A stereoselective route to cis-(2S,3R)-3-hydroxypipecolic acid and two enantiomeric cis-2-hydroxymethyl-3-hydroxypiperidine derivatives

Article abstract of DOI:10.1055/s-0030-1260120

Stereoselective routes to cis-(2S,3R)-3-hydroxypipecolic acid and two enantiomeric cis-2-hydroxymethyl-3-hydroxypiperidine derivatives from a common precursor have been developed, which featured stereocontrolled vinylation of a -chiral aldehyde and ring-closing metathesis as key steps. Georg Thieme Verlag Stuttgart. New York.

Full text of DOI:10.1055/s-0030-1260120

2664
PAPER
A Stereoselective Route to cis-(2S,3R)-3-Hydroxypipecolic Acid and Two
Enantiomeric cis-2-Hydroxymethyl-3-hydroxypiperidine Derivatives
Shital K. Chattopadhyay,* Shankar P. Roy, Tapan Saha
Department of Chemistry, University of Kalyani, Kalyani-741235, West Bengal, India
Fax +91(33)25828282; E-mail: skchatto@yahoo.com
Received 13 May 2011; revised 2 June 2011
under acidic conditions to provide the new serinol deriva-
tive 10. The latter was oxidized under modified Swern
conditions to provide the aldehyde 11, which was used as
such in the next step. Chelation-controlled addition of
Grignard reagents to a-chiral a-amino aldehydes has been
studied extensively,14 and such additions usually proceed
with high level of selectivity.15 Thus, when the aldehyde
11 was added to a solution of vinylmagnesium bromide in
an one-pot manner, the desired syn-allyl alcohol 12 was
indeed formed as the major isomer (87:13 by HPLC), but
as an inseparable mixture with the anti-isomer 13. The
configuration of the major product was assigned syn based
on the assumption that chelation control had prevailed and
was further supported by synthetic work described herein.
This mixture of alcohols was then converted to the corre-
sponding MOM-ethers 14 and 15, which also, unfortu-
nately, could not be separated. However, N-allylation of
this mixture with allyl bromide under conventional condi-
tions led access to the pure syn-isomer 16 in good overall
yield. Unfortunately, the minor isomer could not be ob-
tained pure.
Abstract: Stereoselective routes to cis-(2S,3R)-3-hydroxypipecolic
acid and two enantiomeric cis-2-hydroxymethyl-3-hydroxypiperi-
dine derivatives from a common precursor have been developed,
which featured stereocontrolled vinylation of a a-chiral aldehyde
and ring-closing metathesis as key steps.
Key words: amino acids, diastereoselectivity, piperidines, chiral
pool, metathesis
Various hydroxylated piperidine derivatives constitute
part structure of several biologically active natural
products1 and are also important as inhibitors of carbohy-
drate processing enzymes,2 therapeutic agents and/or syn-
thetic
intermediates.3
Stereoisomeric
piperidine
derivatives 1–4 (Figure 1) are good examples in these re-
gards. For example, (–)-cis-3-hydroxypipecolic acid (1)
constitutes part of the structure of the important antitumor
antibiotic tetrazomine (5).4 The (–)-trans-3-hydroxypipe-
colic acid (3) is a component of a specific inhibitor of a-
D-mannosidase, viz. swainsonine (7).5 Moreover, their
use as conformationally restricted serine or hydroxylated
homoproline is well documented.6 Similarly, the stereo-
isomeric 3-hydroxy-2-hydroxymethylpiperidine deriva-
tives, for example, 2 and 4, are also of importance,7for
example, the cis-isomer 2 is a constituent of the potent an-
timalarial agent isofebrifugine (6).8 These, in turn, have
generated interest in developing flexible route for the syn-
thesis of such type of compounds. Thus, elegant routes to
various stereoisomers of 3-hydroxypipecolic acid have
been developed.9 Moreover, preparation of stereoisomeric
hydroxypipecolic acid derivatives from a common source
has also remained rewarding.10 In particular, the cis-
(2S,3R)-isomer 1 continues to receive attention due to its
several functional attributes.11 In continuation of our
work12 on the synthesis of pipecolic acid derivatives, we
report a short stereoselective route to the cis-(2S,3R)-3-
hydroxypipecolic acid (1) and two globally protected de-
rivatives of cis-(2S,3S)-2-hydroxymethyl-piperidine-3-ol
2 and ent-2 from a common precursor, viz. L-serine.
OR1
R2
OH
OH
N
N
H
H
X
1, R1 = H; R2 = CO2H
2, R1 = H; R2 = CH2OH
3, X = O
4, X = H2
OH
OH
O
NMe
N
N
H
O
NH
OMe
5
OH
O
OH
H
N
O
OH
N
OH
N
H
N
6
7
Figure 1 Stereoisomeric piperidine derivatives 1–4 and biological-
ly active compounds 5–7 possessing part structure of 1–4
Our synthesis of the hydroxypipecolic acid derivative 1
started from the known13 serinol derivative 8 (Scheme 1),
which was protected as its benzyl ether 9 under standard
conditions. The oxazolidine ring in the latter was opened
We considered a RCM-reaction of the N-tethered diene 16
to construct the dihydropiperidine ring.16 Thus, ring-
closing metathesis of 16 with Grubbs’ first-generation
catalyst,17 benzylidene-bis(tricyclohexylphosphine) ru-
thenium(IV) dichloride (17), proceeded well in dichlo-
romethane at ambient temperature and the desired
SYNTHESIS 2011, No. 16, pp 2664–2670
x
x.
x
x
.
2
0
1
1
Advanced online publication: 14.07.2011
DOI: 10.1055/s-0030-1260120; Art ID: Z50011SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
Stereoselective Synthesis of cis-Hydroxypiperidine Derivatives
2665
cis as speculated on the basis of predictive model. The
configuration of the products derived onwards, for exam-
ple, 16, and 18–20 was similarly correlated.
OR
ii
iii
Y
HO
OBn
NHBoc
10
O
OBn
NHBoc
11
O
NBoc
8, R = H
9, R = Bn
Our attention was next focused on the development of a
synthetic route to the enantiomeric piperidine derivatives
related to 19. Thus, the known21 allyl alcohol 21,
(Scheme 2) obtainable from L-serine, was converted into
the piperidine derivative 28 following a seven-step se-
quence detailed below. Conversion of the allyl alcohol 21
to the corresponding MOM-ether 22, opening of the ox-
azolidine ring in 22 to the primary alcohol 23, and its sub-
sequent conversion to the silyl ether 24 proceeded
smoothly. Similarly, N-allylation of compound 24 into the
N-tethered diene 25 followed by a subsequent RCM led to
the dihydropiperidine derivative 26 in good overall yield.
