Palladium(II)-catalyzed intramolecular diamination of unfunctionalized alkenes

Article abstract of DOI:10.1021/ja055190y

Intramolecular diamination reactions are described which yield cyclic ureas as direct products of an oxidative alkene transformation in the presence of palladium acetate and iodosobenzene diacetate as terminal oxidant. The reaction is truly catalytic in metal catalyst and represents the proof of principle for this elusive type of alkene oxidation. Copyright

Full text of DOI:10.1021/ja055190y

Published on Web 10/04/2005
Palladium(II)-Catalyzed Intramolecular Diamination of Unfunctionalized
Alkenes
Jan Streuff, Claas H. Ho¨velmann, Martin Nieger, and Kilian Mun˜iz*
Kekule´-Institut fu¨r Organische Chemie und Biochemie, Gerhard-Domagk-Str. 1, D-53121 Bonn, Germany
Received July 31, 2005; E-mail: kilian.muniz@uni-bonn.de
Table 1. Palladium-Catalyzed Intramolecular Diamination of
Alkenes
The development of efficient nitrogen transfer to carbon bonds
constitutes an important endeavor in both academia and industry.1
Such amination reactions have recently been greatly advanced
through intramolecular reaction courses. Elegant examples in this
area include hydroamination,2 aminohydroxylation,3,4 allylic ami-
nation,5 aziridination,6 alkane amination,7 and aza-Wacker8 reac-
tions. We here describe the first realization of catalytic diamination
of unfunctionalized alkenes, which relies on intramolecular reaction
control.
The oxidative catalytic diamination of alkenes represents an
elusive reaction in modern oxidation catalysis. Starting with
pioneering work by Barluenga in 1974,9 initial investigation devised
oxidation reactions that were stoichiometric in metals.10,11 The
development of an efficient catalysis is usually hampered by the
fact that diamines coordinate to almost all transition metals, which
results in poisoning of a potential catalyst. A pronounced example
is given for imidoosmium reagents, which generate stable mono-
meric osmaimidazolidines.11
Earlier attempts by us for diamination catalysis in palladium,
again, experienced the drawback of metal deactivation by the
diamine products.12 It became obvious that, without preventing the
product from metal coordination, palladium catalysis would remain
inefficient.13 To this end, our initial approach started from the
assumption that ω-alkenyl-substituted urea molecules should un-
dergo cyclization in the presence of an electrophilic palladium(II)
catalyst, leading to an intermediary vicinal amino pallada compound.
Palladium replacement through the second amino group of the
urea under oxidative conditions should then regenerate the
palladium(II) catalyst and release the diamination product as a cyclic
urea:
Oxidative diamination following this concept was found to take
place for a range of different starting materials (Table 1). In all
cases, the appropriate choice of reoxidant was crucial, and among
various reoxidants tested, only the hypervalent iodine reagent PhI-
(OAc)2 was highly efficient. With Pd(OAc)2 as precatalyst and
under mild conditions (CH2Cl2, room temperature), diamination and
concomitant formation of five-, six-, and seven-membered fused
rings was conveniently accomplished (Table 1). All reactions
reached high to full conversion, and no compounds other than the
diamination products were produced. Depending on the final ring
size, three different protocols were developed. Protocol A, which
is most suitable for pyrrolidine formation, employs a catalyst loading
of 5 mol % and calls for a stoichiometric amount of base. The
latter accelerates the reaction and leads to full conversion after 12
h (entry 1). Lowering the catalyst loading to 2 mol % requires an
a Procedure A: 5 mol % of Pd(OAc)2, PhI(OAc)2 (2.2 equiv), NMe4Cl/
NaOAc (1 equiv), CH2Cl2, RT, 12 h. Procedure B: 25 mol % of Pd(OAc)2,
PhI(OAc)2 (2.2 equiv), CH2Cl2, RT, 48 h. Procedure C: 10 mol % of
Pd(OAc)2, PhI(OAc)2 (2.2 equiv), CH2Cl2, RT, 12 h. b Determined from
crude 1H NMR spectra and TLC control. c Given yields refer to isolated
analytically pure material after column chromatography.
enhanced reaction period of up to 48 h, but does not effect the
reaction selectivity. The diamination proceeds well for a variety of
further substrates bearing additional substitution at the carbon
skeleton (entries 2-4). Formation of the seven-membered ring
annulation was slightly slower, and the reaction proceeded best with
10 mol % of palladium catalyst (Procedure C, entry 8). In contrast,
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10.1021/ja055190y CCC: $30.25 © 2005 American Chemical Society

C O M M U N I C A T I O N S
Scheme 1. Palladium-Catalyzed Synthesis of Tricyclic
Heterocycles 2a,b
reductive conditions (LiAlH4, then HCl) and furnished the free
diamine in 95% yield from nondeuterated 4. In contrast to earlier
work with preformed imidoosmium oxidants10c,11 or the stoichio-
metric palladium10a,b and thallium9a diaminations, the intramolecular
reactions described herein afford diamines with predictable dif-
ferentiation of the nitrogen substituents.
In summary, we have described intramolecular diamination
reactions of alkenes, which afford a conceptually novel synthesis
of cyclic ureas and diamines, respectively. This process establishes
the principle of oxidative intramolecular diamination reactions,
which are truly catalytic in metal.
Acknowledgment. Financial support from the Fonds der
Chemischen Industrie and the German-Israeli Foundation to K.M.
is gratefully acknowledged.
Supporting Information Available: Experimental procedures,
X-ray data for 2a, and spectral characterization (1H and 13C NMR) for
reaction products. This material is available free of charge via the
Internet at http://pubs.acs.org.
Scheme 2. Mechanistic Proposal
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