Gold(I)-Catalyzed intermolecular hydroamination of allenes with arylamines

Article abstract of DOI:10.1055/s-0029-1218555

A mixture of [P(t-Bu)²-o-biphenyl]AuCl and AgOTf catalyzes the intermolecular hydroamination of monosubstituted and 1,1- and 1,3-disubstituted allenes with primary and secondary arylamines. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0029-1218555

LETTER
419
Gold(I)-Catalyzed Intermolecular Hydroamination of Allenes with
Arylamines
G
old(I)-Catalyzed
l
Interm
e
olecular
H
y
t
droam
h
ination of
A
l
e
lenes
w
ith
a
A
rylamines N. Duncan, Ross A. Widenhoefer*
French Family Science Center, Duke University, Durham, NC 27708, USA
Fax +1(919)660-1605; E-mail: rwidenho@chem.duke.edu
Received 21 August 2009
hydroamination to include 1,1-disubstituted allenes, nei-
ther the requisite gold CAAC catalyst, nor the ligand from
which it is derived are commercially avialable.13 Here we
report an operationally simple method for the intermolec-
ular hydroamination of monosubstituted and 1,1- and 1,3-
disubstituted allenes with primary and N-alkyl anilines
catalyzed by a commercially available gold(I) complex
under mild conditions.
Abstract: A mixture of [P(t-Bu)2-o-biphenyl]AuCl and AgOTf cat-
alyzes the intermolecular hydroamination of monosubstituted and
1,1- and 1,3-disubstituted allenes with primary and secondary aryl-
amines.
Key words: allylations, allenes, amines, homogenous catalysis,
regioselectivity
The catalyst system optimized for the intermolecular hy-
droamination of allenes with carbamates proved only
modestly effective for the intermolecular hydroamination
of allenes with arylamines. As an example, treatment of
aniline with 3-methyl-1,2-butadiene (1; 2 equiv) and a
catalytic 1:1 mixture of (IPr)AuCl [IPr = 1,3-bis(2,6-di-
isopropylphenyl)imidazol-2-ylidine] and AgOTf in tolu-
ene at room temperature for 24 hours led to 10%
conversion to form N-prenylaniline (2a) as the exclusive
product (Table 1, entry 1). Substitution of the sterically
hindered o-biphenyl phosphine ligand P(t-Bu)2-o-biphe-
nyl (3) for IPr and dioxane for toluene increased the con-
version under these conditions to 35% (Table 1, entry 3).
Raising the temperature to 45 °C led to complete con-
sumption of aniline after 12 hours to form a 4.1:1 mixture
of 2a and N,N-diprenylaniline (2b; Table 1, entry 4).
Aniline derivatives 2a and 2b were isolated in 73% and
17% yield, respectively, from the corresponding prepara-
tive-scale reaction of 1 with aniline (Table 2, entry 1).
Control experiments ruled out silver- and acid-catalyzed
pathways for the hydroamination of 1 with aniline
(Table 1, entries 5–7).
The transition-metal-catalyzed addition of the N–H bond
of an amine across the C=C bond of an allene represents
an attractive, atom economical approach to the synthesis
of allylic amines.1 Although a number of general and effi-
cient methods have been developed for the intramolecular
hydroamination of allenes,2,3 effective methods for the in-
termolecular hydroamination of allenes, particularly those
that utilize alkyl- or arylamines, remain scarce.4–12
Zirconium4 and titanium5 complexes catalyze the inter-
molecular hydroamination of allenes with amines to form
imines via addition of nitrogen to the central carbon atom
of the allene. Palladium(II) complexes catalyze the inter-
molecular hydroamination of allenes with arylamines to
form allylic amines, but these methods are of limited
scope.6,7 More recently, Yamamoto has described
gold(III)-8 and gold(I)-catalyzed9 methods for the inter-
molecular hydroamination of allenes with arylamines and
morpholine, respectively although efficient hydroamina-
tion was restricted to monosubstituted and 1,3-disubstitut-
ed allenes. Bertrand has reported the hydroamination of
allenes with ammonia catalyzed by a cationic gold(I) cy-
clic (alkyl)(amino)carbene (CAAC) complex under forc-
ing conditions (≥ 155 °C).10
In addition to aniline, a number of primary arylamines
reacted with 1 (2 equiv) to form the corresponding N-prenyl-
aniline derivatives in good to excellent yield with exclu-
sive formation of the regioisomer resulting from attack of
aniline at the less substituted allene terminus (Table 2, en-
tries 2–11).14 p-Nitro- and p-bromoaniline were highly ac-
tive nucleophiles that reacted with 1 (2 equiv) at 45 °C for
12 hours to form mixtures of the corresponding N-prenyl-
and N,N-diprenylaniline derivatives (Table 2, entries 6
and 7). However, increasing the 1/aniline ratio to 3:1 led
to exclusive formation of the N,N-diprenylanilines in ex-
cellent yield as single regioisomers (Table 2, entries 8 and
9). Ortho-substituted anilines proved highly selective nu-
cleophiles for the gold(I)-catalyzed hydroamination of 1,
leading to formation of the N-prenylanilines in good to ex-
cellent yield without formation of the corresponding
N,N-diprenylanilines (Table 2, entries 2–4, 10 and 11).
We have recently reported the regio- and diastereoselec-
tive intermolecular hydroamination of allenes with car-
bamates catalyzed by a gold(I) N-heterocyclic carbene
(NHC) complex that displayed excellent scope with re-
spect to the allene.11 We therefore considered that gold(I)
NHC complexes might also catalyze the intermolecular
hydroamination of allenes with arylamines with improved
substrate scope relative to extant protocols. During the
course of these studies, Bertrand and co-workers reported
the intermolecular hydroamination of allenes with aryl-
amines catalyzed by a gold(I) CAAC complex.12 Al-
though this procedure extended the scope of allene
SYNLETT 2010, No. 3, pp 0419–0422
1
2.
0
2.
2
0
1
0
Advanced online publication: 07.01.2010
DOI: 10.1055/s-0029-1218555; Art ID: S09209ST
© Georg Thieme Verlag Stuttgart · New York

