An intermolecular palladium-catalyzed diamination of unactivated alkenes

Article abstract of DOI:10.1002/anie.201003653

Adding 2Ns: Palladium catalysis introduces two nitrogen groups in a new regio and chemoselective diamination of non-activated alkenes that proceeds under entirely intermolecular reaction control. This palladium-catalyzed reaction employs commercial nitrogen sources in combination with a hypervalent iodo(III) reagent as oxidant (see scheme; Tos=toluenesulfonyl).

Full text of DOI:10.1002/anie.201003653

Angewandte
Chemie
DOI: 10.1002/anie.201003653
Synthetic Methods
An Intermolecular Palladium-Catalyzed Diamination of Unactivated
Alkenes**
ꢀlvaro Iglesias, Edwin G. Pꢁrez, and Kilian Muꢂiz*
Dedicated to Professor Josꢁ Barluenga on the occasion of his 70th birthday
1,2-Diamines represent a functional group in organic chemis-
try, which commonly is not conceived in a direct manner, but
rather through a combination of several synthetic steps.[1] An
attractive route to vicinal diamines consists of the direct
oxidative transformation of alkenes.[1d,2–7] Recently, this
reaction has been investigated intensively using palladium
catalysts.[3,4] While the diamination of butadienes and related
Table 1: Optimization of the intermolecular diamination.
À
Entry PdII Salt
Equiv
Oxidant R=
Conversion [%][a]
processes involving allylic and homoallylic C H activation
events[5] have been developed to a large extent, the corre-
sponding direct oxidation of alkenes has only become
available for intramolecular processes.[6,7] We report herein
the first general intermolecular 1,2-diamination of unacti-
vated alkenes employing high-oxidation-state palladium
catalysis.[8,9]
HNTos2
1[b]
2[b]
3
Pd(OAc)2
[Pd(NCMe)2Cl2]
Pd(OAc)2
0
0
1.5
1.5
Me
Me
Me
Me
Me
Me
tBu
tBu
tBu
tBu
tBu
n.d.[c]
68[d]
n.d.
n.d.
37
4
5
[Pd(O2CCF3)2
[Pd(NCMe)2Cl2] 1.5
[Pd(NCMe)2Cl2] 1.5
[Pd(NCMe)2Cl2] 1.3
[Pd(NCPh)2Cl2]
[Pd(NCPh)2Cl2]
[Pd(NCPh)2Cl2]
No Pd Salt
6[e]
7
n.d.
60
Initial attempts to realize an intermolecular diamination
tried to make use of the privileged role of phthalimide as a
nitrogen source in palladium-catalyzed oxidation chemis-
try.[10,11] However, it quickly became evident that for the
present case this compound is not suited in combination with
several nitrogen-based oxidants such as N-bromosuccinimide
(NBS), chloramine-T, N-fluorobis(phenylsulfonyl)imide, or
hypervalent iodo derivatives. In contrast to phthalimide, the
use of saccharide as the nitrogen source led to the long-sought
break-through (Table 1), when working with 1-octene as
alkene in the presence of iodobenzene dicarboxylates as
oxidants.[12] The reaction was developed on a 1 mmol scale for
preparative reasons, and the alkene was the limiting agent.
Attempts to work with saccharin as the only nitrogen source
were not productive (Table 1; entries 1 and 2) and with a
palladium dichloride catalyst led exclusively to enamide
formation.[13] This outcome verifies saccharin as an efficient
nitrogen source for aminopalladation. If a further 1.5 equiv-
alents of bistosylimide are added, this is selectively incorpo-
rated into the products as the second nitrogen source. This
8
1.3
1.3
1.3
1.3
95 (74)[f]
95 (74)[f]
95 (74)[f]
0
9[g]
10[h]
11
[a] Estimated from the 1H NMR spectrum of the crude reaction mixture.
[b] Reaction with 2 equivalents of saccharin. [c] n.d.=not determined,
less than 5% conversion. [d] Enamide product. [e] In the presence of
2 equivalents of NaOAc. [f] Yield of isolated product in parentheses.
[g] Reaction at room temperature. [h] With 5 mol% catalyst. Tos=tolu-
ene-4-sulfonyl.
reaction again requires bis(acetonitrile)palladium dichloride
as the catalyst source (Table 1; entry 5), while related acetate
and trifluoroacetate salts are completely unreactive (Table 1;
entries 3 and 4). Aminoacetoxylation products as known for
reactions with phthalimide[11a] were not obtained at all.
Addition of a base was found to inhibit the reaction
completely (Table 1; entry 6). Yields can be further increased
upon changing iodosobenzene diacetate for iodosobenzene
dipivalate and by use of the benzonitrile complex [Pd-
(NCPh)2Cl2] (Table 1; entries 7 and 8). Finally, the catalyst
loading and the amount of bistosylimide can be decreased to
5 mol% and 1.3 equivalents, respectively, and the temper-
ature lowered to room temperature (Table 1; entries 9 and
10). No conversion takes place in the absence of the
palladium salt (Table 1; entry 11).
[*] Dr. ꢀ. Iglesias, Dr. E. G. Pꢁrez,[+] Prof. Dr. K. Muꢂiz
Institute of Chemical Research of Catalonia (ICIQ)
Av. Paꢃsos Catalans 16, 43007 Tarragona (Spain)
Fax: (+34)977-920-224
E-mail: kmuniz@iciq.es
Homepage: http://www.iciq.es
[+] Permanent address: Facultad de Quꢄmica
Pontificia Universidad Catꢅlica de Chile
A series of terminal alkenes is converted into the
corresponding diamines under these reaction conditions
with saccharin and bistosylimide as nitrogen sources. All of
these reactions proceed with high chemoselectivity and
complete regioselectivity. Representative examples are
depicted in Table 2.
Vicuꢂa Mackenna 4860, Casilla 306, Correo 22, Santiago (Chile)
[**] We thank Fundaciꢅn ICIQ, the Consolider INTECAT 2010 (Project
CSD2006-0003), and the Fonds der Chemischen Industrie for
financial support. E.G.P. was funded by ICM Grant P05-001.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201003653.
Angew. Chem. Int. Ed. 2010, 49, 8109 –8111
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
8109

