Stereoselective synthesis of 2-substituted pyrrolidines

Article abstract of DOI:10.1135/cccc20000816

Using O-pivaloyl protected D-galactopyranosylamine and D-arabinopyranosylamine, (S) or (R) configured α-substituted homoallylamines are synthesized with high diastereoselectivity by reaction of the corresponding aldimines with allyltributylstannane. Electrophile-induced endo-trig-cyclization of these N-glycosylhomoallylamines gave the 2-substituted pyrrolidines of high diastereomeric purity.

Full text of DOI:10.1135/cccc20000816

816
Deloisy, Tietgen, Kunz:
STEREOSELECTIVE SYNTHESIS OF 2-SUBSTITUTED PYRROLIDINES
a
b
b1,
Sandrine DELOISY , Heiko TIETGEN and Horst KUNZ
*
a
Université de Paris-Sud, ICMO, Laboratoire des Carbocycles, F-91405Orsay cedex, France
Institut für Organische Chemie, Universität Mainz, D-55099 Mainz, Germany;
e-mail: hokunz@mail.uni-mainz.de
b
1
Received February 2, 2000
Accepted April 6, 2000
Dedicated to Professor Otakar Červinka on the occasion of his 75th birthday.
Usin g O-pivaloyl protected D-galactopyran osylam in e an d D-arabin opyran osylam in e, (S) or (R)
con figured α-substituted h om oallylam in es are syn th esized with h igh diastereoselectivity by
reaction of th e correspon din g aldim in es with allyltributylstan n an e. Electroph ile-in duced
endo-trig-cyclization of th ese N-glycosylh om oallylam in es gave th e 2-substituted pyrrolidin es
of h igh diastereom eric purity.
Key w ord s: Carboh ydrates; Ch iral auxiliaries; Hom oallylam in es; Electroph ile-in duced
cyclization ; Pyrrolidin es; Norn icotin e; Alkaloids; En an tioselective reaction s.
Stereoselective syn th eses of ch iral n itrogen h eterocycles are of particular in -
terest for th e organ ic ch em istry of drug design an d developm en t1. Alkaloids
con stitute an im portan t class of biologically active n atural products2. Th ey
are con sidered prom isin g lead structures for th e developm en t of drugs. A
n um ber of m eth ods for th e syn th esis of en an tiopure n itrogen h eterocycles
h ave been reported durin g th e past decade. Som e of th em are based on
ex-ch iral-pool strategies usin g en an tiom erically pure startin g m aterials3.
Oth er con cepts in clude separation s of en an tiom ers4. Auxiliary-based
stereoselective syn th eses of alkaloids h ave been perform ed usin g
α-ph en ylalkylam in es5, ph en ylglycin ol-6, cam ph or-7 or prolin e-derived8
auxiliaries. Asym m etric Man n ich reaction s h ave a great poten tial for th e
syn th esis of ch iral h eterocycles9. Usin g glycosylam in es as th e ch iral auxilia-
ries10 en an tiopure piperidin e alkaloids h ave been syn th esized by m ean s of
asym m etric Man n ich reaction s with excellen t diastereoselectivity11,12. Here
we report on th e stereoselective syn th esis of ch iral pyrrolidin es based on
th e stereoselective addition of allyltributylstan n an e to N-glycosylim in es
givin g N-glycosylh om oallylam in es13,14
.
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

Stereoselective Synthesis
817
Asymmetric Synthesis of 1-Substituted Homoallylamines
As h as been in prin ciple described in previous articles13,14, (S)-1-aryl substi-
tuted h om oallylam in es are syn th esized from im in es derived from
2,3,4,6-tetra-O-pivaloyl-β-D-galactopyran osylam in e (1).
Th e Sch iff bases 2 are eith er form ed by reaction of 1 with th e aldeh yde
(ben zaldeh yde) in propan -2-ol in th e presen ce of catalytic am oun ts of ace-
tic acid or pyridin e-3-carbaldeh yde in pen tan e in th e presen ce of m olecular
sieves 4Å. Th e im in es 2 can be isolated or directly used for furth er con ver-
sion .
In con trast to earlier work13, th e allylation of im in es 2 h as been carried
out usin g allyltributylstan n an e in stead of allyltrim eth ylsilan e. To im in e 2
an d tin tetrach loride (2.2 equivalen ts) in tetrah ydrofuran at –78 °C,
allyltributylstan n an e (1.2 equivalen ts) is added. Th e reaction m ixture is
slowly warm ed up to room tem perature. After h ydrolysis, th e correspon d-
in g h om oallylam in es 3 are isolated in h igh yields an d excellen t ratios of
diastereom ers (Sch em e 1).
OPiv
O
PivO
PivO
OPiv
O
PivO
PivO
(i)
R
N
NH2
PivO
PivO
H
1
2a, R = Ph
2c, R = (E)-Ph-CH=CH
2b, R = 3-Pyridyl
2d, R = (E)-2-NO2-Ph-CH=CH
3a, R = Ph, 87%, d.r. > 20 : 1
OPiv
O
PivO
PivO
H
N
(ii)
3b, R = 3-Pyridyl, 74%, d.r. > 25 : 1
3c, R = (E)-Ph-CH=CH, 85%, d.r. = 19 : 1
PivO
R
3d, R = (E)-2-NO2-Ph-CH=CH, 88%,
d.r. > 20 : 1
Piv = (CH3)3CCO
(i) R-CHO; (ii) CH2=CHCH2SnBu3, SnCl4, THF, -78 oC
r.t.
SCHEME 1
For stereoselective reaction s of im in es givin g ch iral products of th e oppo-
site con figuration in com parison with th ose obtain ed with th e
galactosylam in e 1, we successfully used 2,3,4-tri-O-pivaloyl-α-D-arabin osyl-
am in e15 (4). However, th e application of th is pseudo-en an tiom er to 1 was
n ot successful in th e case of th e tin tetrach loride-catalyzed allylation s usin g
allylsilan e or allylstan n an e derivatives13b. Just recen tly, we foun d th e rea-
son for th is aston ish in g differen ce in th e reaction s of im in es derived from 1
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

818
Deloisy, Tietgen, Kunz:
an d 4. In th e presen ce of stron g Lewis acids like tin tetrach loride, th e
N-arabin osylim in es 5 an om erize m ore rapidly th an th e N-galactosyl an a-
logues. Th e β-an om ers of 5 (with axial C–N bon d) do n ot react with th e
allylsilan e or allylstan n an e, but h ydrolyze durin g work-up. Th is un desired
an om erization can be preven ted if th e reaction tem perature in th e Lewis
acid-catalyzed reaction s of th e N-arabin osylim in es with allyltributyl-
stan n an e is kept below 10 °C (Sch em e 2).
