A new homogeneous zinc complex with increased reactivity for the intramolecular hydroamination of alkenes

Article abstract of DOI:10.1039/b607597e

The new zinc compound N-cyclohexyl-2-(cyclohexylamino)troponiminate zinc methyl, [(Cy)₂ATI]ZnMe (2), was synthesized and showed a superior reactivity in the intramolecular hydroamination reaction of non-activated alkenes compared to previously

Full text of DOI:10.1039/b607597e

View Article Online / Journal Homepage / Table of Contents for this issue
COMMUNICATION
www.rsc.org/chemcomm | ChemComm
A new homogeneous zinc complex with increased reactivity for the
intramolecular hydroamination of alkenes{
Maximilian Dochnahl,a Jens-Wolfgang Pissarek,a Siegfried Blechert,*a Karolin Lo¨hnwitzb and
Peter W. Roesky*b
Received (in Cambridge, UK) 30th May 2006, Accepted 11th July 2006
First published as an Advance Article on the web 24th July 2006
DOI: 10.1039/b607597e
The new zinc compound N-cyclohexyl-2-(cyclohexylamino)tro-
poniminate zinc methyl, [(Cy)2ATI]ZnMe (2), was synthesized
and showed a superior reactivity in the intramolecular
hydroamination reaction of non-activated alkenes compared
to previously reported homogeneous zinc complexes.
The synthesis of nitrogen-containing molecules is of particular
interest because a huge number of natural products and
pharmaceuticals include amine or amide moieties.1 Traditionally,
Scheme 2 Reagents and conditions: for R = Cy: a) cyclohexylamine
the synthesis of these compounds requires multistep synthesis
(neat), 0 uC to rt, 16 h, 92%; b) 1. Et3OBF4, CH2Cl2, rt, 3 h; 2.
resulting in the production of many side products and waste. Thus,
cyclohexylamine (exc.), 0 uC to rt, 16 h, 90%; c) ZnMe2 (1.7 eq.), toluene,
rt, 3 h, 88% (Cy = cyclohexyl); for R = iPr see ref. 8.
the direct addition of N–H bonds to C–C multiple bonds
(hydroamination) (Scheme 1) constitutes an environmentally
friendlier and potentially more economic method.2 Many metals
therefore substituted the isopropyl by a cyclohexyl group. Thus,
and catalysts have been employed for this transformation,
the ligand was prepared in two steps from 2-tosyloxytropone
especially the lanthanides,2b,3 group IV transition metals,2b,c,4 the
following a modified literature procedure.9 Both steps can be
platinum metals5 and also calcium6 and gold.7
accomplished in high yields of 92 and 90%, respectively. The
Recently we introduced N-isopropyl-2-(isopropylamino)tropo-
synthesis of the corresponding zinc complex 2 is also high yielding
niminate zinc methyl (1) as a catalyst for the intramolecular
(Scheme 2).{
hydroamination.8 This complex possesses several advantages in
The structure of 2 was established by single crystal X-ray
comparison to the well-established catalysts: it shows unprece-
diffraction analysis (Fig. 1). Compound 2 is a monomer in the
dented tolerance towards polar functional groups and it is
solid state, thus the zinc atom displays trigonal planar geometry.
relatively stable towards air and moisture. Furthermore zinc is
The bond lengths and angles are in the expected range.
an inexpensive and non-toxic metal which makes its use in catalysis
The activity of compound 2 was further investigated in the
attractive.
intramolecular hydroamination reaction. We were pleased to find
On our course to find more reactive complexes for the catalytic
that 2 is indeed highly reactive in this reaction. In most of the
hydroamination reaction we focused our interest on simple
investigated cases it shows a much higher activity than complex 1
modifications of the aminotroponiminate ligand system. We
Scheme 1 Intramolecular hydroamination of amines.
