Syntheses of enantio-enriched chiral building blocks from l-glutamic acid

Article abstract of DOI:10.1016/j.tet.2006.05.013

Starting from lactone-amide 8, easily derived from l-glutamic acid, enantioselective syntheses of (S)-tetrahydrofuran 2-carboxamide derivative 2 and a protected (S)-3-hydroxypiperidin-2-one (3) are reported. The building block 3 was converted to (2S,3R)-3

Full text of DOI:10.1016/j.tet.2006.05.013

Tetrahedron 62 (2006) 7459–7465
Syntheses of enantio-enriched chiral building blocks
from L-glutamic acid
*
Chen-Guo Feng, Jie Chen, Jian-Liang Ye, Yuan-Ping Ruan, Xiao Zheng and Pei-Qiang Huang
Department of Chemistry and The Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry
and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005, PR China
Received 16 March 2006; revised 8 May 2006; accepted 9 May 2006
Available online 5 June 2006
Abstract—Starting from lactone-amide 8, easily derived from L-glutamic acid, enantioselective syntheses of (S)-tetrahydrofuran 2-carbox-
amide derivative 2 and a protected (S)-3-hydroxypiperidin-2-one (3) are reported. The building block 3 was converted to (2S,3R)-3-hydroxy-
pipecolamide (6) by a three-step procedure. A solvent altered H-bonding capacity leading to a highly chemoselective tosylation of the primary
hydroxyl group in the presence of an a-hydroxy-carboxamide was observed.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
3-hydroxypipecolamide (6) is an isomer of 7, the 4-hydroxy-
pipecolamide moiety presented in a class of highly potent
HIV proteases inhibitors such as palinavir.6 Carboxamide
6 may also be useful as an organocatalyst.7
Tetrahydrofuran 2-carboxylic acid derivatives such as 11
(Fig. 1) are key structural units used in designing peptido-
mimetics. Protected 3-hydroxypiperidin-2-ones such as 3
may serve as useful building blocks,2 while substituted
piperidin-3-ols are key components found in a number of
natural products and bioactive compounds.3 For example,
cis-3-hydroxypipecolic acid4 4 constitutes a part of anti-
tumor antibiotic tetrazomine;4b (2S,3R)-55 has been served
as a key intermediate in the asymmetric synthesis5c of (ꢀ)-
swainsonine. In addition, the N-tert-butyl derivative of
In continuation of our ongoing program aimed at the devel-
opment of new multifunctional building blocks starting
from L-glutamic acid,8 we now report the enantioselective
syntheses of (S)-tetrahydrofuran 2-carboxamide 2, protected
(S)-3-hydroxypiperidin-2-one 3 and (2S,3R)-3-hydroxy-
pipecolamide (6).
2. Results and discussion
R1
O
OH
NHPMB
O
OTBS
O
NH
H
N
H
We first investigated the synthesis of tetrahydrofuran 2-carb-
oxamide (S)-2 by the route depicted in Scheme 1. Lactone-
amide8d (S)-8, easily available in multigram quantity from
L-glutamic acid in 70% yield, was chemoselectively reduced
with sodium borohydride (0 ꢁC–rt) to give diol (S)-9 in 89%
yield. For the chemoselective p-tosylation of the primary
hydroxyl group, (S)-9 was treated with p-toluenesulfonyl
chloride at low temperature (p-TsCl, py, ꢀ35 ꢁC, 2 h, then
ꢀ5 ꢁC, overnight). With pyridine as the base, formation of
the expected monotosylate 10 was observed from the TLC
analysis. However, this was unstable and cyclized to tetra-
hydrofuran carboxamide9 2 on standing as well as during
concentration of the extract. Thus, 2 was obtained in 58%
isolated yield along with starting material (30%) and the
ditosylate 12 (5%). HPLC analysis of 2 on a chiral column
revealed its ee as 92%. On the other hand, with triethylamine
as the base,9g,10 although the yield of 2 was marginally
better (62%), its ee was only 8% indicating extensive
R2
H
O
N
PMB
3
O
R
O
1
constrained
hydroxyethylene isosteres
OH
OH
OH
O
H
N
NH2
N
H
COOH
OH
N
H
N
H
t-Bu
O
4 β
-
6
7
5 α
-
OH
Figure 1.
Keywords: 3-Hydroxypipecolamide; 3-Hydroxypiperidin-2-one; Building
block; Hydrogen bond; Chemoselective reaction.
* Corresponding author. Tel.: +86 592218 0992; fax: +86 592 218 6405;
e-mail: pqhuang@xmu.edu.cn
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.05.013

7460
C.-G. Feng et al. / Tetrahedron 62 (2006) 7459–7465
H
OH
NaBH4, MeOH
HO2C
CO2H ref. 8d
O
O
CONHPMB
0 °C ~ rt
89%
H2N
CONHPMB
HO
8
L -Glu
9
OH
CONHPMB
OTs
OTs
+
+
CONHPMB
CONHPMB
TsO
TsO
HO
12
10
11
conditions 1:
Standing
p-TsCl, Py.
(S)-(–)-2, 92% ee
-35 °C ~ -5 °C
(by conditions 1)
CONHPMB
H
H
conditions 2:
O
CONHPMB
O
2, 8% ee
(by conditions 2)
p-TsCl, TEA
CH2Cl2, -35 °C ~ rt
(S)-2
(R)-2
Scheme 1.
racemization. In this case, more ditosylate 12 (12%) was
also formed, while 20% of the starting material was recov-
H
O
O
O
H
H
O
ered. These results demonstrated that, attempted selective
monotosylation of the primary hydroxyl group in diol 9
was always accompanied by tosylation of the secondary
hydroxyl group and both monotosylated isomers 10 and 11
cyclized easily to give the corresponding enantiomer (S)-2
or (R)-2.
H
O
H N
PMB
13b
N
O
H
PMB
13a
It is worth mentioning that, although partial racemization
has been observed in a diethoxytriphenylphosphorane medi-
ated regioselective cyclodehydration of (R)-1,4-pentane-
diol,11 many p-TsCl activated one-pot intramolecular
etherification of chiral 1,4-diols have been reported to pro-
ceed with complete retention of configuration at the chiral
carbinol center.11 Our observations indicated that caution
must be taken when performing a p-TsCl activated one-pot
intramolecular etherification of chiral 1,4-diols, because to-
sylation of the secondary hydroxyl group may occur, leading
to either racemic ethers or diastereomeric mixtures, in par-
ticular when using triethylamine as a base.
