Convenient method for the rapid generation of highly active and enantioselective yttrium catalysts for asymmetric hydroamination

Article abstract of DOI:10.1039/b804745f

A facile method for the preparation of highly active and enantioselective yttrium precatalysts for asymmetric hydroamination of gem-disubstituted aminoalkenes, from the combination of YCl₃ or YCl₃(THF) _3.5 with ligand (R)-

Full text of DOI:10.1039/b804745f

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Convenient method for the rapid generation of highly active and
enantioselective yttrium catalysts for asymmetric hydroaminationw
a
a
a
a
Jerome Hannedouche,* Isabelle Aillaud, Jacqueline Collin,* Emmanuelle Schulz
´
ˆ
b
and Alexander Trifonov
Received (in Cambridge, UK) 19th March 2008, Accepted 22nd April 2008
First published as an Advance Article on the web 2nd June 2008
DOI: 10.1039/b804745f
A facile method for the preparation of highly active and enantio-
selective yttrium precatalysts for asymmetric hydroamination of
gem-disubstituted aminoalkenes, from the combination of YCl3
or YCl (THF) with ligand (R)-L and n-BuLi is described.
constraints and does not involve prior metathetical synthesis
of homoleptic lanthanide precursors in an independent step.
Herein we disclose our current studies toward this goal and
report the first example of in situ generated active and
enantioselective yttrium catalyst from commercially available
3
3.5
1
1
0
Asymmetric catalytic hydroamination of alkenes has recently
emerged as potentially a powerful atom-economic tool for the
stereoselective generation of C–N bond found in numerous
chiral key building blocks and pharmaceutically active com-
anhydrous YCl
3
for AIH of unactivated olefins.
Recently we described a new family of easily prepared lantha-
0
nide ate complexes from LnCl
0
3
and chiral (R)-1,1 -binaphthyl-
2,2 -diamine (BINAM) ligand derivatives as novel catalysts for
AIH reaction. These ate complexes were synthesised by the
1
pounds. Despite time and efforts dedicated to the develop-
ment of efficient chiral catalysts over the last decade, there is to
date, no ‘‘universal’’ chiral catalyst able to promote this
transformation inter- and intramolecularly and in a highly
enantioselective manner. Chiral late transition metal catalysts
are by far the most suitable to promote the enantioselective
intermolecular addition of amines to alkenes and excellent
results were achieved for the addition of aromatic amines to
combination of 2 equiv. of dilithium salt of the corresponding
6
. Despite enantioselectivities up to
ligand with 1 equiv. of LnCl
3
87%, moderate activities were observed for the catalysed intra-
6d
molecular cyclisation of gem-disubstituted aminoalkenes.
As part of these ongoing studies to the development of efficient
chiral catalysts for AIH, we further prepared a neutral hetero-
leptic tris(amido)yttrium complex bearing a chiral biaryl-based
2
,3
4
vinylarenes, diene or norbornene. Chiral group IV and
3
diamido ligand derived from (R)-L (Fig. 1) and a diisopropyla-
7
mido entity. This neutral complex was synthesised via a stepwise
5
–7
rare-earth metal complexes afford the most active catalysts
8
for the asymmetric intramolecular hydroamination (AIH) of
procedure involving 2 consecutive salt metathesis reactions of
9
primary/secondary amines and so have attracted the atten-
3 3 2
YCl with respectively the dilithium salt of (R)-L and LiNiPr .
tion of a large scientific community. However despite intensive
research in this field, only a few catalytic systems accomplish
the hydroamination/cyclisation process with enantioselectivity
Although this neutral complex afforded a better activity for AIH
6
than our previous reported ate complexes, this sequential ap-
proach suffered from practicability issues and turned out to be
1
highly sensitive to the nature of the R substituent of the ligand
4
b,c,5k,8b
4
90% and in only a few cases.
Furthermore, these
7,11
systems involve either the use of homoleptic tris(organo or
amido) rare-earth complexes in conjunction with sophisticated
chiral ligands and thus require additional synthetic steps, or
need harsh reaction conditions to afford an acceptable rate.
(Fig. 1). On a course to find an alternative strategy to this two-
step process, we wondered if chiral active (pre)catalysts for AIH
might be generated directly from the reaction of anhydrous LnCl
3
with chiral BINAM-based ligand and n-BuLi in a single one-pot
procedure and additionally reducing the number of preparative
12
steps.
