A new synthetic route to oxazole and pyrrole 2-deoxy-C-ribosides

Article abstract of DOI:10.1016/j.tet.2007.06.110

The synthesis of oxazole and pyrrole 3-carbethoxy/3-arylsulfonyl d and l-2-deoxyribosides by TosMIC addition/cyclization on d and l-2-deoxyribo-1-carboxaldehyde and unsaturated esters in moderate to good yields is reported.

Full text of DOI:10.1016/j.tet.2007.06.110

Tetrahedron 63 (2007) 9871–9880
A new synthetic route to oxazole and pyrrole
2-deoxy-C-ribosides*
*
Palakodety Radha Krishna, V. V. Ramana Reddy and Ravula Srinivas
D-206/B, Discovery Laboratory, Organic Chemistry Division-III, Indian Institute of Chemical Technology, Hyderabad-500 007, India
Received 8 January 2007; revised 11 June 2007; accepted 28 June 2007
Available online 10 July 2007
Abstract—The synthesis of oxazole and pyrrole 3-carbethoxy/3-arylsulfonyl D and L-2-deoxyribosides by TosMIC addition/cyclization on
D and L-2-deoxyribo-1-carboxaldehyde and unsaturated esters in moderate to good yields is reported.
Ó 2007 Published by Elsevier Ltd.
Het
1. Introduction
O
O
CHO
O
RO
RO
*
*
*
*
O
CHO
*
In recent years nucleoside mimetics have attracted con-
siderable attention in synthetic chemistry owing to their
biological and chemotherapeutic properties.1 Inspired by
the recent upsurge in this area of research, we reported the
synthesis of oxazole and pyrrole C-nucleosides by the
TosMIC (tosylmethyl isocyanide) anion addition to sugar
derivatives and subsequent ring closing reaction.2 Previ-
ously, several groups have synthesized deoxy C-nucleosides
by divergent methods such as C–C bond formation between
the existing deoxyribose moiety and an appropriate nucleo-
phile,3 constructing the heteroaryl ring on 2-deoxy ribosyl
cyanide,4 aryl nucleophilic addition to either ribonolactone
or 2-deoxyribino lactone followed by deoxygenation of
the ensuing hydroxy functionality to afford corresponding
deoxy-C-ribosides5 and a Heck6 type of coupling between
the sugar anomeric carbon and a heterocycle. Interestingly,
however, the above cited researchers were limited to using
2-deoxy-D-ribose as the starting material though some recent
attempts were directed at the synthesis of 2-deoxy-D-ribo-C-
nucleosides.7 Thus the need to devise alternative yet practi-
cal synthetic protocols for deoxy-C-ribosides is warranted.
Therefore, we choose to synthesize deoxy-C-ribosides by
the key reaction of TosMIC addition and cyclization on
2-deoxy-D- and L-ribo-1-carboxaldehydes, which in turn
could be realized by a common strategy from (R) and (S)-
2,3-O-isopropylidene glyceraldehydes, respectively, as de-
lineated in Scheme 1.
*
*
R'O
R'O
H
N
H
N
O
,
,
=
Het
N
SO2Tol
COOEt
Scheme 1.
2. Results and discussion
2.1. Synthesis of D-2-deoxy-ribo oxazole and pyrrole
C-nucleosides from (R)-2,3-O-isopropylidene
glyceraldehyde
Based on our continued interest in the design and synthesis
of modified nucleosides, herein we report the synthesis of
D and L-2-deoxy-ribo oxazole and pyrrole C-nucleosides
starting from (R) and (S)-2,3-O-isopropylidene glyceralde-
hydes, respectively. Thus, the known homoallyl alcohol8 1
(Scheme 2), obtained from (R)-2,3-O-isopropylidene glycer-
aldehyde, was converted to its methyl ether (2a and 2b) by
using NaH, MeI in dry THF in good yields (81%). The
two diastereomers formed were separated by column chro-
matography wherein 2a was obtained in 73% and 2b in
8% yield. The isopropylidene group of 2a was deprotected
using 60% acetic acid to give diol 3 in 81% yield. Compound
3 was selectively protected (BnBr, K2CO3, and acetone) as
its primary benzyl ether 4 in 65% yield. Compound 4 on
treatment with mCPBA afforded a 1:1 diastereomeric mix-
ture of 2-deoxy-D-ribo-1-methanol 5 in 71% yield. The
formation of 5 could be rationalized by an epoxidation and
subsequent ring opening reaction in one pot to afford the
tetrahydrofuran moiety, which is the crucial intermediate
*
IICT Communication No. 041115.
Keywords: TosMIC; Oxazole; Pyrrole; C-ribosides; (R) and (S)-2,3-O-
Isopropylidene glyceraldehydes.
* Corresponding author. Tel.: +91 40 27160123; fax: +91 40 27160387;
e-mail: prkgenius@iict.res.in
0040–4020/$ - see front matter Ó 2007 Published by Elsevier Ltd.
doi:10.1016/j.tet.2007.06.110

9872
P. R. Krishna et al. / Tetrahedron 63 (2007) 9871–9880
O
O
O
NaH, MeI, dry THF
rt, 6 h, 81%
O
O
O
+
OH
1
OMe
2a (73%)
OMe
2b (8%)
OH
OH
60% CH3COOH
rt, 6 h, 81%
K2CO3, BnBr, Acetone
reflux,18 h, 65%
2a
OMe
3
OH
OMe
4
OBn
O
O
CHO
mCPBA, CHCl3
BnO
(COCl)2, DMSO
BnO
OH
rt, 6 h, 71%
Et3N, CH2Cl2
99%
MeO
MeO
5
6
Scheme 2.
in the present study. Further, methanol 5 was oxidized to
aldehyde 6 under Swern oxidation conditions in 99% yield.
After successful preparation of 6, 7, and 8, we aimed at the
construction of oxazole and pyrrole nucleosides (Scheme 4).
Firstly, aldehyde 6 on treatment with potassium salt of Tos-
MIC2 in methanol resulted in a chromatographically separa-
ble a/b anomeric mixture of oxazole-C-ribosides 9a and 9b
in 50% under our earlier reported reaction conditions.2 Like-
wise treatment of 7 and 8 independently with lithium salt of
TosMIC2 afforded the corresponding pyrrole C-nucleosides
10a (36%), 10b (32%), 11a (35%), and 11b (34%). The
a/b anomeric mixtures of all pyrrole C-ribonucleosides
were resolved into pure entities by column chromatography
and thoroughly characterized. The assignment of a,b-nucleo-
sides was made based on Kool’s9 observation for deoxy
nucleosides by comparing the multiplicity of H-1 proton.
The reported 1H NMR values for b-C-nucleosides revealed
2.2. a,b Unsaturated ester/aryl sulfonyl ester function-
ality needs to be developed for obtaining a pyrrole ring
Accordingly, aldehyde 6 (Scheme 3) on treatment with
(ethoxycarbonylmethylene)triphenylphosphorane in reflux-
ing benzene was converted to a,b unsaturated ester 7
(72%, only E isomer). Independently, aldehyde 6 on expo-
sure to the lithium salt of methyl-p-toulyl sulfone in a mix-
ture of THF and HMPA (7:3) led to the addition product,
which was further converted to a,b unsaturated aryl sulfonyl
ester 8 (61%, two steps, only E isomer) on dehydration under
MsCl, NEt3, and CH2Cl2 conditions.
COOEt
O
Ph3PCHCOOEt, C6H6
reflux, 1 h, 72%
1. TolSO2CH3, n-BuLi,
dry THF + HMPA,
-78 °C, 0.5 h, 71%
BnO
O
CHO
7
MeO
BnO
BnO
SO2Tol
O
MeO
6
MeO
2. MsCl, N(Et)3,
CH2Cl2, rt, 2 h, 86%
8
Scheme 3.
N
N
O
O
O
O
BnO
BnO
BnO
TosMIC, K2CO3
+
6
9b
MeO
MeOH, reflux, 1 h
50% (27 + 23)
MeO
9a
H
H
N
N
O
O
COOEt
SO2Tol
COOEt
SO2Tol
BnO
TosMIC, n-BuLi
+
+
7
THF, -78 °C, 0.5 h,
68% (36+32)
10b
MeO
10a
MeO
H
H
N
N
O
O
BnO
TosMIC, n-BuLi
BnO
8
THF, -78 °C, 0.5 h,
69% (35 + 34)
11a
MeO
MeO
11b
Scheme 4.

P. R. Krishna et al. / Tetrahedron 63 (2007) 9871–9880
9873
that H-1 proton resonates as a double doublet (J 10.0,
5.0 Hz) while the same proton for a isomer appears as a trip-
let (J 6.0 Hz). In comparison, for b-C-nucleosides 9a, 10a,
and 11a the H-1 proton resonated as double doublet (J 9–
10, 5–6 Hz) and for a-C-nucleosides 9b, 10b, and 11b H-1
proton appeared as a triplet (7-7.5 Hz). The 1-D-NOE studies
(Fig. 1) carried out on 10a and 10b unequivocally estab-
lished the assigned stereochemistry at the anomeric carbon
for both the isomers was indeed true. The same analogy
was extended to other C-nucleosides for their stereochem-
ical evaluation.
of 2-deoxy L-ribose are already reported,14 their C-nucleo-
sides are rare. Hence, synthesis of C-nucleosides of 2-de-
oxy-L-ribosides was considered important.15 Herein we
also report the synthesis of L-ribose-1-methanol from
(S)-2,3-O-isopropylidene glyceraldehyde and its C-oxazole
and pyrrole derivatives.
