Aluminium-catalyzed intramolecular hydroamination of aminoalkenes

Article abstract of DOI:10.1039/c002760j

A new aluminium complex bearing a dianionic phenylene-diamine based ligand has been synthesized and shown to catalyze the intramolecular hydroamination of various aminoalkenes.

Full text of DOI:10.1039/c002760j

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Aluminium-catalyzed intramolecular hydroamination of aminoalkenesw
Jurgen Koller and Robert G. Bergman*
¨
Received 9th February 2010, Accepted 22nd April 2010
First published as an Advance Article on the web 10th May 2010
DOI: 10.1039/c002760j
A new aluminium complex bearing a dianionic phenylene-diamine
based ligand has been synthesized and shown to catalyze the
intramolecular hydroamination of various aminoalkenes.
The formal addition of a N–H bond across an unsaturated
C–C bond, also known as hydroamination, constitutes a
highly efficient synthetic pathway towards formation of
amines, enamines, and imines.1 Formation of N-heterocycles,
via the intramolecular hydroamination of aminoalkenes, is of
particular interest due to the importance of N-containing
cyclic compounds in biologically relevant systems. Although
the overall reaction is thermodynamically favorable, the electro-
static repulsion between the electron-rich olefin and the amine
nucleophile provides kinetic stability to the aminoalkenes,
rendering uncatalyzed reactions exceedingly slow. The necessity
of finding efficient catalysts for this transformation has
spawned extensive research efforts resulting in the discovery
of catalysts including early2 and late3 transition metals as well
as lanthanide/actinide complexes.4
Scheme 1 Synthesis of 1.
Recently, main group catalysts have received increased
attention.5 Although group 13 metals such as aluminium are
exceedingly inexpensive and show similarities (e.g. electrone-
gativity, atomic radii) to early transition metals such as Zr,
catalytically active systems involving these metals have remarkably
little precedent.6 Our goal was to establish the viability of well-
defined organometallic Al complexes as active catalysts towards
the hydroamination of aminoalkenes.
Fig. 1 ORTEP representation of 1. Thermal ellipsoids are drawn at
40% probability. Hydrogen atoms (except H4A) are omitted for
clarity.
Phenylene-diamine (pda) ligands have been used extensively
in organometallic coordination chemistry and after exploring
a number of other ligands, these were ultimately chosen as a
support for the Al metal center.7 The dianionic binding motif
offers extensive kinetic stability towards protonolysis of the
M–N bonds, which has been proposed as a problem in other
catalytic systems involving primary amines as substrates.
Compound 1 was prepared in moderate yield by treating the
neutral protonated ligand with commercially available
[Al(NMe2)3]2 (Scheme 1).z Despite the dimeric nature of the
metal precursor, compound 1 was isolated as a monomer,
most likely due to the sterically demanding 3,5-di-tert-butyl
substituents on the flanking aryl groups. Unsurprisingly, one
equivalent of dimethylamine remains coordinated to the metal
center to complete the preferred tetrahedral coordination
sphere of Al, as evidenced by well separated signals for the
amide (2.76 and 41.41 ppm) and amine (1.45 and 37.81 ppm)
functionalities in both the 1H and 13C NMR spectra, respectively.
To corroborate the monomeric nature of 1, single-crystal
X-ray diffraction studies were conducted which revealed
the Al metal center in a distorted tetrahedral configuration
as shown in Fig. 1. The Al1A–N1A and Al1A–N2A bond
distances of 1.849(3) and 1.830(3) A, respectively, are similar
to those in the only other example of a pda-ligand coordinated
to Al.8 The observed large bite angle of 88.71 corresponds
well with short Al–N bond distances in analogous transition
metal complexes involving pda-ligands.7b,9 As expected, the
Al1A–N3A bond (1.774(3) A) of the amide functionality is
significantly shorter than the Al1A–N4A bond (1.965(3) A) of
the coordinated amine, indicating considerable multiple bond
character between the metal center and N3A.
Upon heating a solution of 2,2-diphenylpent-4-ene-1-amine
in the presence of 1 (10 mol%), catalytic formation of the
hydroamination product 2-methyl-4,4-diphenylpyrrolidine
was observed. Although catalytic activity was evident at 135 1C
(in C6D6), heating the solution at 150 1C resulted in more
reasonable reaction times (Table 1, entry 1). Control experi-
ments revealed that the reaction rates were not influenced by
Department of Chemistry, University of California, Berkeley,
CA 94720, USA. E-mail: rbergman@berkeley.edu;
Fax: +1 510-642-7714; Tel: +1 510-642-2156
w Electronic supplementary information (ESI) available: NMR data
and experimental details. CCDC 765662. For ESI and crystallographic
data in CIF or other electronic format see DOI: 10.1039/c002760j
ꢀc
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Table 1 Catalytic hydroamination of aminoalkenes using 1
Entrya
Substrate
Product
Time/h %Conv.b %Yieldb
1
38
12
90
91
90
72
81
87
63
2
3
4
123
67
58
a
All reactions were carried out in C6D6 at 150 1C and 10 mol%
catalyst loading. Determined by integration of 1H NMR reactant
and product signals versus an internal standard.
b
Fig. 2 Proposed catalytic cycle.
