1174
S. Basu et al. / Tetrahedron 70 (2014) 1169e1175
mixture was concentrated in vacuo. Purification by column chro-
matography (5% EtOAc/hexane) gave the pyrrolidine 5 (8.36 g, 62%
1669, 1404, 1215, 756, 669 cmꢀ1
; dH (400 MHz, CDCl3): 4.39 (br, 1H),
3.71 (s, 3H), 3.63e3.57 (m, 3H), 3.33e3.28 (m, 1H), 2.78e2.74 (m,
1H), 2.19 (br, 1H), 2.14e2.07 (m, 2H), 1.85 (br, 1H), 1.47 (s, 9H) ppm;
dC (100 MHz, CDCl3):173.9, 156.2, 80.3, 58.7, 56.9, 52.1, 48.5, 38.8,
31.9, 29.6, 28.4, 26.8, 22.7, 14.1 ppm; HRMS (ESI) (m/z): calcd for
from silyl-ether 60) as
EtOAcehexane); [
25 1.67 (c 0.925, CHCl3); nmax (liquid film) 3020,
1729, 1375, 1217, 1046, 759 cmꢀ1
a colourless liquid. Rf 0.4 (10%
a]
D
;
dH (300 MHz, CDCl3): 7.65e7.61
(m, 4H), 7.41e7.23 (m, 11H), 4.45 (t, J¼12.36 Hz, 2H), 3.81 (br, 1H),
3.49 (br, 5H), 3.26 (br, 1H), 2.29e2.27 (m, 1H), 2.01e1.89 (m, 2H),
1.77e1.64 (m, 2H), 1.43 (s, 9H),1.04 (s, 9H) ppm; dc (75 MHz, CDCl3):
154.51, 138.46, 135.52, 133.56, 133.49, 129.63, 128.26, 127.65, 127.50,
127.40, 79.12, 72.94, 68.01, 64.96, 57.15, 46.21, 45.45, 44.57, 34.66,
34.13, 28.48, 26.82, 25.19, 19.20 ppm; HRMS (ESI) (m/z): calcd for
C
13H23NO5Na [MþNa]þ, 296.1474; found 296.1496.
4.2.9. (2R,3S)-tert-Butyl 3-((tert-butyldiphenylsilyloxy)methyl)-2-(2-
methoxy-2-oxoethyl)pyrrolidine-1-carboxylate (12). To a stirred so-
lution of pyrrolidine 5 (2.0 g, 3.47 mM) in MeOH (15 mL), 10% PdeC
(200 mg) were added and subjected to hydrogenation under at-
mospheric pressure using a hydrogen filled balloon. After 6 h the
reaction mixture was filtered through a short Celite pad and the
filter cake was washed with methanol. The filtrate and the wash-
ings were combined and concentrated in vacuo. Purification by
column chromatography (silica gel, 18% EtOAc in hexane eluant)
afforded alcohol (1.53 g, 91%); Rf 0.4 (30% EtOAc/hexane).
C
35H48NO4Si [MþH]þ, 574.3353; found 574.3344.
4.2.7. (2R,3S)-1-tert-Butyl 3-methyl 2-(2-(benzyloxy)ethyl)pyrroli-
dine-1,3-dicarboxylate (1a). To a solution of pyrrolidine 5 (3.3 g,
5.73 mM) in THF (20 mL) was added drop-wise TBAF in THF (8.6 mL,
8.6 mM) at 0 ꢁC. The reaction mixture was stirred for 1 h at the same
temperature and quenched by the addition of saturated aqueous
NH4Cl solution. Then it was extracted with EtOAc (100 mL), washed
with water (2ꢂ20 mL), brine (30 mL) and dried over anhydrous
Na2SO4 and concentrated to dryness. Purification by column chro-
matography (30% EtOAc/hexane) gave the alcohol (1.84 g, 95%) as
a colourless liquid; Rf 0.5 (60% EtOAc/hexane).