Consequently, 2-deoxy-L-ribo-1-methanol (16, Scheme 5) is
identified as an appropriate starting material, which could be
obtained by adopting conceptually a related strategy to that
devised for 5. Thus applying the same sequence of reactions
on the known8 homoallyl alcohol 12 resulted in 16 in 24%
yield, which was oxidized to aldehyde 17 under Swern’s
conditions. TosMIC addition reaction (Scheme 5) on 17
and 18 resulted in both oxazole (19a and 19b) and pyrrole
(20a and 20b) C-nucleosides, respectively, as 1:1 anomeric
mixtures that were easily separated by column chromato-
graphy. The stereochemical assignment was made individu-
ally for each L-nucleosides and it was found that the 1H NMR
spectra displayed the same multiplicity for H-1 as that ob-
served for their corresponding D-ribo-analogs. For instance,
2.3. Synthesis of L-2-deoxy-ribo oxazole and pyrrole
C-nucleosides from (S)-2,3-O-isopropylidene
glyceraldehyde
Next we focused our attention on the preparation of L-nucle-
osides. Due to the specificity of enzymes, L-ribose modified
oligoribonucleotides become attractive candidates for diag-
nostic and therapeutic uses because L-RNA ligands remain
uncleaved in biological fluids.10 For these reasons, modified
L-nucleosides, especially L-ribose and its derivatives are of
interest. So far, several syntheses of L-ribose and L-ribosides
from L-arabinose,11a,b D-glucose,12 D-ribose,11b L-xylose,13
and D-galactose11a have been reported. Besides, the syn-
thesis of L-nucleosides is complicated by the unavailability
of L-sugars as starting materials. Though some syntheses
1
in the H NMR spectra H-1 of a nucleosides resonated as
double doublet and the same proton appeared as a triplet
in b-nucleosides. The b-nucleosides were further confirmed
by comparing the sign of optical rotation values, which
proved to be opposite to that of D-nucleosides [10a. [a]D
+51.6 (c 0.8, CHCl3), 20a. [a]D À46.3 (c 0.6, CHCl3) and
10b. [a]D À15.4 (c 0.8, CHCl3), 20b. [a]D +17.1 (c 0.35,
CHCl3)].
H
N
.
.
4 4
%
4 0
%
%
H
N
After successfully establishing a synthetic route to deoxy
nucleosides, we examined the synthesis of nucleosides
with easily removable protecting groups at C-3 and C-5
(Scheme 6) to demonstrate the efficacy of the protocol and
their potential use in the synthesis of oligomers. Toward
this endeavor, the synthetic sequence was repeated by
changing the protecting group from OMe to OBn (13). Ex-
pectedly, similar observations were made in obtaining the
H
.
2 1
H
H
H
H
H
O
H
H
BnO
O
H
BnO
COOEt
%
.
H4 7
.
COOEt
%
6 5
H
MeO
H
MeO
H
10a
10b
Figure 1.
OH
O
O
60% CH3COOH
MeI, NaH, THF,
rt, 6 h, 70%
O
O
rt, 6 h, 80%
OMe
14
OH
OMe
13
OH
12
OH
O
mCPBA, CHCl3
BnBr, K2CO3, Acetone
reflux, 18 h, 63%
BnO
OH
rt, 6 h, 68%
OMe
15
OBn
O
MeO
16
COOEt
O
CHO
PPh3CHCOOEt, C6H6
reflux, 1 h, 70%
(COCl)2, DMSO
BnO
BnO
ET3N, CH2Cl2, 99%
MeO
MeO
18
17
TosMIC, K2CO3
MeOH, reflux, 1 h
53% (28 + 25)
TosMIC, n-BuLi
THF, -78 °C, 0.5 h,
71% (37 + 34)
N
N
O
O
O
H
N
H
N
O
BnO
+
BnO
O
O
MeO
MeO
COOEt
+
COOEt
19b
BnO
19a
BnO
MeO
MeO
20a
20b
Scheme 5.

9874
P. R. Krishna et al. / Tetrahedron 63 (2007) 9871–9880
OH
O
O
60% CH3COOH
NaH, BnBr, THF
O
O
rt, 6 h, 94%
rt, 6 h, 84%
OBn
OH
OH
1
OBn
21
22
OH
O
K2CO3, BnBr, Acetone
reflux, 18 h, 68%
m-CPBA, CHCl3
(COCl)2, DMSO
BnO
OH
rt, 6 h, 74%
Et3N, CH2Cl2, 96%
OBn
OBn
BnO
23
24
O
COOEt
CHO
O
TosMIC, n-BuLi
dry THF, -78 °C, 0.5 h,
70% (36+34)
PPh3CHCOOEt, C6H6
reflux, 1 h, 69%
BnO
BnO
BnO
BnO
25
26
H
N
H
N
O
O
BnO
COOEt
COOEt
BnO
+
BnO
BnO
27a
27b
Scheme 6.
a,b-anomeric ratios of C-ribosides as observed earlier
(Schemes 1, 2, and 3). The study resulted in pyrrole 2-deoxy
D-ribo-C-nucleosides 27a and 27b.
stirred solution of 1 (8.3 g, 47.1 mmol) in dry THF (80 mL)
at 0 ꢀC was added sodium hydride (3.77 g, 94.2 mmol,
60% dispersion in mineral oil) and the mixture was stirred
for 20 min. Methyl iodide (10 g, 70.7 mmol) was added
and the mixture was stirred for 6 h. The reaction mixture
was quenched by the addition of satd NH4Cl (20 mL) at
0 ꢀC and stirred for 10 min. The organic compound was
extracted into EtOAc (2Â100 mL). The organic layer was
washed with water (1Â50 mL), brine (1Â50 mL), dried
(Na2SO4), and concentrated under reduced pressure. The
crude product was purified by column chromatography
(60–120 Silica gel, 1:50 EtOAc:hexane) to obtain 2a
(6.5 g, 73%) as a colorless liquid. Rf (10% EtOAc/hexane)
0.32; [a]D +7.0 (c 1.0, CHCl3); 1H NMR (300 MHz,
CDCl3): d 5.90–5.76 (m, 1H, –CH]CH2), 5.07–5.10 (m,
2H, –CH]CH2), 4.00–3.92 (m, 2H, –CH2O), 3.84–3.79
(m, 1H, –CHO), 3.40 (s, 3H, –CHOCH3), 3.24 (q, J
6.0 Hz, 1H, –CHOMe), 2.35 (dt, J 13.3, 5.9 Hz, 1H,
–CHCH]CH2), 2.25 (dt, J 13.2, 6.0 Hz, 1H, –CHCH]
CH2), 1.38 (s, 3H, CH3), 1.30 (s, 3H, CH3); 13C NMR
(75 MHz, CDCl3): d 17.2, 28.1, 57.1, 62.5, 70.1, 100.4,
109.5, 126.1; IR (neat): 3100, 2950, 1620, 1460,
1400 cmÀ1; FABMS (m/z, %): 187 (M++H, 16%), 109
(32), 95 (72), 81 (76). Anal. Calcd for C10H18O3; C 64.49,
H 9.74%; found C 64.75, H 9.53%.
3. Conclusion
In conclusion the synthesis of oxazole and substituted
pyrrole 2-deoxy-D and -ribo-C-nucleosides is reported for
the first time by the TosMIC approach. Novel routes were
accomplished for the synthesis of 2-deoxy-D- and L-ribose-
1-methanol from readily accessible (R)- and (S)-2,3-O-iso-
propylidene glyceraldehydes, respectively, in simple steps.
Additionally, synthesis of L-ribo-C-nucleosides, a rare class
of valuable compounds is also disclosed.
4. Experimental
4.1. General
Solvents were dried over standard drying agents and freshly
distilled prior to use. Chemicals were purchased and used
without further purification. All column chromatographic
separations were performed using silica gel (Acme’s, 60–
120 mesh). Organic solutions were dried over anhydrous
Na2SO4 and concentrated below 40 ꢀC vacuo.1H NMR
(200 MHz, 300 MHz, and 400 MHz) and 13C NMR
(50 MHz and 75 MHz) spectra were measured with a Varian
Gemini FT-200 MHz spectrometer, Bruker Avance
300 MHz and Unity 400 MHz with tetramethylsilane as
internal standard for solutions in deuteriochloroform. J
values are given in hertz. IR spectra were recorded on
Perkin–Elmer IR-683 spectrophotometer with NaCl optics.
Optical rotations were measured with JASCO DIP 300
digital polarimeter at 25 ꢀC. Mass spectra were recorded
on CEC-21-11013 or Finnigan Mat 1210 double focusing
mass spectrometers operating at a direct inlet system.
The second eluted was 2b (0.71 g, 8%). Rf (10% EtOAc/
hexane) 0.31; [a]D +2.4 (c 1.0, CHCl3); 1H NMR
(300 MHz, CDCl3): d 5.90–5.76 (m, 1H, –CH]CH2),
5.10–5.00 (m, 2H, –CH]CH2), 4.10 (dd, J 13.9, 6.4 Hz,
1H, –CH2O), 3.92 (dd, J 7.9, 6.7 Hz, 1H, –CH2O), 3.61 (t,
J 7.5 Hz, 1H, –CHO), 3.44 (s, 3H, –OCH3), 3.21 (q, J
6.4 Hz, 1H, –CHOCH3), 2.32–2.08 (m, 2H, –CH2CH]
CH2), 1.38 (s, 3H, CH3), 1.30 (s, 3H, CH3); 13C NMR
(75 MHz, CDCl3): d 16.1, 28.1, 57.1, 63.5, 71.5, 100.5,
109.5, 126.1; IR (neat): 3100, 2950, 1620, 1460,
1400 cmÀ1; FABMS (m/z, %): 187 (M++H, 16%), 109
(32), 95 (72), 81 (76). Anal. Calcd for C10H18O3; C 64.49,
H 9.74%; found C 64.32, H 9.71%.
