Platinum(II)-catalyzed intermolecular hydroamination of monosubstituted allenes with secondary alkylamines

Article abstract of DOI:10.1039/b925859k

A 1 1 mixture of (dppf)PtCl₂ and AgOTf (5 mol%) catalyzed the intermolecular hydroamination of monosubstituted allenes with secondary alkylamines at 80 °C to form allylic amines in good yield with selective formation of the E-diastereomer.

Full text of DOI:10.1039/b925859k

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Platinum(II)-catalyzed intermolecular hydroamination of monosubstituted
allenes with secondary alkylaminesw
Kristina L. Toups and Ross A. Widenhoefer*
Received (in College Park, MD, USA) 8th December 2009, Accepted 6th January 2010
First published as an Advance Article on the web 16th January 2010
DOI: 10.1039/b925859k
A 1 : 1 mixture of (dppf)PtCl2 and AgOTf (5 mol%) catalyzed
the intermolecular hydroamination of monosubstituted allenes
with secondary alkylamines at 80 1C to form allylic amines in
good yield with selective formation of the E-diastereomer.
n-butyl amine with dimethyl 2,3-butadienylmalonate (1; 2 equiv.)
catalyzed by a 1 : 1 mixture of PtCl2 and P(t-Bu)2o-biphenyl
(5 mol%) in dioxane at 80 1C for 24 h led to isolation of allylic
amine 2a in 65% yield as a 4.7 : 1 mixture of E–Z isomers
(eqn (1)). Unfortunately, subsequent modification of ligand led
to no improvement in either the yield or the diastereoselectivity
of hydroamination.
The transition metal-catalyzed addition of the N–H bond of
an amine across a C–C multiple bond represents an attractive
and atom economical approach to the synthesis of functionalized
amines.1 Despite prolonged effort in this area, many of the
possible permutations of catalytic hydroamination remain
poorly developed. As one example, the intermolecular hydro-
amination of allenes with alkylamines remains problematic,
which is unfortunate as this transformation represents a
potentially expedient approach to the synthesis of allylic
amines. Group IV complexes catalyze the intermolecular
hydroamination of allenes with alkylamines at elevated
temperatures but form imines rather than allylic amines.2
Palladium(II) complexes catalyze the intermolecular hydro-
amination of allenes with alkyl amines, but these transformations
are of extremely limited scope.3 More recently, cationic gold(I)
phosphine4 and cyclic (alkyl)(amino)carbene5,6 complexes
have been applied to the intermolecular hydroamination
of allenes with secondary alkylamines. However, the former
method was restricted to morpholine as a nucleophile while
the latter required forcing conditions (130–165 1C) with
monosubstituted allenes and/or simple dialkyl amines. Here
we report an effective Pt(II)-catalyzed protocol for the inter-
molecular hydroamination of monosubstituted allenes with
secondary alkylamines.
ð1Þ
As an alternative to neutral mono(phosphine) complexes,
we targeted cationic platinum bis(phosphine) complexes as
catalysts for allene hydroamination. Although ultimately
successful, an initial experiment employing benzyl n-butyl amine,
1 (2 equiv.), and a catalytic 1 : 1 mixture of (dppp)PtCl2 [dppp =
1,3-bis(diphenylphosphino)propane] and AgOTf led to no
detectable formation of 2a (Table 1, entry 1). The effect of
the natural bite angle (bn)9 of a bidentate phosphine ligand on
the efficiency and/or selectivity of transition metal-catalyzed
transformations is well documented.10 For this reason, we
evaluated the efficiency of platinum-catalyzed conversion of 1
to 2a as a function of phosphine bite angle. The effect was
dramatic, and the yield of 2a increased from 0% to 88% as bn
increased from 911 to Z 1081,11 although the E–Z selectivity
followed no discernable trend (Table 1, entries 1–7). From this
group of complexes, we targeted (dppf)PtCl2 [dppf = 1,10-
bis(diphenylphosphino)ferrocene] and (Nixantphos)PtCl2
[Nixantphos = 4,6-bis(diphenylphosphino)phenoxazine] for
further evaluation, owing to the favorable combination of
yield and diastereoselectivity realized with these precatalysts.
