P′CP′-Pincer palladium complex-catalyzed allylation of N,N-dimethylsulfamoyl-protected aldimines

Article abstract of DOI:10.1016/j.tetlet.2009.02.187

The P′CP′-pincer palladium complex-catalyzed allylation of N,N-dimethylsulfamoyl-protected aldimines with allyl(tributyl)stannane is investigated for the preparation of N-homoallylic sulfamides. The desired N,N-dimethylsulfamoyl-protected products are obt

Full text of DOI:10.1016/j.tetlet.2009.02.187

Tetrahedron Letters 50 (2009) 2232–2235
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
P0CP0-Pincer palladium complex-catalyzed allylation
of N,N-dimethylsulfamoyl-protected aldimines
a
Jie Li a, Adriaan J. Minnaard b, Robertus J. M. Klein Gebbink a, , Gerard van Koten
*
a Chemical Biology and Organic Chemistry, Debye Institute for Nanomaterials Science, Faculty of Science, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands
b Department of Bio-organic Chemistry, Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 4, 9747, AG Groningen, The Netherlands
a r t i c l e i n f o
a b s t r a c t
The P0CP0-pincer palladium complex-catalyzed allylation of N,N-dimethylsulfamoyl-protected aldimines
with allyl(tributyl)stannane is investigated for the preparation of N-homoallylic sulfamides. The desired
N,N-dimethylsulfamoyl-protected products are obtained in moderate to high yields in DMF under very
mild conditions and a high yielding and convenient deprotection of the N,N-dimethylsulfamoyl group
is also demonstrated.
Article history:
Received 18 September 2008
Revised 26 January 2009
Accepted 24 February 2009
Available online 28 February 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Palladium
P0CP0-Pincer catalysis
Homoallylation
N,N-Dimethylsulfamoyl protecting group
Aldimines
The development of novel methods to generate new carbon-
carbon bonds is important for the preparation of compounds of
interest from pharmaceutical, biological or advanced materials
points of view, and belongs to the core of modern organic chemis-
try.1 In particular, the allylation of imines has attracted increasing
attention because of its importance for the preparation of nitrogen-
containing compounds.2,3
To date, numerous indium- and zinc-mediated allylic additions
of imines under typical Barbier-type conditions have been reported
(Scheme 1).4,5 The synthesis often benefits from low toxicity, toler-
ance towards air and moisture and high yields.
In addition, an alternative procedure involving a palladium-cat-
alyzed reaction in which the
g
1-allylpalladium intermediate gen-
erated reacts with electrophilic substrates (Scheme 1) has been
reported.6,7 This reaction proceeds via a very different catalytic cy-
cle compared to Barbier-type metal-mediated allylations. First, all-
ylstannanes or trifluoro(allyl)borates undergo a transmetalation
reaction with the P0CP0-pincer palladium complex [PdTFA(P0CP0)]
TFA
Ph2P
O
Pd
PPh2
O
(Fig. 1).8,9 Subsequently, the resulting nucleophilic
g
1-allylpalla-
dium intermediate reacts with electrophilic aldehydes or aldi-
mines to afford the corresponding allyl product. Szabó and co-
workers reported the [PdTFA(P0CP0)]-catalyzed allylation of tosyli-
mines in the presence of allylstannane or trifluoro(allyl)borates
showing high yields and a wide substrate scope.6,7 One drawback
[PdTFA(P'CP')]
Figure 1.
R2
R3
R2
In or Zn
R2
N
HN
R1
Pd complex
M
Barbier-type conditions
HN
R1
R1
H
R3
Br
M = Sn(nBu)3 or BF3K
R3 = H or Me
Scheme 1.
* Corresponding author. Tel.: +31 30 253 1889; fax: +31 30 252 3615.
E-mail address: r.j.m.kleingebbink@uu.nl (R.J.M. Klein Gebbink).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.02.187

