Rh(I)-catalyzed addition of alkenylzirconocene chlorides to aldimine derivatives

Article abstract of DOI:10.1016/S0040-4039(02)02767-3

[RhCl(COD)]₂ (2 mol%) catalyzed reactions of alkenylzirconocene chloride complexes to N-Ts, -PO(OEt)₂ and COOR aldimine derivatives were efficiently carried out in dioxane at room temperature to give allylic amine derivatives in exce

Full text of DOI:10.1016/S0040-4039(02)02767-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 923–926
Rh(I)-catalyzed addition of alkenylzirconocene chlorides to
aldimine derivatives
Akito Kakuuchi, Takeo Taguchi* and Yuji Hanzawa*
School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan
Received 8 November 2002; revised 29 November 2002; accepted 5 December 2002
Abstract—[RhCl(COD)]2 (2 mol%) catalyzed reactions of alkenylzirconocene chloride complexes to N-Ts, -PO(OEt)2 and COOR
aldimine derivatives were efficiently carried out in dioxane at room temperature to give allylic amine derivatives in excellent yields.
This is the first example of the catalytic addition reactions of alkenylzirconocene chloride complexes to aldimine derivatives.
© 2003 Elsevier Science Ltd. All rights reserved.
nized. Particularly, an efficient enantioselective version
of the Rh-catalyzed addition of the organometallic
reagents to a,b-enone, aldehyde, and imine derivatives
in the presence of a chiral phosphine ligand highlights
the significance of Rh-catalyzed reaction in modern
organic synthesis. In this report, we present Rh(I)-cata-
lyzed addition reactions of alkenylzirconocene chloride
complexes 1 to aldimine derivatives 2. It is the first
example of the catalytic process for the addition of
alkenylzirconocene chloride complexes 1 to aldimine
derivatives 2 (Scheme 2).
Organozirconium compounds are gaining an increasing
importance in organic synthesis.1 Alkyl- or alkenylzir-
conocene chlorides, which are stable complexes at
ambient temperature and readily accessible through
hydrozirconation of alkenes or alkynes with Schwartz
reagent (Cp2ZrHCl),2 are considered convenient
organometallic reagents as donors of alkyl or alkenyl
anions. However, the inherently low reactivity of the
organozirconocene chloride to the electrophilic reagents
(e.g. aldehyde, aldimine, etc.) restrained its use as a
synthetic reagent. Thus, the use of a catalyst or a
stoichiometric mediator for the reaction of organozir-
conocene chlorides is essential to bringing about the
carbonꢀcarbon bond formation (Scheme 1).
At the outset, we examined the Rh(I)-catalyzed reac-
tions of (E)-3,3-dimethyl-1-butenyl zirconocene chlo-
ride (1a), which is obtained by the hydrozirconation of
t-butyl acetylene, with imine compounds derived from
benzaldehyde and amines, and the results are shown in
Table 1.
It has been reported that Ag(I)3 or ZnBr24 is an efficient
catalyst for the addition of alkyl- and alkenylzir-
conocene chloride to aldehydes. It has also been
reported that the Me2Zn-mediated addition of
alkenylzirconocene
chloride
to
aldehydes5
or
aldimines5,6 yields allylic alcohols or amines, respec-
tively. To our knowledge, however, an efficient catalyst
for the addition of organozirconocene chlorides to
aldimine is unknown. Recently, Rh-catalyzed additions
of organometallic reagents, such as tin (Sn),7 bismuth
(Bi),8 titanium (Ti),9 silicon (Si),10 lead (Pb),11 and
boron (B),12 to aldehydes, imines or a,b-unsaturated
carbonyl compounds are being extensively studied by
many research groups, and the validity is well recog-
Scheme 1. Additions of organozirconocene derivatives to car-
bonꢀheteroatom double bonds.
Keywords: alkenylation; alkenylzirconocene chloride; aldimine;
rhodium catalyst.
* Corresponding authors. Tel.: +81-(0)426-76-3274; fax: +81-(0)426-
76-3257; e-mail: hanzaway@ps.toyaku.ac.jp
Scheme 2.
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)02767-3