4.1.1. 1-[2,2-Dimethyl-(4R)-1,3-dioxolan-4-yl]-(1S)-3-bu-
tenyl methyl ether and 1-[2,2-dimethy-L-(4R)-1,3-dioxo-
lan-4-yl]-(1R)-3-butenyl methyl ether (2a and 2b). To a
4.1.2. 3-Methoxy-(2R,3S)-5-hexene-1,2-diol (3). The
methyl ether 2a (3 g, 16.1 mmol) was dissolved in 60% aq

P. R. Krishna et al. / Tetrahedron 63 (2007) 9871–9880
9875
acetic acid (30 mL) and stirred for 6 h. The reaction mixture
was then neutralized with solid NaHCO3 and the organic
compound was extracted with EtOAc (3Â100 mL) and
sequentially washed with satd NaHCO3 soln (2Â100 mL),
water (1Â100 mL), brine (1Â100 mL), dried (Na2SO4),
and concentrated under reduced pressure. The crude product
was purified by column chromatography (60–120 Silica gel,
1:4 EtOAc:hexane) to give 3 (1.9 g, 81%) as a light yellow
liquid. Rf (50% EtOAc/hexane) 0.49; [a]D +2.75 (c 0.81,
CHCl3); 1H NMR (200 MHz, CDCl3): d 5.92–5.69 (m, 1H,
–CH]CH2), 5.16–5.05 (m, 2H, –CH]CH2), 3.64–3.55
(m, 3H, –CH2OH and CHOH), 3.40 (s, 3H, –OCH3), 3.34–
3.24 (m, 1H, –CHOCH3), 2.34 (m, 2H, –CH2CH]CH2);
13C NMR (75 MHz, CDCl3): d 34.0, 57.5, 65.0, 66.5, 72.1,
114.5, 126.0; IR (neat): 3400, 2920, 1630, 1420,
1400 cmÀ1; FABMS (m/z, %): 169 (M++Na, 8), 147
(M++H, 54), 137 (40), 69 (60), 55 (100). Anal. Calcd for
C7H14O3; C 57.51, H 9.65%; found C 57.78, H 9.59%.
215 (4), 181 (6), 136(6), 91(100). Anal. Calcd for
C14H20O4; C 66.65, H 7.99%; found C 66.55, H 7.86%.
4.1.5. 5-Benzyloxymethyl-4-methoxy-(4S,5R)-tetra-
hydro-2-furancarbaldehyde (6). To a stirred solution of
oxalyl chloride (0.37 mL, 3.0 mmol) in dry CH2Cl2 (5 mL)
was added dry DMSO (0.47 mL, 6.1 mmol) drop wise at
À78 ꢀC. After 2 min 5 (0.7 g, 2.7 mmol) dissolved in
CH2Cl2 (5 mL) was added and stirred for 30 min. To this
Et3N (1.6 mL, 16.6 mmol) was added at À78 ꢀC and allowed
to stir at room temperature for 20 min. The reaction mixture
was diluted with CH2Cl2 (10 mL) and washed with water
(2Â5 mL), brine (1Â10 mL), dried (Na2SO4), and concen-
trated under reduced pressure to obtain 6 (0.69 g, 99%) as
a light yellow oil. The crude aldehyde was used without
further purification or characterization.
4.1.6. Ethyl 3-[5-benzyloxymethyl-4-methoxy-(4S,5R)-
tetrahydro-2-furanyl]-(E)-2-propenoate (7). To a stirred
solution of 6 (0.6 g, 2.5 mmol) in benzene (6 mL) at reflux
was added (ethoxycarbonylmethylene)triphenylphosphor-
ane (1.3 g, 3.75 mmol) and the mixture stirred at reflux for
1 h. The reaction mixture was concentrated under reduced
pressure and purified by column chromatography (60–120
Silica gel, 1:5 EtOAc:hexane) to afford 7 (0.55 g, 72%,
only E isomer) as a colorless oil. Rf (40% EtOAc/hexane)
0.52; [a]D +11.1 (c 0.9, CHCl3); 1H NMR (300 MHz,
CDCl3): d 7.27 (br s, 5H, Ar–H), 6.94–6.85 (m, 1H, –CH]
CHCOOEt), 5.98 (t, J 15.8 Hz, 1H, –CH]CHCOOEt),
4.69–4.54 (m, 1H, –CHCH]CHCOOEt), 4.54 (s, 2H,
–OCH2Ph), 4.23–4.05 (m, 2H, –COOCH2CH3), 3.93–3.83
(m, 1H, –CHOMe), 3.50–3.40 (m, 2H, –CH2OBn), 3.30 (s,
3H, –OCH3), 2.40–2.07 (m, 1H, –CH2), 1.85–1.65 (m, 1H,
–CH2), 1.29 (t, J 7.2 Hz, 3H, –COOCH2CH3); 13C NMR
(75 MHz, CDCl3): d 15.0, 31.2, 56.0, 60.0, 71.3, 72.1,
82.0, 83.1, 89.0, 127.4, 127.9, 128.9, 131.0, 135.1, 145.2,
4.1.3. 1-Benzyloxy-3-methoxy-(2R,3S)-5-hexen-2-ol (4).
To a stirred solution of 3 (1.8 g, 12.3 mmol) in acetone
(30 mL) were added K2CO3 (6.8 g, 36.9 mmol), TBAI
(0.02 g), and benzyl bromide (1.6 mL, 13.5 mmol). The
mixture was heated to reflux for 18 h. The reaction mixture
was then concentrated under reduced pressure, the crude
dissolved in water (20 mL) and extracted into EtOAc
(3Â20 mL). The organic layer was washed with water
(1Â20 mL), brine (1Â20 mL), dried (Na2SO4), and concen-
trated under reduced pressure. The crude product was puri-
fied by column chromatography (60–120 Silica gel, 1:10
EtOAc:hexane) to obtain 1-benzyloxy-3-methoxy-(2R,3S)-
5-hexen-2-ol 4 (1.9 g, 65%) as a yellow syrup. Rf (30%
1
EtOAc/hexane) 0.48; [a]D +16.5 (c 1.6, CHCl3); H NMR
(200 MHz, CDCl3): d 7.30 (br s, 5H, Ar–H), 5.90–5.75 (m,
1H, –CH]CH2), 5.12–5.02 (m, 2H, –CH]CH2), 4.53 (s,
2H, –OCH2Ph), 3.78–3.72 (m, 1H, –CHOH), 3.61–3.49
(m, 2H, –CH2OBn), 3.36 (s, 3H, –OMe), 3.24 (q, J 4.9 Hz,
1H, –CHOMe), 2.37–2.30 (m, 2H, –CH2CH]CH2), 1.40
(br s, 1H, –OH); 13C NMR (75 MHz, CDCl3): d 34.2,
57.8, 65.1, 71.1, 73.4, 81.2, 117.0, 126.9, 127.5, 128.4,
134.6, 138.0; FABMS (m/z, %): 259 (M++Na, 18), 237
(M++H, 8), 137 (40), 69(100). Anal. Calcd for C14H20O3;
C 71.16, H 8.53%; found C 71.10, H 8.49%.
163.8; IR (neat): 2960, 1660, 1450, 1190, 1010 cmÀ1
;
FABMS (m/z, %): 343 (M++Na, 2), 321 (M++H, 13), 215
(27), 138 (62), 73 (100). Anal. Calcd for C18H24O5; C
67.48, H 7.55%; found C 67.40, H 7.49%.
4.1.7. 2-Benzyloxymethyl-3-methoxy-5-[2-(4-methylphe-
nylsulfonyl)-(E)-1-ethenyl]-(2R,3S)-tetrahydrofuran (8).
To a stirred solution of methyl p-toulenesulfone (0.52 g,
3.0 mmol) in THF:HMPA (7:3, 10 mL) was added n-BuLi
(2.8 mL, 4.6 mmol, 1.6 M soln in hexanes) at À78 ꢀC and
stirred for 20 min. To this 6 (0.7 g, 2.8 mmol) dissolved in
dry THF (5 mL) was added and the mixture stirred for
30 min. The reaction mixture was quenched with satd
NH4Cl (5 mL) and the organic compound was extracted
into EtOAc (3Â10 mL). The organic layer was washed
with water (1Â10 mL), brine (1Â10 mL), dried (Na2SO4),
and concentrated under reduced pressure. The crude product
was purified by column chromatography (60–120 Silica gel,
1:3 EtOAc:hexane) to obtain the sulfone addition product
(0.83 g, 71%) as a syrupy liquid.
4.1.4. 5-Benzyloxymethyl-4-methoxy-(4S,5R)-tetra-
hydro-2-furanylmethanol (5). To a stirred solution of 4
(1.1 g, 4.7 mmol) in CHCl3 (5 mL) was added m-chloroper-
benzoic acid (1.9 g, 5.6 mmol, 50–55% in water) dissolved
in CHCl3 (10 mL) and stirred for 6 h. The reaction mixture
was diluted with CHCl3 (10 mL), washed with satd NaHCO3
(2Â5 mL), dried (Na2SO4), and concentrated under reduced
pressure. The crude product was purified by column chroma-
tography (60–120 Silica gel, 1:5 EtOAc:hexane) to obtain
alcohol 5 (0.82 g, 71%) as a yellow oil. Rf (50% EtOAc/
hexane) 0.39; [a]D +18.7 (c 1.6, CHCl3); 1H NMR
(300 MHz, CDCl3): d 7.30 (br s, 5H, Ar–H), 4.50 (s, 2H,
–OCH2Ph), 4.21–4.14 (m, 1H, –CHO–), 3.94–3.85 (m, 2H,
–CH2OBn), 3.59–3.35 (m, 3H, –CH2OH and –CHO–),
3.37 (s, 3H, –OCH3), 3.26 (q, J 4.8, 1H, CH–OMe), 2.23–
2.03 (m, 1H, –CH2), 1.90–1.76 (m, 1H, –CH2); 13C NMR
(75 MHz, CDCl3): d 39.1, 58.2, 65.2, 66.3, 72.5, 74.3,
81.9, 83.0, 127.9, 128.6, 135.0, 137.6; IR (neat): 3540,
2920, 1030, 1100 cmÀ1; FABMS (m/z, %): 253 (M++H, 2),
To the above obtained adduct (0.83 g, 1.9 mmol) in CH2Cl2
(10 mL) were added triethylamine (0.82 mL, 5.9 mmol) and
methane sulfonylchloride (0.27 mL, 2.3 mmol) and the
mixture stirred for 2 h at room temperature. The reaction
mixture was diluted with CH2Cl2 (10 mL), washed with
water (1Â10 mL), dried (Na2SO4), and concentrated under

9876
P. R. Krishna et al. / Tetrahedron 63 (2007) 9871–9880
reduced pressure. The crude product was purified by column
chromatography (60–120 Silica gel, 1:9 EtOAc:hexane) to
obtain 8 (0.68 g, 86%, only E isomer) as a syrupy liquid.