PivO
OPiv
O
PivO
OPiv
OPiv
N
OPiv
NH2
(i)
R
O
4
H
5a, R = (E)-Ph-CH=CH
5b, R = 3-Pyridyl
PivO
OPiv
OPiv
H
N
(ii)
O
6a, R = (E)-Ph-CH=CH, 79%, d.r. = 19 : 1
6b, R = 3-Pyridyl, 45%, d.r. > 20 : 1
R
(i) R-CHO; (ii) CH2=CHCH2SnBu3, SnCl4, THF, -78 oC
<10 oC
SCHEME 2
Un der th ese con dition s, th e (R)-h om oallylam in es 6 are obtain ed with ex-
cellen t diastereoselectivity. Sch iff bases of 2,3,4,6-tetra-O-pivaloyl-
β-D-glucopyran osylam in e (7) with allyltributylstan n an e an d tin tetrach lo-
ride give (S)-h om oallylam in es 9 like th e galactosyl an alogues albeit with
sligh tly lower diastereofacial differen tiation (Sch em e 3).
OPiv
O
OPiv
O
(i)
R
PivO
PivO
PivO
PivO
N
NH2
PivO
PivO
H
8a, R = Ph
8b, R = (E)-Ph-CH=CH
7
OPiv
O
H
N
(ii)
PivO
PivO
9a, R = Ph, 65%, d.r. = 15 : 1
PivO
9b R = (E)-Ph-CH=CH, 75%, d.r. = 18 : 1
R
(i) R-CHO; (ii) CH2=CHCH2SnBu3, SnCl4, THF, -78 oC
SCHEME 3
r.t.
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

Stereoselective Synthesis
819
Th erefore, N-galactosylh om oallylam in es are preferen tially used for fur-
th er con version , e.g. for th e form ation of ch iral pyrrolidin es.
α-Substituted Pyrrolidines
Electroph ile-in duced cyclization of ch iral h om oallylam in es is useful for th e
syn th esis of pyrrolidin es. Acid-catalyzed cyclization of 1,5-dien es was suc-
cessfully applied to th e form ation of five- or six-m em bered carbocyclic
rin gs16. Un fortun ately, treatm en t of h om oallylam in e 3a with form ic acid or
acetic acid in dich lorom eth an e results in th e h ydrolytic cleavage of th e
N-glycosidic bon d rath er th an in an acid-catalyzed cyclization . In con trast,
th e N-arabin osylh om oallyam in e 6a reacts with 1.1 equivalen ts of iodin e in
dich lorom eth an e–dieth yl eth er (2 : 1) to form th e (R)-2-styrylpyrrolidin e 10
in h igh yield (Sch em e 4).
I
OPiv
OPiv
OPiv
OPiv
O
O
H
N
(i)
N
OPiv
OPiv
Ph
Ph
6a
10
(i) I2, CH2CH2/Et2O, 63%
SCHEME 4
Stereodifferen tiation in th e form ation of th e iodon ium in term ediate is
on ly low (1.5 : 1). Th is is con sidered less im portan t because th e iodin e is
reductively rem oved durin g subsequen t con version s.
A m ore gen eral an d efficien t electroph ile-in duced cyclization is ach ieved
with m ercury salts as in itiators17. Application of m ercury acetate as an
electroph ile results in varyin g yields of th e cyclized an d open -ch ain prod-
ucts. However, cyclization of th e N-galactosylh om oallylam in es 3 with m er-
cury(II) trifluoroacetate in aceton itrile at 0 °C an d subsequen t reductive
dem ercuration gives th e (S)-pyrrolidin es 11 in h igh yield (Sch em e 5).
Th e syn th esized ch iral h eterocycles are readily detach ed from th e carbo-
h ydrate auxiliary by treatm en t of th e N-galactosyl derivatives 11 with 0.1 M
HCl in aqueous m eth an ol to give h ydroch lorides 12 of th e pyrrolidin es al-
m ost quan titatively. For con firm ation of th eir absolute con figuration , th e
2-ph en yl derivative 12a an d th e 2-(3-pyridyl) derivative 12b are
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

820
Deloisy, Tietgen, Kunz:
OPiv
O
OPiv
O
PivO
PivO
PivO
PivO
H
N
(i)
N
PivO
PivO
R
R
3a, R = Ph
11a, R = Ph, 73%
3b, R = 3-Pyridyl
11b, R = 3-Pyridyl, 74%
3c, R = (E)-Ph-CH=CH
11c, R = (E)-Ph-CH=CH, 70%
OPiv
O
PivO
(ii)
HN
HCl
12a, R = Ph
+
PivO
OH
12b, R = 3-Pyridyl
PivO
R
(i) 1. Hg(OOCCF3)2, CH3CN; 2. NaBH3, NaOH, H2O; (ii) 0.1 M HCl/aq. MeOH
SCHEME 5
deproton ated to give en an tiom erically pure (S)-(–)-2-ph en ylpyrrolidin e18
(13a) an d (S)-(–)-n orn icotin e19 (13b) (Sch em e 6).
Na2CO3
Na2CO3
12b
12a
N
H
N
H
N
13b
13a
SCHEME 6
2-Substituted pyrrolidin es of th e opposite con figuration are obtain ed
from th e N-(D-arabin opyran osyl)h om oallylam in es 6 via m ercury(II) tri-
fluoroacetate-in duced cyclization an d subsequen t reductive rem oval of th e
m ercury substituen t (Sch em e 7).
OPiv
OPiv
OPiv
OPiv
O
O
H
N
(i)
N
OPiv
OPiv
R
R
6a, R = (E)-Ph-CH=CH
6b, R = 3-Pyridyl
14a, R = (E)-Ph-CH=CH, 22%
14b, R = 3-Pyridyl, 44%
(ii)
N
H
15
14b
N
2 HCl
(i) 1. Hg(OOCCF3)2, CH3CN; 2. NaBH3, NaOH, H2O; (ii) 0.1 M HCl/aq. MeOH
SCHEME 7
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

Stereoselective Synthesis
821
In both cases, th e ratio of diastereom ers of 14 is excellen t (R : S > 20 : 1)
accordin g to 400 MHz 1H NMR spectroscopic an alysis. Detach m en t of
(R)-n orn icotin e dih ydroch loride (15) from 14b is ach ieved usin g dilute h y-
drogen ch loride in aqueous m eth an ol. Its opposite en an tiom eric con figura-
tion com pared to 12b is con firm ed by its optical rotation value. Th e yields
of th e electroph ile-in duced cyclization in th e N-arabin osyl series are lower
th an th ose in th e N-galactosyl series. Th is is obviously due to th e fact, th at
th e N-arabin osylh om oallylam in es 6 are m ore pron e to an om erization .
Th eir β-an om ers (with axial an om eric C–N bon d) react m ore slowly in th e
electroph ile-in duced form ation of th e five-m em bered rin g.
Neverth eless, th e com bin ation of th e Lewis acid-catalyzed addition of
allyltributylstan n an e to eith er N-(D-galactosyl)- (2) or N-(D-arabin osyl)im -
in es 5 with th e subsequen t electroph ile-in duced endo-trig-cyclization of th e
N-glycosylh om oallylam in es provides an efficien t an d h igh ly stereoselective
access to 2-substituted pyrrolidin es of both en an tiom eric con figuration s.
