Chiral phenylselenyl derivatives of pyrrolidine and Cinchona alkaloids: nitrogen-selenium donating ligands in palladium-catalyzed asymmetric allylic alkylation

Article abstract of DOI:10.1016/j.tetasy.2006.12.021

Enantiomeric pyrrolidine alcohols and Cinchona alkaloids reacted with PhSeCN/Bu₃P in toluene at 0-25 °C to give the corresponding phenyl selenides with complete inversion of configuration at the substitution centers. Thus, the chiral selenoethe

Full text of DOI:10.1016/j.tetasy.2006.12.021

Tetrahedron: Asymmetry 18 (2007) 131–136
Chiral phenylselenyl derivatives of pyrrolidine and Cinchona
alkaloids: nitrogen–selenium donating ligands in
palladium-catalyzed asymmetric allylic alkylation
*
´
_
Mariola Zielinska-Błajet, Renata Siedlecka and Jacek Skarzewski
Department of Organic Chemistry, Faculty of Chemistry, Wrocław University of Technology, 50-370 Wrocław, Poland
Received 6 December 2006; accepted 18 December 2006
Available online 29 January 2007
Abstract—Enantiomeric pyrrolidine alcohols and Cinchona alkaloids reacted with PhSeCN/Bu3P in toluene at 0–25 ꢀC to give the cor-
responding phenyl selenides with complete inversion of configuration at the substitution centers. Thus, the chiral selenoethers obtained
were tested in the Pd-catalyzed allylic alkylation of dimethyl malonate with rac-1,3-diphenyl-2-propenyl acetate. When chiral selenium
pyrrolidine derivatives were applied, the enantioselectivity observed was improved versus the respective sulfur pyrrolidine derivatives up
to over 98% ee. The results suggest that the pyrrolidine selenoethers served as the effective N(sp3), Se-donating chiral ligands. The
selenoethers obtained from Cinchona alkaloids also gave the allylic alkylation product with a higher ee over those for the correspon-
ding thioethers. The results are in agreement with nucleophilic attack directed at the allylic carbon located trans to the chalcogen
atom in the intermediate g3-allylpalladium complex.
ꢁ 2007 Elsevier Ltd. All rights reserved.
1. Introduction
donor,4 while for strongly r-donating (sp3)-nitrogen and
weakly p-accepting chalcogen atoms, the trans direction
to chalcogen is generally preferred (Fig. 1).5
Properly designed chiral ligands offer great potential in the
synthetic application of catalytic asymmetric reactions.1
The most valuable ligands (privileged catalysts) are effective
in various, often mechanistically different, enantioselective
transformations.2 To this class of catalysts belong the
derivatives of natural cyclic amino acids and Cinchona
alkaloids. Many successful chiral ligands have already been
found for the palladium-catalyzed allylic nucleophilic
alkylation, a powerful tool for enantioselective C–C bond
formation.3 Nevertheless, this reaction is still used for test-
ing new catalysts for transition-metal catalyzed processes,
since its mechanism is well understood and the enantiose-
lectivity of products is determined by both steric and ste-
reoelectronic properties of the chiral ligand coordinated
to the palladium atom.3 Thus, due to the trans effect,4 an
attacking nucleophile favorably approaches the complexed
allylic system from the opposite site to the more p-accep-
ting ligand center. According to this, in the case of biden-
tate C@N (imine)—chalcogen ether ligands, the
nucleophile approaches trans to the more p-accepting imine
Within our investigation program to explore the prepara-
tion and use of chiral organochalcogen compounds in
asymmetric catalysis, we have developed the synthesis of
new sulfur–nitrogen mixed donor chelate ligands suitable
for this purpose. Among them, we obtained the sulfur
derivatives of chiral pyrrolidine alcohols6 and Cinchona
alkaloids.7 On the other hand, nitrogen-containing seleno-
ethers have already been reported as successful catalysts in
the Pd-catalyzed allylic substitutions.8 This subject has
recently been reviewed by Braga et. al.9 Encouraged
by the reported results, we have elaborated upon an easy
Ph
*
N
*
N
Ph
Pd
Pd
Nu
Nu
X
X
Ph
Ph
M-shaped η3-complex
W-shaped η3-complex
*
Corresponding author. Tel.: +48 71 320 2464; fax: +48 71 328 4064;
e-mail: jacek.skarzewski@pwr.wroc.pl
Figure 1.
