Development of the first menthane-based chiral bis(π-allylpalladium) catalysis: Asymmetric allylation of imines

Article abstract of DOI:10.1002/ejoc.201101588

A new ethylidene menthane-based chiral π-allylpalladium complex catalyzes the asymmetric allylation of various imines with allyltributylstannane and 1 equiv. of water to give chiral homoallylamines in good yields and enantioselectivities. The reaction was carried out essentially under neutral conditions and displayed a good transfer of chiral information from the menthane skeleton through the formation of a bis(π-allylpalladium) species. This is the first example of menthane-based chiral bis(π-allylpalladium) catalysis. A menthane-based chiral π-allylpalladium-catalyzed asymmetric allylation of various imines has been developed giving chiral homoallylamines in good yields and enantioselectivities. The reaction displays a good transfer of chiral information from the menthane skeleton through the formation of a bis(π-allylpalladium) complex. Copyright

Full text of DOI:10.1002/ejoc.201101588

FULL PAPER
DOI: 10.1002/ejoc.201101588
Development of the First Menthane-Based Chiral Bis(π-allylpalladium)
Catalysis: Asymmetric Allylation of Imines
Rodney A. Fernandes*[a] and Dipali A. Chaudhari[a]
Dedicated to Professor Yoshinori Yamamoto on the occasion of his 70th birthday
Keywords: Asymmetric catalysis / Homogeneous catalysis / C-C coupling / Allylation / Palladium / Enantioselectivity
A new ethylidene menthane-based chiral π-allylpalladium
complex catalyzes the asymmetric allylation of various
imines with allyltributylstannane and 1 equiv. of water to
give chiral homoallylamines in good yields and enantio-
selectivities. The reaction was carried out essentially under
neutral conditions and displayed a good transfer of chiral in-
formation from the menthane skeleton through the formation
of a bis(π-allylpalladium) species. This is the first example of
menthane-based chiral bis(π-allylpalladium) catalysis.
allylpalladium-catalyzed asymmetric allylation of imines
occurred with an enantioselectivity of up to 82%.[12] The
reaction was further improved by meticulously preparing
the exo-ethylidene-based π–allylpalladium chloride in high
regioisomeric purity (Z/E, 400:1) and by using water
(1 equiv.) to affect the asymmetric allylation which occurred
in good reproducible yields and enantioselectivity (28 exam-
ples, up to 94% yield and up to 91%ee).[14a] The use of
allylsilanes, instead of stannanes, was also explored in the
presence of TBAF (tetra-n-butylammonium fluoride) and
MeOH. The former helped to activate the C–Si bond cleav-
age, and the latter promoted the facile protonation of the
intermediate palladium amide.[13,14b]
The asymmetric allylation of imines or hydrazones repre-
sents an important C–C bond forming reaction in organic
synthesis.[15–18] Although several catalytic asymmetric
methods have been developed, work in this area goes un-
abated. Yamamoto’s catalyst based on the exo-ethylidene
(–)-β-pinene required extensive purification using column
chromatography followed by repeated recrystallizations to
achieve a regiosiomeric purity of 400:1 and resulted in a
low overall yield for the preparation of the catalyst.[14a]
Noting this difficulty and that a limited number of chiral
skeletons were examined, we embarked on investigating the
framework of menthane-based chiral π-allylpalladium
chloride. The menthane framework has been extensively
used as a chiral auxiliary.[19] However, until now, a chiral π-
allyl palladium chloride complex based on the menthane
structure has not been studied as a catalyst. We believe that
the stereochemical information from the menthane frame-
work, previously used as a chiral auxiliary in synthetic
transformations, could be translated through the formation
of chiral bis(π-allylpalladium) species. In addition, the men-
Introduction
A π-allylpalladium complex was first prepared by the ad-
dition of palladium chloride to butadiene, although the
structure was not originally known as a π-allyl complex.[1]
Various π-allylpalladium complexes have been reported
from a wide range of olefins with different substitution pat-
terns.[2] These complexes are electrophilic and widely used
in reactions with a variety of nucleophiles. Although this
chemistry is well explored (e.g., allylic alkylation and the
oxidation of alkenes and conjugated dienes),[3–8] the umpo-
lung of the π-allyl palladium complex is a new arena in
organometallic chemistry with new applications in the area
of catalysis. The key intermediate in such reactions is the
bis(π-allylpalladium) species which has nucleophilic charac-
ter. It has been demonstrated that under catalytic condi-
tions, the bis(π-allylpalladium) complex can undergo an ini-
tial electrophilic attack on one of the allyl moieties followed
by a nucleophilic attack on the other, thereby, displaying
amphiphilic character.[9] The evidence for the in situ forma-
tion of the bis(π-allylpalladium) species is well documen-
ted,[10] and the mechanism and regioselectivity of the elec-
trophilic attack of the bis(π-allylpalladium) complex has
also been studied.[11] Various synthetic applications of the
bis(π-allylpalladium) species including the first catalytic
asymmetric allyation of imines were explored by Yamamo-
to’s group.[12–14] The exo-ethylidene (–)-β-pinene-based π-
[a] Department of Chemistry, Indian Institute of Technology
Bombay,
Powai, Mumbai 400076, Maharashtra, India
Fax: +91-22-25767152
E-mail: rfernand@chem.iitb.ac.in
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201101588.
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R. A. Fernandes, D. A. Chaudhari
FULL PAPER
thane skeleton (as menthol) is available in both enantio- eric π-allylpalladium chloride complexes. For example, a
meric forms to enable synthesis of either enantiomeric cata- clear distinction of peaks was observed in the 1H NMR
lyst.
