Nickel-catalyzed multi-component connection reaction of isoprene, aldimines (lactamines), and diphenylzinc

Article abstract of DOI:10.1016/j.tet.2006.03.116

Ni(acac)₂ catalyzes the four-component connection reaction of diphenylzinc, isoprene, aromatic aldehydes, and aromatic amines in this order and provides stereochemically homogeneous (E)-1-arylamino-1-aryl-3-methyl-5-phenyl-3-pentenes (1) in excellent yields. Aliphatic aldehydes react similarly and give (E)-1-arylamino-1-alkyl-3-methyl-5-phenyl-3-pentenes (1) in slightly reduced yields. When the alkyl groups are bulky, in addition to 1 are formed (E)-1-arylamino-1-alkyl-4-methyl-5-phenyl-3-pentenes (1′) as the minor products. Lactamines prepared in situ from five- and six-membered lactols and aromatic amines are more reactive than alkyl aldehyde aldimines and furnish (E)-4-arylamino-6-methyl-8-phenyl-6-octen-1-ols (4) and (E)-5-arylamino-7-methyl-9- phenyl-7-nonen-1-ols (5), respectively, in good yields with excellent E-stereoselectivity.

Full text of DOI:10.1016/j.tet.2006.03.116

Tetrahedron 62 (2006) 7512–7520
Nickel-catalyzed multi-component connection reaction of
isoprene, aldimines (lactamines), and diphenylzinc
Keisuke Kojima,a Masanari Kimura,a Satoshi Uedab and Yoshinao Tamarub,
*
aGraduate School of Science and Technology, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan
bDepartment of Applied Chemistry, Faculty of Engineering, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan
Received 15 November 2005; revised 2 March 2006; accepted 2 March 2006
Available online 8 June 2006
This manuscript was dedicated to Professor Gunther Wilke for his contribution to the field of organonickel chemistry
¨
Abstract—Ni(acac)2 catalyzes the four-component connection reaction of diphenylzinc, isoprene, aromatic aldehydes, and aromatic amines
in this order and provides stereochemically homogeneous (E)-1-arylamino-1-aryl-3-methyl-5-phenyl-3-pentenes (1) in excellent yields.
Aliphatic aldehydes react similarly and give (E)-1-arylamino-1-alkyl-3-methyl-5-phenyl-3-pentenes (1) in slightly reduced yields. When
the alkyl groups are bulky, in addition to 1 are formed (E)-1-arylamino-1-alkyl-4-methyl-5-phenyl-3-pentenes (10) as the minor products.
Lactamines prepared in situ from five- and six-membered lactols and aromatic amines are more reactive than alkyl aldehyde aldimines
and furnish (E)-4-arylamino-6-methyl-8-phenyl-6-octen-1-ols (4) and (E)-5-arylamino-7-methyl-9- phenyl-7-nonen-1-ols (5), respectively,
in good yields with excellent E-stereoselectivity.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
We also clarified that a similar methodology could be
applied to the reactions with aldimines; phenylative multi-
component connection reaction was best performed with
diphenylzinc (Eq. 1), while methylative reaction was most
successful with trimethylaluminum (Eq. 2).4,5 Methylative
reaction, however, is still not at a practically useful level;
the reaction yields 2 with modest stereoselectivity (E:Z¼
2:1–10:1) along with 3 as minor products, both being in-
separable by conventional column chromatography. Further
improvement of the reaction conditions, enabling the stereo-
selective formation of (E)-2 minimizing the formation 3, has
been under our ongoing extensive study.
Multi-component connection reactions of simple molecules
are straightforward and efficient methods to construct
desired molecules which have been realized mostly by mak-
ing the best use of transition-metal catalysis.1 Isoprene and
aldimines are among the most important building blocks;
isoprene is a ubiquitous constituent of the carbon frame-
works of natural products and aldimines serve as a nitrogen
source of many physiologically interesting compounds.
Regio- (C1 vs C4) and stereoselective (E vs Z) incorporation
of isoprene into molecules is a rather difficult task and it has
been a challenge for synthetic organic chemists to establish
methods to manipulate isoprene in desired ways.2 Aldimines
are among the least reactive carbonyl compounds and many
studies, particularly in the past decade, have been devoted to
their activation and utilization as electrophiles toward
carbonucleophiles.
ArNH2
Ph
RCHO
(1)
NHAr
R
10 mol% Ni(acac)2
360 mol% Ph2Zn
Recently, we demonstrated that a nickel(0) species nicely cat-
alyzed the three-component connection reaction of organo-
metals (M¼Zn and B), isoprene, and aldehydes to afford
homoallyl alcohols, where isoprene reacted regioselectively
with aldehydes at the C1 position and with organometals at
the C4 position.3
only (E)-1
10 mol% Ni(acac)2
360 mol% Me3Al
ArNH2
ArCHO
(2)
Keywords: Aldimine; Diphenylzinc; Isoprene; Lactol; Multi-component
connection; Nickel catalysis.
* Corresponding author. Tel./fax: +81 95 819 2677; e-mail: tamaru@net.
nagasaki-u.ac.jp
Me
NHAr
Ar
Me
NHAr
Ar
3
2
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.03.116

K. Kojima et al. / Tetrahedron 62 (2006) 7512–7520
7513
Table 1. Ni-catalyzed four-component connection reaction of Ph2Zn,
In this article, we disclose a full account of phenylative
multi-component connection reaction, which provides
(E)-1 in good yields and with excellent stereoselectivity
for a variety of aldimines prepared in situ from aromatic
aldehydes and aromatic amines (R¼Ar, Eq. 1). The reaction
can be successfully extended to aliphatic aldehyde-p-anisi-
dine imines (R¼alkyl, Ar¼p-anisyl, Eq. 1), which is high-
lighted by the reaction with lactamines, generated in situ
from lactols (cyclic hemiacetals) and aromatic amines
(Eq. 3). This might be a great achievement, not only because
two important building blocks, isoprene and aldimines, are
incorporated in the products, but also because tri-substituted
(E)-homoallylamines 1 and (E)-homoallylamino alcohols 4
and 5 are produced with a single operation in one flask in the
yields of a synthetically useful level under nickel catalysis.
These products may be of great concern for synthetic organic
chemists and also for life science researchers.
isoprene, aldehydes, and amines (Eq. 1)a
Run
Aldehyde
R
Amine
Time
(h)
Yieldb
3
1
2
3
4
5
6
7
8
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
p-MeOPh
p-MePh
Ph
o-(F)Ph
p-(F)Ph
2
1
1
3
2
24
2
24
3
6
2
6
6
1
2
1
1
1
6
(E)-1a:80
(E)-1b:96
(E)-1c:90
(E)-1d:98
(E)-1e:94
(E)-1f:30
(E)-1g:78
o-(Cl)Ph
p-(Cl)Ph
o-(Br)Ph
p-(Br)Ph
n-Hexyl
p-MeOPh
p-MeOPh
p-MeOPh
p-MeOPh
p-MeOPh
p-MeOPh
p-MeOPh
p-(Cl)Ph
p-MeOPh
p-MeOPh
c
—
(E)-1h:94
—
9
Ph
Ph
c
10
11
12
13
14
15
16
17
18
19
20
p-Tol
p-Anis
o-(Cl)Ph
p-(Cl)Ph
o-(F)Ph
p-(F)Ph
2-Furyl
2-Furyl
n-C7H15
i-Pr
(E)-1i:83
(E)-1j:44
(E)-1k:87d
(E)-1l:61
(E)-1m:94
(E)-1n:96
(E)-1o:98
(E)-1p:81
(E)-1q:76
(E)-1r:57e
2. Results and discussion
2.1. Ni-catalyzed four-component connection reaction of
Ph2Zn, isoprene, aldehydes, and aromatic amines
6
a
Reaction conditions: an aldehyde (1 mmol) and an amine (2 mmol) in
THF (2mL) at 30 ꢀC overnight, and then Ni(acac)2 (0.1 mmol in 3 mL
of THF), isoprene (4 mmol), and Ph2Zn (3.6 mmol) at 30 ꢀC.
Yields for the isolated spectroscopically homogeneous materials.
Complex mixture of products.
(E)-1-p-Anisylamino-3-methyl-5-phenyl-1-[(2-phenyl)phenyl]-3-pentene
((E)-1k, see below).
A mixture of (E)-1r and its regioisomer (E)-1r0 (see below) in a ratio of
2:1.
The reaction of benzaldehyde-p-anisidine imine under the
identical conditions established for the multi-component
connection reaction of aldehydes3 was quite disappointing
and provided the expected product 1a (1, R¼Ph, Ar¼p-anisyl,
Eq. 1) in as low as 14% yield among many other intractable
products (Experiment 1). Use of 1 equiv p-anisidine as an ad-
ditive turned out very effective to increase the yield of 1a
(63%, 30 ꢀC for 2 h, Experiment 2). Remarkable improve-
ment in the yield was brought about when the reaction was
conducted using the aldimine formed in situ from benzalde-
hyde and p-anisidine (2 equiv), where 1a was obtained in
80% yield (run 1, Table 1, Experiment 3). Experiments 2
and 3 only differ in the absence or presence of water
(1 equiv), respectively. Experiment 4, which was undertaken
under the identical conditions to those of Experiment 1 in the
presence of 1 equiv of water, gave 1a (24%) in a slightly
better yield than Experiment 1. All these results combine
to indicate that both water and p-anisidine, 1 equiv each,
are essential to give rise to 1a in satisfactory yield.
b
c
d
e
Ph
NH-p-Anis
Ph
NH-p-Anis
Ph
(E)-1k
(E)-1r'
Benzaldehyde imines of alkyl amines, e.g., n-hexylamine,
on the other hand, showed completely different reactivity
and gave intractable mixtures of products (run 10).
