Lewis acid catalyzed diastereoselective vinylogous Mannich reaction induced by O-pivaloylated d-galactosylamine as the chiral auxiliary: Stereoselective synthesis of 6-arylpiperidin-2-ones

Article abstract of DOI:10.1055/s-0031-1289635

The diastereospecific formation of β-N-glycosidically linked α,β-unsaturated δ-aminocarbonyl derivatives, in the form of (S)-δ-amino-δ-arylpent-2-enoic ester, has been achieved in high yield via a vinylogous Mannich reaction, utilizing poly-O-pivaloylated

Full text of DOI:10.1055/s-0031-1289635

PAPER
111
Lewis Acid Catalyzed Diastereoselective Vinylogous Mannich Reaction
Induced by O-Pivaloylated D-Galactosylamine as the Chiral Auxiliary:
Stereoselective Synthesis of 6-Arylpiperidin-2-ones
C
arbohydrate Ch
i
A
u
n
xiliary g Cui,a Shasha Kong,a Guiping Wu,a Zhiwei Miao,*a,b Ruyu Chen*a
a
State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, Nankai University,
Tianjin 300071, P. R. of China
Fax +86(22)23502351; E-mail: miaozhiwei@nankai.edu.cn
Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Tsinghua University,
Beijing 100084, P. R. of China
b
Received 23 September 2011; revised 9 November 2011
furans as well as acyclic silyl dienolates as nucleophiles in
vinylogous Mannich reactions.9 Several chiral auxiliaries
have also been used to achieve good enantioselectivity of
this reaction. Kawęcki described the use of optically ac-
Abstract: The diastereospecific formation of b-N-glycosidically
linked a,b-unsaturated d-aminocarbonyl derivatives, in the form of
(S)-d-amino-d-arylpent-2-enoic ester, has been achieved in high
yield via a vinylogous Mannich reaction, utilizing poly-O-pivaloy-
lated D-galacosylamine as the chiral auxiliary. (S)-6-p-Tolylpiperi- tive sulfinimines in the vinylogous Mannich reaction with
dine-2-one can be stereoselectively synthesized from (S)-d-amino-
d-arylpent-2-enoic ester by sequential hydrogenation of the double
bond, cyclic lactam formation, and removal of the N-glycosidic
auxiliary under basic conditions.
silylated dienes as well as with lithium dienolates leading
to enantiomerically enriched dihydropyridones and 2,4-
piperidinediones.10 Waldmann applied amino acid esters
as chiral auxiliary groups in Lewis acid catalyzed reac-
tions of electron-rich siloxydienes with imines. Appropri-
ate dihydropyridones were obtained with excellent
stereoselectivities. The cleavage of the chiral auxiliary
group was achieved by means of a Curtius rearrange-
ment.11
Key words: vinylogous Mannich reaction, carbohydrate, chiral
auxiliary, stereoselective synthesis, 6-arylpiperidin-2-ones
The asymmetric Mannich reaction is a fundamental C–C
bond-forming process in organic chemistry, and the reac-
tion products are versatile intermediates in the synthesis
of chiral, enantiomerically enriched b-aminocarbonyl sys-
tems.1 The g-addition of dienolate equivalents to imines,
known as vinylogous Mannich reaction, provides rapid
access to d-amino-a,b-unsaturated carbonyl compounds,
which often served a role as advanced intermediates prior
to their conversion to piperidinones.2 Piperidinones have
been widely used as building blocks in natural product
synthesis and are attractive chiral synthons for the prepa-
ration of piperidines.3 The substituted piperidine-2-ones
are also substructural units of barbiturates and
glutarimides4 and are key intermediates for the synthesis
of aminopentanoic acids.5 Thus, the development of chiral
nonracemic d-amino-a,b-unsaturated carbonyl building
blocks is still challenging and currently the object of in-
tensive synthetic endeavors. Compared with the well es-
tablished methodologies for the addition of imines with
cyclic siloxyfurans,6 the asymmetric vinylogous Mannich
reaction of acyclic silyl dienolates was rarely investigat-
ed.7 In 2008, Schneider reported the first catalytic, enan-
tioselective, vinylogous Mannich reaction of an acyclic
silyl dienolate with imines that was catalyzed by the chiral
Brønsted acid.8 Subsequently, Carretero and co-workers
successfully developed a copper(I) complex of Fesulphos
ligand as catalyst that could be applied both to silyloxy
Carbohydrates have been utilized as enantiomerically
pure candidates, which exert their chirality in chiral pool
syntheses of many chiral natural products and drugs.12
The most pre-eminent feature of carbohydrate auxiliaries
lies in their differing configurations of the carbohydrate
scaffold, which aid in installing diverse template geome-
tries, thus enabling the introduction of a wide variety of
coordinative site.13 The pioneering work of Vasella14a and
Kunz14b exploited carbohydrates as chiral templates in a
1,3-dipolar cycloaddition reaction and in a Diels–Alder
reaction, which prompted the application of carbohydrate
chiral auxiliary to construct highly stereoselective molec-
ular skeletons.14c Among all the carbohydrates, D-galac-
tose and D-glucose have attracted much synthetic
attention because of their great contributions to regio- and
stereoselective bond construction.15 We recently devel-
oped a convenient and efficient synthetic protocol for
preparation of chiral g-butenolide derivatives in high
yields and high enantiostereoselivities, utilizing O-piv-
aloylated D-galactosylamine as chiral auxiliary via vinyl-
ogous Mannich reactions.16 Herein we report a novel
diastereoselective vinylogous Mannich reactions of acy-
clic silyl dienolates and imines to furnish highly valuable
d-amino-a,b-unsaturated carboxylic esters in high yields
and good to excellent diastereoselectivities, and their sub-
sequent transformations.
The synthesis of b-N-glycosidically linked d-amino-a,b-
unsaturated carbonyl derivatives 5 started with the con-
densation of 2,3,4,6-tetra-O-pivaloyl-b-D-galactopyrano-
SYNTHESIS 2012, 44, 111–119
Advanced online publication: 2.12.2011
DOI: 10.1055/s-0031-1289635; Art ID: H91711SS
© Georg Thieme Verlag Stuttgart · New York
0
2
.1
2
.2
0
1
1

112
B. Cui et al.
PAPER
sylamine (1) and arylaldehyde 2. In order to prepare N- vealed that CuCl, CuBr, and CuI only caused anomeriza-
(2,3,4,6-tetra-O-pivaloyl-D-galacopyranosyl)aldimines 3, tion of the Schiff base 3c, and no product of 5c was
N-(2,3,4,6-tetra-O-pivaloylated-D-galacopyranosyl)amine
observed (Table 1, entries 2–4). Other Lewis acids tested
1 was reacted with aldehydes in the presence of acetic acid (e.g., BF3·OEt2, SnCl4, AlCl3, ZnCl2·OEt2, and FeCl3)
in propan-2-ol. The reactions proceeded smoothly within were able to promote the addition and gave moderate
a short period of time at room temperature under dehy- yields and good diastereoselectivities (Table 1, entries 5–
drating conditions.17
9).
We initially investigated the reaction of O-pivaloylated N- Since FeCl3 gave the higher diastereoselectivity
galactosylimine 3c (R = 4-ClC6H4) with silyl dienolate 4 (dr = 19:1:0:0) and higher yield (82%) compared with
in tetrahydrofuran without the aid of Lewis acid – no other Lewis acids, it was used in further investigations.
product 5c was detected (Table 1, entry 1). Since the nu- The ratio of diastereomers 5c was determined by 1H NMR
cleophilicity of silyl dienolate is low and the electrophilic- spectroscopy. Particularly, when increasing the reaction
ity of imines 3 is only moderate, the reaction between temperature to –50 °C and decreasing the loading amount
these compounds requires activation by a Lewis acid to of catalyst, FeCl3 (20 mol%) was able to catalyze the re-
proceed. For this purpose, various Lewis acids were tested action to give the product in 90% yield with a diastereose-
in the reaction of the O-pivaloylated N-galactosylimine 3c lectivity ratio of 19:1:0:0 (Table 1, entries 10, 11). Higher
with silyl dienolate 4 in THF at –78 °C. The results re- diastereoselectivity may be maintained at catalyst load-
Table 1 Survey of the Conditions for the Formation of 5ca
CHO
OPiv
PivO
H
O
4'
2'
OTMS
OEt
6'
N
OPiv
PivO
OPiv
PivO
1'
PivO
O
Cl
OPiv
Cl
2c
3'
5'
O
O
O
4
NH2
OPiv
N
PivO
PivO
OPiv
i-PrOH
Lewis acid
solvent
1
5c
3c
Cl
Entry
1
Lewis acid (equiv)
–
Solvent
THF
Time
Temp ( °C)
–78
Yield (%)b
n.r.d
trace
trace
trace
63
drc
2 d
1 d
1 d
2 d
2 d
1 d
2 d
2 d
1 d
8 h
10 h
15 h
8 h
2 d
2 d
2 d
–
2
CuCl (1)
THF
–78
–
3
CuBr (1)
THF
–50
–
4
CuI (1)
THF
–50
–
5
BF3·OEt2 (1)
SnCl4 (1)
THF
–78
5:1:0:0
7:1:0:0
7:1:0:0
19:1:0:0
19:1:0:0
19:1:0:0
19:1:0:0
19:1:0:0
5:1:0:0
–
6
THF
–78
74
7
AlCl3 (1)
THF
–50
57
8
ZnCl2·OEt2 (1)
FeCl3 (1)
THF
–78
72
9
THF
–78
82
10
11
12
13
14
15
16
FeCl3 (0.5)
FeCl3 (0.2)
FeCl3 (0.1)
BF3·OEt2 (0.5)
FeCl3 (0.2)
FeCl3 (0.2)
FeCl3 (0.2)
THF
–50
88
THF
–50
90
THF
–50
83
THF
–50
93
CH2Cl2
Et2O
toluene
–50
n.r.
n.r.