J. Li et al. / Tetrahedron Letters 50 (2009) 2232–2235
2233
O
O
N
O
N
N
S
3 equiv. allylating agent
3 equiv. In
S
S
HN
Ar1
N
HN
O
phosphoramidite, Rh(I) precursor
O
O
R1
R2
∗
Ar1
H
Ar1
Ar2
THF, r.t.
Ar2B(OH)2
R3
Ar1 = Ph, R1 = R2 = R3 = H, 90%
Ar1 = Ph, R1 = R2 =H, R3 = Me, 87%
Ar1 = Ph, R1 =Me, R2 = R3 = H, 89%
Ar1 = Ph, R1 = R2 = Me, R3 = H, 63%
Ar1 ≠ Ar2
Scheme 2.
O
O
N
N
S
S
5 mol% [PdTFA(P'CP')]
DMF, 40 ºC, 16 h
HN
N
+
O
Sn(nBu)3
O
Ar
Ar
H
1.2 equiv
1.0 equiv
Scheme 3.
Table 1 (continued)
Table 1
[PdTFA(P0CP0)]-catalyzed allylation of various aldimines with allyl(tributyl)stannane
Entry
Substrate
Product
Yielda
(%)
Entry
Substrate
Product
Yielda
(%)
H
NSO2NMe2
H
NSO2NMe2
H
NSO2NMe2
Br
NSO2NMe2
Br
8
80
85
60
68
70
1
81
85
93
H
8
8a
1
1a
H
NSO2NMe2
NSO2NMe2
H
NSO2NMe2
H
NSO2NMe2
NSO2NMe2
NSO2NMe2
9
10
11
12
H
2
3
9
9a
O2N
O2N
2
3
O2N
O2N
2a
3a
H
NSO2NMe2
H
NSO2NMe2
H
NSO2NMe2
H
MeO
10
MeO
10a
H
NSO2NMe2
H
NSO2NMe2
H
NSO2NMe2
H
11
11a
4
5
85
80
4
H
S
4a
NSO2NMe2
NSO2NMe2
S
H
NSO2NMe2
H
NSO2NMe2
NSO2NMe2
H
12
12a
Reagents and conditions: 0.1 mmol of aldimine, 0.12 mmol of allyl(tributyl)stann-
F3C
5
F3C
ane, 0.005 mmol of [PdTFA(P0CP0)], 0.5 mL of DMF, 4 °C, 16 h.
5a
a
Isolated yield (average of two runs).
H
NSO2NMe2
H
6
7
80
96
of this protocol is that removal of the tosyl protecting groups is not
always straightforward, even under quite harsh conditions (i.e., liq.
NH3/Li or NH3/Na), and suffers from limited functional group toler-
ance.10–12 To overcome this problem and to improve the practical-
ity of the allylation procedure, an easily removable protecting
group is highly desirable. In this Letter, the [PdTFA(P0CP0)]-cata-
lyzed allylation of N,N-dimethylsulfamoyl-protected aldimines is
described as an alternative.
NC
Br
6
NC
Br
6a
H
NSO2NMe2
H
NSO2NMe2
7
7a