Rf (30% EtOAc/hexane) 0.47; [a]D +24.2 (c 1.9, CHCl3);
1H NMR (300 MHz, CDCl3): d 7.68 (2H, Ar–H), 7.28 (m,
7H, Ar–H), 6.95–6.88 (m, 1H, –CH]CHSO2Tol), 6.54–6.44
(m, 1H, –CH]CHSO2Tol), 4.78–4.60 (m, 1H, –CHCH]
CHSO2Tol), 4.50 (s, 2H, –OCH2Ph), 4.10–4.02 (m, 1H,
–CHCH2OBn), 3.90–3.82 (s, 1H, –CHOMe), 3.50–3.35
(m, 2H, –CH2OBn), 3.30 (s, 3H, –OCH3), 3.20 (s, 2H,
CH2S), 2.42 (s, 3H, Ar–CH3), 2.20–2.12 (m, 1H, CH2),
1.90–1.70 (m, 1H, –CH2); 13C NMR (75 MHz, CDCl3):
d 21.5, 31.5, 37.1, 56.7, 70.7, 76.3, 82.3, 82.8, 83.8, 127.2,
127.5, 127.6, 128.2, 128.3, 129.7,129.8, 129.8, 130.1,
137.9; FABMS (m/z, %): 425 (M++Na, 2), 296 (54), 200
(24), 154 (100), 107 (38), 57 (92). Anal. Calcd for
C23H28SO5; C 66.32, H 6.78, S 7.70%; found C 66.29, H
6.71, S 7.65%.
ethyl 4-[5-benzyloxymethyl-4-methoxy-(2S,4S,5R)-tetra-
hydro-2-furanyl]-1H-3-pyrrolecarboxylate (10a and
10b). To a stirred solution of TosMIC (0.087 g, 0.45 mmol)
in dry THF (2 mL) at À78 ꢀC was added n-BuLi (0.46 mL,
0.75 mmol, 1.6 M solution in n-hexane) and the solution
stirred for 15 min. To this 7 (0.120 g, 0.375 mmol) dissolved
in dry THF (2 mL) was added and the mixture stirred for
30 min. After completion of the reaction, the mixture was
quenched with satd aq NH4Cl (1 mL), extracted with EtOAc
(2Â5 mL) and the combined organic layers were washed
with water (1Â5 mL), brine (1Â5 mL), dried (Na2SO4),
and concentrated under reduced pressure. The crude product
was purified by column chromatography (Silica gel 60–120,
1:5 EtOAc:hexane), first eluted was the 10a (0.048 g, 36%)
as syrup. Rf (30% EtOAc/hexane) 0.38; [a]D +51.6 (c 0.8,
1
CHCl3); H NMR (300 MHz, CDCl3): d 8.4 (s, 1H, –NH),
7.28 (br s, 5H, Ar–H), 7.21 (s, 1H, pyrrole-H), 6.64 (s, 1H,
pyrrole-H), 5.44 (dd, J 9.4, 5.2 Hz, 1H, –CHpyrrole), 4.55
(s, 2H, –CH2Ph), 4.27–4.23 (m, 2H, –COOCH2CH3), 4.10–
4.05 (m, 1H, –CHCH2OBn), 3.79–3.84 (m, 1H, –CHOCH3),
3.62–3.51 (m, 2H, –CH2OBn), 3.32 (s, 3H, –OCH3), 2.47
(ddd, J 8.2, 5.6, 1.8 Hz, 1H, –CH2), 1.78–1.69 (m, 1H,
–CH2), 1.32 (t, J 7.1 Hz, 3H, –COOCH2CH3); 13C NMR
(75 MHz, CDCl3): d 15.0, 29.9, 39.5, 56.8, 59.5, 60.0,
71.2, 73.3, 83.1, 83.6, 113.6, 116.6, 125.2, 126.9, 127.6,
128.6, 138.3, 164.8; IR (neat): 3260, 2920, 1500, 1450,
1120 cmÀ1; FABMS (m/z, %): 360 (M++H, 4), 327 (4), 207
(6), 147 (12), 91 (54), 69 (64), 55 (100). Anal. Calcd for
C20H25NO5; C 66.83, H 7.01, N 3.90%; found C 66.74, H
7.11, N 3.85%.
4.1.8. 5-[5-Benzyloxymethyl-4-methoxy-(2R,4S,5R)-tetra-
hydro-2-furanyl]-1,3-oxazole and 5-[5-benzyloxymethyl-
4-methoxy-(2S,4S,5R)-tetrahydro-2-furanyl]-1,3-oxazole
(9a and 9b). To a stirred solution of 6 (0.1 g, 0.41 mmol) in
methanol (1 mL) were added TosMIC (0.08 g, 0.41 mmol)
and potassium carbonate (0.172 g, 1.25 mmol) and the con-
tents stirred at reflux for 1 h. The reaction mixture was
concentrated under reduced pressure, the residue dissolved
in water (10 mL) and extracted into EtOAc (2Â10 mL).
The combined organic layers were washed with water
(1Â10 mL), brine (1Â10 mL), dried (Na2SO4), and concen-
trated under reduced pressure. The crude product was purified
by column chromatography (60–120 Silica gel, 1:5 EtOA-
c:hexane) the first eluted was 9a (0.031 g, 27%) as a thick yel-
low syrup. Rf (50% EtOAc/hexane) 0.39; [a]D +0.5 (c 0.8,
The second eluted was 10b (0.042 g, 32%) as syrup. Rf (30%
1
EtOAc/hexane) 0.37; [a]D À15.4 (c 0.8, CHCl3); H NMR
(300 MHz, CDCl3): d 8.92 (br s, 1H, –NH–), 7.28 (br s,
5H, Ar–H), 7.21 (s, 1H, pyrrole-H), 6.64 (s, 1H, pyrrole-H),
5.48 (t, J 7.6 Hz, 1H, –CHpyrrole), 4.58 (s, 2H, –CH2Ph),
4.26–4.16 (m, 3H, –CHCH2OBn and COOCH2CH3), 3.96–
3.91 (m, 1H, –CHOCH3), 3.56 (d, J 5.1 Hz, 2H, –CH2OBn),
3.28 (s, 3H, –OCH3), 2.82–2.72 (m, 1H, –CH2), 1.76–1.85
(m, 1H, –CH2), 1.31 (t, J 7.1 Hz, 3H, –COOCH2CH3); 13C
NMR (75 MHz, CDCl3): d 15.0, 29.9, 39.5, 56.7, 57.1,
59.5, 60.0, 71.2, 74.1, 83.0, 83.6, 113.6 116.6, 125.2,
126.9, 127.6, 128.6, 138.3, 164.8; IR (neat): 3260, 2920,
1500, 1450, 1120 cmÀ1; FABMS (m/z, %): 360 (M++H, 4),
327 (4), 147 (12), 91(54), 69 (64), 55 (100). Anal. Calcd
for C20H25NO5; C 66.83, H 7.01, N 3.90%; found C 66.80,
H 7.10, N 3.79%.
1
CHCl3); H NMR (200 MHz, CDCl3): d 7.78 (s, 1H, oxa-
H), 7.28 (br s, 5H, Ar–H), 6.97 (s, 1H, oxa-H), 5.07 (dd, J
9.8, 6.0 Hz, 1H, –CHoxazole), 4.54 (s, 2H, –CH2Ph), 4.10
(m, 1H, –CHCH2OBn), 3.95 (m, 1H, –CHOCH3), 3.58 (dd,
J 10.2, 4.2 Hz, 1H, –CH2OBn), 3.46 (dd, J 10.2, 5.6 Hz,
1H, –CH2OBn), 3.33 (s, 3H, –OCH3), 2.14–2.24 (m, 2H,
–CH2); 13C NMR (50 MHz): d 36.3, 56.7, 70.9, 71.4, 73.5,
83.0, 83.7, 124.0, 127.6, 128.3, 129.6, 130.2, 138.2, 151.1;
IR (neat): 2920, 1500, 1450, 1120 cmÀ1; LCMS; 312
(M++Na). Anal. Calcd for C16H19NO4: C 66.42, H 6.62, N
4.84%; found C 66.39, H 6.61, N 4.71%.
