)-10a–c
4.2.1. 20-Methylamino-2-trifluoromethanesulfonyl-
amino-1,10-biphenyl 3. To a stirred solution of 2-methyl-
amino-20-amino-1,10-biphenyl14 (198 mg, 1.0 mmol) and
iPr2NEt (174 mL, 1.0 mmol) in CH2Cl2 (10 mL) was added
Tf2O (168 mL, 1.0 mmol) dropwise at ꢂ78 ꢀC. After 3 h of
stirring at ꢂ78 ꢀC, the mixture was poured into water and
extracted with CH2Cl2. The combined organic layers were
washed with brine, dried over Na2SO4, and concentrated.
The residue was purified by flash column chromatography
on silica gel (hexane/CH2Cl2¼1:1 as an eluent) to afford 3
(182 mg, 0.55 mmol, 55% yield): 1H NMR (400 MHz,
CDCl3) d 7.60 (1H, d, J¼7.6 Hz, Ar-H), 7.37–7.46 (4H,
m, Ar-H), 7.17 (1H, dd, J¼1.2, 7.6 Hz, Ar-H), 6.98 (1H,
app t, Ar-H), 6.89 (1H, d, J¼8.4 Hz, Ar-H), 2.83 (3H, s,
NHCH3); 13C NMR (100 MHz, CDCl3) d 144.6, 133.7,
132.5, 131.5, 131.4, 129.8, 129.0, 127.9, 125.9, 125.3, 120.1,
119.4 (q, JC–F¼324 Hz), 112.7, 31.3; IR (neat) 3340, 2360,
4.2.4. (R)-2,20-Diamino-3,30-bis(4-tert-butylphenyl)-
5,50,6,60,7,70,8,80-octahydro-1,10-binaphthyl (R)-8c. Com-
pound (R)-8c was prepared in a similar manner as described
above using 4-tert-butylphenylboronic acid instead of phe-
nylboronic acid (77% yield): [a]2D7 ꢂ64.4 (c 1.0, CHCl3);
1H NMR (400 MHz, CDCl3) d 7.43 (8H, app s, Ar-H), 6.92
(2H, s, Ar-H), 3.54 (4H, br s, NH2), 2.75 (4H, t, J¼5.6 Hz,
ArCH2), 2.30–2.43 (2H, m, ArCHH), 2.17–2.30 (2H, m,
ArCHH), 1.60–1.80 (8H, m, CH2CH2CH2CH2), 1.35 (18H,
s, t-Bu); 13C NMR (100 MHz, CDCl3) d 149.6, 138.9,
137.1, 135.3, 130.3, 128.8, 127.2, 125.5, 122.3, 34.5, 31.4,
29.3, 27.0, 23.5, 23.3 (the signal for an aromatic carbon
was not identified due to the overlap of peaks); IR (neat)
3451, 3348, 2959, 2936, 2914, 2833, 2363, 2330, 2236, 1605,
1364, 1271, 1225, 1196, 1140, 959, 822, 741, 597 cmꢂ1
;
HRMS (ESI-TOF) calcd for C14H14F3N2O2S: 331.0723
([M+H]+); found: 331.0722 ([M+H]+).
1589, 1458, 1393, 1362, 1263, 1244, 907, 837, 731 cmꢂ1
;
HRMS (ESI-TOF) calcd for C40H49N2: 557.3890
([M+H]+); found: 557.3892 ([M+H]+).
4.2.2. (R)-2,20-Diamino-3,30-dibromo-5,50,6,60,7,70,8,80-
octahydro-1,10-binaphthyl (R)-7. To a stirred solution of
(R)-2,20-diamino-5,50,6,60,7,70,8,80-octahydro-1,10-binaphthyl
(292 mg, 1.00 mmol) in anhydrous THF (5 mL) was added
NBS (356 mg, 2.00 mmol) at 0 ꢀC. The reaction mixture
was stirred at 0 ꢀC for 1 min. The mixture was then
quenched with saturated NaHCO3 and saturated Na2SO3 at
0 ꢀC, and extracted with ethyl acetate. The combined or-
ganic layers were washed with brine, dried over Na2SO4,
and concentrated. The residue was purified by flash column
chromatography on silica gel (hexane/ethyl acetate¼40:1 as
an eluent) to afford (R)-7 (446 mg, 0.99 mmol, 99% yield):
4.2.5. (R)-20-Amino-2-trifluoromethanesulfonylamino-
5,50,6,60,7,70,8,80-octahydro-1,10-binaphthyl (R)-9a. To
a stirred solution of (R)-6 (146 mg, 0.50 mmol), Pr2NEt
i
(87 mL, 0.50 mmol), and a catalytic amount of DMAP in
CH2Cl2 (2 mL) was added Tf2O (84 mL, 0.50 mmol) at
0 ꢀC. The mixture was allowed to warm to room temperature
and stirred for 2 h. The reaction mixture was then quenched
with saturated NaHCO3 at 0 ꢀC and extracted with CH2Cl2.
