Hydroaminoalkylation of unactivated olefins with dialkylamines

Article abstract of DOI:10.1021/ja806367e

The intermolecular addition of the α-C-H bonds of unactivated dialkylamines to unactivated olefins in the presence of the chloro amido complex [TaCl₃(NEt₂)₂]₂ (2) is described. This process forms the branched in

Full text of DOI:10.1021/ja806367e

Published on Web 10/21/2008
Hydroaminoalkylation of Unactivated Olefins with Dialkylamines
Seth B. Herzon† and John F. Hartwig*
Department of Chemistry, UniVersity of Illinois, 600 South Mathews AVenue, Urbana, Illinois 61801
Received August 11, 2008; E-mail: jhartwig@uiuc.edu
Table 1. Alkylation of Dialkylamines with 1-Octene
Intermolecular reactions between unstrained alkenes and amines are
rare, and additions of unactivated alkylamines to alkenes are particularly
unusual. In almost all reported cases occurring in substantial yields,
these reactions proceed by addition of the N-H bond and are limited
to processes in which the amine is first activated as an amide or
sulfonamide,1 or to reactions involving strained olefins or ethylene.2
An exception is a single hydroamination of 1-pentene with propylamine
reported by Marks and co-workers.3
We recently described the addition of the R-C-H bonds of N-alkyl
arylamines to alkenes (hydroaminoalkylation, eq 1).4 Complexes
derived from the homoleptic amide Ta(NMe2)5 (1) catalyzed the
hydroaminoalkylation in yields of up to 96%. However, the reactions
required heating at 160-165 °C and an aryl substituent on nitrogen
to modulate the properties of the amine. Until now, no analogous high-
yielding additions of dialkylamines to alkenes have been reported.5
Here, we show that such additions occur in high yield in the presence
of chlorotantalum amide catalysts. This process represents a rare
intermolecular addition of an amine to an alkene that does not require
activating substituents on either reaction partner.6 We also show that
chlorotantalum anilide complexes catalyze the hydroaminoalkylations
of alkenes with N-alkyl-arylamines under mild conditions, and provide
data that suggest the formation of an η2-imine complex is the turnover-
limiting step of the catalytic cycle.
a Determined by integration of the 1H NMR spectrum of the crude
reaction mixture containing added internal standard. b Isolated yield of
sulfonamide after purification by flash-column chromatography. c In a
separate experiment, the amine product was isolated in 77% yield by
flash-column chromatography. d Single diastereomer (stereochemistry not
assigned).
Our studies began with the syntheses of complexes in which a
fraction of the five dimethylamido ligands of the homoleptic dialkyl-
amide 1 were exchanged with chelating polyamines and polyols.7
Although complexes derived from a combination of 1 and biphenols
(such as 2,2′-biphenol) exhibited some catalytic activity, complexes
containing more electron-donating aliphatic alcohols and amines were
inactive. These data led us to test complexes containing less electron-
donating halide ligands, and these displayed the desired reactivity. The
reaction of N-methyl-phenethylamine with 1-octene in the presence
of 2 mol% of the chloroamido complex [TaCl3(NEt2)2]2 (2)8 generated
the branched addition product in high yield for the first time (Table 1,
entry 1). Under otherwise identical conditions, but with 1 as precatalyst,
this product was obtained in <5% yield.
Scheme 1. Proposed Mechanism for Olefin Hydroaminoalkylation
yield, although tert-alkyl methylamines, such as N-methyl-tert-butyl-
amine, were unreactive. N-Methyl-phenethylamine and N-methyl-
benzylamine both reacted selectively at the methyl group, despite the
presence of benzylic hydrogens. The addition of secondary amine
R-C-H bonds also occurred in high yield (entry 7).
A putative mechanism for the hydroaminoalkylation reaction
(Scheme 1) consists of elimination of amine from a tantalum bis(amide)
to form an η2-imine complex (3),9 insertion of the olefin into the
tantalum-carbon bond of this intermediate, and protonolysis by
the amine reagent to regenerate the starting bis(amide) and liberate
the product. To determine the origins of the selectivity for alkylation
at the methyl position in the amine (entries 1-6), a mixture of the
The data in Table 1 illustrate that complex 2 catalyzes the formation
of the branched addition products from reaction of 1-octene with
several types of dialkylamines in high yields and selectivities. Yields
1
of the amine determined by H NMR spectroscopy are provided in
the table. The product from the reaction of entry 1 was isolated by
flash-column chromatography (77% yield), and the products of other
reactions were isolated after conversion to the p-toluenesulfonamide
derivative. The reactions of the unsymmetrical methylamines in entries
1-6 exclusively formed the product from addition of the methyl C-H
bonds. Linear alkyl and branched alkyl methylamines added in high
† Current address: Department of Chemistry, Yale University, New Haven, CT.
9
14940 J. AM. CHEM. SOC. 2008, 130, 14940–14941
10.1021/ja806367e CCC: $40.75
2008 American Chemical Society