Communications
Table 2: Intermolecular palladium-catalyzed diamination of alkenes.[a]
malonate 1n gives rise to the corresponding diamine 2n with
acceptable yield (Table 2; entry 14). These examples consti-
tute the first palladium-catalyzed intermolecular diamination
of simple alkenes and the first to use commercially available
nitrogen sources[14] for the construction of noncyclic vicinal
diamine derivatives. The catalyst loading of 5–10 mol%
remains relatively high, but compares well with respect to
related alkene oxidation reactions.[9,11] Internal alkenes do not
react under these conditions.
Entry Alkene
Product
Yield
[%][b]
All products 2a–n display spectroscopic data in agree-
ment with the expected vicinal diamine motif, this was
unambiguously confirmed by an X-ray structure determina-
tion of derivative 2 f (Figure 1).
1
2
3
4
1-octene (1a)
2a: n=4
2b: n=2
2c: n=6
2d: n=8
74
73
76
87
1-hexene (1b)
1-decene (1c)
1-duodecene (1d)
5[b]
4-phenylbutene (1e)
vinylcyclohexane (1 f)
82
78
6[b]
7[b,c] 3-methylhexene (1g)
93[d]
72
8
9
67
Figure 1. X-ray structure of 2 f C gray, N blue, O red, S yellow.
10
11
12
13
14
11-bromoundecene (1j)
7-bromoheptene (1k)
7-azidoheptene (1l)
94
87
90
35
40
The reaction can also be conducted with bissulfonimides
other than bistosylimide. Scheme 1 shows some examples of
imides of the type (RSO2)2NH in the vicinal diamination of 1-
octene.
2-allyl diethylmalonate
(1n)
[a] Reactions on a 1 mmol scale. [b] Yield of isolated product. [c] With
10 mol% of catalyst, 1.5 equivalents of oxidant, 2 equivalents of
bistosylimide. [d] 3:2 ratio of diastereomers. HNSacc=saccharin.
Scheme 1. Regioselective diamination of 1-octene with different bissul-
fonimides as the nitrogen source; TMS=trimethylsilyl, Tol=tolyl.
At the outset, the oxidation of simple alkenes with
hydrocarbon substituents including a 3,3-disubstitution pat-
tern were investigated, all of which led to regio and chemo-
selective diamination reactions in good yields (Table 2;
entries 1–6). Enamide formation is less than 15% in all
cases, which demonstrates that the competing b-hydride
elimination pathways are efficiently disabled under the
chosen oxidation conditions.[8] The chiral 3-methylhexene
1g is converted into a 3:2-mixture of the two corresponding
diastereomeric diamines 2g/2g’ in high yield (Table 2;
entry 7). Common functional groups, such as esters, amides,
halogenides, azides, and sulfones are all tolerated under these
reaction conditions (Table 2; entries 8–13). Finally, the allyl
For the standard product 2a, the deprotection of the two
amino groups proceeds under acidic conditions (Scheme 2),
and the free diamine was converted into the bisbenzoylamide
3a to allow for a suitable confirmation of identity. Interest-
ingly, treatment of the di-SES-derivative 2r with an excess of
cesium fluoride, not only leads to selective removal of one of
the SES groups,[15] but complete removal of the saccharin
group to give the free primary amine 3b was accomplished.
To conclude, we have developed the first palladium-
catalyzed intermolecular diamination of non-activated termi-
8110
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Scheme 2. Deprotection of the diamination products 2a and 2r.
SES=2-trimethylsilylethyl.
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nitrogen sources and proceeds with complete regioselectivity
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[10] Within strict terminology, the present cases can not be classed as
amine-transfer reactions, as imines are employed as nitrogen
sources. However, recently the term amination reactions has
been used almost exclusively for this type of reaction (see, for
example, Ref. [9e] and [11]). We therefore within this work refer
to the term diamination for the transfer of the two nitrogen
groups onto an alkene, in agreement with earlier work. Please
see also Ref. [6b] for an earlier discussion of this context.
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Received: June 15, 2010
Published online: September 22, 2010
Keywords: alkenes · amides · diamines · oxidation · palladium
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[13] Further details are included in the Supporting Information.
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À
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Angew. Chem. Int. Ed. 2010, 49, 8109 –8111
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
8111