Functional-group manipulation of the latter involving sat-
uration of the double bond leading to 27 followed by
deprotection of the O-silyl group then led to the desired
piperidine derivative 28. Compound 28 displayed an [a]D
value of +11 (c = 2.2, CHCl3) while compound 19 had a
[a]D of –10 (c = 2.2, CHCl3) under similar conditions.
Moreover, their analytical data proved to be nearly super-
imposable. Thus, these appear to be enantiomeric, as ex-
pected.
i
X
X
Y
iv
v
OBn
OBn
NHBoc
NHBoc
12, X = OH; Y = H
13, X = H; Y = OH
14, X = OMOM; Y = H
15, X = H; Y = OMOM
OMOM
OMOM
vii
OMOM
CH2OH
vi
OBn
OBn
N
N
Boc
NBoc
Boc
16
18
19
OMOM
CO2H
viii
ix
1
N
Boc
20
Scheme 1 Reagents and conditions: (i) NaH, BnBr, THF–DMSO
(9:1), 83%; (ii) aq 5% HCl, MeOH, 86%; (iii) Swern oxidation, then
vinylmagnesium bomide, 62% over two steps; (iv) MOMCl, DIPEA,
CH2Cl2, 82%; (v) NaH, allyl bromide, DMF, 90% (vi) catalyst 17 (5
mol%), CH2Cl2, 84%; (vii) Pd/C-H2, EtOAc, 94%; (viii) Dess–Martin
periodinane, then NaClO2, NaH2PO4, 1-methylcyclohex-1-ene, t-
BuOH; 56% over two steps; (ix) aq 6 N HCl, 90 °C, 12 h, 74%.
In short, we have developed a stereoselective synthetic
route to cis-(2S,3R)-3-hydroxypipecolic acid using L-
serine as a common starting material and employing easi-
ly available reagents. We have also prepared two differen-
tially protected and enantiomeric cis-3-hydroxy-2-
hydroxymethylpiperidine derivatives from a common
precursor following operationally simple synthetic steps.
The compounds prepared may serve as building blocks in
organic synthesis and the developed methodology may
complement to those existing in the literature for the prep-
aration of such type of compounds.
dihydropiperidine derivative 18 could be obtained in very
good yield. Hydrogenolytic removal of the benzyl group
in 18 with concomitant saturation of the double bond pro-
ceeded smoothly to provide the primary alcohol 19. This
was then subjected to a two-step oxidation to the corre-
sponding carboxylic acid involving initial formation of
the corresponding aldehyde using Dess–Martin
periodinane18 followed by Pinnick oxidation19 of the latter
to the carboxylic acid 20 in a combined yield of 56% over
two steps. Acedolytic removal of the N-Boc and O-MOM
groups simultaneously then gave the desired 3-hydroxy-
pipecolic acid, which displayed spectroscopic and optical
properties in close agreement to those reported11b,c,20 for
(2S,3R)-3-hydroxypiperidine-2-carboxylic acid. The syn-
thesis of the hydroxypipecolic acid derivative 1 proceeded
in an overall yield of 11% over nine steps from 10. Thus,
the stereochemistry of the major isomer 12 formed during
vinylation of the a-chiral aldehyde 11 was correlated as
Optical rotations were recorded in spectroscopic grade CHCl3 on a
Rudolph Autopol IV polarimeter at 20 °C; [a]D values were record-
ed in units of 10–1 deg cm2 g–1. IR spectra were recorded on a Perkin-
1
Elmer Spectrum-1 spectrophotometer. H and 13C NMR spectra
were recorded on a Bruker Avance 400 spectrometer purchased
through a DST-FIST grant. Data for rotamers are presented within
parentheses wherever appropriate. Chemical shifts are recorded rel-
ative to residual solvent or TMS as standard. Mass spectra were re-
corded on a Jeol-JMS 600 instrument from I. I. C. B., Kolkata or
OMOM
OH
OMOM
OMOM
ii
i
iii
iv
HO
TBDPSO
O
O
NBoc
NBoc
NHBoc
23
NHBoc
24
21
22
TBDPSO
OMOM
OMOM
OMOM
OMOM
OH
vii
vi
v
TBDPSO
OTBDPS
BocN
25
BocN
26
N
N
Boc
Boc
27
28
Scheme 2 Reagents and conditions: (i) MOMCl, DIPEA, CH2Cl2, 80%; (ii) PTSA, MeOH, 78%; (iii) TBDPSCl, Et3N, DMAP, CH2Cl2, 82%;
(iv) NaH, allyl bromide, DMF, 78%; (v) catalyst 17 (5 mol%), CH2Cl2, 83%; (vi) Pd/C-H2, EtOAc, 85%; (vii) TBAF, THF, 82%.
Synthesis 2011, No. 16, 2664–2670 © Thieme Stuttgart · New York

2666
S. K. Chattopadhyay et al.
PAPER
IACS, Kolkata. Elemental analyses were recorded in a PerkinElmer
series II instrument. Petroleum ether (PE) refers to the fraction boil-
ing in the range 60–80 °C. Silica gel (60–120 or 200–230 mesh) for
column chromatography was purchased from Spectrochem, India.
come to –35 °C and stirred for another 30 min. Then, (i-Pr)2EtNH
(1.084 mL, 6.34 mmol) was added dropwise and the mixture was
stirred for 10 min before being transferred to a cooled (–78 °C) so-
lution of vinylmagnesium bromide (3.5 mL, 1 M solution in THF)
in THF (15 mL) via a cannula over 10 min. The stirring was contin-
ued for 1 h at the same temperature, after which it was allowed to
come to r.t. and stirred for 4 h. The mixture was quenched with sat.
aq. NH4Cl (5 mL) and extracted with EtOAc (2 × 25 mL). The com-
bined organic extracts were washed successively with aq 1 N HCl
(50 mL), H2O (50 mL), brine (50 mL), and dried (Na2SO4). After
concentration in vacuo, the crude product was purified by column
chromatography using 15% EtOAc in PE as eluent to provide the
mixture of allyl alcohols 12 and 13 as a colorless liquid; yield: 170
mg (62% over two steps); [a]D –4.2 (c = 1.5, CHCl3).