To initially probe the feasibility of such approach, a prelimin-
ary experiment was performed on the model substrate 1a (n = 1,
2 5
R, R = –(CH ) –). To our delight, in the presence of 6 mol% of
13
14
precatalyst prepared from (R)-L1, YCl3, and n-BuLi in a
molar ratio of 1 : 1 : 3, the reaction of 1a was almost complete
(91% conv.) in 5 h at r.t. affording regioselectively the cyclised
We are interested in developing a convenient route to access
efficient rare-earth catalysts for AIH that overcomes these
product 2a in 75% enantiomeric excess (e.e.) (Table 1, entry 1).
a
Equipe de Catalyse Mole´culaire, ICMMO, UMR CNRS 8182,
Universite´ Paris Sud 11, Bat 420, 91405 Orsay Cedex, France.
E-mail: jacollin@icmo.u-psud.fr; jerome.hannedouche@
icmo.u-psud.fr; Fax: 33(0)169154680; Tel: 33(0)169154740
G. A. Razuvaev Institute of Organometallic Chemistry of Russian
Academy of Sciences, Tropinia 49, 603600 Nizhny Novgorod
GSP-445, Russia
b
Fig.
1 Chiral (R)-N-substituted binaphthyldiamine ligands.
w Electronic supplementary information (ESI) available: Experimental
section. See DOI: 10.1039/b804745f
(Cyp = cyclopentyl).
3
552 | Chem. Commun., 2008, 3552–3554
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Table 1 Precatalyst stoichiometry (L : Ln : n-BuLi) effect on the
asymmetric hydroamination reaction of 1a (n = 1, R, R = –(CH ) –)
2 5
Regardless of a slight decrease in enantioselectivity, it is
a
1 3
worth noting that the precatalyst prepared from (R)-L , YCl
b
c
d
and n-BuLi in a ratio 1 : 0.5 : 2 (entry 7) using this one-pot
Entry
Precatalyst
L : Ln : n-BuLi
t/h
Conv.
%)
e.e.
(%)
(
procedure has a superior activity to the one synthesised by
metathesis reaction of YCl (0.5 equiv.) with the dilithium salt
3
1
2
3
(R)-L
n-BuLi
(R)-L /YCl
n-BuLi
(R)-L
n-BuLi
YCl /n-BuLi
nBuLi
(R)-L
n-BuLi
(R)-L /YCl
n-BuLi
(R)-L /YCl
n-BuLi
(R)-L /YCl
n-BuLi
1
/YCl
3
/
1 : 1 : 3
1 : 1 : 4
1 : 0 : 4
5
2
91
94
0
75
1
of (R)-L (1 equiv.) that we previously reported. With this
7
1
1
3
/
75
—
observation in hand, the method of preparation of the stan-
dard precatalyst system was investigated. However, varying
the amount of THF during the preparative phase of the
precatalyst or changing the order of addition of the reagents
had hardly any influence on the reactivity and enantiocontrol
1
/
24
4
5
6
3
0 : 1 : 4
0 : 0 : 4
1 : 1 : 2
24
24
24
57
0
99
—
—
60
1
/YCl
3
3
3
3
/
/
/
/
18
of the hydroamination/cyclisation of 1a.w We subsequently
varied the R substituent of the chiral BINAM ligand skele-
1
7
8
9
1
1 : 0.5 : 2
1 : 1 : 4
1 : 1 : 4
5
5
94
92
75
63
67
ton. Despite good conversions and moderate e.e. values, we
observed no improvement on the reaction efficiency of the
model substrate by the use of (R)-L or (R)-L ligands (Fig. 1)
2
2
3
3
3.5 96
instead of (R)-L in the standard condition (entries 8, 9 vs. 2).
1
a
1 3
We were next pleased to find that the 1 : 1 : 4 (R)-L /YCl /
6 6
Reactions were carried out in solution (c = 0.33 M) in C D at r.t.
b
with 6 mol% of precatalyst. Precatalyst preparation was performed
n-BuLi precatalyst system was also efficient for the catalysed
intramolecular cyclisation of other gem-disubstituted aminoalk-
enes (Table 2, entries 1–5). In fact, this system promoted the
cyclisation of 1b and 1c into, respectively the corresponding
by dropwise addition of a hexanes solution of n-BuLi to a suspension
of YCl
c
concentration in vacuo, unless otherwise stated. Measured by
3
and (R)-L in THF (c = 0.03 M) at r.t., stirring for 10 min and
1
H
d
NMR spectroscopy. Determined by HPLC analysis of the product
following derivatisation with 2-naphthoyl chloride.