EXPERIMENTAL
1H an d 13C NMR spectra were recorded on a Bruker W T-200 (200 MHz 1H NMR an d
50.3 MHz 13C NMR) an d a Bruker AM 400 (400 MHz 1H NMR an d 100.6 MHz 13C NMR)
NMR spectrom eter. Ch em ical sh ifts (δ) are given in ppm relative to th e sign al of tetram eth yl-
silan e, couplin g con stan ts (J) are given in Hz. Mass spectra were recorded on a FAB/FD m ass
spectrom eter Fin n igan MAT 95. An alytical HPLC was carried out in th e reverse ph ase m ode
usin g an LKB 2150 un it with diode array detection (190–370 n m ) on Eurosph er 100/C18 (5 m µ)
from Kn auer (Berlin , Germ an y). Aceton itrile–water m ixtures served as eluen ts. Th in -layer
ch rom atograph y was carried out usin g silica gel plates of 60F 254, preparative colum n ch ro-
m atograph y was perform ed on silica gel 60 (0.06–0.2 m m ), flash ch rom atograph y was car-
ried out usin g silica gel (0.04–0.063 m m ) all from Merck (Darm stadt, Germ an y).
N-Alkyliden e-2,3,4,6-tetra-O-pivaloyl-β-D-galactopyran osylam in es20 2 an d th e N-alkyliden e-
2,3,4-tri-O-pivaloyl-α-D-arabin opyran osylam in es21 5 h ave been prepared as previously de-
scribed.
N-(3-Pyridylm eth yliden e)-2,3,4,6-tetra-O-pivaloyl-β-D-galactopyran osylam in e20 (2b)
Yield 95%, am orph ous solid, RF 0.7 (petroleum eth er–eth yl acetate 13 : 7), [α]2D2 +8.3 (c 1,
CHCl3), th e com poun d con tain s 15% of th e α-an om er.
N-[3-(2-Nitroph en yl)prop-2-en -1-yliden e]-2,3,4,6-tetra-O-pivaloyl-β-D-galacto-
pyran osylam in e20 (2d )
Yield 74%, yellowish crystals, m .p. 111–114 °C, [α]2D2 –16.7 (c 1.1, CHCl3). 1H NMR (400 MHz,
CDCl3): 1.09 (s, 9 H, C(CH3)3); 1.11 (s, 9 H, C(CH3)3); 1.15 (s, 9 H, C(CH3)3); 1.25 (s, 9 H,
C(CH3)3); 4.05 (dd, 1 H, J6a,6b = 10.0, J6a,5 = 7.4, H-6a); 4.10 (dd, 1 H, J5,6a = 7.2, J5,6b = 5.6,
H-5); 4.22 (dd, J6b.6a = 10.0, J6b,5 = 5.5, H-6b); 4.69 (d, 1 H, J1,2 = 8.1, H-1); 5.21 (dd, 1 H, J3,2
=
10.3, J3,4 = 3.0, H-3); 5.27 (dd, 1 H, J2,3 = 10.3, J2,1 = 8.2, H-2); 5.47 (d, 1 H, J4,3 = 2.9, H-4);
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

822
Deloisy, Tietgen, Kunz:
6.81 (dd, 1 H, J1′,1′ = 15.8, J2′,3′ = 8.8, H-2′); 7.53 (d, 1 H, J1′,2′ = 15.8, H-1′); 7.49 an d 7.43 (2 m ,
3 H, H-4′′, H-5′′, H-6′′); 8.00 (d, 1 H, J3′′,4′′ = 8.0, H-3′′); 8.18 (d, 1 H, J3′,2′ = 8.8, H-3′). 13C NMR
(100.6 MHz, CDCl3): 94.6 (C-1). For C35H50N2O11 (674.7) calculated: 62.30% C, 7.47% H,
4.15% N; foun d: 62.50% C, 7.35% H, 3.99% N.
N-(3-Ph en ylprop-2-en -1-yliden e)-2,3,4-tri-O-pivaloyl-α-D-arabin osylam in e21 (5a)
Yield 48%, crystals, m .p. 135 °C, [α]D22 +4.3 (c 1, CHCl3). H NMR (200 MHz, CDCl3): 1.10 (s,
1
9 H, C(CH3)3); 1.12 (s, 9 H, C(CH3)3); 1.26 (s, 9 H, C(CH3)3); 3.6–3.7 (d, 1 H, J5b,5a = 12.46,
H-5b); 4.04–4.15 (dd, 1 H, J5a,4 = 1.96, H-5a); 4.5–4.55 (d, 1 H, J1,2 = 8.05, H-1); 5.1–5.4 (m ,
3 H, H-2, H-3, H-4); 6.8–7.0 (m , 2 H, H-1′, H-2′); 7.3–7.5 (m , 5 H, Ph ); 8.1–8.1 (d, J3′,2′ = 8.3,
H-3′). 13C NMR (50.3 MHz, CDCl3): 96.0 (C-1). For C33H49NO9 (603.8) calculated: 67.54% C,
8.01% H, 2.71% N; foun d: 67.05% C, 8.19% H, 2.51% N.
N-(3-Pyridylm eth yliden e)-2,3,4-tri-O-pivaloyl-α-D-arabin opyran osylam in e21 (5b)
Yield 44%, crystals, m .p. 131 °C, RF 0.58 (petroleum eth er–eth yl acetate 13 : 7), [α]2D2 –11.8 (c 1,
1
CHCl3). H NMR (200 MHz, CDCl3): 1.11 (s, 9 H, C(CH3)3); 1.13 (s, 9 H, C(CH3)3); 1.24 (s,
9 H, C(CH3)3); 3.78–3.85 (d, 1 H, J5b,5a = 13.30, H-5b); 4.08–4.2 (dd, 1 H, J5a,4 = 1.71, J5a,5b
=
13.30, H-5a); 4.8–5.4 (m , 4 H, H-1, H-2, H-3, H-4); 7.3 (d, 1 H, J4′′,5′′ = 4.98, H-4′′); 8.12 (t,
1 H, J5′′,6′′ = 1.95); 8.45 (s, 1 H, H-1′); 8.65 (d, 1 H, J6′′,5′′ = 1.95, H-6′′); 8.85 (s, 1 H, H-2′′).
13C NMR (50.3 MHz, CDCl3): 93.3 (C-1).
N-Ben zyliden e-2,3,4,6-tetra-O-pivaloyl-β-D-glucopyran osylam in e (8a) an d
N-(3-Ph en ylprop-2-en -1-yliden e)-2,3,4,6-tetra-O-pivaloyl-β-D-glucopyran osylam in e (8b)
Th e Sch iff bases of th e 2,3,4,6-tetra-O-pivaloyl-β-D-glucopyran osylam in e (7; m .p. 110 °C, [α]D22
+21.7 (c 1, CHCl3)) were prepared as described20 for th e N-galactosyl derivatives 2.
