Intramolecular alkene hydroaminations catalyzed by a bis(thiophosphinic amidate) Zr(IV) complex

Article abstract of DOI:10.1039/b505738h

A neutral Zr(IV) complex has been shown to be an effective precatalyst for intramolecular alkene hydroaminations that provide cyclic amines in good to excellent yields. The Royal Society of Chemistry 2005.

Full text of DOI:10.1039/b505738h

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Intramolecular alkene hydroaminations catalyzed by a
bis(thiophosphinic amidate) Zr(IV) complex{
Hyunseok Kim,a Phil Ho Lee*a and Tom Livinghouse*b
Received (in Berkeley, CA, USA) 22nd April 2005, Accepted 15th July 2005
First published as an Advance Article on the web 20th September 2005
DOI: 10.1039/b505738h
cyclization of this substrate would be facilitated by a geminal
A neutral Zr(IV) complex has been shown to be an effective
precatalyst for intramolecular alkene hydroaminations that
provide cyclic amines in good to excellent yields.
Thorpe–Ingold effect.3f,6 Successful generation of the desired NPS
precatalyst 1 proved experimentally straightforward via amine
elimination, involving commercially available Zr(NMe2)4 (2) and
bis(thiophosphinic amide) (3)3d (1 equiv., C6D6, 25 uC, 10 min).
The intramolecular hydroamination of alkenes constitutes a
powerful method for the synthesis of azacycles.1 The seminal
group 3 metallocenes developed by Marks and co-workers2 have
recently been joined by a variety of non-metallocene complexes of
the group 3 metals as catalysts for this important reaction.3,4
Although there are numerous accounts that describe both the
intra- and intermolecular hydroamination of alkynes5a–d and
allenes5e,f catalyzed by various complexes of the group 4 metals,
there have been very few reports of intramolecular alkene
hydroaminations mediated by complexes of metals belonging to
this triad, and all but one6 of these are restricted to cationic
species.7 We have previously disclosed that chelating bis(thiophos-
phinic amidate) ‘‘NPS’’ complexes of the group 3 metals
(particularly Y and Nd) are potent catalysts for intramolecular
alkene hydroamination.3d In this communication, we show that
the neutral Zr(IV) bis(thiophosphinic amidate) complex (1) is a
competent precatalyst for the cyclization of representative primary
aminoalkenes (Scheme 1).
1
The H, 31P and 13C NMR spectra of 1 are consistent with a
monomeric species possessing an octahedral structure with a mer
configuration. The NMe2 resonance (500 MHz) appears as a sharp
singlet at 3.11 ppm and the linker CH2 as a doublet (2.69 ppm,
J 5 10 Hz). The signal for the CH adjacent to P appears as a well-
defined septet centered at 2.00 ppm (J 5 7 Hz), with the
diastereomeric isopropyl methyls appearing as a set of doublets
between 1.16 and 1.10 ppm (J 5 7 Hz). The 31P NMR spectrum of
1 reveals a singlet at 75.10 ppm.8 The thermal stability of 1 was
demonstrated by heating at 150 uC for 19 h, whereupon no
alteration to the NMR spectra was observed. Addition of 4a to 1
(5 mol%), followed by heating at 100 uC, provided the pyrrolidine
5a in 97% yield9 after 105 h. Alternatively, cyclization of 4a at
120 uC (C6D6) and 150 uC (toluene-d8) provided 5a in 94% (12 h)
and 98% (2.5 h) yield, respectively. Closely-related reaction
conditions were subsequently utilized for the cyclization of a series
of representative primary amines 4b–f and, unsuccessfully, for the
secondary amine 4g. A compilation of the reaction times and
yields observed for the cyclization of aminoalkenes 4a–g in the
presence of the Zr(IV)?NPS chelate (1) appears in Table 1.
Significantly, cyclization of 4a, 4b and 4d on a preparative (3 mmol)
scale followed by separation of the products from the catalyst by
vacuum transfer and protonation (HCl–MeOH), furnished 5a, 5b
and 5d as their hydrochloride salts in 90, 88 and 85% isolated
yields, respectively.
Several of the trends that emerge from the foregoing examples
are worthy of comment. The presence of geminal Thorpe–Ingold
buttressing is helpful but not a prerequisite for successful
cyclization, as 5-hexen-2-amine 4b and 4-penten-1-amine 4c
partake in the reaction. Accordingly, 4c was smoothly converted
to 5c in 91% yield in the presence of 1 (10 mol%) in 10 h at 150 uC.
By way of comparison, cyclization of 4c using Zr(NMe2)4 as the
precatalyst (10 mol%, 150 uC, toluene-d8) gave 5c (91%) but