We next examined applicability of the present reaction to
other aromatic aldehydes including 2-furaldehyde using
p-anisidine as an aromatic amine (runs 11–18). Judging
from the yields of 1a–h, p-anisidine may not be the best
choice of aromatic amines; however, we used it from a prac-
tical viewpoint. The p-methoxyphenyl group might be
regarded as a protecting group of amines; it could be easily
removed oxidatively, yielding free primary amines of the
product 1 in good yields.7c,9d,11
Many precedents point to the success of nucleophilic alkyl-
ation of aldimines6 depending on the steric and electronic
effects of both the aldehyde7 and the nitrogen substituents,8
and sometimes heteroatoms on these substituents exert
tremendous effects on the reaction efficiency.6,9
In order to optimize the nitrogen substituents, we examined
a wide range of aniline derivatives either bearing an elec-
tron-donating or an electron-withdrawing substituent under
the conditions established above. The results are summa-
rized in runs 2–9 (Table 1). Except foro-chloro- and o-bromo-
anilines (runs 6 and 8), no significant differences in
reactivity and yields were observed over a wide range of
pKa of aniline derivatives10 (e.g., pKa(o-Br)¼2.53, pKa(p-
OMe)¼5.36). In most cases, the reactions were complete
within 1–3 h and provided 1 in more than 90% yields. The
reactions were monitored with TLC. The sluggishness and
the low yields observed for o-chloro- and o-bromoanilines
might be attributed to deactivation of a nickel catalyst
rather than steric hindrance of the reaction (vide infra).
All aromatic aldehydes, irrespective of the steric (o- and p-)
and electronic (electron-donating and electron-withdraw-
ing) nature of the substituents, reacted smoothly at 30 ꢀC
and provided the expected products 1 in modest to
excellent yields. Interestingly, while the C–Cl bond of the
p-chloro isomer 1l remained intact, the C–Cl bond of the
o-chloro isomer underwent cross-coupling reaction12 with
Ph2Zn and provided 1k exclusively in good yield (runs 13
and 14, footnote d, Table 1). The o-fluoro counterpart 1m
withstood the cross-coupling reaction (run 15).
The reaction could be extended to aliphatic aldehydes with
limited success. Two typical examples, n-octanal (a primary

7514
K. Kojima et al. / Tetrahedron 62 (2006) 7512–7520
aldehyde) and 2-methylpropanal (a secondary aldehyde),
were examined. The results are shown in runs 19 and 20.
n-Octanal-p-anisidine imine provided the expected homo-
allylamine (E)-1q as a single isomer in good yield (run
19); however, sterically demanding 2-methylpropanal-
p-anisidine imine provided an inseparable mixture of two
isomers 1r and 1r0, the latter arising from incorporation of
isoprene in an opposite direction (run 20, see footnote e).
2.2. Ni-catalyzed four-component connection reaction of
Ph2Zn, isoprene, lactols, and aromatic amines
Lactols (2-hydroxy-oxacycloalkanes) share the fundamental
skeleton with many carbohydrates, and establishment of
methodology for their derivatization, enabling of elongation
of carbon chains and especially enabling of introduction of
an amino group, is of significant importance in organic syn-
thesis and life science research.14 The outstanding character-
istics of the present methodology, compatibility with water
and acceleration of the reaction in the presence of a limited
amount of water, encouraged us to examine the multi-com-
ponent connection reaction with lactols (Eq. 3).
This erosion of regioselectivity might be rationalized on the
steric ground as discussed before (Scheme 1);5c the reaction
would avoid a putative transition state I that places both the
imine substituents at a di-equatorial position of a cyclic
structure, since it suffers from severe gauche repulsion be-
tween the ligand on Ni and the aromatic ring on N. Instead,
the reaction would proceed through a transition state II,
where both the aldimine substituents locate in a diaxial
position.13 When R is of great steric bulk, 1,3-quasi-diaxial
repulsion between R and the methyl group of isoprene
becomes substantial in a transition state II, and another tran-
sition state III, placing isoprene in an opposite direction,
would become to contribute to the reaction to a certain extent
and would lead to 10 as a side product.
O
OH
ArNH2
( )n
(3)
Ph
NHAr
( )n
10 mol% Ni(acac)2
360 mol% Ph2Zn
OH
(E)-4 (n = 1)
(E)-5 (n = 2)
1H NMR studies revealed that a mixture of 2-hydroxytetra-
hydrofuran and p-anisidine cleanly formed 2-(p-anisidyl)-
tetrahydrofuran (6, n¼1) (Scheme 2). The mixture did not
contain 4-hydroxybutanal-p-anisidine imine (7, n¼1) in
any detectable amounts. The extremely low concentration
of 7 in the equilibrium with 6 suggested us that phenylative
multi-component connection reaction using lactols and
p-anisidine might proceed with difficulty or, if any, very
slowly as compared with the reactions of alkyl aldehyde-p-
anisidine imines.
R
R
H
Ni
Ni
Ar
Ni
L
L
H
N
Ar
R
N
I
L
N
Ar
H
II
III
Ph2Zn
Ph2Zn
Ph2Zn
R
C4
C4
C1
H
R
C1
C4
C1
Ph
Ph
Ph
Ni
L
Ni
L
N
Ar
Ni
L
N
Ar
R
N
H
H
ZnPh
ZnPh
ZnPh
Ar
Ar
NH
O
( )n
OH
O
H2O
H2N Ar
( )n
1
1
1'
6
Scheme 1. Transition states leading to regioisomers 1 and 10.
X
Zn
H
O
Ar
NH
The stereochemical homogeneity of 1 was confirmed with
1H (400 MHz) and 13C NMR (100 MHz) spectroscopies.
The E structure of 1 was determined on the basis of NOE
experiments. Some representative data are shown in Figure 1.
The E structure of the regioisomer 10 was also determined by
NOE experiments.
Ar
H2O
N
O
( )n
( )n
7
8
Scheme 2.
To our pleasant surprise, however, the reaction of 2-hydroxy-
tetrahydrofuran and p-anisidine under usual conditions pro-
ceeded smoothly, completing within 2 h even at ambient
temperature (cf., run 1, Table 2 and runs 19–20, Table 1).
The expected product (E)-4a (Ar¼p-anisyl) was obtained
as a single isomer in remarkably good yield. The parent
aniline and p-chloroaniline showed almost the same results
regarding the reactivity and the product yields (runs 2 and
3, Table 2).
Cl
2.5%
CH3 HN
O
Ph
H
1p
0%
12.5%
p-Anis
p-Anis
2-Hydroxytetrahydropyran reacted similarly well for variety
combinations with aniline derivatives and provided the ex-
pected products 5 in modest to good yields (runs 4–13, Table
2). o-Chloro- and o-bromoaniline gave rise to the expected
products 5g and 5i about half the yields of the corresponding
p-isomers, 5h and 5j (runs 10–13), respectively. On the other
hand, o-methoxyaniline gave rise to the expected products
H
HN
HN
0%
Ph
Ph
0%
1r'
H
3.3%
1r
Figure 1. Percent increments of area intensities observed by irradiation at
the boldface protons.

K. Kojima et al. / Tetrahedron 62 (2006) 7512–7520
7515
Table 2. Ni-catalyzed four-component connection of Ph2Zn, isoprene,
4. Experimental
lactols (n¼1 and 2), and anilines (Eq. 3)a
Yieldb (%)
4.1. General
Run
n
Anilines
Time (h)
1
2
3
4
5
6
7
8
1
1
1
2
2
2
2
2
2
2
2
2
2
p-MeO
H
p-Cl
o-MeO
p-MeO
H
p-Me
o-F
p-F
o-Cl
p-Cl
o-Br
p-Br
2
2
2
4
2
1
2
2
3
2
2
4
6
(E)-4a:83
(E)-4b:84
(E)-4c:88
(E)-5a:68
(E)-5b:76
(E)-5c:81
(E)-5d:86
(E)-5e:45
(E)-5f:56
(E)-5g:44
(E)-5h:89
(E)-5i:34
(E)-5j:64
Reactions employed oven-dried glassware unless otherwise
noted. Thin layer chromatography (TLC) employed glass
0.25 mm silica gel plates with UV indicator (Merck, Silica
gel 60F254). Flash chromatography columns were packed
with 230–400 mesh silica gel as a slurry in n-hexane. Gradi-
ent flash chromatography was conducted eluting with a con-
tinuous gradient from n-hexane to the indicated solvent.
Proton and carbon NMR data were obtained with a JEOL-
GX400 with tetramethylsilane as an internal standard.
Chemical shift values were given in parts per million down-
field from the internal standard. Infrared spectra were
recorded with a JASCO A-100 FTIR spectrophotometer.
High-resolution mass spectra (HRMS) were measured with
a JEOL JMS-DX303. Combustion analyses were performed
by the Instrumental Analysis Center of Nagasaki University.
Analysis agreed with the calculated values within ꢁ0.4%.
9
10
11
12
13
a
Reaction conditions: a lactol (1 mmol) and an aniline derivative (2 mmol)
in THF (2 mL) at room temperature overnight, and then Ni(acac)2
(0.1 mmol in 3 mL of THF), isoprene (4 mmol), and Ph2Zn (3.6 mmol)
at room temperature.
b
Yields for the isolated and spectroscopically homogeneous materials.
5a in almost the same yield as p-methoxyaniline (runs 4 and
5). These results suggest that the decrease in the yields that
o-bromo- and o-chloro-isomers display is not due to steric
hindrance but probably due to decomposition of products
that might be triggered by oxidative addition of a Ni(0) spe-
cies upon the ortho C-halogen bond followed by elimination
of a Ni-amide species. Although the reason is not clear at the
moment, the decomposition of 5g and 5i is not so serious as
that encountered in runs 6 and 8 in Table 1.