pyrrolidine 2b and 2c without loss of efficiency and enantiocontrol
6d
entries 3, 4). A more pronounced Thorpe–Ingold effect for
(
geminal diphenyl substitution compared to dimethyl might ex-
The precatalyst was prepared in a 10 min reaction after dropwise
plain the relative variation in reaction rate (entry 3 vs. 4). As
6d,7
previously observed,
addition of a hexanes solution of n-BuLi to a suspension of YCl
and (R)-L in THF at ambient temperature and concentration in
vacuo. Increasing the amount of n-BuLi to 4 equiv. (relative to
YCl and (R)-L ) had a significant and beneficial effect on the
3
higher reaction time was needed for the
1
formation of six-membered ring compound 2d and with lower
enantioselectivity (entry 5). The precatalyst loading could also be
reduced to 3 mol% for the cyclisation of 1a with no deterioration
of conversion and e.e. value (entry 2). Under these conditions,
cyclised product 2a was isolated in 72% yield and with 73% e.e.
To gain preliminary insight into the structure of the pre-
3
1
reactivity of the AIH reaction of 1a, while maintaining the same
level of enantioselectivity (Table 1, entry 2). Control experiments
3
emphasised that the chiral ligand, YCl and n-BuLi were essential
1
in the preparative stage of the catalyst to achieve high activity and
8,15
catalyst complex, H NMR spectroscopy was performed on
enantioselectivity in this transformation (Table 1, entries 3–5).
A short tuning of the molar ratio of the (R)-L /YCl /n-BuLi
the in situ generated yttrium complex. This experiment re-
vealed a set of signals in the upfield region between d ꢁ0.07
and ꢁ0.95 ppm (in C D ) characteristic of methylene protons
1
3
precatalyst was then surveyed on our model reaction.w No
improvement in terms of activity and asymmetric induction
was observed by increasing or decreasing the relative stoichio-
metry of each component of the precatalyst system (entries 6, 7
6
6
bound to yttrium metal that disappeared in the presence of
1
9,20
substrate.
Although deeper investigations are needed to
determine the exact structure of the precatalyst, we might
speculate the formation of a (diamido)alkyl yttrium ate com-
plex under the standard condition of catalyst preparation.
1
6
and ESIw). Consequently, the 1 : 1 : 4 (R)-L
1 3
/YCl /n-BuLi
precatalyst system was set as the standard condition.
Table 2 Asymmetric hydroamination of gem-disubstituted aminoalkenes 1a–d catalysed by 1 : 1 : 4 (R)-L
n-BuLi precatalyst system
1
/YCl
3
/n-BuLi or (R)-L
1
/YCl
3
(THF)3.5/
a
b
c
Conv. (%)
d
e.e. (%)
Entry
1
Method
Substrate
R, R
n
Product
t/h
A
1a
1a
1b
1c
1d
1a
1a
1b
1c
1d
–(CH
–(CH
Me, Me
Ph, Ph
–(CH
–(CH
–(CH
Me, Me
Ph, Ph
2
)
)
5
–
–
1
1
1
1
2
1
1
1
1
2
2a
2a
2b
2c
2d
2a
2a
2b
2c
2d
2
3
24
94
92(72 )
83
75
73
76
75
36
65
71
76
77
38
e
f
2
2
5
3
4
5
0.75
495
84
95
90
85
2
2
2
)
)
)
5
–
5
–
5
–
139
17
1
g
6
B
7
8
9
h
23
0.6
96
90
95
10
–(CH
2
)
5
–
a
b
at r.t with 6 mol% of precatalyst. Preparation of the precatalyst: method A:
Reactions were carried out in solution (c = 0.33 M) in C
6
D
6
((R)-L
for 10 min in C
1
/YCl
3
/n-BuLi) (1 : 1 : 4) in THF, stirring for 10 min and concentration in vacuo); method B: ((R)-L
c
1
/YCl
3
(THF)3.5/n-BuLi) (1 : 1 : 4) stirring
1
Measured by H NMR spectroscopy. Determined by HPLC analysis of the product following derivatisation with
d
6
D
6
.
e
-naphthoyl chloride. 3 mol% of precatalyst. Isolated yield. YCl
f
g
h
2
3
is used instead of YCl
3
(THF)3.5
.
Unoptimised reaction time.