spectrum of 4b containing 5b. Only one allyl proton for 4b
was observed as a quartet, and as expected for 5b, minor
peaks were observed as a singlet for Hd and a quartet for
Hc (Scheme 1). Similarly, this was the case for other com-
plexes (R ϶ H, 4c–e) with the only allyl proton assigned as
a triplet. The major complexes 4b–f were purified by flash
column chromatography, however, pure forms of complexes
5b–f were not obtained by column chromatography, and al-
ways contained 4b–f as well. The mixture of complexes 4a/
5a obtained in 3:2 ratio were not separated by flash column
chromatography or by recrystallization. Hence, complexes
4a/5a were used as a mixture. Complexes 4/5 were observed
to be stereochemically stable unlike earlier reports of E to
Z conversion.[14d]
Results and Discussion
We prepared several olefins from (+)-menthone 2 [pre-
pared from (+)-menthol 1] as shown in Scheme 1.[20] Olefins
3a–f were prepared in yields of 51–72% by a conventional
Wittig olefination using alkyltriphenylphosphonium halide
and either nBuLi or tBuOK as the base. Gratifyingly, the
olefins were isolated as single diastereomers (E isomers),
indicated by the presence of a single peak in the olefin re-
gion of the 1H NMR spectra. The E geometry was assigned
using the 1H-1H COSY correlations between Hb and Hc
and also the H-1H NOESY correlations between Ha and
1
Our initial investigation commenced with screening the
mixture of complexes 4a/5a and 4b–f in the asymmetric
allylation of model imine 6a. The results are shown in
Table 1. We employed similar conditions as in the litera-
ture[14a] using water (1 equiv.) and allyltributylstannane
(1.25 equiv.) in the THF solvent. The mixture of inseparable
complexes 4a/5a catalyzed the reaction giving homoallyl-
amine 8a in good yields and enantioselectivity (Table 1, En-
try 1, 68%ee). A better yield and enantioselectivity was ob-
tained by changing to the exo-ethylidene group in 4b pro-
viding 8a in 68% yield and 78%ee (Table 1, Entry 2). In-
creasing the alkyl chain length further from the ethylidene
to the butylidene group (Table 1, Entries 2–4, complexes
4b–4d,) resulted in lower enantioselectivities. Branching on
the alkyl chain (Table 1, Entries 5 and 6, complexes 4e and
f) did not have any positive influence on the enantio-
selectivity. Thus, the optimum chain length was with the
ethylidene group in 4b as shown in Entry 2. In addition, we
investigated the catalyst loading with 1 and 2 mol-% of 4b,
which resulted in a decrease in both the yields and enantio-
Hc in 3b (Scheme 1). The reaction of these olefins with
Pd(OCOCF3)2 and nBu4NCl in acetone furnished in each
case the π-allylpalladium chloride complexes 4a–f along
with the minor regioisomeric complexes 5a–f (1H NMR
shows 4b–f/5b–f, 3.5–4.5:1 and 4a/5a, 3:2). H NMR spec-
troscopy was used to characterize the mixture of regioisom-
1
Table 1. Asymmetric allylation of imine 6a with 7 and 4a/5a mix-
ture or 4b–f.[a]
Entry
π-Allylpalladium chloride
% Yield
% ee[b]
8a
complex [mol-%]
8a
1
2
3
4
5
6
7
8
9
10
4a/5a (5)
4b (5)
4c (5)
4d (5)
4e (5)
4f (5)
4b (1)
4b (2)
4b (10)
4b (20)
62
68
66
45
60
38
52
56
65
71
68
78
52
48
46
48
68
68
72
74
Scheme 1. Synthesis of menthane-based chiral π-allylpalladium
complexes. Reagents and conditions: (a) PCC (pyridinium chloro-
chromate), MS (molecular sieves, 4 Å), CH2Cl2, 0 °C to room
temp., 4 h, 94%; (b) Ph3P+CH2RX– (X = Br, I), THF (tetra-
hydrofuran), nBuLi, 0 °C, 30 min, 80 °C, 48 h or tBuOK, room
temp., 30 min, 80 °C, 48 h, 51–72%; (c) Pd(OCOCF3)2, acetone,
room temp., 1 h then nBu4NCl, room temp., 1 h, 55–78%.
[a] Allyltributylstannane (1.25 equiv.). [b] ee determined by HPLC.
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Asymmetric Allylation of Imines
selectivities (Table 1, Entries 7 and 8). An increase in the yields (71%), but a lower ee of 74% (Table 1, Entry 10).
catalyst loading to 10 or 20 mol-% gave comparable results Thus, 5 mol-% of catalyst was the optimum requirement for
(Table 1, Entries 9 and 10). The latter case resulted in better the reaction.
Table 2. Catalytic asymmetric allylation of imines with allyltributylstannane using catalyst 4b.[a]
[a] Allyltributylstannane (1.25 equiv.), H2O (1 equiv.), catalyst 4b (5 mol-%), 0 °C. [b] ee determined by HPLC.
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1947

R. A. Fernandes, D. A. Chaudhari
FULL PAPER
We then focused on investigating the scope of complex through a six-membered chair-like transition state to the si
4b in the asymmetric allylation of various imines using allyl- face of the imine. This explains the formation of the (S)-
tributylstannane and 1 equiv. of water at 0 °C. The results homoallylamines. In transition-state model 10 which gives
are presented in Table 2. Benzaldehyde imine 6b delivered the (R)-homoallylamines, the imine RЈ group encounters
homoallylamine 8b in good yield (70%) and an enantio- steric repulsion from bulky isopropyl group of the complex,
selectivity of 70%ee (Table 2, Entry 1). Imines with elec- and therefore the structure is less favored. A smaller sized
tron-donating groups in the para position resulted in a R group, such as R = Me (as in 4b), is required for complex-
slight increase in enantioselectivity, for example, 6c and d ation to occur from front α side and not from the rear side.
gave homoallylamines 8c and d in 76 and 72%ee, respec- A further increase in the chain length or branching in the
tively (Table 2, Entries 2 and 3). However, the ortho-meth- alkyl R group has no influence. For Yamamoto’s cata-
oxy group in 6e yielded 8e with a remarkably lower enantio- lyst,[12,14] the complexation of imine occurs from backside
selectivity (42%ee, Table 2, Entry 4). Similarly, having the of the ethylidene pinene catalyst, and in our case, it occurs
electron-withdrawing NO2 group in the para position of the from front α side which explains the formation of the oppo-
imine also resulted in a lower enantioselectivity (6f gave 8f, site enantiomer of homoallylamines.
22%ee, Table 2, Entry 5). 4-Chlorobenzaldehyde imine 6g
reacted well giving homoallylamine 8g in good yield (68%,
Table 2, Entry 6) and a moderate enantioselectivity of
56%ee. α-Naphthaldehyde imine 6h gave homoallylamine
8h in 72% yield and a moderate 62%ee (Table 2, Entry 7).
Heterocyclic imines 6i–k reacted well to produce the corre-
sponding homoallylamines 8i–k in good yields of 67, 61,
and 41% and enantioselectivities of 36, 48, and 52%ee,
respectively (Table 2, Entries 8–10). The pyridine-based im-
ine 6k was sluggish in the reaction and required a longer
reaction time (Table 2, Entry 10). Piperonyl imine 6a with
the benzyl group furnished 8a in good yields and the best
ee of 78% (Table 2, Entry 11). However, substituting a p-
methoxybenzyl group for the benzyl group as in 6l resulted
Scheme 2. Transition-state models.
in 8l with a slight decrease in enantioselectivity, 64%ee
(Table 2, Entry 12). Homoallylamine 8a is a precursor for
α-propylpiperonylamine which is an important building
block of the human leukocyte elastase inhibitor L-
Conclusions
694,458.[21] The p-methoxybenzyl group containing imines
6m–o reacted well with good yields of 80, 79, and 78% and
moderate enantioselectivities of 68, 60, and 56%ee, respec-
tively (Table 2, Entries 13–15). Benzaldehyde imine 6p with
the N-allyl group furnished homoallylamine 8p in 72%
yield and a moderate 64%ee (Table 2, Entry 16). Nonaryl
imines like cyclohexylimine 6q and n-heptylimine 6r pro-
duced homoallylamines 8q and 8r in moderate yields and
enantioselectivities of 36 and 30%ee, respectively (Table 2,
Entries 17 and 18).
In summary, we have developed for the first time a
menthane-based chiral π-allylpalladium catalyst which cata-
lyzed the asymmetric allylation of various imines to give
chiral homoallylamines in good yields and enantioselectivi-
ties. The homoallylamines have the opposite configuration
to that obtained in previous reports.[14a] The reaction was
carried out essentially under neutral conditions and dis-
played a good transfer of chiral information from the men-
thane skeleton through formation of a bis(π-allylpalladium)
complex.