90
–50
–
–50
7:1:0:0
a Unless otherwise noted all the reactions were performed with 0.3 mmol of 3, 0.6 mmol silyl dienolate in 3 mL of solvent.
b After purification by chromatography.
c Diastereomeric ratio (dr) values were determined from the crude product by 1H NMR spectroscopy.
d No reaction.
Synthesis 2012, 44, 111–119
© Thieme Stuttgart · New York

PAPER
Carbohydrate Chiral Auxiliary
113
ings as low as 10 mol% but the yield is decreased (Table 2). It was found that O-pivaloylated N-galacto-
(19:1:0:0 dr, 83% yield, Table 1, entry 12). Compared sylimine 3, bearing both electron-rich and electron-poor
with FeCl3, BF3·OEt2 applied in THF at –50 °C can cata- aromatic groups, gave the corresponding asymmetric vi-
lyze this reaction in high yield, but with lower diastereo- nylogous Mannich products 5a–p in good to high yields
selectivities (Table 1, entry 13).
and diastereoselectivities (Table 2). As for the aldimine in
which R was a phenyl group, relatively lower yield and
diastereoselectivity was realized under identical condi-
tions (Table 2, 5a). Particularly, this process was efficient
for cinnamaldehyde and afforded the desired product with
90% diastereoselectivity in 75% yield (Table 2, 5p). No-
tably, the aldimine derived from heteroaromatic aldehyde
gave the adduct in good yield but with poor diastereose-
lectivity (Table 2, 5o). Furthermore, the reaction of Schiff
base 3 of aliphatic aldehyde with silyl dienolate 4 led to
the product in very poor yield, only anomerization and de-
composition occurred. The reaction of 1-trimethylsiloxy-
buta-1,3-diene with aldimine 3m in the presence of 0.3
equivalent AlCl3 as catalyst in THF at –50 °C, led to the
Following this evaluation of Lewis acids, a solvent
screening was undertaken. The reaction could not proceed
in CH2Cl2 and Et2O to afford the desired product (Table 1,
entries 14, 15). Toluene gave a high conversion rate, but
with a decrease in the diastereomeric excess (Table 1, en-
try 16). Among the solvents tested, THF was found to be
the best with respect to catalytic activity and asymmetric
induction.
The optimized procedure was broadly applicable to reac-
tions with various aldimines 3 with silyl dienolate 4,
which were converted into the corresponding vinylogous
Mannich products 5 in good to excellent diastereoselec-
tivities (up to dr 99:1:0:0) and typically high yields
Table 2 Vinylogous Mannich Reaction of N-(2,3,4,6-Tetra-O-pivaloylated D-galactosyl)aldimines 5a–p
OTMS
OPiv
PivO
OPiv
PivO
OEt
4 (2.0 equiv)
H
O
O
N
S
R
N
R
OEt
PivO
PivO
FeCl3 (0.2 equiv)
THF, –50 °C
OPiv
OPiv
H
O
3
5
Product
5a
R
Time (h)
24
Yield (%)a
81
drb
Ph
94:6:0:0
99:1:0:0
94:6:0:0
99:1:0:0
94:6:0:0
95:5:0:0
99:1:0:0
98:2:0:0
99:1:0:0
98:2:0:0
94:6:0:0
99:1:0:0
93:7:0:0
97:3:0:0
59:1:39:1
95:5:0:0
99:1:0:0
5b
5c
4-O2NC6H4
4-ClC6H4
4-FC6H4
10
90
16
91
5d
5e
19
78
4-BrC6H4
4-F3CC6H4
4-MeC6H4
4-MeOC6H4
2-ClC6H4
2-BrC6H4
2-MeC6H4
3-FC6H4
18
83
5f
14
81
5g
22
80
5h
5i
22
97
17
97
5j
17
96
5k
5l
10
93
24
88
5m
5n
5o
3-ClC6H4
3-MeC6H4
furan-2-yl
(E)-PhCH=CH
3-ClC6H4
17
88
16
79
24
65
5p
5qc
24
75
54
98
a After purification by chromatography.
b Diastereomeric ratio determined from the crude product by HPLC.
c The reaction was performed with 3m (0.3 mmol), 1-trimethylsiloxybuta-1,3-diene (0.6 mmol), and AlCl3 (0.09 mmol) in THF (5 mL) at –50 °C.
© Thieme Stuttgart · New York
Synthesis 2012, 44, 111–119

114
B. Cui et al.
PAPER
formation of product 5q in good yield and excellent enan- The possible mechanism for the reactions is shown in
tioselectivity (Table 2, 5q), The products 5 contained ex- Figure 2. The preferred formation of the configured dia-
clusively E-double bonds, and accordingly no cyclization stereomer of 5 can be rationalized by an attack of silyl di-
to the corresponding 5,6-dihydro-2-pyridones was ob- enolate from Si side of N-galactosylaldimines 3. In the
served.
transition state, the iron atom has hexacoordination, the
sites of which are occupied by the imine nitrogen and car-
bonyl oxygens (C-2 and C-6) of the pivaloyloxy group, re-
spectively; and one of the three chlorines may be removed
when silyl dienolate was introduced. According to this ra-
tionalization, the SN2¢-type attack of silyl dienolate from
the back side of the plane of C=N is initiated. Based on
these results, this hypothesis would explain the course of
the main isomer synthesis. The mechanism indicates that
the pivaloyl group in the aldimines 3 plays a significant
role in controlling the diastereoselective addition of silyl
dienolate to N-galactosylaldimines 3.
The ratio of the obtained diastereomers 5 was determined
by HPLC from the crude mixture of the reaction. It should
be noted that because of the anomeric carbon and one ste-
reogenic center created at the a-position of ethyl acrylate,
the four anomeric diastereomers have the bS, bR, aR and
aS configurations. The experiment results showed that the
corresponding a-anomer could be restricted in this reac-
tion. A synthetically relevant advantage of using O-piv-
aloylated D-galactosylamine as the chiral auxiliary is the
facile deprotection of the vinylogous Mannich products 5
by simple treatment with MeONa in MeOH. Adduct 5g
was converted to the d-lactam 8g by hydrogenation of the
double bond catalyzed by Pd/C and subsequent cyclized
to (S)-6-p-tolylpiperidine-2-one (8g) in quantitative yield
(Scheme 1). In order to determine the absolute configura-
tion of the main isomer of silyl dienolate addition to N-ga-
lactosylaldimines 3, a single crystal X-ray diffraction
study of 5b was performed.18 The molecular structure of
5b is shown in Figure 1, and the structure shows that the
relative configuration of b-N-glycoside-a,b-unsaturated
d-amino carbonylate main product can be assigned as bS.
Me
Me
O
Me Si
O
Cl
t-Bu
Cl
Cl
O
O
PivO
Fe
O
O
N
Ph
PivO
O
H
t-Bu
Figure 2 Plausible reaction mechanism
In conclusion, we have developed a new efficient synthet-
ic protocol for the preparation of chiral d-lactam deriva-
tives in high yields and high enantiostereoselectivity,
utilizing FeCl3 as the promoter and O-pivaloylated D-ga-
lactosylamine 1 as chiral auxiliary via vinylogous
Mannich reactions. The O-pivaloylated galactosylamine 1
is an effective chiral template in the synthesis of chiral N-
galactosyl d-amino a,b-unsaturated carbonyl derivatives 5.
FeCl3 can form the hexacoordinated intermediate induc-
ing the S-configuration at the Ca center by attack at the Si-
side of the C=N plane of the imine carbon atom. The mild
carbohydrate deprotection allows the resulting products to
be readily transformed into optically active d-lactam de-
rivatives. Further studies are being conducted with regard
to scope of this reaction and related vinylogous Mannich
reaction induced by carbohydrate as chiral auxiliary.
Figure 1 The ORTEP drawing of 5b
All reactions were carried out under an inert atmosphere and in
heat-dried glassware. Anhyd THF was obtained by distillation from
Na silk. Flash column chromatography was performed on silica gel
OPiv
O
OPiv
O
PivO
PivO
PivO
PivO
O
H
H
OPiv
N
N
HN
PivO
PivO
OEt
OEt
OPiv
OPiv
NaOMe
MeOH
Pd/C, H2
MeOH
+
O
OH
OPiv
O
O
7
5g
6g
8g
Scheme 1 Synthesis of (S)-6-p-tolylpiperidine-2-one (8g)
Synthesis 2012, 44, 111–119
© Thieme Stuttgart · New York

PAPER
Carbohydrate Chiral Auxiliary
115
3
(particle size 10–40 mm, Ocean Chemical Factory of Qingdao, P. R.
H, CH=CH), 5.80 (d, J3¢,4¢ = 15.6 Hz, 1 H, CH=CH), 5.35 (d,
3J3,4 = 2.6 Hz, 1 H, 4-H), 5.08 (dd, 3J2,3 = 10.3 Hz, 3J1,2 = 8.5 Hz, 1
H, 2-H), 5.02 (dd, 3J2,3 = 10.3 Hz, 3J3,4 = 2.6 Hz, 1 H, 3-H), 4.42 (t,
of China). N2 (99.999%) was purchased from Boc Gas Inc. 1H, and
1
13C spectra were recorded on Bruker-400 (400 MHz for H, 101
MHz for 13C) spectrometers. Chemical shifts were reported in ppm
downfield from internal SiMe4. The crystal structure was deter-
mined on a Bruker SMART 1000 CCD diffractometer. Mass spec-
tra were recorded on a LCQ advantage spectrometer with ESI
resource. HRMS were recorded on APEXII and ZAB-HS spectrom-
eter. Melting points were determined on a T-4 melting point appa-
ratus (uncorrected).