The easy tosylation of the secondary hydroxyl group of diol 9
may be explained by H-bonding effects as shown in 13a and
13b (Fig. 2).12 Quantum chemistry calculation showed that
13a is more stable than 13b by 2.90 kcal/mol (Fig. 2). The
higher stability of 13a and thus lower reactivity of the pri-
mary hydroxyl group toward tosylation can be attributed to
the strong hydrogen-bond formation betweenthe primary hy-
droxyl group and the carbonyl of the amide functional group
in 13a. In more polar and more basic medium, such as when
using pyridine as the solvent, formation of the intramolecular
hydrogen bonds is efficiently inhibited,13 thus the primary
hydroxyl group shows normally higher reactivity during
the tosylation. The phenomena of weakening of hydrogen
bonds by polar solvents have been noted previously.12f,13e
Figure 2. Energy-minimized structures of 13a and 13b.
compounds 8 and 14. Compounds 8 and 14 showed similar
Rf and were difficult to separate by column chromatography
on silica gel. To our delight, pure 14 could be obtained by re-
crystallization from EtOAc/Et2O. The subsequent silyl-
ation14 (TBSCl, imid., DMAP, DMF, rt, 3 h) proceeded
smoothly to give compound 15 in 92% yield. Chemoselec-
tive ester reduction15 (NaBH4, CaCl2, THF–EtOH, rt, over-
night) followed by mesylation (MsCl, NEt3) at ꢀ35 ꢁC for
15 min furnished 17 in excellent overall yield. Treatment
of 17 with NaH at rt for 21 h afforded the desired piperi-
dine-2-one 3 in 84% yield. HPLC analysis on a chiral col-
umn showed that the ee of 3 was 94% (Scheme 2).
Next, we turned our attention to the synthesis of protected 3-
hydroxypiperidin-2-one 3. We decided to protect firstly the
latent hydroxyl group in 8. Thus, stirring a methanolic
solution of 8 in the presence of a catalytic amount of concen-
trated H2SO4 at rt for 1.5 h led smoothly to the ring-opening
product 14. TLC monitoring of the reaction showed that
a small amount of the starting material remained intact
even after prolongation of the reaction time. This might
reflect that an equilibrium has been established between
To demonstrate the utility of 3 as a building block, we sought
the synthesis of 6 (Scheme 3). Thus, 3 was subjected to one-
pot reductive cyanation,16,17 which consisted in controlled
chemoselective partial reduction of the amide by LiAlH4
(3 molar equiv, THF, ꢀ50 ꢁC, 15 min) followed by addition

C.-G. Feng et al. / Tetrahedron 62 (2006) 7459–7465
7461
OH
was performed under catalytic hydrogenolytic conditions
(20% Pd(OH)2/C, H2, HCO2H (cat.), rt, 5 h, EtOH, yield:
82%), or catalytic transfer hydrogenolytic conditions (10%
Pd/C, HCO2H (cat.), rt, 3 h, EtOH, yield: 79%). The 3-
hydroxypipecolamide (6) thus obtained may find application
in the asymmetric organocatalysis.7,13a–d,20
H2SO4, MeOH
H
O
O
rt
MeO2C
CONHPMB
CONHPMB
93%
8
14
OTBS
CONHPMB
15
TBSCl, imid.
DMAP, DMF, rt
92%
NaBH4, CaCl2
MeO2C
THF-EtOH, rt
96%
OTBS
CONHPMB
OTBS
CONHPMB
16
MsCl, TEA
3. Conclusion
CH2Cl2, -35 °C
98%
MsO
HO
In summary, we have shown that by proper selection of syn-
thetic procedures and reaction conditions, one can achieve
chemoselective manipulation of multifunctional chiral
building block 8. The compounds thus obtained are also
useful motifs. The usefulness of the protected 3-hydroxy-
piperidin-2-one 3 as a new building block was demonstrated
by its conversion into 3-hydroxypipecolamide 6. Impor-
tantly, the observations made during the synthesis of
(S)-tetrahydrofuran 2-carboxamide derivative 2 from diol 9
indicated that H-bonding may affect the chemoselectivity
of the tosylation reaction, which can be tuned by changing
the reaction medium.
17
OTBS
O
NaH, THF
rt, 21 h
84%
N
PMB
3
Scheme 2.
of MeOH, and treating the in situ formed N,O-semiacetal
intermediate with aqueous KCN at rt for 1 h. Under such
conditions, concomitant O-desilylation6,18 occurred and
a separable diastereomeric mixture of cyanides 18a and
18b was obtained in 72:28 ratio with a combined yield of
86%. The a-amino nitriles 18a/18b were assumed to be
formed via the intermediacy of the N,O-acetal A and the
N-acyliminium ion B. The stereochemistry of the major
diastereomer was tentatively assigned as trans (18a) in anal-
ogy with its lower homologous.17
4. Experimental
4.1. General
Melting points were determined (uncorrected) on a Yanaco
MP-500 micro melting point apparatus. Infrared spectra
were measured with a Nicolet Avatar 360 FTIR spectro-
OTBS
O
OY
1
1. LiAlH4, THF, -50 °C
meter. H NMR spectra were recorded on a Varian unity
+500 spectrometer with tetramethylsilane as an internal
standard. Chemical shifts are expressed in d (ppm) units
downfield from TMS. Mass spectra were recorded on
a Bruker Dalton Esquire 3000 plus LC–MS apparatus (ESI
direct injection). Optical rotations were measured with
Perkin–Elmer 341 automatic polarimeter. THF used in the
reactions were dried by distillation over metallic sodium
and benzophenone; dichloromethane were distilled over
P2O5. Silica gel (Zhifu, 300–400 mesh) was used for column
chromatography, eluting (unless otherwise stated) with ethyl
acetate/petroleum ether (PE) (60–90 ꢁC) mixtures.
N
N
PMB
A
OAlX3
2. MeOH, KCN-H2O
-50 °C ~ rt
PMB
3
86%
OY
OH
OH
CN
+
+
CN
N
N
PMB
18a
N
PMB
18b
AlX4
PMB
B
(Y = TBS; H)
(X = H; OMe)
OH
CONH2
12 N HCl, 50 °C
2-3 days
18a
N
PMB
19
50 ~ 60%
The calculations were performed with the GAUSSIAN 98
package. The hybrid density functional method including
Becke’s 3-parameter non-local-exchange functional with
the correlation functional of Lee–Yang–Parr (B3LYP) was
employed. The basis set used is 6-31G* including the polari-
zation d-function on non-hydrogen atoms. Geometry opti-
mizations and vibrational analyses were performed without
any constraint. The optimized structures of compounds 13a
and 13b are characterized by none imaginary frequency. Re-
ported energies are ZPE (zero-point energy)-corrected.
(based on the recovered
starting material 28%)
H2, 10%Pd(OH)2/C
HCO2H, EtOH, rt
OH
CONH2
or Pd/C, HCO2H,
EtOH, rt
82%
N
H
6
Scheme 3.