The reaction is expected to follow a similar mechanistic
pathway as reported in the literature.[14a] The bis(π-allylpal-
ladium) complex is initially formed. It is this key intermedi-
ate that is nucleophilic and transfers the allyl group to the
imine, directed by the chiral menthane skeleton and re-
Experimental Section
General Remarks: The solvents were dried by standard procedures.
Thin layer chromatography was performed on EM 250 Kieselgel
sulting in the observed chiral induction. The transfer of the 60 F254 silica gel plates. The spots were visualized by staining with
1
KMnO4 or by using a UV lamp. H and 13C NMR spectroscopic
bulky menthane allyl moiety was not observed, which is a
data were recorded with a Bruker AvanceIII 400 spectrometer, and
remarkable feature. The opposite sign of optical rotation
the chemical shifts are based on the TMS peak at δ = 0.00 pm for
for the homoallylamines were obtained using Yamamoto’s
the 1H NMR and the CDCl3 peak at δ = 77.00 ppm (t) for the
(–)-ethylidene pinene π-allylpalladium complex, whereas,
13C NMR spectra. IR spectra were recorded with a Perkin–Elmer
the homoallylamines in our work have the (S) configura-
tion. The probable transition state models are shown in
Scheme 2. The backside of palladium complex 9 is occupied
Spectrum One FTIR spectrometer. Optical rotations were mea-
sured with a Jasco P-2000 polarimeter. The HRMS data were re-
corded with a Micromass: Q-Tof micro (YA-105) spectrometer.
by an alkyl group, and thus, the imine is forced to approach
HPLC was performed with a JASCO-(PU-2089PLUS) quaternary
gradient pump equipped with a MD-2010PLUS mutiwavelength
from front α side. In η3,η1-π-allylpalladium complex 9, the
smaller allyl group is transferred to the coordinated imine detector. Imines were prepared as previously reported.[22] Though
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Asymmetric Allylation of Imines
solids, we did not determine melting points of the π-allylpalladium
chloride complexes, as they decomposed upon slight heating.
2957, 2930, 2871, 1662, 1456, 1382, 1366, 1065, 923, 885, 867, 818,
1
764 cm–1. H NMR (400 MHz, CDCl3): δ = 0.85 (d, J = 6.6 Hz, 3
H), 0.87 (d, J = 6.6 Hz, 3 H), 0.89 (d, J = 6.6 Hz, 3 H), 0.91 (t, J
= 7.4 Hz, 3 H), 1.09–1.15 (m, 1 H), 1.23–1.40 (m, 3 H), 1.53–1.61
(m, 1 H), 1.62–1.81 (m, 4 H), 1.88–2.03 (m, 3 H), 2.29–2.34 (m, 1
H), 5.09 (t, J = 7.4 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 13.9, 19.8, 20.6, 22.1, 23.4, 26.4, 26.8, 29.3, 31.9, 32.3, 35.0,
51.2, 121.7, 139.8 ppm. LRMS (ESI): calcd. for C14H27 [M + H]+
195.2; found 195.1.
(1R,4S)-1-Isopropyl-4-methyl-2-methylenecyclohexane (3a):[23] To a
stirred solution of Ph3P+CH3I– (2.37 g, 5.83 mmol) in THF
(15 mL) at 0 °C under an argon atmosphere was added nBuLi
(1.6 m in hexane, 5.5 mL, 8.75 mmol, 1.5 equiv.), and the mixture
was stirred for 30 min. A solution of (+)-2[20] (0.6 g, 3.89 mmol) in
THF (5 mL) was added, and the mixture was stirred for 48 h at
80 °C. It was then cooled to room temp. and quenched with a satu-
rated aqueous solution of NH4Cl (1 mL), and the resulting mixture
was extracted with EtOAc (2ϫ50 mL). The combined organic lay-
ers were washed with brine, dried with Na2SO4, and concentrated.
Silica gel column chromatography of the crude product using pe-
troleum ether as the eluent gave 3a (0.37 g, 62%) as a colorless oil.
(1R,4S,E)-1-Isopropyl-4-methyl-2-(3-methylbutylidene)cyclohexane
(3e): The title compound was prepared from (+)-2 (0.6 g,
3.89 mmol) and Ph3P+CH2CH2CH(CH3)2 Br– (3.21 g, 7.78 mmol,
2.0 equiv.) by a similar procedure to that described for 3b to give
3e (0.526 g, 65%) as a colorless oil. [α]2D5 = +42.2 (c = 0.34, CHCl3).
[α]2D5 = +40.5 (c = 0.12, CHCl ). IR (CHCl ): ν = 3084, 2954, 2928,
˜
3
3
IR (neat): ν = 2955, 2928, 2870, 1661, 1464, 1382, 1366, 1258, 1166,
˜
1645, 1457, 1385, 1163, 891, 861 cm–1. 1H NMR (400 MHz,
CDCl3): δ = 0.88 (d, J = 6.7 Hz, 3 H), 0.90 (d, J = 6.5 Hz, 3 H),
0.92 (d, J = 6.7 Hz, 3 H), 1.04–1.25 (m, 3 H), 1.55–1.81 (m, 4 H),
1.92–1.98 (m, 1 H), 2.27 (dd, J = 12.6, 4.0 Hz, 1 H), 4.58 (s, 1 H),
4.69 (s, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 19.0, 21.4,
22.1, 27.1, 27.4, 33.4, 34.0, 44.4, 49.4, 106.1, 151.2 ppm. LRMS
(ESI): calcd. for C11H21 [M + H]+ 153.1; found 153.1.
1086, 1063, 867, 774 cm–1. 1H NMR (400 MHz, CDCl3): δ = 0.84–
0.95 (m, 15 H), 1.0–1.18 (m, 1 H), 1.23–1.32 (m, 1 H), 1.51–1.84
(m, 6 H), 1.85–1.98 (m, 3 H), 2.27–2.35 (m, 1 H), 5.10 (t, J =
7.2 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 19.9, 20.8,
22.3, 22.6, 22.8, 26.7, 27.1, 29.4, 32.2, 32.6, 35.4, 36.6, 51.5, 120.9,
140.4 ppm. LRMS (ESI): calcd. for C15H29 [M + H]+ 209.2; found
209.2.