4.2. Solvents and reagents
Tetrahydrofuran was dried and distilled from benzophenone
and sodium immediately prior to use under nitrogen atmo-
sphere. Ni(acac)2 (purity 95%, Aldrich), PhMgBr (1.0 M
THF solution, KANTO), ZnCl2 (1.0 M ether solution,
Aldrich), isoprene (Tokyo Kasei Kogyo Co., Ltd), aniline,
o-anisidine, p-anisidine, o-fluoroaniline, p-fluoroaniline,
o-chloroaniline, p-chloroaniline, o-bromoaniline, and p-
bromoaniline were purchased and used as received. The
following aldehydes were purchased and distilled prior to
use by Kugelrohr apparatus: benzaldehyde, o-tolualdehyde,
p-tolualdehyde, o-anisaldehyde, p-anisaldehyde, o-fluoro-
benzaldehyde, p-fluorobenzaldehyde, o-chlorobenzalde-
hyde, p-chlorobenzaldehyde, 2-furaldehyde, 1-octanal, and
2-methylpropanal.
The unexpectedly smooth reaction of lactamines might be
attributed to an intermediacy of 8, which is formed by che-
lation of 7 to zinc(II) through its hydroxy and imine nitrogen
(Scheme 2); the C¼N/Zn(II) bond would increase the
electrophilic reactivity of the imine moiety, hence facilitate
the reaction.6a,15
4.2.1. Preparation of Ph2Zn. Into a N2 purged Schlenk
flask, were introduced dry THF (10 mL) and ZnCl2
(10 mL, 1 M ether solution; 10 mmol) via syringe. PhMgBr
(20 mL, 1 M THF solution; 20 mmol) was successively
added to the solution, and then the mixture was stirred at
ambient temperature for 3 h. This stock solution was used
as 0.25 M Ph2Zn.
3. Conclusion
This paper demonstrates that Ni(acac)2 serves as an efficient
catalyst for the four-component connection reaction of
diphenylzinc, isoprene, aromatic aldehydes, and aromatic
amines and provides (E)-1-arylamino-1-aryl-3-methyl-5-
phenyl-3-pentenes (1) in excellent yields. Aliphatic alde-
hydes show limited success; primary aldehydes provide
(E)-1-arylamino-1-alkyl-3-methyl-5-phenyl-3-pentenes (1)
selectively, while secondary aldehydes provide mixtures of
1 and (E)-1-arylamino-1-alkyl-4-methyl-5-phenyl-3-pen-
tenes (10), the positional isomers of the isoprene methyl
group, as the minor products. Lactamines prepared in situ
from five- and six-membered lactols and aromatic amines
undergo the multi-component connection reaction smoothly
and furnish (E)-4-arylamino-6-methyl-8-phenyl-6-octen-
1-ols (4) and (E)-5-arylamino-7-methyl-9-phenyl-7-nonen-
1-ols (5), respectively, in good yields with excellent
E-selectivity. The reaction presented here is operationally
simple and can be performed with a single flask procedure.
The products, tri-substituted (E)-homoallylamines 1 and
(E)-homoallylamino alcohols 4 and 5, may be of great inter-
est for synthetic organic chemists as synthetic intermediates
and for life science researchers as probes in their studies.
4.2.2. Preparation of hemiacetals. 3,4-Dihydro-2H-pyran
(8.3 g, 100 mmol) was added into 2 M HCl (20 mL) at
0 ꢀC over 30 min. The mixture was allowed to warm to
room temperature, stirred for an additional 1 h, neutralized
with satd NaHCO3, and then extracted with dichloromethane
(2ꢂ20 mL). The combined extracts were dried (MgSO4),
filtered, and concentrated in vacuo. The residue was purified
by means of Kugelrohr distillation (85 ꢀC/2 mmHg) to give
2-hydroxytetrahydropyran in 93% yield. 2-Hydroxytetra-
hydrofuran was prepared from 2,3-dihydrofuran as
described above (67%, 75 ꢀC/2 mmHg).
4.3. New compounds listed in Table 1
4.3.1. A typical procedure for the Ni-catalyzed four-
component connection reaction of Ph2Zn, isoprene, an
aldehyde and an aromatic amine (run 17, Table 1). Into

7516
K. Kojima et al. / Tetrahedron 62 (2006) 7512–7520
a N2 purged two-necked round-bottomed flask containing
p-anisidine (246 mg, 2.0 mmol), were added dry THF
(2.0 mL) and 2-furaldehyde (96 mg, 1.0 mmol) via syringe.
The mixture was stirred at 30 ꢀC overnight to form aldimine,
which was detected by TLC (Rf ¼0.59, n-hexane/ethyl
acetate ¼ 2:1, v/v). A solution of Ni(acac)2 (25.7 mg,
0.1 mmol) in THF (3.0 mL) was introduced into the aldi-
mine solution via a cannula. Isoprene (400 ml, 4.0 mmol)
and a Ph2Zn solution (14.4 mL, 0.25 M, 3.6 mmol) were
successively introduced via syringe and the homogeneous
mixture was stirred for 1 h. After completion of reaction
(TLC), the mixture was poured into ice-water (20 mL) and
extracted with ethyl acetate (30 mL). The water phase was
extracted with ethyl acetate (2ꢂ20 mL). Combined organic
extracts were washed with 2 M HCl (20 mL) and satd
NaHCO3 (25 mL), and then dried (MgSO4) and concen-
trated in vacuo. The residue was subjected to column chro-
matography over silica gel (eluent: n-hexane/ethyl
acetate ¼ 100:1, v/v) to provide 1o (Rf ¼0.74, n-hexane/ethyl
acetate ¼ 2:1, v/v) in 98% as a single isomer.
126.1, 126.4, 126.7, 127.6, 128.2, 128.47, 128.51, 129.4,
133.0, 141.1, 144.6, 145.4; HRMS calcd for C25H27N:
341.2143; Found m/z (relative intensity): 341.2131 (M+,
100).
4.3.1.4.
benzenamine (1c). IR (neat) 3402 (w), 3024 (w), 1605 (s),
1504 (s), 748 (s) 694 (s) cmꢃ1 1H NMR (CDCl3,
(E)-N-(3-Methyl-1,5-diphenylpent-3-enyl)-
;
400 MHz) d 1.76 (s, 3H), 2.34 (dd, J¼13.7, 10.2 Hz, 1H),
2.55 (dd, J¼13.7, 4.3 Hz, 1H), 3.33 (dd, J¼15.2, 7.5 Hz,
1H), 3.39 (dd, J¼15.2, 7.5 Hz, 1H), 4.37 (dd, J¼10.2,
4.3 Hz, 1H), 5.51 (t, J¼7.5 Hz, 1H), 6.39 (d, J¼7.4 Hz,
2H), 6.62 (t, J¼7.4 Hz, 1H), 7.02–7.37 (m, 12H); 13C
NMR (CDCl3, 100 MHz) d 15.7, 34.3, 50.0, 55.7, 113.3,
117.2, 125.8, 125.9, 126.7, 128.1, 128.4, 128.5, 128.8,
132.8, 141.0, 144.3, 147.5; HRMS calcd for C24H25N:
327.1987; Found m/z (relative intensity): 327.1967 (M+,
100).
4.3.1.5. (E)-2-Fluoro-N-(3-methyl-1,5-diphenylpent-3-
enyl)benzenamine (1d). Mp 71.1–71.6 ꢀC (n-hexane); IR
(KBr disk) 3425 (m), 3024 (w), 2909 (w), 1620 (m), 1520
4.3.1.1. (E)-N-(1-(Furan-2-yl)-3-methyl-5-phenylpent-
3-enyl)-4-methoxybenzenamine (1o). IR (neat) 3396 (w),
(s), 1450 (m), 1335 (m), 1188 (m), 741(s), 702 (m) cmꢃ1
;
2831 (w), 1603 (w), 1514 (s), 1238 (m), 1037 (w) cmꢃ1
;
1H NMR (CDCl3, 400 MHz) d 1.75 (s, 3H), 2.44 (dd,
J¼13.8, 9.3 Hz, 1H), 2.58 (dd, J¼13.8, 4.6 Hz, 1H), 3.36
(dd, J¼15.9, 7.3 Hz, 1H), 3.43 (dd, J¼15.9, 7.3 Hz, 1H),
4.42 (dd, J¼9.3, 4.6 Hz, 1H), 4.44 (br s, 1H), 5.51 (t,
J¼7.3 Hz, 1H), 6.35 (t, J¼7.8 Hz, 1H), 6.51–6.57 (m, 1H),
6.77 (t, J¼7.8 Hz, 1H), 6.94 (dd, J¼12.0, 7.8 Hz, 1H),
7.12–7.37 (m, 10H); 13C NMR (CDCl3, 100 MHz) d 15.7,
34.2, 49.8, 55.6, 113.1, 113.2, 113.9, 114.1, 116.37,
116.44, 124.2, 124.2, 125.7, 125.9, 126.9, 127.6, 128.1,
128.3, 128.5, 132.5, 135.9, 136.0, 140.8, 143.8; HRMS calcd
for C24H24FN: 345.1893; Found m/z (relative intensity):
345.1895 (M+, 22), 278 (21), 277 (100). Anal. Calcd for
C24H24FN: C, 83.44; H, 7.00; F, 5.55; N, 4.05. Found: C,
83.20; H, 7.20; N, 4.08.
