Generation of prenylhafnlum and α-selectlve addition to imines

Article abstract of DOI:10.1002/ejoc.200900445

Allylhafnium compounds were generated by transmetalation between allyl-SnBu₃ and HfCl₄ in EtCN. A highly α-selective addition reaction of prenyltributyltin to imines was observed.

Full text of DOI:10.1002/ejoc.200900445

SHORT COMMUNICATION
DOI: 10.1002/ejoc.200900445
Generation of Prenylhafnium and α-Selective Addition to Imines
Ikuya Shibata,*[a] Shinji Miyamoto,[a] Shinji Tsunoi,[a] Kazuya Sakamoto,[b] and
Akio Baba[b]
Keywords: Allylation / Regioselectivity / Hafnium / Tin / Transmetalation / Imines
Allylhafnium compounds were generated by transmetalation
between allyl-SnBu3 and HfCl4 in EtCN. A highly α-selective
addition reaction of prenyltributyltin to imines was observed.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2009)
the homoallylamine 3a (entry 1). In particular, the use of
2 equiv. of allyltin/HfCl4 affords 3a in quantitative yield
(entry 2). γ-Substituted allyltin compounds like crotyl- and
cinnamylSnBu3 (1b and 1c) react with the γ-carbon of allyl-
Sn compounds to give homoallylic amines 3b and 3c,
respectively (entries 3 and 4).
Introduction
Allylation of imines is a representative method to give
homoallylic amines,[1] but limitations of the method remain
to be resolved. First, the scope of application to imines is
still narrow due to the instability of the starting material.
Second, the regioselectivity is difficult to control. In most
cases, allylation to imines has been performed via γ-ad-
dition. In particular, no effective methods for the α-al-
lylation of imines derived from aliphatic aldehydes have
thus far been reported. Allyltin compounds are often used
in combination with another acidic metal for the allylation
of carbonyls and imines.[2] Herein, we report the generation
of allylhafnium compounds via the allyltin/HfCl4 system,
and their characteristic reactivity toward imines. High α-
selectivity for the prenylation reaction of various imines was
achieved (Scheme 1).
Table 1. Allylation of benzylideneaniline (2a).[a]
Scheme 1. Prenylation to imines.
Results and Discussion
[a] Reduction was performed by the reaction of 2a (1 mmol) with
1/HfCl4 in EtCN at –40 °C for 2 h. [b] dr = 64:36. [c] dr = 79:21.
Table 1 shows the results of the allylation of benzyl-
ideneaniline (2a) by the allyltributyltin (1a)-hafnium tetra-
chloride (HfCl4) system. In propionitrile as solvent the al-
lylation of the C=N group of 2a proceeds effectively to give
Next, we focused on the prenylation of imines starting
from prenylSnBu3 (1d) (Table 2). We have already reported
that the allyltantalum system (allylSnBu3/TaCl5) exhibits ef-
ficient reactivity toward imines.[3b] However, the system
could not be applied to prenylSnBu3 (1d) because no reac-
tion occurs with imines. This can be attributed to steric hin-
drance at the nucleophilic carbon of the generated prenyl-
tantalum species. By contrast, the presented reaction with
prenylSnBu3 (1d)/HfCl4 proceeds well. The regioselectivity
of the reaction is noteworthy. When benzylideneaniline (2a)
[a] Research Center for Environmental Preservation, Osaka Uni-
versity,
2-4 Yamadaoka, Suita, Osaka, 565-0871, Japan
Fax: +81-6-6879-8978
E-mail: shibata@epc.osaka-u.ac.jp
[b] Department of Applied Chemistry, Graduate School of Engi-
neering, Osaka University,
2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.200900445.
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Eur. J. Org. Chem. 2009, 3508–3511

