Platinum-catalyzed intramolecular hydroamination of unactivated olefins with secondary alkylamines

Article abstract of DOI:10.1021/ja043278q

Reaction of benzyl-2,2-diphenyl-4-pentenylamine with a catalytic 1:2 mixture of [PtCl₂(H₂C=CH₂)]₂ (2.5 mol %) and PPh₃ in dioxane at 120 °C for 16 h led to isolation of 1-benzyl-2-methyl-4,4-diphenylp

Full text of DOI:10.1021/ja043278q

Published on Web 01/08/2005
Platinum-Catalyzed Intramolecular Hydroamination of Unactivated Olefins
with Secondary Alkylamines
Christopher F. Bender and Ross A. Widenhoefer*
P. M. Gross Chemical Laboratory, Duke UniVersity, Durham, North Carolina 27708-0346
Received November 8, 2004; E-mail: rwidenho@chem.duke.edu
Table 1. Hydroamination of Amino Olefins Catalyzed by a Mixture
of [PtCl2(H2CdCH2)]2 (2) (2.5 mol %) and PPh3 (5 mol %) in
Dioxane at 120 °C
The prevalence of nitrogen heterocycles in naturally occurring
and biologically active molecules,1 coupled with the limitations
associated with traditional methods for C-N bond formation,2 has
stimulated considerable interest in catalytic olefin amination as a
route to nitrogen heterocycles.3 However, despite significant
progress in this area, the intramolecular hydroamination of unac-
tivated olefins with alkylamines remains problematic.3-11 For
example, Pd(II) complexes catalyze the intramolecular oxidative
amination of unactivated olefins with arylamines4 and amides5 but
are not compatible with alkylamines.6 Conversely, lanthanide
metallocene7 and amido8 complexes catalyze the intramolecular
hydroamination of unactivated olefins with alkylamines, but the
synthetic utility of these protocols is compromised by the poor
functional group compatibility and extreme moisture sensitivity of
the lanthanide catalyst. A number of other systems for the
hydroamination of unactivated olefins with alkylamines have been
identified, but these are either of limited scope,9 are restricted to
the intermolecular hydroamination of vinyl arenes,10 or require a
stoichiometric amount of transition metal complex.11
The attack of nucleophiles on olefins complexed to Pt(II) has
been known for nearly a century.12 However, efficient catalytic
processes that exploit this reactivity have not been forthcoming,
presumably due to the high kinetic and thermodynamic stability of
platinum alkyl and olefin complexes.13 Nevertheless, we have
recently reported effective Pt(II)-catalyzed protocols for the addition
of carbon,14 nitrogen,15 and oxygen16 nucleophiles to unactivated
olefins.17 Although this group of transformations includes the Pt(II)-
catalyzed hydroamination of ethylene with carboxamides,15 all our
attempts to achieve the hydroamination of ethylene with alkylamines
have been unsuccessful. Despite these failures, we considered that
the Pt-catalyzed hydroamination of unactivated olefins with alkyl-
amines might be realized under intramolecular conditions. Indeed,
here we report the Pt(II)-catalyzed intramolecular hydroamination
of γ- and δ-amino olefins to form nitrogen heterocycles.
Heating a concentrated dioxane solution of γ-amino olefin 1 (0.5
M) with a catalytic mixture of [PtCl2(H2CdCH2)]2 (2) (2.5 mol
%) and PPh3 (5 mol %) at 120 °C for 16 h led to isolation of
pyrrolidine 3 in 75% yield (eq 1). Platinum-catalyzed hydro-
a Isolated product of g95% purity. b Reaction mixture contained water
(0.5 equiv). c GC yield given in parentheses. d Diastereomeric ratio given
in parentheses. e Substrate added slowly to reaction mixture.
and 10-14). Furthermore, neither the rate nor yield of hydro-
amination was affected by the presence of water (0.5 equiv) in the
reaction mixture (Table 1, entries 4 and 5). δ-Amino olefins also
underwent Pt-catalyzed hydroamination to form piperidine deriva-
tives in moderate yield (Table 1, entry 15).
To gain insight into the mechanism of the Pt-catalyzed hydro-
amination of amino olefins, we investigated the stoichiometric
reaction of 1 with the platinum phosphine dimer [PtCl2(PPh3)]2 (4).18
Reaction of 1 (15 mM) and 4 (0.5 equiv) in CDCl3 at -20 °C led
to rapid (e5 min) formation of the platinum amine complex trans-5
in 97 ( 5% yield (1H NMR) (Scheme 1).19 Warming a CDCl3
solution of trans-5 at 20 °C for 1 h and at 40 °C for 0.5 h led to
formation of the zwitterionic complex 6 in 94 ( 5% yield (1H
NMR) (Scheme 1).20 Thermolysis of a dioxane-d8 solution of 6 at
amination of γ-amino olefins tolerated substitution at the allylic
and internal olefinic carbon atoms and tolerated both primary and
secondary N-bound alkyl groups (Table 1, entries 1-7). gem-
Dialkyl substitution at the â-position of the γ-amino olefin
facilitated hydroamination, but was not required (Table 1, entries
8 and 9). Platinum-catalyzed hydroamination tolerated a range of
functionality including bromo, nitro, and cyano groups, carboxylic
esters, acetals, and benzyl and silyl ethers (Table 1, entries 2, 6,
9
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J. AM. CHEM. SOC. 2005, 127, 1070-1071
10.1021/ja043278q CCC: $30.25 © 2005 American Chemical Society