1H NMR (CDCl3, 400 MHz) d 1.68 (s, 3H), 2.52 (dd,
J¼13.4, 8.5 Hz, 1H), 2.65 (dd, J¼13.4, 5.9 Hz, 1H), 3.33
(dd, J¼15.1, 7.3 Hz, 1H), 3.39 (dd, J¼15.1, 7.3 Hz, 1H),
3.71 (s, 3H), 4.47 (dd, J¼8.5, 5.9 Hz, 1H), 5.47 (t,
J¼7.2 Hz, 1H), 6.13 (d, J¼3.2 Hz, 1H), 6.26 (dd, J¼3.2,
1.7 Hz, 1H), 6.48 (d, J¼8.9 Hz, 2H), 6.71 (d, J¼8.9 Hz,
2H), 7.12 (d, J¼7.3 Hz, 2H), 7.18 (t, J¼7.3 Hz, 1H), 7.26
(t, J¼3.3 Hz, 2H), 7.32 (d, J¼1.7 Hz, 1H); 13C NMR
(CDCl3, 100 MHz) d 15.8, 34.3, 45.7, 51.3, 55.7, 105.7,
110.0, 114.6, 114.8, 125.7, 127.4, 128.1, 128.3, 132.3,
141.0, 141.1, 141.4, 152.2, 156.5; HRMS calcd for
C23H25NO2: 347.4501; Found m/z (relative intensity):
347.1869 (M+, 100).
4.3.1.2.
pent-3-enyl)benzenamine (1a). IR (neat) 3387 (w), 2831
(w), 1605 (w), 1512 (s), 1242 (s), 1034 (m) cmꢃ1 1H
(E)-4-Methoxy-N-(3-methyl-1,5-diphenyl-
4.3.1.6. (E)-4-Fluoro-N-(3-methyl-1,5-diphenylpent-3-
enyl)benzenamine (1e). IR (neat) 3402 (w), 3024 (w), 2916
(w), 1605 (w), 1512 (s), 1219 (m) cmꢃ1; 1H NMR (CDCl3,
400 MHz) d 1.76 (s, 3H), 2.34 (dd, J¼13.8, 10.1 Hz, 1H),
2.54 (dd, J¼13.8, 4.6 Hz, 1H), 3.34 (dd, J¼15.4, 7.4 Hz,
1H), 3.44 (dd, J¼15.4, 7.4 Hz, 1H), 3.99 (br s, 1H), 4.30
(dd, J¼10.1, 4.6 Hz, 1H), 5.51 (br t, J¼7.4 Hz, 1H), 6.29
(d, J¼8.9 Hz, 1H), 6.30 (d, J¼8.9 Hz, 1H), 6.74 (t,
J¼8.9 Hz, 2H), 7.13–7.36 (m, 10H); 13C NMR (CDCl3,
100 MHz) d 15.7, 34.3, 50.0, 56.3, 114.0, 114.1, 115.1,
115.3, 125.8, 126.0, 127.7, 128.1, 128.4, 128.5, 132.7,
141.0, 143.9, 154.4, 156.7; HRMS calcd for C24H24FN:
345.1893; Found m/z (relative intensity): 345.1894 (M+,
100).
;
NMR (CDCl3, 400 MHz) d 1.76 (s, 3H), 2.34 (dd, J¼13.7,
10.1 Hz, 1H), 2.52 (dd, J¼13.7, 4.5 Hz, 1H), 3.34 (dd,
J¼15.4, 7.4 Hz, 1H), 3.44 (dd, J¼15.4, 7.4 Hz, 1H), 3.67
(s, 3H), 3.87 (br s, 1H), 4.30 (dd, J¼10.1, 4.5 Hz, 2H),
5.53 (t, J¼7.4 Hz, 1H), 6.34 (d, J¼8.9 Hz, 2H), 6.64 (d,
J¼8.9 Hz, 2H), 7.12–7.38 (m, 10H); 13C NMR (CDCl3,
100 MHz) d 15.7, 34.3, 50.0, 55.7, 56.5, 114.4, 114.6,
125.8, 126.0, 126.7, 127.6, 128.2, 128.4, 132.9, 141.0,
141.9, 144.6, 151.8; HRMS calcd for C25H27NO:
357.2093; Found m/z (relative intensity): 357.2100 (M+,
100).
4.3.1.3. (E)-4-Methyl-N-(3-methyl-1,5-diphenylpent-
3-enyl)benzenamine (1b). IR (neat) 3395 (w), 3024 (m),
4.3.1.7. (E)-2-Chloro-N-(3-methyl-1,5-diphenylpent-
3-enyl)benzenamine (1f). IR (neat) 3395 (w), 3024 (w),
2916 (m), 1620 (m), 1520 (s), 1450 (m), 1304 (m) cmꢃ1
;
2924 (w), 1597 (s), 1504 (s), 1450 (m), 1319 (m) cmꢃ1
;
1H NMR (CDCl3, 400 MHz) d 1.76 (s, 3H), 2.17 (s, 3H),
2.42 (dd, J¼13.7, 10.2 Hz, 1H), 2.54 (dd, J¼13.7, 4.6 Hz,
1H), 3.33 (dd, J¼15.4, 7.3 Hz, 1H), 3.44 (dd, J¼15.4,
7.3 Hz, 1H), 3.99 (br s, 1H), 4.34 (dd, J¼10.2, 4.6 Hz,
1H), 5.51 (t, J¼7.3 Hz, 1H), 6.32 (d, J¼8.5 Hz, 1H), 6.86
(d, J¼8.5 Hz, 1H), 7.13–7.37 (m, 10H); 13C NMR (CDCl3,
100 MHz) d 15.7, 20.4, 34.4, 50.1, 56.0, 113.5, 125.9,
1H NMR (CDCl3, 400 MHz) d 1.74 (s, 3H), 2.46 (dd,
J¼13.7, 9.8 Hz, 1H), 2.60 (dd, J¼13.7, 4.6 Hz, 1H), 3.40
(d, J¼6.9 Hz, 2H), 4.44 (dt, J¼9.8, 4.6 Hz, 1H), 4.88 (d,
J¼2.9 Hz, 1H), 5.55 (br t, J¼6.9 Hz, 1H), 6.32 (d,
J¼7.8 Hz, 1H), 6.54 (t, J¼7.8 Hz, 1H), 6.90 (t, J¼7.8 Hz,
1H), 7.14–7.36 (m, 11H); 13C NMR (CDCl3, 100 MHz)
d 15.8, 34.4, 50.0, 55.8, 112.6, 117.1, 119.4, 125.8, 126.0,

K. Kojima et al. / Tetrahedron 62 (2006) 7512–7520
7517
127.0, 127.4, 127.9, 128.3, 128.4, 128.7, 128.8, 132.5, 140.8,
143.3, 143.7; HRMS calcd for C24H24ClN: 361.1597; Found
m/z (relative intensity): 361.1581 (M+, 100).
387.2198; Found m/z (relative intensity): 387.2195 (M+,
100).
4.3.1.12. (E)-1-p-Anisylamino-3-methyl-5-phenyl-1-
[(2-phenyl)phenyl]-3-pentene (1k). IR (neat) 3387 (w),
3024 (m), 2909 (m), 1597 (w), 1512 (s), 1242 (s), 1042 (m)
4.3.1.8. (E)-4-Chloro-N-(3-methyl-1,5-diphenylpent-
3-enyl)benzenamine (1g). IR (neat) 3402 (w), 3024 (w),
1
1
2916 (w), 1597 (s), 1497 (s), 1312 (m) cmꢃ1; H NMR
cmꢃ1; H NMR (CDCl3, 400 MHz) d 1.30 (s, 3H), 2.12
(CDCl3, 400 MHz) d 1.76 (s, 3H), 2.33 (dd, J¼13.7,
10.1 Hz, 1H), 2.55 (dd, J¼13.7, 4.3 Hz, 1H), 3.35 (dd,
J¼15.4, 7.4 Hz, 1H), 3.44 (dd, J¼15.4, 7.4 Hz, 1H), 4.10
(br s, 1H), 4.33 (m, 1H), 5.51 (br t, J¼7.4 Hz, 1H), 6.29
(d, J¼8.9 Hz, 1H), 6.97 (d, J¼8.9 Hz, 1H), 7.12–7.34 (m,
10H); 13C NMR (CDCl3, 100 MHz) d 15.7, 34.4, 49.9,
55.9, 114.5, 118.1, 118.8, 121.5, 121.9, 126.0, 127.0,
127.98, 128.2, 128.5, 128.6, 128.7, 129.2, 129.4, 132.7,
141.0, 143.8, 146.1; HRMS calcd for C24H24ClN:
361.1597; Found m/z (relative intensity): 361.1590 (M+,
100).
(dd, J¼13.7, 10.6 Hz, 1H), 2.41 (br d, 1H), 3.24 (dd,
J¼15.3, 7.3 Hz, 1H), 3.36 (dd, J¼15.3, 7.3 Hz, 1H), 3.69
(s, 3H), 3.74 (br s, 1H), 4.47 (dd, J¼10.6, 3.4 Hz, 1H), 5.43
(br t, J¼7.3 Hz, 1H), 6.31 (d, J¼8.8 Hz, 2H), 6.65 (d,
J¼8.8 Hz, 2H), 7.09 (d, J¼7.1 Hz, 2H), 7.16–7.44 (m,
11H), 7.58 (d, J¼7.1 Hz, 1H); 13C NMR (CDCl3,
100 MHz) d 15.7, 34.3, 50.1, 55.2, 55.7, 56.0, 113.9, 114.5,
114.6, 125.8, 127.1, 127.4, 128.2, 128.4, 133.0, 136.6,
141.0, 142.0, 151.8, 158.3; HRMS calcd for C31H31NO:
433.2406; Found m/z (relative intensity): 433.2413 (M+,
100), 432 (6).
