Comparison of yttrium binaphthylamido alkyl and amide complexes for enantioselective intramolecular hydroamination

Article abstract of DOI:10.1016/j.tetlet.2010.07.023

A chiral trisamido yttrium complex Y[(R)-C₂₀H ₁₂(NC₅H₉)₂][NiPr₂][THF] ₂·LiCl coordinated by N-cyclopentyl binaphthylamine ligand has been prepared in situ and characterised by NM

Full text of DOI:10.1016/j.tetlet.2010.07.023

Tetrahedron Letters 51 (2010) 4742–4745
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Comparison of yttrium binaphthylamido alkyl and amide complexes
for enantioselective intramolecular hydroamination
Isabelle Aillaud , Jacqueline Collin a,b,*, Jérôme Hannedouche a,b, Emmanuelle Schulz a,b
a
,
c
Alexander Trifonov
Univ Paris-Sud, Laboratoire de Catalyse Moléculaire, ICMMO, UMR 8182, Orsay F-91405, France
a
b
CNRS, Orsay F-91405, France
c
G.A. Razuvaev Institute of Organometallic Chemistry of Russian Academy of Sciences, Tropinina 49, 603950 Nizhny Novgorod GSP-445, Russia
a r t i c l e i n f o
a b s t r a c t
Article history:
A chiral trisamido yttrium complex Y[(R)-C20H12(NC H ) ][NiPr ][THF] ꢀLiCl coordinated by N-cyclopen-
5
9 2
2
2
Received 24 February 2010
Revised 25 June 2010
Accepted 2 July 2010
Available online 8 July 2010
tyl binaphthylamine ligand has been prepared in situ and characterised by NMR spectroscopy. It has been
revealed as an efficient catalyst for intramolecular hydroamination of aminoolefins. Comparison with
neutral alkyl, ate alkyl or ate tetraamido complexes coordinated by the same ligand indicated that this
complex was the most efficient catalyst of the series for its both activity and enantioselectivity values.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Asymmetric intramolecular hydroamination
Catalysis
Amines
Pyrrolidines
Carbon–nitrogen bond formation
1
. Introduction
lamido ligands.11–13 After studying a family of tetraalkyl amido ate
complexes {Li(THF)
active neutral [(R)-C20
[(R)-C20 12(NC ]Ln[(
plexes. We now aim to report the preparation of a neutral trisamido
yttrium complex based on binaphthylamido ligand and the compar-
ison of its activity in enantioselective intramolecular hydroamina-
tion of aminoalkenes with that of alkyl and amido ate and in
neutral complexes coordinated with the same ligand.
4
}{Ln[(R)-C20
12(NC
-Me)
H
12(NR)
]LnCH
-Me)Li(THF)] alkyl com-
2
]
2
} we next found more
Chiral nitrogen-containing molecules represent an important
H
l
5
H
9
)
2
2
SiMe (DME) and ate
3
class of biologically active compounds. Catalytic asymmetric intra-
molecular hydroamination of aminoolefins, an atom-economical
process which formally consists in the addition of an –NH unit on
a non-activated carbon–carbon double-bond, is one of the most ele-
H
5
9
H )
2
2
Li(THF)
2
(
l
1
gant procedures for the synthesis of nitrogen heterocycles. In the
first example of asymmetric cyclisation of aminoolefins, Marks
and co-workers reported the use of chiral lanthanocenes for the
preparation of several pyrrolidines with up to 74% ee.2 Since the
We have previously synthesised a new family of rare-earth ate
complexes {Li(THF) }{Ln[(R)-C20H12(NR) ] } (1, Fig. 1) derived from
4 2 2
publication by Livinghouse of intramolecular hydroamination cata-
various chiral disubstituted (R)-binaphthylamido ligands that
3
lysed by rare-earth trisamides {Ln[N(SiMe
3
)
2
]
3
}, chiral catalysts
proved to be efficient catalysts for the enantioselective intramolec-
4
11
coordinated by a large variety of ligands such as binaphtholates,
ular hydroamination of aminoolefins. A large screening of alkyl
5
6
7
aminobisphenolates, aminobisthiolates, bisoxazolinato and bis-
substituents R and rare-earth atoms allowed us to prepare a spiro-
pyrrolidine with up to 87% ee at room temperature in 20 h using