The combined organic layers were washed with brine, dried
over Na2SO4, and concentrated. The residue was purified by
flash column chromatography on silica gel (hexane/ethyl
acetate¼5:1 as an eluent) to afford (R)-9a (72 mg,
1
[a]2D2 30.9 (c 1.0, CHCl3); H NMR (400 MHz, CDCl3)
1
d 7.21 (2H, s, Ar-H), 3.72 (4H, br s, NH2), 2.70 (4H, t,
J¼6.0 Hz, ArCH2), 2.16–2.25 (2H, m, ArCHH), 2.03–2.13
(2H, m, ArCHH), 1.60–1.74 (8H, m, CH2CH2CH2CH2);
13C NMR (100 MHz, CDCl3) d 139.1, 135.6, 132.3, 129.0,
122.4, 107.0, 29.0, 26.7, 23.1, 22.9; IR (neat) 3472, 3375,
0.17 mmol, 34% yield): [a]2D2 ꢂ12.4 (c 0.8, CHCl3); H
NMR (400 MHz, CDCl3) d 7.45 (1H, d, J¼8.4 Hz, Ar-H),
7.12 (1H, d, J¼8.4 Hz, Ar-H), 6.97 (1H, d, J¼8.0 Hz, Ar-
H), 6.62 (1H, d, J¼8.0 Hz, Ar-H), 4.41 (2H, br s, NH2),
2.80 (2H, t, J¼6.0 Hz, ArCH2), 2.72 (2H, t, J¼6.0 Hz,
ArCH2), 2.18–2.34 (2H, m, ArCH2), 2.09 (2H, t,
J¼6.0 Hz, ArCH2), 1.60–1.80 (8H, m, CH2CH2CH2CH2);
13C NMR (100 MHz, CDCl3) d 141.1, 137.4, 136.1, 135.8,
2930, 2855, 2359, 2332, 1601, 1456, 1013, 908, 733 cmꢂ1
;
HRMS (ESI-TOF) calcd for C20H23Br2N2: 449.0223
([M+H]+); found: 449.0211 ([M+H]+).

8662
T. Kano et al. / Tetrahedron 63 (2007) 8658–8664
130.8, 130.4, 129.8, 128.5, 128.2, 119.5 (q, JC–F¼324 Hz),
118.7, 117.3, 113.6, 29.5, 29.1, 27.13, 27.08, 23.0, 22.94,
22.90, 22.6; IR (neat) 3304, 2932, 2859, 2359, 1614, 1476,
ArCH2), 2.73 (2H, t, J¼6.0 Hz, ArCH2), 2.72 (3H, s,
NHCH3), 2.21 (2H, t, J¼6.4 Hz, ArCH2), 2.05 (2H, t, J¼
6.4 Hz, ArCH2), 1.58–1.82 (8H, m, CH2CH2CH2CH2); 13
C
1412, 1356, 1217, 1194, 1142, 980, 735, 602 cmꢂ1
;
HRMS (ESI-TOF) calcd for C21H24F3N2O2S: 425.1505
NMR (100 MHz, CDCl3) d 144.0, 137.7, 136.0, 135.5, 131.0,
130.6, 129.8, 127.7, 126.8, 119.5 (q, JC–F¼324 Hz), 117.7,
116.7, 108.4, 30.6, 29.5, 29.0, 27.2, 27.0, 23.13, 23.10, 22.9,
22.6; IR (neat) 3428, 3300, 2932, 2859, 2359, 2330, 1726,
1599, 1504, 1476, 1418, 1354, 1234, 1217, 1194, 1142, 806,
743, 602 cmꢂ1; HRMS (ESI-TOF) calcd for C22H26F3N2O2S:
439.1662 ([M+H]+); found: 439.1680 ([M+H]+).