420
A. N. Duncan, R. A. Widenhoefer
LETTER
Table 1 Gold(I)-Catalyzed Hydroamination of 3-Methyl-1,2-butadiene (1; 0.8 M) with Aniline (0.4 M) as a Function of Ligand and Reaction
Conditions
Me
catalyst (5 mol%)
+
Me
H2N
1
Me
Me
Me
N
+
Me
N
H
2a
Me
Me
2b
Entry
Catalyst
Solvent
toluene
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
Temp (°C)
Time (h)
24
Conv (%)a
2a/2ba
>25:1
>25:1
>25:1
4.1:1
–
1
2
3
4
5
6
7
(IPr)AuCl–AgOTf
(IPr)AuCl–AgOTf
(3)AuCl–AgOTf
(3)AuCl–AgOTf
AgOTf
25
25
25
45
45
45
45
10
17
35
100
0
24
24
12
12
3–AgOTf
12
0
–
3–HOTf
12
0
–
Ar
i-Pr
i-Pr
t-Bu
P
t-Bu
N
Ar =
IPr
N
Ar
3
a Conversion and product ratio determined by GC analysis versus hexadecane internal standard.
N-Methylanilines were also effective nucleophiles for the aniline 6 in 93% isolated yield as a 4.4:1 mixture of Z- and
gold(I)-catalyzed hydroamination of 1, forming the corre- E-isomers (Table 3, entry 5).
sponding N-methyl-N-prenylanilines in good yield as sin-
gle regioisomers (Table 2, entries 12 and 13).
Dialkylamines, however, were not effective nucleophiles
for the hydroamination of allenes under these conditions.
alcohols15 supported mechanisms involving outer-sphere
Stereochemical analysis of the gold(I)-catalyzed intramo-
lecular hydroamination of N-g-allenyl carbamates3 and
the intermolecular hydroalkoxylation of allenes with
In addition to 3-methyl-1,2-butadiene (1), monosubstitut- attack of the nucleophile on a gold p-allene complex.
ed, functionalized 1,1-disubstituted, and 1,3-disubstituted Largely on the basis of these precedents, we proposed an
allenes also underwent gold(I)-catalyzed intermolecular outer-sphere mechanism for the gold(I)-catalyzed inter-
hydroamination with arylamines in good yield with good molecular hydroamination of allenes with carbamates.11
regio- and diastereoselectivity (Table 3). As an example Conversely, Yamamoto8 and Bertrand12,13 have proposed
of the hydroamination of a monosubstituted allene, reac- inner-sphere pathways for the gold-catalyzed intermolec-
tion of m-bromoaniline with 1-cyclohexyl-1,2-propadiene ular hydroamination of allenes with arylamines and am-
at 45 °C for 24 hours led to isolation of N-(3-cyclohexyl- monia. Therefore, we have considered both outer-sphere
2-propenyl)aniline (4) in 91% yield as a 5.2:1 mixture of and inner-sphere mechanisms for the gold(I)-catalyzed in-
E- and Z-isomers (Table 3, entry 1). As an example of the termolecular hydroamination of allenes with arylamines.
hydroamination of a 1,3-disubstituted allene, reaction of In the former pathway, endoergonic displacement of
m-bromoaniline with 1-phenyl-1,2-butadiene at 45 °C for aniline from I via the 16-electron, three-coordinate inter-
24 hours led to isolation of the N-(1-methyl-3-phenyl-2- mediate II would form gold(I) p-allene complex III. Out-
propenyl)aniline (5) in 86% yield as a >25:1 mixture of E- er-sphere attack of the aniline on III would then form the
and Z-isomers resulting from addition of the nucleophile gold s-alkenyl ammonium complex IV. Deprotonation of
to the methyl-substituted allene terminus (Table 3, entry IV with free aniline followed by protonolysis of the Au–
4). As an example of the hydroamination of a functional- C bond of V would then release the N-prenylaniline with
ized 1,1-disubstituted allene, reaction of m-bromoaniline regeneration of I. Alternatively, b-migratory insertion of
with ethyl 3-hexyl-3,4-pentadienoate formed N-allylic the coordinated allene into the Au–N bond of II would
likewise generate IV (Scheme 1).
Synlett 2010, No. 3, 419–422 © Thieme Stuttgart · New York

