Intramolecular hydroamination of aminoalkenes catalyzed by a cationic zirconium complex

Article abstract of DOI:10.1021/ol201731m

A new cationic [N^-O^-S]zirconium complex (cat.) was developed to be an excellent catalyst for the intramolecular hydroamination of aminoalkenes with a large substrate scope from terminal alkenes to internal alkenes, and primary amines to secondary amines. The catalyst system can also tolerate various functional groups and perform sequential hydroamination of primary aminodienes.

Full text of DOI:10.1021/ol201731m

ORGANIC
LETTERS
2011
Vol. 13, No. 18
4758–4761
Intramolecular Hydroamination of
Aminoalkenes Catalyzed by a Cationic
Zirconium Complex
Xinke Wang,† Zhou Chen,† Xiu-Li Sun,† Yong Tang,*,† and Zuowei Xie*,‡
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of
Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032,
China, and Shanghai-Hong Kong Joint Laboratory in Chemical Synthesis,
Shanghai Institute of Organic Chemistry and Department of Chemistry,
The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China
tangy@mail.sioc.ac.cn; zxie@cuhk.edu.hk
Received March 24, 2011
ABSTRACT
A new cationic [NÀOÀS]zirconium complex (cat.) was developed to be an excellent catalyst for the intramolecular hydroamination of
aminoalkenes with a large substrate scope from terminal alkenes to internal alkenes, and primary amines to secondary amines. The catalyst
system can also tolerate various functional groups and perform sequential hydroamination of primary aminodienes.
N-containing compounds play a significant role in
pharmaceuticals and materials, and the synthesis of these
compounds is of considerable interest in both academic
and industrial research. Hydroamination,1À4 a formal
Scheme 1. Design of Zirconium Cation Catalyst for Hydro-
amination of Primary Aminoalkenea
addition of an NÀH bond to carbonÀcarbon unsaturated
bonds, provides an easy access to N-containing com-
pounds. Recently, cationic zirconocenes proved to be good
catalysts for such transformations but the reaction was
restricted to intramolecular cyclization of secondary
aminoalkenes.4a,b When the substrates were extended to
primary aminoalkenes, such a hydroamination of alkenes
did not work, probably due to the formation of the
zirconium imido species II that was reported to be less
active in hydroamination (Scheme 1).4a,b,5 If the two
cyclopentadienyl π ligands in II were replaced by a dia-
a Counteranion was omitted for clarity.
nionic tridentate σ ligand, the resultant 10eÀ zirconium
imide would be destabilized, which favors the formation of
zirconium amide leading to the hydroamination reaction
(Scheme 1). In this regard, it is possible to control the
catalytic behaviors of a cationic zirconium complex on the
hydroamination of alkenes by the change of ligands. We
report here a cationic [OÀNÀS]zirconium complex
(Scheme 2) catalyzed the intramolecular hydroamination
of both primary and secondary aminoalkenes, disubsti-
tuted unactivated alkenes, and alkenes with functional
† Chinese Academy of Sciences.
‡ The Chinese University of Hong Kong.
(1) For review on the hydroamination of alkenes and alkynes, see:
€
Muller, T. E.; Hultzsch, K. C.; Yus, M.; Foubelo, F.; Tada, M. Chem.
Rev. 2008, 108, 3795–3892.
r
10.1021/ol201731m
Published on Web 08/12/2011
2011 American Chemical Society

groups such as ester and nitro groups. Moreover, the
aminodienes can afford bicyclic amines via tandem hydro-
amination of primary and secondary aminoalkenes, thus
broadening the substrate scope of zirconium-catalyzed
hydroamination.
85% isolated yield. Single-crystal X-ray analyses of the
obtained complex displayed a dianionic tridentate ligating
system.7 The corresponding cationic complex 5 was then
generated in situ by treating 4 with [Ph3C][B(C6F5)4]
(Scheme 2).8
Hydroamination of 2,2-diphenylpent-4-enyl-amine 6a
was initially examined. It was found that this amine was
completely converted into pyrroline 7a at 100 °C within
1.5 h (Table 1, entry 1), which supported our initial idea. A
similar result was obtained when 4 was activated with
[PhMe2NH][B(C6F5)4], showing that the released NPhMe2
has no influence on this reaction (entry 2). A longer
reaction time was required if the catalyst loading was
reduced to 5 mol % (entry 3). Meanwhile, the neutral
complex 4 also catalyzed the reaction under the same
conditions but with a longer reaction time, indicating that
the cationic one is more active than its neutral counterpart
(entry 1 vs 4).9,10 In sharp contrast, Cp2ZrMe2 8 was almost
inactive under the same conditions (entries 5À7), even if it
was activated with [PhMe2NH][B(C6F5)4] or [Ph3C]-
[B(C6F5)4]. Only a trace amount of desired product was
observed when the reaction was prolonged to 120 h (entries
6 and 7). Thus, it represents the first example of a group 4
metal cationic catalyst for hydroamination of the primary
aminoalkenes.