C O M M U N I C A T I O N S
Scheme 1
Dreyfus Foundation and GlaxoSmithKline for unrestricted financial
assistance. We thank Cong Liu and Xiaoqing Han for performing
some preliminary experiments.
Supporting Information Available: Experimental procedures and
spectroscopic data for products. This material is available free of charge
via the Internet at http://pubs.acs.org.
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80 °C for 16 h led to decomposition without formation of
pyrrolidine 3. Conversely, treatment of a dioxane-d8 solution of 6
(32 mM) with N-benzyl-4-pentenylamine (7; 5 equiv) at 25 °C for
5 min led to complete consumption of 6 and formation of the
heterobicyclic platinum amine complex trans-8 (Scheme 1);19-21
subsequent thermolysis of this solution at 120 °C for 16 h formed
3 in 101 ( 5% yield from trans-8 (1H NMR). In a separate
experiment, treatment of 6 with HNEt2 (1 equiv) at 25 °C for 5
min formed trans-8 in 104 ( 5% yield (1H NMR) (Scheme 1).
The experiments described in the preceding paragraph support
a mechanism for the platinum-catalyzed hydroamination of 1
initiated by formation of platinum amine complex trans-5 (Scheme
2). C-N bond formation presumably occurs via intramolecular
ligand exchange followed by outer-sphere attack12 of the pendant
amine on the olefin of I to form 6 (Scheme 2). Because thermolysis
of 6 in the absence of 7 formed no detectable amounts of 3 and
because 6 reacted rapidly and quantitatvely with amine to form
trans-8, intramolecular protonolysis of the Pt-C bond of 6 appears
unlikely. Rather, our data support a mechanism involving depro-
tonation/chloride displacement from 6 followed by intermolecular
protonolysis of the Pt-C bond of trans-8,22 presumably via a Pt(IV)
hydride intermediate such as II (Scheme 2).23 Ligand exchange
from Pt-amine complex III would release 3 and regenerate trans-
5.
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(18) Complexes 4 and 2 were equally effective as catalysts for the conversion
of 1 to 3.
(19) See Supporting Information for details regarding the synthesis and
characterization of complexes trans-5, 6, and trans-8.
(20) (a) For related zwitterionic and heterocyclic amine complexes see ref 12c
and 20b, respectively. (b) Al-Najjar, I. M.; Green, M.; Kerrison, S. J. S.;
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(21) Accurate determination of the yield of conversion of 6 to trans-8 under
these conditions was hindered by the presence of excess 7.
(22) We cannot rule out a mechanism involving reversible formation of trans-8
followed by intermolecular protonolysis of 6.
In summary, we have developed an effective late-transition metal-
catalyzed protocol for the intramolecular hydroamination of unac-
tivated olefins with alkylamines and we have identified a number
of potential intermediates in the catalytic cycle.
(23) Stahl, S. S.; Labinger, J. A.; Bercaw, J. E. J. Am. Chem. Soc. 1996, 118,
5961.
Acknowledgment is made to the NSF (CHE-03-04994) for
support of this research. R.W. thanks the Camille and Henry
JA043278Q
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