924
A. Kakuuchi et al. / Tetrahedron Letters 44 (2003) 923–926
Table 1. Rh(I)-catalyzed reactions of 1a with phenylaldiminesa
Entry
R1
Rh catalyst
Solvent
Time (h)
Yield (%)b
1
2
3
4
5
6
7
8
Ph 2a
Ts 2b
2b
2b
2b
PO(OEt)2
COt-Bu
COOMe
2b
2b
2b
[RhCl(cod)]2
[RhCl(cod)]2
[RhCl(cod)]2
[RhCl(cod)]2
[RhCl(cod)]2
[RhCl(cod)]2
[RhCl(cod)]2
[RhCl(cod)]2
[Rh(cod)2]BF4
[Rh(OH)(cod)]2
Rh(PPh3)3Cl
Rh(acac)(C2H4)2
Dioxane
Dioxane
Toluene
THF
CH2Cl2
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
24
1
5
24
24
1
24
12
3
–
3a 99
92
69
B10
63
–
70
Quant.
96
B10
25
9
10
11
12
2.5
7
7
2b
a Reactions were carried out at ambient temperature and monitored by TLC. Ratio of 1a:phenylaldimines=2:1.16
b Yields were isolated and calculated from phenlaldimines.
the reaction at ambient temperature (entries 1, 3, 5 and
7, Table 2). Heating of the reaction mixture at 80°C,
however, gave 3a in excellent yields in a short period of
time (0.5 h, entries 4 and 6). A similar observation
about the addition of phosphine ligand has been made
in Rh(I)-catalyzed reactions of arylstannanes to
aldimines.7f It should be mentioned that the addition of
phosphine ligands, such as PPh3, dppe, and dppb, to
the Rh(acac)(C2H4)2 catalyst, which is known to be an
efficient catalyst for the conjugate addition reactions of
organometallics, did not improve the yield of 3. The
present [RhCl(cod)]2-catalyzed alkenylation procedure
of N-Ts aldimine through the use of alkenylzirconocene
chloride 1 was extended to a variety of N-Ts aldimine
derivatives and alkenylzirconocene chloride complexes,
and the results are shown in Table 3.
The reaction of 1a with N-benzylidene aniline (2a) by
using a [RhCl(cod)]2 (2 mol%) catalyst yielded no trace
of the addition product (entry 1). The lack of the
reactivity of 2a would be a result of the low elec-
trophilicity of the imine 2a. The same observation has
been reported in the Rh(I)-catalyzed reaction of aryl-
stannane compound with 2a.7h The reaction of 1a with
N-benzylidene p-toluenesulfonamide (2b), which is acti-
vated by the electron-withdrawing sulfonyl group, thus,
indicated an excellent reactivity to give product 3a in
99% yield (entry 2). In the [RhCl(cod)]2-catalyzed reac-
tions of 1a with 2b, dioxane turned out to be an
excellent solvent compared to THF, toluene, or CH2Cl2
(entries 2–5). Instead of using N-p-toluenesulfonyl
group (N-Ts) of 2b, N-substituents, such as N-
PO(OEt)2 and N-COOMe, also indicated a high reac-
tivity under identical conditions, albeit the reactions
were less efficient (entries 6 and 8). It should be men-
tioned that the bulky N-COt-Bu group retarded the
reaction (entry 7). As for the examined catalysts, a
cationic Rh(I) complex, [Rh(cod)2]BF4, exhibited excel-
lent catalytic activity (entry 9). It is interesting to note
that [Rh(OH)(cod)]2 showed a high efficiency as well
(entry 10). The neutral Rh catalyst, such as
Rh(PPh)3Cl, or Rh(acac)(C2H4)2, was an inefficient cat-
alyst (entries 11 and 12). Since the Rh(I)-catalyzed
reaction of alkenylstannane with N-Ts aldimine 2b has
been reported to proceed under heating conditions
(60°C, 20 h),7 the mildness of the present Rh-catalyzed
additions of alkenylzirconocene chlorides 1 to N-Ts
aldimine 2b (ambient temperature, 0.5–3 h) is notable.
Next, we investigated the effect of phosphine ligand as
an additive and the results are listed in Table 2.
N-Ts aldimines derived from aromatic or aliphatic
aldehydes reacted with 1 to give allylic amine products
in good to excellent yields (entries 1–6). The electron-
Table 2. [RhCl(cod)]2-catalyzed reactions of 1a with 2b in
dioxane in the presence of phosphine liganda
Entry
P-ligand
Temp. (°C)
Time (h)b
3a Yield (%)c
1
2
3
4
5
6
7
8
PPh3
PPh3
Ambient
80
Ambient
80
Ambient
80
Ambient
80
12
0.5
12
0.5
12
0.5
12
48
40
90
95
39
87
74
80
Dpped
Dppe
Dppbe
Dppb
Dppff
Dppf
12
a The ratio of P/Rh is 2/1.
Although the 2 mol% [RhCl(cod)]2-catalyzed reaction
of 1a with 2b efficiently proceeds to give 3a without
adding phosphine ligand (1 h, 99% yield) (entry 2,
Table 1), an addition of a monodentate or bidentate
phosphine ligand (P/Rh=2/1) to the mixture retarded
b Reactions were monitored by TLC.
c Isolated yields.
d 1,2-Bis(diphenylphosphino)ethane.
e 1,4-Bis(diphenylphosphino)butane.
f 1,1%-Bis(diphenylphosphino)ferrocene.