{Li(THF) }{Yb[(R)-C20H12(NC H ) ] } as the catalyst. We also described
4 5 9 2 2
8
binaphthylamido have been studied. Despite the increased number
9
of catalysts, based on rare earth or more recently on lithium or on
1
0
group IV metals, until now they have been used almost for the cyc-
lisation of simple substrates only. Since only a few catalytic systems
promoted this transformation with more than 90% ee the develop-
ment of more active and enantioselective catalysts remains a chal-
lenging task. Research in our group has been focused on the study
of chiral rare-earth hydroamination catalysts based on binaphthy-
the synthesis of neutral amido catalyst 2a consisting in a unique
N-isopropyl-bis-binaphthylamido ligand and a diisopropylamido
1
2
moiety. Higher enantiomeric excesses and/or higher rates of reac-
tion were generally observed with 2a than with chiral ate analogue
1a for the formation of various pyrrolidines. With the aim of increas-
ing both activity and enantioselectivity we recently reported the
preparation and characterisation of new chiral binaphthylamido
alkyl ate {[(R)-C20H12(NC H
5 9
)
2
]Ln[(
l
-Me)
2
Li(THF)
2
(l-Me)Li(THF)]}
*
Corresponding author. Tel.: +33 1 69154740.
E-mail address: jacqueline.collin@u-psud.fr (J. Collin).
3 and neutral {[(R)-C20
H12(NC
5
9
H )
2
]LnCH
2
SiMe (THF)
3
2
} 4 yttrium
0
040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.07.023

I. Aillaud et al. / Tetrahedron Letters 51 (2010) 4742–4745
4743
R
N
N
R
N
N
R
R
N
N
R
Ln
YNiPr (THF) .LiCl
2 2
R
Li(THF)4
R = CH CMe , CH CHMe , CH Ph,
2
3
2
2
2
CH Ar, iPr, Ph, cy, cyp
2
Ln = Nd, Sm, Yb, Lu, Y
R = iPr, Ln = Y 1a
R = cyp, Ln = Y 1b
R = iPr, 2a
R = cyp, 2b
O
N
N
Me
Me
Ln
O
Li
Si
(THF)2
N
O
Ln
N
Li Me
Ln = Yb, Y
Ln = Y
Ln = Yb, Y
3
Ln = Y
4
Figure 1. Structure of studied catalysts.
NH
NH
nBuLi (2 equiv.)
N Li
N Li
YCl
THF, rt, 3h
2LiCl
3
N
N
YCl(THF)2
Hexane, rt, 10 min
−
5
LiNiPr2
THF, rt, 15 min
N
N
N
YNiPr (THF) .LiCl
YCl(THF)2
N
2
2
5
2b
5 9 2 2 2
Scheme 1. Synthesis of yttrium amido complex {Y[(R)-C20H12(NC H ) ][NiPr ][THF] [LiCl]} 2b.
The first step consisted in the formation of the bis lithium salt
{Li [(R)-C20 12(NC ]} using nBuLi at room temperature in hex-
ane. The solvent was quickly removed in vacuo and the crude
dilithium salt was used immediately after its preparation without
and ytterbium complexes, containing a unique N-cyclopentyl-bis-
binaphthylamido ligand (Fig. 1).13 Yttrium alkyl ate 3 and neutral
2
H
5 9 2
H )
4
complexes turned out to be by far more active for this transforma-
tion than the yttrium ate tetraamido catalyst 1b coordinated by the
same N-cyclopentyl-bis-binaphthylamido ligand previously de-
scribed. We thus focused on the preparation and the evaluation as
hydroamination catalyst of an yttrium neutral trisamido complex
further purification. Intermediate {Y[(R)-C20
5 was obtained by the salt metathesis reaction of anhydrous YCl
and 1 equiv of {Li [(R)-C20 12(NC
H
12(NC
5
H
9
)
2
]Cl(THF)
2
}
3
2
H
5 9
H )
2
]}, in THF at room tempera-
ture. Complex 5 was purified after the evaporation of THF by
2
b, bearing the same N-cyclopentyl-binaphthylamido ligand for a
extraction of the solid residue with toluene and subsequent recrys-
1
comparison with neutral alkyl and amido yttrium catalysts in terms
of activity and enantioselectivity.
tallisation from THF/hexane mixtures and characterised by H and
1
3
C NMRs. The spectra showed the expected sets of resonances cor-
0
0
0
0
0
Complex 2b was prepared from an (R)-N,N -dicyclopentyl-1,1 -
responding to the (R)-N,N -dicyclopentyl-1,1 -binaphthyl-2,2 -
0
binaphthyl-2,2 -diamido ligand, in three steps involving the forma-
diamido ligand and the coordinated THF molecules, similar to that
tion of the chiral diamido yttrium chloride complex 5 (Scheme 1).