Scheme 2. Synthesis of Zirconium Complexes
We have previously developed a tridentate [OÀNS] ligand
system for an olefin polymerization catalyst such as
[OÀNS]titanium complexes 1.6 Treatment of the ligand 2
with ZrBn4 (Bn = C6H5CH2) did not afford the desired
product 3, but rather gave [NÀOÀS]zirconium dibenzyl 4 in
Table 1. Catalytic Trial on Hydroamination of 2,2-Diphenyl-
pent-4-enyl-amine 6aa
(2) For selected papers on intramolecular hydroaminations of
alkenes catalyzed by lanthanide and actinide complexes, see: (a) Hong,
S.; Marks, T. J. Acc. Chem. Res. 2004, 37, 673–686. (b) Kim, Y. K.;
Livinghouse, T.; Horino, Y. J. Am. Chem. Soc. 2003, 125, 9560–9561. (c)
Stubbert, B. D.; Marks, T. J. J. Am. Chem. Soc. 2007, 129, 4253–4271.
(d) Rastatter, M.; Zulys, A.; Roesky, P. W. Chem.;Eur. J. 2007, 13,
3606–3616. (e) Stubbert, B. D.; Marks, T. J. J. Am. Chem. Soc. 2007, 129,
6149–6167. (f) Stanlake, L.; Schafer, L. L. Organometallics 2009, 28,
3990–3998. (g) Reznichenko, A. L.; Hampel, F.; Hultzsch, K. C.
Chem.;Eur. J. 2009, 15, 12819–12827. (h) Xu, X.; Chen, Y.; Feng, J.;
Zou, G.; Sun, J. Organometallics 2010, 29, 549–553.
(3) For late transition metal catalyzed intramolecular hydroamina-
tion of alkenes, see: (a) Bender, C. F.; Widenhoefer, R. A. J. Am. Chem.
Soc. 2005, 127, 1070–1071. (b) Liu, Z.; Hartwig, J. F. J. Am. Chem. Soc.
2008, 130, 1570–1571. (c) Bender, C. F.; Hudson, W. B.; Widenhoefer,
R. A. Organometallics 2008, 27, 2356–2358. (d) Ohmiya, M.; Moriya, T.;
Sawamura, M. Org. Lett. 2009, 11, 2145–2147. (e) Hesp, K. D.; Tobisch,
S.; Stradiotto, M. J. Am. Chem. Soc. 2010, 132, 413–426. (f) Shen, X.;
Buchwald, S. L. Angew. Chem., Int. Ed. 2010, 49, 564–567. (g) Liu, Z.;
Yamamichi, H.; Madrahimov, S.; Hartwig, J. F. J. Am. Chem. Soc. 2011,
133, 2772–2782.
entry
cat.
time (h)
yield (%)b
1
2
3c
4
5
6
7
4/TB
4/AB
4/TB
4
1.5
1.5
4
>95
>95
>95
>95
-- d
-- d
-- d
3
Cp2ZrMe2 (8)
6
Cp2ZrMe2 (8)/TB
Cp2ZrMe2 (8)/AB
6
6
a Conditions: 6a (23.7 mg, 0.1 mmol), cat. (0.01 mmol), TB or AB
(0.01 mmol) if necessary, d5-PhBr (0.5 mL), 100 °C. TB
=
[Ph3C][B(C6F5)4], AB = [PhMe2NH][B(C6F5)4]. b Yield determined by
1H NMR; ferrocene (2.0 mg) as internal standard. c 5 mol % catalyst
loading (0.2 mmol 6a). d A trace amount of product was detected when
the reaction time was prolonged to 120 h.
(4) For selected papers on intramolecular hydroaminations of
alkenes catalyzed by group 4 metals, see: (a) Knight, P. D.; Munslow,
I.; O’Shaughnessy, P. N.; Scott, P. Chem. Commun. 2004, 894–895. (b)
Gribkov, D. V.; Hultzsch, K. C. Angew. Chem., Int. Ed. 2004, 43, 5542–
5546. (c) Wood, M. C.; Leitch, D. C.; Yeung, C. S.; Kozak, J. A.;
Schafer, L. L. Angew. Chem., Int. Ed. 2007, 46, 354–358. (d) Majumder,
Under the optimal conditions, a variety of aminoalkenes
with different structures were examined. The results were
summarized in Table 2. Primary aminoalkenes worked
well, affording the desired cyclic secondary amines in high
€
S.; Odom, A. L. Organometallics 2008, 27, 1174–1177. (e) Muller, C.;
Saak, W.; Doye, S. Eur. J. Org. Chem. 2008, 2731–2739. (f) Cho, J.;
Hollis, T. K.; Helgert, T. R.; Valente, E. J. Chem. Commun. 2008, 5001–
5003. (g) Leitch, D. C.; Payne, P. R.; Dunbar, C. R.; Schafer, L. L. J. Am.