The second eluted was 5-[5-benzyloxymethyl-4-methoxy-
(2S,4S,5R)-tetrahydro-2-furanyl]-1,3-oxazole 9b (0.027 g,
23%) as a thick syrup. Rf (50% EtOAc/hexane) 0.38; [a]D
4.1.10. 3-[5-Benzyloxymethyl-4-methoxy-(2R,4S,5R)-
tetrahydro-2-furanyl]-4-ethylsulfonyl-1H-pyrrole and
3-[5-benzyloxymethyl-4-methoxy-(2S,4S,5R)-tetrahydro-
2-furanyl]-4-ethylsulfonyl-1H-pyrrole (11a and 11b). To
a stirred solution of TosMIC (0.058 g, 0.29 mmol) in dry
THF (1 mL) was added n-BuLi (0.23 mL, 0.37 mmol,
1.6 M soln in n-hexane) and the mixture stirred for 15 min.
To this 8 (0.1 g, 0.24 mmol) dissolved in dry THF (1 mL)
was added and the mixture stirred for 30 min. The mixture
was quenched with satd NH4Cl (1 mL), extracted with
EtOAc (2Â5 mL) and the combined organic layers were
washed with water (1Â5 mL), brine (1Â5 mL), dried
(Na2SO4), and concentrated under reduced pressure. The
crude product was purified by column chromatography (Sil-
ica gel 60–120, 1:5 EtOAc:hexane) the first eluted was the
1
+7.4 (c 0.35, CHCl3); H NMR (200 MHz, CDCl3): d 7.80
(s, 1H, oxa-H), 7.30 (br s, 5H, Ar–H), 7.00 (s, 1H, oxa-H),
5.17 (t, J 7.3 Hz, 1H, –CHoxazole), 4.58 (d, J 2.9 Hz, 2H,
–CH2Ph), 4.14–3.98 (m, 2H, –CHOCH3 and –CHCH2OBn),
3.58 (d, J 3.6 Hz, 2H, –CH2OBn), 3.32 (s, 3H, –OCH3), 2.53
(m, 1H, –CH2), 2.19 (m, 1H, –CH2); 13C NMR (50 MHz):
d 36.2, 56.6, 70.9, 71.5, 73.5, 83.1, 84.0, 124.5, 127.0,
128.5, 129.6, 130.1, 138.5, 152.0; IR (neat): 2920, 1500,
1450, 1120 cmÀ1; LCMS; 307 (M+NH4)+. Anal. Calcd for
C16H19NO4: C 66.42, H 6.62, N 4.84%; found C 66.35, H
6.59, N 4.69%.
4.1.9. Ethyl 4-[5-benzyloxymethyl-4-methoxy-(2R,4S,5R)-
tetrahydro-2-furanyl]-1H-3-pyrrolecarboxylate and

P. R. Krishna et al. / Tetrahedron 63 (2007) 9871–9880
9877
1
11a (0.037 g, 35%) as a yellow oil. Rf (40% EtOAc/hexane)
0.35; [a]D +69.85 (c 1.7, CHCl3); 1H NMR (300 MHz,
CDCl3): d 9.15 (s, 1H, –NH), 7.70 (2H, Ar–H), 7.28–7.13
(9H, Ar–H), 6.92 (s, 1H, pyrrole-H), 6.59 (s, 1H, pyrrole-
H), 5.09 (dd, J 10.6, 5.9 Hz, 1H, –CHpyrrole), 4.50 (s, 2H,
–SO2CH2Ar), 3.99 (m, 1H, –CHCH2OBn), 3.78 (m, 1H,
–CHOMe), 3.50 (dd, J 12.7, 5.9 Hz, 2H, –CH2OBn), 3.30
(s, 3H, –OCH3), 2.35 (s, 3H, Ar–CH3), 2.28 (dd, J 9.8,
5.9 Hz, 1H, –CH2), 1.75–1.68 (m, 1H, –CH2); 13C NMR
(75 MHz, CDCl3): d 24.3, 29.5, 57.1, 68.1, 71.4, 73.7,
83.4, 83.5, 116.2, 118.2, 124.6, 125.1, 125.3, 126.2, 126.2,
127.1, 127.3, 127.9, 128.8, 129.8; FABMS (m/z, %): 464
(M++Na, 100), 442 (M++H, 38), 391 (36), 288 (34), 248
(66), 167 (72), 154 (92). Anal. Calcd for C25H29NO5S; C
65.91, H 6.42, N 3.07, S 7.04%; found C 65.79, H 6.40, N
3.00, S 6.95%.
EtOAc/hexane) 0.49; [a]D À2.7 (c 1.0, CHCl3); H NMR
(200 MHz, CDCl3): d 5.92–5.69 (m, 1H, –CH]CH2),
5.15–5.06 (m, 2H, –CH]CH2), 3.72–3.61 (m, 3H,
–CH2OH and CHOH), 3.42 (s, 3H, –OCH3), 3.34 (q, 1H,
–CHOCH3), 2.44–2.23 (m, 2H, –CH2CH]CH2), 1.45 (br
s, 1H, –OH); 13C NMR (50 MHz, CDCl3): d 34.1, 57.5,
64.9, 66.5, 72.1, 116.7, 126.1; IR (neat): 3400, 2920, 1630,
1420, 1400 cmÀ1; FABMS (m/z, %): 169 (M++Na, 8), 147
(M++H, 54), 137 (40), 69 (60), 55 (100). Anal. Calcd for
C7H14NO3; C 57.51, H 9.65%; found C 57.50, H 9.59%.
4.1.13. 1-Benzyloxy-3-methoxy-(2S,3R)-5-hexen-2-ol
(15). To a stirred solution of 14 (1.4 g, 9.5 mmol) in acetone
were added K2CO3 (4.14 g, 30.0 mmol), TBAI 0.02 g), and
benzyl bromide (1.3 mL, 10.5 mmol) and the mixture heated
for 18 h. The workup and purification as described for 4
afforded 15 (1.42 g, 63%) as a colorless liquid. Rf (30%
1
The second eluted was 11b (0.035 g, 34%) as a yellow oil. Rf
EtOAc/hexane) 0.48; [a]D À15.4 (c 1.0, CHCl3); H NMR
1
(40% EtOAc/hexane) 0.34; [a]D À22.7 (c 0.8, CHCl3); H
(300 MHz, CDCl3): d 7.30 (br s, 5H, Ar–H), 5.89–5.75 (m,
1H, –CH]CH2), 5.12–5.02 (m, 2H, –CH]CH2), 4.53 (s,
2H, –OCH2Ph), 3.77–3.71 (m, 1H, –CHOH), 3.57(dd,
J 9.0, 6.7 Hz, 1H, –CH2OBn), 3.51 (dd, J 9.0, 6.8 Hz, 1H,
–CH2OBn), 3.35 (s, 3H, –OMe), 3.24 (q, 1H, –CHOMe),
2.32 (m, 2H, –CH2CH]CH2), 1.4 (br s, 1H, –OH); 13C
NMR (75 MHz, CDCl3): d 34.0, 57.5, 65.0, 66.5, 72.1; IR
(neat): 3400, 2920, 1630, 1420, 1400 cmÀ1; FABMS (m/z,
%): 259 (M++Na, 11), 237 (M++H, 21), 69 (100). Anal.
Calcd for C14H20NO3; C 71.16, H 8.53%; found C 71.09,
H 8.49%.
NMR (300 MHz, CDCl3): d 8.99 (s, 1H, –NH), 7.71 (2H,
Tol-H), 7.29–7.09 (m, 9H, Ar–H), 6.89 (s, 1H, pyrrole-H),
6.66 (s, 1H, pyrrole-H), 5.25 (t, J 7.4 Hz, 1H, –CHpyrrole),
4.54 (s, 2H, –OCH2Ph), 4.10–4.04 (m, 1H, –CHCH2OBn),
3.93–3.85 (m, 1H, –CHOMe), 3.50 (dd, J 9.6, 5.8 Hz, 2H,
–CH2OBn), 3.25 (s, 3H, –OCH3), 2.69–2.52 (m, 1H, –CH2),
2.33 (s, 3H, Ar–CH3), 1.88–1.74 (m, 1H, –CH2); 13C
NMR (75 MHz, CDCl3): d 24.3, 29.5, 37.9, 57.1, 68.0,
71.4, 73.7, 73.8, 83.4, 84.3, 116.2, 118.2, 124.5, 125.3,
126.2, 126.2, 127.1, 127.3, 127.9, 128.7, 129.8; FABMS
(m/z, %): 464 (M++Na, 100), 442 (M++H, 38), 391 (36),
288 (34), 248 (66), 167 (72), 154 (92). Anal. Calcd for
C25H29NO5S; C 65.91, H 6.42, N 3.07, S 7.04%; found C
65.90, H 6.39, N 2.99, S 7.00%.
4.1.14. 5-Benzyloxymethyl-4-methoxy-(4R,5S)-
2H,3H,4H-2-furanylmethanol (16). To a stirred solution
of 15 (1 g, 4.2 mmol) in CHCl3 (5 mL) was added m-chloro-
perbenzoic acid (3.8 g, 6.2 mmol, 50–55% in water) dis-
solved in CHCl3 (5 mL) and stirred for 6 h. The workup
and purification as described for compound 5 afforded 16
(0.72 g, 68%) as a colorless liquid. Rf (50% EtOAc/hexane)
0.39; [a]D +3.2 (c 1.8, CHCl3); 1H NMR (300 MHz, CDCl3):
d 7.30 (br s, 5H, Ar–H), 4.53 (s, 2H, –OCH2Ph), 4.25–3.87
(m, 3H, –CH2OBn, CHOMe, and CHCH2OH), 3.62–3.41
(m, 4H, –CH2OH and CH2OBn), 3.30 (s, 3H, –OCH3),
2.28–2.04 (m, 1H, –CH2), 1.93–1.79 (m, 1H, –CH2); 13C
NMR (50 MHz, CDCl3): d 39.0, 58.1, 65.3, 66.3, 72.5,
74.2, 81.9, 128.0, 128.6, 135.0, 137.3; IR (neat): 3540,
2920, 1030, 1100 cmÀ1; FABMS (m/z, %): 253 (M++H, 2),
215 (4), 181 (6), 136(6), 91(100). Anal. Calcd for
C14H20O4; C 66.65, H 7.99%; found C 66.64, H 7.85%.