tert-Butyl (R)-4-(Benzyloxymethyl)-2,2-dimethyloxazolidine-3-
carboxylate (9)
A solution of the alcohol 8 (1.0 g, 4.32 mmol) in THF (5 mL) was
added dropwise to an ice-cooled stirred suspension of NaH (218
mg, 9 mmol) in THF–DMSO (9:1; 20 mL). Benzyl bromide (0.77
mL, 6.48 mmol) was added dropwise and the reaction mixture was
allowed to come to r.t. while stirring for 12 h. The mixture was
cooled back to 0 °C and quenched with sat. aq NH4Cl (10 mL), ex-
tracted with EtOAc (2 × 25 mL), and the combined organic extracts
were washed successively with H2O (25 mL), brine (25 mL), and
dried (Na2SO4). After filtration, the filtrate was evaporated in vacuo
to leave a crude product, which was purified by chromatography
over silica gel using a mixture of PE–EtOAc (20:1) as eluent to pro-
vide 9 as a colorless liquid; yield: 1.15 g (83%); [a]D –23 (c = 1.2,
CHCl3).
IR (neat): 3445, 2977, 1695, 1704, 1514, 1505, 1367, 1170 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.38–7.26 (m, 5 H), 5.93–5.80 (m,
1 H), 5.33 (dd, J = 11.2, 17.1 Hz, 1.5 H), 5.22–5.16 (m, 1.8 H), 4.53
(d, J = 3.6 Hz, 1 H), 4.49 (d, J = 6.4 Hz, 1 H), 4.42 (br s, 0.8 H), 4.27
(br s, 0.5 H), 3.78–3.76 (m, 1.6 H), 3.68–3.58 (m, 2 H), 3.24 (d,
J = 7.8 Hz, 0.4 H), 3.08 (0.5 H, br s), 1.45 and 1.43 (merged
singlets, 9 H).
13C NMR (100 MHz, CDCl3): d = 156.1, 155.9, 137.7, 137.6, 137.5,
137.4, 128.5, 128.0, 127.9, 127.8, 127.7, 116.2, 116.0, 79.7, 74.4,
73.6, 73.5, 73.0, 71.1, 70.0, 53.6, 28.4, 28.3.
IR (neat): 2981, 1700, 1389, 1366, 1261, 1175, 1089, 1037 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.21–7.08 (m, 5 H), 4.42–4.29 (m,
2 H), 3.97–3.96 (m, 0.4 H), 3.87 (d, J = 8.4 Hz, 1 H), 3.80–3.74 (m,
1.5 H), 3.53 (d, J = 5.2 Hz, 0.4 H), 3.40 (m, 0.5 H), 3.23 (dt, J = 18,
8.8 Hz, 1 H), 1.39 (s, 3 H), 1.35 (s, 3 H), 1.31 and 1.24 (two over-
lapping singlets for rotamers, 9 H).
MS (TOF MS ES+): m/z = 330 (M+ + Na).
13C NMR (100 MHz, CDCl3): d = 152.2 (151.7), 138.3 (138.1),
128.4 (128.3), 127.8 (127.7), 127.6, 93.7 (93.3), 80.2 (79.7), 73.2,
69.6 (69.2), 65.7 (65.4), 56.5 (56.4), 28.4, 27.5 (26.8), 24.4 (23.1).
Mixture of MOM Ethers 14 and 15
(i-Pr)2EtNH (283 mL, 1.628 mmol) followed by MOMCl (92 mL,
1.22 mmol) were added sequentially dropwise to an ice-cooled so-
lution of the mixture of alcohols 12 and 13 (250 mg, 0.81 mmol) in
anhyd CH2Cl2 (3 mL) and the resulting solution was stirred for 24 h
at r.t. The mixture was diluted with CH2Cl2 (25 mL) and the organic
layer was washed successively with H2O (25 mL) and brine (25
mL), and dried (Na2SO4). After filtration, the filtrate was concen-
trated under vacuo to leave a crude product, which was purified by
column chromatography using 10% EtOAc in PE as eluent to give
compounds 14 and 15 as an inseparable mixture; yield: 234 mg
(82%); [a]D –10.4 (c = 3.0, CHCl3).
MS (TOF MS ES+): m/z = 344 (M+ + Na).
Anal. Calcd for C18H27NO4: C, 67.26; H, 8.47; N, 4.36. Found: C,
67.32; H, 8.38; N, 4.51.
tert-Butyl (S)-1-(Benzyloxy)-3-hydroxypropan-2-ylcarbamate
(10)
Aq 5% HCl (5 mL) was added dropwise to an ice-cooled solution of
compound 9 (1.0 g, 3.12 mmol) in MeOH (15 mL) and the mixture
was allowed to come to r.t. and stirred for 4 h. The mixture was
quenched with sat. aq NaHCO3 (10 mL) at 0 °C and extracted with
EtOAc (2 × 25 mL). The combined organic layers were washed
successively with H2O (25 mL) and brine (25 mL), and dried
(Na2SO4). After filtration, the filtrate was evaporated in vacuo to
provide a pale yellow oil, which was purified by chromatography
over silica gel using a mixture of PE and EtOAc (4:1) as eluent to
provide compound 10 as a colorless liquid; yield: 0.75 g (86%); [a]D
–13 (c = 1.7, CHCl3).
IR(neat): 3226, 2926, 1694, 1365, 1155, 1029, 920 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.33–7.25 (m, 5 H), 5.75–5.73 (m,
1 H), 5.30–5.24 (m, 2 H), 4.88 (d, J = 4.1 Hz, 1 H), 4.66 (d, J = 6.6
Hz, 1 H), 4.53–4.47 (m, 3 H), 4.29–4.27 (m, 1 H), 3.89 (br s, 1 H),
3.54 (d, J = 5.9 Hz, 2 H), 3.33 (s, 3 H), 1.42 and 1.41(overlapping
singlets, 9 H).
13C NMR (100 MHz, CDCl3): d = 155.7, 138.1, 135.4 135.0, 128.5,
128.4, 128.0, 127.9, 127.7, 127.5, 119.4, 118.9, 95.7, 94.2, 79.3,
73.7, 73.2, 69.2, 68.7, 55.7, 55.4, 53.1, 28.4, 28.3.