Compound 8a. Yield 78%, crystals, m .p. 129 °C, [α]2D2 –21.3 (c 1, CHCl3). Th e com poun d
con tain ed 8% of th e α-an om er. 1H NMR (400 MHz, CDCl3): 1.09 (s, 18 H, C(CH3)3); 1.14 (s,
9 H, C(CH3)3); 1.19 (s, 9 H, C(CH3)3); 3.84–3.92 (m , 1 H, J5,6a = 1.76, J5,6b = 5.28, H-5);
4.1–4.2 (dd, 1 H, J6b,5 = 5.28, J6b,6a = 12.63, H-6b); 4.21–4.3 (dd, 1 H, J
= 1.76, J6a,6b =
5,6a
12.62, H-6a); 4.85–4.9 (t, 1 H, J1,2 = 9.10, H-1); 4.98–5.02 (dd, 1 H, J2,1 = 9.09, H-2);
5.18–5.23 (t, 1 H, J3,4 = 9.69, H-3); 5.4–5.5 (t, 1 H, J4,3 = 9.69, H-4); 7.3–7.4 an d 7.6–7.7 (2 m ,
5 H, Ph ); 8.3 (s, 1 H, H-1′). 13C NMR (100.6 MHz, CDCl3): 92.3 (C-1). For C33H49NO9 (603.8)
calculated: 65.5% C, 8.18% H, 2.32% N; foun d: 65.68% C, 8.27% H, 2.24% N.
Compound 8b. Yield 95%, crystals, m .p. 176 °C, [α]2D2 –33.9 (c 0.75, CHCl3). 1H NMR (400
MHz, CDCl3): 1.10 (s, 9 H, C(CH3)3); 1.11 (s, 9 H, C(CH3)3); 1.14 (s, 9 H, C(CH3)3); 1.20 (s,
9 H, C(CH3)3); 3.83–4.02 (m , 1 H, J5,6a = 2.2, J5,6b = 4.39, H-5); 4.1–4.3 (2 dd, 2 H, J6b,5
=
J6a,6b = 12.45, J6a,5 = 2.2); 4.63–4.72 (d, 1 H, J1,2 = 8.79, H-1); 4.09–5.10 (dd, 1 H, J2,1 = 8.83,
J2,3 = 9.27, H-2); 5.18–5.3 (dd, 1 H, J3,2 = 9.27, J3,4 = 9.53, H-3); 6.8–7.0 (m , 2 H, J2′,1′ = 8.54,
H-2′, H-3′); 7.3–7.5 (m , 5 H, Ph ); 8.1 (d, 1 H, J1′,2′′ = 8.54, H-1′). 13C NMR (100.6 MHz,
CDCl3): 94.1 (C-1). For C35H51NO9 (629.7) calculated: 66.75% C, 8.16% H, 2.22% N; foun d:
66.69% C, 8.06% H, 2.26% N.
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Stereoselective Synthesis
823
1-Substituted N-Galactosyl- (3) an d N-Glucosylh om oallylam in es (9). Gen eral Procedure
A solution of N-galactosylim in e 2 or N-glucosylim in e 8 (2 m m ol) in dry tetrah ydrofuran
(20 m l) was cooled to –78 °C. Tin tetrach loride (4.4 m m ol) was added an d th e m ixture
stirred for 2.5 h at –78 °C. Allyltributylstan n an e (2.4 m m ol) was th en added. After stirrin g
for 1 h at –78 °C, th e m ixture was slowly h eated up to room tem perature an d h ydrolyzed
with 2 M aqueous NaOH (10 m l). Dieth yl eth er (50 m l) was added, th e aqueous layer sepa-
rated an d th ree tim es extracted with dich lorom eth an e (15 m l). Th e com bin ed organ ic layers
were wash ed with saturated aqueous NaHCO3 solution , dried over an h ydrous MgSO4, an d
th e solven t was evaporated. Th e rem ain in g oil was purified by flash ch rom atograph y.
N-(2,3,4,6-Tetra-O-pivaloyl-β-D-galactopyranosyl)-1(S)-amino-1-phenyl-3-butene22 (3a). Flash
ch rom atograph y in petroleum eth er–eth yl acetate (10 : 1), RF 0.26, yield 87%, colorless
am orph ous solid, [α]2D2 +4.4 (c 1, CHCl3). Th e com poun d con tain s 4% of th e (R)-diastereom er
(ref.22 gives [α]D22 +2.2 (c 1.3, CHCl3) for a m ixture of diastereom ers 11 : 1). 1H NMR (400 MHz,
CDCl3): 3.76 (d, 1 H, J1,2 = 8.5, H-1); 5.29 (d, 1 H, J4,3 = 3.1, H-4). 13C NMR (100.6 MHz,
CDCl3): 86.4 (C-1); 117.8 (C-4′); 134.5 (C-3′).
N-(2,3,4,6-Tetra-O-pivaloyl-β-D-galactopyranosyl)-1(S)-amino-1-(3-pyridyl)-3-butene22 (3b ).
Flash ch rom atograph y in petroleum eth er–eth yl acetate (2 : 1), RF 0.16 (petroleum
eth er–eth yl acetate 3 : 1), yield 74%, colorless am orph ous solid, [α]2D2 –3.9 (c 1.0, CHCl3).
1H NMR (400 MHz, CDCl3): 3.70 (dd, 1 H, J1,NH = 11.1, J1,2 = 8.7, H-1); 4.13 (t, 1 H, J1′,2′
=
6.8, Pyr-CH-N). 13C NMR (100.6 MHz, CDCl3): 86.3 (C-1). Th e ratio of diastereom ers is
>25 : 1 accordin g to th e 1H NMR spectrum . Th e com poun d described in ref.22 sh owed a ra-
tio of diastereom ers 11 : 1 an d [α]2D2 +2.2 (c 1.0, CHCl3).
N-(2,3,4,6-Tetra-O-pivaloyl-β-D-galactopyranosyl)-3(S)-amino-1(E)-phenyl-1,5-hexadiene22 (3c).
Yield 91%, RF 0.33 (petroleum eth er–eth yl acetate 10 : 1), colorless am orph ous solid, [α]D22
–5.1 (c 1.05, CHCl3), ratio of diastereom ers 19 : 1 (ref.22 gives [α]D22 –3.6 (c 1.03, CHCl3), ratio
of diastereom ers 15 : 1).