0957-4166/$ - see front matter ꢁ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2006.12.021

132
M. Zielin´ska-Błajet et al. / Tetrahedron: Asymmetry 18 (2007) 131–136
preparation of the respective phenyl selenides derived from
the chiral amino alcohols belonging to the privileged cata-
lysts class. Herein, we report their syntheses and catalytic
use as new enantioselective N, Se-ligands, easily available
in both enantiomeric forms. We also compare their cata-
lytic performance to the results obtained for the respective
N,S-analogues.
pyridine. This simple procedure gave the required products
in good to reasonable yields (Scheme 1). Commercially
available primary amino alcohols N-Boc-L-valinol 1h and
(S)-1-benzyl-2-pyrrolidinemethanol 1g as well as the unhin-
dered secondary ones (S)- and (R)-1-benzyl-3-hydroxypyr-
rolidines 1e and 1f reacted smoothly, while the Cinchona
alcohols 1a–d, namely, quinine (QN), dihydroquinine
(DHQN), cinchonine (CN), and dihydroquinidine
(DHQD) required longer reaction time and the yield was
lower. It was observed before that the phenylsulfanyl deriv-
atives of Cinchona alkaloids 2 of the same 8,9-configura-
tions (i.e., 8R,9R or 8S,9S) gave in the Pd-catalyzed
allylic substitution much higher enantioselectivities than
those of unlike configurations,7 the selenium compounds
of the like-type were only prepared. All the respective sele-
nylated products were obtained as a single enantio- or dia-
stereoisomer. It is noteworthy that the direct substitution
of the hydroxy group, even if not high yielding, gave pure
phenyl selenide along with the easily separable unchanged
substrate. When the substitution of QN-tosylate with
PhSeꢁNa+ in DMF was attempted, the desired product
could not be separated from the resulting mixture.
2. Results and discussion
The unknown chiral phenyl selenides were synthesized
directly from the easily available enantiomeric alcohols
1a–h via nucleophilic substitution with phenyl selenocya-
nate and tributylphosphine.10 Analogously to the Mitsu-
nobu reaction, the hydroxy groups were activated as the
oxophosphonium salts generated from tributylphosphine
oxidized with phenyl selenocyanate. The intermediates that
formed, underwent an SN2 reaction with the phenylseleno-
ate anion generated, thus bringing about the desired con-
version of alcohols into phenyl selenides. For the
secondary alcohols, an inversion of configuration at the
stereogenic centers took place.
PhSeCN þ Bu3P ! Bu3PþSePhꢀCNꢁ
Thus, the chiral selenides obtained were applied in the Pd-
catalyzed allylic alkylation. The previously prepared corre-
sponding sulfides 2a–g previously prepared had also been
tested in this reaction model.6,7 We studied the alkylation
of dimethyl malonate with rac-1,3-diphenyl-2-propenyl
acetate, using N,O-bis(trimethylsilyl)acetamide (BSA)—
potassium acetate (3 mol %) as a base, [Pd(g3-C3H5)Cl]2
Bu3PþSePhꢀCNꢁ þ ROH ! Bu3PþOR þ HCN þ PhSeꢁ
Bu3PþOR þ PhSeꢁ ! RSePh þ Bu3P@O ðSN2Þ
Practically, we adopted the Grieco protocol,10 using tolu-
ene as the solvent instead of the originally used THF or
OCH3
OCH3
CH2Ph
N
N
N
3
9
9
∗
3 or 9
i
OH
OH
OH
SePh
N
N
(3S)-3e
9-PhSe-epi-QN 3a
DHQN 1b
QN 1a
1f
9-PhSe-epi-DHQN 3b
OCH3
OH
OH
OH
SePh
3
i
N
N
9
9
∗
N
3 or 9
N
CH2Ph
N
(3R)-3f
CN 1c
9-PhSe-epi-CN 3c
9-PhSe-epi-DHQD 3d
1e
DHQD 1d
NCH2Ph
CH2OH
NCH2Ph
i
CH2SePh
(2S)-3g
1g
NHBoc
CH2OH
NHX
N
iii
i
Cl
CH2SePh
X: Boc 3h
CH2SePh
1h
3j
ii
X: H 3i
Scheme 1. Reagents and conditions: (i) PhSeCN, Bu3P, toluene; (ii) TFAA, CH2Cl2; (iii) 2-ClC6H4CHO, CH2Cl2/MgSO4.