LETTER
Gold(I)-Catalyzed Intermolecular Hydroamination of Allenes with Arylamines
421
Table 3 Intermolecular Hydroamination of Monosubstituted, 1,3-
Disubstituted, and Functionalized 1,1-Disubstituted Allenes with
m-Bromoaniline Catalyzed by a Mixture of (3)AuCl (5 mol%) and
AgOTf (5 mol%) in Dioxane at 45 °C
Table 2 Intermolecular Hydroamination of 1 (0.8 M) with Aryl-
amines (0.4 M) Catalyzed by a Mixture of (3)AuCl (5 mol%) and
AgOTf (5 mol%) in Dioxane at 45 °C
(3)AuCl (5 mol%)
Me
R
Producta
Yield E/Zc
AgOTf (5 mol%)
Entry Allene
+
H
(%)b
N
dioxane, 45 °C
Me
R1
1
Ar
N
Me
R
H
1
91
5.2:1
Me
Me
N
R
+
4
Me
N
R1
E
E
2
72
87
86
>25:1
7.7:1
Me
Me
Ar
N
E
A
B
E
H
E = CO2Me
Entry Aniline
Time (h) Yield A
Yield B (%)a
R
(%)a
R
R
3
4
Ar
N
R
R = n-pentyl
1
24
73
17
H
H2N
R
Me
Ar
R = H
R = o-Br
>25:1
Me
Ph
N
H
Ph
2
3
4
5
6
7
8
9
24
24
24
12
12
12
12
12
87
83
66
72
33
40
0
0
0
5
R = o-i-Pr
R = o-t-Bu
R = m-Br
R = p-NO2
R = p-Br
CO2Et
CO2Et
0
5
93
1:4.4
Ar
N
H
n-hexyl
n-hexyl
23
66
56
99
99
6
a Ar = 3-BrC6H4.
b Isolated yield of material of >95% purity (E + Z isomers).
c E/Z ratio determined by 1H NMR analysis of the purified reaction
R = p-NO2
R = p-Br
mixture.
0
H2NAr
Me
AuL
Me
H2NAr
III
Me
10
11
24
24
86
84
0
0
Me
– H2NAr
H2N
Cl
Me
Me
Me
H2N
Me
LAu(NH2Ar)
Me
NH2Ar
IV
LAu
I
AuL
NH2Ar
Me
II
H2NAr
Me
Me
H
N
Me
NHAr
R
12
13
24
12
73
94
–
–
NHAr
H3NAr
Me
H3NAr
V
AuL
R = H
R = Br
Scheme 1 Potential mechanisms for the gold(I)-catalyzed hydro-
amination of 1 with aniline
a Isolated yield of material of >95% purity.
b [Aniline]/[1] = 1:3.
In summary, we have developed an effective gold(I)-cat-
alyzed protocol for the intermolecular hydroamination of
allenes with arylamines to form N-allyl aniline derivatives
with excellent regioselectivity and good diastereoselectiv-
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
ity. We continue to work toward the elucidation of the Acknowledgment
mechanism of gold(I)-catalyzed allene hydroamination
and toward the development of effective methods for the
catalytic hydroamination of allenes with alkyl amines.
Acknowledgment is made to the NIH (GM-080422) for support of
this research.
Synlett 2010, No. 3, 419–422 © Thieme Stuttgart · New York