To a solution of oxalyl chloride (0.7 mL, 8.16 mM) in dry CH2Cl2
(25 mL) at ꢀ78 ꢁC, DMSO (1.25 mL, 17.41 mM) was added slowly in
a drop-wise manner with stirring under nitrogen atmosphere. After
15 min stirring, alcohol (1.84 g, 5.44 mM, dissolved in 15 mL of dry
CH2Cl2) was added to the reaction mixture. After 0.5 h of stirring at
ꢀ78 ꢁC, Et3N (3.8 mL, 27.2 mM) was added and stirred for another
0.5 h at ꢀ78 ꢁC and then for 0.5 h at 0 ꢁC. Then the reaction mixture
was quenched with saturated aqueous NH4Cl solution and extrac-
ted with EtOAc (100 mL). The combined organic layers were
washed with water (2ꢂ30 mL), brine (30 mL), dried (Na2SO4) and
concentrated in vacuo, Rf 0.5 (30% EtOAc/hexane). The aldehyde,
thus obtained, was directly used for the next reaction.
To a solution of oxalyl chloride (0.407 mL, 4.73 mM) in dry
CH2Cl2 (18 mL) at ꢀ78 ꢁC, DMSO (0.716 mL, 10.1 mM) was added
slowly in a drop-wise manner, with stirring under nitrogen at-
mosphere. After 15 min stirring, alcohol (1.53 g, 3.154 mM, dis-
solved in 15 mL of dry CH2Cl2) was added to the reaction mixture.
After 0.5 h of stirring at ꢀ78 ꢁC, Et3N (2.19 mL, 15.77 mM) was
added and stirred for another 0.5 h at ꢀ78 ꢁC and then for 0.5 h at
0
ꢁC. Then the reaction mixture was quenched with saturated
aqueous NH4Cl solution and extracted with EtOAc (100 mL). The
combined organic layers were washed with water (2ꢂ30 mL),
brine (30 mL), dried (Na2SO4) and concentrated in vacuo; Rf 0.6
(10% EtOAc/hexane) The aldehyde, thus obtained, was directly used
for the next reaction.
To the solution of aldehyde in 2-methyl-2-butene (4 mL) and
tBuOH (8 mL), the mixture of NaClO2 (904 mg,10 mM) and NaH2PO4
(1.56 g, 10 mM), dissolved in minimum amount of water, was added
and stirring continued for 3 h at room temperature. The solvents of
reaction mixture were evaporated under vacuum; the residue was
diluted with EtOAc (100 mL), washed with 1 N HCl (2ꢂ20 mL),
water (2ꢂ20 mL), brine (20 mL), dried over Na2SO4 and concen-
trated in vacuo. Crude acid was dissolved in Et2O and treated with
excess CH2N2 in ether at 0 ꢁC. Then the solvent was evaporated and
purification by column chromatography (8% EtOAc/hexane) affor-
ded methyl ester 12 (1.37 g, 77% from pyrrolidine 70). Rf 0.4 (20%
To the solution of the aldehyde in 2-methyl-2-butene (4 mL) and
tBuOH (8 mL), the mixture of NaClO2 (1.48 g, 16.32 mM) and
NaH2PO4 (2.54 g, 16.32 mM), dissolved in minimum amount of
water, was added and stirring continued for 3 h at room temper-
ature. The solvents of reaction mixture were evaporated under
vacuum; the residue was diluted with EtOAc (100 mL), washed with
1 N HCl (2ꢂ20 mL), water (2ꢂ20 mL), brine (20 mL), dried over
Na2SO4 and concentrated in vacuo. Crude acid was dissolved in
Et2O and treated with excess CH2N2 in ether at 0 ꢁC. Then the
solvent was evaporated and purification by column chromatogra-
phy (15% EtOAc/hexane) afforded methyl ester 1a (1.52 g, 73% from
EtOAc/hexane); [
a
]
25 ꢀ0.697 (c 2.7, CHCl3); nmax (liquid film) 3019,
D
1731, 1401, 1248, 1217, 758 cmꢀ1
;
dH (300 MHz, CDCl3): 7.64 (m, 4H),
7.42e7.37 (m, 6H), 4.02(m, 1H), 3.61 (s, 3H), 3.55e3.49 (m, 2H),
3.40e3.30 (m, 2H), 2.85e2.70 (m, 1H), 2.49e2.36 (m, 2H),
2.01e1.89 (m, 1H), 1.77 (m, 1H), 1.45 (s, 9H), 1.05 (s, 9H); dC (75 MHz,
CDCl3): 171.8, 154.2, 135.6, 133.53, 133.50, 129.76, 127.77, 79.67,
79.31, 65.21, 64.83, 56.66, 56.39, 51.57, 46.23, 45.38, 44.91, 39.08,
38.36, 29.75, 28.54, 26.89, 26.18, 26.04, 25.18, 19.30; HRMS (ESI) (m/
z): calcd for C29H41NO5SiNa [MþNa]þ, 534.2652; found 534.2610.