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To circumvent the need to remove the THF solvent during
the phase of catalyst preparation and so improving the
synthetic usefulness of this methodology, the AIH reaction
of 1a was tested in the presence of 6 mol% of precatalyst
(d) D. A. Watson, M. Chiu and R. G. Bergman, Organometallics,
2
. (a) M. A. Giardello, V. P. Conticello, L. Brard, M. Sabat,
A. L. Rheingold, A. L. Stern and T. J. Marks, J. Am. Chem.
Soc., 1994, 116, 10212; (b) M. R. Douglass, M. Ogasawara,
S. Hong, M. V. Metz and T. J. Marks, Organometallics, 2002,
006, 25, 4731.
5
6
generated in situ in d -benzene from (R)-L , YCl and n-BuLi
1
3
2
1, 283; (c) S. Hong, S. Tian, M. V. Metz and T. J. Marks, J. Am.
(
Table 2, entry 6). As expected, the activity of the (pre)catalyst
Chem. Soc., 2003, 125, 14768; (d) J.-S. Ryu, T. J. Marks and
F. E. McDonald, J. Org. Chem., 2004, 69, 1038;
(e) P. N. O’Shaughnessy, P. D. Knight, C. Morton,
K. M. Gillespie and P. Scott, Chem. Commun., 2003, 1770;
(f) P. N. O’Shaughnessy, K. M. Gillespie, P. D. Knight,
I. J. Munslow and P. Scott, Dalton Trans., 2004, 2251;
was diminished by contrast to that prepared in THF (entry 1
vs. 6). To restore the high activity previously observed, we
turned our attention to the use of easily accessible
2
1
YCl
3
(THF)3.5 as a substitute to anhydrous YCl
3
.
Gratify-
ingly, intramolecular cyclisation of 1a catalysed by yttrium
(
g) J. Y. Kim and T. Livinghouse, Org. Lett., 2005, 7, 1737;
complex (6 mol%) generated in situ from the 1 : 1 : 4 molar
6
(h) H. Kim, Y. K. Kim, J. H. Shim, M. Kim, M. Han,
T. Livinghouse and P. H. Lee, Adv. Synth. Catal., 2006, 348,
ratio combination of (R)-L
1
, YCl
3
(THF)3.5 and n-BuLi in d -
2
2
609; (i) N. Meyer, A. Zulys and P. W. Roesky, Organometallics,
006, 25, 4179; (j) K. C. Hultzsch, D. V. Gribkov and F. Hampel,
benzene attained 90% conversion in 1 h giving pyrrolidine 2a
as sole product (entry 7). Enhanced activity was also noted for
the hydroamination/cyclisation reaction of other substrates
J. Organomet. Chem., 2005, 690, 4441; (k) D. V. Gribkov,
K. C. Hultzsch and F. Hampel, J. Am. Chem. Soc., 2006, 128,
3
748.
1
b–d catalysed by the in situ generated precatalyst (method B)
6
. (a) J. Collin, J.-C. Daran, E. Schulz and A. Trifonov, Chem.
Commun., 2003, 3048; (b) J. Collin, J.-C. Daran, O. Jacquet,
E. Schulz and A. Trifonov, Chem. Eur. J., 2005, 11, 3455;
compared to that prepared in THF (method A) (entries 8–10).
To our delight, no noticeable loss in asymmetric induction was
observed with this in situ methodology.
(
c) D. Riegert, J. Collin, A. Meddour, E. Schulz and
A. Trifonov, J. Org. Chem., 2006, 71, 2514; (d) I. Aillaud,
J. Collin, C. Duhayon, R. Guillot, D. Lyubov, E. Schulz and
A. Trifonov, Chem. Eur. J., 2008, 14, 2189; (e) I. Aillaud,
K. Wright, J. Collin, E. Schulz and J.-P. Mazaleyrat,
Tetrahedron: Asymmetry, 2008, 19, 82.