(1R,4S,E)-2-Ethylidene-1-isopropyl-4-methylcyclohexane (3b): To a
stirred solution of Ph3P+CH2CH3 Br– (2.41 g, 6.48 mmol,
2.0 equiv.) in THF (20 mL) at room temp. under an argon atmo-
sphere was added tBuOK (0.547 g, 4.86 mmol, 1.5 equiv.), and the
mixture was stirred for 30 min. A solution of (+)-2 (0.5 g,
3.24 mmol) in THF (5 mL) was added, and the mixture was stirred
for 48 h at 80 °C. It was then quenched with a saturated aqueous
solution of NH4Cl (1 mL), and the resulting mixture was extracted
with EtOAc (2ϫ50 mL). The combined organic layers were washed
with brine, dried with Na2SO4, and concentrated. Silica gel column
chromatography of the crude product using petroleum ether as the
eluent gave 3b (0.355 g, 66%) as a colorless oil. [α]2D5 = +55.9 (c =
(1R,4S,E)-1-Isopropyl-4-methyl-2-(2-methylpropylidene)cyclohexane
(3f): The title compound was prepared from (+)-2 (0.6 g,
3.89 mmol) and Ph3P+CH2CH(CH3)2 Br– (3.21 g, 7.78 mmol,
2.0 equiv.) by a similar procedure to that described for 3a to give
3f (0.385 g, 51%) as a colorless oil. [α]2D5 = +8.6 (c = 0.36, CHCl3).
IR (neat): ν = 3021, 2957, 2929, 2871, 1639, 1456, 1378, 1019, 901,
˜
1
761 cm–1. H NMR (400 MHz, CDCl3): δ = 0.85–0.94 (m, 15 H),
1.05–1.18 (m, 1 H), 1.22–1.41 (m, 3 H), 1.60–1.81 (m, 3 H), 1.89–
2.08 (m, 2 H), 2.28–2.36 (m, 1 H), 5.10 (t, J = 7.2 Hz, 1 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 19.7, 20.6, 22.1, 23.4, 26.4, 26.8,
29.3, 29.7, 31.9, 32.3, 35.0, 51.2, 121.7, 139.8 ppm. LRMS (ESI):
calcd. for C14H27 [M + H]+ 195.2; found 195.1.
0.32, CHCl ). IR (neat): ν = 3033, 2954, 2927, 1666, 1455, 1382,
˜
3
1367, 1093, 1062, 862, 829, 805 cm–1. 1H NMR (400 MHz, CDCl3):
δ = 0.84 (d, J = 6.7 Hz, 3 H), 0.88 (d, J = 6.5 Hz, 3 H), 0.91 (d, J
= 6.4 Hz, 3 H), 1.07–1.17 (m, 1 H), 1.24–1.32 (m, 1 H), 1.58 (d, J
= 6.7 Hz, 3 H), 1.54–1.61 (m, 1 H), 1.62–1.82 (m, 4 H), 1.86–1.96
(m, 1 H), 2.29–2.35 (m, 1 H), 5.17 (q, J = 6.9 Hz, 1 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 12.7, 19.7, 20.5, 22.1, 26.4, 26.8,
32.0, 32.2, 34.6, 51.2, 115.1, 140.6 ppm. LRMS (ESI): calcd. for
C12H23 [M + H]+ 167.1; found 167.09.
General Procedure for the Preparation of π-Allylpalladium Chloride
Complexes 4a–f: To a solution of Pd(OCOCF3)2 (0.2 g, 0.6 mmol,
1.0 equiv.) in dry acetone (10 mL) at room temp. and under an
argon atmosphere was added olefin 3 (0.722 mmol, 1.2 equiv.). The
mixture was stirred for 1 h (TLC monitored). nBu4NCl (0.183 g,
0.66 mmol, 1.1 equiv.) in acetone (2 mL) was added, and the reac-
tion mixture was stirred for 1 h. The clear brown solution was then
filtered through a plug of Celite to remove the suspended Pd-black.
The filtrate was concentrated, and the residue was purified by silica
gel column chromatography using petroleum ether/EtOAc (5:1) as
(1R,4S,E)-1-Isopropyl-4-methyl-2-propylidenecyclohexane (3c): The
title compound was prepared from (+)-2 (0.6 g, 3.89 mmol) and
Ph3P+CH2CH2CH3 Br– (3.0 g, 7.78 mmol, 2.0 equiv.) by a similar
procedure to that described for 3b to give 3c (0.505 g, 72%) as a
1
the eluent to give a mixture of complexes 4 and 5 (analyzed by H
NMR) as a yellow semisolid. Complex 4 was separated from 5 by
flash column chromatography using petroleum ether as the eluent
to give pure complex 4 as a yellow solid. [Yields are based on Pd-
(OCOCF3)2 and are given below for the 4/5 mixture and isolated
major complex 4]. In the case of 4a/5a, the mixture could not be
separated.
colorless oil. [α]2D5 = +33.7 (c = 1.14, CHCl ). IR (neat): ν = 2955,
˜
3
2929, 2870, 1661, 1455, 1378, 1265, 1164, 1063, 895, 877, 762 cm–1.
1H NMR (400 MHz, CDCl3): δ = 0.84 (d, J = 6.7 Hz, 3 H), 0.87
(d, J = 6.6 Hz, 3 H), 0.90 (d, J = 6.6 Hz, 3 H), 0.94 (t, J = 7.5 Hz,
3 H), 1.08–1.16 (m, 1 H), 1.24–1.33 (m, 1 H), 1.54–1.60 (m, 1 H),
1.63–1.83 (m, 4 H), 1.87–1.96 (m, 1 H), 1.97–2.08 (m, 2 H), 2.28–
2.35 (m, 1 H), 5.07 (t, J = 7.2 Hz, 1 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 14.9, 19.8, 20.5 (2 C), 22.1, 26.4, 26.7, 31.8, 32.3, 34.8,
51.2, 123.6, 139.0 ppm. LRMS (ESI): calcd. for C13H25 [M + H]+
181.2; found 181.2.
π-Allylpalladium Chloride Complexes 4a/5a: Obtained as a 3:2 in-
separable mixture of 4a/5a (97.0 mg, 55%). Rf = 0.29 (petroleum
ether). IR (CHCl ): ν = 2958, 2928, 2871, 1652, 1455, 1363, 1261,
˜
3
1040, 930, 805, 755 cm–1. H NMR (400 MHz, CDCl3): δ = 0.75–
1
1.05 (m, 12 H), 1.2 (d, J = 6.8 Hz, 3 H), 1.2–1.41 (m, 7 H), 1.42–
1.55 (m, 2 H), 1.56–1.65 (m, 2 H), 1.7–1.85 (m, 2 H), 1.86–2.05 (m,
2 H), 2.25–2.51 (m, 1 H), 2.52–2.65 (m, 1 H), 2.72–2.82 (m, 1 H),
3.0 (s, 1 H), 3.14 (s, 1 H), 3.52 (s, 1 H), 3.66 (s, 1 H), 4.12 (s,
1 H) ppm. HRMS (ESI-TOF) calcd. for C22H38Pd2Cl [M – Cl]+
549.0728; found 549.0733.
