Mild, rhodium-catalyzed intramolecular hydroamination of unactivated terminal and internal alkenes with primary and secondary amines

Article abstract of DOI:10.1021/ja710126x

We report a series of mild, rhodium-catalyzed hydroaminations of unactivated olefins with primary and secondary alkylamines to form the corresponding five- and six-membered products in excellent yields. The reactions form exclusively the product from hydroamination without competitive oxidative amination or olefin isomerization with catalysts generated from a biaryl dialkyl phosphine and an analogue of Xantphos. A variety of functional groups were tolerated by the hydroamination process, including hydroxyl, halo, cyano, and carboalkoxyl groups. Copyright

Full text of DOI:10.1021/ja710126x

Published on Web 01/10/2008
Mild, Rhodium-Catalyzed Intramolecular Hydroamination of Unactivated
Terminal and Internal Alkenes with Primary and Secondary Amines
Zhijian Liu and John F. Hartwig*
Department of Chemistry, UniVersity of Illinois Urbana-Champaign, 600 South Mathews AVenue, Urbana, Illinois 61801
Received November 7, 2007; E-mail: jhartwig@uiuc.edu
The hydroamination of olefins1 is one of the simplest and most
atom-economical methods to prepare alkylamines, and much effort
has now been spent to develop catalysts for this process. Some of
Table 1. Effect of Ligand on the Selectivity for
Rhodium-Catalyzed Intramolecular Hydroamination of the
Aminoalkene in Equation 1a
most reactive catalysts contain lanthanides2 and group IV transition
metals.3 However, the high sensitivity of these catalysts toward air
and moisture and their low tolerance of polar functional groups
have limited their use and motivated efforts to develop late-metal
hydroamination catalysts. Although several catalysts based on late
metals have been published for additions of amines to vinylarenes4-6
and for the addition of amides and sulfonamides to alkenes, allenes,
and dienes,7 few catalysts for additions of amines to alkenes, argu-
ably the most important donors and acceptors, have been reported.
The existing late-metal catalyst for the intramolecular additions
of amines to olefins8 is generated from [PtCl2(H2CdCH2)]2 and
PPh3. This system operates at 120 °C, catalyzes only reactions of
secondary amines, not primary amines, and catalyzes additions to
only terminal olefins, not internal olefins.9 Moreover, this catalyst
requires substituents that bias the substrate toward cyclization.
Alterative palladium catalysts for additions of amides and carbam-
ates at lower temperature have been reported,10 but these N-H bond
donors require installation and removal of the activating group in
most synthetic sequences and do not provide products that would
result from addition of a secondary amine. Thus, a catalyst that
tolerates polar functional groups and that induces additions of both
primary and secondary amines without activating groups to both
terminal and internal alkenes is needed.
We report the identification of such a system. We report a
rhodium catalyst for the hydroamination of terminal and internal
alkenes with primary and secondary amines, with or without
substituents that favor cyclization to form five- or six-membered
ring products. In addition to spanning a broader scope of amine
and alkene than other late metal catalysts, this system operates in
the presence of functional groups, including esters and free hydroxyl
groups, which do not tolerate early metal and lanthanide catalysts.
These results demonstrate that complexes of group 9 metals, which
are classic catalysts for alkene hydrogenation and hydrosilylation,
can also be made useful for alkene hydroamination.
entry
catalyst
ligandb
%Ac
%Bc
%Cc
%Dc
1
2
3
4
5
6
7
8
9
[Rh(COD)2]BF4
[Rh(COD)2]BF4
[Rh(COD)2]BF4
[Rh(COD)2]BF4
[Rh(COD)2]BF4
[Rh(COD)2]BF4
[Rh(COD)2]BF4
[Rh(COD)2]BF4
DPEphos
DPPB
PPh3
0
10
0
0
40
0
93
10
92
30
10
10
0
0
30
0
PCy3
0
30
30
10
0
30
30
10
0
DPPF
t-BuXantphos 60
L1
L2
20
86
93
92
28
9
0
0
0
[Rh(MeCN)2(COD)]BF4 L2
0
0
0
10d [Rh(COE)2Cl]2
L2
L2
L2
0
0
0
11d [Rh(COD)Cl]2
12
0
0
0
5% HBF4‚OEt2
0
0
0
0
a Reaction conditions: 0.5 mmol of amine 1, 2.5 mol % of Rh, and 2.5
mol % of biphosphine or 5 mol % monophosphine in 0.5 mL of dioxane at
70 °C for 7 h unless otherwise specified. b Ligand structures are shown
above the table. c GC yields. d Reaction run using 1.25 mol % catalyst.
cyclized pyrrolidine product. The major product of this reaction