M. Zielin´ska-Błajet et al. / Tetrahedron: Asymmetry 18 (2007) 131–136
133
Ph
Ph
Ph
H2C(CO2Me)2, BSA (3 eq.), AcOK (3 mol%)
Ph
∗
Pd2(C3H5)2Cl2 (2.5 mol%), Ligand (10 mol%)
CH2Cl2, r.t.
OAc
MeO2C
CO2Me
Scheme 2.
(2.5 mol %) as the palladium pre-catalyst and the respective
selenide or sulfide as the chiral ligand (10 mol %). The reac-
tion was carried out in methylene chloride at 25 ꢀC for 3–
10 days (Scheme 2). In the absence of a ligand, no product
could be detected after this period of time.
for 3j. In the case of selenium pyrrolidine derivatives, the
palladium atom fits into the coordination space, thus easily
forming the complexes. Due to the stronger electron-
donating ability (softness) of selenium, the corresponding
Pd-complexes are more stable than those of sulfur ligands.
As a consequence, a higher yield of the allylic substitution
product was observed. The malonate anion attack on the
g3-allylpalladium complex intermediate is directed to the
allylic carbon, located trans to the more p-accepting sele-
nium center, resulting in a higher enantioselectivity for
N, Se-ligands.
The obtained results are presented in Table 1. The config-
uration of product obtained in the reaction was the same
for the corresponding sulfur and selenium derivatives.
As can be seen from the results, for all sterically congested
Cinchona derivatives 3a–d, the yield of the product was less
for the more sterically demanding Se-ligand than for the
respective S-ligands 2a–d. This steric crowding is supported
by the highly deshielded 77Se NMR signals observed for 3a–
d (d ca. 500 ppm) as opposed to ca. 400 ppm observed for 3e
and 3f.12 Since there was no reaction in the absence of li-
gand, we believed that the substitution of sulfur by selenium
in the Cinchona derivatives could lead to the less favorable
complexation of palladium. Nevertheless, for compounds
the softer donating selenium still increases enantioselectiv-
ity versus the corresponding sulfur ligands (cf. Table 1, en-
3. Conclusion
In conclusion, the catalytic activity and enantioselectivity
of the chiral pyrrolidine phenyl selenides in the Pd-cata-
lyzed allylic alkylation not only rivals but generally outper-
forms that of the corresponding sulfur analogues. The
practical advantages of the selenium-based catalysts in-
clude their straightforward synthesis, high activity and
enantioselectivity.
tries
1 and 2). The selenium ligands of opposite
configuration (8R,9R) demonstrated worse results and gave
a less ee than their sulfur analogues. The examination of
molecular models for the [Pd+ (8S,9S)-3a g3-1,3-diphenyl-
allyl] cation shows that the M-shaped complex is clearly fa-
vored. The nucleophilic attack at the allylic carbon, located
trans to the selenium atom in the M complex, lead to the
product of (R)-configuration (cf. Fig. 1), that is observed.
