Intermolecular regioselective 1,2-diamination of allylic ethers

Article abstract of DOI:10.1002/adsc.201000813

Homogeneous palladium catalysis enables a novel intermolecular regioselective diamination of allylic ethers, which offers a convenient entry into 1,2,3-trisubstituted products. These represent suitable building blocks with differently protected nitrogen atoms for subsequent synthetic application. Copyright

Full text of DOI:10.1002/adsc.201000813

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DOI: 10.1002/adsc.201000813
Intermolecular Regioselective 1,2-Diamination of Allylic Ethers
Kilian MuÇiz,a,b,* Jonathan Kirsch,a and Patricia Chꢀveza
a
Institute of Chemical Research of Catalonia (ICIQ), Av. Paꢁsos Catalans 16, E-43007 Tarragona, Spain
Fax : (+34)-97-792-0224; phone: (+34)-97-792-0200; e-mail: kmuniz@iciq.es
Catalan Institution for Research and Advanced Studies (ICREA), Pg. Lluꢂs Companys 23, 08010 Barcelona, Spain
b
Received: October 28, 2010; Revised: December 19, 2010; Published online: March 15, 2011
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201000813.
Abstract: Homogeneous palladium catalysis enables
a novel intermolecular regioselective diamination of
allylic ethers, which offers a convenient entry into
1,2,3-trisubstituted products. These represent suita-
ble building blocks with differently protected nitro-
gen atoms for subsequent synthetic application.
catalysis.[12] While quite general for terminal alkenes,
we found that allylic ethers do not react under these
conditions and are beyond the scope of the reaction.
Since allylic ethers can be considered as versatile sub-
strates for alkene oxidation because they lead to an
interesting 1,2,3-trifunctionalization, we sought to de-
velop a suitable protocol for this type of substrates.
We here report on the regio- and chemoselective in-
termolecular diamination of allylic ethers and exem-
plify the utility of the products as versatile building
blocks for subsequent organic synthesis.
Keywords: alkenes; amides; diamines; oxidation;
palladium
At the outset, we took inspiration in the seminal
report on intermolecular aminoacetoxylation of allylic
The 1,2-diamination of alkenes is an oxidation process ethers by Stahl and Liu.[13,14] This work demonstrated
to convert carbon-carbon double bonds into vicinal the versatile combination of phthalimide and a palla-
diamine derivatives,[1] which are of high significance dium dichloride catalyst to initiate intermolecular
in a variety of areas.[2]
aminopalladation. Initial efforts then focused on the
Recent progress has demonstrated the ability of exploration of N-fluoro-bis(phenylsulfonyl)imide
several transition metals to catalyze this transforma- (NFSI) as a suitable nitrogen source for the second
tion, including palladium,[3,4] copper,[5] nickel[6] and carbon-nitrogen bond installment.[4,15,16]
gold.[7] These reactions share a common concept of in-
For the diamination reactions of benzyl allyl ether
tramolecular aminometalation as the initial step and 1a with phthalimide as nitrogen source and NFSI as
hence give rise to concomitant formation of heterocy- oxidant and nitrogen source, a screening of some
cles such as pyrrolidines.[8]
common palladium salts led only to varyingly low
In addition to these diamination reactions of non- amounts of diamination product (Table 1, entries 1–
activated and activated alkenes, Shi has developed el- 3). Only palladium bis(hexafluoroacetylacetonate)
À
egant sequential d,g-C H activation/diamination reac- [Pd
tions of terminal alkenes as well as diamination reac- induce moderate product formation (entry 4). Under
(hfacac)2] as the catalyst precursor was able to
tions of 1,3-butadienes.[9,10]
these conditions, phthalimide could also be replaced
We recently developed a first strictly intermolecular by saccharin (entry 5). A subsequent screening of sol-
palladium catalyzed diamination of alkenes vents revealed that ethyl acetate represented the opti-
(Scheme 1),[11] using high oxidation state palladium mum solvent for the present transformation (en-
tries 5–9). For n-butyl allyl ether 1b, similar reactivity
was observed for the two nitrogen sources saccharin
and phthalimide, giving rise to products 2c and 2d, re-
spectively (entries 10 and 11).
These reactions proceed with complete regioselec-
tivity and no other 1,2-dioxidation products than the
diamine derivatives were obtained. However, the re-
action suffered from low conversion and yields usual-
Scheme 1. Intermolecular diamination of alkenes.
ly remained below 50%. Finally, addition of iodoso-
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Table 1. Palladium-catalyzed diamination of alkenes: optimization of the process.
Entry
1
R
Y
Pd Catalyst
Solvent
EtOAc
Diamine
Yield [%]
Bn (1a)
CO
(MeCN)2PdCl2
<10
2
3
4
Bn (1a)
Bn (1a)
Bn (1a)
CO
CO
CO
Pd
Pd
Pd
N
EtOAc
EtOAc
EtOAc
2a
2a
2a
<10
15
32
5
Bn (1a)
SO2
EtOAc
37
6
7
8
9
Bn (1a)
Bn (1a)
Bn (1a)
Bn (1a)
SO2
SO2
SO2
SO2
CH2Cl2
MeCN
acetone
dioxane
2b
2b
2b
2b
<10
25
28
<10
10
11
n-Bu (1b)
SO2
EtOAc
35
n-Bu (1b)
n-Bu (1b)
CO
CO
EtOAc
EtOAc
32
70
12[b]
2d
[a]
hfacac=hexafluoroacetylacetonate.
2 mmol alkene, phthalimide (1 mmol), NFSI (1.6 mmol), PhIACTHNUGTRENUNG(OPiv)2 (1.6 mmol).
[b]
benzene dipivalate to the reaction mixture containing tions[12] is noteworthy. A benzoyl-protected allylic
phthalimide and NFSI led to a great improvement in substrate was diaminated in 68% yield (entry 7) and