4.1.11. 1-[2,2-Dimethyl-(4S)-1,3-dioxolan-4-yl]-(1R)-3-
butenyl methyl ether (13). To a stirred solution of 12
(2.8 g, 16.2 mmol) in dry THF (30 mL) at 0 ꢀC was added
sodium hydride (1.3 g, 32.5 mmol, 60% dispersion in min-
eral oil) and stirred for 20 min. Methyl iodide (3.46 g,
24.4 mmol) was added and stirred for 6 h. The mixture
was quenched with satd NH4Cl (1 mL), extracted with
EtOAc (2Â5 mL), and the combined organic layers were
washed with water (1Â5 mL), brine (1Â5 mL), dried
(Na2SO4), and concentrated under reduced pressure. The
crude product was purified by column chromatography
(Silica gel 60–120, 1:5 EtOAc:hexane) to afford 13 (2.1 g,
70%) as a light yellow oil. Rf (10% EtOAc/hexane) 0.32;
1
[a]D À6.8 (c 1.0, CHCl3); H NMR (300 MHz, CDCl3):
d 5.88–5.76 (m, 1H, –CH]CH2), 5.12–5.07 (m, 2H, –CH]
CH2), 4.00–3.92 (m, 2H, –CH2O–), 3.84–3.79 (m, 1H,
–CHO–), 3.40 (s, 3H, –CHOCH3), 3.23 (q, J 10.0, 6.0 Hz,
1H, –CHOMe), 2.42–2.32 (m, 1H, –CHCH]CH2), 2.30–
2.21 (m, 1H, –CHCH]CH2), 1.38 (s, 3H, CH3), 1.30 (s,
3H, CH3); 13C NMR (75 MHz, CDCl3): d 17.2, 28.1, 57.1,
62.5, 70.1, 100.4, 109.5, 126.1; IR (neat): 3100, 2950,
1620, 1460, 1400 cmÀ1; FABMS (m/z, %): 187 (M++H,
16%), 109 (32), 95 (65), 81 (79). Anal. Calcd for
C10H18O3; C 64.19, H 9.74%; found C 63.94, H 9.53%.
4.1.15. 5-Benzyloxymethyl-4-methoxy-(4R,5S)-tetra-
hydro-2-furancarbaldehyde (17). To a stirred solution of
oxallyl chloride (0.37 mL, 3.0 mmol) in dry CH2Cl2
(5 mL) was added dry DMSO (0.47 mL, 6.1 mmol) drop
wise at À78 ꢀC, after 2 min 16 (0.35 g, 1.35 mmol) dis-
solved in CH2Cl2 (5 mL) was added and stirred for
30 min. To this Et3N (0.8 mL, 8.4 mmol) was added at
À78 ꢀC and the mixture allowed to stir at room temperature
for 20 min. The workup and purification as described for
compound 6 afforded 17 (0.69 g, 99%) as a colorless liquid.
The crude aldehyde was used without further purification
and characterization.
4.1.12. 3-Methoxy-(2S,3R)-5-hexene-1,2-diol (14). The 13
(1.8 g, 9.6 mmol) was dissolved in 60% aq AcOH (15 mL)
and stirred for 6 h. The workup and purification as described
for compound 3 afforded 14 (1.13 g, 80%) as syrup. Rf (50%
4.1.16. Ethyl 3-[5-benzyloxymethyl-4-methoxy-(4R,5S)-
2H,3H,4H-2-furanyl]-(E)-2-propenoate (18). To a stirred

9878
P. R. Krishna et al. / Tetrahedron 63 (2007) 9871–9880
solution of 16 (0.35 g, 1.4 mmol) in benzene (3 mL) at reflux
(ethoxycarbonylmethylene)triphenylphosphorane (0.73 g,
2.1 mmol) was added and the mixture allowed to reflux for
1 h. The workup and purification as described for compound
7 afforded 18 (0.31 g, 70% only E isomer) as a yellow syrup.
Rf (40% EtOAc/hexane) 0.52; [a]D +9.3 (c 0.7, CHCl3); 1H
NMR (300 MHz, CDCl3): d 7.27 (br s, 5H, Ar–H), 6.94–6.85
(m, 1H, –CH]CHCOOEt), 5.98 (t, J 15.8 Hz, 1H, –CH]
CHCOOEt), 4.69–4.54 (m, 1H, –CHCH]CHCOOEt),
4.54 (s, 2H, –OCH2Ph), 4.23–4.05 (m, 3H, –COOCH2CH3
and –CHO–), 3.93–3.83 (m, 1H, –CHOMe), 3.55–3.40 (m,
2H, –CH2OBn), 3.30 (s, 3H, –OCH3), 2.41–2.07 (m, 1H,
–CH2), 1.85–1.65 (m, 1H, –CH2), 1.29 (t, J 7.2 Hz, 3H,
–COOCH2CH3); 13C NMR (50 MHz, CDCl3): d 15.0, 31.2,
56.0, 60.1, 71.2, 72.1, 82.1, 83.0, 89.1, 127.4, 127.9, 128.8,
131.1, 135.1, 145.2, 163.8; IR (neat): 2960, 1660, 1450,
1190, 1010 cmÀ1; FABMS (m/z, %): 343 (M++Na, 2), 321
(M++H, 13), 215 (27), 138 (62), 73 (100). Anal. Calcd for
C18H24O5; C 67.48, H 7.55%; found C 67.38, H 7.50%.
4-[5-benzyloxymethyl-4-methoxy-(2R,4R,5S)-2H,3H,4H-
2-furanyl]-1H-3-pyrrolecarboxylate (20a and 20b). To
a stirred solution of TosMIC (0.080 g, 0.41 mmol) in dry
THF (2 mL) at À78 ꢀC was added n-BuLi (1.6 M solution
in n-hexane, 0.25 mL, 1.2 mmol) and the mixture stirred
for 15 min. To this 18 (0.110 g, 0.34 mmol) dissolved in
dry THF (2 mL) was added and the mixture stirred for
30 min. After completion of the reaction, the mixture was
quenched with satd NH4Cl (1 mL), extracted with EtOAc
(2Â5 mL), and the combined organic layers were washed
with water (1Â5 mL), brine (1Â5 mL), dried (Na2SO4),
and concentrated under reduced pressure. The crude product
was purified by column chromatography (Silica gel 60–120,
1:5 EtOAc:hexane), first eluted was 20a (0.046 g, 37%) as
a light yellow syrup. Rf (30% EtOAc/hexane) 0.38; [a]D
1
À48.3 (c 1.6, CHCl3); H NMR (300 MHz, CDCl3): d 8.4
(s, 1H, –NH–), 7.27 (br s, 5H, Ar–H), 7.21 (s, 1H, pyrrole-
H), 6.64 (s, 1H, pyrrole-H), 5.42 (dd, J 9.4, 5.2 Hz, 1H,
–CHpyrrole), 4.54 (s, 2H, –CH2Ph), 4.22 (m, 2H,
–COOCH2CH3), 4.09–4.05 (m, 1H, –CHCH2OBn), 3.84–
3.79 (m, 1H, –CHOCH3), 3.62–3.51 (m, 2H, –CH2OBn),
3.32 (s, 3H, –OCH3), 2.47 (ddd, J 8.2, 5.6, 1.8 Hz, 1H,
–CH2–), 1.78–1.69 (m, 1H, –CH2–), 1.32 (t, J 7.1 Hz, 3H,
–COOCH2CH3); 13C NMR (75 MHz, CDCl3): d 15.0,
29.9, 39.5, 56.8, 59.5, 60.0, 71.2, 73.3, 83.1, 83.6, 113.6,
116.6, 125.2, 126.9, 127.6, 128.6, 138.3, 164.8; IR (neat):
3260, 2920, 1500, 1450, 1120 cmÀ1; FABMS (m/z, %):
360 (M++H, 9), 327 (14), 207 (3), 147 (19), 91 (59), 69
(74), 55 (100). Anal. Calcd for C20H25NO5: C 66.83, H
7.01, N 3.90%; found C 66.74, H 7.11, N 3.85%.
4.1.17. 4-Methoxy-2-(1,3-oxazol-5-yl)-(2S,4R,5S)-
2H,3H,4H-5-furanylmethoxy-(phenyl)methane and
4-methoxy-2-(1,3-oxazol-5-yl)-(2R,4R,5S)-2H,3H,4H-5-
furanylmethoxy (phenyl)methane (19a and 19b). To
a stirred solution of aldehyde 17 (0.15 g, 0.6 mmol) in meth-
anol (2 mL) were added TosMIC (0.14 g, 0.72 mmol) and
potassium carbonate (0.248 g, 1.8 mmol) and the mixture
allowed to reflux for 1 h. The reaction mixture was concen-
trated under reduced pressure, the residue dissolved in water
(10 mL) and extracted into EtOAc (2Â10 mL). The com-
bined organic layers were washed with water (1Â10 mL),
brine (1Â10 mL), dried (Na2SO4), and concentrated under
reduced pressure. The crude product was purified by column
chromatography (60–120 Silica gel, 1:5 EtOAc:hexane) the
first eluted was 19a (0.048 g, 28%) as a thick yellow syrup.