N-(2,3,4,6-Tetra-O-pivaloyl-β-D-galactopyranosyl)-3-(S)-amino-1(E)-(2-nitrophenyl)-1,5-hexadiene
(3d). Flash ch rom atograph y in petroleum eth er–eth yl acetate (4 : 1), RF 0.40, yield 88%, yel-
lowish am orph ous solid, [α]2D2 –12.6 (c 1.0, CHCl3). 1H NMR (400 MHz, CDCl3): 1.07 (s, 9 H,
C(CH3)3); 1.12 (s, 9 H, C(CH3)3); 1.15 (s, 9 H, C(CH3)3); 1.23 (s, 9 H, C(CH3)3); 1.97 (bs, 1 H,
NH); 2.25 (m , 2 H, 2 H-4′); 3.75 (dd, 1 H, J3′,2′ = 8.3, J3′,4′ = 6.4, H-3′); 3.97 (m , 2 H, H-5,
H-6a); 4.13 (dd, 1 H, J6b,6a = 9.7, J6b,5 = 5.7, H-6b); 4.18 (d, 1 H, J1,2 = 8.8, H-1); 5.06 (m , 3 H,
2 H-6′, H-2); 5.13 (dd, 1 H, J3,2 = 10.3, J3,4 = 3.3, H-3); 5.39 (d, 1 H, J4,3= 3.1, H-4); 5.74 (m ,
1 H, 5-5′); 5.75 (dd, 1 H, J2′,1′ = 15.6, J2′,3′ = 8.3, H-2′); 6.88 (d, 1 H, J1′,2′ = 15.6, H-1′); 7.38
(dt, 1 H, J4′′,3′′ = J4′′,5′′ = 8.4, J4′′,6′′ = 1.4, H-4′′); 7.47 (dd, 1 H, J6′′,5′′ = 7.8, J6′′,4′′ = 1.2, H-6′′);
7.55 (ddd, 1 H, J5′′,4′′ = 8.5, J5′′,6′′ = 7.5, J5′′,3′′ = 1.0, H-5′′); 7.93 (dd, 1 H, J3′′,4′′ = 8.2, J5′′,3′′
=
1.0, H-3′′). 13C NMR (100.6 MHz, CDCl3): 86.6 (C-1); 147.8 (C-NO2). Ratio of diastereom ers
is >20 : 1 accordin g to th e 1H NMR spectrum .
N-(2,3,4,6-Tetra-O-pivaloyl-β-D-glucopyranosyl)-1(S)-amino-1-phenyl-3-butene (9a). Flash ch ro-
m atograph y in petroleum eth er–eth yl acetate (10 : 1), RF 0.52 (petroleum eth er–eth yl acetate
4 : 1), yield 65%, colorless am orph ous solid, [α]2D2 –12.8 (c 1.0, CHCl3). 1H NMR (400 MHz,
CDCl3): 1.06 (s, 9 H, C(CH3)3); 1.17 (s, 9 H, C(CH3)3); 1.18 (s, 9 H, C(CH3)3); 1.24 (s, 9 H,
C(CH3)3); 2.18 (bs, 1 H, NH); 2.27–2.38 (m , 2 H, 2 H-2′); 3.58–3.61 (m , 1 H, J5,6a = 7.1, J5,6b
=
6.6., H-5); 3.77 (d, 1 H, J1,2 = 7.7, H-1); 3.94 (dd, J6b,6a = 11.2, J6b,5 = 6.6, H-6b); 4.07 (dd,
1 H, J6a,6b = 11.2, J6a,5 = 7.1, H-6a); 4.12 (dd, 1 H, J1′,2a′ = 6.9, J1′,2b′ = 6.9, H-1′); 5.01 (m , 4 H,
H-2, H-3, 2 H-4′); 5.29 (d, J4,3 = 2.9, H-4); 5.61 (m , 1 H, H-3′); 7.21–7.29 (m , 5 H, Ph ). 13C NMR
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

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Deloisy, Tietgen, Kunz:
(100.6 MHz, CDCl3): 86.1 (C-1). Ratio of diastereom ers is 17 : 1 accordin g to th e 1H NMR
spectrum . For C36H55NO9 (645.8) calculated: 66.95% C, 8.58% H, 2.17% N; foun d: 67.17% C,
8.65% H, 2.06% N.
N-(2,3,4,6-Tetra-O-pivaloyl-β-D-glucopyranosyl)-3(S)-amino-1(E)-phenyl-1,5-hexadiene (9b ).
Flash ch rom atograph y in petroleum eth er–eth yl acetate (7 : 1), RF 0.53 (petroleum
ether–ethyl acetate 6 : 1), yield 75%, colorless amorphous solid, [α]2D2 –14.8 (c 1.0, CHCl3). 1H NMR
(400 MHz, CDCl3): 1.08 (s, 9 H, C(CH3)3); 1.10 (s, 9 H, C(CH3)3); 1.16 (s, 9 H, C(CH3)3); 1.23
(s, 9 H, C(CH3)3); 1.85–1.92 (bs, 1 H, NH); 2.08–2.12 (m , 1 H, J4b,4a = 13.69, H-4b); 2.24–2.29
(m , 1 H, J4a,4b = 13.7); 3.58–3.61 (m , 1 H, J5,6b = 6.26, H-5); 3.65–3.70 (m , 1 H, H-3);
3.96–4.01 (dd, 1 H, J6b,5 = 6.26, J6b,6a = 12.31, C-6b); 4.1–4.2 (m , 2 H, J6a,5 = 1.56, J6a,6b
=
12.13, H-6a, H-1); 4.81–4.86 (t, 1 H, J2,1 = J2,3 = 9.39, H-2); 4.99–5.89 (m , 3 H, J4,3 = 9.78,
H-4, 2 H-6′); 5.24–5.29 (dd, 1 H, J3,2 = 9.39, J3,4 = 9.78, H-3); 5.7–5.86 (m , 2 H, J2′,1′ = 16.04,
H-2′, H-5′); 6.42 (d, 1 H, J1′,2′ = 16.04); 7.2–7.34 (m , 5 H, Ph ). 13C NMR (100.6 MHz, CDCl3):
86.5 (C-1). Ratio of diastereom ers is 18 : 1 accordin g to th e 1H NMR spectrum . For
C
38H57NO9 (671.8) calculated: 67.93% C, 8.55% H, 2.08% N; foun d: 67.50% C, 8.52% H,
2.00% N.
1-Substituted N-(D-Arabin opyran osyl)h om oallylam in es (6). Gen eral Procedure
A solution of N-arabin osylim in e 5 (1.5 m m ol) in dry tetrah ydrofuran (20 m l) was cooled to
–78 °C. Tin tetrachloride (3.3 m m ol) was added dropwise, and the m ixture was stirred for 3 h at
–78 °C. Th en , allyltributylstan n an e (3.1 m m ol) was added an d th e reaction is allowed to warm
up to 0–5 °C with in 15 h . After stirrin g for an addition al 24 h at th is tem perature, 2 M aqueous
NaOH (15 m l) an d, subsequen tly, eth yl acetate (60 m l) were added. Th e aqueous layer was sep-
arated an d extracted twice with eth yl acetate (20 m l). Th e com bin ed organ ic layers were
wash ed with 2 M NaOH (30 m l), brin e (20 m l) an d water, an d dried over an h ydrous MgSO4. Af-
ter evaporation of th e solven t, th e product was purified by colum n ch rom atograph y.