([M+H]+); found: 425.1503 ([M+H]+).
4.2.6. (R)-20-Amino-3,30-diphenyl-2-trifluoromethanesul-
fonylamino-5,50,6,60,7,70,8,80-octahydro-1,10-binaphthyl
(R)-9b. Compound (R)-9b was prepared in a similar manner
as described above using (R)-8b instead of (R)-6 (38%
1
yield): [a]2D5 ꢂ152.1 (c 0.9, CHCl3); H NMR (400 MHz,
4.2.9. (R)-20-Methylamino-3,30-diphenyl-2-trifluoro-
methanesulfonylamino-5,50,6,60,7,70,8,80-octahydro-1,10-
binaphthyl (R)-10b. Compound (R)-10b was prepared in
a similar manner as described above using (R)-9b instead
of (R)-9a (35% yield): [a]2D6 ꢂ95.3 (c 0.5, CHCl3); 1H
NMR (400 MHz, CDCl3) d 7.28–7.49 (10H, m, Ar-H), 7.15
(1H, s, Ar-H), 7.01 (1H, s, Ar-H), 2.66–2.98 (4H, m,
ArCH2), 2.25–2.47 (4H, m, ArCH2), 2.22 (3H, s, NHCH3),
1.50–1.92 (8H, m, CH2CH2CH2CH2); 13C NMR
(100 MHz, CDCl3) d 141.6, 139.6, 139.5, 138.8, 138.7,
137.7, 137.0, 132.3, 132.1, 131.8, 131.1, 129.4, 129.0, 128.9,
128.1, 127.5, 127.3, 127.1, 118.6 (q, JC–F¼323 Hz), 35.7,
29.71, 29.65, 29.4, 28.7, 27.4, 22.92, 22.89, 22.79 (the signals
for two aromatic carbons were not identified due to the over-
lap of peaks); IR (neat) 3354, 2932, 2859, 2351, 1605, 1450,
1410, 1358, 1202, 1188, 1136, 974, 910, 770, 733, 702, 640,
602 cmꢂ1; HRMS (ESI-TOF) calcd for C34H34F3N2O2S:
591.2288 ([M+H]+); found: 591.2297 ([M+H]+).
CDCl3) d 7.32–7.52 (10H, m, Ar-H), 7.17 (1H, s, Ar-H),
6.97 (1H, s, Ar-H), 3.53 (2H, br s, NH2), 2.70–2.94 (4H,
m, ArCH2), 2.50–2.62 (1H, m, ArCHH), 2.26–2.44 (3H,
m, ArCH2), 1.60–1.86 (8H, m, CH2CH2CH2CH2); 13C
NMR (100 MHz, CDCl3) d 139.7, 139.5, 139.4, 139.2,
137.4, 137.1, 137.0, 135.6, 132.1, 131.0, 129.4, 129.3,
129.1, 128.9, 128.2, 127.5, 127.3, 127.24, 127.19, 123.1,
118.6 (q, JC–F¼324 Hz), 29.7, 29.2, 27.8, 27.6, 23.1, 22.9,
22.7, 22.6; IR (neat) 3426, 3341, 2932, 2859, 2357, 2328,
1605, 1460, 1418, 1358, 1206, 1190, 1134, 910, 766, 735,
702 cmꢂ1; HRMS (ESI-TOF) calcd for C33H32F3N2O2S:
577.2131 ([M+H]+); found: 577.2131 ([M+H]+).