4.3.1.9. (E)-4-Bromo-N-(3-methyl-1,5-diphenylpent-
3-enyl)benzenamine (1h). IR (neat) 3402 (w), 3024 (w),
4.3.1.13. (E)-N-(1-(4-Chlorophenyl)-3-methyl-5-phe-
nylpent-3-enyl)-4-methoxybenzenamine (1l). IR (neat)
3384 (w), 2831–3026 (w), 1601 (w), 1512 (s), 1238 (m),
1
2916 (w), 1597 (m), 1497 (s), 1312 (m) cmꢃ1; H NMR
1
(CDCl3, 400 MHz) d 1.75 (s, 3H), 2.33 (dd, J¼13.7,
10.2 Hz, 1H), 2.55 (dd, J¼13.7, 4.1 Hz, 1H), 3.33 (dd,
J¼15.2, 7.4 Hz, 1H), 3.44 (dd, J¼15.4, 7.4 Hz, 1H), 4.11
(br s, 1H), 4.32 (m, 1H), 5.51 (br t, J¼7.4 Hz, 1H), 6.24
(d, J¼8.8 Hz, 1H), 7.10 (d, J¼8.8 Hz, 1H), 7.13 (d,
J¼7.6 Hz, 2H) 7.18–7.33 (m, 8H); 13C NMR (CDCl3,
100 MHz) d 15.6, 34.3, 49.8, 55.7, 114.9, 125.9, 126.9,
127.9, 128.1, 128.4, 128.6, 131.5, 132.6, 140.9, 143.6,
146.4; HRMS calcd for C24H24BrN: 405.1092; Found m/z
(relative intensity): 405.1094 (M+, 100).
1038 (w) cmꢃ1; H NMR (CDCl3, 400 MHz) d 1.74 (s,
3H), 2.32 (dd, J¼13.5, 9.8 Hz, 1H), 2.48 (dd, J¼13.5,
4.7 Hz, 1H), 3.33 (dd, J¼15.3, 7.4 Hz, 1H), 3.42 (dd,
J¼15.3, 7.4 Hz, 1H), 3.67 (s, 3H), 4.27 (dd, J¼9.8, 4.7 Hz,
1H), 5.48 (t, J¼7.4 Hz, 1H), 6.33 (d, J¼8.8 Hz, 2H), 6.65
(d, J¼8.8 Hz, 2H), 7.12 (d, J¼7.5 Hz, 2H), 7.20 (t,
J¼7.5 Hz, 1H), 7.27 (d, J¼8.0 Hz, 4H), 7.28 (t, J¼7.5 Hz,
2H); 13C NMR (CDCl3, 100 MHz) d 15.7, 34.3, 49.8, 55.6,
55.7, 56.1, 56.2, 114.6, 125.8, 127.5, 127.9, 128.0, 128.4,
128.6, 132.3, 132.4, 140.9, 141.3, 143.0, 152.1; HRMS calcd
for C25H26ClNO: 391.1703; Found m/z (relative intensity):
391.1738 (M+, 10), 282 (3), 249 (10), 248 (66), 247 (32),
246 (100).
4.3.1.10. (E)-4-Methoxy-N-(3-methyl-5-phenyl-1-p-
tolylpent-3-enyl)benzenamine (1i). IR (neat) 3386 (w),
2831 (m), 1605 (w), 1512 (s), 1242 (s), 1034 (m) cmꢃ1
;
1H NMR (CDCl3, 400 MHz) d 1.75 (s, 3H), 2.32 (s, 3H),
2.33 (dd, J¼13.5, 10.1 Hz, 1H), 2.50 (dd, J¼13.5, 4.7 Hz,
1H), 3.34 (dd, J¼15.4, 7.5 Hz, 1H), 3.43 (dd, J¼15.4,
7.5 Hz, 1H), 3.68 (s, 3H), 4.27 (dd, J¼10.1, 4.7 Hz, 1H),
5.50 (br t, J¼7.5 Hz, 1H), 6.35 (d, J¼8.8 Hz, 2H), 6.64 (d,
J¼8.8 Hz, 2H), 7.09–7.30 (m, 9H); 13C NMR (CDCl3,
100 MHz) d 15.7, 34.3, 50.1, 55.7, 56.2, 114.4, 114.6,
125.8, 125.9, 127.4, 128.2, 128.4, 129.1, 133.0, 136.1,
141.0, 141.6, 142.0, 151.8; HRMS calcd for C26H30NO:
371.2249; Found m/z (relative intensity): 371.2259 (M+,
100).
4.3.1.14. (E)-N-(1-(2-Fluorophenyl)-3-methyl-5-phe-
nylpent-3-enyl)-4-methoxybenzenamine (1m). IR (neat)
3387 (w), 3024 (m), 2909 (m), 1589 (w), 1512 (s), 1242
1
(s), 1042 (m) cmꢃ1; H NMR (CDCl3, 400 MHz) d 1.77
(s, 3H), 2.33 (dd, J¼13.5, 9.7 Hz, 1H), 2.62 (dd, J¼13.5,
4.8 Hz, 1H), 3.33 (dd, J¼15.4, 7.5 Hz, 1H), 3.42 (dd,
J¼15.4, 7.5 Hz, 1H), 3.68 (s, 3H), 3.82 (br s, 1H), 4.70
(dd, J¼9.7, 4.8 Hz, 1H), 5.47 (br t, J¼7.5 Hz, 1H), 6.37
(d, J¼9.0 Hz, 2H), 6.66 (d, J¼9.0 Hz, 2H), 6.68–7.41 (m,
9H); 13C NMR (CDCl3, 100 MHz) d 15.6, 34.3, 47.7, 50.1,
55.2, 55.7, 56.0, 114.3, 114.6, 115.1, 115.3, 124.2, 124.3,
125.8, 127.5, 127.6, 127.7, 128.07, 128.13, 128.4, 130.9,
131.0, 132.8, 141.0, 141.4, 152.0, 159.0, 161.5; HRMS calcd
for C25H26FNO: 375.1998; Found m/z (relative intensity):
375.1976 (M+, 100).
4.3.1.11. (E)-4-Methoxy-N-(1-(4-methoxyphenyl)-3-
methyl-5-phenylpent-3-enyl)benzenamine (1j). IR (neat)
3384 (w), 2833–3026 (m), 1610 (w), 1512 (s), 1240 (s),
1
1035 (m) cmꢃ1; H NMR (CDCl3, 400 MHz) d 1.75 (s,
3H), 2.33 (dd, J¼13.5, 9.9 Hz, 1H), 2.49 (dd, J¼13.5,
4.7 Hz, 1H), 3.34 (dd, J¼15.4, 7.4 Hz, 1H), 3.43 (dd,
J¼15.4, 7.4 Hz, 1H), 3.68 (s, 3H), 3.78 (s, 3H), 3.85 (br s,
1H), 4.26 (dd, J¼9.9, 4.7 Hz, 1H), 5.49 (br t, J¼7.4 Hz,
1H), 6.35 (d, J¼9.0 Hz, 2H), 6.50 (d, J¼9.0 Hz, 2H), 6.50
(d, J¼9.0 Hz, 2H), 6.83 (d, J¼8.8 Hz, 1H), 7.14 (d,
J¼7.2 Hz, 2H), 7.20 (t, J¼7.2 Hz, 1H), 7.27 (d, J¼8.8 Hz,
2H), 7.28 (t, J¼7.2 Hz, 2H); 13C NMR (CDCl3, 100 MHz)
d 15.7, 34.3, 50.1, 55.2, 55.7, 56.0, 113.9, 114.5, 114.6,
125.8, 127.1, 127.4, 128.2, 128.4, 133.0, 136.6, 141.0,
142.0, 151.8, 158.3; HRMS calcd for C26H29NO2:
4.3.1.15. (E)-N-(1-(4-Fluorophenyl)-3-methyl-5-phe-
nylpent-3-enyl)-4-methoxybenzenamine (1n). IR (neat)
3387 (w), 2924 (m), 1605 (w), 1512 (s), 1234 (s), 1034
1
(m) cmꢃ1; H NMR (CDCl3, 400 MHz) d 1.75 (s, 3H),
2.32 (dd, J¼13.8, 9.9 Hz, 1H), 2.48 (dd, J¼13.8, 4.9 Hz,
1H), 3.34 (dd, J¼15.4, 7.4 Hz, 1H), 3.43 (dd, J¼15.4,
7.4 Hz, 1H), 3.68 (s, 3H), 3.86 (br s, 1H), 4.28 (dd, J¼9.9,
4.9 Hz, 1H), 5.49 (br t, J¼7.4 Hz, 1H), 6.32 (d, J¼9.0 Hz,
2H), 6.65 (d, J¼9.0 Hz, 2H), 6.97 (t, J¼8.6 Hz, 2H), 7.13
(d, J¼8.6 Hz, 2H), 7.19–7.33 (m, 5H); 13C NMR (CDCl3,
100 MHz) d 15.8, 34.4, 50.2, 55.8, 56.0, 114.6, 114.7,

7518
K. Kojima et al. / Tetrahedron 62 (2006) 7512–7520
115.2, 115.5, 125.9, 127.50, 127.53, 127.6, 127.8, 127.9,
128.2, 128.5, 132.7, 140.25, 140.27, 141.0, 141.8, 152.0,
160.5, 162.9; HRMS calcd for C25H26FNO: 375.1998;
Found m/z (relative intensity): 375.1988 (M+, 100).
4.4. New compounds listed in Table 2
4.4.1. A typical procedure for the four-component con-
nection reaction of Ph2Zn, isoprene, tetrahydro-2H-
pyran-2-ol, and p-anisidine (run 5, Table 2). Into a N2
purged two-necked round-bottomed flask containing p-anisi-
dine (246 mg, 2.0 mmol), were added dry THF (2.0 mL) and
2-hydroxytetrahydropyran (102 mg, 1.0 mmol) via syringe.