3J1¢,2¢ = 6.6 Hz, JNH,1¢ = 12.8 Hz, 1 H, CHNH), 4.16 (q, 3J5¢,6¢ = 7.1
3
Hz, 2 H, OCH2CH3), 4.11 (dd, 2J6a,6b = 11.2 Hz, 3J6b,5 = 6.8 Hz, 1 H,
6b-H), 3.98 (dd, 2J6a,6b = 11.2 Hz, J6a,5 = 6.8 Hz, 1 H, 6a-H), 3.78
3
(dd, 3J1,2 = 8.5 Hz, 1 H, 1-H), 3.69 (t, 3J5,6 = 6.8 Hz, 1 H, 5-H), 2.55
(t, 3J2¢,1¢ = 6.6 Hz, 2 H, CH2CH=CH), 2.23 (d, 3JNH,1¢ = 12.8 Hz, 1 H,
NH), 1.26–1.28 [m, 12 H, C(CH3)3, OCH2CH3], 1.19–1.20 [m, 18
H, 2 C(CH3)3], 1.09 [s, 9 H, C(CH3)3].
13C NMR (101 MHz, CDCl3): d = 176.82, 176.62, 176.06, 175.80,
164.79 (C=O), 147.94, 146.57, 141.63, 127.32, 123.81, 122.82
(Arom-C6H4, CH=CH), 85.31, 70.81, 70.10, 67.69, 66.14, 60.52,
59.40, 54.85 (C–O, C–N), 39.78, 38.05, 37.84, 37.70, 28.67, 26.25,
26.20, 26.099, 26.07, 13.19.
O-Pivaloylated N-Galactosylimines of Aromatic Aldehydes 3;
General Procedure
To a solution of 2,3,4,6-tetra-O-pivaloyl-b-D-galactopyranosyl-
amine (1; 0.515 g, 1 mmol) and aldehyde 2 (1.3 mmol) in propan-
2-ol (2.5 mL) was added AcOH (2–3 drops) and the mixture was
stirred at r.t. for about 0.5 h. The appearance of a precipitate from
the solution indicated the formation of 3. The precipitate was col-
lected by filtration, washed with ice-cold propan-2-ol (15 mL), and
dried in vacuum to afford N-galactosylaldimines 3 as colorless sol-
ids.
MS (ESI): m/z = 785.40 [M + Na]+.
HRMS (ESI): m/z calcd for C39H58N2O13 + Na+: 785.3831 [M +
Na]+; found: 785.3831.
Ethyl (5S,2E)-5-[(2,3,4,6-Tetra-O-pivaloyl-b-D-galactopyrano-
syl)amino]-5-(4-chlorophenyl)pent-2-enoate (5c)
Yield: 137 mg (91%); white solid; mp 57–58 °C.
Formation of b-N-Glycosidic Linkages; d-Amino-a,b-unsatur-
ated Carbonyl Derivatives 5; General Procedure
1H NMR (400 MHz, CDCl3): d = 7.29 (d, J = 8.4 Hz, 2 Harom), 7.19
A solution of N-galactosylaldimine 3 (0.2 mmol) and FeCl3 (6.44
mg, 0.04 mmol) in THF (3 mL) was cooled to –50 °C under N2 pro-
tection, and 1-trimethylsilyloxy-1-ethoxybuta-1,3-diene (4; 74.4
mg, 0.4 mmol) was added. The mixture was stirred at this tempera-
ture until no starting material was monitored by TLC (ca. 10–24 h).
The mixture was hydrolyzed with sat. aq NaHCO3 (5 mL) and then
stirred at r.t. for 15 min. The aqueous phase was extracted with
EtOAc (3 × 5 mL), and the organic layers were combined, dried
(MgSO4), filtered, and concentrated in vacuo. After purification by
flash column chromatography on silica gel [petroleum ether (bp 60–
90 °C)–EtOAc, 15:1 (v/v)], pure products 5 were obtained
(Table 2).
(d, J = 8.4 Hz, 2 Harom), 6.73 (dt, 3J3¢,4¢ = 15.3 Hz, 3J2¢,3¢ = 7.4 Hz, 1
3
H, CH=CH), 5.79 (d, J3¢,4¢ = 15.3 Hz, 1 H, CH=CH), 5.34 (d,
3J3,4 = 2.5 Hz, 1 H, 4-H), 4.99–5.08 (m, 2 H, 2-H, 3-H), 4.26 (t,
3
3J1¢,2¢ = 6.4 Hz, J1¢,NH = 13.1 Hz, 1 H, CHNH), 4.16 (q, 3J5¢,6¢ = 7.3
Hz, 2 H, OCH2CH3), 4.09 (dd, 2J6a,6b = 11.1 Hz, 3J5,6b = 6.7 Hz, 1 H,
3
6b-H), 3.98 (dd, 2J6a,6b = 11.1 Hz, J5,6a = 6.7 Hz, 1 H, 6a-H), 3.77
(dd, 3J1,2 = 7.9 Hz, 1 H, 1-H), 3.67 (t, 3J5,6 = 6.7 Hz, 1 H, 5-H), 2.50
(t, 3J1¢,2¢ = 6.4 Hz, 2 H, CH2CH=CH), 2.14 (d, 3J1¢,NH = 13.1 Hz, 1 H,
NH), 1.26–1.28 [m, 12 H, C(CH3)3, OCH2CH3], 1.19–1.20 [m, 18
H, 2 C(CH3)3], 1.09 [s, 9 H, C(CH3)3].
13C NMR (101 MHz, CDCl3): d = 176.87, 176.63, 176.08, 175.86,
165.04 (C=O), 142.68, 138.52, 132.42, 127.92, 127.71, 123.25
(Arom-C6H4, CH=CH), 85.14, 70.69, 70.21, 67.67, 66.29, 60.66,
59.29, 54.70 (C–O, C–N), 40.01, 38.05, 37.80, 37.70, 28.67, 26.23,
26.20, 26.11, 26.07, 13.20.
Ethyl (5S,2E)-5-[(2,3,4,6-Tetra-O-pivaloyl-b-D-galactopyrano-
syl)amino]-5-phenylpent-2-enoate (5a)
Yield: 117 mg (81%); white solid; mp 56–58 °C.
1H NMR (400 MHz, CDCl3): d = 7.29–7.32 (m, 5 H, C6H5), 6.77
MS (ESI): m/z = 752.20 [M + H]+, 774.27 [M + Na]+.
3
(dt, J3¢,4¢ = 15.6 Hz, 3J2¢,3¢ = 7.4 Hz, 1 H, CH=CH), 5.81 (d,
HRMS (ESI): m/z calcd for C39H58ClNO11 + Na+: 774.3591 [M +
3
3J3¢,4¢ = 15.6 Hz, 1 H, CH=CH), 5.33 (d, J3,4 = 3.0 Hz, 1 H, 4-H),
Na]+; found: 774.3582.
3
3
5.06 (dd, J1,2 = 8.7 Hz, J2,3 = 10.3 Hz, 1 H, 2-H), 5.00 (dd,
3J3,4 = 3.0 Hz, 3J2,3 = 10.3 Hz, 1 H, 3-H), 4.27 (t, J1¢,2¢ = 6.1 Hz, 1
3
Ethyl (5S,2E)-5-[(2,3,4,6-Tetra-O-pivaloyl-b-D-galactopyrano-
syl)amino]-5-(4-fluorophenyl)pent-2-enoate (5d)
Yield: 115 mg (78%); light yellow solid; mp 58–59 °C.
3
H, CHNH), 4.15 (q, J5¢,6¢ = 7.1 Hz, 2 H, OCH2CH3), 4.09 (dd,
3J5,6b = 6.7 Hz, J6a,6b = 11.1 Hz, 1 H, 6b-H), 3.99 (dd, J5,6a = 6.7
2
3
2
3
Hz, J6a,6b = 11.1 Hz, 1 H, 6a-H), 3.80 (dd, J1,2 = 8.7 Hz,
1H NMR (400 MHz, CDCl3): d = 7.25 (t, J = 8.6 Hz, 2 Harom), 7.02
(t, J = 8.6 Hz, 2 Harom), 6.75 (dt, 3J3¢,4¢ = 15.3 Hz,3J2¢,3¢ = 7.9 Hz, 1 H,
CH=CH), 5.81 (d, 3J3¢,4¢ = 15.3 Hz, 1 H, CH=CH), 5.35 (d, 3J3,4 = 1.8
Hz, 1 H, 4-H), 5.00–5.11 (m, 2 H, 2-H, 3-H), 4.28 (t, 3J1¢,2¢ = 6.6 Hz,
3J1,NH = 12.4 Hz, 1 H, 1-H), 3.66 (t, J5,6 = 6.7 Hz, 1 H, 5-H), 2.52
3
(t, 3J1¢,2¢ = 6.1 Hz, 2 H, CH2CH=CH), 2.12 (d, 3JNH,1 = 12.4 Hz, 1 H,
NH), 1.26–1.27 [m, 12 H, C(CH3)3, OCH2CH3], 1.19–1.20 [m, 18
H, 2 C(CH3)3], 1.09 [s, 9 H, C(CH3)3].