In pursuing the cyano group hydrolysis, both acidic and basic
conditions were investigated,17 and at the best case (12 N HCl,
50 ꢁC, 2–3 days), amide 19 was obtained from 18a in 50–
74% yields based on the recovered starting material (ca.
20%). A single crystal X-ray crystallographic analysis of
amide 19,19 derived from the major diastereomer 18a,
revealed its trans-stereochemistry, which confirmed our
previous stereochemical assumption. Cleavage of PMB
4.1.1. (S)-2,5-Dihydroxy-N-(4-methoxybenzyl)pentan-
amide 9. To a methanolic solution (16 mL) of 88 (1.000 g,
4.02 mmol) was added NaBH4 (473 mg, 12.45 mmol) at
0 ꢁC. The mixture was allowed to warm to rt and stirred
for 1 h. The reaction mixture was quenched by addition of
brine (5 mL) and aqueous NaHCO3 (5 mL) at 0 ꢁC. MeOH
was removed under reduced pressure. The mixture was

7462
C.-G. Feng et al. / Tetrahedron 62 (2006) 7459–7465
diluted with water (6 mL) and extracted with EtOAc
(3ꢂ10 mL). The combined organic layers were washed
with brine, dried over anhydrous Na2SO4, filtered, and con-
centrated in vacuo. Flash chromatographic purification on
silica gel (eluent: EtOAc/MeOH) provided 9 (903 mg, yield:
89%) as a colorless solid. Mp 103 ꢁC (EtOAc/PE); [a]2D0
ꢀ24.3 (c 1.1, CHCl3); IR (film) 3394, 3301, 2950, 2932,
2913, 2866, 1617, 1532, 1507, 1430, 1314, 1109, 1085,
Compound 2: colorless oil. IR (film) 3349, 2923, 2853, 1665,
1
1513, 1247, 1175, 1073, 1032 cmꢀ1; H NMR (500 MHz,
CDCl3) d 1.82–1.96 (m, 2H, CH2CH2CH2O), 2.05–2.14
(m, 1H, CH2CH2CH2O), 2.27–2.36 (m, 1H, CH2CH2CH2O),
3.80 (s, 3H, OCH3), 3.82–3.94 (m, 2H, CH2CH2CH2O),
4.34–4.44 (m, 3H, COCHO, NHCH2), 6.86 (d, J¼8.5 Hz,
2H, Ar–H), 7.20 (d, J¼8.5 Hz, 2H, Ar–H), 6.92 (s, 1H,
NH); 13C NMR (125 MHz, CDCl3) d 25.5, 30.2, 42.3, 55.3,
69.4, 78.5, 114.1 (2C), 129.0, 130.2 (2C), 159.0, 173.0; MS
(ESI) m/z 236 (M+H+, 100); HR-MALDIMS calcd for
C13H17NO3Na (M+Na)+: 258.1106; found: 258.1110.
1
1021 cmꢀ1; H NMR (500 MHz, CDCl3) d 1.60–1.80 (m,
3H, CH2CH2CH2OH), 1.97–2.05 (m, 1H, CH2CH2CH2OH),
3.20 (br s, 1H, OH, D2O exchangeable), 3.60–3.75 (m, 2H,
CH2OH), 3.78 (s, 3H, OCH3), 4.17–4.20 (m, 1H, COCH),
4.28–4.40 (m, 2H, PhCH2N), 4.85 (br s, 1H, OH, D2O
exchangeable), 6.86 (d, J¼8.5 Hz, 2H, Ar–H), 7.20 (d,
J¼8.5 Hz, 2H, Ar–H), 7.18 (br s, 1H, NH, D2O exchange-
able); 13C NMR (125 MHz, CDCl3) d 28.2, 32.4, 42.5,
55.3, 62.5, 72.0, 114.1 (2C), 129.0, 130.1 (2C), 159.0,
174.0; MS (ESI) m/z 254 (M+H+, 100). Anal. Calcd for
C13H19NO4: C, 61.64; H, 7.56; N, 5.53. Found: C, 62.05;
H, 7.44; N, 5.47.
4.1.3. Methyl (S)-4-hydroxy-5-(4-methoxybenzylamino)-
5-oxopentanoate 14. To a solution of 8 (2.045 g,
8.03 mmol) in MeOH (10 mL) was added a catalytic amount
of concentrated H2SO4. After stirred for 1.5 h at rt, the
mixture was neutralized with solid CaCO3 and filtered
through Celite. Flash chromatographic purification of the
residue on silica gel (eluent: EtOAc/PE ¼ 1.5:1) provided
14 (2.152 g, yield: 93%) as a colorless solid. Mp 97–98 ꢁC
(EtOAc/Et2O); [a]2D0 ꢀ16.4 (c 1.0, CHCl3); IR (film) 3366,
2928, 1735, 1650, 1513, 1438, 1248, 1176, 1103,
4.1.2. (S)-N-(4-Methoxybenzyl)-tetrahydrofuran-2-
carboxamide 2. Procedure 1: To a solution of 9 (200 mg,
0.79 mmol) in pyridine (1 mL) was rapidly added p-TsCl
(166 mg, 0.87 mmol) at about ꢀ35 ꢁC under nitrogen atmo-
sphere. The mixture was kept at about ꢀ20 ꢁC for 2 h, then
at ꢀ5 ꢁC overnight before quenched by addition of ice-water
(1 mL). The mixture was washed with 1 N aqueous HCl
(2ꢂ1 mL) and extracted with ether (3ꢂ1.5 mL). The com-
bined organic layers were dried over anhydrous Na2SO4,
filtered, and concentrated in vacuo. Flash chromatographic
purification of the residue on silica gel (eluent: EtOAc/
PE ¼ 1:1) provided, besides the recovered starting material
(ca. 30%), ditosylated product 12 (19 mg, yield: 5%)
and a mixture of monotosylated product 10 and (S)-2
(132 mg). The latter was formed during the purification
and concentration. Upon standing at rt, a complete transfor-
mation of 10 to (S)-2 was observed, giving (S)-2 (104 mg)
in 58% yield. The enantiomeric excess (ee) of (S)-2 was
determined to be 92% by HPLC analysis using a chiral
column OD-H (4.6 mmꢂ250 mm, eluting with hexane:2-
propanol ¼ 9:1, 1.0 mL/min; detected at 225 nm. [a]2D0 ꢀ9.6
(c 1.3, CHCl3).