IR (neat): 3364, 1682, 1525, 1482, 1369, 1244, 1175, 1044 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.30–7.19 (m, 5 H), 5.11 (br s, 1
H), 4.45 (s, 2 H), 3.73 (dd, J = 8.0, 4.1 Hz, 2 H), 3.63–3.58 (m, 2 H),
3.52 (dd, J = 8.4, 4.0 Hz, 1 H), 2.37 (br s, 1 H), 1.37 (s, 9 H).
13C NMR (100 MHz, CDCl3): d = 156.1, 137.8, 128.5, 127.9, 127.7,
79.7, 73.4, 70.3, 63.4, 51.6, 28.4.
MS (TOF MS ES+): m/z = 374 (M+ + Na).
tert-Butyl (2R,3R)-Allyl[1-(benzyloxy)-3-(methoxymeth-
oxy)pent-4-en-2-yl]carbamate (16)
NaH (55 mg, 2.28 mmol) was added in a single portion to a solution
of the epimers 14 and 15 (200 mg, 0.569 mmol) in anhyd DMF (2.5
mL) at 0 °C under N2 and the reaction mixture was stirred for 10 min
at the same temperature. Allyl bromide (145 mL, 1.70 mmol) was
added to the mixture and the stirring was continued for 15 min. The
mixture was allowed to come to r.t. and stirred for 12 h. The mixture
was cooled back to 0 °C, quenched with sat aq. NH4Cl (3 mL), di-
luted with H2O (10 mL), and extracted with EtOAc (2 × 25 mL).
The combined organic layers were washed successively with H2O
(25 mL), brine (25 mL), and dried (Na2SO4). After filtration, and the
filtrate was concentrated under vacuo to leave the crude product,
which was purified by column chromatography over silica gel using
MS (TOF MS ES+): m/z = 304 (M+ + Na).
Anal. Calcd for C15H23NO4: C, 64.03; H, 8.24; N, 4.98. Found: C,
64.21; H, 8.35; N, 4.82.
Epimeric Allyl Alcohols 12 and 13
A solution of DMSO (129 mL, 1.82 mmol) in CH2Cl2 (0.5 mL) was
added dropwise under N2 to a stirred solution of oxalyl chloride
(137 mL, 1.57 mmol) in anhyd CH2Cl2 (2.85 mL), at –78 °C over 5
min. The stirring was continued for 20 min and then a solution of
the alcohol 10 (250 mg, 0.89 mmol) in anhyd CH2Cl2 (6 mL) was
added dropwise over 10 min. The reaction mixture was allowed to
Synthesis 2011, No. 16, 2664–2670 © Thieme Stuttgart · New York

PAPER
Stereoselective Synthesis of cis-Hydroxypiperidine Derivatives
2667
5% EtOAc in PE to give the N-allylated product 16 as a viscous col-
orless liquid; yield: 197 mg (90%); [a]D –4.0 (c = 1.5, CHCl3).
IR (neat): 2928, 1693, 1391, 1154, 1029, 920 cm–1.
mL) at r.t. and the stirring was continued for 1 h. The mixture was
diluted with Et2O (10 mL) and quenched with sat. aq NaHCO3 (1.5
mL) containing Na2S2O3 (420 mg). The aqueous phase was extract-
ed with Et2O (2 × 15 mL) and the combined organic extracts were
washed successively with sat. aq NaHCO3 (10 mL) and brine (10
mL), and dried (Na2SO4). After filtration, and the filtrate was con-
centrated under reduced pressure to give the crude aldehyde as a
yellowish oil, which was used as such in the next step. To this crude
aldehyde, t-BuOH (2 mL), 1-methylcychlohex-1-ene (1.90 mL) and
a solution of NaH2PO4 (75 mg) in H2O (1 mL) were sequentially
added. The reaction mixture was cooled to 0 °C and a solution of
NaClO2 (50 mg) in H2O (0.5 mL) was added dropwise and then al-
lowed to warm to r.t., and stirred for 12 h. The mixture was then bas-
ified with sat. aq NaHCO3 and extracted with hexane (2 × 10 mL).
The aqueous layer was acidified to pH 2–3 with aq 1 N HCl and ex-
tracted with EtOAc (2 × 15 mL). The combined organic extracts
were washed with brine (10 mL) and dried (Na2SO4). After filtra-
tion, the filtrate was concentrated under reduced pressure to give the
crude product as a yellowish oil, which was purified by chromatog-
raphy (SiO2) using a mixture of PE and EtOAc (1:2) to provide the
product 20 as a colorless viscous liquid; yield: 30 mg (56% over two
steps); [a]D +10.3 (c = 1.5, CHCl3).
1H NMR (400 MHz, CDCl3): d = 7.31–7.28 (m, 5 H), 5.87–5.76 (m,
1 H), 5.72–5.63 (m, 1 H), 5.31–5.21 (m, 2 H), 5.15–5.00 (m, 2 H),
4.64 (d, J = 6.7 Hz, 1 H), 4.53–4.40 (m, 3 H), 4.37–4.07 (m, 2 H),
3.96–3.81 (m, 1 H), 3.75–3.67 (m, 2 H), 3.63–3.62 (m, 1 H), 3.32
(3.28) (s, 3 H), 1.43 (1.41) (9 H, s).
13C NMR (100 MHz, CDCl3): d = 155.6, (155.5), 138.4 (138.2),
136.3 (136.1), 135.9 (135.4), 128.4 (128.3) 127.6 (127.5), 119.5,
118.9, 115.3 (115.0), 94.0 (93.8), 80.0 (79.5), 76.6 (76.5), 72.9, 69.1
(68.7), 59.3 (58.9), 55.7 (55.6), 48.7, 28.5 (28.4).
MS (TOF MS ES+): m/z = 414 (M+ + Na).
Anal. Calcd for C22H33NO5: C, 67.49; H, 8.50; N, 3.58. Found: C,
67.62; H, 8.74; N, 3.32.
tert-Butyl (5R,6R)-6-(Benzyloxymethyl)-5-(methoxymethoxy)-
5,6-dihydropyridine-1(2H)-carboxylate (18)
Grubbs’catalyst 17 (11 mg, 5 mol%) was added to a stirred solution
of the diene 16 (100 mg, 0.25 mmol) in anhyd degassed CH2Cl2 (30
mL) under argon and the homogeneous mixture was stirred at r.t. for
4 h. The mixture was concentrated in vacuo and the residual mass
was chromatographed over silica gel using 8% EtOAc in PE as elu-
ent to give the product 18 as a colorless viscous liquid; yield: 78 mg
(84%); [a]D –14.2 (c = 2.5, CHCl3).