2 2
obtained for the complex {Y[(R)-C20H12(NiPr) ]Cl(THF) } previ-

4
744
I. Aillaud et al. / Tetrahedron Letters 51 (2010) 4742–4745
Table 1
Asymmetric intramolecular hydroamination catalysed by yttrium amido complexes
R
R
cat* (6 mol%)
R
NH
NH2
*
C
D
R
6
6
n
n
6a
6b
6c
R,R = -(CH ) -, n = 1
7a
7b
7c
2
5
R,R = Ph,
n = 1
R,R = -(CH ) -, n = 2
2
5
Entry
Substrate
Catalyst
Time (h)
1.2
Temperature (°C)
Conversiona (%)
eeb (%)
81
1
2
3
4
5
6
7
8
9
6a
2b
2a
1b
3
25
25
25
25
25
25
25
25
25
25
60
60
60
25
60
95
100
93
90
89
c
e
4
68
f
15
2.3
3.3
1
12
5
81
g
75
75
g
4
6b
6c
2b
2a
1b
3
92
72
e
100
100
100
100
100
100
100
87
65
f
75
g
1.9
2.3
19
72
66
g
10
11
12
13
14
15
4
2b
2a
1b
3
34
d
e
8
18
f
24
120
27
41
g
33
25
g
4
100
a
Conversion was measured by 1H NMR.
b
ee was determined by GC analysis following derivatisation of the product with (S)-Mosher’s acid chloride for products 7a and 7b, or by HPLC analysis of the product
following derivatisation with 2-naphtoyl chloride for product 7c.
c
4
1
mol % cat. ratio.
4 mol % cat. ratio.
d
e
f
Ref. 12.
Ref. 11d.
Ref. 13.
g
ously described.12 It should be noted that no trace of free ligand or
ate complex {[Li(THF)
served in the NMR spectra.
second metathesis reaction, from complex 5 and 1 equiv of LiNiPr
4
]-[Y((R)-C20
H
12(NC
5
H
9
)
2
)
2
]} 1b was ob-
room temperature with an almost complete conversion and the
same enantiomeric excess (entry 3). Gratifyingly, new yttrium tri-
samido catalyst 2b appeared to be more reactive than yttrium alkyl
ate 3 and neutral 4 complexes, which were up to now our most ac-
tive well-defined complexes for the cyclisation of compound
11d
Complex 2b was synthesised by a
2
1
in THF at room temperature. After the evaporation of THF, H NMR
of the crude product revealed the presence of the diisopropylamido
moiety coordinated to yttrium indicating the expected structure
1
5,16
6a.
Using these catalysts, the spiropyrrolidine 7a was obtained,
{Y[(R)-C20H12(NC H
5 9
)
2
][NiPr
2
][THF]
2
[LiCl]}.14 It is noticeable for
respectively, in 2.3 h and 3.3 h with different values of enantio-
meric excesses slightly lower (75% ee, entries 4 and 5). Similar
trends were observed for the cyclisation of gem-diphenylamin-
opentene 6b. The formation of gem-diphenylpyrrolidine 7b was
performed in an hour at room temperature and the cyclised prod-
uct was obtained with 72% ee in the presence of catalyst 2b (entry
6). Complex 2b was thus the most active yttrium amido catalyst of
our series for the preparation of those pyrrolidines (entries 6–10).
For the cyclisation of the more challenging and demanding sub-
strate 6c the new complex 2b was more active than complexes
1b and 4 and that was the best compromise in terms of activity
and enantioselectivity. (entries 11–15). Spiropiperidine 7c was in-
deed obtained after 19 h at 60 °C with 34% ee using catalyst 2b (en-
try 11). It is worth noting that in this case, the ate complex 1b
showed a slightly enhanced enantioselectivity (entry 13).
this last step that it is required to use recrystallised complex 5 to
get yttrium neutral amido complex 2b in good yield and purity.
