Rhodium(I)-catalyzed hydroaminomethylation of 2-isopropenylanilines as a novel route to 1,2,3,4-tetrahydroquinolines

Article abstract of DOI:10.1039/b702497e

A new atom economical approach for the preparation of 1,2,3,4- tetrahydroquinolines can be achieved by means of the intramolecular hydroaminomethylation of 2-isopropenylanilines, mediated by an ionic diamino rhodium catalyst that does not require phosphine - this reaction is highly chemo- and regioselective, and it occurs in good isolated yields. The Royal Society of Chemistry.

Full text of DOI:10.1039/b702497e

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Rhodium(I)-catalyzed hydroaminomethylation of 2-isopropenylanilines
as a novel route to 1,2,3,4-tetrahydroquinolines{
Tiago O. Vieira and Howard Alper*
Received (in Cambridge, UK) 16th February 2007, Accepted 3rd April 2007
First published as an Advance Article on the web 19th April 2007
DOI: 10.1039/b702497e
A new atom economical approach for the preparation of
,2,3,4-tetrahydroquinolines can be achieved by means of the
considered whether 1 could be valuable for hydroaminomethyla-
tion reactions. We now report a new atom economical preparation
of 1,2,3,4-tetrahydroquinolines by means of a phosphine free
rhodium catalyzed intramolecular hydroaminomethylation of
1
intramolecular hydroaminomethylation of 2-isopropenylani-
lines, mediated by an ionic diamino rhodium catalyst that does
not require phosphine—this reaction is highly chemo- and
regioselective, and it occurs in good isolated yields.
2-isopropenylanilines, in high chemo- and regioselectivity.
To test the viability of our catalytic system for the hydro-
aminomethylation reaction, we first performed the reaction
between a-methylstyrene and aniline, catalyzed by 1 (Scheme 2).
We were gratified to observe that the linear amine could be
obtained as the only regioisomer in 80% isolated yield, using
2.5 mol% of catalyst. This result suggested that the catalytic system
is an active and efficient one.
The hydroaminomethylation reaction is an elegant approach to
the synthesis of secondary and tertiary amines from olefins, due to
1
its high atom economy. It was originally discovered by Reppe and
2
co-workers in the early 1950s and consists of a tandem hydro-
formylation reaction followed by reductive amination (Scheme 1).
Only in the last two decades has the potential of this reaction been
extensively explored, and a wide range of quite efficient protocols
were established for hydroaminomethylation, including alkyl (or
When the same conditions were investigated for 2-isopropenyl-
aniline (2), only 60% conversion was achieved (Table 1, entry 1).
After optimization, 3 could be obtained as the single product by
1,3
aryl) olefins and aliphatic (or aromatic) amines. It has also been
using 5.0 mol% of 1 (Table 1, entry 5), under CO/H .
2
4
used for the synthesis of dendrimers and macroheterocycles. In
5
Having found the optimum conditions for our catalytic system,
we extended the scope of our protocol to 2-isopropenylanilines
substituted at the nitrogen and in the aromatic ring. The protocol
proved to be general and the 1,2,3,4-tetrahydroquinolines were
obtained in very good isolated yields (Table 2). Due to lower
reactivity for the halogenated substrates, the catalyst load had to
be increased to 7.5 mol%. Partial substrate hydrogenation was
noticed for the electron poor fluorosubstituted derivative (entry 7).
contrast, the intramolecular version has been demonstrated for
6
only a few examples, and usually in low chemoselectivity. The
main problem resides in the first step, hydroformylation, and
lactams can be formed—sometimes exclusively—via cleavage of
1
the intermediate rhodium–acyl species.
Tetrahydroquinolines play an important role in the fields of
7
natural products and medicinal chemistry. They are of synthetic
interest for the preparation of pharmaceuticals and agrochemicals,
8
as well as in material sciences. While there are a number of
9
methods to prepare this heterocyclic system, the most convenient
10
and direct route is still the partial hydrogenation of quinolines,
the preparation of which often requires harsh conditions such as
high temperatures and/or strong acidic media.
We have recently reported the use of diamine rhodium catalysts
Scheme 2 Reaction between a-methylstyrene and aniline.
11
for the highly regioselective hydroformylation of styrenes. As a
potentially different application of using 1 as a catalyst, we
Table 1 Selected screening for the hydroaminomethylation of
2
a
-isopropenylaniline (2)
Entry
Catalyst 1 (mol%)
CO/H
2
(psi)
3 (%)
4 (%)
Scheme 1 Hydroaminomethylation reaction.
1
2
3
4
5
a
2.5
5.0
7.5
7.5
5.0
500/500
500/500
500/500
700/300
700/300
60
80
90
.98
.98
—
—
10
Trace
—
Contribution from the Centre for Catalysis Research and Innovation,
Department of Chemistry, University of Ottawa, 10 Marie Curie,
Ottawa, Ontario, Canada K1N 6N5. E-mail: howard.alper@uottawa.ca;
Fax: 1 613 562 5871; Tel: 1 613 562 5189
Electronic supplementary information (ESI) available: Experimental
details, full characterization of new compounds and NMR spectra. See
DOI: 10.1039/b702497e
All reactions were performed in toluene at 120 uC for 48 h. The
1
conversion and the product ratios were determined by H NMR on
the crude product mixture.
{
2
710 | Chem. Commun., 2007, 2710–2711
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b
Yield (%)
Entry
Substrate
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R = F
R = Br
R = Me
61
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1
1
0
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n = 1
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a
The reactions were performed on a 1 mmol scale with 5.0 mol%
7.5 mol% for the halogenated substrates) of 1, at 120 uC, in toluene
2 mL), for 48 h, under 1000 psi CO/H (7 : 3). Isolated yields.
2
(
b
(
c
20% substrate hydrogenation.
An important feature of this novel hydroaminomethylation
catalytic system is the air compatibility of 1, and thus it is not
necessary to degas the solvent prior to charging the autoclave,
simplifying the manipulation.
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entry to 1,2,3,4-tetrahydroquinolines through a phosphine free
hydroaminomethylation of 2-isopropenylanilines, in good yields
and in high chemo- and regioselectivity. We believe this new
catalytic approach represents a significant advance in heterocyclic
chemistry, and is promising for the synthesis of pharmaceuticals.
We are indebted to SASOL Technology for financial support of
this work, and to the summer student Vikas Sikervar for the
preparation of some of the substrates.
2
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