IR (neat): 3458, 2938, 1690, 1686, 1420, 1366, 1154, 1039, 918
cm–1.
1H NMR (400 MHz, CDCl3): d = 5.03 (br s, 1 H), 4.75 (d, J = 7.2
Hz, 1 H), 4.73 (d, J = 6.8 Hz, 1 H), 3.95–3.72 (m, 3 H), 3.36 (s, 3
H), 2.88–2.66 (m, 1 H), 1.89–1.76 (m, 1 H), 1.70–1.55 (m, 2 H),
1.49–1.43 (m, 1 H), 1.37 (s, 9 H).
13C NMR (75 MHz, CDCl3): d = 170.4, 155.5, 95.7, 80.8, 73.7,
58.9, 56.1, 36.3, 28.3, 23.8, 23.4.
HRMS (TOF MS ES+): m/z calcd for C13H23NO6 + Na (M+ + Na):
312.1423; found: 312.1422.
IR (neat): 2977, 1698, 1368, 1274, 1165, 1039, 918 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.32–7.24 (m, 5 H), 5.66 (br s, 2
H), 4.74–4.55 (m, 4 H), 4.41 (br s, 2 H), 4.22–4.03 (m, 1 H), 3.65–
3.61 (m, 1 H), 3.56–3.54 (m, 1 H), 3.46–3.42 (m, 1 H), 3.38 (s, 3 H),
1.46 (s, 9 H).
13C NMR (100 MHz, CDCl3): d = 155.2, 138.6, 128.1, 127.3, 126.3,
125.3, 124.9, 95.8, 79.9, 72.5, 70.9, 65.2, 55.6, 51.7 (49.4), 40.5
(39.7), 28.3.
(2S,3R)-3-Hydroxypiperidine-2-carboxylic Acid (1)
Compound 20 (58 mg, 0.2 mmol) was dissolved in a mixture of
EtOH (0.5 mL) and aq 6 N HCl (2 mL) and the mixture was heated
to 90 °C for 12 h while stirring. The mixture was allowed to come
to r.t. and concentrated in vacuo to leave a crude residue. This was
purified by flash chromatography over silica gel using a mixture of
CHCl3–MeOH–30% aq NH3 (4:5:1) to provide compound 1 as an
off-white solid; yield: 22 mg (74%); [a]D –51.6 (c = 0.8, H2O)
{Lit.20 [a]D –52.8 (c = 0.6, H2O)}.
1H NMR (400 MHz, D2O): d = 4.51–4.44 (m, 1 H), 3.59 (d, J = 1.8
Hz, 1 H), 3.41–3.35 (m, 1 H), 2.99–2.87 (m, 1 H), 1.98–1.89 (m, 2
H), 1.77–1.65 (m, 2 H).
HRMS (TOF MS ES+): m/z calcd for C20H29NO5 + Na (M+ + Na):
386.1943; found: 386.1925.
tert-Butyl (2R,3R)-2-(Hydroxymethyl)-3-(methoxymethoxy)pi-
peridine-1-carboxylate (19)
Pd/C (10%, 20 mg) was added to a stirred solution of the cycloolefin
18 (100 mg, 0.275 mmol) in EtOAc (4.0 mL) and the heterogeneous
mixture was stirred for 12 h. at r.t. under H2. The mixture was fil-
tered through Celite and the filter cake was washed with EtOAc
(1 × 5 mL). The combined filtrates were concentrated under re-
duced pressure to leave the crude product as a colorless liquid,
which was passed through a short pad of silica gel using 10%
EtOAc in PE as eluent to provide the product 19 as a colorless liq-
uid; yield: 72 mg (94%); [a]D –10.3 (c = 2.25, CHCl3).
13C NMR (100 MHz, D2O): d = 172.6, 65.9, 63.6, 44.8, 30.1, 17.5.
tert-Butyl (S)-4-[(S)-1-(Methoxymethoxy)allyl]-2,2-dimethylox-
azolidine-3-carboxylate (22)
IR (neat): 3454, 2939, 1693, 1367, 1156, 1041, 771 cm–1.
(i-Pr)2EtNH (540 mL, 3.12 mmol) and MOMCl (175 mL, 234 mmol)
were sequentially added dropwise to a stirred ice-cooled solution of
the allyl alcohol 21 (400 mg, 1.56 mmol) in anhyd CH2Cl2 (5 mL)
under N2. The reaction mixture was stirred for 24 h at r.t. and then
diluted with CH2Cl2 (25 mL). The organic layer was washed succes-
sively with H2O (25 mL) and brine (25 mL), and dried (Na2SO4). It
was then filtered and the filtrate was concentrated under vacuo to
leave a crude product, which was purified by column chromatogra-
phy using 10% EtOAc in PE as eluent to give 22 as a colorless oil;
yield: 375 mg (80%); [a]D –71.4 (c = 1.2, CHCl3).
1H NMR (400 MHz, CDCl3): d = 4.62 (d, J = 6.8 Hz, 1 H), 4.60 (d,
J = 6.8 Hz, 1 H), 4.45 (br s, 1 H), 3.93 (dd, J = 11.2, 6.8 Hz, 1 H),
3.88–3.82 (m, 1 H), 3.74–3.65 (m, 2 H), 3.32 (s, 3 H), 2.72–2.61 (m,
1 H), 1.85–1.82 (m, 2 H), 1.66–1.61 (m, 1 H), 1.51–1.43 (m, 1 H),
1.40 (s, 9 H).
13C NMR (100 MHz, CDCl3): d = 155.3, 94.7, 79.6, 73.7, 58.2,
55.1, 54.4, 38.4, 27.8, 25.7, 23.4.
HRMS (TOF MS ES+): m/z calcd for C13H25NO5 + Na (M+ + Na):
298.1630; found: 298.1648.
IR (neat): 2978, 2932, 1699, 1386, 1098, 1029 cm–1.
1H NMR (400 MHz, CDCl3): d = 5.79–5.74 (m, 1 H), 5.35–5.27 (m,
2 H), 4.71 (d, J = 6 Hz, 1 H), 4.56 (d, J = 6 Hz, 1 H), 4.53–4.41 (m,
1 H), 4.08–4.06 (m, 1 H), 4.03–3.92 (m, 2 H), 3.37 (3.35) (s, 3 H),
1.52–1.46 (merged singlets, 15 H).