1
1032 cmꢀ1; H NMR (500 MHz, CDCl3) d 1.08–2.26 (m,
1H, COCH2CH2CH2), 2.19–2.27 (m, 1H, COCH2CH2CH2),
2.48–2.63 (m, 2H, COCH2CH2CH2), 3.70 (s, 3H, OCH3),
3.80 (s, 3H, OCH3), 4.15 (d, J¼3.5 Hz, 1H, OH, D2O ex-
changeable), 4.19 (ddd, J¼7.8, 3.5, 3.2 Hz, 1H, CHOH),
4.38 (dd, J¼15.4, 5.9 Hz, 1H, PhCH2N), 4.41 (dd, J¼15.4,
5.9 Hz, 1H, PhCH2N), 6.84 (d, J¼8.5 Hz, 2H, Ar–H), 7.18
(d, J¼8.5 Hz, 2H, Ar–H), 7.03 (br s, 1H, NH, D2O ex-
changeable); 13C NMR (125 MHz, CDCl3) d 29.2, 30.6,
42.7, 52.2, 55.3, 72.0, 114.1 (2C), 129.1 (2C), 130.1,
159.1, 172.9, 175.8; MS (ESI) m/z 282 (M+H+, 100).
Anal. Calcd for C14H19NO5: C, 59.78; H, 6.81; N, 4.98.
Found: C, 60.06; H, 6.84; N, 4.76.
4.1.4. Methyl (S)-4-(tert-Butyldimethylsilyloxy)-5-(4-
methoxybenzylamino)-5-oxopentanoate 15. A mixture of
14 (1.711 g, 6.09 mmol), imidazole (1.029 g, 15.23 mmol),
TBSCl (1.120 g, 7.31 mmol), and a catalytic amount of
DMAP in dry DMF (12 mL) was stirred at rt for 3 h and
then quenched by the addition of water (50 mL). The mix-
ture was extracted with Et2O (6ꢂ10 mL). The combined
organic layers were washed with brine (5 mL), dried over
anhydrous Na2SO4, filtered, and concentrated in vacuo.
Flash chromatographic purification of the residue on silica
gel (eluent: EtOAc/PE ¼ 1:5) provided 15 (2.112 g,
yield: 92%) as a colorless oil. [a]2D0 ꢀ22.0 (c 1.0, CHCl3);
IR (film) 3427, 2953, 2930, 1740, 1678, 1613, 1514,
Procedure 2: To a solution of 9 (200 mg, 0.79 mmol) in
CH2Cl2 (1.5 mL) was added Et3N (0.15 mL, 1.03 mmol).
p-TsCl (166 mg, 0.87 mmol) in CH2Cl2 (0.5 mL) was drop-
ped into the solution at about ꢀ35 ꢁC. The reaction tempera-
ture was allowed to rise to rt, then stirred at rt for 36 h. The
reaction mixture was quenched by addition of 1 mL ice-
water and the resulting mixture was extracted with CH2Cl2
(3ꢂ1.5 mL). The combined organic layers were dried over
anhydrous Na2SO4, filtered, and concentrated in vacuo.
Flash chromatographic purification of the residue on silica
gel (eluent: EtOAc/PE ¼ 1:1) provided, besides the recov-
ered starting material (ca. 20%), ditosylated product 12
(53 mg, yield: 12%) and a mixture of two monotosylated
products 10/11 and 2 (138 mg). The latter was formed during
the purification and concentration. Compound 2 obtained at
this stage showed [a]D20 ꢀ7.0 (c 1.2, CHCl3) and 52% ee.
Upon standing at rt, a complete transformation of 10/11 to
2 was observed, giving 2 (115 mg) in 62% yield, which
showed [a]2D0 0 (c 1.3, CHCl3) and 8% ee.
1464, 1439, 1250, 1174, 1107, 1034 cmꢀ1 1H NMR
;
(500 MHz, CDCl3) d 0.22 (s, 3H, Si(CH3)2), 0.23 (s, 3H,
Si(CH3)2), 0.92 (s, 9H, SiC(CH3)3), 2.02–2.15 (m, 2H,
COCH2CH2CH2), 2.30–2.44 (m, 2H, COCH2CH2CH2),
3.62 (s, 3H, OCH3), 3.80 (s, 3H, OCH3), 4.24 (dd, J¼5.2,
5.2 Hz, 1H, CHCON), 4.30 (dd, J¼5.8, 14.5 Hz, 1H,
PhCH2N), 4.45 (dd, J¼5.8, 14.5 Hz, 1H, PhCH2N), 6.79
(br s, 1H, NH), 6.88 (d, J¼8.5 Hz, 2H, Ar–H), 7.20 (d,
J¼8.5 Hz, 2H, Ar–H); 13C NMR (125 MHz, CDCl3)
d ꢀ5.4, ꢀ5.0, 17.9, 25.6 (3C), 28.9, 30.3, 42.5, 51.6, 55.3,
72.4, 114.1 (2C), 129.0 (2C), 130.0, 159.1, 172.6, 173.5;
MS (ESI) m/z 396 (M+H+, 100). Anal. Calcd for
C20H33NO5Si: C, 60.73; H, 8.41; N, 3.54. Found: C,
60.41; H, 8.08; N, 3.79.