4.2.7. (R)-20-Amino-3,30-bis(4-tert-butylphenyl)-2-tri-
fluoromethanesulfonylamino-5,50,6,60,7,70,8,80-octahy-
dro-1,10-binaphthyl (R)-9c. Compound (R)-9c was
prepared in a similar manner as described above using (R)-
8c instead of (R)-6 (38% yield): [a]2D2 ꢂ169.6 (c 1.0,
1
CHCl3); H NMR (400 MHz, CDCl3) d 7.47 (2H, d, J¼
4.2.10. (R)-3,30-Bis(4-tert-butylphenyl)-20-methylamino-
2-trifluoromethanesulfonylamino-5,50,6,60,7,70,8,80-octa-
hydro-1,10-binaphthyl (R)-10c. Compound (R)-10c was
prepared in a similar manner as described above using (R)-
9c instead of (R)-9a (53% yield): [a]2D4 ꢂ185.3 (c 1.0,
CHCl3); 1H NMR (400 MHz, CDCl3) d 7.47 (2H, d,
J¼8.4 Hz, Ar-H), 7.38 (2H, d, J¼8.0 Hz, Ar-H), 7.31 (2H,
d, J¼8.0 Hz, Ar-H), 7.30 (2H, d, J¼8.4 Hz, Ar-H), 7.15
(1H, s, Ar-H), 7.02 (1H, s, Ar-H), 2.65–2.97 (5H, m,
ArCH2), 2.30–2.50 (3H, m, ArCH2), 2.23 (3H, s, NHCH3),
1.54–1.92 (8H, m, CH2CH2CH2CH2), 1.37 (9H, s, t-Bu),
1.33 (9H, s, t-Bu); 13C NMR (100 MHz, CDCl3) d 150.4,
150.0, 141.7, 139.5, 139.0, 138.5, 137.5, 136.7, 136.5, 136.4,
132.2, 132.0, 131.7, 128.99, 128.96, 127.4, 125.8, 124.9,
118.6 (q, JC–F¼323 Hz), 35.7, 34.6, 34.5, 31.4, 31.3, 29.6,
29.4, 28.7, 27.4, 22.95, 22.90, 22.8 (the signals for two aro-
matic carbons and an aliphatic carbon were not identified
due to the overlap of peaks); IR (neat) 3354, 2961, 2866,
2359, 2342, 1402, 1362, 1204, 1186, 1022, 912, 837, 783,
737 cmꢂ1; HRMS (ESI-TOF) calcd for C42H50F3N2O2S:
703.3539 ([M+H]+); found: 703.3533 ([M+H]+).
8.0 Hz, Ar-H), 7.41 (2H, d, J¼8.0 Hz, Ar-H), 7.39 (2H, d,
J¼8.0 Hz, Ar-H), 7.31 (2H, d, J¼8.0 Hz, Ar-H), 7.17 (1H,
s, Ar-H), 6.97 (1H, s, Ar-H), 3.55 (2H, br s, NH2), 2.68–
2.96 (4H, m, ArCH2), 2.48–2.62 (1H, m, ArCHH), 2.22–
2.44 (3H, m, ArCH2), 1.57–1.85 (8H, m, CH2CH2CH2CH2),
1.36 (9H, s, t-Bu), 1.35 (9H, s, t-Bu); 13C NMR (100 MHz,
CDCl3) d 150.2, 150.1, 139.6, 139.2, 137.5, 137.2, 136.8,
136.6, 136.1, 135.3, 132.0, 131.1, 129.0, 128.8, 127.6,
127.0, 125.7, 125.0, 123.0, 118.6 (q, JC–F¼324 Hz), 34.6,
34.5, 31.4, 31.3, 29.7, 29.2, 27.7, 27.6, 26.9, 23.1, 23.0,
22.6 (the signal for an aromatic carbon was not identified
due to the overlap of peaks); IR (neat) 3428, 2959, 2936,
2864, 2839, 2322, 1607, 1460, 1408, 1362, 1269, 1206,
1188, 1136, 968, 910, 837, 775, 733, 631, 598, 577 cmꢂ1
;
HRMS (ESI-TOF) calcd for C41H48F3N2O2S: 689.3383
([M+H]+); found: 689.3381 ([M+H]+).
4.2.8. (R)-20-Methylamino-2-trifluoromethanesulfonyl-
amino-5,50,6,60,7,70,8,80-octahydro-1,10-binaphthyl (R)-
10a. To a stirred solution of (R)-9a (72 mg, 0.17 mmol) in
CH3CN (2 mL) was added MeOTf (19 mL, 0.17 mmol) at
room temperature and the reaction mixture was stirred at
80 ꢀC overnight. The reaction mixture was then quenched
with saturated NaHCO3 and extracted with CH2Cl2. The
combined organic layers were washed with brine, dried
over Na2SO4, and concentrated. The residue was purified
by flash column chromatography on silica gel (hexane/ethyl
acetate¼8:1 as an eluent) to afford (R)-10a (29 mg,
4.3. Representative procedure for the oxy-Michael
addition of an alcohol to an a,b-unsaturated aldehyde
and their characterization
To a solution of catalyst 3 (4.1 mg, 0.0125 mmol) in MeOH/
H2O (95:5 v/v, 0.25 M) was added (E)-2-heptenal (33 mL,
0.25 mmol) at 0 ꢀC. Upon consumption of the starting
material, the reaction mixture was directly purified by flash
column chromatography on silica gel (pentane/diethyl
ether¼4:1 as an eluent) to afford 3-methoxyheptanal
(31.4 mg, 0.218 mmol, 87% yield).
