A R T I C L E S
Julian and Hartwig
Catalysts derived from zinc complexes21,22 and Bronsted
acids23-26 have also been shown to catalyze intramolecular
hydroamination with a limited range of reactivities. For example,
the reaction of a secondary aminoalkene lacking geminal
substitution in the presence of a catalyst derived from diethylzinc
and a protic additive required 21 days at 180 °C. Primary
aminoalkenes containing geminal disubstitution of the alkyl
linker required 120 °C, and a single example of a substrate
lacking geminal disubstitution on the alkyl chain (2-aminohex-
5-ene) gave the product with only 19% conversion after 36 h.21
Hydroaminations catalyzed by Brønsted acids required high
temperatures or protection of the nitrogen with an electron-
withdrawing group.24-26
Complexes of late transition metals are more stable toward
air and moisture and more tolerant of polar functional groups
than complexes containing early transition metals and lan-
thanides.27 However, intramolecular hydroaminations catalyzed
by late-transition-metal complexes often require a N-H donor
in which the nitrogen is electron-deficient and contained in an
amide, carbamate, or sulfonamide functionality.26,28-31 In the
last five years, complexes of platinum,32,33 copper,34 rhodium,35-37
and iridium38-40 have been shown to catalyze the intramolecular
hydroamination of aminoalkenes containing more basic second-
ary alkylamines. In 2008, the author’s group reported a cationic
rhodium complex that catalyzed the cyclization of both second-
ary and primary aminoalkenes.35
been reported with any catalyst. Thus, the identification of a
complex containing a late transition metal that catalyzes the
cyclization of unactivated, unbiased aminoalkenes, as well as
an understanding of the factors controlling the reactions of
primary amines catalyzed by late-transition-metal complexes,
is needed.26,41,42
We previously investigated the cyclization of a secondary
aminoalkene catalyzed by a series of rhodium complexes
containing bisphosphine ligands.35 One example of the cycliza-
tion of a secondary aminoalkene catalyzed by the combination
of bis(diethylamino)xantphos ligand L1′ (see Table 1)43 and a
cationic rhodium precursor was included in that study. Com-
plexes of aminophosphines have rarely been investigated as
components of catalysts, let alone for hydroamination.44 Thus,
we have investigated the structure of this catalyst and its
reactivity toward a broader range of aminoalkenes.
Here we report a full account of our findings, which reveal
the high reactivity of this unusual metal-ligand system for the
hydroamination of primary amines, along with detailed mecha-
nistic studies that reveal the origins of the high reactivity of
this system. These new studies show that the active catalyst
possesses a rhodium-POP-pincer structure and is highly active
for the hydroamination of primary amines. The reactions
catalyzed by this complex typically proceed at mild temperatures
(room temperature to 70 °C), occur with primary aminoalkenes
lacking any substituents on the alkyl chain that would bias the
system toward cyclization, and exhibit a high degree of tolerance
for polar functional groups, including aryl chlorides, esters,
ethers, enolizable ketones, nitriles, and unprotected alcohols.
Initial results imply that the aminophosphine groups on the
ligand are involved in creating the high rates and selectivity,
and mechanistic data show that the reactions of primary amines
catalyzed by these complexes occur with a turnover-limiting
step that is different from that of secondary aminoalkenes
catalyzed by complexes of Pd,45 Pt,32 and Ir.46
Although data for this rhodium catalyst35,37 and for catalysts
based on copper34 and iridium40,46 reported since that time have
demonstrated that primary aminoalkenes can undergo cycliza-
tion, reactions of such amines catalyzed by these systems have
significant limitations. First, the cyclization of primary ami-
noalkenes catalyzed by late-metal systems has been limited to
cases that are biased toward cyclization by a Thorpe-Ingold
effect. Second, these reactions have been limited to aminoalk-
enes containing terminal olefins. Third, these reactions require
high temperatures (>100 °C). Finally, reactions of primary
aminoalkenes containing a second functional group have not
Results and Discussion
Our prior observation that bis(diethylamino)xantphos L1′ and
Rh(COD)2BF4 catalyze the cyclization of a secondary ami-
noalkene, in combination with the novelty of a diaminophos-
phine as a component for catalysis, the potential flexibility and
ease of synthesis of this class of ligand, and the possibility that
this catalyst combination could lead to more hydroaminations
than just the cyclization of secondary amines with geminal
disubstitution, led us to explore the reactivity of this catalyst
toward aminoalkenes that have resisted cyclization with previous
late-transition-metal catalysts. To do so, we explored the activity
of the catalyst generated from L1 and cationic rhodium(I)
precursors for reactions of primary aminoalkenes possessing and
lacking geminal disubstitution on the alkyl linker. We found
thatjusta1mol%loadingofthecomplexgeneratedfrom[Rh(CH3-
CN)2COD]BF4 and L1 catalyzed the hydroamination of primary
aminoalkene 1a, containing 3,3-diphenyl substituents, in THF
at 70 °C to form the pyrrolidine product 2a with high selectivity
(14:1:1:0.4) over the combination of imine product 3a and
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13814 J. AM. CHEM. SOC. VOL. 132, NO. 39, 2010