the presence of one or two catalytic equivalents of a sterically
hindered non-coordinating base such as 1,2,2,6,6-penta-
methylpiperidine, thus ruling out the possibility of acid
catalysis.10 Additionally, reactions carried out in the absence
of 1 did not yield the hydroamination products even after
extended reaction times (>5 days at 150 1C).
Decreasing the steric bulk at the geminal position resulted in
slower conversion of the aminoalkene to the corresponding
hydroamination product as has been observed with other
catalytic systems (Thorpe–Ingold effect).5b In the case of
(1-allylcyclohexyl)-methanamine (Table 1, entry 3), extended
reaction times were necessary to achieve moderate yields of
the hydroamination product. Similarly, formation of larger
heterocycles such as 2,5,5-trimethylpiperidine required much
longer reaction times to achieve reasonable conversion
(Table 1, entry 4), an observation consistent with Baldwin’s
guidelines for ring formation.11
consistent with the formation of a new Al amide species
(structure I, Fig. 2) via the loss of dimethylamine. At elevated
temperatures (>135 1C), disappearance of the olefin signals
was observed, accompanied by the appearance of diagnostic
alkyl resonances consistent with the formation of ring-closed
pyrrolidine (structure III, Fig. 2 and Fig. S2, ESIw).
In conclusion, we have demonstrated the viability of an Al
complex supported by a pda-ligand as a catalyst for the intra-
molecular hydroamination of aminoalkenes. Compound 1
offers a cost-effective alternative to late transition metal and
lanthanide based catalysts with the added benefit of facile
synthesis.
This work was supported by the Director, Office of Science,
Office of Basic Energy Sciences, and the Division of Chemical
Sciences, Geosciences, and Biosciences of the U.S. Department
of Energy at LBNL under Contract DE-AC02-05CH11231.
Methyl-substitution at the internal position of the olefin
moiety had a significant positive impact on the reaction
rate, resulting in near quantitative conversion of 4-methyl-
2,2-diphenylpent-4-en-1-amine to 2,2-dimethyl-4,4-diphenyl-
pyrrolidine in 12 h (Table 1, entry 2). Preliminary kinetic
experiments revealed the rate of hydroamination of the methyl
substituted substrate (kobs = 5.0(ꢁ0.3) ꢂ 10ꢃ6 mol Lꢃ1 sꢃ1) to
be significantly faster than that of its unsubstituted counter-
Notes and references
z The synthesis was carried out under nitrogen using standard Schlenk
and vacuum line techniques. Synthesis of 1: a Schlenk flask was
charged with N1,N2-bis(3,5-di-tert-butylphenyl)benzene-1,2-diamine
(400 mg, 0.825 mmol), [Al(NMe2)3]2 (131 mg, 0.416 mmol), and
toluene (20 mL). The clear solution was heated at 100 1C for one
hour. After cooling to ambient temperature, the solvent was removed
in vacuo to yield crude 1 as an off-white solid. The crude product was
recrystallized from 20 mL of toluene/diethyl ether (1 : 5) as colorless
crystals at ꢃ35 1C. Yield after recrystallization: 229 mg (0.382 mmol,
46%). 1H NMR (benzene-d6, 298 K): d 7.64 (m, 2H, Ph), 7.51 (m, 4H,
Ph), 7.25 (m, 2H, Ph), 6.91 (m, 2H, Ph), 2.76 (s, 6H, N(CH3)2), 1.45
(s, 6H, HN(CH3)2), 1.44 (s, 36H, C(CH3)3), 1.08 (br s, 1H,
HN(CH3)2). 13C NMR (benzene-d6, 298 K): d 152.26 (s, Ph), 148.71
(s, Ph), 142.06 (s, Ph), 118.80 (s, Ph), 117.98 (s, Ph), 115.26 (s, Ph),
111.04 (s, Ph), 41.41 (s, N(CH3)2), 37.81 (s, HN(CH3)2), 35.44
(s, C(CH3)3), 32.24 (s, C(CH3)3). Anal. calcd for C38H59N4Al: C,
76.21; H, 9.93; N, 9.36%. Found: C, 75.89; H, 10.17; N, 9.57%.
part (kobs = 1.5(ꢁ0.1) ꢂ 10ꢃ6 mol Lꢃ1
s
ꢃ1). A similar effect
has been observed in lanthanide catalysis and was attributed
to stabilization of the transition state (upon alkyl-substitution)
during the rate determining olefin insertion into the M–N
bond (structure II, Fig. 2).12
To obtain some more insight into the reaction mechanism, a
stoichiometric reaction of 1 with 2,2-diphenylpent-4-ene-1-
amine on an NMR scale (in C6D6) was conducted to determine
whether the resting state of the catalyst could be observed. The
aminoalkene was consumed in less than 5 minutes at room
Crystal data for
1 with Mo-Ka radiation (l = 0.71073 A):
C39.50H62.56AlN4O0.43, M = 627.33, monoclinic, a = 26.378(5), b =
25.722(5), c = 28.451(5) A, V = 17202(6) A3, a = 901, b =
116,980(3)1, g = 901, T = 183(2) K, space group P21/n (no. 14),
Z = 16, Dc = 0.969 g cmꢃ3, m = 0.067 mmꢃ1, 152 676 reflections
measured, 31 601 unique (Rint = 0.0916) which were used in all
calculations. Final R1 values were 0.0850 (I > 2s(I)) and 0.1690
1
temperature (determined by H NMR), accompanied by the
appearance of new signals. The emergence of a significantly
upfield shifted N–H resonance (ꢃ0.26 ppm) as well as the
convergence of the dimethyl-amine/-amide resonances are
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(all data). Final wR(F2) values were 0.2335 (I > 2s(I)) and 0.2721
(all data). Data collection was performed on a Bruker APEX-I CCD
instrument. The structure was solved by direct methods and refined by
full matrix least squares method, SHELXTL6.13 SQUEEZE was used to
partially remove solvent contribution from the overall intensity data.14
Complete crystal composition: 1ꢄ0.5Et2O. CCDC 765662. Refinement
parameters including discussion of disorder can be found in the ESI.w
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