1
0.068 mmol, 40% yield): [a]2D6 ꢂ17.9 (c 0.8, CHCl3); H
NMR (400 MHz, CDCl3) d 7.47 (1H, d, J¼8.8 Hz, Ar-H),
7.12 (1H, d, J¼8.8 Hz, Ar-H), 7.08 (1H, d, J¼8.8 Hz, Ar-
H), 6.56 (1H, d, J¼8.8 Hz, Ar-H), 2.80 (2H, t, J¼6.0 Hz,

T. Kano et al. / Tetrahedron 63 (2007) 8658–8664
8663
4.3.1. 3-Methoxyheptanal (entry 1 in Table 2 and entry 1
in Table 4). [a]2D4 6.5 [c 2.2, CHCl3 (51% ee)] in the case of
entry 1 in Table 4; 1H NMR (400 MHz, CDCl3) d 9.81 (1H, t,
J¼2.4 Hz, CHO), 3.71 (1H, m, CHOMe), 3.35 (3H, s, OMe),
2.60 (1H, ddd, J¼2.4, 7.2, 16.4 Hz, CHHCHO), 2.52 (1H,
ddd, J¼2.0, 5.2, 16.4 Hz, CHHCHO), 1.25–1.65 (6H, m,
CH2CH2CH2), 0.91 (3H, t, J¼7.2 Hz, CH3); 13C NMR
(100 MHz, CDCl3) d 201.4, 76.3, 56.8, 48.0, 33.6, 27.3,
22.8, 14.1; IR (neat) 2957, 2930, 2860, 2826, 2725, 2342,
1724, 1466, 1094, 1032, 748 cmꢂ1; HRMS (ESI-TOF) calcd
for C8H16O2Na: 167.1043 ([M+Na]+); found: 167.1048
([M+Na]+); GLC analysis: Chiraldex B-DM (30 mꢁ0.25
mm) column (carrier gas: N2¼74 kPa, He¼98 kPa, 80 ꢀC
isotherm), retention time: 17.4 min and 18.5 min (major).
J¼1.8, 3.8, 16.0 Hz, CHHCHO), 1.96 (1H, m, CHMe2),
0.92 (3H, d, J¼8.0 Hz, CHCH3), 0.90 (3H, d, J¼8.0 Hz,
CHCH3); 13C NMR (100 MHz, CDCl3) d 202.0, 81.0,
57.5, 44.7, 30.5, 18.2, 17.1; IR (neat) 2957, 2924, 2855,
2363, 2336, 1730, 1516, 1456, 1377, 1314, 1098, 1024,
912, 743 cmꢂ1; HRMS (ESI-TOF) calcd for C7H14O2Na:
153.0886 ([M+Na]+); found: 153.0880 ([M+Na]+).
4.3.5. 3-Methoxy-4,4-dimethylpentanal (entry 5 in Table
1
2). H NMR (400 MHz, CDCl3) d 9.89 (1H, t, J¼2.2 Hz,
CHO), 3.40 (3H, s, OMe), 3.38 (1H, m, CHOMe), 2.59
(1H, app d, CHHCHO), 2.57 (1H, app dd, CHHCHO),
0.90 (9H, s, t-Bu); 13C NMR (100 MHz, CDCl3) d 201.7,
84.4, 60.0, 45.7, 35.7, 26.0; IR (neat) 2924, 2855, 2358,
2330, 1730, 1464, 1028, 912, 739 cmꢂ1; HRMS (ESI-
TOF) calcd for C8H16O2Na: 167.1043 ([M+Na]+); found:
167.1050 ([M+Na]+).