(1R,4S,E)-2-Butylidene-1-isopropyl-4-methylcyclohexane (3d): The
title compound was prepared from (+)-2 (0.6 g, 3.89 mmol) and
Ph3P+CH2CH2CH2CH3 Br– (3.11 g, 7.78 mmol, 2.0 equiv.) by a
similar procedure to that described for 3b to give 3d (0.491 g, 65%)
as a colorless oil. [α]2D5 = +42.7 (c = 0.86, CHCl ). IR (neat): ν =
˜
3
Eur. J. Org. Chem. 2012, 1945–1952
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1949

R. A. Fernandes, D. A. Chaudhari
FULL PAPER
π-Allylpalladium Chloride Complex 4b: Obtained as a 3.5:1 mixture
24.1, 27.4, 29.1, 29.9, 31.2, 32.4, 36.0, 74.6, 100.5, 117.0 ppm.
of 4b/5b (143.9 mg, 78%). Pure complex 4b (83.3 mg, 45%) was HRMS (ESI-TOF) calcd. for C28H50Pd2Cl [M – Cl]+ 633.1671;
isolated as a yellow powder. Rf = 0.28 (petroleum ether). [α]2D5
+15.7 (c = 0.1, CHCl ). IR (CHCl ): ν = 2959, 2927, 2871, 1660,
=
found 633.1681.
˜
3
3
General Procedure for Asymmetric Allylation of Imines Using Cata-
lyst 4b: The imine (0.5 mmol) was placed in a Wheaton microreac-
tor (5 mL capacity), and under an argon atmosphere, dry THF
(1.25 mL), degassed water (9 μL, 0.5 mmol, 1 equiv.), and allyltri-
butylstannane (194 μL, 0.625 mmol, 1.25 equiv.) were added se-
quentially. The mixture was cooled to 0 °C, and the chiral palla-
dium chloride complex 4b (14.56 mg, 0.025 mmol, 5 mol-%) was
added under argon. The reaction mixture was flushed with argon
and stirred at 0 °C for the specified time. The reaction progress was
monitored by TLC. After completion, the turbid reaction mixture
was quenched with HCl (1 n solution, 2.5 mL). CH3CN (1 mL) was
added, and the reaction mixture was stirred at room temperature
for 10 min. The two-layered solution was extracted with hexane
(2ϫ3 mL), and the hexane layer was discarded. The aqueous layer
was basified with NaOH (10% aqueous solution, 1.25 mL), and
the resulting solution was stirred for 5 min. The solution was ex-
tracted with EtOAc (2ϫ5 mL), dried with Na2SO4, and concen-
trated. Purification by silica gel column chromatography (hexane/
EtOAc, 5:1) gave the corresponding homoallylamine 8 as a color-
less oil. Characterization data (1H NMR is only included) for the
known homoallylamines were identical to literature data.[14a] The
enantiomeric excesses were determined by HPLC of the trifluoro-
acetylamide forms of all of the homoallylamines with UV detection
at 254 nm.
1
1456, 1424, 1375, 1318, 1257, 1230, 1085, 1032, 986, 666 cm–1. H
NMR (400 MHz, CDCl3): δ = 0.89 (d, J = 6.8 Hz, 3 H), 1.02 (d,
J = 6.0 Hz, 3 H), 1.22 (d, J = 6.4 Hz, 3 H), 1.25 (d, J = 7.0 Hz, 3
H), 1.26–1.35 (m, 2 H), 1.45–1.53 (m, 1 H), 1.61–1.70 (m, 1 H),
1.77–1.88 (m, 1 H), 1.89–1.96 (m, 1 H), 2.34–2.45 (m, 2 H), 3.99
(q, J = 6.4 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 14.5,
20.1, 21.9, 24.0, 27.4, 29.1, 30.0, 32.3, 36.2, 69.2, 100.4, 118.1 ppm.
HRMS (ESI-TOF) calcd. for C24H42Pd2Cl [M – Cl]+ 577.1041;
found 577.1026.
π-Allylpalladium Chloride Complex 4c: Obtained as a 4:1 mixture
of 4c/5c (131 mg, 68%). Pure complex 4c (79 mg, 41%) was isolated
as a yellow powder. Rf = 0.27 (petroleum ether). [α]2D5 = +12.5 (c =
0.42, CHCl ). IR (CHCl ): ν = 3033, 2954, 2929, 2870, 1638, 1455,
˜
3
3
1382, 1262, 1120, 1093, 1045, 760 cm–1. 1H NMR (400 MHz,
CDCl3): δ = 0.89 (d, J = 6.9 Hz, 3 H), 1.00 (d, J = 6.0 Hz, 3 H),
1.16 (t, J = 7.4 Hz, 3 H), 1.26 (d, J = 6.8 Hz, 3 H), 1.28–1.32 (m,
1 H), 1.45–1.56 (m, 3 H), 1.62–1.72 (m, 2 H), 1.78–1.88 (m, 1 H),
1.89–1.97 (m, 1 H), 2.38–2.45 (m, 2 H), 3.78 (t, J = 6.4 Hz, 1
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 13.0, 20.0, 21.9, 22.6,
24.1, 27.4, 29.0, 29.9, 32.3, 35.9, 76.4, 100.5, 116.9 ppm. HRMS
(ESI-TOF) calcd. for C26H46Pd2Cl [M – Cl]+ 605.1358; found
605.1365.
π-Allylpalladium Chloride Complex 4d: Obtained as a 3.5:1 mixture
of 4d/5d (125 mg, 62%). Pure complex 4d (76.7 mg, 38%) was iso-
lated as a yellow powder. Rf = 0.28 (petroleum ether). [α]2D5 = +15.1
N-Benzyl-1-phenyl-3-butenylamine (8b):[14a] Colorless oil. [α]2D5
=
–44.8 (c = 0.14, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 1.25
(br. s, 1 H), 2.38–2.45 (m, 2 H), 3.51 (d, J = 13.3 Hz, 1 H), 3.67
(dd, J = 7.6, 6.8 Hz, 2 H), 5.02–5.10 (m, 2 H), 5.65–5.75 (m, 1 H),
7.21–7.36 (m, 10 H) ppm. HPLC (CHIRALCEL OD-H column;
hexane/iPrOH, 99.8:0.2; flow rate: 0.5 mL/min): tR (retention time)
= 16.85 min (minor enantiomer) and 19.5 min (major enantiomer);
70%ee.
(c = 0.34, CHCl ). IR (CHCl ): ν = 2961, 2927, 2870, 1686, 1460,
˜
3
3
1384, 1261, 1117, 1088, 1036, 899 cm–1. 1H NMR (400 MHz,
CDCl3): δ = 0.89 (d, J = 6.8 Hz, 3 H), 0.96 (t, J = 7.1 Hz, 3 H),
1.0 (d, J = 5.9 Hz, 3 H), 1.26 (d, J = 5.4 Hz, 3 H), 1.21–1.31 (m, 3
H), 1.44–1.59 (m, 3 H), 1.61–1.72 (m, 2 H), 1.75–1.88 (m, 1 H),
1.89–1.98 (m, 1 H), 2.41–2.50 (m, 2 H), 3.85 (t, J = 6.3 Hz, 1
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 14.2, 20.0, 21.8, 21.9,
24.1, 27.4, 29.1, 29.9, 31.2, 32.4, 36.0, 74.6, 100.5, 117.0 ppm.
HRMS (ESI-TOF) calcd. for C28H50Pd2Cl [M – Cl]+ 633.1671;
found 633.1684.
N-Benzyl-1-(4-methylphenyl)-3-butenylamine (8c):[14a] Colorless oil.