4. Experimental
4.1. General
Melting points were determined using a Boetius hot-stage
apparatus and are uncorrected. IR spectra were recorded
on a Perkin–Elmer 1600 FTIR spectrophotometer. 1H
NMR and 13C NMR spectra were measured on a Bruker
CPX (1H, 300 MHz) spectrometer using TMS as an internal
standard. 77Se NMR spectra were recorded at 115 MHz on
a Bruker AvanceTM 600 MHz spectrometer using dimethyl
selenide as an external standard. Optical rotations at
589 nm were measured using an Optical Activity Ltd. Mod-
el AA-5 automatic polarimeter. Separations of the products
by chromatography were performed on silica gel 60 (230–
400 mesh) purchased from Merck. TLC was performed
using silica gel 60 precoated plates (Merck). All procedures
with PhSeCN were carried out under dry argon.
Contrary to the results for the Cinchona-derived ligands, in
all cases of the pyrrolidine derivatives 3e–g, the exchange of
sulfur into selenium gave the catalysts of excellent yield and
clearly increased enantioselectivity. Also the selenium
derivative of valinol 3j gave a higher ee than the respective
sulfur compound. As before, the stereochemistry of the
product was the same as observed for the corresponding
sulfur ligands.6,7,11 The stereochemical outcomes are again
in agreement with the trans effect, directing the nucleophile
along the Se–Pd–C axis for 3e–g and along N–Pd–C axis
Table 1. Pd-catalyzed alkylation of dimethyl malonate with 1,3-diphenyl-2-propenyl acetate in the presence of N,Se- and N,S-donating ligandsa
Entry
Ligand 3
Yield (%)
ee (%)
Sulfur analogue 2
Yield ee (%)
Configuration of product
1
2
3
4
5
6
7
8
9-PhSe-epi-QN 3a
9-PhSe-epi-DHQN 3b
9-PhSe-epi-CN 3c
9-PhSe-epi-DHQD 3d
3R-3e
3S-3f
2S-3g
S-3j
23
17
20
16
93
90
80
80
66
60
62
48
>98
95
46
67
22
22
73
75
78
87
56
46
76
62
90
90
79
94
(+)-R
(+)-R
(ꢁ)-S
(ꢁ)-S
(+)-R
(ꢁ)-S
(+)-R
(+)-R
86
>98
a The results for the sulfur compounds were taken from Ref. 7 (2a–d), Ref. 6 (2e–g), and Ref. 11 (2j).

134
M. Zielin´ska-Błajet et al. / Tetrahedron: Asymmetry 18 (2007) 131–136
4.2. Ligand synthesis
yellow oil; [a]D = +69.1 (c 0.98, CH2Cl2). 1H NMR
(300 MHz, CDCl3): d 1.09–1.16 (m, 1H), 1.56–1.62 (m,
2H), 1.66–1.70 (m, 2H), 2.29–2.36 (m, 1H), 3.03–3.20 (m,
5H), 5.05–5.12 (m, 2H, CH2@), 5.46 (d, J = 11.2 Hz, 1H,
C9H), 5.80–5.92 (m, 1H, CH@), 6.79 (t, J = 7.5 Hz, 2H,
SePh), 6.90–6.95 (m, 1H, SePh), 7.08–7.11 (m, 2H, SePh),
7.38–7.44 (m, 2H, ArH), 7.59 (d, J = 7.6 Hz, 1H, ArH),
7.86 (d, J = 8.5 Hz, 1H, ArH), 7.95 (d, J = 8.5 Hz, 1H,
ArH), 8.75 (d, J = 4.7 Hz, 1H, ArH); 13C NMR
(75 MHz, CDCl3): d 26.5, 27.9, 28.0, 39.7, 43.4, 47.5,
49.7, 60.3, 114.7, 120.2, 122.5, 126.2, 127.9, 128.1, 128.8,
129.2, 130.1, 131.6, 136.7, 140.7, 146.3, 148.2, 149.8; 77Se
NMR (115 MHz, CDCl3): d 506.2; IR (film): 3067, 2941,
4.2.1. General procedure for the synthesis of selenium
compounds 3. To a solution of alkaloids or appropriate
pyrrolidine alcohols (1 mmol) and PhSeCN (0.219 g,
1.2 mmol) in toluene (5 mL) stirred at 0 ꢀC under an argon
atmosphere a solution of Bu3P (0.176 g, 1.2 mmol) in tolu-
ene (1 mL) was added by syringe for 10 min. The mixture
was allowed to warm to rt and it was further stirred for
2.5–3.5 h (pyrrolidine alcohols) or overnight (alkaloids).