N-(2,3,4-Tri-O-pivaloyl-α-D-arabinopyranosyl)-3(R)-amino-1(E)-phenyl-1,5-hexadiene (6a). Col-
um n ch rom atograph y in petroleum eth er–eth yl acetate (8 : 1), RF 0.69 (petroleum
eth er–eth yl acetate 5 : 1), yield 79%, crystals, m .p. 126 °C, [α]2D2 –47.0 (c 1.0, CHCl3). 1H NMR
(400 MHz, CDCl3): 1.08 (s, 9 H, C(CH3)3); 1.12 (s, 9 H, C(CH3)3); 1.16 (s, 9 H, C(CH3)3); 1.20
(s, 9 H, C(CH3)3); 1.85–1.92 (bs, 1 H, NH); 2.15 (m , 2 H, H-4′); 3.49–3.51 (d, 1 H, J1,2
12.62, H-1); 3.65–3.71 (dd, 1 H, J5b,4 = 6.75, J5b,5a = 14.6, H-5b); 3.86–3.91 (dd, 1 H, J5a,4
=
=
2.05, J5a,6b = 13.21, H-5a); 4.0 (m , 1 H, H-3′); 4.98–5.1 (m , 5 H, H-2, H-3, H-4, 2 H-6′);
5.68–5.8 (m , 1 H, H-5′); 5.81–5.9 (dd, 1 H, J2′,3 = 8.22, J2′,1′ = 15.85, H-2′); 6.43–6.4 (d, 1 H,
J1′,2′′ = 16.14, H-1′); 7.2–7.4 (m , 5 H, Ph ). 13C NMR (100.6 MHz, CDCl3): 70.1 (-CH-NH); 87.2
(C-1). Accordin g to th e 1H NMR spectrum , th e ratio of diastereom ers is 19 : 1. For
C
33H47NO7 (557.7) calculated: 68.85% C, 8.49% H, 2.51% N; foun d: 68.84% C, 8.42% H,
2.12% N.
N-(2,3,4-Tri-O-pivaloyl-α-D-arabinopyranosyl)-1(R)-amino-1-(3-pyridyl)-3-butene (6b). Colum n
ch rom atograph y in petroleum eth er–eth yl acetate (5 : 2), RF 0.19, yield 45%, colorless oil, [α]D22
–21.1 (c 1.0, CHCl3). 1H NMR (200 MHz, CDCl3): 1.06 ((s, 9 H, C(CH3)3); 1.16 (s, 9 H,
C(CH3)3); 1.21 (s, 9 H, C(CH3)3); 2.2–2.4 (m , 2 H, H-2′); 3.28–3.38 (dd, 1 H, J6b,6a = 13.43,
J6b,5 = 1.05, H-6b); 3.55–3.65 (d, 1 H, J1,2 = 8.3); 3.78–3.88 (dd, 1 H, J6a,6b = 13.42, J6a,5
=
13.23, H-6a); 4.1-4.2 (t, 1 H, J1′,2a′ = 6.59, J1′,2b′ = 7.08, H-1′); 4.93–5.10 (m , 5 H, H-2, H-3,
H-4, 2 H-4′); 5.1–5.65 (m , 1 H, H-3′); 7.17–7.24 (dd, 1 H, J5′′,3′′ = 7.81, H-5′′); 7.54–7.59 (dd,
J4′′,5′′ = 7.81, H-4′′); 8.46 (bs, 2 H, H-2′′, H-6′′). 13C NMR (100.6 MHz, CDCl3): 86.7 (C-1). Th e
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

Stereoselective Synthesis
825
ratio of diastereom ers was 13 : 1 accordin g to an alytical HPLC. For C29H44N2O7 (532.7) cal-
culated: 65.39% C, 8.33% H, 5.26% N; foun d: 65.41% C, 8.37% H, 5.28% N.
2-Substituted 1-Glycosylpyrrolidin es (11) an d (14). Gen eral Procedure
To a solution of th e N-glycosylh om oallylam in e 3 or 6 (0.5 m m ol), in aceton itrile (10 m l) at
0 °C, a solution of m ercury(II) trifluoroacetate (324 m g, 0.75 m m ol) in aceton itrile (1.5 m l)
was added. The solution was stirred for 2 h at 0 °C. Then, sodium borohydride (38 mg, 1.0 mmol)
in 3 M NaOH (1.1 m l, 3.2 m m ol) was added. After stirrin g for 30 m in at 0 °C (precipitation
of m ercury) an d addition of saturated aqueous NaHCO3 solution (50 m l), th e aqueous layer
was extracted four tim es with 30 m l of CH2Cl2. Th e organ ic layer was dried over an h ydrous
MgSO4, an d th e solven t was evaporated in vacuo. Pyrrolidin es 11 an d 14 were purified by
ch rom atograph y.
(S)-1-(2,3,4,6-Tetra-O-pivaloyl-β-D-galactopyranosyl)-2-phenylpyrrolidine (11a). Flash ch rom a-
tograph y in petroleum eth er–eth yl acetate (10 : 1), RF 0.31, yield 73%, colorless crystals,
m .p. 160 °C, [α]2D2 –24.2 (c 1.0, CHCl3). 1H NMR (400 MHz, CDCl3): 1.07 ((s, 9 H, C(CH3)3);
1.16 (s, 9 H, C(CH3)3); 1.17 (s, 9 H, C(CH3)3); 1.25 (s, 9 H, C(CH3)3); 1.65 (m , 1 H, H-3′);
1.82 (m , 2 H, 2 H-4′); 2.12 (m , 1 H, H-3′); 3.16 (m , 2 H, 2 H-5′); 3.72 (t, 1 H, J5,6a = J5,6b
=
6.8, H-5); 3.94 (dd, 1 H, J6a,6b = 11.1, J6a,5 = 6.6, H-6a); 4.00 (d, 1 H, J1,2 = 9.3, H-1); 4.10 (m ,
2 H, H-2′, H-6b); 4.93 (dd, 1 H, J3,2 = 10.0, J3,4 = 3.1, H-3); 5.29 (d, 1 H, J4,3 = 3.0, H-4); 5.39
(t, 1 H, J2,1 = J2,3 = 9.6, H-2); 7.21–7.27 (m , 5 H, Ph ). Ratio of diastereom ers determ in ed by
1H NMR is >20 : 1. For C36H55NO9 (645.8) calculated: 66.95% C, 8.58% H, 2.70% N; foun d:
66.93% C, 8.53% H, 2.10% N.
(S)-1-(2,3,4,6-Tetra-O-pivaloyl-β-D-galactopyranosyl)-2-(3-pyridyl)pyrrolidine (11b). Flash ch ro-
m atograph y in petroleum eth er–eth yl acetate (2 : 1), RF 0.13 (petroleum eth er–eth yl acetate
4 : 1), yield 70%, colorless crystals (pen tan e), m .p. 126–127 °C, [α]2D2 –32.9 (c 1, CHCl3).