Optimization with respect to solvent revealed that toluene
provided higher yield of 2a without significant deterioration
of diastereoselectivity (Table 1, entries 10 and 11).zy
We have previously employed neutral platinum(II) mono-
(phosphine) complexes as catalysts for the intramolecular
hydroamination of unactivated alkenes with secondary alkyl
amines.7 Furthermore, Panunzi et al. have shown that
alkylamines react with the platinum(II) p-allene complex
(PPh3)PtCl2(Z2-H2CQCQCMe2) to form zwitterionic platinum
s-alkenyl complexes (PPh3)PtCl2(Z1-Me2CQCCH2NR3) that
react with HCl to form allylic ammonium chloride salts.8
Together these steps constitute a potential catalytic cycle for
allene hydroamination. For these reasons, we targeted neutral
platinum mono(phosphine) complexes as catalysts for the
intermolecular hydroamination of allenes with alkylamines.
Initial experiments were encouraging, and treatment of benzyl
Employment of (dppf)PtCl2 or (Nixantphos)PtCl2 as
precatalysts allowed for the efficient hydroamination of allene
1 with a range of secondary alkylamines. The former generally
provided superior yields and reaction of 1 with benzyl methyl
amine, di-n-butyl amine, diethyl amine, morpholine, piperidine,
or pyrrolidine catalyzed by a 1 : 1 mixture of (dppf)PtCl2 and
AgOTf in toluene at 80 1C led to isolation of the corresponding
allylic amines 2b–2g in Z 78% yield with Z 7.6 : 1 E–Z
diastereoselectivity (Table 2, entries 1–6). Alternatively, reaction
of 1 with dibenzyl amine catalyzed by (Nixantphos)PtCl2–AgOTf
French Family Science Center, Duke University, Durham, NC, USA.
E-mail: rwidenho@chem.duke.edu; Fax: +1-919-6601605;
Tel: +1-919-6601533
w Electronic supplementary information (ESI) available: Experimental
procedures, spectroscopic data, and scans of NMR spectra (35 pages).
See DOI: 10.1039/b925859k
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Table 1 Platinum(II)-catalyzed hydroamination of dimethyl 2,3-
butadienylmalonate (1; 2 equiv.) with benzyl n-butyl amine as a
function of supporting ligand and solvent
Table 2 Intermolecular hydroamination of monosubstituted allenes
(2 equiv.) with secondary alkylamines catalyzed by a mixture of
(dppf)PtCl2 (5 mol%) and AgOTf (5 mol%) in toluene at 80 1C
Time/
h
Yielda
Product (%)
Entry Amine
1
Allene
E : Zb
24
86
10 : 1
1
2b
Entry
P–P
bna/1
Solvent
Yieldb (%)
E : Zc
1
2
3
4
5
6
7
8
dppp
biphep
binap
dppf
DPEphos
xantphos
Nixantphos
dppf
Nixantphos
dppf
Nixantphos
91
92
93
99
104
108
114
99
114
99
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Methanol
Methanol
Toluene
Toluene
0
22
27
70
79
88
86
20
85
81
91
—
7.0 : 1
4.1 : 1
11 : 1
5.6 : 1
5.0 : 1
6.5 : 1
17 : 1
7.8 : 1
10 : 1
6.7 : 1
2
3
X = O
X = CH2
1
1
24
24
24
2c
2d
89
78
78
7.8 : 1
7.6 : 1
8.4 : 1
4
1
2e
9
10
11
114
5
R = n-Bu 1
24
24
24
2f
2g
2h
82
86
66
17 : 1
9.6 : 1
6.9 : 1
a
b
Bite angle data taken from ref. 11. Isolated material of Z 95%
6
R = Et
R = Bn
1
1
purity. E/Z ratio determined by 1H NMR analysis of the purified
reaction mixture.