pyrrolidine). Rf 0.3 (20% EtOAc/hexane); [
a]
25 2.27 (c 0.545, CHCl3);
D
nmax (liquid film) 3020, 2400, 1729, 1374, 1216, 1046, 756, 668 cmꢀ1
;
dH (400 MHz, CDCl3): 7.35e7.29 (m, 5H), 4.49 (d, J¼11.89 Hz, 1H),
4.45 (d, J¼11.89 Hz, 1H), 4.16 (br, 1H), 3.67 (s, 3H), 3.55 (br, 3H),
3.32e3.26 (m, 1H), 3.04e3.03 (m, 1H), 2.11e2.07 (m, 3H), 1.81e1.73
(m, 1H), 1.44 (s, 9H) ppm; dC (175 MHz, CDCl3): 174.2, 154.5, 137.9,
128.4, 127.7, 127.6, 127.5, 79.5, 73.3, 68.1, 59.3, 52, 47.1, 45.6, 29.7,
28.5, 27.0 ppm; HRMS (ESI) (m/z): calcd for C20H30NO5 [MþH]þ,
364.2124; found 364.2115.
4.2.10. (2R,3S)-tert-Butyl 3-(hydroxymethyl)-2-(2-methoxy-2-
oxoethyl)pyrrolidine-1-carboxylate (2b). To a solution of methyl
ester 12 (1.01 g, 1.94 mM) in THF (8 mL) was added drop-wise TBAF
in THF (4.0 mL, 4.0 mM) at 0 ꢁC. The reaction mixture was stirred for
1 h at the same temperature and quenched by the addition of
saturated aqueous NH4Cl solution. Then it was extracted with
EtOAc (40 mL), washed with water (2ꢂ10 mL), brine (10 mL) and
dried over anhydrous Na2SO4 and concentrated to dryness. Purifi-
cation by column chromatography (30% EtOAc/hexane) gave the
alcohol 2b (503 mg, 93%) as a colourless liquid. Rf 0.4 (50% EtOAc/
4.2.8. (2R,3S)-1-tert-Butyl 3-methyl 2-(2-hydroxyethyl)pyrrolidine-
1,3-dicarboxylate (1b). To a stirred solution of ester 1a (300 mg,
0.826 mM) in MeOH (10 mL), 10% PdeC (100 mg) were added and
subjected to hydrogenation under atmospheric pressure using
a hydrogen filled balloon. After 6 h the reaction mixture was filtered
through a short Celite pad and the filter cake was washed with
methanol. The filtrate and the washings were combined and con-
centrated in vacuo. Purification by column chromatography (30%
EtOAc/hexane) afforded methyl ester 1b (196 mg, 87%). Rf 0.4 (50%
hexane); [
a
]
D
25 ꢀ27.36 (c 1.345, CHCl3); nmax (liquid film) 3019, 1669,
1404, 1215, 756, 669 cmꢀ1
;
dH (400 MHz, CDCl3): 4.00 (m, 1H), 3.68
(s, 3H), 3.57 (br, 2H), 2.91 (m, 1H), 2.45 (m, 1H), 2.28 (m, 1H), 1.99
(m, 1H), 1.70 (m, 1H), 1.47 (m, 1H) ppm; dC (100 MHz, CDCl3): 172.5,
154.2, 79.9, 79.6, 64.1, 56.7, 51.8, 47.0, 46.2, 45.2, 44.9, 29.7, 28.5,
EtOAc/hexane); [a]
25 11.213 (c 0.51, CHCl3); nmax (liquid film) 3019,
D