As products of ligand-redistribution reactions were observed
2 2 2 2
when the analogous {Y[(R)-C20H12(NiPr ) ][NiPr ][THF] [LiCl]} 2a
was extracted with toluene and recrystallised from THF/hexane
1
2
mixture,
F] [LiCl]} 2b was not purified but used in situ immediately after
its preparation and the evaporation of THF. In this case, crude com-
plex {Y[(R)-C20 12(NC ][NiPr ][THF] [LiCl]} 2b proved to be an
5 9 2 2
the new complex {Y[(R)-C20H12(NC H ) ][NiPr ][TH-
2
H
5
9
H )
2
2
2
efficient catalyst for the hydroamination/cyclisation of two amino-
pentenes and an aminohexene derivative (Table 1).
We first investigated the cyclisation of C-(1-allylcyclohexyl)-
methyl amine 6a. The corresponding spiropyrrolidine 7a was ob-
tained only after 1.2 h at room temperature and with 81% ee (Table
1
, entry 1) using the new yttrium trisamido catalyst 2b. The latter
The new chiral yttrium trisamido complex 2b afforded the
hydroamination/cyclisation of several aminoolefins with the same
level of enantioselectivity than yttrium ate tetraamido catalyst 1b
bearing the same N-substituents, but with a sharp increase in
activity. Complex 2b proved to be even more active than yttrium
alkyl ate 3 and neutral 4 catalysts recently described. These differ-
ences both in terms of activity and enantioselectivity suggest that
different active species are involved in this transformation, accord-
ing to the complex used. If we assume for the neutral amido or al-
kyl precatalysts 2 and 4 a mechanism for the formation of the
promoted this transformation in a shorter time and with higher
enantioselectivity than the N,N -diisopropyl-binaphthyl trisamido
complex 2a (68% ee in 4 h at 25 °C, entry 2). Similar differences
in terms of enantioselectivity and activity for catalysts which differ
only in N-substituents have already been observed with the ate
tetraamido complexes series previously described, due to steric ef-
0
1
1,12
fects.
active than the corresponding yttrium ate tetraamido complex
b to promote the intramolecular hydroamination of aminopen-
tene 6a. Catalyst 1b afforded the spiropyrrolidine 7a in 15 h at
Moreover, catalyst 2b proved to be more than 10 times
1
1
7
active species similar to that proposed by Marks, the coordina-

I. Aillaud et al. / Tetrahedron Letters 51 (2010) 4742–4745
4745
tion of diisopropyl amine (arising from the protonolysis of the ami-
do moiety by the substrate) to yttrium may not obviously explain
the difference in reactivity between amido and alkyl complexes.
5. O’Shaughnessy, P. N.; Knight, P. D.; Morton, C.; Gillespie, K. M.; Scott, P. Chem.
Commun. 2003, 1770–1771.
6
7
.
.
Kim, J. Y.; Livinghouse, T. Org. Lett. 2005, 7, 1737–1739.
Hong, S.; Tian, S.; Metz, M. V.; Marks, T. J. J. Am. Chem. Soc. 2003, 125, 14768–
14783.
1
8
The second major difference between precatalysts 2 and 4 is the
presence in the former of 1 equiv of LiCl.19 Preliminary experi-
8.
(a) Kim, H.; Kim, Y. K.; Shim, J. H.; Han, M.; Livinghouse, T.; Lee, P. H. Adv. Synth.
Catal. 2006, 348, 2609–2618; (b) Zi, G.; Xiang, L.; Song, H. Organometallics 2008,
2
0
ments emphasise the role of LiCl on the outcome of the reaction.
2
7, 1242–1246.
9. (a) Horrillo Martinez, P.; Hultzsch, K. C.; Hampel, F. Chem. Commun. 2006,
221–2223; (b) Ogata, T.; Ujhara, A.; Tsuchida, S.; Shimizu, T.; Kaneshige, A.;
Although deeper investigations are definitely required to deter-
mine the exact role of LiCl on the structure and reactivity of precat-
alysts 2, we might speculate coordination of the alkali-metal halide
2
Tomioka, K. Tetrahedron Lett. 2007, 48, 6648–6650.