Generation of Prenylhafnium and α-Selective Addition to Imines
Table 2. Prenylation to imines.[a]
Entry
Ar1 (2)
Ar2 (2)
% Yield of 4
α/γ
1
2
3
4
5
6
7
8
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
a
a
a
b
c
d
e
f
92
87[b]
46[c]
70
60
51
98
70
77
60
100:0
100:0
24:76
100:0
100:0
100:0
0:100
0:100
100:0
100:0
p-ClC6H5
p-FC6H5
p-MeOC6H5
p-NO2C6H5
SO2Ph
Ph
Ph
Ph
Ph
9
p-ClC6H5
p-FC6H5
p-MeOC6H5
p-NO2C6H5
g
h
i
10
11
12
(traces)
55
j
0:100
[a] Reduction was performed by the reaction of 2 (1 mmol), with allylSnBu3/HfCl4 (3 mmol) in EtCN at –40 °C for 2 h. [b] –78 °C. [c]
CH2Cl2.
is treated with 3 equiv. of prenylSnBu3 (1d)/HfCl4 in pro- ed.[6a,6e] Table 3 summarizes the three-component reactions,
pionitrile, the addition to the imine proceeds at the α-car- including the combination of aliphatic aldehyde and aniline.
bon of 1d (Table 2, entry 1). α-Allylation takes place at low In the hafnium chloride-mediated prenylation using ali-
temperature (–78 °C, entry 2). To the best of our knowl- phatic aldehydes, including nonbranched ones, the reaction
edge, only the prenylbarium reagent shows α-selectivity.[4] proceeds smoothly in the α-addition way to afford homo-
The influence of solvents on the regioselectivity is drastic. allylic amines 4k/α–4n/α in moderate yields. These results
In CH2Cl2, the γ adduct 4a is obtained predominantly (en- are noteworthy because no effective methods have thus far
try 3). When the reaction is performed in CH2Cl2, the ad- been reported for the α-allylation of imines derived from
dition of EtCN solvent to the reaction mixture does not aliphatic aldehydes.
change the regioselectivity. Hence, it can be concluded that
the α adduct is obtained directly rather than by a rearrange-
Table 3. Prenylation to imines by three component reactions.[a]
ment of the γ adduct.
Table 2 shows the prenylation to various imines and a
summarizing of the role of the substituents on the nitrogen
atom. The halogen and methoxy groups[5] on the N-aro-
matic rings induced α-selective addition to 4b–4d/α (entries
4–6). By contrast, highly electrophilic groups such as N-
p-nitrophenyl- and N-phenylsulfonyl (2e and 2f) selectively
afforded γ adducts 4e/γ and 4f/γ (entries 7 and 8). As to
Entry
R
Conditions
Product
% Yield
imines 2g–2j, aromatic substituents bonded to acyl carbon
also affected the α/γ-selectivity. Haloaryl-substituted groups
such as 2g and 2h gave α adducts 4g/α and 4h/α, respectively
(entries 9 and 10). In the case of p-methoxyphenyl-substi-
tuted imine 2i, no reaction proceeded due to its low electro-
philicity (entry 11). The reaction of imine 2j, a strong elec-
trophile, selectively gave γ adduct 4j/γ (entry 12).
1
2
3
4
PhCH2CH2 –40 °C, 9 h
4k/α
47
58
62
27
n-C5H11
c-C6H11
i-C3H7
–78 °C to room temp., 14 h 4l/α
–40 °C, 2 h
–40 °C, 2 h
4m/α
4n/α
[a] Reduction was performed by the reaction of aldehyde (1 mmol),
amine (1 mmol) with allylSnBu3/HfCl4 (1 mmol) in EtCN.
The three-component reaction in which aldehyde, amine,
The assumption of a transmetalation reaction between
and allylating reagents are treated in one portion is ac- the highly reactive allyltin species and HfCl4 is supported
cepted as the method of choice to generate labile imines in by the detection of Bu3SnCl after quenching the reaction
situ, in which the allylating reagents should indicate high mixture. When prenylSnBu3 (1d) is treated with HfCl4 at
imine selectivity and must tolerate the generated water.[6] –40 °C for 2 h in EtCN, Bu3SnCl is obtained in 63% yield
The reaction using aliphatic aldehydes having α-protones (GLC analysis). At the initial stage (30 min at –40 °C),
incurs severe side reactions to decrease the yields in the Bu3SnCl is observed only in 5% yield. When the measure-
Lewis acid-catalyzed reactions,[1,7] and such examples of ment is performed at room temp., Bu3SnCl can be detected
three-component reactions have only scarcely been report- in quantitative yield. In CH2Cl2, only small amounts of
Eur. J. Org. Chem. 2009, 3508–3511
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I. Shibata, S. Miyamoto, S. Tsunoi, K. Sakamoto, A. Baba
SHORT COMMUNICATION