4.3.2. 3-Methoxyhexanal (entry 2 in Table 2 and entry 2
in Table 4). [a]2D8 3.1 [c 2.14, CHCl3 (46% ee)] in the case
of entry 2 in Table 4; H NMR (400 MHz, CDCl3) d 9.81
1
(1H, t, J¼2.4 Hz, CHO), 3.72 (1H, m, CHOMe), 3.35 (3H,
s, OMe), 2.62 (1H, ddd, J¼2.4, 6.8, 16.0 Hz, CHHCHO),
2.53 (1H, ddd, J¼2.4, 8.8, 16.0 Hz, CHHCHO), 1.33–1.65
(4H, m, CH2CH2), 0.94 (3H, t, J¼7.6 Hz, CH3); 13C NMR
(100 MHz, CDCl3) d 201.4, 76.1, 56.8, 48.0, 36.1, 18.4,
14.2; IR (neat) 2959, 2926, 2855, 2357, 1726, 1462, 1379,
1261, 1094, 1022, 768 cmꢂ1; HRMS (ESI-TOF) calcd for
C7H14O2Na: 153.0886 ([M+Na]+); found: 153.0880 ([M+
Na]+); GLC analysis: Chiraldex B-DM (30 mꢁ0.25 mm)
column (carrier gas: N2¼74 kPa, He¼98 kPa, 70 ꢀC iso-
therm), retention time: 16.7 min and 17.9 min (major).
4.3.6. 3-Ethoxyheptanal (entry 8 in Table 2 and entry 4 in
Table 4). [a]2D8 6.9 [c 0.5, CHCl3 (48% ee)] in the case of en-
try 4 in Table 4; 1H NMR (400 MHz, CDCl3) d 9.81 (1H, t,
J¼2.4 Hz, CHO), 3.79 (1H, m, CHOEt), 3.52 (2H, m,
OCH2), 2.61 (1H, ddd, J¼2.8, 7.2, 16.4 Hz, CHHCHO),
2.52 (1H, ddd, J¼2.0, 4.8, 16.4 Hz, CHHCHO), 1.25–1.70
(6H, m, CH2CH2CH2), 1.18 (3H, t, J¼6.8 Hz, OCH2CH3),
0.91 (3H, t, J¼7.2 Hz, CH3); 13C NMR (100 MHz, CDCl3)
d 201.9, 74.6, 64.5, 48.4, 34.1, 27.3, 22.7, 15.4, 14.0; IR
(neat) 2959, 2932, 2862, 2723, 2363, 2338, 1724, 1456,
1371, 1346, 1099, 1076 cmꢂ1; HRMS (ESI-TOF) calcd for
C9H18O2Na: 181.1199 ([M+Na]+); found: 181.1190 ([M+
Na]+); GLC analysis: Chiraldex B-DM (30 mꢁ0.25 mm)
column (carrier gas: N2¼74 kPa, He¼98 kPa, 80 ꢀC iso-
therm), retention time: 22.0 min and 23.1 min (major).
4.3.3. 3-Methoxy-5-phenylpentanal (entry 3 in Table 2
and entry 3 in Table 4). [a]2D6 3.2 [c 1.47, CHCl3 (53%
ee)] in the case of entry 3 in Table 4; H NMR (400 MHz,
1
CDCl3) d 9.80 (1H, t, J¼2.2 Hz, CHO), 7.21–7.30 (2H, m,
Ar-H), 7.17–7.19 (3H, m, Ar-H), 3.74 (1H, m, CHOMe),
3.37 (3H, s, OMe), 2.62–2.76 (3H, m, PhCH2 and
CHHCHO), 2.56 (1H, ddd, J¼2.0, 5.2, 16.4 Hz, CHHCHO),
1.78–1.98 (2H, m, BnCH2); 13C NMR (100 MHz, CDCl3)
d 201.3, 141.5, 128.4, 128.3, 125.9, 75.4, 56.8, 47.8, 35.7,
31.2; IR (neat) 3026, 2926, 2849, 2826, 2725, 1722, 1603,
1454, 1364, 1186, 1115, 1080, 748, 700 cmꢂ1; HRMS
(ESI-TOF) calcd for C12H16O2Na: 215.1043 ([M+Na]+);
found: 215.1037 ([M+Na]+). The enantiomeric excess was
determined by reduction [2.0 equiv NaBH4, MeOH
(0.2 M)] to 3-methoxy-5-phenylpentanol: [a]2D7 13.8 [c 0.6,
4.3.7. 3-Propoxyheptanal (entry 10 in Table 2). 1H NMR
(400 MHz, CDCl3) d 9.82 (1H, t, J¼2.2 Hz, CHO), 3.78
(1H, m, CHOPr), 3.41 (2H, m, OCH2), 2.61 (1H, ddd,
J¼2.4, 6.8, 16.0 Hz, CHHCHO), 2.51 (1H, ddd, J¼2.0,
5.2, 16.0 Hz, CHHCHO), 1.20–1.67 (8H, m, CH2CH2CH2
and OCH2CH2), 0.91 (6H, app t, CH3 and OCH2CH2CH3);
13C NMR (100 MHz, CDCl3) d 202.0, 74.9, 71.0, 48.4,
34.1, 27.3, 23.2, 22.7, 14.0, 10.6; IR (neat) 2959, 2932,
2874, 2862, 2723, 2361, 2330, 1726, 1466, 1379, 1352,
1098, 1084, 1028 cmꢂ1; HRMS (ESI-TOF) calcd for
C10H20O2Na: 195.1356 ([M+Na]+); found: 195.1346 ([M+
Na]+); GLC analysis: Chiraldex B-DM (30 mꢁ0.25 mm)
column (carrier gas: N2¼74 kPa, He¼98 kPa, 70 ꢀC iso-
therm), retention time: 65.3 min and 68.2 min (major).