aTechnische Universita¨t Berlin, Institut fu¨r Chemie, Straße des 17. Juni
135, 10623 Berlin, Germany. E-mail: blechert@chem.tu-berlin.de;
Fax: +49 (0)30-31 42 36 19; Tel: +49 (0)30-31 42 23 55
bFreie Universita¨t Berlin, Institut fu¨r Chemie und Biochemie,
Fig. 1 Perspective ORTEP-view of the molecular structure of 2. Thermal
Fabeckstraße 34-36, 14195 Berlin, Germany. E-mail: roesky@chemie.fu-
ellipsoids are drawn to encompass 50% probability. Hydrogen atoms are
berlin.de; Fax: +49 (0)30-83 85 24 40; Tel: +49 (0)30-83 85 40 04
omitted for clarity. Selected distances [pm] and angles [u]: Zn–N1 197.0(2),
{ Electronic supplementary information (ESI) available: Complete
Zn–N2 1.96.6(2), Zn–C20 194.4(3); Zn–N1–C1 114.8(2), Zn–N1–C8
spectral data of the complex and its precursors, complete spectral data
123.5(2), Zn–N2–C7 114.77(2), Zn–N2–C14 124.5(2), N2–Zn–C20
of the obtained products and experimental procedure of the hydroamina-
tion. See DOI: 10.1039/b607597e
137.12(11), N–Zn1–C20 140.47(11), N1–Zn–N2 82.17(8).
This journal is ß The Royal Society of Chemistry 2006
Chem. Commun., 2006, 3405–3407 | 3405

View Article Online
bearing isopropyl groups. All reactions were run at 80 uC with a
catalyst loading of only 2.5 mol% and 2.5 mol% of
[PhNMe2H][B(C6F5)4] as a cocatalyst. Excellent isolated yields of
more than 80% were obtained in each case (Table 1). There is a
notable substrate dependence on the reaction time, resulting in a
timescale from ten minutes to four weeks for substrates bearing
chelating functional groups. In the case of the strained norbornene
derivatives (entries 1–2) the cyclization took place solely at the
terminal double bond. With the second generation catalyst 2 both
substrates were cyclized with short reaction times. It is noteworthy
that the reaction with catalyst 1 took around ten times longer for
complete conversion to be reached. However, no diastereo-
selectivity was observed with either catalyst, leading to an
inseparable 1 : 1 mixture of diastereoisomers. Substrates bearing
bulky substituents in the b position with respect to the amine
cyclized with short reaction times of 10–20 minutes, respectively
(entries 3–4). Changing from a thiophene to a furan moiety
resulted in a 15 times longer reaction time for both catalysts
(entries 4–5). These prolonged reaction times could be explained by
the more effective chelation of the aminofuran to the zinc catalysts.
Table 1 Synthesized pyrrolidines and comparison of the catalystsa
Catalyst 1
Catalyst 2
Entry
1
Substrate
Product
Time
Conversion
93%b
Time
Conversion
30 h
2 h
96%b
86%c
2
20 h
quant.b
3 h
quant.b
90%c
3
4
5
6
7
95 min
20 min
6 h
quant.b
quant.b,d
quant.b
quant.b
60%b
20 min
10 min
2.5 h
quant.b
91%c
quant.b,d
97%c
quant.b
95%c
4.5 h
13 h
75 min
13 h
quant.b
88%c
quant.b
83%c
8
9
13 d
27 d
36%b
49%b
13 d
27 d
84%b
97%b
95%c
20 d
21 d
86%b
7 d
18 d
b
85%b
82%c
10
quant.b
quant.b
96%c
Reagents and conditions: Substrate (430 mmol), catalyst (2.5 mol%), [PhNMe2H][B(C6F5)4] (2.5 mol%), C6D6, 80 uC. Determined by 1H
a
c
NMR. Isolated yield of . 95% purity. The reaction was performed with 0.8 mol% [PhNMe2H][B(C6F5)4].
d
3406 | Chem. Commun., 2006, 3405–3407
This journal is ß The Royal Society of Chemistry 2006

View Article Online
can be grown from toluene at 240 uC. (Found: C, 65.7; H, 8.7; N, 7.3.