[α]2D5 = –41.5 (c = 0.84, CHCl3). H NMR (400 MHz, CDCl3): δ =
1
1.79 (br. s, 1 H), 2.34 (s, 3 H), 2.32–2.40 (m, 2 H), 3.48 (d, J =
13.2 Hz, 1 H), 3.62–3.65 (m, 2 H), 5.03–5.09 (m, 2 H), 5.64–5.75
(m, 1 H), 7.15 (d, J = 7.4 Hz, 2 H), 7.21–7.31 (m, 7 H) ppm. HPLC
(CHIRALCEL OD-H column; hexane/iPrOH, 99.5:0.5; flow rate:
0.7 mL/min): tR = 8.40 min (minor enantiomer) and 10.06 min
(major enantiomer); 76%ee.
π-Allylpalladium Chloride Complex 4e: Obtained as a 3.5:1 mixture
of 4e/5e (136.5 mg, 65%). Pure complex 4e (84 mg, 40%) was iso-
lated as a yellow powder. Rf = 0.28 (petroleum ether). [α]2D5 = +17.2
(c = 0.3, CHCl ). IR (CHCl ): ν = 2928, 2957, 2870, 1653, 1463,
˜
3
3
N-Benzyl-1-(4-methoxyphenyl)-3-butenylamine (8d):[14a] Colorless
1383, 1367, 1166, 1086, 988, 936 cm–1. 1H NMR (400 MHz,
CDCl3): δ = 0.89 (d, J = 7.4 Hz, 3 H), 0.93 (d, J = 6.6 Hz, 3 H),
0.96 (d, J = 6.6 Hz, 3 H), 1.00 (d, J = 5.9 Hz, 3 H), 1.20–1.35 (m,
6 H), 1.42–1.55 (m, 2 H), 1.58–1.68 (m, 2 H), 1.77–1.88 (m, 1 H),
1.90–2.01 (m, 1 H), 2.38–2.47 (m, 2 H), 3.95 (t, J = 6.3 Hz, 1
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 19.9, 21.9, 22.4, 22.9,
24.1, 27.8, 29.1, 29.9, 32.5, 34.6, 36.3, 37.4, 73.8, 100.3, 117.2 ppm.
HRMS (ESI-TOF) calcd. for C30H54Pd2Cl [M – Cl]+ 661.1984;
found 661.1974.
1
oil. [α]2D5 = –32.1 (c = 0.56, CHCl3). H NMR (400 MHz, CDCl3):
δ = 2.39 (ddt, J = 7.5, 6.4, 2.1 Hz, 2 H), 3.51 (d, J = 13.1 Hz, 1
H), 3.67 (t, J = 6.5 Hz, 1 H), 3.67 (d, J = 13.1 Hz, 1 H), 3.82 (s, 3
H), 5.03–5.09 (m, 2 H), 5.64–5.75 (m, 1 H), 6.9 (d, J = 8.7, Hz, 2
H), 7.22–7.33 (m, 7 H) ppm. HPLC (CHIRALCEL OD-H column;
hexane/iPrOH, 99.5:0.5; flow rate: 0.7 mL/min): tR = 10.42 min
(minor enantiomer) and 11.20 min (major enantiomer); 72%ee.
N-Benzyl-1-(2-methoxyphenyl)-3-butenylamine (8e):[14a] Colorless
1
oil. [α]2D5 = –19.2 (c = 0.2, CHCl3). H NMR (400 MHz, CDCl3):
π-Allylpalladium Chloride Complex 4f: Obtained as a 3.8:1 mixture
of 4f/5f (111 mg, 55%). Pure complex 4f (62.5 mg, 31%) was iso-
lated as a yellow powder. Rf = 0.28 (petroleum ether). [α]2D5 = +15.2
δ = 1.25 (br. s, 1 H), 2.43–2.60 (m, 2 H), 3.56 (d, J = 13.1 Hz, 1
H), 3.69 (d, J = 13 Hz, 1 H), 3.81 (s, 3 H), 4.09–4.13 (m, 1 H),
4.97–5.05 (m, 2 H), 5.71 (ddt, J = 15.6, 9.5, 7.1 Hz, 1 H), 6.90 (d,
J = 7.9 Hz, 1 H), 6.97 (t, J = 7.7 Hz, 1 H), 7.23–7.51 (m, 7 H) ppm.
HPLC (CHIRALCEL OD-H column; hexane/iPrOH, 99:1; flow
rate: 0.8 mL/min): tR = 8.50 min (minor enantiomer) and 10.00 min
(major enantiomer); 42%ee.
(c = 0.4, CHCl ). IR (CHCl ): ν = 3033, 2960, 2929, 1654, 1456,
˜
3
3
1427, 1383, 1262, 1089, 1054, 944 cm–1. 1H NMR (400 MHz,
CDCl3): δ = 0.89 (d, J = 6.7 Hz, 6 H), 0.96 (d, J = 6.9 Hz, 3 H),
1.01 (d, J = 5.5 Hz, 3 H), 1.24 (d, J = 6.7 Hz, 3 H), 1.21–1.31 (m,
1 H), 1.41–1.55 (m, 2 H), 1.56–1.75 (m, 2 H), 1.78–1.86 (m, 1 H),
1.87–1.98 (m, 1 H), 2.35–2.50 (m, 2 H), 3.85 (t, J = 6.3 Hz, 1 N-Benzyl-1-(4-nitrophenyl)-3-butenylamine (8f): Colorless oil. [α]2D5
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 14.2, 20.0, 21.8, 21.9,
= –6.8 (c = 1.2, CHCl ). IR (CHCl ): ν = 3335, 3078, 3029, 2924,
˜
3
3
1950
www.eurjoc.org
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 1945–1952

Asymmetric Allylation of Imines
2849, 1640, 1599, 1520, 1455, 1347, 1109, 996, 920, 856, 754 cm–1. HRMS (ESI-TOF): calcd. for C16H19N2 [M + H]+ 239.1548; found
1H NMR (400 MHz, CDCl3): δ = 1.91 (br. s, 1 H), 2.32–2.43 (m, 239.1551. HPLC (CHIRALCEL OD-H column; hexane/iPrOH,
2 H), 3.49 (d, J = 13.1 Hz, 1 H), 3.63 (d, J = 13.2 Hz, 1 H), 3.66–
3.84 (m, 1 H), 5.05–5.10 (m, 2 H), 5.62–5.72 (m, 1 H), 7.22–7.33
(m, 5 H), 7.54 (d, J = 8.4 Hz, 2 H), 8.19 (d, J = 8.5 Hz, 2 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 42.8, 51.5, 61.1, 118.5, 123.6 (2
C), 127.0, 127.9 (2 C), 128.1 (2 C), 128.4 (2 C), 134.2, 139.9, 147.1,
151.8 ppm. HRMS (ESI-TOF): calcd. for C17H19N2O2 [M + H]+
283.1447; found 283.1443. HPLC (CHIRALPAK AD-H column;
hexane/iPrOH, 99.5:0.5; flow rate: 0.5 mL/min): tR = 50.32 min
(minor enantiomer) and 54.87 min (major enantiomer); 22%ee.