A. Kakuuchi et al. / Tetrahedron Letters 44 (2003) 923–926
925
Table 3. [RhCl(cod)]2-catalyzed reactions of 1 with N-Ts
aldimine derivativesa
Entry R1
R2
Time Yield
(h)
(%)b
1
2
3
4
5
6
t-Bu 1a
1a
1a
1a
1a
Ph 2b
p-CF3C6H5
p-CH3OC6H5
n-C8H17
cy-C6H11
t-Bu
1
1
1
3
1
2
3a 99
83
96
75
97
1a
91
7
8
1a
OEt
PhCHꢁCH
2b
12
6
B10
70
9
Ph
2b
2b
2b
2b
12
3.5
12
12
24
58
10
11
12
13
n-C4H9
BnOC2H4
BnOCH2
(E)-n-C3H7CHꢁC(n-C3H7)- 2b
ZrCp2Cl
98
Scheme 3. Supposed catalytic cycle for the formation of 3.
83c
72c
80c
access of alkenylzirconocene chlorides 1 and the present
efficient reaction with aldimine compounds 2 could
increase the significance of alkenylzirconocene chloride
complex 1 as an alkenyl organometallic reagent. Fur-
ther work on the Rh(I)-catalyzed addition of 1 to
aldehydes and a,b-unsaturated carbonyl compounds
(enone, ester, and amide) is now in progress and
detailed results will be published in due course.
14
Ph(CH2)4ZrCp2Cl
2b
24
–
a Ratio of 1:N-Ts aldimines=2:1. Reactions were monitored by TLC.
b Yields were isolated and calculated from N-Ts aldimines.
c Ratio of 1:N-Ts aldimines=3:1.
Typical experimental procedure
withdrawing or -donating substituent had little effect
on the reaction rate (monitored by TLC) and product
yields (entries 1–3). N-Ts imine derived from cin-
namaldehyde proceeded to give product in a low yield
(<10%) under identical conditions (entry 7). Alkenylzir-
conocene chloride complexes other than 1a indicated a
comparable reactivity under the same conditions
(entries 8–13). Although alkenylzirconocene chloride
generated from internal alkyne, 4-octyne, reacted with
N-Ts aldimine 2b to give a product in good yield, it
took a longer time (24 h) for the completion of the
reaction (entry 13). Alkylzirconocene chloride complex
did not react with N-Ts aldimine even by the use of
Rh(I) catalysts listed in Table 1 (entry 14). Thus, the
present Rh(I)-catalyzed addition of zirconocene com-
plex to N-Ts aldimine is restricted to the alkenylzir-
conocene complex. It is known that the transfer of alkyl
ligand from zirconocene to other metals (transmetala-
tion) is more difficult than that of alkenyl ligands.13
This could explain the nonreactivity of the alkylzir-
conocene chloride complex under the described reaction
conditions. These results suggest that the present reac-
tion involves the transfer of an alkenyl group from
zirconium to rhodium metal (transmetalation) giving an
alkenylrhodium species 4 and the following insertion of
the carbonꢀnitrogen double bond of aldimine 2 into the
Rhꢀcarbon bond (Scheme 3).
Preparation of a solution of alkenylzirconocene chloride
1a in dioxane. A suspension of Cp2ZrHCl14 (258 mg, 1.0
mmol)15 in dry CH2Cl2 (4 mL) was treated at room
temperature with 3,3-dimethyl-1-butyne (0.13 mL, 1.07
mmol), and the mixture was allowed to stir for 15 min.
After the removal of all volatiles in vacuum, the result-
ing white solid 1a was then dissolved in dry dioxane (4
mL), and the solution was directly used with the next
reaction.
[RhCl(cod)]2-catalyzed reaction of 1a with 2b. A solution
of N-benzylidene-4-methyl-benzenesulfonamide (2b)16
(130 mg, 0.5 mmol) in dry dioxane (1 mL) and
[RhCl(cod)]2 (4.9 mg, 0.01 mmol) were added to a
solution of 1a, prepared as described, at room tempera-
ture. The reaction mixture was stirred for 1 h before
being quenched with saturated aq. NaHCO3. The solu-
tion was extracted (3×) with EtOAc, and washed with
brine before drying (MgSO4). After the usual workup,
the crude product was purified by a silica gel column
chromatography (hexane:EtOAc=10:1) to give N-(4,4-
dimethyl-1-phenyl-pent-2-eny)-4-methyl-benzenesulfon
amide (3a) in 99% yield.
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