1H NMR (400 MHz, CDCl3): 1.03 (s, 9 H, C(CH3)3); 1.11 (s, 9 H, C(CH3)3); 1.14 (s, 9 H,
C(CH3)3); 1.21 (s, 9 H, C(CH3)3); 1.63 (m , 1 H, H-3′); 1.80 (m , 2 H, 2 H-4′); 2.13 (m , 1 H,
H-3′); 3.17 (t, 1 H, J5′,4′ = 7.0, 2 H-5′); 3.72 (t, 1 H, J5,6a = J5,6b = 6.7, H-5); 3.91 (dd, 1 H, J5,6a
=
6.7, J6a,6b = 11.3, H-6a); 3.94 (d, 1 H, J1,2 = 9.4, H-1); 4.07 (dd, 1 H, J5,6b = 6.7, J6a,6b = 11.3,
H-6b); 4.11 (t, 1 H, J2′3′ = 7.7, H-2′); 4.91 (dd, 1 H, J3,2 = 10.0, J3,4 = 3.0, H-3); 5.28 (d, 1 H,
J4,3 = 2.9, H-4); 5.35 (t, 1 H, J2,1 = J2,3 = 9.7, H-2); 7.17 (dd, 1 H, J5′′,4′′ = 7.7, J5′′,6′′ = 4.8,
H-5′′); 7.55 (d, 1 H, J4′′,5′′ = 7.7, H-4′′); 8.46 (m , 2 H, H-2′′, H-6′′). 13C NMR (100.6 MHz,
CDCl3): 61.2 (C-2′); 87.4 (C-1). Ratio of diastereom ers determ in ed from th e 1H NMR spec-
trum is >20 : 1. For C35H54N2O9 (646.8) calculated: 64.99% C, 8.41% H, 4.33% N; foun d:
64.94% C, 8.41% H, 4.30% N.
(E)-(S)-1-(2,3,4,6-Tetra-O-pivaloyl-β-D-galactopyranosyl)-2-styrylpyrrolidine (11c). Flash ch ro-
m atograph y in petroleum eth er–eth yl acetate (10 : 1), RF 0.29, yield 74%, colorless crystals,
m .p. 109–110 °C (pen tan e), [α]2D2 –36.4 (c 1.2, CHCl3). 1H NMR (400 MHz, CDCl3): 1.07 (s,
9 H, C(CH3)3); 1.15 (s, 9 H, C(CH3)3); 1.18 (s, 9 H, C(CH3)3); 1.24 (s, 9 H, C(CH3)3); 1.55 (m ,
1 H, H-3′); 1.73 (m , 2 H, 2 H-2′); 1.96 (m , 1 H, H-3′); 3.06 (m , 2 H, 2 H-5′); 3.62 (q, 1 H, J2′,3′
=
J2′,CH = 8.2, H-2); 3.84 (t, 1 H, J5,6a = J5,6b = 6.8, H-5); 3.95 (dd, 1 H, J6a,6b = 11.0, J6a,5 = 6.9,
H-6a); 4.13 (dd, 1 H, J6b,6a = 11.0, J6b,5 = 6.8, H-6b); 4.22 (d, 1 H, J1,2 = 9.3, H-1); 5.04 (dd,
1 H, J3,2 = 10.0, J3,4 = 3.1, H-3); 5.32 (t, 1 H, J2,1 = J2,3 = 9.9, H-2); 5.34 (d, 1 H, J3,4 = 2.7,
H-4); 5.88 (dd, 1 H, JCH=CH = 8.4, CH=); 6.41 (d, 1 H, JCH=CH = 15.8, =CH); 7.19–7.32 (m ,
5 H, Ph ). 13C NMR (100.6 MHz, CDCl3): 62.3 (C-2′); 87.3 (C-1). Ratio of diastereom ers de-
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

826
Deloisy, Tietgen, Kunz:
term ined by 1H NMR is >20 : 1. For C38H57NO9 (671.8) calculated: 67.93% C, 8.55% H, 2.08% N;
foun d: 67.97% C, 8.53% H, 1.97% N.
(E)-(R)-1-(2,3,4-Tri-O-pivaloyl-α-D-arabinopyranosyl)-2-styrylpyrrolidine (14a). Colum n ch ro-
m atograph y in petroleum eth er–eth yl acetate (15 : 1), RF 0.65 (petroleum eth er–eth yl acetate
10 : 1), yield 22%, crystals, m .p. 200 °C, [α]2D2 –13.8 (c 1, CHCl3). 1H NMR (400 MHz, CDCl3):
1.09 (s, 9 H, C(CH3)3); 1.16 (s, 9 H, C(CH3)3); 1.25 (s, 9 H, C(CH3)3); 1.51–1.54 (m , 1 H,
H-3′); 1.70–1.74 (m , 2 H, H-4′); 1.91–2.01 (m , 1 H, H-3′); 3.05–3.1 (t, 2 H, J5a′,4′ = 6.84, J5′,4
7.08, H-5′); 3.59–3.77 (m , 2 H, J2′,3′ = 8.3, H-2′, H-5b); 3.85–3.98 (dd, 1 H, J5a,5b = 12.94, J5a,4
=
=
2.2, H-5a); 4.15–4.18 (d, 1 H, J1,2 = 9.28, H-1); 4.9–5.05 (dd, 1 H, J3,2 = 10.0, J3,4 = 4.48, H-3);
5.15–5.21 (m , 1 H, H-4); 5.3–5.41 (dd, 1 H, J2,1 = 9.28, J2,3 = 10.0, H-2); 5.8–6.0 (dd, 1 H,
J1′′,2′ = 8.55, J1′′,2′′ = 8.55, J1′′,2′′ = 15.87, H-1′′); 6.4–6.55 (dd, 1 H, J2′′,1′′ = 15.84, H-2′′);
7.2–7.43 (m , 5 H, Ph ). 13C NMR (100.6 MHz, CDCl3): 62.3 (C-2′); 87.8 (C-1); 131.4
(CH-CH=CH-Ph ). Ratio of diastereom ers determ in ed by 1H NMR >20 : 1. FD MS: m/z 557.6
(M+).