3
1 H, CHNH), 4.17 (q, J5¢,6¢ = 7.1 Hz, 2 H, OCH2CH3), 4.11 (dd,
13C NMR (101 MHz, CDCl3): d = 176.86, 176.64, 176.08, 175.88,
165.12 (C=O), 143.30, 139.97, 127.46, 126.73, 126.61, 122.94 (Ph,
CH=CH), 85.24, 70.61, 70.26, 67.67, 66.36, 60.72, 59.18, 55.29
(C–O, C–N), 40.15, 38.04, 37.79, 37.68, 26.23, 26.20, 26.10, 26.06,
13.20.
2J6a,6b = 11.2 Hz, 3J5,6b = 6.5 Hz, 1 H, 6b-H), 4.00 (dd, 2J6a,6b = 11.2
3
Hz, 3J5,6a = 6.5 Hz, 1 H, 6a-H), 3.78 (d, J1,2 = 5.8 Hz, 1 H, 1-H),
3
3
3.69 (t, J5,6 = 6.5 Hz, 1 H, 5-H), 2.51 (t, J2¢,1¢ = 6.6 Hz, 2 H,
CH2CH=CH), 2.15 (s, 1 H, NH), 1.26–1.29 [m, 12 H, C(CH3)3,
OCH2CH3], 1.21 [s, 18 H, 2 C(CH3)3], 1.11 [s, 9 H, C(CH3)3].
MS (ESI): m/z = 718.27 [M + H]+, 740.33 [M + Na]+.
13C NMR (101 MHz, CDCl3): d = 176.85, 176.61, 176.08, 175.85,
165.03 (C=O), 161.26 (1JC,F = 246.1 Hz), 142.85, 135.69
(4JC,F = 3.0 Hz), 128.10 (3JC,F = 8.0 Hz), 123.18, 114.40
(2JC,F = 21.3 Hz), 85.20, 70.73, 70.28, 67.70, 66.35, 60.70, 59.24,
54.69 (C–O, C–N), 40.16, 38.06, 37.81, 37.71, 28.68, 26.23, 26.12,
26.09, 26.05, 13.21.
HRMS (ESI): m/z calcd for C39H59NO11 + Na+: 740.3980 [M +
Na]+; found: 740.3988.
Ethyl (5S,2E)-5-[(2,3,4,6-Tetra-O-pivaloyl-b-D-galactopyrano-
syl)amino]-5-(4-nitrophenyl)pent-2-enoate (5b)
Yield: 137 mg (90%); light yellow solid; mp 69–70 °C.
MS (ESI): m/z = 758.47 [M + Na]+.
1H NMR (400 MHz, CDCl3): d = 8.19 (d, J = 8.7 Hz, 2 Harom), 7.44
(d, J = 8.7 Hz, 2 Harom), 6.72 (dt, 3J3¢,4¢ = 15.6 Hz, 3J2¢,3¢ = 7.4 Hz, 1
© Thieme Stuttgart · New York
Synthesis 2012, 44, 111–119

116
B. Cui et al.
PAPER
HRMS (ESI): m/z calcd for C39H58FNO11 + Na+: 758.3886 [M +
C(CH3)3, OCH2CH3], 1.19–1.20 (m, 18 H, 2 C(CH3)3], 1.09 [s, 9 H,
C(CH3)3].
Na]+; found: 758.3884.
13C NMR (101 MHz, CDCl3): d = 176.90, 176.65, 176.10, 175.91,
165.18 (C=O), 143.51, 136.79, 136.37, 128.16, 126.56, 122.83 (Ar-
C6H4, CH=CH), 85.17, 70.60, 70.28, 67.66, 66.41, 60.76, 59.19,
54.98 (C–O, C–N), 40.17, 38.05, 37.79, 37.69, 28.67, 26.24, 26.21,
26.12, 26.07, 20.10, 13.21.
Ethyl (5S,2E)-5-[(2,3,4,6-Tetra-O-pivaloyl-b-D-galactopyrano-
syl)amino]-5-(4-bromophenyl)pent-2-enoate (5e)
Yield: 132 mg (83%); white solid; mp 70–71 °C.
1H NMR (400 MHz, CDCl3): d = 7.44 (d, J = 8.2 Hz, 2 Harom), 7.13
(d, J = 8.2 Hz, 2 Harom), 6.72 (dt, 3J3¢,4¢ = 15.6 Hz, 3J2¢,3¢ = 7.2 Hz, 1
MS (ESI): m/z = 732.27 [M + H]+, 754.33 [M + Na]+.
3
H, CH=CH), 5.79 (d, J3¢,4¢ = 15.6 Hz, 1 H, CH=CH), 5.34 (d,
HRMS (ESI): m/z calcd for C40H61NO11 + Na+: 754.4137 [M +
3J3,4 = 2.8 Hz, 1 H, 4-H), 5.00–5.08 (m, 2 H, 2-H, 3-H), 4.24 (t,
Na]+; found: 754.4125.
3
3J1¢,2¢ = 6.4 Hz, JNH,1¢ = 12.2 Hz, 1 H, CHNH), 4.16 (q, 3J5¢,6¢ = 7.1
Hz, 2 H, OCH2CH3), 4.09 (dd, 2J6a,6b = 11.2 Hz, 3J5,6b = 6.8 Hz, 1 H,
3
6b-H), 3.98 (dd, 2J6a,6b = 11.2 Hz, J5,6a = 6.8 Hz, 1 H, 6a-H), 3.77
Ethyl (5S,2E)-5-[(2,3,4,6-Tetra-O-pivaloyl-b-D-galactopyrano-
syl)amino]-5-(4-methoxyphenyl)pent-2-enoate (5h)
Yield: 145 mg (97%); white solid; mp 66–68 °C.
(dd, 3J1,2 = 8.5 Hz, 1 H, 1-H), 3.67 (t, 3J6a,6b,5 = 6.8 Hz, 1 H, 5-H),
2.49 (t, 3J2¢,1¢ = 6.4 Hz, 2 H, CH2CH=CH), 2.13 (d, 3JNH,1¢ = 12.2 Hz,
1 H, NH), 1.25–1.28 [m, 12 H, C(CH3)3, OCH2CH3], 1.17–1.19 [m,
18 H, 2 C(CH3)3], 1.09 [s, 9 H, C(CH3)3].
1H NMR (400 MHz, CDCl3): d = 7.16 (d, J = 8.6 Hz, 2 Harom), 6.84
(d, J = 8.6 Hz, 2 Harom), 6.76 (dt, 3J3¢,4¢ = 15.6 Hz, 3J2¢,3¢ = 7.7 Hz, 1
3
13C NMR (101 MHz, CDCl3): d = 176.79, 176.57, 176.01, 175.81,
164.94 (C=O), 142.59, 139.17, 130.66, 128.30, 123.32, 120.53
(Arom-C6H4, CH=CH), 85.20, 70.74, 70.25, 67.72, 66.33, 60.68,
59.24, 54.79 (C–O, C–N), 39.95, 38.05, 37.80, 37.69, 26.25, 26.22,
26.12, 26.09, 20.00, 13.22.
H, CH=CH), 5.80 (d, J3¢,4¢ = 15.6 Hz, 1 H, CH=CH), 5.33 (d,
3J3,4 = 2.3 Hz, 1 H, 4-H), 4.97–5.07 (m, 2 H, 2-H, 3-H), 4.21 (t,
3
3J1¢,2¢ = 6.6 Hz, JNH,1¢ = 12.8 Hz, 1 H, CHNH), 4.15 (q, 3J5¢,6¢ = 7.2
Hz, 2 H, OCH2CH3), 4.09 (dd, 2J6a,6b = 11.1 Hz, 3J5,6b = 7.6 Hz, 1 H,
6b-H), 3.98 (dd, 2J6a,6b = 11.1 Hz, 3J6a,5 = 7.6 Hz, 1 H, 6a-H), 3.82
(s, 3 H, OCH3), 3.77 (dd, 3J1,2 = 7.7 Hz, 1 H, 1-H), 3.66 (t, 3J5,6 = 7.6
Hz, 1 H, 5-H), 2.49 (t, 3J1¢,2¢ = 6.6 Hz, 2 H, CH2CH=CH), 2.10 (d,
3JNH,1¢ = 12.8 Hz, 1 H, NH), 1.24–1.28 [m, 12 H, C(CH3)3,
OCH2CH3], 1.19–1.20 [m, 18 H, 2 C(CH3)3], 1.09 [s, 9 H, C(CH3)3].
MS (ESI): m/z = 798.20 [M + H]+, 820.20 [M + Na]+.
HRMS (ESI): m/z calcd for C39H58BrNO11 + Na+: 818.3085 [M +
Na]+; found: 818.3084.
13C NMR (101 MHz, CDCl3): d = 177.87, 177.63, 177.08, 176.89,
166.17 (C=O), 159.10, 144.51, 132.72, 128.71, 123.84, 113.85 (Ar-
C6H4, CH=CH), 86.13, 71.60, 71.29, 68.65, 67.40, 61.74, 60.18,
55.69, 55.21 (C–O, C–N), 41.19, 39.04, 38.78, 38.76, 38.69, 27.24,
27.21, 27.12, 27.07, 14.21.
Ethyl (5S,2E)-5-[(2,3,4,6-Tetra-O-pivaloyl-b-D-galactopyrano-
syl)amino]-5-(4-trifluoromethylphenyl)pent-2-enoate (5f)
Yield: 128 mg (81%); white solid; mp 69–70 °C.