C.-G. Feng et al. / Tetrahedron 62 (2006) 7459–7465
7463
4.1.5. (S)-2-(tert-Butyldimethylsilyloxy)-5-hydroxy-N-
(4-methoxybenzyl)pentanamide 16. To a mixture of 15
(1.400 g, 3.54 mmol) and CaCl2 (1.690 g, 14.89 mmol) in
EtOH (4.7 mL)/THF (9.4 mL) was added NaBH4 (1.030 g,
27.11 mmol) in one portion at 0 ꢁC. The mixturewas allowed
to warm to rt and stirred overnight. The reaction mixture was
quenched by the addition of saturated aqueous NaHCO3
(10 mL) and brine (20 mL) at 0 ꢁC. The mixture was ex-
tracted with EtOAc (6ꢂ20 mL). The combined organic
layers were washed with brine, dried over anhydrous
Na2SO4, filtered, and concentrated invacuo. Flash chromato-
graphic purification of the residue on silica gel (eluent:
EtOAc/PE ¼ 1:1) provided 16 (1.303 g, yield: 96%) as a
colorless oil. [a]2D0 ꢀ25.2 (c 1.0, CHCl3); IR (film) 3423,
2953, 2930, 2857, 1664, 1613, 1514, 1464, 1250, 1176,
dropwise a suspension of NaH (137 mg, 60% w/w) in anhy-
drous THF (2.5 mL) over a period of 20 min. The mixture
was allowed to warm to rt and stirred overnight. The reaction
mixture was quenched with water (30 mL) at 0 ꢁC. The or-
ganic layer was separated and the aqueous layer extracted
with Et2O (3ꢂ20 mL). The combined organic layers were
washed with brine, dried over anhydrous Na2SO4, filtered,
and concentrated in vacuo. Flash chromatographic purifica-
tion on silica gel (eluent: EtOAc/PE¼1:8) provided 3
(400 mg, yield: 84%) as a colorless oil. [a]2D0 ꢀ34.0 (c 1.1,
CHCl3). The enantiomeric excess (ee) of 3 was determined
to be 94% by HPLC analysis using a chiral column OD-H
(4.6 mmꢂ250 mm, eluting with hexane:2-propanol ¼ 99:1,
0.75 mL/min; detected at 254 nm). IR (film) 2952, 2928,
2854, 1654, 1611, 1512, 1489, 1247, 1172, 1148, 1109,
1
1
1111, 1037 cmꢀ1; H NMR (500 MHz, CDCl3) d 0.30 (s,
1039 cmꢀ1; H NMR (500 MHz, CDCl3) d 0.48 (s, 3H,
3H, Si(CH3)2), 0.32 (s, 3H, Si(CH3)2), 0.85 (s, 9H,
SiC(CH3)3), 1.55–1.70 (m, 2H, OCH2CH2CH2), 1.74–1.95
(m, 2H, OCH2CH2CH2), 2.10 (br s, 1H, OH, D2O exchange-
able), 3.62 (dd, J¼6.2, 6.2 Hz, 2H, CH2OH), 3.80 (s, 3H,
OCH3), 4.25 (dd, J¼5.1, 5.1 Hz, 1H, CHCON), 4.31 (dd,
J¼5.8, 14.6 Hz, 1H, PhCH2N), 4.45 (dd, J¼6.2, 14.6 Hz,
1H, PhCH2N), 6.79 (br s, 1H, NH), 6.85 (d, J¼8.5 Hz,
2H, Ar–H), 7.20 (d, J¼8.5 Hz, 2H, Ar–H); 13C NMR
(125 MHz, CDCl3) d ꢀ5.4, ꢀ4.9, 17.9, 25.6 (3C), 27.5,
31.7, 42.5, 55.3, 62.5, 73.1, 114.1 (2C), 129.0 (2C), 130.0,
159.0, 173.4; MS (ESI) m/z 368 (M+H+, 100). Anal. Calcd
for C19H33NO4Si: C, 62.09; H, 9.05; N, 3.81. Found: C,
61.91; H, 9.35; N, 3.78.
Si(CH3)2), 0.51 (s, 3H, Si(CH3)2), 0.92 (s, 9H, SiC(CH3)3),
1.63–1.71 (m, 1H, H-5), 1.82–1.91 (m, 1H, H-5), 1.90–
2.02 (m, 2H, H-4), 3.08–3.21 (m, 2H, H-6), 3.79 (s, 3H,
OCH3), 4.16 (dd, J¼7.1, 4.6 Hz, 1H, H-3), 4.46 (d, J¼
14.4 Hz, 1H, PhCH2N), 4.53 (d, J¼14.4 Hz, 1H, PhCH2N),
6.90 (d, J¼8.5 Hz, 2H, Ar–H), 7.20 (d, J¼8.5 Hz, 2H,
Ar–H); 13C NMR (125 MHz, CDCl3) d ꢀ5.4, ꢀ4.5, 18.3,
19.0, 25.8 (3C), 30.8, 46.7, 49.4, 55.2, 69.6, 113.9 (2C),
129.3, 129.4 (2C), 158.9, 170.0; MS (ESI) m/z 350
(M+H+, 100); HR-MALDIMS calcd for C19H31NO3Si
(M+H)+: 350.2151; found: 350.2153.
4.1.8. (2RS,3S)-2-Cyano-3-hydroxy-1-(4-methoxybenzyl)
piperidines 18a and 18b. To a cooled (ꢀ50 ꢁC) suspension
of LiAlH4 (332 mg, 2.81 mmol) in anhydrous THF (18 mL)
was added a solution of 3 (980 mg, 2.81 mmol) in anhydrous
THF (10 mL) over a period of 20 min. After stirred at the
same temperature for 15 min, the mixture was quenched
with MeOH (2.2 mL) and a solution of KCN (732 mg,
11.24 mmol) in water (2.2 mL) was added. The mixture
was allowed to warm to rt and stirred for another 1 h. After
diluted with water (10 mL), the organic layer was separated
and the aqueous layer extracted with EtOAc (3ꢂ10 mL).
The combined organic layers were washed with brine, dried
over anhydrous Na2SO4, filtered, and concentrated in vacuo.
Flash chromatographic purification on silica gel (eluent:
EtOAc/PE ¼ 1:2) provided (2R,3S)-18a and (2S,3S)-18b in
72:28 ratio with a combined yield of 86%.
4.1.6. (S)-4-(tert-Butyldimethylsilyloxy)-5-(4-methoxy-
benzylamino)-5-oxopentyl methanesulfonate 17. To a
solution of 16 (814 mg, 2.22 mmol) and Et3N (0.46 mL,
3.33 mmol) in CH2Cl2 (8.9 mL) was added dropwise MsCl
(0.22 mL, 2.88 mmol) at ꢀ35 ꢁC. The mixture was stirred
at the same temperature for 15 min and then quenched
with water (6 mL). The organic layer was separated and
the aqueous layer extracted with CH2Cl2 (3ꢂ5 mL). The
combined organic layers were washed with brine, dried
over anhydrous Na2SO4, filtered, and concentrated in vacuo.
Flash chromatographic purification on silica gel (eluent:
EtOAc/PE ¼ 1:2) provided 17 (970 mg, yield: 98%)
as a colorless oil. [a]2D0 ꢀ6.6 (c 1.0, CHCl3); IR (film)
3424, 2955, 2932, 2857, 1673, 1613, 1515, 1467, 1354,
1250, 1174, 1111, 1033 cmꢀ1
;
1H NMR (500 MHz,
CDCl3, two rotamers in a ratio of 4.5:1) d 0.40 (s, 3H,
Si(CH3)2, m+M), 0.45 (s, 3H, Si(CH3)2, M+m), 0.90 (s,
9H, SiC(CH3)3, m+M), 1.70–1.95 (m, 4H, OCH2CH2CH2,
m+M), 3.01, 3.03 (s, 3H, OCH3, M+m), 3.79, 3.81 (s, 3H,
CH3SO2, m+M), 4.18–4.24 (m, 3H, MsOCH2, COCH,
M+m), 4.32 (dd, J¼5.4, 14.6 Hz, 1H, PhCH2N, M+m),
4.44 (dd, J¼6.3, 14.6 Hz, 1H, PhCH2N, M+m), 6.80 (br s,
1H, NH, M+m), 6.86 (d, J¼8.5 Hz, 2H, Ar–H, M+m),
7.20 (d, J¼8.5 Hz, 2H, Ar–H, M+m); 13C NMR
(125 MHz, CDCl3) d ꢀ5.4, ꢀ4.9, 17.9, 24.1, 25.6 (3C),
31.1, 37.4, 42.5, 55.3, 69.6, 72.6, 114.1 (2C), 129.1 (2C),
129.9, 159.1, 172.7; MS (ESI) m/z 446 (M+H+, 100). The
product is too labile to perform the required elementary anal-
ysis or HRMS measurement.