97:3; flow rate: 1 mL/min): tR = 9.06 min (minor enantiomer) and
10.80 min (major enantiomer); 52%ee.
N-Benzyl-1-piperonyl-3-butenylamine (8a):[14a] Colorless oil. [α]2D5
=
–49.1 (c = 0.28, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 1.84
(br. s, 1 H), 2.31–2.39 (m, 2 H), 3.51 (d, J = 13.3 Hz, 1 H), 3.6 (t,
J = 6.5 Hz, 1 H), 3.68 (d, J = 13.3 Hz, 1 H) 5.03–5.10 (m, 2 H),
5.7 (ddt, J = 15.6, 9.7, 6.9 Hz, 1 H), 5.96 (s, 2 H), 6.78 (s, 2 H),
6.92 (s, 1 H), 7.23–7.35 (m, 5 H) ppm. HPLC (CHIRALCEL OD-
H column; hexane/iPrOH, 98:2; flow rate: 0.8 mL/min): tR
=
N-Benzyl-1-(4-chlorophenyl)-3-butenylamine (8g): Colorless oil.
9.61 min (minor enantiomer) and 10.40 min (major enantiomer);
78%ee.
[α]2D5 = –39.1 (c = 0.4, CHCl ). IR (CHCl ): ν = 3396, 3077, 2931,
˜
3
3
2844, 1646, 1460, 1046, 917, 765 cm–1. 1H NMR (400 MHz,
CDCl3): δ = 1.79 (br. s, 1 H), 2.35–2.37 (m, 2 H), 3.49 (d, J =
13.3 Hz, 1 H), 3.62 (d, J = 13.2 Hz, 1 H), 3.62–3.68 (m, 1 H), 5.03–
5.08 (m, 2 H), 5.61–5.72 (m, 1 H), 7.2–7.4 (m, 9 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 43.0, 51.3, 60.9, 117.9, 126.9, 128.0 (2 C),
128.4 (2 C), 128.5 (2 C), 128.7 (2 C), 132.5, 134.9, 140.3, 142.3 ppm.
LRMS (ESI): calcd. for C17H19NCl [M + H]+ 272.1; found 272.1.
HPLC (CHIRALPAK IA column; hexane/iPrOH, 99:1; flow rate:
0.5 mL/min): tR = 12.59 min (minor enantiomer) and 14.25 min
(major enantiomer); 56%ee.
N-(4-Methoxybenzyl)-1-piperonyl-3-butenylamine (8l):[14a] Colorless
1
oil. [α]2D5 = –38.6 (c = 0.28, CHCl3). H NMR (400 MHz, CDCl3):
δ = 1.96 (br. s, 1 H), 2.34–2.40 (m, 2 H), 3.46 (d, J = 13.0 Hz, 1
H), 3.62 (d, J = 13.0 Hz, 1 H), 3.61–3.65 (m, 1 H), 3.79 (s, 3 H),
5.01–5.07 (m, 2 H), 5.62–5.72 (m, 1 H), 5.95 (s, 2 H), 6.77 (s, 2 H),
6.84 (d, J = 8.7 Hz, 2 H), 6.9 (s, 1 H), 7.17 (d, J = 8.6 Hz, 2 H) ppm.
HPLC (CHIRALCEL OD-H column; hexane/iPrOH, 99:1; flow
rate: 1 mL/min): tR = 15.87 min (minor enantiomer) and =
20.61 min (major enantiomer); 64%ee.
N-(4-Methoxybenzyl)-1-phenyl-3-butenylamine (8m):[14a] Colorless
N-Benzyl-1-(1-naphthyl)-3-butenylamine (8h): Colorless oil. [α]2D5
–21.8 (c = 0.86, CHCl ). IR (CHCl ): ν = 3437, 3062, 2928, 2856,
=
oil. [α]2D5 = –32.6 (c = 0.31, CHCl3). H NMR (400 MHz, CDCl3):
1
˜
3
3
δ = 1.99 (br. s, 1 H), 2.35–2.42 (m, 2 H), 3.45 (d, J = 13 Hz, 1 H),
3.6 (d, J = 13 Hz, 1 H), 3.67 (dd, J = 7.5, 6.2 Hz 1 H), 3.78 (s, 3
H), 5.01–5.08 (m, 2 H), 5.63–5.74 (m, 1 H), 6.84 (ddd, J = 8.7, 2.9,
2.4 Hz, 2 H), 7.15 (dd, J = 8.6, 2.3 Hz, 2 H), 7.23–7.28 (m, 1 H),
7.32–7.35 (m, 4 H) ppm. HPLC (CHIRALCEL OD-H column;
hexane/iPrOH, 99.8:0.2; flow rate: 1 mL/min): tR = 6.29 min
(minor enantiomer) and 7.64 min (major enantiomer); 68%ee.
N-(4-Methoxybenzyl)-1-(4-methylphenyl)-3-butenylamine (8n):[14a]
Colorless oil. [α]2D5 = –31.5 (c = 0.19, CHCl3). 1H NMR (400 MHz,
CDCl3): δ = 1.90 (br. s, 1 H), 2.35 (s, 3 H), 2.38–2.41 (m, 2 H),
3.46 (d, J = 13.0 Hz, 1 H), 3.62 (d, J = 13.0 Hz, 1 H), 3.58–3.66
(m, 1 H), 3.79 (s, 3 H), 5.01–5.08 (m, 2 H), 5.68 (ddt, J = 16.0, 9.9,
6.9 Hz, 1 H), 6.84 (d, J = 8.7 Hz, 2 H), 7.15 (d, J = 8.1 Hz, 4 H),
7.25 (d, J = 8.0 Hz, 2 H) ppm. HPLC (CHIRALCEL OD-H col-
umn; hexane/iPrOH, 99.3:0.7; flow rate: 1 mL/min): tR = 7.23 min
(minor enantiomer) and 9.70 min (major enantiomer); 60%ee.
N-(4-Methoxybenzyl)-1-(4-methoxyphenyl)-3-butenylamine (8o):[14a]
Colorless oil. [α]2D5 = –35.2 (c = 0.24, CHCl3). 1H NMR (400 MHz,
CDCl3): δ = 1.77 (br. s, 1 H), 2.35–2.39 (m, 2 H), 3.44 (d, J =
13.1 Hz, 1 H), 3.61 (d, J = 13.0 Hz, 1 H), 3.58–3.64 (m, 1 H), 3.79
(s, 3 H), 3.81 (s, 3 H), 5.0–5.08 (m, 2 H), 5.68 (ddt, J = 16.0, 9.5,
6.4 Hz, 1 H), 6.84 (d, J = 8.7 Hz, 2 H), 6.88 (d, J = 8.7 Hz, 2 H),
7.15 (d, J = 8.6 Hz, 2 H), 7.26 (d, J = 7.8 Hz, 2 H) ppm. HPLC
(CHIRALCEL OD-H column; hexane/iPrOH, 98:2; flow rate:
1 mL/min): tR = 8.45 min (minor enantiomer) and 9.73 min (major
enantiomer); 56%ee.
1638, 1597, 1456, 1394, 1167, 1106, 1028, 997, 917, 800, 778 cm–1.