1H NMR (400 MHz, CDCl3): d = 7.58 (d, J = 8.1 Hz, 2 Harom), 7.38
(d, J = 8.1 Hz, 2 Harom), 6.74 (dt, 3J3¢,4¢ = 15.3 Hz, 3J2¢,3¢ = 7.4 Hz, 1
MS (ESI): m/z = 748.27 [M + H]+, 770.40 [M + Na]+.
3
H, CH=CH), 5.81 (d, J3¢,4¢ = 15.3 Hz, 1 H, CH=CH), 5.34 (d,
HRMS (ESI): m/z calcd for C40H61NO12 + Na+: 770.4086 [M +
3J3,4 = 2.9 Hz, 1 H, 4-H), 5.00–5.10 (m, 2 H, 2-H, 3-H), 4.36 (t,
Na]+; found: 770.4083.
3
3J1¢,2¢ = 6.6 Hz, JNH,1¢ = 12.7 Hz, 1 H, CHNH), 4.16 (q, 3J5¢,6¢ = 7.1
Hz, 2 H, OCH2CH3), 4.10 (dd, 2J6a,6b = 11.1 Hz, 3J5,6b = 6.8 Hz, 1 H,
3
6b-H), 3.98 (dd, 2J6a,6b = 11.1 Hz, J5,6a = 6.8 Hz, 1 H, 6a-H), 3.78
Ethyl (5S,2E)-5-[(2,3,4,6-Tetra-O-pivaloyl-b-D-galactopyrano-
syl)amino]-5-(2-chlorophenyl)pent-2-enoate (5i)
Yield: 146 mg (97%); white solid; mp 60–62 °C.
(dd, 3J1,2 = 8.5 Hz, 1 H, 1-H), 3.68 (t, 3J5,6 = 6.8 Hz, 1 H, 5-H), 2.53
(t, 3J1¢,2¢ = 6.6 Hz, 2 H, CH2CH=CH), 2.18 (d, 3JNH,1¢ = 12.7 Hz, 1 H,
NH), 1.25–1.28 [m, 12 H, C(CH3)3, OCH2CH3], 1.19–1.20 [m, 18
H, 2 C(CH3)3], 1.09 [s, 9 H, C(CH3)3].
1H NMR (400 MHz, CDCl3): d = 7.46–7.48 (m, 1 Harom), 7.33-7.36
3
(m, 1 Harom), 7.20–7.22 (m, 2 Harom), 6.81 (dt, J3¢,4¢ = 15.5 Hz,
3J2¢,3¢ = 7.5 Hz, 1 H, CH=CH), 5.86 (d, 3J3¢,4¢ = 15.5 Hz, 1 H,
CH=CH), 5.35 (d, 3J3,4 = 1.9 Hz, 1 H, 4-H), 5.03–5.10 (m, 2 H, 2-
H, 3-H), 4.85 (t, 3J1¢,2¢ = 6.5 Hz, 3JNH,1¢ = 11.9 Hz, 1 H, CHNH), 4.16
13C NMR (101 MHz, CDCl3): d = 176.84, 176.64, 176.06, 175.84,
164.95 (C=O), 144.35, 142.29, 129.05 (2JC,F = 32.3 Hz), 126.87,
124.50 (4JC,F = 3.6 Hz), 124.38, 121.67 (1JC,F = 272.1 Hz), 123.47
(Arom-C6H4, CH=CH), 85.22, 70.72, 70.16, 67.68, 66.23, 60.59,
59.32, 54.92 (C–O, C–N), 39.94, 38.05, 37.82, 37.70, 28.68, 26.23,
26.20, 26.09, 26.07, 13.19.
3
2
(q, J5¢,6¢ = 7.1 Hz, 2 H, OCH2CH3), 4.09 (dd, J6a,6b = 11.1 Hz,
3J5,6b = 6.9 Hz, 1 H, 6b-H), 4.01 (dd, 2J6a,6b = 11.1 Hz, 3J5,6a = 6.9 Hz,
1 H, 6a-H), 3.86 (dd, 3J1,2 = 8.9 Hz, 1 H, 1-H), 3.77 (t, 3J5,6 = 6.9 Hz,
3
1 H, 5-H), 2.55 (t, J1¢,2¢ = 6.5 Hz, 2 H, CH2CH=CH), 2.11 (d,
MS (ESI): m/z = 786.13 [M + H]+, 808.27 [M + Na]+.
3JNH,1¢ = 11.9 Hz, 1 H, NH), 1.26–1.28 [m, 12 H, C(CH3)3,
OCH2CH3], 1.19 [s, 9 H, C(CH3)3], 1.17 [s, 9 H, C(CH3)3], 1.10 [s,
9 H, C(CH3)3].
HRMS (ESI): m/z calcd for C40H58F3NO11 + Na+: 808.3854 [M +
Na]+; found: 808.3845.
13C NMR (101 MHz, CDCl3): d = 176.90, 176.59, 176.13, 175.84,
165.02 (C=O), 142.88, 137.91, 132.57, 128.70, 127.50, 127.46,
125.78, 123.13 (Ar-C6H4, CH=CH), 85.73, 70.69, 70.35, 67.85,
66.28, 60.55, 59.19, 50.96 (C–O, C–N), 38.32, 38.05, 37.81, 37.70,
37.67, 26.24, 26.20, 26.15, 26.09, 13.22.
Ethyl (5S,2E)-5-[(2,3,4,6-Tetra-O-pivaloyl-b-D-galactopyrano-
syl)amino]-5-(4-methylphenyl)pent-2-enoate (5g)
Yield: 117 mg (80%); white solid; mp 69–71 °C.
1H NMR (400 MHz, CDCl3): d = 7.13–7.16 (m, 4 Harom), 6.77 (dt,
3J3¢,4¢ = 15.5 Hz, 3J2¢,3¢ = 7.7 Hz, 1 H, CH=CH), 5.83 (d, 3J3¢,4¢ = 15.5
MS (ESI): m/z = 752.13 [M + H]+, 774.33 [M + Na]+.
Hz, 1 H, CH=CH), 5.32 (d, 3J3,4 = 3.0 Hz, 1 H, 4-H), 5.05 (t, 3J2,3
=
HRMS (ESI): m/z calcd for C39H58ClNO11 + Na+: 774.3591 [M +
10.3 Hz, 1 H, 2-H), 5.01 (dd, 3J2,3 = 10.3 Hz, 3J3,4 = 3.0 Hz, 1 H, 3-
H), 4.23 (t, 3J1¢,2¢ = 6.5 Hz, 1 H, CHNH), 4.15 (q, 3J5¢,6¢ = 7.1 Hz, 2
Na]+; found: 774.3588.
3
H, OCH2CH3), 4.08 (dd, 2J6a,6b = 11.3 Hz, J5,6b = 6.9 Hz, 1 H, 6b-
H), 3.99 (dd, 2J6a,6b = 11.3 Hz, 3J5,6a = 6.9 Hz, 1 H, 6a-H), 3.79 (dd,
3J1,2 = 8.4 Hz, 3JNH,1 = 12.3 Hz, 1 H, 1-H), 3.65 (t, 3J5,6 = 6.9 Hz, 1
Ethyl (5S,2E)-5-[(2,3,4,6-Tetra-O-pivaloyl-b-D-galactopyrano-
syl)amino]-5-(2-bromophenyl)pent-2-enoate (5j)
Yield: 153 mg (96%); white solid; mp 72–74 °C.
1H NMR (400 MHz, CDCl3): d = 7.54 (d, J = 7.9 Hz, 1 Harom), 7.46
(d, J = 7.9 Hz, 1 Harom), 7.25–7.28 (m, 1 Harom), 7.11–7.15 (m, 1
3
H, 5-H), 2.50 (t, J1¢,2¢ = 6.5 Hz, 2 H, CH2CH=CH), 2.35 (s, 3 H,
3
ArCH3), 2.09 (d, JNH,1 = 12.3 Hz, 1 H, NH), 1.24–1.29 [m, 12 H,
Synthesis 2012, 44, 111–119
© Thieme Stuttgart · New York

PAPER
Carbohydrate Chiral Auxiliary
117
Harom), 6.83 (dt, 3J3¢,4¢ = 15.2 Hz, 3J2¢,3¢ = 7.6 Hz, 1 H, CH=CH), 5.87
(d, 3J3¢,4¢ = 15.2 Hz, 1 H, CH=CH), 5.36 (d, 3J3,4 = 1.7 Hz, 1 H, 4-H),
5.05 (m, 2 H, 2-H, 3-H), 4.81 (t, 3J1¢,2¢ = 5.5 Hz, 3JNH,1¢ = 12.5 Hz, 1
HRMS (ESI): m/z calcd for C39H58FNO11 + Na+: 758.3886 [M +
Na]+; found: 758.3886.
3
H, CHNH), 4.16 (q, J5¢,6¢ = 7.1 Hz, 2 H, OCH2CH3), 4.11 (dd,
Ethyl (5S,2E)-5-[(2,3,4,6-Tetra-O-pivaloyl-b-D-galactopyrano-
syl)amino]-5-(3-chlorophenyl)pent-2-enoate (5m)
Yield: 132 mg (88%); white solid; mp 65–67 °C.
