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Angewandte
Communications
DOI: 10.1002/anie.201308874
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C N Bond formation
A General Catalytic Hydroamidation of 1,3-Dienes: Atom-Efficient
Synthesis of N-Allyl Heterocycles, Amides, and Sulfonamides**
Debasis Banerjee, Kathrin Junge, and Matthias Beller*
Abstract: Transition-metal-catalyzed hydroamination reac-
the synthesis of an intermediate for the Takasago (À)-
menthol process.[6] As compared to analogous reactions of
amines,[7] the selective addition of electron-deficient N-
heterocycles, amides, and sulfonamides to olefins and dienes
is scarce and has rarely been investigated.[8] To the best of our
knowledge, no hydroamidation reactions of 1,3-dienes in the
presence of palladium catalysts exist.
On the basis of our long-standing interest in the catalytic
hydroamination of alkynes,[9] and our recent studies on the
synthesis of allylic amines by the palladium-catalyzed amina-
tion of allylic alcohols,[10] we became interested in the related
hydroamidation of 1,3-dienes (Scheme 1). Unfortunately, the
use of previous catalyst systems for the hydroamidation of
isoprene was not successful. However, [{Pd(p-cinnamyl)Cl}2]
in the presence of 1,3-bis(diphenylphosphino)propane (L7) or
1,4-bis(dicyclohexylphosphino)butane (L10) enabled the gen-
eral and regioselective 1,4-addition of a variety of electron-
deficient N-heterocycles, cyclic and acyclic amides, and
sulfonamides.
À
tions are sustainable and atom-economical C N bond-forming
processes. Although remarkable progress has been made in the
inter- and intramolecular amination of olefins and 1,3-dienes,
related intermolecular reactions of amides are still much less
known. Control of the regioselectivity without analogous
telomerization is the particular challenge in the catalytic
hydroamidation of alkenes and 1,3-dienes. Herein, we report
a general protocol for the hydroamidation of electron-deficient
N-heterocyclic amides and sulfonamides with 1,3-dienes and
vinyl pyridines in the presence of a catalyst derived from
[{Pd(p-cinnamyl)Cl}2] and ligand L7 or L10. The reactions
proceeded in good to excellent yield with high regioselectivity.
The practical utility of our method is demonstrated by the
hydroamidation of functionalized biologically active sub-
strates. The high regioselectivity for linear amide products
makes the procedure useful for the synthesis of a variety of
allylic amides.
À
T
he selective construction of C N bonds continues to be an
At the start of this study, we investigated the intermo-
lecular hydroamidation of isoprene (1a) and 4-methylphthal-
imide (2a) as a model reaction in the presence of [{Pd(p-
cinnamyl)Cl}2] and different phosphine ligands L1–L15
(Scheme 2). The application of monodentate ligands L1–L3
resulted in no conversion. Similarly, ligands L4 and L5
containing a biaryl backbone gave no desired product 3a.
Also, various bidentate ligands, for example, 1,4-bis(diphe-
nylphosphino)butane (dppb, L8), 1,5-bis(diphenylphosphi-
no)pentane (dpppent, L9), and L15 proved to be catalytically
inert. However, 1,4-bis(dicyclohexylphosphino)butane (L10),
1,2-bis(diphenylphosphinomethyl)benzene (L11), L12, Xant-
phos (L13), DPEphos (L14), and 1,2-bis(diphenylphosphino)-
ethane (L6) gave the desired product 3a in 5–60% yield.
Notably, the best results were obtained using 1,3-bis(diphe-
nylphosphino)propane (L7) and gave 75% yield of 3a as
a single regioisomer.
Next, we studied the influence of different catalyst
precursors, solvents, and temperatures for the intermolecular
hydroamidation with L7 as the most promising ligand
(selected results are summarized in Table 1). The use of
a number of different PdII and Pd0 precursors led to poor or
no product yield. [{Pd(p-cinnamyl)Cl}2] was identified as the
best precatalyst (Table 1, entries 1–6). The choice of solvent
also played a crucial role in the hydroamidation reaction; for
example, applying 1,4-dioxane did not result in any product of
3a (Table 1, entry 7). However, the use of tert-amyl alcohol
and n-heptane gave 3a in 34 and 75% yield, respectively
(Table 1, entries 8 and 9). The optimal result was achieved in
toluene. We studied the influence of different bases and found
that inexpensive Na2CO3 afforded 3a in 80% yield (Table 1,
important goal in catalysis and organic synthesis. Most well-
established methodologies for the synthesis of amides and
related compounds rely on the condensation of acids with
amines in the presence of activating/dehydration reagents and
involve significant amounts of waste generation. In contrast,
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À
the direct addition of N H bonds to unsaturated C C bonds,
commonly known as hydroamination, is a more sustainable
and atom-efficient process.[1] Especially in the last two
decades, the utility of catalytic hydroamination reactions
has been extensively explored. On the basis of elegant
mechanistic investigations, several intramolecular reactions
have been developed.[2] Despite notable progress in this
area,[3,4] the development of a general intermolecular process
with non-activated alkenes is still a challenging task.[5] On the
other hand, simple base-catalyzed hydroamination reactions
with 1,3-dienes or styrenes proceed smoothly owing to the
increased stabilization of the anionic intermediate. In fact, the
best-known example of an intermolecular hydroamination is
[*] Dr. D. Banerjee, Dr. K. Junge, Prof. Dr. M. Beller
Leibniz-Institut fꢀr Katalyse an der Universitꢁt Rostock
Albert-Einstein-Strasse 29a, 18059 Rostock (Germany)
E-mail: matthias.beller@catalysis.de
[**] This research was funded by the State of Mecklenburg–Western
Pomerania, the BMBF, and the DFG (Leibniz Prize). We thank Dr. W.
Baumann, Dr. C. Fischer, S. Buchholz, S. Schareina, A. Koch, and S.
Rossmeisl (all at LIKAT) for their excellent technical and analytical
support.
Supporting information for this article is available on the WWW
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ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2014, 53, 1630 –1635