(2S,3R)-1-(tert-Butoxycarbonyl)-3-(methoxymethoxy)piperi-
dine-2-carboxylic Acid (20)
Dess–Martin periodinane (86 mg, 0.20 mmol) was added to a stirred
solution of the alcohol 19 (50 mg, 0.18 mmol) in anhyd CH2Cl2 (2.5
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S. K. Chattopadhyay et al.
PAPER
13C NMR (100 MHz, CDCl3): d = 151.9 (152.4), 133.7 (134.4),
120.2 (119.8), 94.3 (93.8), 79.9 (80.2), 76.3 (76.0), 63.6 (63.4), 59.5
(59.7), 55.3 (55.5), 28.4, 25.8 (26.6), 22.8 (23.2).
mixture was extracted with EtOAc (25 mL) and the organic extract
was successively washed with H2O (25 mL), brine (25 mL), and
dried (Na2SO4). After filtration, and the filtrate was concentrated
under vacuo to leave a crude product, which was purified by column
chromatography over silica gel using 5% EtOAc in PE as eluent to
give the N-allylated product 25 as a colorless liquid; yield: 168 mg
(78%); [a]D –23.2 (c = 2.2, CHCl3).
MS (TOF MS ES+): m/z = 324 (M+ + Na).
Anal. Calcd for C15H27NO5: C, 59.78; H, 9.03; N, 4.65. Found: C,
59.61; H, 8.84; N, 4.79.
IR (neat): 3073, 2932, 1694, 1473, 1365, 1112, 1029, 703 cm–1.
tert-Butyl (2S,3S)-1-Hydroxy-3-(methoxymethoxy)pent-4-en-2-
ylcarbamate (23)
1H NMR (400 MHz, CDCl3): d = 7.65–7.63 (m, 4 H), 7.42–7.35 (m,
6 H), 5.91–5.88 (m, 1 H), 5.63–5.55 (m, 1 H), 5.27–4.99 (m, 4 H),
4.61 (d, J = 6.8 Hz, 1 H), 4.47 (dd, J = 10.8, 6.8 Hz, 1 H), 4.34–4.23
(m, 2 H), 3.95–3.87 (m, 2 H), 3.80–3.76 (m, 2 H), 3.28 (s, 3 H), 1.45
(s, 9 H), 1.04 (s, 9 H).
13C NMR (100 MHz, CDCl3): d = 155.8, 136.3, 135.4, 134.8, 133.4,
129.7, 127.7, 118.9, 115.1, 94.0, 79.8, 76.7, 62.0, 60.4, 55.7, 55.6,
28.4, 26.6, 19.2.
PTSA (35 mg) was added to a solution of the oxazolidine 22 (300
mg, 0.99 mmol) in MeOH (4 mL) and the reaction mixture was
stirred at r.t. for 4 h. The mixture was then quenched with 5% aq
NaHCO3 (5 mL) and concentrated, diluted with H2O (10 mL), and
extracted with EtOAc (25 mL). The combined organic extracts were
washed with H2O (2 × 20 mL) followed by brine (10 mL). After
drying (Na2SO4) and filtration, the filtrate was concentrated in
vacuo. The residue was chromatographed on silica gel using 30%
EtOAc in PE as eluent to give the product 23 as a colorless liquid;
yield: 203 mg (78%); [a]D –63.2 (c = 1.5, CHCl3).
MS (TOF MS ES+): m/z = 562 (M+ + Na).
Anal. Calcd for C31H45NO5Si: C, 68.98; H, 8.40; N, 2.59. Found: C,
68.77; H, 8.24; N, 2.64.
IR (neat) 3445, 2930, 1699, 1170, 1033, 772 cm–1.
1H NMR (400 MHz, CDCl3): d = 5.81–5.73 (m, 1 H), 5.37–5.29 (m,
2 H), 5.00 (br s, 1 H), 4.68 (d, J = 6.4 Hz, 1 H), 4.56 (d, J = 6.8 Hz,
1 H), 4.28 (dd, J = 7.2, 2.4 Hz, 1 H), 3.79–3.65 (m, 3 H), 3.40 (s, 3
H), 1.44 (s, 9 H).
13C NMR (100 MHz, CDCl3): d = 156.4, 134.6, 119.1, 94.2, 79.7,
76.5, 63.2, 55.8, 55.4, 28.4.
tert-Butyl (2S,3S)-6-[(tert-Butyldiphenylsilyloxy)methyl]-5-
(methoxymethoxy)-5,6-dihydropyridine-1(2H)-carboxylate
(26)
Grubbs’catalyst 17 (15 mg, 5 mol%) was added to a stirred solution
of the diene 25 (200 mg, 0.37 mmol) in anhyd degassed CH2Cl2 (40
mL) and the homogeneous mixture was stirred for 4 h under argon.
The solvent was removed in vacuo and the residual mass was chro-
matographed over silica gel using 8% EtOAc in PE as eluent to give
the cycloolefin 26 as a colorless liquid; yield: 157 mg (83%); [a]D
+18.6 (c = 1.2, CHCl3).
MS (TOF MS ES+): m/z = 262 (M+ + H).
Anal. Calcd for C12H23NO5: C, 55.16; H, 8.87; N, 5.36. Found: C,
54.98; H, 8.89; N, 5.27.
IR (neat): 2931, 1698, 1412, 1365, 1104, 1053, 1037, 770 cm–1.
tert-Butyl (5S,6S)-10,10-Dimethyl-9,9-diphenyl-5-vinyl-2,4,8-
trioxa-9-silaundecan-6-ylcarbamate (24)
1H NMR (400 MHz, CDCl3): d = 7.67–7.65 (m, 4 H), 7.43–7.35 (m,
6 H), 5.64–5.56 (m, 2 H), 4.90–4.69 (m, 1 H), 4.56 (s, 2 H), 4.35–
4.31 (m, 2 H), 4.09–4.07 (m, 1 H), 3.82 (dd, J = 10.8, 4 Hz, 1 H),
3.67 (t, J = 7.2 Hz, 1 H), 3.24 (s, 3 H), 1.48 (s, 9 H), 1.03 (s, 9 H).