C20H30N2Zn requires C, 66.0; H, 8.3; N, 7.7%); dH(400 MHz, C6D6) 0.08
(3 H, s), 1.05–1.91 (20 H, m), 3.50–3.59 (2 H, m), 6.38 (1 H, t, J 9.1), 6.73
(2 H, d, J 11.6), 6.99 (2 H, dd, J 9.1, J 11.6); dC(100 MHz, C6D6) 1.1, 25.7,
26.0, 35.2, 57.1, 111.3, 117.5, 134.1, 159.9 (Cq); m/z (EI) 362 [M+] (17%),
347 [M 2 CH3+] (11), 284 [M 2 ZnCH3+] (16).
However, by using catalyst 2 the reaction time could be halved in
both cases. A cyclohexane derivative was cyclized to the
corresponding spiro compound three times faster with the new
catalyst (entry 6). Even with slowly reacting substrates (entries 7–8)
substantial differences in the reactivity between the zinc catalysts 1
and 2 were observed. In both cases quantitative conversion could
only be obtained when the second generation catalyst was
employed. We attribute this to a higher stability of catalyst 2.
An amine bearing a disubstituted double bond took seven days to
reach 85% conversion with catalyst 2, however the same amount
was reached with catalyst 1 after three weeks (entry 9). Only in the
case of the ortho-substituted pyridine (entry 10) did minor
differences in reaction time occur. It is noteworthy that in the
cases of previously reported substrates (entries 3 and 6) the
reactions with our new zinc catalyst 2 were performed at
significantly lower reaction temperature (80 uC compared to
120 uC) but were nevertheless faster.5d In principle there are two
possibilities for the mechanism of the reaction: activation of the
double bonds by zinc or activation of the amine by forming a zinc
amide moiety. So far we have not been able to clearly ascertain
which of the two mechanisms operates in the zinc catalyzed
hydroamination. Mechanistic investigations are currently in
progress.
¯
Crystal data for 2: C20H30N2Zn, M = 363.83, triclinic, space group P1,
a = 973.58(7) pm, b = 1100.97(8) pm, c = 2007.60(13) pm, a = 76.685(5),
b = 86.477(6), c = 64.209(5)u, V = 1883.6(2)106 pm3, T = 200(2) K, Z = 4,
m = 0.711 mm21, 14223 reflections collected, 6621 unique, R1 = 0.0341
(I . 2s(I)), wR2 = 0.0874 for all 6621 data, 417 parameters, all non
hydrogen atoms calculated anisotropic; the positions of the H atoms were
calculated for idealised positions. The structure was solved and refined
using SHELXS-97 and SHELXL-97.10 CCDC 609557. For crystal-
lographic data in CIF or other electronic format see DOI: 10.1039/
b607597e
General Procedure for the zinc-catalyzed hydroamination. A predried
NMR-tube was charged with the aminoalkene (430 mmol). A solution of 2
(4 mg, 11 mmol, 2.5 mol%) and [PhNMe2H][B(C6F5)4] (9 mg, 11 mmol,
2.5 mol%) in 0.5 mL C6D6 was added under a nitrogen atmosphere. The
NMR-tube was flamesealed under vacuum. The reaction mixture was then
heated to 80 uC for the stated time. The reaction progress was monitored
1
by H NMR. When the reaction was judged to be completed, the crude
reaction mixture was directly subjected to column chromatography on
silica.
1 D. O’Hagan, Nat. Prod. Rep., 2000, 17, 435.
2 For recent reviews see: (a) K. C. Hultzsch, Adv. Synth. Catal., 2005, 347,
367–391; (b) S. Hong and T. J. Marks, Acc. Chem. Res., 2004, 37,
673–686; (c) I. Bytschkov and S. Doye, Eur. J. Org. Chem., 2003,
935–946; (d) F. Pohlki and S. Doye, Chem. Soc. Rev., 2003, 32, 104–114;