3
2J6a,6b = 11.1 Hz, J5,6b = 7.3 Hz, 1 H, 6b-H), 4.01 (d, 2J6a,6b = 11.1
Hz, 3J5,6a = 7.3 Hz, 1 H, 6a-H), 3.85 (dd, 3J1,2 = 8.1 Hz, 1 H, 1-H),
3
3
3.78 (t, J5,6 = 7.3 Hz, 1 H, 5-H), 2.54 (t, J1¢,2¢ = 5.5 Hz, 2 H,
CH2CH=CH), 2.12 (d, 3JNH,1¢ = 12.5 Hz, 1 H, NH), 1.26–1.29 [m, 12
H, C(CH3)3, OCH2CH3], 1.17–1.18 [m, 18 H, 2 C(CH3)3], 1.10 [s, 9
H, C(CH3)3].
1H NMR (400 MHz, CDCl3): d = 7.09–7.28 (m, 4 Harom), 6.75 (dt,
3J2¢,3¢ = 7.4 Hz, 3J3¢,4¢ = 15.4 Hz, 1 H, CH=CH), 5.81 (d, 3J3¢,4¢ = 15.4
Hz, 1 H, CH=CH), 5.34 (d, 3J3,4 = 2.7 Hz, 1 H, 4-H), 5.01–5.09 (m,
3
2 H, 2-H, 3-H), 4.26 (t, J1¢,2¢ = 6.3 Hz, 1 H, CHNH), 4.16 (q,
13C NMR (101 MHz, CDCl3): d = 176.85, 176.56, 176.10, 175.79,
164.69 (C=O), 142.83, 139.48, 131.99, 127.91, 127.74, 126.41,
123.16, 122.97 (Ar-C6H4, CH=CH), 85.69, 70.61, 70.35, 67.85,
66.20, 60.41, 59.18, 53.48 (C–O, C–N), 52.43, 38.46, 38.04, 37.80,
37.70, 26.25, 26.20, 26.12, 26.09, 13.23.
3J5¢,6¢ = 7.1 Hz, 2 H, OCH2CH3), 4.09 (dd, 2J6a,6b = 11.3 Hz, 3J5,6b
=
6.8 Hz, 1 H, 6b-H), 3.99 (dd, 2J6a,6b = 11.3 Hz, 3J5,6a = 6.8 Hz, 1 H,
6a-H), 3.81 (dd, 3J1,2 = 7.7 Hz, 3J1,NH = 12.0 Hz, 1 H, 1-H), 3.70 (t,
3J5,6 = 6.8 Hz, 1 H, 5-H), 2.50 (t, 3J2¢,3¢ = 7.4 Hz, 2 H, CH2CH=CH),
2.13 (d, 3J1,NH = 12.0 Hz, 1 H, NH), 1.25–1.27 [m, 12 H, C(CH3)3,
OCH2CH3], 1.21 [s, 9 H, C(CH3)3], 1.19 [s, 9 H, C(CH3)3], 1.09 [s,
9 H, C(CH3)3].
MS (ESI): m/z = 798.07 [M + H]+, 820.20 [M + Na]+.
HRMS (ESI): m/z calcd for C39H58BrNO11 + Na+: 818.3085 [M +
13C NMR (101 MHz, CDCl3): d = 176.84, 176.67, 176.06, 175.84,
164.97 (C=O), 142.57, 142.45, 133.60, 128.74, 126.98, 126.35,
124.94, 123.31 (Ar-C6H4, CH=CH), 85.17, 70.74, 70.25, 67.63,
66.31, 60.70, 59.26, 54.83 (C–O, C–N), 40.01, 38.78, 38.04, 37.82,
37.69, 26.28, 26.20, 26.11, 26.07, 13.20.
Na]+; found: 818.3082.
Ethyl (5S,2E)-5-[(2,3,4,6-Tetra-O-pivaloyl-b-D-galactopyrano-
syl)amino]-5-(2-methylphenyl)pent-2-enoate (5k)
Yield: 136 mg (93%); white solid; mp 61–62 °C.
MS (ESI): m/z = 774.33 [M + Na]+.
1H NMR (400 MHz, CDCl3): d = 7.39–7.42 (m, 1 Harom), 7.16–7.20
(m, 3 Harom), 6.81 (dt, 3J2¢,3¢ = 8.0 Hz, 3J3¢,4¢ = 15.4 Hz, 1 H,
CH=CH), 5.86 (d, 3J3¢,4¢ = 15.4 Hz, 1 H, CH=CH), 5.38 (d, J = 1.9
Hz, 1 H, 4-H), 4.99–5.11 (m, 2 H, 2-H, 3-H), 4.61 (t, 3J1¢,2¢ = 6.6 Hz,
HRMS (ESI): m/z calcd for C39H58ClNO11 + Na+: 774.3591 [M +
Na]+; found: 774.3584.
3
1 H, CHNH), 4.18 (q, J5¢,6¢ = 7.2 Hz, 2 H, OCH2CH3), 4.09 (dd,
Ethyl (5S,2E)-5-[(2,3,4,6-tetra-O-pivaloyl-b-d-galactopyrano-
syl)amino]-5-(3-methylphenyl)pent-2-enoate (5n)
Yield: 116 mg (79%); white solid; mp 60–61 °C.
3J5,6b = 7.0 Hz, 2J6a,6b = 11.2 Hz, 1 H, 6b-H), 4.01 (dd, 3J5,6a = 7.0 Hz,
2J6a,6b = 11.2 Hz, 1 H, 6a-H), 3.80 (t, 3J1,2 = 4.1 Hz, 1 H, 1-H), 3.71
(t, 3J5,6 = 6.6 Hz, 1 H, 5-H), 2.50 (t, 3J2¢,3¢ = 8.0 Hz, 3J1¢,2¢ = 6.6 Hz, 2
H, CH2CH=CH), 2.33 (s, 3 H, OCH3), 1.26–1.29 [m, 12 H,
C(CH3)3], 1.22 [s, 9 H, C(CH3)3], 1.18 [s, 9 H, C(CH3)3], 1.11 [s, 9
H, C(CH3)3].
1H NMR (400 MHz, CDCl3): d = 7.19–7.21 (m, 1 Harom), 7.03–7.10
3
(m, 3 Harom), 6.77 (dt, 3J2¢,3¢ = 14.2 Hz, J3¢,4¢ = 15.4 Hz, 1 H,
CH=CH), 5.81 (d, 3J3¢,4¢ = 15.4 Hz, 1 H, CH=CH), 5.33 (d, 3J3,4 = 2.9
Hz, 1 H, 4-H), 5.06 (t, 3J2,3 = 10.2 Hz, 1 H, 2-H), 5.01 (dd, 3J3,4 = 2.9
Hz, 3J2,3 = 10.2 Hz, 1 H, 3-H), 4.23 (t, 3J1¢,2¢ = 6.9 Hz, 1 H, CHNH),
4.15 (q, 3J5¢,6¢ = 7.1 Hz, 2 H, OCH2CH3), 4.09 (dd, 3J5,6b = 7.0 Hz,
2J6a,6b = 11.2 Hz, 1 H, 6b-H), 3.99 (dd, 3J5,6a = 7.0 Hz, 2J6a,6b = 11.2
Hz, 1 H, 6a-H), 3.82 (d, 3J1,2 = 8.4 Hz, 1 H, 1-H), 3.67 (t, 3J5,6 = 7.0
13C NMR (101 MHz, CDCl3): d = 175.49, 175.25, 174.71, 174.43,
163.73 (C=O), 142.04, 136.74, 133.61, 128.07, 124.81, 124.46,
123.80, 121.55 (Ar-C6H4, CH=CH), 84.13, 69.11, 68.98, 66.44,
64.90, 59.13, 57.80, 48.83 (C–O, C–N), 38.03, 36.69, 36.46, 36.33,
36.31, 24.91, 24.86, 24.81, 24.72, 16.92, 11.85.
3
3
Hz, 1 H, 5-H), 2.50 (dd, J1¢,2¢ = 6.9 Hz, J2¢,3¢ = 14.2 Hz, 2 H,
CH2CH=CH), 2.33 (s, 3 H, ArCH3), 2.10 (s, 1 H, NH), 1.26–1.28
[m, 12 H, OCH2CH3, C(CH3)3], 1.21 [s, 9 H, C(CH3)3], 1.19 [s, 9 H,
C(CH3)3], 1.09 [s, 9 H, C(CH3)3].
MS (ESI): m/z = 732.13 [M + H]+, 754.33 [M + Na]+.
HRMS (ESI): m/z calcd for C40H61NO11 + Na+: 754.4137 [M +
Na]+; found: 754.4136.
13C NMR (101 MHz, CDCl3): d = 176.88, 176.62, 176.10, 175.90,
165.16 (C=O), 143.48, 139.96, 137.03, 127.50, 127.29, 127.06,
123.86, 122.84 (Ar-C6H4, CH=CH), 85.22, 70.62, 70.29, 67.68,
66.42, 60.78, 59.17, 55.22 (C–O, C–N), 40.21, 38.04, 37.79, 37.69,
28.64, 26.25, 26.21, 26.12, 26.07, 20.39, 13.21.
Ethyl (5S,2E)-5-[(2,3,4,6-Tetra-O-pivaloyl-b-D-galactopyrano-
syl)amino]-5-(3-fluorophenyl)pent-2-enoate (5l)
Yield: 130 mg (88%); light yellow solid; mp 60–61 °C.
1H NMR (400 MHz, CDCl3): d = 7.28–7.30 (m, 1 Harom), 7.00–7.02
(m, 3 Harom), 6.75 (dt, 3J3¢,4¢ = 15.4 Hz,3J2¢,3¢ = 7.9 Hz, 1 H, CH=CH),
5.81 (d, 3J3¢,4¢ = 15.4 Hz, 1 H, CH=CH), 5.34 (d, 3J3,4 = 2.3 Hz, 1 H,
MS (ESI): m/z = 732.27 [M + H]+, 754.33 [M + Na]+.