2234
J. Li et al. / Tetrahedron Letters 50 (2009) 2232–2235
Recently, Minnaard and co-workers presented the N,N-dim-
In contrast, the yield was considerably lower for substrate 10 bear-
ing the stronger electron-donating methoxy group. Remarkably,
halogenated substrates 7 and 8 gave the desired products in good
yields without loss of the bromine atoms, that is, no products from
palladium-catalyzed C–Br activation were observed. Undoubtedly,
this is an attractive feature of this approach allowing further mod-
ification, that is, tandem reactions17 via cross-coupling reactions
using a different metal catalyst. Furthermore, successful transfor-
mation of the halogenated substrates strongly indicates that no
Pd leaching from [PdTFA(P0CP0)] occurs, for example, by decompo-
sition, as otherwise, the formed active Pd(0) species could insert
oxidatively into the C–Br bond affording undesired by-products.
Moreover, cinnamylaldimine 11 and 2-thienylaldimine 12 were
also converted into the corresponding homoallylic products (en-
tries 11 and 12).
It is worth mentioning that the isolated yields obtained in this
study are generally 10–15% lower than those of the tosyl-protected
aldimines.7 This is most likely due to the presence of the strongly
electron-donating Me2N group instead of the p-tolyl group which
decreases the electrophilicity of the corresponding aldimine. In
particular, for the electron-enriched substrates (entries 10 and
11), both conversion and yield were lower in comparison with
the corresponding tosyl-protected aldimines.
ethylsulfamoyl group as an inexpensive, low-molecular-weight
protecting/activating group for Rh(I)-catalyzed asymmetric aryla-
tion of aldimines and described an efficient method for its removal
using a microwave-assisted procedure.13 Encouraged by these re-
sults, we extended this research to the Barbier-type allylation for
the preparation of N-homoallylic sulfamides in high yields with
different allyl bromides in THF as the optimal solvent (Scheme
2).14 Interestingly, Minnaard found that even by using simple con-
ventional heating, the N-homoallylic sulfamides could be depro-
tected. So far, the latter procedure has been applied to only one
substrate.
In the present study we demonstrate how the scope of this reac-
tion can be extended by using the [PdTFA(P0CP0)]-catalyzed allyla-
tion of a series of N,N-dimethylsulfamoyl-protected aldimines.
Using the typical reaction conditions reported by Szabó and co-
workers,7 1 equiv of aldimine was reacted with 1.2 equiv of allylst-
annane in the presence of 5 mol % of [PdTFA(P0CP0)] at 40 °C in
DMF for 16 h (Scheme 3). After completion, the reaction mixture
was quenched with saturated aqueous KF solution (1 mL) and the
resulting mixture was stirred at room temperature (16 h) to re-
move toxic organic tin residues.15 The products were extracted
from the solution with ethyl acetate (3 ꢀ 2 mL) and were subjected
to flash column chromatography to isolate analytically pure
products.16
These experiments show that N,N-dimethylsulfamoyl-protected
aldimines can be allylated smoothly under mild conditions in mod-
erate to excellent yields (data shown are those of the isolated, puri-
fied products) and show good functional group tolerance (Table 1).
For benchmark substrate 1, the corresponding homoallylic product
1a was obtained in a good yield of 81%. Similarly, substrates 2, 3, 5
and 6 bearing various electron-withdrawing para-substituents
were converted into the corresponding homoallylic products in
80–93% yield. The presence of weakly electron-donating functional
groups in substrates 4 and 9 did not result in any loss of reactivity
and both afforded the respective products 4a and 9a in 85% yield.
On the basis of the catalytic cycle proposed by Szabó and
Yao,6,9,15 the [PdTFA(P0CP0)]-catalyzed allylation of N,N-dimethyl-
sulfamoyl aldimines can be depicted stepwise as shown in Scheme
4: (1) Transmetalation of tri(n-butyl)allyltin with [PdTFA(P0CP0)]
and formation of an
g
1-allyl-palladium complex; (2) electrophilic
1-allyl moiety by the aldimine
attack on the -position of the
c
g
and formation of the Pd-coordinated homoallylic amide and (3)
product exchange with the organotin salt and regeneration of the
catalyst.
As a proof of concept, deprotection of N-homoallylic sulfamide
1a was carried out in refluxing 1,3-diaminopropane by conven-
tional heating in an oil bath (Scheme 5).14 The conversion was
monitored by TLC. The reaction was found to go to completion
SnBu3NSO2NMe2
O
O
Ph2P
Pd
TFA
PPh2
Ar
SnBu3
transmetalation
TFASnBu3
TFASnBu3
O
O
O
O
Ph2P
Pd
PPh2
Ph2P
Pd
α
PPh2
NSO2NMe2
β
γ
Ar
electrophilic
attack
NSO2NMe2
Ar
H
Scheme 4.

J. Li et al. / Tetrahedron Letters 50 (2009) 2232–2235
2235
H
References and notes
NH2
NSO2NMe2
1,3-diaminopropane
reflux, 2.5 h
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95% isolated yield
Scheme 5.
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(95% yield) within 2.5 h. This result is in full agreement with pre-
vious reports13,14 and confirms the efficiency and reliability of this
deprotection procedure.
In conclusion, [PdTFA(P0CP0)] is shown to be an excellent homo-
geneous catalyst for the allylation of N,N-dimethylsulfamoyl-pro-
tected aldimines, affording the corresponding homoallylic
products which are easily deprotected to homoallylic primary
amines. The ease of deprotection and wide functional group toler-
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Acknowledgements
16. General catalysis procedure: Aldimine 1–12 (0.1 mmol), allylstannane
(0.12 mmol) and [PdTFA(P0CP0)] (0.005 mmol) in DMF (0.5 mL) were stirred
for 16 h at 40 °C. The reaction was then quenched by addition of 1 mL
saturated aqueous KF solution and was stirred overnight at room temperature,
followed by extraction with EtOAc (3 ꢀ 2 mL). The combined organic layers
were washed with brine (1 ꢀ 5 mL), then dried over MgSO4 and concentrated
under vacuum. The crude products were immediately subjected to silica gel
column chromatography using hexanes/EtOAc (7:3) as eluent. 1H and 13C NMR
spectral data of products 1a–12a are available in the Supplementary data.
17. Gagliardo, M.; Selander, N.; Mehendale, N. C.; van Koten, G.; Klein Gebbink, R. J.
M.; Szabóm, K. J. Chem. Eur. J. 2008, 14, 4800–4809.
Utrecht University is thanked for financial support. Dr. Johann
Jastrzebski is acknowledged for his critical reading of the
manuscript.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2009.02.187.