C O M M U N I C A T I O N S
monitored the thermolysis of isolated complexes 2 and 4 by 1H NMR
spectroscopy at 150 and 90 °C, respectively. Under these conditions
with either complex, no free amine or η2-imine complex was observed.
Taken together, these data imply that the proposed metallayclopentane
intermediate is consumed faster than it is formed, that the equilibrium
constant for elimination of amine from 2 and 4 is much less than unity,
and that formation of the putative η2-imine intermediate is turnover-
limiting under the reaction conditions.
We also conducted deuterium-labeling studies to provide information
on the origin of the relative reactivities of Ta(NR2)5 and the chloro-
tantalum amido catalysts. We previously showed that the hydroami-
noalkylation of 1-octene with N-(methyl-d3)-aniline using homoleptic
amide 1 as precatalyst formed product 6-dn, in which only 45% of the
deuterium was retained at the methylene position of the product (eq
4).4 The loss of deuterium implies that formation of the η2-imine
intermediate during reactions catalyzed by 1 is reversible. In contrast,
the reaction of N-(methyl-d3)-aniline with 1-octene catalyzed by 4
formed product 6-dn that retained almost all of the expected deuterium
on the R-carbon (eq 4).10 This result suggests that reversion to a
bis(amide) by protonlysis of the Ta-C bond of 3 by the N-H bond
of the reagent does not occur to a significant extent in reactions
catalyzed by 4 and that the partitioning of the η2-imine complex toward
insertion of alkene versus reversion to a bis(anilide) is more favorable
for complexes derived from 4 than from 1.
Table 2. Coupling of N-Methylaniline and 1-Octene at 90 °C by
Mixed Chloroanilido Complexes
% yield 6a
entry
catalyst precursor
2.3 h
5.1 h
24 h
1
2
3
[Cl3Ta(NMePh)2]2 (4)
Ta(NMe2)5 (1)
[Cl4Ta(NMePh)]•OEt2 (5)
34b
0c
2.1
53b
0c
3.8
72b
0c
14
a Determined by GC using dodecane as an internal standard. b Yield
corrected for additional substrate introduced by catalyst. c None was
observed under conditions where >0.05% could be detected.
catalyst precursor 2 and N-methyl-propylamine-N-d were heated at
150 °C for 25 h. Analysis of the crude reaction mixture by 1H and 2H
NMR spectroscopy revealed the presence of deuterium in the methyl
group of the amine (0.56 D-atom), but none could be detected in the
propyl substituent. These results imply that the observed regioselectivity
derives from selective metalation at a methyl group in the presence of
a methylene group.
Hydroaminoalkylations of R-olefins with N-alkyl-arylamines occur
when catalyzed by the closely related chlorotantalum anilide 4, prepared
by the two-step sequence shown in equation 2.7 Use of the anilide 4
rather than the chlorotantalum amide 2 for this reaction eliminates
complications arising from exchange of the arylamine with the
alkylamido groups of catalyst 2. Complex 4 catalyzed the addition of
N-alkyl-arylamines to alkenes under milder conditions than the
homoleptic amido complex 1. Additions catalyzed by 4 generated
product 6 at temperatures as low as 90 °C (Table 2, entry 1), whereas
the same reaction catalyzed by 1 required heating to 160-165 °C.4
This reaction catalyzed by 1 did not generate detectable amounts of
product at 90 °C (entry 2).
In summary, we have shown that chlorotantalum amide and anilide
complexes catalyze the hydroaminoalkylation of olefins with unprec-
edented efficiency. We attribute the enhanced activity to a more
favorable partitioning of an η2-imine complex toward addition of the
olefin, rather than reversion to the starting bis(amide), and we attribute
the more favorable partitioning of this intermediate to the reduced steric
hindrance and electron density on the chlorotantalum complex. The
alkylations of dialkylamines in this work constitute rare examples of
intermolecular reactions between an alkylamine and an alkene without
preactivation of either substrate.
In contrast to reactions catalyzed by bis(anilide) 4, little product
was obtained when the mono(anilide) 5 was used instead (Table 2,
entry 3). This result suggests that the key η2-imine intermediate 3
does not form as readily by elimination of HCl ·amine (eq 3) as by
elimination of amine.
Acknowledgment. Financial support from the National Institutes
of Health (NRSA fellowship to S.B.H.) and the NSF (to J.F.H.) is
gratefully acknowledged.
Supporting Information Available: Detailed experimental proce-
dures and spectral data of all new compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
References
To gain further information on the relative rates of different steps
of the catalytic cycle, we conducted NMR and deuterium-labeling
studies of reactions mediated by 2 and 4. First, the catalytic alkylation
of N-methylaniline with 1-octene was conducted with 15 mol% 4 (30
mol% Ta) and monitored by 1H NMR spectroscopy. Although several
tantalum complexes derived from binding and exchange of the reactant
and product amines were identified, no signals that we could assign
to a metalacyclopentane complex were observed. Moreover, reactions
conducted with 15 mol% 4 and terminated after 69% conversion by
addition of excess DCl in D2O did not lead to detectable amounts of
product containing deuterium at the methyl substituent, as determined
by 1H NMR and GC-mass spectrometry. The analogous experiment
conducted using 15 mol% 2 with diethylamine as substrate also did
not lead to detectable amounts of deuterium incorporation at the methyl
substituent of the product. Next, to probe the equilibrium between a
bis(amide) complex and an η2-imine complex and free amine, we
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(10) The amount shown is corrected for the N-CH3 groups of the catalyst.
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