c
7c
8
9
10
11
12
R = n-octyl
R = Cy
R = Bn
R = Ph
R = 2-naphthyl 40
48
48
42
38
2i
2j
2k
2l
2m
93
89
73
99
86
15 : 1
32 : 1
39 : 1
450 : 1
450 : 1
led to isolation of 2h in 66% yield as a 6.9 : 1 mixture of E–Z
diastereomers (Table 2, entry 7). In addition, a number of
aliphatic and aromatic monosubstituted allenes including
n-octyl-, cyclohexyl-, benzyl-, phenyl-, and 2-naphthylallene
underwent efficient hydroamination with benzyl n-butyl amine
in the presence of (dppf)PtCl2–AgOTf to form the corresponding
a
b
Yields refer to isolated material of >95% purity. E/Z ratio
determined by 1H NMR analysis of the purified reaction mixture.
c
(Nixantphos)PtCl2 employed as precatalyst.
allylic amines 2i–2m in good yield with Z 15
: 1 E–Z
diastereoselectivity (Table 2, entries 8–12). Neither 1,1- nor
1,3-disubstituted allenes underwent efficient intermolecular
hydroamination with benzyl n-butyl amine under these
conditions.
s-alkenyl complex IV with ammonium salt would release
allylic amine 2 with regeneration of I (Scheme 1).
In summary, we have developed a platinum(II)-catalyzed
protocol for the intermolecular hydroamination of mono-
substituted allenes with secondary alkylamines to form allylic
amines in good yield with selective formation of the E-
diastereomer. We are currently working toward the develop-
ment of more general and more effective hydroamination
protocols that employ alkylamines as nucleophiles.
Guided by the precedents of Panunzi et al.8,12 and
others13–16 we propose a mechanism for the platinum-
catalyzed hydroamination of allenes with secondary alkyl-
amines initiated by chloride abstraction from (P–P)PtCl2 with
AgOTf to initially form the cationic platinum amine complex I
(Scheme 1).14 Displacement of the amine ligand of I with free
allene would form cationic platinum p-allene complexes II.
Although a number of platinum(II) p-allene complexes are
known,15,16 complexes of monosubstituted allenes are not
among them and hence, the preferred binding mode of mono-
substituted allenes to Pt(II) is not known. However, platinum
p-allene complexes are known to undergo intramolecular
exchange of all four possible allene p-faces, presumably via
an Z1-allene intermediate or transition state.16,17 Therefore,
preferential outer-sphere addition of amine to the unsubstituted
allene terminus of platinum p-allene isomer cis-II would lead
to selective formation of platinum s-alkenyl complex (Z)-III.
A control experiment ruled out Z–E isomerization of the
allylic amine under reaction conditions.z Protonolysis of the
Pt–C bond of (Z)-III could occur through a number of
pathways. As one possibility, deprotonation of the ammonium
moiety of (Z)-III with free amine followed by intermolecular
protonolysis of the Pt–C bond of the resulting neutral
Acknowledgement is made to the NIH (GM-080422) for
support of this research. KLT was supported in part though a
Pharmacological Sciences Training Program fellowship.
Scheme 1
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z Experimental procedure: a suspension of (dppf)PtCl2 (8.2 mg,
0.010 mmol), AgOTf (2.6 mg, 0.010 mmol), ferrocene (3.7 mg, 0.020 mmol;
internal standard), benzyl n-butyl amine (36 mL, 33 mg, 0.20 mmol)
and 1 (74 mg, 0.40 mmol) in toluene (0.4 mL) was heated at 80 1C
for 24 h. Column chromatography of the crude reaction mixture
(SiO2 pretreated with Et3N; hexanes–EtOAc = 9 : 1) gave 2a (pale
yellow oil, 56 mg, 81%) as a 10 : 1 mixture of E and Z diastereomers.
y Control experiments ruled out the significant contribution of acid- or
silver-catalyzed pathways to the intermolecular hydroamination of 1
and benzyl n-butyl amine (see ESIw).
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mixture of (dppf)PtCl2 and AgOTf in toluene at 80 1C for 24 h led to
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