Rf (50% EtOAc/hexane) 0.39; [a]D À0.5 (c 0.8, CHCl3); 1H
NMR (300 MHz, CDCl3): d 7.78 (s, 1H, oxazole-H), 7.28 (br
s, 5H, Ar–H), 6.96 (s, 1H, oxazole-H), 5.08 (dd, J 9.8,
6.0 Hz, 1H, –CHoxazole), 4.53 (s, 2H, –CH2Ph), 4.10 (m,
1H, –CHCH2OBn), 3.95–3.89 (m, 1H, –CHOCH3), 3.57
(dd, J 10.5, 5.2 Hz, 1H, –CH2OBn), 3.46 (dd, J 10.5,
5.2 Hz, 1H, –CH2OBn), 3.33 (s, 3H, –OCH3), 2.21–2.16
(m, 2H, –CH2); 13C NMR (50 MHz, CDCl3): d 36.3, 56.7,
70.8, 71.3, 73.5, 83.0, 83.7, 124.0, 127.5, 128.3, 129.6,
130.1, 138.1, 151.0; LCMS: 307 (M+NH4)+. Anal. Calcd
for C16H19NO4; C 66.42, H 6.62, N 4.84%; found C 66.40,
H 6.59, N 4.80%.
The second eluted was 20b (0.042 g, 34%) as a colorless
syrup. Rf (30% EtOAc/hexane) 0.37; [a]D +17.1 (c 0.35,
CHCl3); H NMR (300 MHz, CDCl3): d 8.90 (br s, 1H,
1
–NH–), 7.27 (br s, 5H, Ar–H), 7.21 (s, 1H, pyrrole-H),
6.69 (s, 1H, pyrrole-H), 5.47 (t, J 7.3 Hz, 1H, –CHpyrrole),
4.60 (s, 2H, –CH2Ph), 4.25–4.18 (m, 3H, –CHCH2OBn and
–COOCH2CH3), 3.96–3.90 (m, 1H, –CHOCH3), 3.56 (d, J
5.2 Hz, 2H, –CH2OBn), 3.26 (s, 3H, –OCH3), 2.81–2.72
(m, 1H, –CH2), 1.85–1.76 (m, 1H, –CH2), 1.31 (t, J
7.1 Hz, 3H, –COOCH2CH3); 13C NMR (75 MHz, CDCl3):
d 15.0, 29.8, 39.5, 56.6, 57.2, 59.5, 60.1, 71.1, 74.2, 83.0,
83.6, 113.5, 116.6, 125.1, 126.9, 127.5, 128.6, 138.4,
164.9; IR (neat): 3260, 2920, 1500, 1450, 1120 cmÀ1
;
FABMS (m/z, %): 360 (M++H, 5), 327 (2), 147 (21),
91(59), 69 (72), 55 (100). Anal. Calcd for C20H25NO5: C
66.83, H 7.01, N 3.90%; found C 66.80, H 7.10, N 3.79%.
The second eluted was 19b (0.043 g, 25%) as a yellow syrup.
Rf (50%EtOAc/hexane)0.38; [a]D À8.5(c 10.35, CHCl3); 1H
NMR (300 MHz, CDCl3): d 7.78 (s, 1H, Oxazole-H), 7.27
(br s, 5H, Ar–H), 7.01 (s, 1H, Oxazole-H), 5.16 (t, J 7.5 Hz,
1H, –CHOxazole), 4.56 (d, J 2.9 Hz, 2H, –OCH2Ph), 4.12–
4.08 (m, 1H, –CHCH2OBn), 4.03–3.97 (m, 1H, –CHOCH3),
3.56 (d, J 4.5 Hz, 2H, –CH2OBn), 3.32 (s, 3H, –OCH3), 2.56–
2.47 (m, 1H, –CH2), 2.20–2.15 (m, 1H, –CH2); 13C NMR
(50 MHz, CDCl3): d 36.3, 56.7, 70.8, 71.3, 73.5, 83.0, 83.7,
124.0, 127.5, 128.3, 129.6, 130.1, 138.1, 151.0; LCMS: 312
(M++Na). Anal. Calcd for C16H19NO4; C 66.42, H 6.62, N
4.84%; found C 66.29, H 6.65, N 4.83%.
4.1.19. (4S)-4-[(1R)-1-(Benzyloxy)-3-butenyl]-2,2-di-
methyl-1,3-dioxolane (21). To a stirred solution of 1
(2.5 g, 14.5 mmol) in dry DMF (8 mL) at 0 ꢀC was added
sodium hydride (0.68 g, 29.04 mmol, 60% dispersion in
mineral oil) and stirred for 20 min. Benzyl bromide
(2.47 g, 14.5 mmol) was added and the reaction stirred for
6 h. The reaction mixture was quenched with satd NH4Cl
(20 mL) at 0 ꢀC and stirred for 10 min. The organic com-
pound was extracted into EtOAc (2Â100 mL). The organic
layer was washed with water (1Â50 mL), brine
(2Â50 mL), dried (Na2SO4), and concentrated under re-
duced pressure. The crude product was purified by column
chromatography (60–120 Silica gel, 1:50 EtOAc:hexane)
to obtain 21 (2.48 g, 94%) as a colorless liquid. Rf (10%
4.1.18. Ethyl 4-[5-benzyloxymethyl-4-methoxy-(2S,4R,5S)-
2H,3H,4H-2-furanyl]-1H-3-pyrrolecarboxylate and ethyl
1
EtOAc/hexane) 0.41; [a]D +8.1 (c 1.25, CHCl3); H NMR

P. R. Krishna et al. / Tetrahedron 63 (2007) 9871–9880
9879
(300 MHz, CDCl3): d 7.27 (br s, 5H, Ar–H), 5.91–5.76 (m,
1H, –CH]CH2), 5.07 (t, J 10.3 Hz, 2H, –CH]CH2),
4.60–4.55 (m, 2H, –OCH2Ph), 4.01–3.92 (m, 2H, –CH2O),
3.84–3.74 (m, 1H, –CHO), 3.24 (q, J 6.0 Hz, 1H, –CHOBn),
2.55–2.35 (m, 2H, –CH2CH]CH2), 1.38 (s, 3H, –CH3),
1.30 (s, 3H, –CH3); 13C NMR (50 MHz, CDCl3): d 18.1,
28.0, 34.3, 65.8, 66.7, 82.3, 83.1, 100.8, 115.5, 126.1,
127.1, 128.3, 131.4, 135.0; IR (neat): 3100, 2950, 1620,
1460, 1400 cmÀ1; FABMS (m/z, %): 263 (M++H, 16%),
155 (32), 95 (72), 81 (76). Anal. Calcd for C16H22O3: C
73.5, H 8.30%; found C 73.42, H 8.26%.
91(100). Anal. Calcd for C20H24O4: C 73.45, H 7.55%;
found C 73.39, H 7.52%.
4.1.23. (4R,5R)-4-(Benzyloxy)-5-[(benzyloxy)methyl]-
tetrahydro-2-furancarbaldehyde (25). To a stirred solu-
tion of oxallyl chloride (0.2 mL, 2.27 mmol) in dry CH2Cl2
(5 mL) was added dry DMSO (0.32 mL, 4.55 mmol) drop-
wise at À78 ꢀC, after 2 min. Compound 24 (0.68 g,
2.07 mmol) dissolved in CH2Cl2 (5 mL) was added and
stirred for 30 min. To this Et3N (1.74 mL, 9.9 mmol) was
added at À78 ꢀC and allowed to stir at room temperature
for 20 min. The workup and purification as reported for com-
pound 17 afforded 25 (0.68, 96%) as a colorless liquid. The
crude aldehyde was used without further purification and
characterization.
4.1.20. (2S,3R)-3-(Benzyloxy)-5-hexene-1,2-diol (22). The
methyl ether 21 (3.2 g, 12.3 mmol) was dissolved in 60% aq
acetic acid (30 mL) and stirred for 6 h. The reaction mixture
was neutralized with solid NaHCO3. The workup and purifi-
cation as described for compound 3 afforded 22 (2.25 g,
84%) as a colorless oil. Rf (50% EtOAc/hexane) 0.52; [a]D
+4.28 (c 0.92, CHCl3); 1H NMR (300 MHz, CDCl3):
d 7.52 (br s, 5H, Ar–H), 5.92–5.72 (m, 1H, –CH]H2),
5.17–5.05 (m, 2H, –CH]CH2), 4.68–4.46 (m, 2H, –O–
CH2–Ar), 3.65–3.55 (m, 4H, –CHOBn, –CH2OH, and
–CHOH), 2.55–2.35 (m, 2H, –CH2CH]CH2); 13C NMR
(50 MHz, CDCl3): d 33.1, 66.2, 69.8, 71.9, 80.2, 116.5,
126.0, 127.6, 128.9, 133.2, 137.1; IR (neat): 3400, 2920,
1630, 1420, 1400 cmÀ1; FABMS (m/z, %): 245 (M++Na,
8), 223 (M++H, 54), 137 (40), 69 (60), 55 (100). Anal. Calcd
for C13H18O3: C 70.10, H 8.00%; found C 70.09, H 7.95%.
4.1.24. Ethyl 3-[5-benzyloxymethyl-4-benzyloxy-(4R,5S)-
2H,3H,4H-2-furanyl]-(E)-2-propenoate (26). To a stirred
solution of 25 (0.5 g, 1.53 mmol) in benzene (5 mL) at reflux
was added (ethoxycarbonylmethylene)triphenylphosphor-
ane (0.8 g, 2.3 mmol) and the reaction was allowed to stir
at reflux for 1 h. The workup and purification as described
for compound 6 afforded 26 (0.62 g, 69%) as a light yellow
liquid. Rf (30% EtOAc/hexane) 0.48; [a]D À3.5 (c 1.85,
1
CHCl3); H NMR (200 MHz, CDCl3): d 7.27 (br s, 10H,
Ar–H), 6.97–6.86 (m, 1H, –CH]CHCOOEt), 6.05–5.95
(m, 1H, –CH]HCOOEt), 4.55–4.49 (m, 5H, –OCH2Ph and
–CH–CH]CHCOOEt), 4.24–4.15 (m, 4H, –COOCH2CH3
and –CH2OBn), 3.57–3.51 (m, 1H, –CHO–), 3.46–3.36
(m, 1H, –CHOBn), 2.32–2.13 (m, 1H, –CH2–), 1.95–1.69
(m, 1H, –CH2–), 1.29 (t, J 7.2 Hz, 3H, –COOCH2CH3);
13C NMR (75 MHz, CDCl3): d 15.2, 31.3, 60.2, 71.5, 72.2,
81.9, 82.8, 83.2, 89.2, 127.1, 127.3, 127.4, 127.7, 127.8,
128.9, 129.2, 131.0, 135.3, 145.1, 163.8; IR (neat): 2960,
1660, 1450, 1190, 1010 cmÀ1; FABMS (m/z, %): 419
(M++Na, 2), 397 (M++H, 13), 215 (27), 138 (62), 73
(100). Anal. Calcd for C24H28O5: C 72.6, H 7.41%; found
C 72.58, H 7.43%.