13C NMR (100 MHz, CDCl3): d = 155.0, 135.6, 133.6, 129.6, 127.6,
126.5, 125.0, 95.6, 79.7, 71.0 (70.8), 59.1, 55.5, 53.8 (51.8), 40.6
(39.6), 28.5, 26.8, 19.2.
Et3N (640 mL, 4.60 mmol) and TBDPSCl (558 mL, 2.30 mmol) were
added sequentially to an ice-cold solution of the alcohol 23 (400
mg, 1.53 mmol) and DMAP (5 mg) in anhyd CH2Cl2 (2 mL) under
N2 and the reaction mixture was stirred for 12 h. The mixture was
diluted with CH2Cl2 (25 mL) and the organic extract was washed
successively with aq 1 N HCl (25 mL), H2O (25 mL), and brine (20
mL), and dried (Na2SO4). After filtration, the filtrate was concen-
trated under reduced pressure to leave a crude product, which was
purified by chromatography over silica gel using a mixture of
EtOAc and PE (1:20) to afford the silyl ether 24 as a colorless oil;
yield: 626 mg (82%); [a]D –35.1 (c = 1.5, CHCl3).
HRMS (TOF MS ES+): m/z calcd for C29H41NO5Si + Na (M+ + Na):
534.2652; found: 534.2658.
tert-Butyl (2S,3S)-2-[(tert-Butyldiphenylsilyloxy)methyl]-3-
(methoxymethoxy)piperidine-1-carboxylate (27)
IR (neat): 2487, 2930, 1699, 1263, 1130, 772 cm–1.
Pd/C (10%, 10 mg) was added to a stirred solution of the olefin 26
(150 mg, 0.293 mmol) in EtOAc (4.0 mL) and the heterogeneous
mixture was stirred for 12 h at r.t. under H2. The mixture was fil-
tered on Celite and the filter cake was washed with EtOAc (1 × 5
mL). The combined filtrates were concentrated to leave a crude
mass, which was passed through a short pad of silica gel using 10%
EtOAc in PE as eluent to give the product 27 as a colorless liquid;
yield: 127 mg (85%); [a]D +27.5 (c = 1.5, CHCl3).
1H NMR (400 MHz, CDCl3): d = 7.67–7.65 (m, 4 H), 7.45–7.36 (m,
6 H), 5.81–5.74 (m, 1 H), 5.32–5.25 (m, 2 H), 4.80 (d, J = 9.6 Hz, 1
H), 4.65 (d, J = 6.4 Hz, 1 H), 4.52 (d, J = 6.4 Hz, 1 H), 4.34 (dd,
J = 7.2, 3.6 Hz, 1 H), 3.85–3.84 (m, 1 H), 3.74–3.69 (m, 2 H), 3.30
(s, 3 H), 1.42 (s, 9 H), 1.06 (s, 9 H).
13C NMR (100 MHz, CDCl3): d = 155.6, 135.6, 135.3, 133.4, 129.8,
127.7, 118.8, 94.4, 79.1, 75.8, 63.0, 55.7, 55.1, 28.4, 26.9, 19.3.
IR (neat): 2930, 1698, 1416, 1252, 1108, 1040, 704 cm–1.
HRMS (TOF MS ES+): m/z calcd for C28H41NO5Si: 522.2652;
found: 522.2656.
1H NMR (400 MHz, CDCl3): d = 7.70–7.68 (m, 4 H), 7.42–7.36 (m,
6 H), 4.60–4.54 (m, 3 H), 3.96–3.91 (m, 3 H), 3.68–3.67 (m, 1 H),
3.29 (s, 3 H), 2.75–2.72 (m, 1 H), 1.79–1.78 (m, 1 H), 1.61–1.49 (m,
3 H), 1.46 (s, 9 H), 1.03 (s, 9 H).
tert-Butyl Allyl[(5S,6S)-10,10-dimethyl-9,9-diphenyl-5-vinyl-
2,4,8-trioxa-9-silaundecan-6-yl]carbamate (25)
A solution of the compound 24 (200 mg, 0.4 mmol) in anhyd DMF
(0.5 mL) was added dropwise to an ice-cooled solution of NaH (24
mg, 1.0 mmol) in anhyd DMF (2 mL) under N2. The mixture was
stirred for 10 min at the same temperature. Allyl bromide (102 mL,
1.20 mmol) was then added dropwise to the reaction mixture and it
was allowed to come to r.t. while stirring for 12 h. The mixture was
cooled back to 0 °C and quenched with sat. aq NH4Cl (5 mL). The
13C NMR (100 MHz, CDCl3): d = 155.0, 135.7, 133.6, 129.6, 127.6,
95.0, 79.4, 73.7, 59.0, 55.4, 51.8, 40.6, 29.7, 28.5, 26.8, 24.9, 19.2.
MS (TOF MS ES+): m/z = 536 (M+ + Na).
Anal. Calcd for C29H43NO5Si: C, 67.80; H, 8.44; N, 2.73. Found: C,
68.11; H, 8.65; N, 2.58.
Synthesis 2011, No. 16, 2664–2670 © Thieme Stuttgart · New York

PAPER
Stereoselective Synthesis of cis-Hydroxypiperidine Derivatives
2669
tert-Butyl (2S,3S)-2-(Hydroxymethyl)-3-(methoxymethoxy)pip-
eridine-1-carboxylate (28)
(7) (a) Enders, D.; Nolte, B.; Runsink, J. Tetrahedron:
Asymmetry 2002, 13, 587. (b) Lillelund, V. H.; Jensen, H.
H.; Liang, X.; Bols, M. Chem. Rev. 2002, 102, 515.
(c) Meyers, A. I.; Andres, C. J.; Resek, J. E.; Woodall, C. C.;
McLaughlin, M. A.; Lee, P. H.; Price, D. A. Tetrahedron
1999, 55, 8931.
Bu4NF (57 mg, 0.219 mmol) was added in one portion to a solution
of the silyl ether 27 (75 mg, 0.146 mmol) in anhyd THF (2 mL) and
the resulting solution was stirred for 4 h at r.t. The mixture was di-
luted with CH2Cl2 (25 mL) and the organic layer was washed suc-
cessively with H2O (20 mL), brine (25 mL), and dried (Na2SO4).
After filtration, the filtrate was concentrated under reduced pressure
to leave the crude product, which was purified by column chroma-
tography over silica gel using 25% EtOAc in PE as eluent to give
the alcohol 28 as a colorless liquid; yield: 33 mg (82%); [a]D +11.1
(c = 2.2, CHCl3).