1
CHCl3 (53% ee)]; H NMR (400 MHz, CDCl3) d 7.25–
7.35 (2H, m, Ar-H), 7.15–7.23 (3H, m, Ar-H), 3.71–3.85
(2H, m, CH2OH), 3.45 (1H, m, CHOMe), 3.37 (3H, s,
OMe), 2.66 (2H, t, J¼8.0 Hz, PhCH2), 2.60 (1H, br s,
OH), 1.70–2.00 (4H, m, BnCH2 and CH2CH2OH); 13C
NMR (100 MHz, CDCl3) d 142.0, 128.4, 128.3, 125.8,
80.0, 60.7, 56.4, 35.4, 34.8, 31.2; IR (neat) 3389, 3026,
2938, 2880, 2824, 2359, 2340, 1495, 1454, 1364, 1184,
1080, 1053, 745, 698 cmꢂ1; HRMS (ESI-TOF) calcd for
C12H18O2Na: 217.1199 ([M+Na]+); found: 217.1209 ([M+
Na]+); GLC analysis: Chirasil-DEX CB (25 mꢁ0.25 mm)
column (carrier gas: N2¼80 kPa, He¼85 kPa, 130 ꢀC iso-
therm), retention time: 60.8 min and 62.2 min (major).
4.3.8. 3-Allyloxyheptanal (entry 12 in Table 2 and entry 5
in Table 4). [a]2D4 2.2 [c 2.5, CHCl3 (16% ee)] in the case of
entry 5 in Table 4; 1H NMR (400 MHz, CDCl3) d 9.81 (1H, t,
J¼2.2 Hz, CHO), 5.89 (1H, m, CH]CH2), 5.26 (1H, dd,
J¼1.6, 17.6 Hz, CH]CHH), 5.16 (1H, dd, J¼1.6,
10.4 Hz, CH]CHH), 4.01 (2H, m, CHOCH2), 3.86 (1H,
m, CHOCH2), 2.63 (1H, ddd, J¼2.4, 6.8, 16.4 Hz,
CHHCHO), 2.53 (1H, ddd, J¼2.0, 4.8, 16.4 Hz, CHHCHO),
1.25–1.70 (6H, m, CH2CH2CH2), 0.91 (3H, t, J¼6.8 Hz,
CH3); 13C NMR (100 MHz, CDCl3) d 201.8, 134.8, 117.0,
74.3, 70.2, 48.3, 34.0, 27.3, 22.7, 14.0; IR (neat) 2957,
2932, 2860, 2727, 2357, 1726, 1464, 1339, 1070, 1038,
924 cmꢂ1; HRMS (ESI-TOF) calcd for C10H18O2Na:
193.1199 ([M+Na]+); found: 193.1197 ([M+Na]+). The
4.3.4. 3-Methoxy-4-methylpentanal (entry 4 in Table 2).
1H NMR (400 MHz, CDCl3) d 9.83 (1H, t, J¼2.2 Hz,
CHO), 3.53 (1H, m, CHOMe), 3.36 (3H, s, OMe), 2.55
(1H, ddd, J¼2.4, 8.0, 16.0 Hz, CHHCHO), 2.46 (1H, ddd,

8664
T. Kano et al. / Tetrahedron 63 (2007) 8658–8664
3. Ramachary, D. B.; Mondal, R. Tetrahedron Lett. 2006, 47,
7689.
enantiomeric excess was determined by conversion to 3-pro-
poxyheptanal ([a]2D5 2.3 [c 1.5, CHCl3 (16% ee)]) by hydro-
genation of an allyl group [H2 (1 atm), 20 wt % Pd/C, THF
(0.2 M)].