4.1.21. (2S,3R)-1,3-Di(benzyloxy)-5-hexen-2-ol (23). To
a stirred solution of 22 (2.25 g, 10.2 mmol) in acetone
were added K2CO3 (3.0 g, 30.5 mmol), TBAI (0.02 g), and
benzyl bromide (1.3 mL, 11.2 mmol) and the mixture
allowed to reflux for 18 h. The workup and purification as
described for 4 afforded 23 (2.15 g, 68%) as a light yellow
oil. Rf (30% EtOAc/hexane) 0.53; [a]D +19.5 (c 0.69,
1
CHCl3); H NMR (200 MHz, CDCl3); d 7.30 (br s, 10H,
Ar–H), 5.98–5.75 (m, 1H, –CH]CH2), 5.12–5.02 (m, 2H,
–CH]CH2), 4.65–4.45 (m, 4H, –OCH2Ph), 3.85–3.74 (m,
1H, –CHOH), 3.65–3.45 (m, 3H, –CH2OBn and –CHOBn),
2.47–2.37 (m, 2H, –CH2CH]CH2), 1.41 (br s, 1H, –OH);
13C NMR (75 MHz, CDCl3): d 34.2, 57.8, 65.1, 71.1, 73.9,
81.2, 82.3, 117.0, 126.9, 127.5, 127.7, 128.4, 128.4, 134.6,
138.0; FABMS (m/z, %): 335 (M++Na, 18), 313 (M++H,
8), 137 (40), 69 (100). Anal. Calcd for C20H24O3: C 76.90,
H 7.10%; found C 76.87, H 7.11%.
4.1.25. Ethyl 5-(2R,4R,5R)-4-(benzyloxy)-5-[(benzyloxy)-
methyl]tetrahydro-2-furanyl-1H-3-pyrrolecarboxylate
and ethyl 5-(2S,4R,5R)-4-(benzyloxy)-5-[(benzyloxy)-
methyl]tetrahydro-2-furanyl-1H-3-pyrrolecarboxylate
(27a and 27b). To a stirred solution of TosMIC (0.06 g,
0.31 mmol) in dry THF (1 mL) at À78 ꢀC was added n-
BuLi (1.6 M soln in n-hexane, 0.19 mL, 0.41 mmol) fol-
lowed by 18 (0.1 g, 0.26 mmol) dissolved in dry THF
(1 mL) and the reaction was stirred for 30 min. After com-
pletion of the reaction mixture, it was quenched with satd
NH4Cl (1 mL), extracted with EtOAc (2Â5 mL), and the
combined organic layers were washed with water
(1Â5 mL), brine (1Â5 mL), dried (Na2SO4), and concen-
trated under reduced pressure. The crude product was puri-
fied by column chromatography (Silica gel 60–120, 1:5
EtOAc:hexane) the first eluted 27a (0.040 g, 36%) was ob-
tained as a yellow syrup. Rf (30% EtOAc/hexane) 0.41;
4.1.22. (4R,5R)-4-(Benzyloxy)-5-[(benzyloxy)methyl]-
tetrahydro-2-furanylmethanol (24). To a stirred solution
of 23 (0.88 g, 2.8 mmol) in CHCl3 (5 mL) was added m-
chloroperbenzoic acid (0.73 g, 4.2 mmol, 50–55% in water)
dissolved in CHCl3 (5 mL) and stirred for 6 h. The workup
and purification as described for compound 5 afforded 24
(0.68 g, 74%) as a light yellow syrup. Rf (50% EtOAc/
hexane) 0.43; [a]D +34.3 (c 1.85, CHCl3); 1H NMR
(200 MHz, CDCl3): d 7.30 (br s, 10H, Ar–H), 4.67–4.47
(m, 4H, –OCH2Ph), 4.35–4.05 (m, 4H, –CH2OBn, –CH–O–,
and –CH–OBn), 3.67–3.37 (m, 3H, –CH2OH and –CHO),
2.90 (br s, 1H, –OH), 2.30–1.85 (m, 2H, –CH2); 13C NMR
(50 MHz, CDCl3): d 38.7, 65.1, 66.5, 67.2, 72.4, 74.5,
82.4, 83.1, 127.0, 127.6, 127.9, 128.6, 134.5, 135.0, 137.6,
138.1; IR (neat): 3540, 2920, 1030, 1100 cmÀ1; FABMS
(m/z, %): 329 (M++H, 2), 245 (4), 181 (6), 136(6),
1
[a]D +44.7 (c 0.6, CHCl3); H NMR (200 MHz, CDCl3):
d 9.02 (s, 1H, –NH), 7.27 (br s, 11H, Ar–H), 6.70 (s, 1H,
pyrl-H), 5.52 (dd, J 9.5, 5.5 Hz, 1H, –CHpyrrole), 4.60–
4.42 (m, 4H, –CH2Ph), 4.40–4.38 (m, 1H, –CHO–), 4.30–
4.02 (m, 4H, –CHOBn, –CHO–, –COOCH2CH3), 3.60–3.35
(m, 2H, –CH2OBn), 2.62 (ddd, J 9.2, 4.7, 2.2 Hz, 1H,
–CH2), 1.85–1.71 (m, 1H, –CH2), 1.27 (t, J 6.8 Hz, 3H,

9880
P. R. Krishna et al. / Tetrahedron 63 (2007) 9871–9880
–COOCH2CH3); 13C NMR (75 MHz, CDCl3): d 15.5, 31.2,
56.5, 60.2, 61.7, 71.3, 82.9, 83.5, 84.0, 113.1, 115.9, 125.3,
126.1, 126.2, 127.3, 127.5, 127.5, 128.2, 128.2, 128.3, 138.1,
3. (a) Ren, R.; Chaudhuri, N. C.; Pairs, P. L.; Rumney, P. S.; Kool,
E. T. J. Am. Chem. Soc. 1996, 118, 7671–7678; (b) Pirrung,
M. C.; Zhao, X.; Harria, S. V. J. Org. Chem. 2001, 66, 2067–
2071; (c) Beuck, C.; Singh, I.; Bhattachraya, A.; Hecker, W.;
Parmer, V. S.; Seitz, O.; Weinhold, E. Angew. Chem., Int. Ed,
2003, 42, 3958–3960.
4. (a) Adlington, R. M.; Baldwin, J. E.; Pritchard, G. J.; Spencer,
K. C. Tetrahedron Lett. 2000, 41, 575–578; (b) Miller, T. J.;
Farquar, H. D.; Sheybani, A.; Tallini, C. E.; Saurage, A. S.;
Fronczek, F. R.; Hammer, R. P. Org. Lett. 2002, 4, 877–880.
5. (a) Reese, C. B.; Wu, Q. Org. Biomol. Chem. 2003, 1, 3160–
3172; (b) Chen, D. W.; Beuscher, A. E., IV; Stevens, R. C.;
Wirsching, P.; Learner, R. A.; Janda, K. D. J. Org. Chem.
À1
164.7; IR (neat): 3260, 2920, 1500, 1450, 1120 cm
;
FABMS (m/z, %): 436 (M++H, 4), 377 (4), 147 (12), 91
(54), 69 (64), 55 (100). Anal. Calcd for C26H29NO5: C
71.90, H 6.5%; found C 71.92, H 6.54%.
The second eluted 27b (0.038 g, 34%) was obtained as a
yellow syrup. Rf (40% EtOAc/hexane) 0.40; [a]D À18.8 (c
1
0.35, CHCl3); H NMR (200 MHz, CDCl3): d 8.74 (br s,
1H, –NH–), 7.27 (br s, 11H, Ar–H), 6.72 (s, 1H, Ar–H),
5.48 (t, J 7.3 Hz, 1H, –Ar–H), 4.61–4.40 (m, 4H, –OCH2Ph),
4.38–4.32 (m, 1H, –CHO–), 4.30–4.10 (m, 3H, –CHO–
and –COOCH2CH3), 3.73–3.46 (m, 3H, –CH2OBn and
–CHOBn), 2.82–2.72 (m, 1H, –CH2), 1.92–1.80 (m, 1H,
–CH2), 1.27 (t, J 6.8 Hz, 3H, –COOCH2CH3); 13C NMR
(75 MHz, CDCl3): d 15.5, 31.0, 56.3, 60.1, 61.5, 71.9,
83.1, 83.9, 84.5, 113.9, 116.4, 123.0, 126.2, 126.3, 127.3,
127.5, 127.6, 128.1, 128.2, 128.3, 138.2, 164.9; IR (neat):
3260, 2920, 1500, 1450, 1120 cmÀ1; FABMS (m/z, %):
436 (M++H, 7), 377 (2), 147 (19), 91 (62), 69 (71), 55
(100). Anal. Calcd for C26H29NO5: C 71.90, H 6.5%; found
C 71.89, H 6.51%.
€
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