Bu3SnCl are detected. In our previously reported al- would generate the prenylhafnium species B at a higher
lylSnBu3/TaCl5 system, Bu3SnCl was obtained quantita- concentration than A. However, reagent B bears a sterically
tively even at –78 °C for 5 min.[3] This result indicates that hindered nucleophic γ-carbon. The less reactive 2a cannot
the Sn–Hf exchange proceeds at a relatively slow rate com- react with B, and therefore can only react with A to provide
pared with the Sn–Ta exchange. When the EtCN solution the product 4a/α. More reactive imines such as 2j can react
of prenylSnBu3 (1d)/HfCl4 was measured at –40 °C by 119Sn with either complex. Since the major complex in solution is
NMR, the formation of Bu3SnCl was detected, but the B, the major product is compound 4j/γ (path b).[9]
original prenyltin 1d was also observed as a major peak
(Figure 1).
Conclusions
α-Addition of prenylSnBu3 to imines was established in
the presence of HfCl4. A variety of aldimines were appli-
cable including in situ generated ones. As active species for
forming α adducts, (dimethylallyl)hafnium was generated
by transmetalation between prenylSnBu3 and HfCl4.
Experimental Section
General Procedure for the Preparation of N-Aromatic Imines:
(Table 2, entry 1). To a dry nitrogen-filled 10 mL round-bottomed
flask containing HfCl4 (0.96 g, 3 mmol) in EtCN (3 mL) was added
prenyltributyltin (1d) (1.08 g, 3 mmol) at –40 °C. After stirring at
–40 °C for 2 h, to the resulting solution was added benzylideneani-
line (2a) (0.181 g, 1 mmol). As the reaction proceeded, the mixture
gradually turned homogeneous. During the reaction, the solution
indicated a slight pale yellow color. After stirring the mixture at
–40 °C for 2 h, the reaction mixture was quenched by saturated
NaHCO3 (2 mL). To the mixture were added saturated NH4F
(2 mL) and ether (10 mL). After stirring at room temp. for 30 min,
the precipitated Bu3SnF was filtered off and the filtrate was ex-
tracted with diethyl ether (3ϫ15 mL), dried with MgSO4 and fil-
tered. Volatile components were removed under reduced pressure.
The residue was chromatographed on silica-gel column [FL100-DX
(Fuji Silysia Chemical Ltd.)], eluting with hexane/EtOAc (99:5,
v/v) to give homoallylamine 4a (0.231 g, 92%).
Figure 1. Transmetalation between prenylSnBu3 and HfCl4.
According to the results obtained in the present study,
the α-selective addition of prenylSnBu3 (1d) can be ex-
plained as shown in Scheme 2. Initially, the Sn–Hf exchange
occurs to generate the (dimethylallyl)hafnium species A
which reacts at the αЈ-C atom with imine 2 to give the α
adduct 4a/α (path a). Generally, transmetalation of γ-sub-
stituted allyltin compounds quickly results in a similar type
of stable γ-substituted allylic metals B.[2] Thus, the (dimeth-
ylallyl)metal species A is regarded as a transient intermedi-
ate in the isomerization to B. Hence, the trapping of an
intermediate like A is generally difficult except for the
crotylSnBu3/Bu2SnX2 system.[8] In the case of the Sn–Hf
exchange, the rate to A is so slow that the initially formed
(dimethylallyl)hafnium A can react with imine 2 (path a).
An excess amount of reagents is required to obtain good
yields because of the slow generation of the reactive allylic
hafnium species. Of course, rapid isomerization from A
Supporting Information (see also the footnote on the first page of
this article): Experimental and characterization data of all new
compounds.
Acknowledgments
This research was supported by the Mizuho-Espec Foundation, the
Kurata Memorial-Hitachi Science and Technology Foundation,
and the Naito Foundation.
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[9] In CH2Cl2 as solvent, HfCl4 acts as Lewis acid and activates
the imine (Table 2, entry 3). Thus, free 1d reacts with the imine
to give the γ adduct.
[5] The reaction using anisidine is expedient because the p-meth-
Received: April 22, 2009
Published Online: June 16, 2009
oxyphenyl group of the products can be removed.[6c]
[6] The three-component synthesis of homoallylic amines has been
carried out by using aromatic amines: a) S. Kobayashi, T. But-
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