422
A. N. Duncan, R. A. Widenhoefer
LETTER
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References and Notes
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(14) Experimental Procedure and Spectroscopic Data for the
Gold(I)-Catalyzed Hydroamination of 1 with o-Bromo-
aniline (Table 2, entry 2): Dioxane (0.50 mL) was added to
a mixture of o-bromoaniline (39 mg, 0.23 mmol), (3)AuCl
(6.2 mg, 1.1 × 10–2 mmol), and AgOTf (2.8 mg, 1.1 × 10–2
mmol) and the resulting suspension was stirred for 10 min at
r.t. 3-Methyl-1,2-butadiene (1; 29 mg, 0.43 mmol) was
added via syringe and the resulting mixture was stirred at 45
°C for 24 h. Column chromatography of the reaction mixture
(SiO2; hexanes–EtOAc, 15:1) gave N-(3-methyl-2-butenyl)-
o-bromoaniline (48 mg, 87%) as a pale yellow oil. 1H NMR
(400 MHz, CDCl3): d = 7.41 (dd, J = 1.5, 8.5 Hz, 1 H), 7.17
(dd, J = 1.5, 7.8 Hz, 1 H), 6.62 (dd, J = 1.0, 8.3 Hz, 1 H), 6.55
(dt, J = 1.5, 7.5 Hz, 1 H), 5.31–5.35 (m, 1 H), 4.23 (br s, 1
H), 3.72 (d, J = 6.8 Hz, 2 H), 1.76 (d, J = 1.0 Hz, 3 H), 1.72
(s, 3 H). 13C{1H} NMR (100 MHz, CDCl3): d = 145.1, 136.1,
132.3, 128.4, 121.1, 117.5, 111.4, 109.7, 41.9, 25.7, 18.1.
HRMS: m/z [M+] calcd for C11H14BrN: 239.0310; found:
239.0313.
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Synlett 2010, No. 3, 419–422 © Thieme Stuttgart · New York

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