In conclusion, we have developed a new strategy for the
rapid preparation of efficient chiral yttrium precatalysts for
asymmetric intramolecular hydroamination. This approach
that relies on the combination of an yttrium chloride precur-
sor, a chiral diamine ligand and n-BuLi in a ‘‘single pot’’,
avoids the requirement of prior synthesis of homoleptic tris-
7
. D. Riegert, J. Collin, J.-C. Daran, T. Fillebeen, E. Schulz, D. Lyubov,
G. Fukin and A. Trifonov, Eur. J. Inorg. Chem., 2007, 1159.
8. Lithium metal-based catalysts for asymmetric intramolecular
hydroamination of alkenes were also reported: (a) P. Horrillo
Martinez, K. C. Hultzsch and F. Hampel, Chem. Commun., 2006,
(
organo or amido) rare-earth complexes. To our knowledge,
this is the first example of the use of such a strategy to easily
access rare-earth (pre)catalysts for asymmetric hydroamina-
tion. Studies are currently underway to define the structure
and scope of the precatalyst formed under these conditions,
and results will be reported in due course.
2
221; (b) T. Ogata, A. Ujihara, S. Tsuchida, T. Shimizu,
A. Kaneshige and K. Tomioka, Tetrahedron Lett., 2007, 48, 6648.
9. A highly promising rhodium-catalysed intramolecular hydroami-
nation of primary (and secondary) amines was recently reported:
Z. Liu and J. F. Hartwig, J. Am. Chem. Soc., 2008, 130, 1570.
0. For examples of in situ generated chiral catalysts using tris(organo
or amido) rare-earth precursors for AIH: see refs. 5c,f,g,k.
1
We are grateful to the CNRS for financial support and the
Conseil Ge
´
ne
´
ral de L’Essonne for a PhD grant for I. A. We are
11. This sequential metathetic route was also not suitable for the
preparation of chiral diamido alkylyttrium complexes, see ref. 7.
indebted to Ms Emilie Kolodziej for her HPLC technical
assistance.
1
2. Indeed, all lithium salts mentioned above were prepared by
deprotonation of the related amine or diamine with n-BuLi in
an individual reaction.
1
3. (R)-L
1
was the ligand of choice in terms of activity and enantio-
selectivity for AIH catalysed by our previously reported lantha-
Notes and references
6d
nide ate complexes.
14. Anhydrous YCl was chosen for its tendency to afford stable neutral
.
1. (a) I. Aillaud, J. Collin, J. Hannedouche and E. Schulz, Dalton
Trans., 2007, 5105; (b) K. C. Hultzsch, Adv. Synth. Catal., 2005,
3
alkyl complexes. For examples of isolated chiral neutral bis(amido)
alkyl yttrium bearing a methyl, ethyl or 1-hexyl group, see:
T. I. Gountchev and T. D. Tilley, Organometallics, 1999, 18, 2896.
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1623; (b) C. Quinet, P. Jourdain, C. Hermans, A. Ates, I. Lucas
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673.
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. (a) R. Dorta, P. Egli, F. Zu
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¨
rcher and A. Togni, J. Am. Chem. Soc.,
1
¨
J. F. Hartwig, J. Am. Chem. Soc., 2001, 123, 4366; (d) K. Li,
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´
16. Review on rare-earth/alkali metal heterobimetallic complexes that
catalyse various asymmetric reactions: M. Shibasaki and
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17. Indeed, AIH reaction of 1a catalysed by 6 mol% of fully char-
3
. Other examples of chiral late transition metal-catalysed asym-
metric hydroamination: (a) L. M. Lutete, I. Kadota and
Y. Yamamoto, J. Am. Chem. Soc., 2004, 126, 1622;
acterised ate complex prepared by metathesis reaction of YCl
equiv.) with the dilithium salt of (R)-L (1 equiv.) was complete
(93% conv.) in 15 h affording 2a in 81% e.e.
18. For convenience, addition of the solution of n-BuLi to a suspen-
3
(0.5
1
6d
.
(b) R. L. Lalonde, B. D. Sherry, E. J. Kang and F. D. Toste,
J. Am. Chem. Soc., 2007, 129, 2452; (c) Z. Zhang, C. F. Bender
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sion of YCl
procedure.
3
and ligand in THF was chosen as the standard
19. For typical chemical shifts of methylene protons bound to
yttrium, see ref. 14.
20. No trace of yttrium amide ate complex bearing two chiral ligands per
yttrium as previously described was observed in the spectrum .
21. For examples of the influence of THF or thiophene on the
preparation of rare-earth metal catalysts for AIH, see, respectively
refs. 5k and g.
129, 14148.
4
. (a) P. D. Knight, I. Munslow, P. N. O’Shaughnessy and P. Scott,
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G. J. Clarkson and P. Scott, Organometallics, 2007, 26, 1729;
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6d
3
554 | Chem. Commun., 2008, 3552–3554
This journal is ꢀc The Royal Society of Chemistry 2008