4. (a) Stewart, I. C.; Bergman, R. G.; Toste, F. D. J. Am. Chem.
Soc. 2003, 125, 8696; See also: (b) Jenner, G. Tetrahedron
Lett. 2001, 42, 4807; (c) Jenner, G. Tetrahedron 2002, 58,
4311; (d) Kisanga, P. B.; Ilankumaran, P.; Fetterly, B. M.;
Verkade, J. G. J. Org. Chem. 2002, 67, 3555.
4.3.9. 3-Benzyloxyheptanal (entry 13 in Table 2). 1H NMR
(400 MHz, CDCl3) d 9.80 (1H, t, J¼2.0 Hz, CHO), 7.22–
7.40 (5H, m, Ar-H), 4.56 (1H, d, J¼11.6 Hz, PhCHH),
4.51 (1H, d, J¼11.6 Hz, PhCHH), 3.95 (1H, m, CHOBn),
2.67 (1H, ddd, J¼2.4, 7.2, 16.4 Hz, CHHCHO), 2.56 (1H,
ddd, J¼2.0, 4.4, 16.4 Hz, CHHCHO), 1.27–1.75 (6H, m,
CH2CH2CH2), 0.91 (3H, t, J¼6.8 Hz, CH3); 13C NMR
(100 MHz, CDCl3) d 201.8, 138.2, 128.4, 127.8, 127.7,
74.3, 71.2, 48.3, 33.9, 27.2, 22.7, 14.0; IR (neat) 2955,
5. Murtagh, J. E.; McCooey, S. H.; Connon, S. J. Chem. Commun.
2005, 227.
6. Wabnitz, T. C.; Spencer, J. B. Org. Lett. 2003, 5, 2141.
7. (a) Nikitin, A. V.; Kholuiskaya, S. N.; Rubailo, V. L. J. Chem.
Biochem. Kinet. 1997, 3, 37; (b) Miller, K. J.; Kitagawa, T. T.;
Abu-Omar, M. M. Organometallics 2001, 20, 4403; (c)
Ganguly, S.; Roundhill, D. M. Organometallics 1993, 12,
4825; (d) van Lingen, H. L.; Zhuang, W.; Hansen, T.; Rutjes,
F. P. J. T.; Jørgensen, K. A. Org. Biomol. Chem. 2003, 1,
1953; (e) Farnworth, M. V.; Cross, M. J.; Louie, J.
Tetrahedron Lett. 2004, 45, 7441.
2930, 2860, 1724, 1454, 1094, 1067, 1028, 735, 698 cmꢂ1
;
HRMS (ESI-TOF) calcd for C14H20O2Na: 243.1356
([M+Na]+); found: 243.1362 ([M+Na]+).
ꢀ
8. Marigo, M.; Schulte, T.; Franzen, J.; Jørgensen, K. A. J. Am.
Chem. Soc. 2005, 127, 15710.
Acknowledgements
9. Takasu, K.; Maiti, S.; Ihara, M. Heterocycles 2003, 59, 51.
10. (a) Chen, Y. K.; Yoshida, M.; MacMillan, D. W. C. J. Am. Chem.
Soc. 2006, 128, 9328; (b) Vesely, J.; Ibrahem, I.; Rios, R.; Zhao,
This work was partially supported by a Grant-in-Aid for Sci-
entific Research on Priority Areas ‘Advanced Molecular
Transformation of Carbon Resources’ from the Ministry of
Education, Culture, Sports, Science and Technology, Japan.
Y.T. is grateful to the Japan Society for the Promotion of Sci-
ence for Young Scientists for a Research Fellowship.
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G.-L.; Xu, Y.; Cordova, A. Tetrahedron Lett. 2007, 48, 2193.
11. Diner, P.; Nielsen, M.; Marigo, M.; Jørgensen, K. A. Angew.
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Chem., Int. Ed. 2007, 46, 1983.
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J. Am. Chem. Soc. 2007, 129, 1536; (b) Li, H.; Wang, J.;
E-Nunu, T.; Zu, L.; Jiang, W.; Wei, S.; Wang, W. Chem.
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