entry 6) and n ) 1, R ) Bn (ca. 14%, entry 8)] formed
under the latter conditions was hardly separable from 7a and
7b, respectively, by conventional column chromatography.9
The formation of 8 (and also 5) as the byproduct is quite
general for all the reactions undertaken in the absence of
3-hexyne. The mechanism by which 5 and 8 is formed,
especially the origin of a hydride that might be involved for
the activation of 1,3-butadiene as a crotyl anion equivalent,
is not clear at the moment.
Table 1. Ni-Catalyzed Multicomponent Connection Reaction
of Ph2Zn, 1,3-Butadiene, Lactols, and Aminesa
The findings disclosed here clearly indicate that 3-hexyne
serves as a critical spectator ligand and effects the selective
formation of 1 and 6 for aromatic amines and 2 and 7 for
aliphatic amines.
The contrasting reactivity between Ph2Zn (yielding 1 and
6 or 2 and 7) and Me2Zn (yielding 3 or 4) may be attributed
to the lower activation energy of the reductive elimination
process of Ni(0) from III or IV (R′ ) Ph) as compared with
that from III or IV (R′ ) Me), which precludes 3-hexyne
from undergoing coordination-insertion over these Ni(II)
complexes.
entry
lactamine
alkyneb time (h) % yield 6 or 7
1
2
3
4
5
6
7
8
n ) 2, R ) PMP
n ) 2, R ) PMP
n ) 1, R ) PMP
n ) 1, R ) PMP
n ) 2, R ) Bn
n ) 2, R ) Bn
n ) 1, R ) Bn
n ) 1, R ) Bn
yes
no
3
2
4
4
4
6
4
6
6a: 71
6a: 71c
6b: 57
6b: 58c
7a: 48
7a: 71c
7b: 35
7b: 58c
yes
no
yes
no
yes
no
In summary, under the catalysis of Ni(acac)2, Ph2Zn reacts
with the aldimines of p-anisidine incorporating one molecule
of 1,3-butadiene to provide (3E)-5-phenyl-3-pentenylamines
1 or their 1-(ω-hydroxyalkyl)-substituted derivatives 6
selectively. On the other hand, under the identical conditions,
the aldimines of benzylamine selectively incorporated two
molecules of 1,3-butadiene, yielding (3E,7E)-9-phenyl-3,7-
nonadienylamines 2 or their 1-(ω-hydroxyalkyl)-substituted
derivatives 7 selectively. In these reactions, 3-hexyne serves
as a spectator ligand and bestows high selectivity upon the
reaction; otherwise, inseparable mixtures of 1, 2 and 5, 6
and 8, or 7 and 8, result. As aldehydes, aromatic aldehydes
and aliphatic aldehydes as well as ω-hydroxyaldehydes
(lactols) nicely participate in the reaction. Finally, it should
be noted that the reaction can be performed nearly at room
temperature (30 °C) in one flask without removing the water
generated during in situ preparation of aldimines and without
using any phosphine ligands. The success of nucleophilic
addition of electronically neutral 1,3-butadiene to the putative
aldimines of low reactivity, especially those composed of
aliphatic aldehydes and aliphatic amines, also should be
noted.
a Reaction conditions: a lactol (1 mmol) and an amine (2 mmol) in THF
(2 mL) at 30 °C overnight, and then Ni(acac)2 (0.1 mmol) in THF (3 mL),
3-hexyne (4 mmol, when applied), 1,3-butadiene (4 mmol), and Ph2Zn (3.6
mmol) at 30 °C for the period of time indicated. b Yes and no correspond
to 3-hexyne applied and not applied, respectively. c In addition to 6 or 7, 8
[n ) 2, R ) PMP (ca. 20%, based on 1H NMR, entry 2); n ) 1, R ) PMP
(ca. 10%, entry 4); n ) 2, R ) Bn (ca. 8%, entry 6); n ) 1, R ) Bn (ca.
14%, entry 8)] was produced.
3-hexyne, each of 6a and 6b was contaminated by a
considerable amount of 8 [n ) 2, R ) PMP (ca. 20%, based
on 1H NMR, entry 2) and n ) 1, R ) PMP (ca. 10%, entry
4), respectively].9
The lactamines of benzylamine, in the presence of 3-hex-
yne, provided the expected products 7a and 7b, albeit in
modest yields (entries 5 and 7). Much better yields were
recorded when the reactions were undertaken in the absence
of 3-hexyne (entries 6 and 8). From a practical viewpoint,
however, the former conditions are strongly recommended,
since each of the byproducts 8 [n ) 2, R ) Bn (ca. 8%,
(8) The reaction was performed typically as follows (preparation of
2a): Into a N2 purged two-necked round bottom flask containing benzy-
lamine (214 mg, 2.0 mmol) were added THF (2 mL) and benzaldehyde
(106 mg, 1.0 mmol) via syringe. The mixture was stirred at 30 °C overnight
(aldimine, Rf 0.57, hexane:ethyl acetate ) 4:1, v/v). Into this mixture were
introduced a solution of Ni(acac)2 (25.7 mg, 0.1 mmol) in THF (3.0 mL)
via cannula and 3-hexyne (457 µL, 4.0 mmol), butadiene (400 µL, 4.0
mmol), and Ph2Zn (3.6 mmol). The mixture was stirred at 30 °C for 3 h,
then poured into ice-water (25 mL) and extracted with ethyl acetate (25
mL). The water phase was extracted with ethyl acetate (2 × 20 mL). The
combined organic phase was dried (MgSO4) and concentrated in vacuo,
and the residue was subjected to column chromatography over silica gel
(eluent; hexane/ethyl acetate ) 200:1, v/v) to give 2a [Rf 0.58, (hexane/
ethyl acetate ) 4:1, v/v)] in 94% yield.
Acknowledgment. Financial support from the Ministry
of Education, Culture, Sports, Science and Technology,
Japanese Government [Grant-in-Aid for Scientific Research
(B) 16350058 and Priority Areas 17035065 and 18037059],
is gratefully acknowledged.
Supporting Information Available: Experimental de-
tails. This material is available free of charge via the Internet
(9) Since 8 was hardly separable from 6 and 7, the yields of these
1
products were estimated on the basis of H NMR spectra of the mixtures.
OL0703480
Org. Lett., Vol. 9, No. 10, 2007
1873
Kimura, Masanari