required 28 h. In addition, the styrenyl substrate 4d, containing
an internal alkene, underwent cyclization at 150 uC to provide
5d in 93% yield after 120 h. In this instance, the reaction time
could be shortened to 39 h when 10 mol% of the precatalyst
was employed. A similar result was observed in the case of the
1,1-disubstituted aminoalkene 4f. That the latter substrate under-
goes cyclization to give the product derived from exocyclic
addition to the alkene is consistent with the mechanism shown
in Scheme 2. It is also of significance that the secondary
Scheme 1
The internal hydroamination of 2,2-dimethylpent-4-ene-1-amine
(4a) was selected for initial examination as it was expected that
aDepartment of Chemistry, Kangwon National University, Chunchon,
200-701, Republic of Korea
bDepartment of Chemistry, Montana State University, Bozeman,
MT 59717, USA. E-mail: livinghouse@chemistry.montana.edu
{ Electronic supplementary information (ESI) available: Experimental
procedures and characterization data for all new compounds. See http://
dx.doi.org/10.1039/b505738h
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Table 1 Internal alkene hydroaminations catalyzed by 1a
The dynamics of the hydroamination involving precatalyst
1 can be conveniently monitored by 31P NMR. Addition of 4a
to a C6D6 solution of 1 (5 mol%) results in the immediate
disappearance of the phosphorus resonance at 75.10 ppm and
the concomitant appearance of a new signal at 78.12 ppm. That
this is accompanied by the production of 2 equiv. of Me2NH
(1H NMR) is strongly indicative of a quantitative exchange
of the amido ligands at zirconium, resulting in the incorpora-
tion of two substrate aminoalkene substituents. Significantly,
cyclization of 4a at 120 uC over 12 h results in a 92%
conversion to 5a with no change to the 31P resonance at
78.12 ppm, thus providing evidence that the Zr catalyst is
robust under the reaction conditions. In addition, at no time
during this reaction did the 31P resonance associated with
Yield
(%)b
Entry
1
Substrate
Product
Temp./uC
Time/h
120
150
12
2.5
94
98
2
3
120
150
172
22
98c
96c
120d
150d
41
10
89
91
the free proligand
3 at 89.54 ppm appear. A probable
mechanistic pathway for the intramolecular hydroamination
of 4a, involving the putative Zr(IV) imido complex A10 and
azazirconacyclobutane B based on these observations, is depicted
in Scheme 2.
4
5
150
150d
120
39
93
91
In conclusion, we have shown that the neutral Zr(IV)?NPS
complex (1) is a competent precatalyst for intramolecular alkene
hydroaminations involving primary amines. Although the catalytic
activity of 1 is lower than that exhibited by the corresponding
Y(III)?NPS chelate,3d the results presented here are among the
first examples of internal alkene hydroamination catalyzed by a
neutral complex of a group 4 metal.6 Studies utilizing cationic
Zr(IV)?NPS and related complexes for this process are currently
under way.
120
150
9
1
99
99
6
7
150
150d
104
45
92
94
150
18
0
Generous financial support for this research was provided by
the National Institutes of Health and the National Science
Foundation.
a
Benzene-d6 (120 uC) or toluene-d8 (150 uC) were used as solvents,
b
Notes and references
respectively. NMR yields based on p-xylene as an internal
standard. trans : cis 5 1.3 : 1.0. 10 mol% Catalyst was used.
c
d
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Scheme 2
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L. L. Schafer, Organometallics, 2004, 23, 2234; as well as calcium
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aminoalkene 4g is resistant to cyclization. This stands in sharp
contrast to the results of Scott and Hultzsch who have reported
that secondary, but not primary, aminoalkenes participate in
internal hydroamination, catalyzed by cationic Zr(IV) com-
plexes.7a,b Finally, the Zr(IV)?NPS complex 1 shows higher activity
as a precatalyst than Zr(NMe2)4 2.
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8
1H NMR, 13C NMR and 31P NMR of NPS and NPS?Zr(NMe2)2 are
available as ESI.{.
9 J. Young NMR tubes, purchased from Aldrich or J. Young Ltd, were
used under refluxing conditions (bath temperature, 120 uC or 150 uC)
without any special precautions.
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Chem. Commun., 2005, 5205–5207 | 5207