HRMS (ESI): m/z calcd for C40H61NO11 + Na+: 754.4137 [M +
4-H), 5.00–5.09 (m, 2 H, 2-H, 3-H), 4.28 (t, 3J1¢,2¢ = 6.5 Hz, 3JNH,1¢
=
Na]+; found: 754.4149.
12.9 Hz, 1 H, CHNH), 4.16 (q, 3J5¢,6¢ = 7.1 Hz, 2 H, OCH2CH3), 4.09
2
(dd, 2J6a,6b = 11.2 Hz, 3J5,6b = 6.8 Hz, 1 H, 6b-H), 3.99 (d, J6a,6b
=
Ethyl (5S,2E)-5-[(2,3,4,6-Tetra-O-pivaloyl-b-D-galactopyrano-
syl)amino]-5-(furan-2-yl)pent-2-enoate (5o)
Yield: 92 mg (65%); yellow solid; mp 58–59 °C.
11.2 Hz, 3J6a,5 = 6.8 Hz, 1 H, 6a-H), 3.82 (dd, 3J1,2 = 8.2 Hz, 1 H, 1-
3
3
H), 3.69 (t, J5,6 = 6.8 Hz, 1 H, 5-H), 2.51 (t, J1¢,2¢ = 6.5 Hz, 2 H,
CH2CH=CH), 2.13 (d, 3JNH,1¢ = 12.9 Hz, 1 H, NH), 1.25–1.27 [m, 12
H, C(CH3)3, OCH2CH3], 1.21 [s, 9 H, C(CH3)3], 1.19 [s, 9 H,
C(CH3)3], 1.09 [s, 9 H, C(CH3)3].
1H NMR (400 MHz, CDCl3): d = 7.31 (d, 3J = 1.5 Hz, 1 H, H-furan),
6.83 (dt, 3J2¢,3¢ = 8.2 Hz, 3J3¢,4¢ = 15.6 Hz, 1 H, CH=CH), 6.26–6.33
3
(m, 1 H, H-furan), 6.15 (t, J = 1.5 Hz, 1 H, H-furan), 5.84 (d,
13C NMR (101 MHz, CDCl3): d = 176.87, 176.69, 176.09, 175.86,
165.01 (C=O), 162.06 (1JC,F = 246.2 Hz), 142.97 (3JC,F = 6.5 Hz),
142.66, 128.98 (3JC,F = 8.1 Hz), 123.24, 122.32 (4JC,F = 3.4 Hz),
113.72 (2JC,F = 21.3 Hz), 113.18 (2JC,F = 21.7 Hz), 85.22, 70.72,
70.24, 67.64, 66.30, 60.68, 59.27, 54.85 (C–O, C–N), 40.01, 38.04,
37.89, 37.69, 26.23, 26.20, 26.10, 26.70, 21.65, 13.19.
3J3¢,4¢ = 15.6 Hz, 1 H, CH=CH), 5.39 (d, J3,4 = 2.9 Hz, 1 H, 4-H),
3
5.27–5.28 (m, 1 H, 2-H), 4.98–5.09 (m, 1 H, 3-H), 4.56–4.66 (m, 1
H, CHNH), 4.13–4.20 (m, 3 H, OCH2CH3, NH), 4.08 (d,
2
2J6a,6b = 6.6 Hz, 1 H, 6b-H), 3.99 (d, J6a,6b = 6.6 Hz, 1 H, 6a-H),
3.91 (d, 3J1,2 = 3.8 Hz, 1 H, 1-H), 3.83 (s, 1 H, 5-H), 2.58–2.76 (m,
2 H, CH2CH=CH), 1.26–1.28 (m, 3 H, OCH2CH3), 1.25 [s, 9 H,
C(CH3)3], 1.21 [s, 9 H, C(CH3)3], 1.16 [s, 9 H, C(CH3)3], 1.11 [s, 9
H, C(CH3)3].
MS (ESI): m/z = 736.00 [M + H]+, 758.33 [M + Na]+.
© Thieme Stuttgart · New York
Synthesis 2012, 44, 111–119

118
B. Cui et al.
PAPER
13C NMR (101 MHz, CDCl3): d = 176.86, 176.66, 176.31, 176.17,
175.95, 175.84, 175.60, 165.05, 164.98 (C = O), 154.26, 152.46,
143.48, 143.32, 141.06, 140.63, 123.05, 122.87, 122.83, 109.13,
106.96,105.40 (CH=CH), 86.45, 80.84, 70.58, 70.36, 67.64, 67.18,
67.10, 66.63, 66.14, 65.05, 61.04, 60.30, 59.20, 51.09, 50.10, 38.05,
37.72, 36.55, 35.89, 26.19, 26.15, 26.09, 26.00, 13.23.
with EtOAc (3 × 5 mL) and the combined organic phases were
washed with sat. aq NaHCO3 (3 × 5 mL), dried (MgSO4), filtered,
and concentrated in vacuo to yield the crude product 8g. The residue
was purified by column chromatography on silica gel (EtOAc–
MeOH, 30:1, with 0.1% Et3N] to afford 8g (70 mg, 93%) as a white
solid; mp 115–117 °C; [a]D25 –59.6 (c = 1.0, CHCl3).
MS (ESI): m/z = 708.3 [M + H]+, 730.4 [M + Na]+.
1H NMR (400 MHz, CDCl3): d = 7.10 (s, 4 Harom), 5.78 (s, 1 H, NH),
5.13 (dd, 3JH,H = 4.3 Hz, 3JH,H = 9.0 Hz, 1 H, CHNH), 2.45–2.49 (m,
1 H, COCH2), 2.35 (s, 3 H, ArCH3), 2.05–2.14 (m, 1 H, COCH2),
1.67–1.92 (m, 4 H, 2 CH2).
HRMS (ESI): m/z calcd for C37H57NO12 + Na+: 730.3773 [M +
Na]+; found: 730.3765.
Ethyl (5S,2E,6E)-5-[(2,3,4,6-Tetra-O-pivaloyl-b-D-galactopyra-
nosyl)amino]-7-phenylhepta-2,6-dienoate (5p)
13C NMR (101 MHz, CDCl3): d = 171.38, 138.56, 136.66, 128.45,
124.98, 56.49, 31.18, 30.25, 20.04, 18.67.
Yield: 111.5 mg (75%); yellow solid; mp 62–63 °C.
MS (ESI): m/z = 190.0 [M + H]+, 212.0 [M + Na]+.
1H NMR (400 MHz, CDCl3): d = 7.33–7.35 (m, 5 H, C6H5), 6.89
(dt, 3J2¢,3¢ = 6.9 Hz, 3J3¢,4¢ = 15.5 Hz, 1 H, CH=CH), 6.50 (d, J = 15.9
Hz, 1 H, PhCH=CH), 5.88 (d, 3J3¢,4¢ = 15.5 Hz, 1 H, CH=CH), 5.84
(t, J = 15.9 Hz, 1 H, PhCH=CH), 5.39 (d, 3J3,4 = 2.5 Hz, 1 H, 4-H),
5.03–5.14 (m, 2 H, 2-H, 3-H), 4.16–4.20 (m, 3 H, CHNH,
OCH2CH3), 4.10–4.15 (m, 2 H, 6a-H, 6b-H), 4.00–4.03 (m, 1 H, 1-
H), 3.86–3.98 (m, 1 H, 5-H), 2.43 (t, 3J2¢,3¢ = 6.9 Hz, 2 H,
CH2CH=CH), 1.90 (d, 3JNH,1¢ = 12.4 Hz, 1 H, NH), 1.24–1.29 [m, 12
HRMS (ESI): m/z calcd for C12H15NO + Na+: 212.1046 [M + Na]+;
found: 212.1052.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.
H, OCH2CH3, C(CH3)3], 1.21 [s, 9 H, C(CH3)3], 1.19 [s, 9 H, Acknowledgment
C(CH3)3], 1.09 [s, 9 H, C(CH3)3].
We thank the National Natural Science Foundation of China
13C NMR (101 MHz, CDCl3): d = 177.84, 177.58, 177.06, 176.88,
166.10 (C=O), 144.10, 136.41, 132.58, 130.12, 128.65, 127.82,
126.36, 124.14 (Ar-C6H4, CH=CH), 86.86, 71.73, 71.28, 68.63,
67.38, 61.71, 60.33, 60.20, 55.18 (C–O, C–N), 39.35, 39.05, 38.74,
38.72, 38.70, 27.21, 27.14, 27.07, 14.23.
(21072102), the Committee of Science and Technology of Tianjin
(11JCYBJC04200), and the State Key Laboratory of Elemento-
Organic Chemistry in Nankai University for financial support.
References
MS (ESI): m/z = 744.2 [M + H]+, 766.4 [M + Na]+.
HRMS (ESI): m/z calcd for C41H61NO11 + Na+: 766.4137 [M +
(1) Reviews: (a) Arend, M.; Westermann, B.; Risch, N. Angew.
Chem. Int. Ed. 1998, 37, 1044. (b) Denmark, S. E.; Nicaise,
O. J.-C. In Comprehensive Asymmetric Catalysis; Jacobsen,
E. N.; Pfaltz, A.; Yamamoto, H., Eds.; Springer: Berlin,
1999, 923. (c) Arend, M. Angew. Chem. Int. Ed. 1999, 38,
2873. (d) Kobayashi, S.; Ishitani, H. Chem. Rev. 1999, 99,
1069. (e) Córdova, A. Acc. Chem. Res. 2004, 37, 102.