Thereafter the mixture was diluted with Et2O (4 mL) and
washed with 5% NaOH (4 mL). The organic phase was
washed with water (2 · 4 mL) and then 1 M HCl
(3 · 4 mL). The combined acid layer was alkalinized to
pH >7 with 10% NaOH and extracted with Et2O
(3 · 4 mL). The ether solution was washed with water,
brine, dried over Na2SO4, and the solvent was evaporated.
Chromatography of the residue on silica gel using CHCl3/
t-BuOMe, 1:1 gave selenide as a yellow oil or crystals.
2875, 1592, 1508, 1455, 1111, 995, 905, 762, 634 cmꢁ1
.
Rf = 0.18 (CHCl3/t-BuOMe, 1:1). Anal. Calcd for
C25H26N2Se (M = 433.46): C, 69.27; H, 6.05; N, 6.46.
Found: C, 69.19; H, 6.12; N, 6.30.
4.2.5. (1S,3R,4S,8R,9R)-10,11-Dihydro-60-methoxy-9-phe-
nylselenylcinchonine (9-phenylselenyl-epi-dihydroquinidine,
9-PhSe-epi-DHQD) 3d. Yield 46%, yellow crystals, mp
4.2.2. (1S,3R,4S,8S,9S)-60-Methoxy-9-phenylselenylcincho-
1
nine
(9-phenylselenyl-epi-quinine,
9-PhSe-epi-QN)
147.5–149 ꢀC; [a]D = +160.4 (c 0.96, CH2Cl2). H NMR
3a. Yield 35%, yellow oil; [a]D = ꢁ46.7 (c 1.20, CH2Cl2).