Chem. Soc. 2009, 131, 18246–18247. (h) Reznichenko, A. L.; Hultzsch,
K. C. Organometallics 2010, 29, 24–27. (i) Manna, K.; Ellern, A.; Sadow,
A. D. Chem. Commun. 2010, 46, 339–341. (j) Bexrud, J. A.; Schafer, L. L.
Dalton Trans. 2010, 39, 361–363. See also refs 1, 2b.
(5) (a) Kissounko, D. A.; Epshteyn, A.; Fettinger, J. C.; Sita, L. R.
Organometallics 2006, 25, 1076–1078. (b) Gott, A. L.; Clarke, A. J.;
Clarkson, G. J.; Scott, P. Chem. Commun. 2008, 1422–1424.
(6) (a) Wang, C.; Sun, X. -L.; Guo, Y. -H.; Gao, Y.; Liu, B.; Ma, Z.;
Xia, W.; Shi, L. -P.; Tang, Y. Macromol. Rapid Commun. 2005, 26, 1609–
1614. (b) Wang, C.; Ma, Z.; Sun, X.-L.; Gao, Y.; Guo, Y.-H.; Tang, Y.;
Shi, L.-P. Organometallics 2006, 25, 3259–3266. (c) Gao, M.; Wang, C.;
Sun, X.; Qian, C.; Ma, Z.; Bu, S.; Tang, Y.; Xie, Z. Macromol. Rapid
Commun. 2007, 28, 1511–1516. (d) Yang, X.-H.; Liu, C.-R.; Wang, C.;
Sun, X.-L.; Guo, Y.-H.; Wang, X.; Wang, Z.; Xie, Z.; Tang, Y. Angew.
Chem., Int. Ed. 2009, 48, 8099–8102.
Org. Lett., Vol. 13, No. 18, 2011
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cationic zirconium complex 5 is much more active than the
corresponding neutral one. Only a few group 4 metal
complexes could catalyze the hydroamination of ami-
noalkenes with nonterminal olefins.4d,e,g,j Fortunately,
the cationic zirconium 5 proved to be suitable for the
internal aminoalkenes (entries 5, 8, and 9).
Table 2. Intramolecular Hydroamination of Primary and Sec-
ondary Aminoalkenes Catalyzed by Cationic Zirconiuma
When 1,2-disubstituted alkenyl methylamines 6h and 6i
were employed, the desired products 7h and 7i were
obtained in excellent yields, respectively.
The tolerability toward various functional groups is one
of the major challenges for early transition metal catalysts.11
Very recently, a bis(amido) zirconium complex was re-
ported to be an efficient catalyst for the hydroamination
of both primary and secondary amine substrates bearing a
protected catechol, a pyrrole, or a tertiary aniline.4g In our
study, the catalyst was examined (Table 3), and it was found
that the cationic catalyst 5 was compatible with secondary
aminoalkenes bearing polar groups such as methoxy (entry 1),
halide (entry 2), ester (entry 3), furanyl (entry 5), and nitro
groups (entry 4). In all of these cases, high yields were
obtained as shown in Table 3.
Table 3. Hydroamination of Functional Aminoalkenes Cata-
lyzed by Cationic Zirconiuma
a Conditions: 6 (1.0 mmol), 4 (39 mg, 5 mol %), [Ph3C][B(C6F5)4]
(46 mg, 0.05 mmol, 5 mol %), PhBr (2.5 mL). b Isolated yield; average of
two runs. c 10 mol % catalyst was used; isolated as its tosylate product.
to excellent yields. For example, in the presence of 5 mol %
precatalyst, aminoalkene 6a gave the corresponding pyr-
rolidine in 92% yield (entry 1). The ThorpeÀIngold
effect was also investigated, and substrate 6c worked well
(entry 3). The reactions of secondary amines proceeded
nicely, providing tertiary amines in excellent yields (entries
6À9). For instance, the reaction of 6f proceeded smoothly
at room temperature. In contrast, only a 35% yield of
product 7f was obtained when complex 4 was used as the
catalyst under the same conditions, showing again that
a Conditions: 6 (1.0 mmol), 4 (39 mg, 5 mol %), [Ph3C][B(C6F5)4] (TB)
(46 mg, 0.05 mmol, 5 mol %), PhBr (2.5 mL), 110 °C. b Isolated yield.