(8) (a) Kuehl, F. A. Jr.; Spencer, C. F.; Folkers, K. J. Am. Chem.
Soc. 1948, 70, 2091. (b) Kobayashi, S.; Ueno, M.; Suzuki,
R. Tetrahedron Lett. 1999, 40, 2175.
(9) For synthetic reports on trans-(2S,3S)-3-hydroxypipecolic
acid, see: (a) Chavan, S. P.; Dumare, N. B.; Harale, K. R.;
Kalkote, U. R. Tetrahedron Lett. 2011, 52, 404. (b) Lemire,
A.; Charette, A. B. J. Org. Chem. 2010, 75, 2077. (c) Liu,
L.-X.; Peng, Q.-L.; Huang, P.-Q. Tetrahedron: Asymmetry
2008, 19, 1200. (d) Kim, I. S.; Ji, Y. J.; Jung, Y. H.
Tetrahedron Lett. 2006, 47, 7289. (e) Agami, C.; Couty, F.;
Mathieu, H. Tetrahedron Lett. 1996, 37, 4001. For the
(2R,3R)-isomer, see: (f) Alegret, C.; Ginesta, X.; Riera, A.
Eur. J. Org. Chem. 2008, 1789. (g) Haddad, M.;
IR (neat): 3437, 2931, 1690, 1365, 1154, 1041 cm–1.
1H NMR (400 MHz, CDCl3): d = 4.70 (d, J = 6.8 Hz, 1 H), 4.68 (d,
J = 6.8 Hz, 1 H), 4.55 (br s, 1 H), 4.00 (dd, J = 11.2, 6 Hz, 1 H), 3.94
(br s, 1 H), 3.82–3.73 (m, 2 H), 3.39 (s, 3 H), 2.75 (br s, 1 H), 1.94–
1.91 (m, 2 H), 1.73–1.70 (m, 1 H), 1.62–1.55 (m, 1 H), 1.46 (s, 9 H).
13C NMR (100 MHz, CDCl3): d = 155.3, 95.2, 80.2, 74.3, 59.0,
55.7, 54.7, 39.0, 28.4, 26.2, 23.9.
Larcheveque, M. Tetrahedron Lett. 2001, 42, 5223. For
common approaches to both (2S,3S)- and (2R,3R)-isomers,
see: (h) Kumar, P.; Bodas, M. S. J. Org. Chem. 2005, 70,
360. (i) Scott, J. D.; Tippie, T. N.; Williams, R. M.
Tetrahedron Lett. 1998, 39, 3659. (j) Battistini, L.; Zanardi,
F.; Rassu, G.; Spanu, P.; Pelosi, G.; Fava, G. G.; Ferrari, M.
B.; Casiraghi, G. Tetrahedron: Asymmetry 1997, 8, 2975.
(k) Greck, C.; Ferreira, F.; Genet, J. P. Tetrahedron Lett.
1996, 37, 2031.
HRMS (TOF MS ES+): m/z calcd for C13H25NO5 + Na (M+ + Na):
298.1630; found: 298.1633.
Acknowledgment
We are thankful to DST, New Delhi, for funds (Grant No. SR/S1/
OC-35/2009), and CSIR, New Delhi, for fellowships.
(10) For common approach for the synthesis of cis- and trans-3-
hydroxypipecolic acid, see: (a) Cochi, A.; Burger, B.;
Navarro, C.; Pardo, D. G.; Cossy, J.; Zhao, Y.; Cohen, T.
Synlett 2009, 2157. (b) Wang, B.; Liu, R.-H. Eur. J. Org.
Chem. 2009, 2854. (c) Yoshimura, Y.; Ohara, C.; Imahori,
T.; Saito, Y.; Kato, A.; Miyauchi, S.; Adachi, I.; Takahata,
H. Bioorg. Med. Chem. 2008, 16, 8273. (d) Kim, I. S.; Oh,
J. S.; Zee, O. P.; Jung, Y. H. Tetrahedron 2007, 63, 2622.
(e) Liang, N.; Datta, A. J. Org. Chem. 2005, 70, 10182.
(f) Jourdant, A.; Zhu, J. Tetrahedron Lett. 2000, 41, 7033.
(11) Reports on cis-(2S,3R)-3-hydroxypipecolic acid: (a)Chung,
H. S.; Shin, W. K.; Choi, S. Y.; Chung, Y. K.; Lee, E.
Tetrahedron Lett. 2010, 51, 707. (b) Kalamkar, N. B.;
Kasture, V. M.; Dhavale, D. D. J. Org. Chem. 2008, 73,
3619. (c) Pham, V.-T.; Joo, J.-E.; Tian, Y.-S.; Chung, Y.-S.;
Lee, K.-Y.; Oh, C.-Y.; Ham, W.-H. Tetrahedron:
Asymmetry 2008, 19, 318. (d) Scott, J. D.; Williams, R. M.
Tetrahedron Lett. 2000, 41, 8413. Synthesis of cis-(2R,3S)-
3-hydroxypipecolic acid: (e) Senthil Kumar, P.; Baskaran,
S. Tetrahedron Lett. 2009, 50, 3489. (f) Roemmele, R. C.;
Rapoport, H. J. Org. Chem. 1998, 54, 1866. (g) Knight, D.
W.; Lewis, N.; Share, A. C.; Haigh, D. J. Chem. Soc., Perkin
Trans. 1 1998, 3673.
(12) Chattopadhyay, S. K.; Biswas, T.; Biswas, T. Tetrahedron
Lett. 2008, 49, 1365.
(13) (a) Garner, P.; Park, J. M. J. Org. Chem. 1988, 53, 2979.
(b) McKillop, A.; Taylor, R. J. K.; Watson, R.; Lewis, N.
Synthesis 1994, 31.
(14) (a) Denis, J.-N.; Correa, A.; Greene, A. E. J. Org. Chem.
1991, 56, 6939. (b) Ibuka, T.; Habashita, H.; Otaka, A.;
Fujii, N.; Oguchi, Y.; Uyehara, T.; Yamamoto, Y. J. Org.
Chem. 1991, 56, 4370. (c) Sames, D.; Polt, R. J. Org. Chem.
1994, 59, 4596. (d) Ravikumar, J. S.; Dutta, A. Tetrahedron
Lett. 1999, 40, 1381.
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