Regioselective Intermolecular Diamination and Aminooxygenation of Alkenes with Saccharin

Article abstract of DOI:10.1021/acs.orglett.6b01368

Palladium catalysis enables the regioselective difunctionalization of alkenes using saccharin as the nitrogen source in the initial step of aminopalladation. Depending on the reaction conditions, diamination or aminooxygenation pathways can be accessed using hypervalent iodine reagents as the terminal oxidants. The aminooxygenation of allylic ethers originates from an unprecedented ambident behavior of saccharin. The participating palladium catalysts contain a palladium-saccharide unit. Two representative complexes of this type could be isolated and characterized.

Full text of DOI:10.1021/acs.orglett.6b01368

Letter
pubs.acs.org/OrgLett
Regioselective Intermolecular Diamination and Aminooxygenation
of Alkenes with Saccharin
†
†,$
†
†
,†,‡
́
Claudio Martínez, Edwin G. Perez, Alvaro Iglesias, Eduardo C. Escudero-Adan, and Kilian Muniz*
́
́
̃
†Institute of Chemical Research of Catalonia (ICIQ), The Barcelona Institute of Science and Technology, Av Països Catalans 16,
43007 Tarragona, Spain
$Departamento de Química Organ
306, Santiago 22, Chile
́ ́
ica, Facultad de Química, Pontificia Universidad Catolica de Chile, Vicuna Mackenna 4860, Casilla
̃
‡Catalan Institution for Research and Advanced Studies (ICREA), Pg Lluís Companys 23, 08010 Barcelona, Spain
S
* Supporting Information
ABSTRACT: Palladium catalysis enables the regioselective
difunctionalization of alkenes using saccharin as the nitrogen
source in the initial step of aminopalladation. Depending on
the reaction conditions, diamination or aminooxygenation
pathways can be accessed using hypervalent iodine reagents as
the terminal oxidants. The aminooxygenation of allylic ethers
originates from an unprecedented ambident behavior of
saccharin. The participating palladium catalysts contain a palladium−saccharide unit. Two representative complexes of this
type could be isolated and characterized.
he oxidative difunctionalization of alkenes represents a
initial palladium dichloride or diacetate salt is readily trans-
Tpowerful tool for the efficient 1,2-introduction of formed into the corresponding bisphthalimidato palladium
derivatives at the outset of the reaction.
heteroatoms into organic frameworks and thus for structural
diversification from common hydrocarbon groups.1 Within
such vicinal difunctionalization, palladium catalysis constitutes a
particularly effective approach. In this specific area, the
development of conditions that are applicable to intermolecular
reaction control are of particular challenge. A currently limited
number of different protocols have become available, including
dihalogenation,2 dioxygenation,3 aminooxygenation,4 amino-
fluorination,5 and diamination6 reactions.
Since vicinal diamines constitute an important class of
functional groups that are present in a number of molecular
entities of pharmaceutical and medicinal interest7 and function
as effective ligands to transition metals to provide catalysts,8,9
the development of new avenues for their synthesis is of major
interest. Within this context, the direct vicinal diamination of
alkenes offers a straightforward access,10 and we have been
interested in devising suitable reaction conditions that enable
palladium catalysis to operate under completely intermolecular
conditions.6,11
Some time ago, we introduced saccharin as a useful nitrogen
source in the palladium-catalyzed vicinal diamination of alkenes
under intermolecular reaction control.6a The combination of
this particular imine together with iodosobenzene diacetate and
bissulfonylimines as a second nitrogen source enabled the
realization of the first regio- and chemoselective diamination of
terminal alkenes. Saccharin owes its attractiveness as a nitrogen
source to its commercial availability and low price.
We were intrigued to study the performance of these
common palladium salts in the presence of saccharin 1 as well.
Indeed, when an acetonitrile solution of palladium diacetate 2
was treated with 2 equiv of saccharin 1, clean formation of the
new bisacetonitrile palladium disaccharide complex 3 was
observed. This complex was obtained as a stable yellowish solid
(Scheme 1). Attempts to crystallize this compound from
organic solvents were not successful. Instead, loss of the
acetonitrile ligands occurred, leading to formation of the
trimeric palladium complex 5. For the reaction in dichloro-
methane, 5 was obtained as a yellow to orange solid in
quantitative yield. In a similar manner, when palladium
dichloride 4 was treated with saccharin 1 at elevated
temperature, quantitative formation of complex 5 was observed.
Crystals suitable for X-ray crystallographic analysis were grown
from a solution in warm toluene. The resulting solid-state
structure of 5 is depicted in Figure 1. In contrast to the related
phthalimido complex, [Pd3(NPhth)6],12 complex
[Pd3(NSacc)6] 5 displays C3 helical chirality.
The two compounds 3 and 5 display the expected features.
Complex 3 is stable in the presence of hypervalent iodine
reagents such as PhI(OAc)2 and PhI(O2CtBu)2 as expected for
a palladium(II) compound involved in oxidation reactions in
the presence of these reagents. Complex 5 is stable in isolated
form in the solid state and in solution, while it dissociates back
to monomeric palladium complexes in the presence of donor
We recently investigated the composition of the active
palladium catalyst in related oxidative amination reactions of
alkenes with phthalimide.12 We could demonstrate that the
Received: May 11, 2016
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.6b01368
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Letter
Scheme 1. Formation of Bissaccharido Palladium(II)
Complexes 3 and 5
Scheme 2. Palladium-Catalyzed Diamination of Terminal
Alkenes with Isolated Complex 3