As catalyst 5 is active for both primary and secondary
aminoalkenes, it might also be effective for the subsequent
hydroamination of intramolecular aminodienes. As shown
in Table 4, 6o and 6p worked well giving the corresponding
bicyclic tertiary amines 7o and 7p in 96% and 85% yield,
respectively (entries 1À2). Symmetrical aminodiene 6q
smoothly underwent cyclization to quantitatively afford
hexahydro-1H-pyrrolizine 7q. Thus, this method provides
an easy access to bicyclic amines.
The cationic species derived from Cp2ZrMe2 did not
promote the hydroamination of primary amines. How-
ever, as described above, cationic zirconium complex 5
worked well for both primary and secondary amines.
(7) See Supporting Information.
(8) (a) Chien, J. C.; Tsai, W. W.-M.; Rausch, M. D. J. Am. Chem.
Soc. 1991, 113, 8570–8571. (b) Chen, E. Y.; Marks, T. J. Chem. Rev.
2000, 100, 1391–1434.
(9) (a) Lauterwasser, F.; Hayes, P. G.; Brase, S.; Piers, W. E.; Schafer,
L. L. Organometallics 2004, 23, 2234–2237. (b) Bambirra, S.; Tsurugi,
H.; van Leusen, D.; Hessen, B. Dalton Trans. 2006, 1157–1161.
(10) Bergman and co-workers reported that a cationic zirconium
complex generated by treating Cp2ZrMe2 with B(C6F5)3 was active for
the intramolecular hydroamination of aminoallene. See: Ackermann,
L.; Bergman, R. G.; Loy, R. N. J. Am. Chem. Soc. 2003, 125, 11956–
11963.
(11) No desired imido complex was obtained even if 3 equiv of
pyridine was added and the mixture was heated at 110 °C for 3 days.
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Org. Lett., Vol. 13, No. 18, 2011

In summary, the cationic zirconium complex bearing
a planar [NOS] ligand has been demonstrated to be an
efficient catalyst for the intramolecular hydroamina-
tion of both terminal and internal alkenes with a
primary and/or secondary amino moiety. Such a cat-
alyst is tolerant to many functional groups. In the
presence of a catalytic amount of such a complex,
tandem intramolecular hydroamination of primary
aminodienes proceeds very well, providing an easy
access to bicyclic amines. The results greatly broaden
the scope of the cationic zirconium-catalyzed hydro-
amination and provide clues for catalyst design for
hydroamination of olefins.
Table 4. Hydroamination of Aminodienes Catalyzed by Catio-
nic Zirconiuma
Acknowledgment. Financial support was provided by
the National Natural Science Foundation of China (Nos.
20821002 and 20932008), the Major State Basic Research
Development Program (Grant No. 2009CB825300),
NSFC/RGC Joint Research Scheme (N_CUHK470/10
to Z.X. and No. 21061160493 to T.Y.), and the CAS-
Croucher Funding Scheme (Project No. GJHZ200816).
Prof. Guangyu Li and Prof. Huaping Mo are thanked for
their help on NMR analyses. This work is dedicated to
Prof. Christian Bruneau on the occasion of his 60th
birthday.
a Conditions: 6 (1.0 mmol), 4 (39 mg, 5 mol %), [Ph3C][B(C6F5)4]
(46 mg, 0.05 mmol, 5 mol %), PhBr (2.5 mL). b Isolated yield; 1.2:1
mixture of diastereomers. c Yield of NMR reaction in d5-PhBr; ferrocene
as internal standard; 10 mol % cat was used; 1:1 mixture of diaster-
eomers. d A single diastereoisomer was obtained; isolated as HCl salt.
In order to gain some insight into the mechanism, treat-
ment of 4 with tert-butylamine did not give the imido-Zr
complex,7,11 but rather afforded the bisamide complex
[OÀNÀS]Zr(NHBut)2 9 that was confirmed by X-ray
analyses.7 This result suggests that the imido-Zr complex
may not be involved in the reaction. It is likely that this
reaction proceeds via a Zr-amide intermediate shown in
Scheme 1.2c,4d,5
Supporting Information Available. General experimen-
tal procedures, complete characterization data, and X-ray
data for 4 and 9 in CIF format. This material is available
free of charge via the Internet at http://pubs.acs.org.
Org. Lett., Vol. 13, No. 18, 2011
4761