resulted from isomerization of the olefin from the terminal to the
internal position.11 Reactions catalyzed by 2.5% [Rh(COD)2]BF4
and 2.5% DPPB (1,4-bis(diphenylphosphino)butane), which cata-
lyzed the intramolecular hydroamination of vinylarenes,5 led to a
mixture of cyclic amine, isomerized olefin, cyclic enamine, and
alkylamine, with the cyclic amine comprising only 10% of the
material. Reactions catalyzed by complexes of other ligands (entries
3-6) also formed mixtures, but two systems formed exclusively
cyclic amine. The catalyst generated from [Rh(COD)2]BF4 and an
amino analogue of Xantphos L1 or the biarylphosphine ligand L2
developed in the Buchwald laboratory for cross-coupling12 formed
the cyclic amine as the sole detectable product in 86 and 93% yield
by GC (entries 7 and 8). Studies with various rhodium precursors
(entries 8-11) showed that [Rh(COD)2]BF4 formed the most active
catalyst. Reactions with protic acid as catalyst, which could be
generated from the rhodium precursor,13a formed no product (entry
12).13b
The scope of the hydroamination of 5- and 6-N-alkyl aminoalk-
enes to form pyrrolidines and piperidines under these reaction
conditions are summarized in Table 2. Cyclizations to form five-
membered rings with aminoalkenes containing not only N-methyl
(Table 1), but more bulky N-cyclohexylmethyl and N-benzyl amines
(Table 2, entries 1-2) generated high yields of cyclized products.
These cyclizations occurred for substrates with (entries 1-4) or
without (entries 5-7) gem-disubstitution on the linker chain.
Likewise, cyclizations to form six-membered rings occurred with
substrates possessing (entry 8) or fully lacking substituents in the
linking chain (entry 9).
Stimulated by our previous studies on rhodium-catalyzed addi-
tions of amines to vinylarenes,5,6 we investigated combinations of
rhodium precursors and dative ligands as catalysts for cyclization
of the N-methyl aminopentene in eq 1. Experiments to develop
conditions for the cyclization of aminoalkene 1 are summarized in
Table 1. These reactions were conducted at 70 °C over 7 h, unless
otherwise stated.
Reaction of aminoalkene 1 in the presence of 2.5 mol % [Rh-
(COD)2]BF4 and 2.5 mol % DPEphos, which catalyzed the anti-
Markovnikov hydroamination of vinylarenes,6 formed none of the
9
1570
J. AM. CHEM. SOC. 2008, 130, 1570-1571
10.1021/ja710126x CCC: $40.75 © 2008 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Rhodium Catalyzed Intramolecular Hydroamination of
Table 3. Rhodium Catalyzed Intramolecular Hydroamination of
Secondary Aminoalkenea
Primary Aminoalkenea
a Reaction conditions: 0.5 mmol aminoalkene, 5 mol % of rhodium,
and 6 mol % of L2 in 0.5 mL of dioxane at 100 °C for 10 h unless otherwise
specified. b Isolated yield. c Reaction was run for 1 d. d NMR yield.
common functional groups. Studies on the mechanism of this
process and development of enantioselective versions of this process
are ongoing.
Acknowledgment. We thank the NIH (NIGMS GM-55382) for
support of this work and Johnson-Matthey for rhodium.
Supporting Information Available: All experimental procedures
and characterization data of new compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
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of functional groups, such as halides, nitriles, and esters (entries
5-7). Perhaps most remarkable, reaction of the substrate in entry
10 containing an allylic alcohol function occurred in good yield
with high diastereoselectivity without significant decomposition of
the alcohol or deactivation of the catalyst. The reaction of N-benzyl-
2,2-diphenylpent-4-en-1-amine even occurred in an 82% yield in
the presence of 5.0 equiv of added water.
Most additions of amines to alkenes have been conducted with
terminal, monosubstituted olefins. However, reactions with disub-
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The rhodium catalyst also increased the scope of amines that
would add to alkenes. For example, the species generated from
5% Rh(COD)2BF4 and 6% of L2 catalyzed the cyclization of
aminoalkenes containing primary amine units (Table 3). Reactions
of primary aminoalkenes to form five- and six-membered rings
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In summary, we report a rhodium complex that catalyzes
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containing primary or secondary amines, terminal or internal
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