yield and the diamination product 2d could be isolat- two substrates with stereogenic allylic positions gave
ed in 70% yield. Importantly, the corresponding reac- the corresponding diamination products as single dia-
tion with saccharin does not experience this increase stereomers (entries 8 and 9). Their relative configura-
in yield.
tion was assessed by comparison with literature prece-
This latter procedure was then employed for the dents and matches the outcome from the earlier ami-
synthesis of a series of different diamination products noacetoxylation reaction.[13,17] A more sterically de-
from allylic ethers. Table 2 shows representative ex- manding ether with a gem-disubstituted allylic posi-
amples. Various alkyl allyl ethers undergo clean di- tion still gave selective diamination (entry 10). Benzyl
ACHTUNGTRENNUNGamination in 64–72% isolated yield with the expected methallyl ether showed an equally reduced reactivity,
complete regioselectivity as detected from the crude but again the reaction proceeded with complete
reaction mixture (entries 1–6). This chemoselectivity regio- and chemoselectivity (entry 11). Internal al-
over potentially competing aminooxygenation reac- kenes were found to be beyond the scope of the reac-
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Intermolecular Regioselective 1,2-Diamination of Allylic Ethers
Table 2. Palladium-catalyzed intermolecular diamination of allylic ethers.
Entry
1
R
R’
R’’
R’’’
Diamine
Yield [%][a]
Bn
H
H
H
72
2
3
4
5
6
n-Bu
Me
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
70
65
64
68
67
Et
n-Pr
n-Oct
7
8
9
PhCO
H
H
H
H
H
H
H
68
Bn
Ph
Ph
65b
55b
691
Me
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Table 2. (Continued)
Entry
R
R’
R’’
R’’’
Diamine
Yield [%][a]
10
Bn
Me
Me
H
40
11
Bn
H
H
H
H
H
Me
H
43
32
12[b]
[a]
Isolated yield after purification.
100% de according to the H NMR spectrum of the reaction crude.
[b]
1
tion. Finally, even free allylic alcohol could be oxi- some representative reactions (Scheme 2). In order to
dized under the present conditions (entry 12). allow for further differentiation of the two nitrogen
All products show the expected spectroscopic data groups, standard treatment of diamination product 2d
in agreement with the depicted structures[17] and the with methylhydrazine led to clean conversion of the
constitution of the diamination products was unam- phthalimide group into the free primary amine, which
biguously established by an X-ray crystallographic was isolated as the corresponding methyl carbamate 3
analysis of product 2d (Figure 1).[18]
for the sake of convenient manipulation.
The synthetic utility of these diamination products
The free alcohol 2n as generated via direct diami-
as suitable building blocks was investigated within nation of allylic alcohol can be obtained otherwise via
hydrogenolysis of the benzyl ether 2a. By this route,
2n is available in an overall 68% yield from benzyl
allyl ether. Again, compound 2n serves as an interest-
ing starting compound for further derivatization. For
example, it can selectively be oxidized to the corre-
sponding 2,3-diaminopropionaldehyde 4 containing
differentiated nitrogen groups. Alternatively, conver-
sion of the free alcohol 2n into the 1,2,3-triaminated
azide-containing compound 5 proceeds with partial
deprotection of the bis-sulfonimide. Compound 5
allows for a subsequent cycloaddition process to
arrive at the triazole 6, thereby demonstrating that
the densely functionalized triamine derivative 5 can
be successfully employed in “click chemistry”.[19]
In summary, we have realized the catalytic intermo-
lecular diamination of allylic ethers. The reaction em-
ploys catalytic amounts of palladium(II) compounds
as catalyst source and proceeds with complete regio-
selectivity. It represents a significant advance in oxi-
dative 1,2-difunctionalization of alkenes. Work in
order to understand the underlying mechanism and
the cooperative effect of the two oxidants as well as
to extend the intermolecular diamination to internal
alkenes is ongoing.
Figure 1. Structure of product 2d in the solid state (N black,
O dark grey, S light grey, C white).
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Intermolecular Regioselective 1,2-Diamination of Allylic Ethers
Scheme 2. Reactions employing 1,2,3-trifunctionalized diamination products. [a] 10 mol% Pd(OH)/C, 1 atm. H2, EtOAc.
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[3] a) J. Streuff, C. H. Hçvelmann, M. Nieger, K. MuÇiz, J.
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PdACHTUNGTRENNUNG(hfacac)2 (0.028 mmol, 14.5 mg), phthalimide (0.4 mmol,
60 mg), PhI[OC(O)t-Bu]2 (0.64 mmol, 260 mg), N-fluorodi-
benzenesulfonimide (0.64 mmol, 200 mg) and the allyl ether
substrate (0.8 mmol) were suspended in 0.4 mL of ethyl ace-
tate (EtOAc) in a pyrex tube. The mixture was heated at
708C for 12 h. After cooling, the solution was evaporated
under reduced pressure and the crude product was purified
by chromatography on silica gel to give the diamination
product.
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Acknowledgements
This work was financially supported by ICREA and by ICIQ
Foundation. JK is a predoctoral student from Strasbourg
University on leave at ICIQ. We thank Dr. J. Benet, Dr. E. C.
Escudero and Dr. M. Martꢀnez from the X-Ray Diffraction
Unit at ICIQ for the X-ray structure determination and Dr.
A. Iglesias for several discussions.
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