1H NMR (300 MHz, CDCl3): d 0.72–0.78 (m, 1H), 1.60–
1.70 (m, 4H), 2.28–2.37 (m, 1H), 2.89–2.96 (m, 2H),
3.35–3.45 (m, 3H), 3.87 (s, 3H, OMe), 5.02–5.08 (m, 2H,
CH2@), 5.23 (d, J = 11.3 Hz, 1H, C9H), 5.80–5.92 (m,
1H, CH@), 6.82 (t, J = 7.5 Hz, 3H, SePh), 6.94–7.01 (m,
2H, SePh), 7.10 (d, J = 7.1 Hz, 2H, ArH), 7.31 (d,
J = 4.7 Hz, 1H, ArH), 7.86 (t, J = 9.2 Hz, 1H, ArH), 8.63
(d, J = 4.7 Hz, 1H, ArH); 13C NMR (75 MHz, CDCl3): d
27.9, 28.1, 28.8, 39.2, 41.1, 44.4, 55.5, 56.5, 60.1, 101.4,
114.5, 120.2, 120.9, 127.9, 128.1, 128.8, 131.6, 136.9,
141.6, 142.2, 144.4, 144.5, 147.4, 157.4; 77Se NMR
(115 MHz, CDCl3): d 506.4; IR (film): 3071, 2940, 2883,
1621, 1584, 1508, 1474, 1234, 1032, 915, 831, 740,
693 cmꢁ1. Rf = 0.19 (CHCl3/t-BuOMe, 1:1). Anal. Calcd
for C26H28N2OSe (M = 463.46): C, 67.38; H, 6.09; N,
6.04. Found: C, 67.25; H, 6.13; N, 6.00.
(300 MHz, CDCl3): d 0.88 (t, J = 7.2 Hz, 3H, Me), 1.02–
1.10 (m, 1H), 1.26–1.60 (m, 7H), 2.72–2.79 (m, 1H),
3.00–3.19 (m, 3H), 3.38–3.48 (m, 1H), 3.88 (s, 3H, OMe),
5.34 (d, J = 11.2 Hz, 1H, C9H), 6.82 (t, J = 7.5 Hz, 2H,
SePh), 6.88–7.05 (m, 3H, SePh), 7.11 (d, J = 7.0 Hz, 2H,
ArH), 7.38 (d, J = 4.7 Hz, 1H, ArH), 7.86 (t, J = 9.2 Hz,
1H, ArH), 8.63 (d, J = 4.7 Hz, 1H, ArH); 13C NMR
(75 MHz, CDCl3): d 12.0, 26.0, 26.2, 27.3, 27.8, 37.7,
43.8, 49.5, 49.9, 55.4, 60.5, 100.9, 120.4, 121.2, 127.9,
128.1, 128.9, 131.6, 136.6, 142.5, 144.4, 144.8, 147.4,
157.5; 77Se NMR (115 MHz, CDCl3): d 500.6; IR (KBr):
3058, 2933, 2868, 1619, 1586, 1505, 1472, 1219, 1029,
848, 826, 739, 694 cmꢁ1. Anal. Calcd for C26H30N2OSe
(M = 465.50): C, 67.09; H, 6.49; N, 6.02. Found: C,
66.92; H, 6,47; N, 6.01.
4.2.6. (+)-(R)-1-Benzyl-3-phenylselenylpyrrolidine 3e. Yield
1
60%, light yellow oil; [a]D = +17.6 (c 0.82, CH2Cl2). H
4.2.3. (1S,3R,4S,8S,9S)-10,11-Dihydro-60-methoxy-9-phe-
nylselenylcinchonine (9-phenylselenyl-epi-dihydroquinine, 9-
PhSe-epi-DHQN) 3b. Yield 49%, yellow oil; [a]D = ꢁ73.3
NMR (300 MHz, CDCl3): d 1.90–1.97 (m, 1H), 2.34–2.41
(m, 1H), 2.55–2.63 (m, 2H), 2.66–2.71 (m, 1H), 3.11 (dd,
J1 = 10.0 Hz, J2 = 7.2 Hz, 1H), 3.61 and 3.68 (ABq,
J = 12.9 Hz, 2H, CH2Ph), 3.74–3.80 (m, 1H), 7.23–7.32
(m, 8H, ArH), 7.49–7.53 (m, 2H, ArH); 13C NMR
(75 MHz, CDCl3): d 32.8, 38.0, 53.4, 60.1, 61.3, 127.0,
127.1, 128.3, 128.8, 129.1, 130.7, 133.4, 138.9; 77Se NMR
(115 MHz, CDCl3): d 399.8; IR (film): 3060, 3027, 2960,
2791, 1579, 1477, 1437, 1375, 1346, 1145, 1073, 1023, 736,
698 cmꢁ1. Rf = 0.46 (CHCl3/t-BuOMe, 1:1). Anal. Calcd
for C17H19NSe (M = 316.31): C, 64.55; H, 6.06; N, 4.43.
Found: C, 64.41; H, 6.00; N, 4.37.
1
(c 1.80, CH2Cl2). H NMR (300 MHz, CDCl3): d 0.87 (t,
J = 7.2 Hz, 3H, Me), 1.24–1.65 (m, 8H), 2.55–2.63 (m,
1H), 2.84–2.94 (m, 1H), 3.32–3.50 (m, 3H), 3.88 (s, 3H,
OMe), 5.25 (d, J = 11.3 Hz, 1H, C9H), 6.81 (t,
J = 7.5 Hz, 2H, SePh), 6.94–7.02 (m, 3H, SePh), 7.10 (d,
J = 7.1 Hz, 2H, ArH), 7.35 (d, J = 4.7 Hz, 1H, ArH),
7.86 (t, J = 9.2 Hz, 1H, ArH), 8.64 (d, J = 4.7 Hz, 1H,
ArH); 13C NMR (75 MHz, CDCl3): d 12.1, 25.7, 27.6,
28.6, 28.8, 37.0, 41.2, 44.5, 55.5, 58.2, 60.1, 101.4, 120.3,
120.9, 128.0, 128.1, 128.9, 131.5, 136.8, 142.3, 144.4,
144.7, 147.4, 157.4; 77Se NMR (115 MHz, CDCl3): d
506.3; IR (film): 3070, 2932, 2862, 1621, 1584, 1508,
1474, 1238, 1032, 852, 833, 740, 693 cmꢁ1. Rf = 0.32
(CHCl3/t-BuOMe, 1:1). Anal. Calcd for C26H30N2OSe
(M = 465.50): C, 67.09; H, 6.49; N, 6.02. Found: C,
66.98; H, 6.38; N, 5.96.