(R)-1-(2,3,4-Tri-O-pivaloyl-α-D-arabinopyranosyl)-2-(3-pyrridyl)pyrrolidine (14b). After evapora-
tion of th e solven t, th e rem ain in g crude product was recrystallized from aceton itrile, yield
44%, crystals, m .p. 217 °C (decom p.), [α]2D2 –12.9 (c 1, CHCl3). 1H NMR (200 MHz, CDCl3):
1.06 (s, 9 H, C(CH3)3); 1.15 (s, 9 H, C(CH3)3); 1.21 (s, 9 H, C(CH3)3); 1.54 (m , 1 H, H-3′);
1.72–1.92 (m , 2 H, H-4′); 2.1–2.25 (m , 1 H, H-3′); 3.18–3.25 (m , 2 H, H-5′); 3.4–3.5 (dd, 1 H,
J5b,5a = 12.45, H-5b); 3.8–3.98 (m , 2 H, J5a,5b = 12.35, H-5a, H-1); 4.08–4.1 (t, 1 H, J2′3′
=
7.57); 4.85–4.95 (dd, 1 H, J3,2 = 10.01, J3,4 = 3.42, H-3); 5.08–5.18 (m , 1 H, H-4); 5.38–5.5 (t,
1 H, J2,1 = 9.52, J2,3 = 9.77, H-2); 7.18–7.23 (dd, 1 H, J5′′,4′′ = 7.81, J5′′,6′′ = 4.88, H-5′′);
7.55–7.63 (dt, 1 H, J4′′,5′′ = 7.81, H-4′′); 8.5 (bs, 2 H, H-2′′, H-6′′). 13C NMR (50.3 MHz,
CDCl3): 61.2 (C-2′); 87.8 (C-1). Th e ratio of diastereom ers was determ in ed by th e 1H NMR
spectrum >20 : 1. For C29H44N2O7 (532.7) calculated: 65.34% C, 8.33% H, 5.26% N; foun d:
65.12% C, 8.32% H, 5.15% N.
(E)-(2R)-1-(2,3,4-Tri-O-pivaloyl-α-D-arabin opyran osyl)-4-iodo-2-styrylpyrrolidin e (10)
To a solution of N-arabin osylh om oallylam in e 6a (100 m g, 0.18 m m ol) in dieth yl eth er–
dich lorom eth an e (3 m l, 1 : 2) at 0 °C, iodin e (50 m g, 0.19 m m ol) was added. Th e solution
was stirred at 0 °C for 2 h . After addition of dich lorom eth an e (20 m l), wash in g with satu-
rated NaHCO3 solution (20 m l), 0.5 M Na2S2O3 solution (20 m l) an d water, th e organ ic layer
was dried over MgSO4. Th e solven t was evaporated, th e residue dissolved in eth yl acetate
(20 m l) an d filtered th rough n eutral Al2O3. Evaporation of th e solven t gave 10 as a yellow-
ish oil. Yield 77 m g (63%), RF 0.18 (petroleum eth er–eth yl acetate 7 : 1), [α]2D2 –27.8 (c 1.0,
CHCl3). Accordin g to th e 1H NMR an alysis, th e substan ce con sists of two diastereom ers dif-
ferin g in th e con figuration at C-4 of th e pyrrolidin e rin g.
(–)-(S)-2-Ph en ylpyrrolidin e (13a)
To a solution of 1-galactosyl-2-ph en ylpyrrolidin e 11a (234 m g, 0.36 m m ol) in m eth an ol (4 m l),
1
M HCl (0.54 m l, 0.54 m m ol) was added. After addition of dich lorom eth an e (0.5 m l), th e
m ixture was stirred at room tem perature for 20 h an d th en con cen trated in vacuo. Th e resi-
due was dissolved in 1 M HCl (20 m l) an d extracted th ree tim es with pen tan e (40 m l). Th e
aqueous solution was evaporated in vacuo. Th e rem ain in g h ydroch loride 12a was dissolved
in saturated aqueous Na2CO3 solution an d extracted with dich lorom eth an e (twice with 20 m l).
Collect. Czech. Chem. Commun. (Vol. 65) (2000)

Stereoselective Synthesis
827
Th e organ ic layer was dried with MgSO4 an d th e solven t evaporated in vacuo to give 51 m g
(96%) of th e 2-ph en ylpyrrolidin e 13a. Brown ish oil, RF 0.25 (petroleum eth er–eth yl acetate
3 : 1), [α]2D2 –22.9 (c 0.3, MeOH) (ref.18 gives [α]D22 –22.0 (MeOH)). 1H NMR (400 MHz, CDCl3):
1.76 (m , 1 H, H-3); 1.89 (m , 2 H, 2 H-4); 2.18 (m , 1 H, H-3); 3.00 (m , 1 H, H-5); 4.14 (t, 1 H,
J2,3 = 7.7, H-2); 4.66 (bs, 1 H, NH); 7.27–7.39 (m , 5 H, Ph ). 13C NMR (100 MHz, CDCl3): 62.6
(C-2).
(S)-(–)-Norn icotin e (13b)
To a solution of th e 1-galactosyl-2-(3-pyridyl)pyrrolidin e 11b (152 m l, 0.23 m m ol) in m eth a-
n ol (3 m l), 1 M HCl (0.82 m l, 0.82 m m ol) was added. Dich lorom eth an e was added to th e
stirred solution un til dissolution of th e form ed precipitate. Th e m ixture was stirred for 24 h
at room tem perature, an d th e solven t evaporated in vacuo. Th e residue was dissolved in 0.5
M
HCl (10 m l) an d extracted th ree tim es with dich lorom eth an e (30 m l). Th e aqueous solution
was evaporated in vacuo to give th e dih ydroch loride 12b (52 m g), [α]2D2 +5.4 (c 1, MeOH).
Th e salt was dissolved in saturated aqueous Na2CO3 solution an d th e product extracted with
dich lorom eth an e (th ree tim es 10 m l). Evaporation of th e solven t gave (S)-n orn icotin e as a
brown ish oil. Yield 34 m g (quan titative), [α]2D2 –29.3 (c 0.25, MeOH) (ref.19 gives [α]2D2 –34.9 (c
0.3, MeOH)). 1H NMR of th e dih ydroch loride 13b (400 MHz, CDCl3): 2.38 (bm , 3 H, H-3, 2
H-4); 2.70 (m , 1 H, H-3); 3.63 (m , 2 H, 2 H-5); 4.96 (m , 1 H, H-2); 8.27, 8.94, 9.02, 9.21 (4 s,
4 H, H-2′, H-4′, H-5′, H-6′). 13C NMR (100.6 MHz, D2O): 25.8 (C-4); 32.5 (C-3); 48.7 (C-5);
62.1 (C-2); 130.5 (C-4′); 137.5 (C-5′); 143.4 (C-3′); 144.6 (C-6′); 148.9 (C-2′).
(R)-Norn icotin e Dih ydroch loride 15
To a solution of th e 1-arabin osyl-2-(3-pyridyl)pyrrolidin e (14b) (126 m g, 0.19 m m ol) in
m eth an ol (5 m l) 1 M HCl (2 m l, 2 m m ol) was added. After stirrin g for 1 h at room tem pera-
ture th e m ixture was poured in to 0.5 M HCl (25 m l) an d dich lorom eth an e (25 m l). Th e or-
gan ic layer was separated an d th e aqueous solution extracted twice with dich lorom eth an e
(25 m l). After evaporation of th e aqueous solution , th e dih ydroch loride 15 was isolated:
yield 35 m g (84%), [α]2D2 –3.8 (c 1.0, MeOH), EI MS, m/z: 148.2 (M + H).
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Deloisy, Tietgen, Kunz:
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