1-hexene 6b, 1-decene 6c, and 1-duodecene 6d give the
corresponding diamination products 7b−d in 60−73% yield. 4-
Phenylbutene 6e provides diamine 7e in 55% yield.
Importantly, allylbenzene 6f gives a clean diamination product
7f in 63% yield, while under the previous conditions the
predominant product is alkene isomerization catalyzed by
Pd(NCMe)2Cl2.13 As observed for the related compound
Pd(NCMe)2(NPhth)2,12 Pd(NCMe)2(NSacc)2 does not pro-
mote alkene isomerization under the reaction conditions of
diamination. This reaction outcome of chemoselective
diamination of allylbenzene 7f is also obtained when the
bissulfonylimide is bismesylimide or mesyltosylimide, which
leads to formation of compounds 7g and 7h, respectively.
When the diamination reaction was attempted under the
same conditions with allyl propyl ether 8a, no desired
diamination product was observed in the crude reaction
mixture. This result matches previous observations that had
led us to develop the corresponding diamination reactions
using phthalimide as nitrogen source.6b However, in the present
case, a small amount of the unprecedented difunctionalization
product could be obtained in less than 10% yield. This
compound turned out to be the vicinal aminooxygenated
product 9a from incorporation of two saccharin units (Scheme
3). Since there was no apparent incorporation of the
bistosylimide into the oxidation product, subsequent exper-
imentation employed a double amount of saccharin. In this
way, aminooxygenation product 9a was obtained in 73%
isolated yield. Its structure was unambiguously determined by
X-ray analysis.
Figure 1. Molecular structure of [Pd3(NSacc)6] 5 in the solid state (X-
ray structure). Selected bond lengths (Å) and angles (deg) for one
palladium unit: Pd1 N1 1.996(5), Pd1 N2 1.999(6), Pd1 O10
2.007(5), Pd1 O13 2.022(5), N1 Pd1 N2 90.2(2), N1 Pd1 O10
86.6(2), N2 Pd1 O10 174.5(2), N1 Pd1 O13 168.1(2).
ligands. With the isolated bissaccharidato palladium complex 3
containing defined palladium−nitrogen bonds in hand, we
investigated its behavior in the catalytic diamination of alkenes
and started our exploration for the known transformation of 1-
octene 6a. Using catalytic amounts of preformed 3, this alkene
undergoes the reported diamination reaction to the expected
product 7a in 80% yield (Scheme 2). This compares well to the
74% yield obtained for the corresponding diamination with the
previously reported Pd(NCMe)2Cl2 catalyst.6a Related alkenes
This unprecedented aminooxygenation reaction proved
general under the given reaction conditions. In addition to
9a, related allyl n-alkyl ethers 8b−e gave the corresponding
difunctionalization products 9b−e in 50−65% yield. The benzyl
derivative 9f was formed in 74%, and the reaction could be
extended to secondary alkyl ethers such as the pentyl derivative
B
DOI: 10.1021/acs.orglett.6b01368
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Scheme 3. Palladium-Catalyzed Aminooxygenation of Allyl
Ethers and Esters 8
Figure 2. Mechanistic scenario for palladium-catalyzed difunctionaliza-
tion reactions with saccharin.
study on an oxidation of an isolated palladium saccharinato
complex had suggested clean C−N bond formation.16c
Moreover, studies by Mayr had revealed exclusive amination
of the diphenylmethyl cation in the reaction with saccha-
ride.17,18 Obviously aminooxygenation products 9 represent
kinetic products. We explain the notable difference in the
present catalysis by the fact that reductive elimination from the
intermediary palladium(IV) catalyst state B is a fast process
resulting in kinetic C−O bond formation. More detailed
mechanistic studies are ongoing.
In summary, we have synthesized the first bissaccharido
palladium complexes and have investigated their behavior in the
vicinal difunctionalization of terminal alkenes.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.6b01368.
9g (49% yield). The benzoyl ester 9h was obtained in 67%
yield, and higher functionalized products 9i and 9j incorporat-
ing a methoxyethylenyl and glycidyl unit were produced in 49
and 67% yield, respectively. Importantly, under these
conditions, terminal alkenes 6 are completely unreactive.
The mechanistic proposal for the present difunctionalization
reactions is given in Figure 2. The reaction starts from
palladium catalyst 3, which engages in aminometalation with
saccharin to arrive regioselectively at the anti-Markovnikov
aminopalladated intermediate A.1a−c,14 Metal oxidation to high
oxidation state palladium(IV) intermediate B15 is accomplished
with the hypervalent iodine reagent. The diamination pathway
proceeds through commonly observed nucleophilic attack of
bissulfonimide at the α-carbon of the σ-alkylpalladium(IV)
leading to diamination products 7.16 In the case of nucleophilic
addition of saccharin, the nucleophilic displacement takes place
via oxygenation to provide aminooxygenation products 9. In
both cases, the palladium(II) catalyst 3 is regenerated.
Full experimental details and characterization data for
new compounds (PDF)
X-ray data for compound 5 (CIF)
X-ray data for compound 9a (CIF)
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: kmuniz@iciq.es.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support for this project was provided from the
Spanish Ministry for Economy and Competitiveness and
FEDER (CTQ2014-56474R grant to K.M. and Severo Ochoa
Excellence Accreditation 2014-2018 to ICIQ, SEV-2013-0319)
and the Cellex-ICIQ Program (fellowship to C.M.).
Obviously, saccharin displays an ambident behavior in the
latter alkene difunctionalization. While it engages in a C−N
bond formation within the initial aminopalladation, after
oxidation to B, the subsequent reductive elimination involves
the tautomeric anion of saccharide resulting in C−O bond
formation. This outcome is rather unexpected as an earlier
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