4.2.7. (ꢁ)-(S)-1-Benzyl-3-phenylselenylpyrrolidine 3f. Yield
1
63%, yellow oil; [a]D = ꢁ16.9 (c 0.94, CH2Cl2). H NMR
(300 MHz, CDCl3): d 1.87–1.96 (m, 1H), 2.33–2.40 (m,
1H), 2.53–2.61 (m, 2H), 2.64–2.70 (m, 1H), 3.09 (dd,
J1 = 10.0 Hz, J2 = 7.2 Hz, 1H), 3.59 and 3.67 (ABq,
J = 12.9 Hz, 2H, CH2Ph), 3.71–3.79 (m, 1H), 7.22–7.30
(m, 8H, ArH), 7.46–7.52 (m, 2H, ArH). Rf = 0.46 (CHCl3/
t-BuOMe, 1:1).
4.2.4. (1S,3R,4S,8R,9R)-9-Phenylselenylcinchonine (9-phe-
nylselenyl-epi-cinchonine, 9-PhSe-epi-CN) 3c. Yield 31%,

M. Zielin´ska-Błajet et al. / Tetrahedron: Asymmetry 18 (2007) 131–136
135
4.2.8. (ꢁ)-(S)-1-Benzyl-2-(phenylselenylmethyl)pyrrolidine
3g. Yield 73%, light yellow oil; [a]D =ꢁ70.2 (c 0.94,
(CDCl3): d 18.7, 19.8, 32.6, 33.4, 76.9, 126.7, 126.9,
128.8, 129.0, 129.7, 130.6, 131.4, 132.6, 133.3, 135.1,
157.7; 77Se NMR (115 MHz, CDCl3): d 274.0; IR (film):
3067, 2960, 2874, 1636, 1579, 1473, 1439, 1383, 1052,
1
CH2Cl2). H NMR (300 MHz, CDCl3): d 1.67–1.83 (m,
3H), 1.97–2.20 (m, 2H), 2.36–2.42 (m, 1H), 2.76–2.86 (m,
1H), 2.91–3.04 (m, 1H), 3.10–3.12 (m, 1H), 3.28 and 4.02
(ABq, J = 12.9 Hz, 1H, CH2Ph), 3.47 and 3.90 (ABq,
J = 13.1 Hz, 1H, CH2Ph), 7.18–7.35 (m, 8H, ArH), 7.44–
7.50 (m, 2H, ArH); 13C NMR (75 MHz, CDCl3): d 22.5,
23.5, 31.0, 54.5, 58.7, 63.2, 126.5, 127.2, 128.2, 128.4,
128.7, 128.9, 134.4, 139.1; 77Se NMR (115 MHz, CDCl3):
d 255.5; IR (film): 3061, 3027, 2966, 2796, 1579, 1495,
1454, 1355, 1124, 1073, 1028, 738, 699 cmꢁ1. Rf = 0.62
(CHCl3/t-BuOMe, 1:1). Anal. Calcd for C18H21NSe
(M = 330.34): C, 65.45; H, 6.41; N, 4.24. Found: C,
65.23; H, 6.23; N, 4.30.
736, 693 cmꢁ1
.
Anal. Calcd for C18H20NClSe
(M = 364.78): C, 59.27; H, 5.53; N, 3.84. Found: C,
59.50; H, 5.38; N, 3.84.