(f) Ting, A.; Schaus, S. E. Eur. J. Org. Chem. 2007, 5797.
(2) For reviews on vinylogous Mannich-type reactions,
including synthetic applications, that occur with complete
g-site regiocontrol and high asymmetry, see: (a) Bur, S. K.;
Martin, S. F. Tetrahedron 2001, 57, 3221. (b) Martin, S. F.
Acc. Chem. Res. 2002, 35, 895.
Na]+; found: 766.4134.
(5S,2E)-5-[(2,3,4,6-Tetra-O-pivaloyl-b-D-galactopyrano-
syl)amino]-5-(3-chlorophenyl)but-2-enal (5q)
Yield: 139 mg (98%); light yellow solid; mp 56–58 °C.
3
1H NMR (400 MHz, CDCl3): d = 9.46 (d, J4¢,5¢, = 7.7 Hz, 1 H,
3
CHO), 7.13–7.32 (m, 4 Harom), 6.62 (dt, J3¢,4¢ = 15.7 Hz, 1 H,
3
3
CH=CHCHO), 6.12 (dd, J3¢,4¢ = 15.7 Hz, J4¢,5¢ = 7.7 Hz, 1 H,
CH=CHCHO), 5.38 (d, 3J3,4 = 3.0 Hz, 1 H, 4-H), 5.06–5.10 (m, 2 H,
2-H, 3-H), 4.34 (t, 3J1¢,2¢ = 6.3 Hz, 1 H, CHNH), 4.14 (dd, 3J5,6b = 6.7
2
3
Hz, J6a,6b = 11.1 Hz, 1 H, 6b-H), 4.02 (dd, J5,6a = 6.7 Hz,
2J6a,6b = 11.1 Hz, 1 H, 6a-H), 3.86 (dd, 3J1,2 = 8.7 Hz, 1 H, 1-H), 3.75
(3) (a) Weintraub, P. M.; Sabol, J. S.; Kane, J. M.; Borcherding,
D. R. Tetrahedron 2003, 59, 2953. (b) Cook, G. R.; Beholz,
L. G.; Stille, J. R. J. Org. Chem. 1994, 59, 3575.
(t, J5,6 = 6.7 Hz, 1 H, 5-H), 2.68 (t, 3J4¢,5¢ = 6.3 Hz, 2 H,
3
3
CH2CH=CH), 2.19 (d, JNH,1¢ = 12.4 Hz, 1 H, NH), 1.30 [s, 9 H,
C(CH3)3], 1.23–1.24 [m, 18 H, 2 C(CH3)3], 1.13 [s, 9 H, C(CH3)3].
(c) Meyers, A. I.; Shawe, T. T.; Gottlieb, L. Tetrahedron
Lett. 1992, 33, 867.
13C NMR (101 MHz, CDCl3): d = 193.29 (CHO), 177.88, 177.77,
177.11, 176.85 (C=O), 152.45, 142.95, 135.34, 134.79, 129.88,
128.25, 127.34, 125.88 (Ar-C6H4, CH=CH), 86.13, 71.83, 71.17,
68.65, 67.29, 61.69, 55.87 (C–O, C–N), 41.42, 41.27, 39.06, 38.86,
38.72, 27.29, 27.20, 27.13, 27.08.
(4) Laycock, G. M.; Shulman, A. Nature 1963, 200, 849.
(5) Meyers, C. Y.; Miller, L. E. Org. Synth. 1963, 32, 13.
(6) For selected catalytic asymmetric vinylogous Mannich
reactions of cyclic siloxyfurans, see: (a) Carswell, E. L.;
Snapper, M. L.; Hoveyda, A. H. Angew. Chem. Int. Ed.
2006, 45, 7230. (b) Wieland, L. C.; Vieira, E. M.; Snapper,
M. L.; Hoveyda, A. H. J. Am. Chem. Soc. 2009, 131, 570.
(c) Mandai, H.; Mandai, K.; Snapper, M. L.; Hoveyda, A. H.
J. Am. Chem. Soc. 2008, 130, 17961. (d) Yuan, Z. L.; Jiang,
J. J.; Shi, M. Tetrahedron 2009, 65, 6001. (e) Deng, H. P.;
Wei, Y.; Shi, M. Adv. Synth. Catal. 2009, 351, 2897.
(f) Akiyama, T.; Honma, Y.; Itoh, J.; Fuchibe, K. Adv. Synth.
Catal. 2008, 350, 399. (g) Zhao, Q. Y.; Yuan, Z. L.; Shi, M.
Adv. Synth. Catal. 2011, 353, 637. (h) Zhao, Q. Y.; Shi, M.
Tetrahedron 2011, 67, 3724. (i) Ruan, S. T.; Luo, J. M.; Du,
Y.; Huang, P. Q. Org. Lett. 2011, 13, 4938.
MS (ESI): m/z = 708.1 [M + H]+, 730.4 [M + Na]+.
(6S)-6-(4-Methylphenyl)piperidin-2-one (8g)
A solution of 5g (295 mg, 0.4 mmol) in anhyd MeOH (5 mL) was
reduced with H2 on Pd/C (5%). The reaction mixture was stirred for
4 h [TLC monitoring, eluent: petroleum ether (bp 60–90 °C)–
EtOAc, 15:1 (v/v)] at r.t. The mixture was filtered and concentrated
in vacuo to yield the crude product 6g. Then a solution of 6g in an-
hyd MeOH (5 mL) was treated with freshly prepared (0.5 M) solu-
tion of NaOMe in MeOH (5 mL). The mixture was stirred at r.t. for
4 h [TLC monitoring, eluent: EtOAc–MeOH, 30:1 (v/v)]. Then a
few drops of H2O were added to the mixture, neutralized with
AcOH, and stirred at r.t. for another 4 h. The mixture was extracted
Synthesis 2012, 44, 111–119
© Thieme Stuttgart · New York

PAPER
(7) (a) For reviews on vinylogous Mannich reactions, see:
Carbohydrate Chiral Auxiliary
119
(14) (a) Vasella, A. Helv. Chim. Acta 1977, 60, 1273. (b) Kunz,
H.; Müller, B.; Schanzenbach, D. Angew. Chem., Int. Ed.
Engl. 1987, 26, 267. (c) Boysen, M. M. K. Chem. Eur. J.
2007, 13, 8648.
(15) (a) Laschat, S.; Kunz, H. Synthesis 1992, 90. (b) Wang, Y.
D.; Wang, Y. Y.; Yu, J. P.; Miao, Z. W.; Chen, R. Y. Chem.
Eur. J. 2009, 15, 9290. (c) Knauer, S.; Weymann, M.; Kunz,
H. Z. Naturforsch., B: J. Chem. Sci. 2009, 64, 1639.
(d) Kunz, H.; Burgard, A.; Schanzenbach, D. Angew. Chem.,
Int. Ed. Engl. 1997, 36, 386. (e) Deloisy, S.; Kunz, H.
Tetrahedron Lett. 1998, 39, 791. (f) Zhou, G. B.; Zhang, P.
F.; Pan, Y. J. Tetrahedron 2005, 61, 5671.
Casiraghi, G.; Battistini, L.; Curti, C.; Rassu, G.; Zanardi, F.
Chem. Rev. 2011, 111, 3076. (b) Zhang, Q.; Hui, Y. H.;
Zhou, X.; Lin, L. L.; Liu, X. H.; Feng, X. M. Adv. Synth.
Catal. 2010, 352, 976. (c) Yang, Y.; Phillips, D. P.; Pan, S.
F. Tetrahedron Lett. 2011, 52, 1549.
(8) (a) Sickert, M.; Schneider, C. Angew. Chem. Int. Ed. 2008,
47, 3631. (b) Sickert, M.; Abels, F.; Lang, M.; Sieler, J.;
Birkemeyer, C.; Schneider, C. Chem. Eur. J. 2010, 16, 2806.
(9) González, A. S.; Arrayás, R. G.; Rivero, M. R.; Carretero, J.
C. Org. Lett. 2008, 10, 4335.
(10) (a) Kawęcki, R. Tetrahedron 2001, 57, 8385. (b) Kawęcki,
R. Tetrahedron: Asymmetry 2006, 17, 1420.
(16) Yu, J. P.; Miao, Z. W.; Chen, R. Y. Org. Biomol. Chem.
(11) (a) Waldmann, H.; Braun, M.; Dräger, M. Angew. Chem.,
Int. Ed. Engl. 1990, 29, 1468. (b) Waldmann, H.; Braun,
M.; Dräger, M. Tetrahedron: Asymmetry 1991, 2, 1231.
(12) Levy, D. E.; Fügedi, P. The Organic Chemistry of Sugars;
Taylor and Francis: Boca Raton, 2006, Chap. 11-16, 490–
845.
(13) (a) Howland, J. L. Biochem. Educ. 1996, 24, 69. (b) Cai, S.;
Gorityala, B. K.; Ma, J. M.; Leow, M. L.; Liu, X. W. Org.
Lett. 2011, 13, 1072.
2011, 9, 1756.
(17) Kunz, H.; Sager, W.; Schanzenbach, D.; Decker, M. Liebigs
Ann. Chem. 1991, 649.
(18) Crystallographic data for the structural analysis of
compound 5b has been deposited at the Cambridge
Crystallographic Data Centre under No. CCDC 802525.
These data can be obtained free of charge by contacting The
Cambridge Crystallographic Data Centre, 12, Union Road,
Cambridge CB2 1EZ, UK; fax: +44(1223)336033; E-mail:
deposit@ccdc.cam.ac.uk.
© Thieme Stuttgart · New York
Synthesis 2012, 44, 111–119