1H NMR (400 MHz, CDCl3): δ = 1.89 (br. s, 1 H), 2.43–2.51 (m,
1 H), 2.64–2.68 (m, 1 H), 3.58 (d, J = 13.2 Hz, 1 H), 3.75 (d, J =
13.5 Hz, 1 H), 4.59 (dd, J = 7.7, 4.4 Hz, 1 H), 5.05–5.14 (m, 2 H),
5.75–5.85 (m, 1 H), 7.20–7.36 (m, 5 H), 7.47–7.52 (m, 3 H), 7.76–
7.89 (m, 3 H), 8.18 (d, J = 6.2 Hz, 1 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 42.1, 51.6, 57.1, 117.7, 123.0, 123.9, 125.3, 125.6,
125.7, 126.9, 127.4, 128.2 (2 C), 128.3 (2 C), 129.0, 131.6, 134.0,
135.5, 139.0, 140.6 ppm. HRMS (ESI-TOF): calcd. for C21H22N
[M + H]+ 288.1752; found 288.1744. HPLC (CHIRALCEL OD-H
column; hexane/iPrOH, 97:3; flow rate: 0.8 mL/min): tR = 9.06 min
(minor enantiomer) and 10.80 min (major enantiomer); 62%ee.
N-Benzyl-1-(2-furfuryl)-3-butenylamine (8i):[14a] Colorless oil. [α]2D5
1
= –25.8 (c = 0.56, CHCl3). H NMR (400 MHz, CDCl3): δ = 1.89
(br. s, 1 H), 2.51–2.55 (m, 2 H), 3.59 (d, J = 13.1 Hz, 1 H), 3.71
(d, J = 13.2 Hz, 1 H), 3.71–3.77 (m, 1 H), 5.03–5.11 (m, 2 H), 5.65–
5.75 (m, 1 H), 6.18 (d, J = 2.8 Hz, 1 H), 6.33 (d, J = 2.8 Hz, 1
H), 7.23–7.31 (m, 6 H) ppm. HPLC (CHIRALCEL AD-H column;
hexane/iPrOH, 99.5:0.5; flow rate: 0.7 mL/min): tR = 10.29 min
(minor enantiomer) and 13.10 min (major enantiomer); 36%ee.
N-Benzyl-1-(2-thiophenyl)-3-butenylamine (8j):[14a] Colorless oil.
[α]2D5 = –15.5 (c = 0.12, CHCl3). H NMR (400 MHz, CDCl3): δ =
1
1.85 (br. s, 1 H), 2.47–2.50 (m, 2 H), 3.60 (d, J = 13.5 Hz, 1 H),
3.79 (d, J = 13.5 Hz, 1 H), 3.97 (t, J = 6.6 Hz, 1 H), 5.05–5.11 (m,
2 H), 5.69 (ddt, J = 15.8, 9.6, 6.5 Hz, 1 H), 6.91–6.95 (m, 2 H),
7.21–7.32 (m, 6 H) ppm. HPLC (CHIRALCEL AD-H column;
hexane/iPrOH, 99.5:0.5; flow rate: 0.5 mL/min): tR = 14.15 min
(minor enantiomer) and 17.55 min (major enantiomer); 48%ee.
N-Allyl-1-phenyl-3-butenylamine (8p):[14a] Colorless oil. [α]2D5
=
–21.3 (c = 0.15, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 1.66
(br. s, 1 H), 2.40–2.44 (m, 2 H), 2.98–3.04 (m, 1 H), 3.09–3.14 (m,
1 H), 3.70 (dd, J = 6.2, 1.2 Hz, 1 H), 5.03–5.13 (m, 4 H), 5.68–
5.76 (m, 1 H), 5.8–5.90 (m, 1 H), 7.22–7.34 (m, 5 H) ppm. HPLC
(CHIRALCEL OD-H column; hexane/iPrOH, 98.2:1.8; flow rate:
0.6 mL/min): tR = 8.48 min (minor enantiomer) and, = 9.0 min
(major enantiomer); 64%ee.
N-Benzyl-1-(3-pyridyl)-3-butenylamine (8k): Colorless oil. [α]2D5
–18.8 (c = 0.12, CHCl ). IR (CHCl ): ν = 3412, 3030, 2925, 2852,
=
˜
3
3
1645, 1455, 1428, 1262, 1106, 1028, 995, 920, 808 cm–1. H NMR
(400 MHz, CDCl3): δ = 2.38–2.53 (m, 3 H), 3.51 (d, J = 13.3 Hz,
1 H), 3.65 (d, J = 13.3 Hz, 1 H), 3.73 (t, J = 7.1 Hz, 1 H), 5.01–
5.08 (m, 2 H), 5.62–5.72 (m, 1 H), 7.22–7.34 (m, 6 H), 7.73 (d, J
1
= 7.8 Hz, 1 H), 8.5 (d, J = 4.8 Hz, 1 H), 8.55 (d, J = 2 Hz 1 H) ppm. N-Benzyl-1-cyclohexyl-3-butenylamine (8q):[14a] Colorless oil. [α]2D5
13C NMR (100 MHz, CDCl3): δ = 42.6, 51.3, 59.2, 118.5, 123.6, = –1.7 (c = 0.14, CHCl3). H NMR (400 MHz, CDCl3): δ = 1.1–
1
127.1, 128.2 (3 C), 128.5 (3 C), 134.3, 135.0, 148.7, 149.4 ppm. 1.76 (m, 11 H), 2.09–2.15 (m, 1 H), 2.24–2.31 (m, 1 H), 2.38–2.42
Eur. J. Org. Chem. 2012, 1945–1952
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1951

R. A. Fernandes, D. A. Chaudhari
FULL PAPER
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(m, 1 H), 3.75 (br. s, 2 H), 5.03–5.1 (m, 2 H), 5.74–5.83 (m, 1 H),
7.2–7.34 (m, 5 H) ppm. HPLC (CHIRALCEL OD column; hex-
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˜
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3
1074, 759 cm–1. 1H NMR (400 MHz, CDCl3): δ = 0.87 (t, J =
7.0 Hz, 3 H), 1.22–1.40 (m, 11 H), 2.13–2.20 (m, 1 H), 2.23–2.30
(m, 1 H), 2.57–2.63 (m, 1 H), 3.77 (s, 2 H), 5.06–5.11 (m, 2 H),
5.73–5.83 (m, 1 H), 7.21–7.41 (m, 5 H) ppm. 13C NMR (100 MHz,
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flow rate: 1 mL/min): tR = 4.8 min (minor enantiomer) and 7.7 min
(major enantiomer); 30%ee.
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Supporting Information (see footnote on the first page of this arti-
1
cle): Copies of H and 13C NMR spectra for compounds 3a–f, 4a/
5a mixture, 4b–f, 8f, 8g, 8h, 8k, and 8r.
Acknowledgments
Research funding by the Council of Scientific and Industrial Re-
search (CSIR), New Delhi [grant number 01(2267)/08/EMR-II] is
gratefully acknowledged.
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Received: October 31, 2011
Published Online: February 13, 2012
1952
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Eur. J. Org. Chem. 2012, 1945–1952