4.3. Catalytic reaction procedure
A solution of the allylpalladium chloride dimer (4 mg,
0.01 mmol) and ligand (0.04 mmol) in dry dichloromethane
(1.0 mL) was stirred under argon atmosphere at room tem-
perature for 15 min before a solution of the corresponding
substrate (0.4 mmol) in dichloromethane (1.5 mL) was
added. The resulting yellow solution was treated succes-
sively with dimethyl malonate (1.2 mmol, 0.159 g,
0.137 mL), N,O-bis(trimethylsilyl)acetamide (1.2 mmol,
0.244 g, 0.296 mL), and anhydrous potassium acetate
(1.2 mg, 0.012 mmol). The reaction was carried out at
room temperature for 3–8 days until conversion was com-
plete according to TLC analysis. The reaction mixture
was diluted with ether (10 mL) and quenched with satd
NH4Cl. The organic layer was washed with brine and dried
over MgSO4. The product was purified by column chroma-
tography (hexane/ethyl acetate, 5:1). The enantiomeric ex-
4.2.9. (S)-N-20-Chlorobenzylidene-2-amino-3-methyl-1-phen-
ylselenylbutane 3j. Schiff base 3j was prepared from
aminoselenide 3i, obtained from N-protected by Boc group
selenium compound 3h.
Selenium compound 3h was prepared from N-Boc-L-vali-
nol (1 mmol) similarly as described above. Yield 40%, oil,
Rf = 0.49 (t-BuOMe/CHCl3/hexane, 2.5:2.0:14.0). 1H
NMR (300 MHz, CDCl3): d 0.99 (dd, J1 = 6.8 and J2=
3.1 Hz, 6H), 1.42 (s, 9H), 1.80–1.91 (m, 1H), 3.07
(d, J = 4.9 Hz, 2H), 3.62–3.67 (m, 1H), 4.56 (d, J =
7.2 Hz, 1H), 7.22–7.27 (m, 3H, ArH), 7.50–7.56 (m, 2H,
ArH).
1
cess was determined by H NMR using the chiral shift
reagent Eu(hfc)3 (0.5 equiv). Observed Dd = 11 Hz down-
field for the dextrorotatory (R)-enantiomer. The assign-
ment of the absolute configuration was based on the
specific rotation according to the literature data.
4.2.9.1. Removing the Boc-group. The N-protected sele-
nium compound 3h (0.4 mmol) was added to an equimolar
mixture of CF3COOH (40 mmol, 3.06 mL) and CH2Cl2
(40 mmol, 2.66 mL). The solution was stirred at room tem-
perature for 1.5 h. The reaction was monitored by TLC.
The solvent was evaporated and 3 M NaOH (5 mL) then
added to the residue. The solution was extracted with chlo-
roform (4 · 5 mL). The organic layers were collected,
washed with brine, and dried over Na2SO4 to afford
98 mg of pure 3i as a crystallizing oil (95% yield).
Rf = 0.13 (t-BuOMe/CHCl3, 5:4), [a]D = +70.9 (c 1.98,
CHCl3). 1H NMR (CDCl3): d 0.92 (dd, J1 = 6.8 and
J2 = 3.2 Hz, 6H), 1.39 (br s, 2H), 1.65–1.76 (m, 1H),
2.67–2.73 (m, 1H), 2.79 (dd, J1 = 11.6 and J2 = 9.3 Hz,
1H), 3.15 (dd, J1 = 11.6 and J2 = 3.1 Hz, 1H), 7.22–7.26
(m, 3H), 7.49–7.53 (m, 2H). 13C NMR (CDCl3): d 17.7,
19.3, 33.6, 35.3, 56.3, 126.9, 129.1, 130.3, 132.7; IR (film):
3366, 3071, 3057, 2958, 2929, 2871, 1579, 1478, 1437,
Acknowledgment
We are grateful to the Ministry of Science and Higher Edu-
cation for financial support (Grant PBZ-KBN-126/T09/
2004).
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