(e) T. E. Mu¨ller, in Encyclopedia of Catalysis, J. T. Horva´th (ed.), John
Wiley & Sons, New York, 2002; (f) J. Seayad, A. Tillack, C. G. Hartung
and M. Beller, Adv. Synth. Catal., 2002, 344, 795–813; (g) J.-J. Brunet
and D. Neibecker, in Catalytic Heterofunctionalizations, A. Togni,
H. Gru¨tzmacher (eds.), VCH, Weinheim, 2001; (h) T. E. Mu¨ller and
M. Beller, Chem. Rev., 1998, 98, 675.
In conclusion, a new homogeneous zinc complex, its synthesis
and crystal structure have been reported. We have demonstrated
that subtle changes in the ligand structure can lead to a strong
effect on the reactivity of the catalyst. The latter is available from
low-cost starting materials in a high yielding procedure. In most of
the investigated cases the new catalyst 2 showed superior reactivity
in the hydroamination of non-activated alkenes and a higher
stability in solution compared to the first generation catalyst 1,
which makes its application to catalysis more useful.
3 (a) D. Riegert, J. Collin, A. Meddour, E. Schulz and A. Trifonov, J. Org.
Chem., 2006, 71, 2514; (b) D. K. Gribkov, K. C. Hultzsch and
F. Hampel, J. Am. Chem. Soc., 2006, 128, 3748.
4 (a) L. T. Kasper, B. Fingerhut and L. Ackermann, Angew. Chem., Int.
Ed., 2005, 44, 5972; (b) A. Heutling, F. Pohlki, I. Bytschkov and
S. Doye, Angew. Chem., Int. Ed., 2005, 44, 2951; (c) J. A. Bexrud,
J. D. Beard, D. C. Leitch and L. L. Schafer, Org. Lett., 2005, 7, 1959.
5 Recent examples: (a) A. Takemiya and J. F. Hartwig, J. Am. Chem.
Soc., 2006, 128, 6042; (b) F. E. Michael and B. M. Cochran, J. Am.
Chem. Soc., 2006, 128, 4246; (c) G. B. Bajracharya, Z. Huo and
Y. Yamamoto, J. Org. Chem., 2005, 70, 4883; (d) C. F. Bender and
R. A. Widenhoefer, J. Am. Chem. Soc., 2005, 127, 1070.
This work was supported by the Deutsche Forschungs-
gemeinschaft (Graduiertenkolleg: Synthetische, mechanistische
und reaktionstechnische Aspekte von Metallkatalysatoren). We
thank the Fonds der Chemischen Industrie for a fellowship to
M.D. (K174/11).
Notes and references
6 M. R. Crimmin, I. J. Caseley and M. S. Hill, J. Am. Chem. Soc., 2005,
127, 2042.
{ Dimethyl zinc solution was purchased from Aldrich. [PhNMe2H]
[B(C6F5)4] was purchased from Strem.
7 (a) X. Han and R. A. Widenhoefer, Angew. Chem., Int. Ed., 2006, 45,
1747; (b) C. Brouwer and C. He, Angew. Chem., Int. Ed., 2006, 45, 1744.
8 A. Zulys, M. Dochnahl, D. Hollmann, K. Lo¨hnwitz, J.-S. Herrmann,
P. W. Roesky and S. Blechert, Angew. Chem., Int. Ed., 2005, 44, 7794.
9 H. V. R. Dias, W. Jin and R. E. Ratcliff, Inorg. Chem., 1995, 34, 6100.
10 (a) G. M. Sheldrick, SHELXS-97, Universita¨t Go¨ttingen, Germany,
1997; (b) G. M. Sheldrick, SHELXL-97, Universita¨t Go¨ttingen,
Germany, 1997.
N-Cyclohexyl-2-(cyclohexylamino)troponiminate zinc methyl,
[(Cy)2ATI]ZnMe (2). A solution of ZnMe2 (2.0 M in toluene, 4.5 mL,
9.0 mmol) was diluted in toluene (15 mL) at rt. A solution of [(Cy)2ATI]H
(150 mg, 5.27 mmol) in toluene was added slowly. The reaction mixture
was stirred for 3 h, then the solution was filtered and the solvent evaporated
under reduced pressure. The resulting yellow solid was washed with
n-pentane and dried in vacuo. Yield: 169 mg (88%). X-ray quality crystals
This journal is ß The Royal Society of Chemistry 2006
Chem. Commun., 2006, 3405–3407 | 3407