The mixture was stirred at room temperature. 2-p-Anisidyl-
tetrahydropyran was detected by TLC (Rf ¼0.56, n-hexane/
ethyl acetate ¼ 2:1, v/v). A solution of Ni(acac)2 (25.7 mg,
0.1 mmol) in THF (3.0 mL) was introduced into the lact-
amine solution via a cannula. Isoprene (400 ml, 4.0 mmol)
and a Ph2Zn solution (14.4 mL, 0.25 M, 3.6 mmol) were suc-
cessively introduced via syringe and the homogeneous mix-
ture was stirred for 2 h at room temperature. The reaction
mixture was poured into ice-water (20 mL) and extracted
with 30 mL of ethyl acetate. The water phase was extracted
with ethyl acetate (2ꢂ20 mL). The combined organic ex-
tracts were washed with 2 M HCl (20 mL) and with satd
NaHCO3 (25 mL), and then dried (MgSO4) and concentrated
in vacuo. The residue was subjected to column chromato-
graphy over silica gel (eluent: n-hexane/ethyl acetate ¼ 8:1,
v/v) to give 5b (Rf ¼0.66, n-hexane/ethyl acetate ¼ 2:1, v/v)
in 76% yield as a single isomer.
4.3.1.16. (E)-4-Chloro-N-(1-(furan-2-yl)-3-methyl-5-
phenylpent-3-enyl)benzenamine (1p). IR (neat) 3408
(w), 3026–2853 (w), 1601 (m), 1499 (s), 1313 (s), 1005 (s)
1
cmꢃ1; H NMR (CDCl3, 400 MHz) d 1.68 (s, 3H), 2.51
(dd, J¼13.6, 8.7 Hz, 1H), 2.67 (dd, J¼13.6, 5.7 Hz, 1H),
3.33 (dd, J¼15.7, 7.7 Hz, 1H), 3.39 (dd, J¼15.7, 7.7 Hz,
1H), 3.93 (br s, 1H), 4.50 (dd, J¼8.7, 5.7 Hz, 1H), 5.48 (br
t, J¼7.7 Hz, 1H), 6.12 (d, J¼3.3 Hz, 1H), 6.27 (dd, J¼3.3,
1.8 Hz, 1H), 6.42 (d, J¼8.8 Hz, 2H), 7.05 (d, J¼8.8 Hz,
2H), 7.13 (d, J¼7.5 Hz, 2H), 7.19 (t, J¼7.5 Hz, 1H), 7.26
(d, J¼7.5 Hz, 2H), 7.32 (d, J¼7.5 Hz, 1H); 13C NMR
(CDCl3, 100 MHz) d 15.7, 34.3, 45.6, 50.4, 106.0, 110.2,
114.5, 122.4, 126.0, 127.9, 128.3, 128.6, 128.9, 132.1,
141.1, 141.5, 146.0, 155.9; HRMS calcd for C22H22ClNO:
351.139; Found m/z (relative intensity): 351.13850 (M+,
100).
4.3.1.17. (E)-4-Methoxy-N-(3-methyl-1-phenyldodec-
2-en-5-yl)benzenamine (1q). IR (neat) 3395 (w), 2924 (s),
1
1604 (w), 1512 (s), 1242 (m), 1041 (w) cmꢃ1; H NMR
(CDCl3, 400 MHz, a major isomer is assigned) d 0.87 (t,
J¼6.9 Hz, 3H), 1.26–1.51 (m, 12H), 1.71 (s, 3H), 2.22 (d,
J¼5.9 Hz, 2H), 3.35 (d, J¼7.3 Hz, 3H), 3.74 (br s, 1H),
5.40 (t, J¼7.3 Hz, 1H), 6.51 (d, J¼8.8 Hz, 2H), 6.75 (d,
J¼8.8 Hz, 2H), 7.13–7.28 (m, 5H); 13C NMR (CDCl3,
100 MHz) d 14.1, 16.3, 22.6, 25.8, 29.3, 29.8, 31.8, 34.3,
34.9, 45.3, 46.4, 52.3, 55.8, 114.5, 125.6, 126.1, 128.2,
128.3, 133.5, 141.3; HRMS calcd for C26H37NO: 379.2875;
Found m/z (relative intensity): 379.2799 (M+, 100).
4.4.1.1. (E)-5-(4-Methoxyphenylamino)-7-methyl-9-
phenylnon-7-en-1-ol (5b). IR (neat) 3387 (m), 2932 (s),
1736 (m), 1512 (s), 1450 (m), 1242 (s), 1042 (m), 818
1
(m), 741 (w) cmꢃ1; H NMR (CDCl3, 400 MHz) d 1.24–
1.59 (m, 7H), 1.71 (s, 3H), 2.23 (d, J¼6.2 Hz, 2H), 3.35
(d, J¼7.4 Hz, 2H), 3.39 (t, J¼6.2 Hz, 1H), 3.60 (t,
J¼6.3 Hz, 2H), 3.74 (s, 3H), 5.40 (t, J¼7.4 Hz, 1H), 6.50
(d, J¼8.9 Hz, 2H), 6.75 (d, J¼8.9 Hz, 2H), 7.14 (d,
J¼7.5 Hz, 2H), 7.17 (t, J¼7.5 Hz, 1H), 7.26 (t, J¼7.5 Hz,
2H); 13C NMR (CDCl3, 100 MHz) d 16.4, 22.0, 32.9, 34.4,
34.7, 45.4, 52.1, 55.9, 62.8, 114.4, 115.0, 125.7, 126.3,
128.2, 128.4, 133.5, 141.3, 142.2, 151.7; HRMS calcd for
C23H31NO2: 353.2355; Found m/z (relative intensity):
353.2350 (M+, 100).
4.3.1.18. (E)-N-(2,5-Dimethyl-7-phenylhept-5-en-3-yl)-
4-methoxybenzenamine (1r). A mixture of 1r and 1r0 in
a ratio of 2:1; IR (neat) 3402 (w), 2955 (m), 1605 (w),
1512 (s), 1234 (m), 1041 (w) cmꢃ1 1H NMR (CDCl3,
;
400 MHz) d 0.90 (d, J¼6.9 Hz, 3H), 0.95 (d, J¼6.9 Hz,
3H), 1.67 (s, 3H), 1.96 (br hept, J¼6.9 Hz, 1H), 2.05 (dd,
J¼13.7, 9.5 Hz, 1H), 2.27 (dd, J¼13.7, 4.6 Hz, 1H), 3.29
(ddm, J¼9.5, 4.6 Hz, 1H), 3.30 (m, 1H, coalescing to d,
J¼15.0 Hz by irradiation at 5.40), 3.35 (m, 1H, coalescing
to d, J¼15.0 Hz by irradiation at 5.40), 3.74 (s, 3H), 5.40
(t, J¼7.6 Hz, 1H), 6.49 (d, J¼8.8 Hz, 2H), 6.74 (d,
J¼8.8 Hz, 2H), 7.09–7.27 (m, 5H); 13C NMR (CDCl3,
100 MHz) d 16.1, 18.07, 18.15, 30.7, 34.4, 41.5, 55.9,
56.9, 114.1, 114.9, 125.7, 126.0, 128.2, 128.3, 133.9,
136.3, 140.2, 141.3, 142.9, 151.4.
4.4.1.2. (E)-4-(4-Methoxyphenylamino)-6-methyl-8-
phenyloct-6-en-1-ol (4a). IR (neat) 3379 (m), 2931 (s),
1604 (m), 1512 (s), 1450 (m), 1234 (w), 740 (s), 702 (s)
1
cmꢃ1; H NMR (CDCl3, 400 MHz) d 1.44–1.66 (m, 4H),
1.69 (s, 3H), 2.16 (dd, J¼6.9, 13.8 Hz, 1H), 2.25 (dd,
J¼6.9, 13.8 Hz, 1H), 2.79 (s, 1H), 3.34 (d, J¼7.1 Hz, 2H),
3.39 (dd, J¼4.4, 6.9 Hz, 1H), 3.56 (t, J¼6.2 Hz, 2H), 3.71
(s, 3H), 5.39 (t, J¼7.1 Hz, 1H), 6.51–7.25 (m, 9H); 13C
NMR (CDCl3, 100 MHz) d 16.3, 29.2, 31.6, 34.3, 45.3,
51.5, 55.7, 62.8, 114.8, 115.0, 125.7, 126.4, 128.1, 128.3,
133.2, 141.2, 141.7, 152.0; HRMS calcd for C22H29NO2:
339.2198; Found m/z (relative intensity): 339.2178 (M+,
100).
4.3.1.19. (E)-N-(2,6-Dimethyl-7-phenylhept-5-en-3-
yl)-4-methoxybenzenamine (1r0). 1H NMR (CDCl3,
400 MHz) d 0.94 (d, J¼6.8 Hz, 3H), 0.97 (d, J¼6.8 Hz,
3H), 1.51 (s, 3H), 1.89 (dhept, J¼4.9, 6.8 Hz, 1H), 2.15
(dt, J¼14.5, 7.3 Hz, 1H), 2.27 (dm, J¼14.5 Hz, 1H), 3.15
(dt, J¼7.3, 4.9 Hz, 1H), 3.26 (s, 2H), 3.74 (s, 3H), 5.30 (t,
J¼7.3 Hz, 1H), 6.52 (d, J¼8.9 Hz, 2H), 6.75 (d, J¼8.9 Hz,
2H), 7.09–7.27 (m, 5H); 13C NMR (CDCl3, 100 MHz)
d 16.1, 18.5, 18.9, 30.1, 31.1, 46.5, 59.8, 114.3, 114.9,
123.3, 125.9, 128.1, 128.7, 133.9, 140.2, 141.3, 142.9,
151.4; HRMS calcd for C22H29NO: 323.2249; Found m/z
(relative intensity): 323.2233 (M+, 100).