Compound (2R,3S)-18a: colorless crystals, mp 72–73 ꢁC
(CH2Cl2/PE); [a]2D0 ꢀ133.4 (c 1.0, CHCl3); IR (film) 3493,
2946, 2835, 2219, 1616, 1513, 1465, 1442, 1249, 1178,
1132, 1109, 1033 cmꢀ1 1H NMR (500 MHz, CDCl3)
;
d 1.56–1.70 (m, 2H, H-5), 1.78–1.90 (m, 2H, H-4), 2.48–
2.56 (m, 1H, H-6), 2.76–2.84 (m, 2H, H-6, OH, D2O
exchangeable), 3.49 (d, J¼12.7 Hz, 1H, PhCH2N), 3.70 (d,
J¼4.0 Hz, 1H, H-2), 3.71 (d, J¼12.7 Hz, 1H, PhCH2N),
3.80 (s, 3H, OCH3), 3.97–4.20 (m, 1H, H-3), 6.95 (d,
J¼8.5 Hz, 2H, Ar–H), 7.23 (d, J¼8.5 Hz, 2H, Ar–H); 13C
NMR (125 MHz, CDCl3) d 19.2, 27.2, 49.0, 55.3, 56.7,
59.6, 66.1, 114.1 (2C), 115.0, 128.0, 130.3 (2C), 159.4;
MS (ESI) m/z 247 (M+H+, 100). Anal. Calcd for
C14H18N2O2: C, 68.27; H, 7.37; N, 11.37. Found: C,
68.44; H, 7.69; N, 11.15.
4.1.7. (S)-3-(tert-Butyldimethylsilyloxy)-1-(4-methoxy-
benzyl)piperidin-2-one 3. To a cooled (0 ꢁC) solution of
17 (608 mg, 1.37 mmol) in dry THF (3 mL) was added
Compound (2S,3S)-18b: colorless oil; [a]2D0 +97.2 (c 1.0,
CHCl3); IR (film) 3435, 2934, 2835, 2226, 1612, 1585,

7464
C.-G. Feng et al. / Tetrahedron 62 (2006) 7459–7465
1513, 1465, 1248, 1174, 1128, 1104, 1064, 1033 cmꢀ1; 1H
NMR (500 MHz, CDCl3) d 1.48–1.64 (m, 2H, H-5), 1.70–
1.76 (m, 1H, H-4), 1.97–2.03 (m, 1H, H-4), 2.35 (dt,
J¼11.8, 2.9 Hz, 1H, H-6), 2.72–2.77 (m, 1H, H-6), 3.49
(d, J¼12.8 Hz, 1H, PhCH2N), 3.69 (d, J¼12.8 Hz, 1H,
PhCH2N), 3.74 (ddd, J¼15.4, 9.3, 4.6 Hz, 1H, H-3), 3.80
(s, 3H, OCH3), 3.89 (d, J¼4.6 Hz, 1H, H-2), 6.95 (d,
J¼8.5 Hz, 2H, Ar–H), 7.23 (d, J¼8.5 Hz, 2H, Ar–H); 13C
NMR (125 MHz, CDCl3) d 23.0, 30.0, 48.3, 55.3, 59.4
(2C), 67.8, 113.9 (2C), 115.0, 128.5, 130.2 (2C), 159.2;
MS (ESI) m/z 247 (M+H+, 100).
104201), and the NSF of Fujian Province (China)
(C0510001) for financial support.
References and notes
1. (a) Hanessian, S.; Brassard, M. Tetrahedron 2004, 60, 7621–
7628; (b) Hanessian, S.; Hou, Y.; Bayrakdarian, M.;
Tintelnot-Blomley, M. J. Org. Chem. 2005, 70, 6735–6745.
2. (a) Gibbs, G.; Hateley, M. J.; McLaren, L.; Welham, M.; Willis,
C. L. Tetrahedron Lett. 1999, 40, 1069–1072; (b) Kamal, A.;
Ramana, K. V.; Ramana, A. V.; Babu, A. H. Tetrahedron:
Asymmetry 2003, 14, 2587–2594.
3. For two reviews on the piperidine alkaloids, see: (a) Schneider,
M. Pyridine and Piperidine Alkaloids: An Update. In Alkaloids:
Chemical and Biochemical Perspectives; Pelletier, S. W., Ed.;
Elsevier Science: Oxford, 1996; Vol. 10, pp 155–299;
(b) Plunkett, O.; Sainsbury, M. Pyridine and Piperidine
Alkaloids. In Second Supplements to the 2nd Edition of
Rodd’s Chemistry of Carbon Compounds; Sainsbury, M., Ed.;
Elsevier Science: Amsterdam, 1998; Vol. IV F/G, pp 365–421.
4. (a) Roemmele, R. C.; Rapoport, H. J. Org. Chem. 1989, 54,
1866–1875; (b) Scott, J. D.; Tippie, T. N.; Williams, R. M.
Tetrahedron Lett. 1998, 39, 3659–3662; (c) Horikawa, M.;
Busch-Petersen, J.; Corey, E. J. Tetrahedron Lett. 1999, 40,
3843–3846.
4.1.9. (2S,3S)-2-Aminocarbonyl-3-hydroxy-1-(4-methoxy-
solution of 18a (100 mg,
benzyl)piperidine 19.
A
0.41 mmol) in 12 N aqueous HCl (25 mL) was stirred at
60 ꢁC for 2 days and then neutralized with solid Na2CO3.