1
0. (a) Watson, D. A.; Chiu, M.; Bergman, R. G. Organometallics 2006, 25, 4731–
4733; (b) Wood, M. C.; Leitch, D. C.; Yeung, C. S.; Kozak, J. A.; Schafer, L. L.
Angew. Chem., Int. Ed. 2007, 46, 354–358; (c) Gott, A. L.; Clarke, A. J.; Clarkson,
G. J.; Scott, P. Chem. Commun. 2008, 1422–1424; (d) Reznichenko, A. L.;
Hultzsch, K. C. Organometallics 2010, 29, 24–27.
2 5 9 2 2
to the {Y[(R)-C20H12(NR) (R = C H , iPr )][NiPr ]} fragment of 2
during the second metathesis reaction (in a coordinating solvent)
LiCl-adduct.2
1,22
to afford a (THF)
2
This difference in the precatalyst
structure may account for the disparity in reactivity between 2 and
. Studies are ongoing to get the insights into the structure of these
complexes for a better catalyst design.
11. (a) Collin, J.; Daran, J.-C.; Schulz, E.; Trifonov, A. Chem. Commun. 2003, 3048–
3049; (b) Collin, J.; Daran, J.-C.; Jacquet, O.; Schulz, E.; Trifonov, A. Chem. Eur. J.
4
2005, 11, 3455–3462; (c) Riegert, D.; Collin, J.; Meddour, A.; Schulz, E.;
Trifonov, A. J. Org. Chem. 2006, 71, 2514–2517; (d) Aillaud, I.; Collin, J.;
Duhayon, C.; Guillot, R.; Lyubov, D.; Schulz, E.; Trifonov, A. Chem. Eur. J. 2008,
14, 2189–2200.
Acknowledgements
1
1
1
1
2. Riegert, D.; Collin, J.; Daran, J.-C.; Fillebeen, T.; Schulz, E.; Lyubov, D.; Fukin, G.;
Trifonov, A. Eur. J. Inorg. Chem. 2007, 1159–1168.
We thank for the financial support by MENSR and ANR (Grant
3. Aillaud, I.; Lyubov, D.; Collin, J.; Guillot, R.; Hannedouche, J.; Schulz, E.;
Trifonov, A. Organometallics 2008, 27, 5929–5936.
0
7 367). CNRS is acknowledged for giving financial support, for a
1
4. The H NMR experiment did not allow to determine whether the THF
doctoral grant (together with the Conseil Général de l’Essonne)
for I.A. A.T. thanks the Russian Foundation for Basic Research
molecules are coordinated to yttrium or lithium.
5. Spiropyrrolidine 7a was obtained after 1 h at room temperature with 90% conv.
(
Grant 08-03-92501). CNRS and Russian Academy of Sciences are
and 71% ee using an yttrium precatalyst synthesised in situ in C
YCl (THF)3.5 and the same ligand (see Ref. 16).
6. Hannedouche, J.; Aillaud, I.; Collin, J.; Schulz, E.; Trifonov, A. Chem. Commun.
008, 3552–3554.
17. Gagné, M. R.; Stern, C. L.; Marks, T. J. J. Am. Chem. Soc. 1992, 114, 275–294.
8. As suggested by referee, the catalytic amount of sterically bulky
diisopropylamine ligand should be a much weaker ligand than the substrate
bearing a primary amine) or the cyclised product (bearing a secondary amine).
6 6
D from nBuLi,
3
acknowledged for GDRE support.
1
2
Supplementary data
1
a
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2010.07.023.
(
19. The authors would like to thank a referee for pointing out that complex 2b is
not a LiCl-free complex.
2
0. Indeed, the hydroamination reaction of 6a and 6b catalysed by a complex
References and notes
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0
0
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2
SiMe
3
)
3
(THF)
2
, (R)-N,N -dicyclopentyl-1,1 -binaphthyl-
0
1
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during the preparative phase of the catalyst restores the enantiomeric excess
values reported with complex 2b.
1
(
2
.
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.
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3
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22. As attempts to purify and recrystallise complex 2a were unsuccessful (see Ref.
12), no efforts were engaged to obtain an alkali metal-free complex 2b.