4.4.1.3. (E)-6-Methyl-8-phenyl-4-(phenylamino)oct-6-
en-1-ol (4b). IR (neat) 3394 (m), 2931 (s), 1604 (m), 1504
1
(s), 1434 (m), 1319 (w), 748 (s), 694 (s) cmꢃ1; H NMR
(CDCl3, 400 MHz) d 1.50–1.70 (m, 4H), 1.72 (s, 3H), 2.22
(dd, J¼6.9, 13.5 Hz, 1H), 2.27 (dd, J¼6.9, 13.5 Hz, 1H),
3.35 (dd, J¼2.4, 7.4 Hz, 2H), 3.53 (dd, J¼4.6, 6.9 Hz,
1H), 3.62 (t, J¼6.0 Hz, 2H), 5.41 (t, J¼7.4 Hz, 1H), 6.54–
7.25 (m, 9H); 13C NMR (CDCl3, 100 MHz) d 16.4, 29.2,

K. Kojima et al. / Tetrahedron 62 (2006) 7512–7520
7519
1
31.4, 34.4, 45.5, 51.2, 63.0, 113.2, 117.1, 125.7, 126.5,
128.2, 128.4, 129.2, 133.2, 141.2, 147.7; HRMS calcd for
C21H27NO: 309.2093; Found m/z (relative intensity):
309.2074 (M+, 100).
1620 (m), 1520 (s), 1450 (m), 1335 (m), 740 (s) cmꢃ1; H
NMR (CDCl3, 400 MHz) d 1.26–1.64 (m, 7H), 1.71 (s,
3H), 2.26 (d, J¼6.3 Hz, 2H), 3.34 (d, J¼7.3 Hz, 2H), 3.52
(t, J¼6.3 Hz, 1H), 5.41 (t, J¼7.3 Hz, 2H), 6.56 (q,
J¼7.6 Hz, 1H), 6.67 (t, J¼8.5 Hz, 1H), 6.92 (d, J¼8.5 Hz,
1H), 6.95 (t, J¼7.3 Hz, 1H), 7.12 (d, J¼7.3 Hz, 2H), 7.16
(t, J¼7.3 Hz, 1H), 7.25 (t, J¼7.3 Hz, 2H); 13C NMR
(CDCl3, 100 MHz) d 16.3, 22.0, 32.7, 34.2, 34.7, 45.4,
51.0, 62.7, 111.9, 111.94, 114.3, 114.5, 115.7, 115.8,
124.36, 124.39, 125.6, 126.4, 128.1, 128.2, 132.9, 136.2,
136.4, 141.1, 150.2, 152.6; HRMS calcd for C22H28FNO:
341.2155; Found m/z (relative intensity): 341.2141 (M+,
100).
4.4.1.4. (E)-4-(4-Chlorophenylamino)-6-methyl-8-
phenyloct-6-en-1-ol (4c). IR (neat) 3402 (m), 2931 (s),
1596 (s), 1496 (s), 1450 (w), 1056 (w), 740 (s), 702 (s)
1
cmꢃ1; H NMR (CDCl3, 400 MHz) d 1.50–1.68 (m, 4H),
1.71 (s, 3H), 2.21 (d, J¼6.8 Hz, 2H), 3.36 (dd, J¼6.8,
15.6 Hz, 2H), 3.46 (dd, J¼6.8, 10.0 Hz, 1H), 3.62 (t,
J¼6.0 Hz, 2H), 5.40 (t, J¼6.8 Hz, 1H), 6.44–7.23 (m, 9H);
13C NMR (CDCl3, 100 MHz) d 16.3, 29.0, 31.4, 34.4,
45.4, 51.4, 62.9, 114.1, 121.5, 125.8, 126.8, 128.2, 129.0,
133.0, 141.2, 146.4; HRMS calcd for C21H26ClNO:
343.1703; Found m/z (relative intensity): 343.1696 (M+,
83), 267 (100).
4.4.1.9. (E)-5-(4-Fluorophenylamino)-7-methyl-9-
phenylnon-7-en-1-ol (5f). IR (neat) 3395 (s), 2932 (s),
1
1647 (w), 1512 (s), 1450 (w), 1219 (m) cmꢃ1; H NMR
(CDCl3, 400 MHz) d 1.26–1.57 (m, 6H), 1.70 (s, 3H), 2.21
(t, J¼6.2 Hz, 2H), 3.34 (d, J¼7.1 Hz, 2H), 3.39 (t,
J¼6.2 Hz, 1H), 3.57 (t, J¼6.3 Hz, 2H), 5.39 (t, J¼7.1 Hz,
1H), 6.43 (dd, J¼8.8, 4.4 Hz, 2H), 6.83 (t, J¼8.8 Hz, 2H),
7.12 (d, J¼7.3 Hz, 2H), 7.16 (t, J¼7.3 Hz, 1H), 7.24 (t,
J¼7.3 Hz, 2H); 13C NMR (CDCl3, 100 MHz) d 16.3, 22.0,
32.7, 34.3, 34.7, 45.3, 51.9, 62.6, 113.6, 113.7, 115.4,
115.6, 125.7, 126.4, 128.1, 128.3, 133.2, 141.2, 144.24,
144.26, 154.1, 156.5; HRMS calcd for C22H28FNO:
341.2155; Found m/z (relative intensity): 341.2146 (M+,
100).
4.4.1.5. (E)-5-(2-Methoxyphenylamino)-7-methyl-9-
phenylnon-7-en-1-ol (5a). IR (neat) 3418 (m), 2932 (s),
1597 (m), 1512 (s), 1458 (m), 1227 (m), 1034 (m), 733 (s)
1
cmꢃ1; H NMR (CDCl3, 400 MHz) d 1.24–1.59 (m, 7H),
1.72 (s, 3H), 2.23 (dd, J¼13.6, 6.8 Hz, 1H), 2.30 (dd,
J¼13.6, 6.8 Hz, 1H), 3.34 (d, J¼7.3 Hz, 2H), 3.50 (t,
J¼6.8 Hz, 1H), 3.59 (t, J¼6.1 Hz, 2H), 3.77 (s, 3H), 5.41
(t, J¼7.3 Hz, 1H), 6.59 (dd, J¼7.7, 1.3 Hz, 1H), 6.61 (dd,
J¼7.7, 1.3 Hz, 1H), 6.74 (dd, J¼7.7, 1.3 Hz, 1H), 6.83 (dt,
J¼7.7, 1.3 Hz, 1H), 7.12–7.17 (m, 3H), 7.22–7.26 (t, J¼
7.5, 2H); 13C NMR (CDCl3, 100 MHz) d 16.5, 22.0, 32.9,
34.3, 34.6, 45.4, 50.9, 55.4, 62.9, 109.6, 109.7, 115.6,
121.2, 125.6, 126.0, 128.2, 128.3, 133.4, 137.8, 141.3,
146.7; HRMS calcd for C23H31NO2: 353.2355; Found m/z
(relative intensity): 353.2356 (M+, 100).
4.4.1.10. (E)-5-(2-Chlorophenylamino)-7-methyl-9-
phenylnon-7-en-1-ol (5g). IR (neat) 3410 (s), 2932 (s),
1597 (s), 1512 (s), 1458 (m), 1327 (m), 1034 (m), 741 (s),
1
694 (m) cmꢃ1; H NMR (CDCl3, 400 MHz) d 1.22–1.67
(m, 7H), 1.72 (s, 3H), 2.29 (d, J¼6.3 Hz), 3.34 (d,
J¼7.3 Hz, 2H), 3.55 (q, J¼6.3 Hz, 1H), 3.61 (t, J¼5.7 Hz,
2H), 4.15 (d, J¼7.3 Hz, 1H), 5.43 (t, J¼7.3 Hz, 1H), 6.57
(t, J¼7.6 Hz, 1H), 6.63 (d, J¼7.6 Hz, 1H) 7.07–7.18 (m,
3H), 7.21–7.26 (m, 2H); 13C NMR (CDCl3, 100 MHz)
d 16.4, 22.0, 32.8, 34.4, 34.6, 45.3, 51.2, 62.8, 111.1,
116.5, 119.1, 125.7, 126.6, 128.2, 128.3, 129.2, 132.9,
141.2, 143.6; HRMS calcd for C22H28ClNO: 357.1859;
Found m/z (relative intensity): 357.1848 (M+, 100).
4.4.1.6. (E)-7-Methyl-9-phenyl-5-(phenylamino)non-
7-en-1-ol (5c). IR (neat) 3400 (m), 2934 (s), 1601 (s),
1504 (s), 1452 (w), 1431 (w), 1072 (w), 746 (s), 694 (s)
1
cmꢃ1; H NMR (CDCl3, 400 MHz) d 1.40–1.61 (m, 7H),
1.72 (s, 3H), 2.24 (d, J¼6.1 Hz, 2H), 3.35 (d, J¼7.3 Hz,
2H), 3.50 (t, J¼6.1 Hz, 1H), 3.60 (t, J¼6.2 Hz, 2H), 5.41
(t, J¼7.3 Hz, 1H), 6.53 (d, J¼8.1 Hz, 2H), 6.65 (t,
J¼7.3 Hz, 1H), 7.12–7.15 (m, 5H), 7.24–7.28 (m, 2H); 13C
NMR (CDCl3, 100 MHz) d 16.3, 21.9, 32.8, 34.3, 34.6,
45.3, 51.0, 62.8, 112.8, 116.7, 125.7, 126.3, 128.2, 128.3,
129.1, 133.3, 141.2, 147.8; HRMS calcd for C22H29NO:
323.2249; Found m/z (relative intensity): 324.2247 (M+,
22), 323 (46).