The mixture was extracted with EtOAc (6ꢂ25 mL) and the
combined organic layers were dried over anhydrous
Na2SO4, filtered, and concentrated in vacuo. Flash chroma-
tographic purification on silica gel (eluent: EtOAc/
MeOH ¼ 30: 1) provided 19 (50 mg, yield: 46%) and the re-
covered starting material 18a (28 mg, 28%). Compound 19:
colorless solid, mp 159–160 ꢁC (EtOAc/PE); [a]D20 ꢀ77.8 (c
0.6, CHCl3); IR (film) 3379, 3200, 2959, 2927, 2855, 2789,
1688, 1662, 1614, 1513, 1444, 1381, 1258, 1113, 1067,
1
1034 cmꢀ1; H NMR (500 MHz, CDCl3) d 1.25–1.55 (m,
ˆ
2H, H-5), 1.62–1.72 (m, 1H, H-4), 1.95–2.05 (m, 1H, H-
4), 2.04–2.14 (m, 1H, H-6), 2.70 (d, J¼8.7 Hz, 1H, H-2),
2.83–2.88 (m, 1H, H-6), 3.22 (d, J¼13.6 Hz, 1H, PhCH2N),
3.67 (ddd, J¼10.8, 8.7, 4.6 Hz, 1H, H-3), 3.79 (s, 3H,
OCH3), 3.85 (d, J¼13.6 Hz, 1H, PhCH2N), 6.10 (br s, 1H,
OH, D2O exchangeable), 6.80 (br s, 2H, NH2, D2O ex-
changeable), 6.95 (d, J¼8.5 Hz, 2H, Ar–H), 7.23 (d,
J¼8.5 Hz, 2H, Ar–H); 13C NMR (125 MHz, CDCl3)
d 22.0, 32.0, 50.6, 55.3, 59.7, 70.5, 73.5, 113.9 (2C),
129.4, 129.8 (2C), 158.9, 176.5; MS (ESI) m/z 265
(M+H+, 100); HR-MALDIMS calcd for C14H20N2O3
(M+H)+: 265.1552; found: 265.1557.
5. (a) Greck, C.; Ferreira, F.; Genet, J. P. Tetrahedron Lett. 1996,
37, 2031–2034; (b) Agami, C.; Couty, F.; Mathieu, H.
Tetrahedron Lett. 1996, 37, 4001–4002; (c) Ferreira, F.;
Greck, C.; Genet, J. P. Bull. Soc. Chim. Fr. 1997, 134, 615–
621; (d) Battistini, L.; Zanardi, F.; Rassu, G.; Spanu, P.;
Pelosi, G.; Fava, G. G.; Ferrari, M. B.; Casiraghi, G.
Tetrahedron: Asymmetry 1997, 8, 2975–2987; (e) Jourdant,
A.; Zhu, J. Tetrahedron Lett. 2000, 41, 7033–7036; (f)
ˆ
ˆ
Haddad, M.; Larcheveque, M. Tetrahedron Lett. 2001, 42,
5223–5225; (g) Kumar, P.; Bodas, M. S. J. Org. Chem. 2005,
70, 360–363.
6. Gillard, J.; Abraham, A.; Anderson, P. C.; Beaulieu, P. L.;
´
Bogri, T.; Bousquet, Y.; Grenier, L.; Guse, I.; Lavallee, P.
J. Org. Chem. 1996, 61, 2226–2231.
4.1.10. (2S,3S)-3-Hydroxy-2-piperidine-carboxamide 6.
To a suspension of 20% Pd(OH)2/C (26 mg) in EtOH
(1 mL) were added a solution of 19 (52 mg) in EtOH
(1 mL) and a catalytic amount of HCO2H. The mixture
was stirred at rt and under an atmosphere of H2 for 5 h. After
filtration of the catalyst, the filtrate was concentrated in
vacuo. The residue was purified by flash chromatography
on silica gel (eluent: MeOH/EtOAc/aqueous NH3 ¼ 1:4:0.1)
to provide 6 (23 mg, yield: 82%) as a colorless solid. Mp
149–150 ꢁC (MeOH/Et2O); [a]2D0 +43.8 (c 0.4, 10% HCl);
IR (KBr) 3376, 3317, 3198, 2947, 2857, 1773, 1677, 1635,
7. (a) Wang, Z.; Ye, X.; Wei, S.; Wu, P.; Zhang, A.; Sun, J. Org.
Lett. 2006, 8, 999–1001; (b) For a use of pipecolic acid as a
superior organocatalyst, see: Aroyan, C. E.; Vasbinder, M. M.;
Miller, S. J. Org. Lett. 2005, 7, 3849–3851 (c) Cheong,
P. H.-Y.; Zhang, H.; Thayumanavan, R.; Tanaka, F.; Houk,
K. N.; Barbas, C. F., III. Org. Lett. 2006, 8, 811–814; For
related examples, see: (d) Kawabata, T.; Stragies, R.; Fukaya,
T.; Nagaoka, Y.; Schedel, H.; Fuji, K. Tetrahedron Lett. 2003,
44, 1545–1548; (e) Cobb, A. J. A.; Shaw, D. M.; Longbottom,
D. A.; Gold, J. B.; Ley, S. V. Org. Biomol. Chem. 2005, 3, 84–
96; (f) Wang, W.; Mei, Y.; Li, H.; Wang, J. Org. Lett. 2005, 7,
601–604; (g) Tang, Z.; Yang, Z. H.; Chen, X. H.; Cun, L. F.;
Mi, A. Q.; Jiang, Y. Z.; Gong, L. Z. J. Am. Chem. Soc. 2005,
127, 9285–9289; (h) Chen, J.-R.; Lu, H.-H.; Li, X.-Y.; Cheng,
L.; Wan, J.; Xiao, W.-J. Org. Lett. 2005, 7, 4543–4545.
8. For an account, see: (a) Huang, P.-Q. Synlett 2006, 1133–1149;
For other papers, see: (b) Huang, P.-Q.; Liu, L.-X.; Wei, B.-G.;
Ruan, Y.-P. Org. Lett. 2003, 5, 1927–1929; (c) Huang, P.-Q.;
Wei, B.-G.; Ruan, Y.-P. Synlett 2003, 1663–1667; (d) Liu,
L. X.; Ruan, Y.-P.; Guo, Z. Q.; Huang, P.-Q. J. Org. Chem.
2004, 69, 6001–6009; (e) Ruan, Y.-P.; Wei, B.-G.; Xu, X.-Q.;
Liu, G.; Yu, D.-S.; Liu, L.-X.; Huang, P.-Q. Chirality 2005,
17, 595–599; (f) Wei, B. G.; Chen, J.; Huang, P.-Q.
1
1507, 1077 cmꢀ1; H NMR (500 MHz, D2O) d 1.42–1.62
(m, 2H, H-4, H-5), 1.76–1.86 (m, 1H, H-5), 2.10–2.18 (m,
1H, H-4), 2.56 (dt, J¼12.9, 2.8 Hz, 1H, H-6), 3.04 (dd,
J¼12.9, 1.7 Hz, 1H, H-6), 3.14 (d, J¼9.6 Hz, 1H, H-2),
3.66 (ddd, J¼10.7, 9.6, 4.4 Hz, H-3); 13C NMR (125 MHz,
D2O) d 27.0, 35.0, 46.7, 67.4, 71.4, 178.2; MS (ESI) m/z
145 (M+H+, 100); HR-EIMS calcd for [C6H12N2O2]+:
144.0899; found: 144.0892.