4.4.1.11. (E)-5-(4-Chlorophenylamino)-7-methyl-9-
phenylnon-7-en-1-ol (5h). IR (neat) 3404 (m), 2936 (s),
1599 (s), 1497 (s) 1319 (m), 814 (m), 743 (m), 698 (s)
1
cmꢃ1; H NMR (CDCl3, 400 MHz) d 1.39–1.58 (m, 6H),
1.71 (s, 3H), 2.19 (d, J¼13.7, 7.6 Hz, 1H), 2.26 (dd,
J¼13.7, 6.0 Hz, 1H), 3.34 (dd, J¼7.3 Hz, 2H), 3.43 (dd,
J¼7.6, 6.0 Hz, 1H), 3.60 (t, J¼6.3 Hz, 2H), 5.40 (t, J¼
7.3 Hz, 1H), 6.43 (d, J¼8.8 Hz, 2H), 7.06 (d, J¼8.8 Hz,
2H), 7.12 (d, J¼7.3 Hz, 2H), 7.17 (t, J¼7.3 Hz, 1H), 7.25
(t, J¼7.3 Hz, 2H); 13C NMR (CDCl3, 100 MHz) d 16.3,
22.0, 32.8, 34.4, 34.7, 45.3, 51.4, 62.8, 113.9, 121.2,
125.8, 126.6, 128.2, 128.4, 129.0, 133.1, 141.2, 146.5;
HRMS calcd for C22H28ClNO: 357.1859; Found m/z (rela-
tive intensity): 357.1844 (M+, 100).
4.4.1.7. (E)-4-(p-Tolylamino)-6-methyl-8-phenyloct-6-
en-1-ol (5d). IR (neat) 3394 (m), 2931 (s), 1620 (m), 1519
1
(s), 1450 (m), 1319 (w), 732 (s), 702 (s) cmꢃ1; H NMR
(CDCl3, 400 MHz) d 1.57–1.63 (m, 6H), 1.81 (s, 3H), 2.32
(d, J¼7.8 Hz, 2H), 2.32 (s, 3H), 3.44 (dd, J¼2.8, 7.3 Hz,
2H), 3.55 (dd, J¼7.8, 11.7 Hz, 1H), 3.65 (t, J¼6.3 Hz,
2H), 5.49 (t, J¼7.3 Hz, 1H), 6.54–7.25 (m, 9H); 13C NMR
(CDCl3, 100 MHz) d 15.9, 20.0, 21.6, 32.4, 34.0, 45.0,
50.1, 62.3, 112.7, 125.3, 125.5, 125.9, 127.8, 127.9, 129.3,
133.0, 140.9, 145.2; HRMS calcd for C23H31NO:
337.2406; Found m/z (relative intensity); 337.2391 (M+,
9), 64.17 (1), 192.14 (100).
4.4.1.12. (E)-5-(2-Bromophenylamino)-7-methyl-9-
phenylnon-7-en-1-ol (5i). IR (neat) 3402 (s), 2932 (m),
1597 (s), 1504 (s), 1458 (m), 1319 (m), 1281 (w), 1018
1
4.4.1.8. (E)-5-(2-Fluorophenylamino)-7-methyl-9-
phenylnon-7-en-1-ol (5e). IR (neat) 3418 (m), 2932 (s),
(w), 741 (s) cmꢃ1; H NMR (CDCl3, 400 MHz) d 1.43–
1.69 (m, 6H), 1.72 (s, 3H), 2.29 (dd, J¼6.5, 3.4 Hz, 2H),

7520
K. Kojima et al. / Tetrahedron 62 (2006) 7512–7520
Kimura, M.; Miyachi, A.; Kojima, K.; Tanaka, S.; Tamaru, Y.
J. Am. Chem. Soc. 2004, 126, 14360–14361; (d) Solin, N.;
3.35 (d, J¼7.3 Hz, 2H), 3.56 (quintet, J¼6.5 Hz, 1H), 3.61
(t, J¼6.5 Hz, 2H), 4.17 (d, J¼7.4 Hz, 2H), 5.44 (t,
J¼7.4 Hz, 1H), 6.50 (t, J¼7.6 Hz, 1H), 6.61 (d, J¼8.0 Hz,
1H), 7.11–7.18 (m, 4H), 7.24 (t, J¼7.3 Hz, 2H), 7.39 (d,
J¼8.0 Hz); 13C NMR (CDCl3, 100 MHz) d 16.5, 22.0,
32.8, 34.4, 34.6, 45.3, 51.4, 62.8, 109.9, 111.3, 117.0,
125.7, 126.7, 128.25, 128.30, 128.32, 132.5, 132.9, 141.1,
144.5; HRMS calcd for C22H28BrNO: 401.1354; Found
m/z (relative intensity): 401.1342 (M+, 100).
´
Kjellgren, J.; Szabo, K. J. J. Am. Chem. Soc. 2004, 126,
7026–7033; (e) Sakaguchi, S.; Mizuta, T.; Furuwan, M.;
Kubo, T.; Ishii, Y. Chem. Commun. 2004, 1638–1639; (f)
Davis, J. L.; Dhawan, R.; Arndtsen, B. A. Angew. Chem., Int.
Ed. 2004, 43, 590–595; (g) Patel, S. J.; Jamison, T. F. Angew.
Chem., Int. Ed. 2004, 43, 3941–3944; (h) Sebelius, S.;
´
Wallner, O. A.; Szabo, K. J. Org. Lett. 2003, 5, 3065–3068;
(i) Fernandes, R. A.; Stimac, A.; Yamamoto, Y. J. Am. Chem.
Soc. 2003, 125, 14133–14139; (j) Patel, S. J.; Jamison, T. F.
Angew. Chem., Int. Ed. 2003, 42, 1364–1367; (k) Kang,
S.-K.; Kim, K.-J.; Hong, Y.-T. Angew. Chem., Int. Ed. 2002,
41, 1584–1586.
4.4.1.13. (E)-5-(4-Bromophenylamino)-7-methyl-9-
phenylnon-7-en-1-ol (5j). IR (neat) 3402 (m), 2932 (s),
1597 (m), 1497 (s), 1450 (w), 1319 (w), 1072 (w), 741
1
(w), 694 (w) cmꢃ1; H NMR (CDCl3, 400 MHz) d 1.26–
6. Reviews: (a) Alvaro, G.; Savoia, D. Synlett 2002, 651–673; (b)
Kobayashi, S.; Ishitani, H. Chem. Rev. 1999, 99, 1069–1094.
7. (a) Ogawa, C.; Sugiura, M.; Kobayashi, S. Angew. Chem., Int.
Ed. 2004, 43, 6491–6493; (b) Marigo, M.; Kjærsgaard, A.;
Juhl, K.; Gathergood, N.; Jørgensen, K. A. Chem.—Eur. J
2003, 9, 2359–2367; (c) Niwa, Y.; Shimizu, M. J. Am. Chem.
1.49 (m, 6H), 1.63 (s, 3H), 2.11 (dd, J¼13.1, 7.6 Hz, 1H),
2.19 (dd, J¼13.1, 5.9 Hz, 1H), 3.27 (dd, J¼6.9 Hz, 4.3 Hz,
2H), 3.37 (br s, 1H), 3.53 (t, J¼6.3 Hz, 2H), 5.32 (t,
J¼6.9 Hz, 1H), 6.31 (d, J¼8.8 Hz, 2H), 7.04 (d, J¼7.3 Hz,
2H), 7.10 (t, J¼7.3 Hz, 1H), 7.12 (d, J¼8.8 Hz, 2H), 7.19
(t, J¼7.3 Hz, 2H); 13C NMR (CDCl3, 100 MHz) d 16.3,
22.0, 32.8, 34.4, 34.7, 45.3, 51.3, 62.8, 108.2, 114.3,
125.8, 126.7, 128.2, 128.4, 131.9, 141.2, 146.9; HRMS calcd
for C22H28BrNO: 401.1354; Found m/z (relative intensity):
401.1338 (M+, 100).
´
Soc. 2003, 125, 3720–3721; (d) Cordova, A.; Notz, W.;
Zhong, G.; Betancort, J. M.; Barbas, C. F., III. J. Am. Chem.
Soc. 2002, 124, 1842–1843.
8. (a) Weix, D. J.; Shi, Y.; Ellman, J. A. J. Am. Chem. Soc. 2005,
127, 1092–1093; (b) Matsui, K.; Takizawa, S.; Sasai, H. J. Am.
Chem. Soc. 2005, 127, 3680–3681; (c) Li, S.-W.; Batey, R. A.
Chem. Commun. 2004, 1382–1383; (d) Zhu, X.-F.; Lan, J.;
Kwan, O. J. Am. Chem. Soc. 2003, 125, 4716–4717; (e)
References and notes
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2. (a) Jeong, Y. C.; Ji, M.; Lee, J. J. S.; Yang, J.-D.; Jin, J.; Bail,
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G.; Lueers, S.; Schmidt, F. Synthesis 2004, 634–638; (c)
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397–400.
3. (a) Shibata, K.; Kimura, M.; Kojima, K.; Tanaka, S.; Tamaru, Y.
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K.; Tamaru, Y. Angew. Chem., Int. Ed. 1999, 38, 3386–3388;
See also: (d) Kimura, M.; Ezoe, A.; Mori, M.; Tamaru, Y.
J. Am. Chem. Soc. 2005, 127, 201–209; (e) Ezoe, A.;
Kimura, M.; Inoue, T.; Mori, M.; Tamaru, Y. Angew. Chem.,
Int. Ed. 2002, 41, 2784–2786.
Hermanns, N.; Dahmen, S.; Bohm, C.; Brase, S. Angew.
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Chem., Int. Ed. 2002, 41, 3692–3694; (f) Fujihara, H.; Magai,
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