Acknowledgements
The authors are grateful to the NSF of China (20390050,
20572088), the Ministry of Education (Key Project

C.-G. Feng et al. / Tetrahedron 62 (2006) 7459–7465
7465
Tetrahedron 2006, 62, 190–198; (g) Huang, P.-Q.; Guo, Z.-Q.;
Ruan, Y.-P. Org. Lett. 2006, 8, 1435–1438.
Lett. 1999, 1, 1087–1090; (e) Salas-Coronado, R.; Vasquez-
Badillo, A.; Medina-Garcia, M.; Garcia-Colon, J. G.; Noth,
H.; Contreras, R.; Flores-Parra, A. J. Mol. Struct. (Theochem)
2001, 543, 259–275; (f) Kim, K. M.; Park, H.; Kim, H.-J.;
Chin, J.; Nam, W. Org. Lett. 2005, 7, 3525–3527.
13. For reviews on the hydrogen bonding controlled selective reac-
tions, see: (a) Schreiner, P. R. Chem. Soc. Rev. 2003, 32,
289–296; (b) Pihko, P. M. Angew. Chem., Int. Ed. 2004, 43,
2062–2064; (c) Dalko, P. I.; Moisan, L. Angew. Chem., Int.
Ed. 2004, 43, 5138–5175; (d) Bolm, C.; Rantanen, T.;
Schiffers, I.; Zani, L. Angew. Chem., Int. Ed. 2005, 44,
1758–1763; For selective examples, see: (e) Thevenet, S.;
Wernicke, A.; Belniak, S.; Descotes, G.; Bouchu, A.;
Queneau, Y. Carbohydr. Res. 1999, 318, 52–66; (f) Huang, Y.;
Unni, A. K.; Thadani, A. N.; Rawal, V. H. Nature 2003, 424,
146; (g) Cook, G. R.; Yu, H.; Sankaranarayanan, S.; Shanker,
P. S. J. Am. Chem. Soc. 2003, 125, 5115–5120; (h) Du, H. F.;
Zhao, D. B.; Ding, K. L. Chem.—Eur. J. 2004, 10, 5964–
5970.
14. Corey, E. J.; Venkateswarlu, A. J. Am. Chem. Soc. 1972, 94,
6190–6191.
15. Lewis, N.; McKillop, A.; Taylor, R. J. K.; Watson, R. J. Synth.
Commun. 1995, 25, 561–568.
16. (a) Gless, R. D.; Rapoport, H. J. Org. Chem. 1979, 44, 1324–
1336; (b) Compernolle, F.; Saleh, M. A.; Branden, S. V. D.;
Toppet, S.; Hoornaert, G. J. Org. Chem. 1991, 56, 2386–2390.
17. Huang, P.-Q.; Huang, H. Y. Synth. Commun. 2004, 34, 1377–
1382.
9. (a) Buchanan, J. G.; Dunn, A. D.; Edgar, A. R. J. Chem. Soc.,
Perkin Trans. 1 1974, 1943–1949; (b) Buchanan, J. G.; Dunn,
A. D.; Edgar, A. R. J. Chem. Soc., Perkin Trans. 1 1975,
1191–1200; (c) Bukownik, R. R.; Wilcox, C. S. J. Org.
Chem. 1988, 64, 463–471; (d) Lehmann, T. E.; Berkessel, A.
J. Org. Chem. 1997, 62, 302–309; (e) Kelly, D. K.; Nally, J.
Tetrahedron Lett. 1999, 40, 2209–2212; (f) Ninomiya, M.;
Hirohara, H.; Onishi, J.; Kusumi, T. J. Org. Chem. 1999, 64,
5436–5440; (g) Paquette, L. A.; Ohmori, N.; Lowinger, T. B.;
Rogers, R. D. J. Org. Chem. 2000, 65, 4303–4308; (h)
Ref. 10; For a method of selective monotosylation of sym-
´
metric diols, see: (i) Bouzide, A.; Sauve, G. Org. Lett. 2002,
4, 2329–2332.
10. Jirgensons, A.; Marinozzi, M.; Pellicciari, R. Tetrahedron
2005, 61, 373–377.
11. For the regioselective cyclodehydration of a chiral 1,4-diol,
see: (a) Robinson, P. L.; Barry, C. N.; Bass, S. W.; Jarvis,
S. E.; Evans, S. A., Jr. J. Org. Chem. 1983, 48, 5396–5398;
(b) Robinson, P. L.; Evans, S. A., Jr. J. Org. Chem. 1985, 50,
3860–3863; (c) Robinson, P. L.; Barry, C. N.; Kelly, J. W.;
Evans, S. A., Jr. J. Am. Chem. Soc. 1985, 107, 5210–5219;
(d) Sharma, G. V. M.; Kumar, K. R.; Sreenivas, P.; Krishna,
P. R.; Chorghade, M. S. Tetrahedron: Asymmetry 2002, 13,
687–690; For the regioselective cyclodehydration of a chiral
1,5-diol, see: (e) Flamme, E. M.; Roush, W. R. Beilstein J.
Org. Chem. 2005, 1–5; http://bjoc.beilstein-journals.org/.
12. For selected examples of formation of intramolecular hydrogen
bond in hydroxyketones, see: (a) Heathcock, C. H.; Pirrung,
M. C.; Sohn, J. E. J. Org. Chem. 1979, 44, 4294–4299;
(b) Battaglia, A.; Barbaro, G.; Giorgianni, P.; Guerrini, A.;
Bertucci, C.; Geremia, S. Chem.—Eur. J. 2000, 6, 3551–
3557; For selected examples of formation of hydrogen bonds
involving amides, see: (c) Johansson, A.; Kollman, P. A.
J. Am. Chem. Soc. 1972, 94, 6196–6198; (d) Bennes, R.;
Philp, D.; Spencer, N.; Kariuki, B. M.; Harris, K. D. M. Org.
18. de Vries, E. F. J.; Brussee, J.; van der Gen, A. J. Org. Chem.
1994, 59, 7133–7137.
19. Feng, C.-G.; Fang, H.; Huang, P.-Q. Acta Crystallogr. 2004,
E60, o1075–o1077.
20. For selected reviews on the asymmetric organocatalysis, see:
(a) Jarvo, E. R.; Miller, S. J. Tetrahedron 2002, 58, 2481–
2495; (b) Clarke, M. L. Lett. Org. Chem. 2004, 1, 292–296;
(c) Saito, S.; Yamamoto, H. Acc. Chem. Res. 2004, 37,
570–579. See also Refs. 13a–d.