Enantioselective intramolecular hydroamination catalyzed by lanthanide ate complexes coordinated by N-substituted (R)-1,1′-binaphthyl-2,2′- diamido ligands

Article abstract of DOI:10.1021/jo052322x

Ytterbium and lutetium ionic complexes derived from enantiopure substituted (R)-binaphthylamine ligands, of the general formula [Li(THF) _n][Ln[(R)-C₂₀H₁₂(NR)₂]₂], have been investigated for the hydroa

Full text of DOI:10.1021/jo052322x

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SCHEME 1. Intramolecular Hydroamination Test Reaction
Enantioselective Intramolecular Hydroamination
Catalyzed by Lanthanide Ate Complexes
Coordinated by N-Substituted
(R)-1,1′-Binaphthyl-2,2′-diamido Ligands†
reviews have been published.3 Molander and Pack have
furthermore explored this efficient process toward the rapid
synthesis of pharmaceutically active molecules.4
David Riegert,‡ Jacqueline Collin,*,‡ Abdelkrim Meddour,§
Emmanuelle Schulz,*,‡ and Alexander Trifonov|
The first enantioselective intramolecular hydroamination of
alkenes, catalyzed by ansa lanthanocene complexes substituted
by a menthyl or neomenthyl group, has been reported by Marks
et al.5 These catalysts afforded the pyrrolidine depicted in
Scheme 1 with up to 74% ee. This transformation is now
considered as the test hydroamination/cyclization to evaluate
the efficiency of new catalysts.3b
Laboratoire de Catalyse Mole´culaire, ICMMO, UMR CNRS
8182, UniVersite´ Paris-sud, 91405 Orsay, France, Laboratoire
de Chimie Structurale Organique, ICMMO, UMR CNRS 8182,
UniVersite´ Paris-Sud, 91405 Orsay, France, and
G. A. RazuVaeV Institute of Organometallic Chemistry of
Russian Academy of Sciences, Tropinia 49, 603600 Nizhny
NoVgorod GSP-445, Russia
Enantioenriched piperidines (up to 67% ee) were obtained
with similar lanthanide complexes, including an octahydro-
fluorenyl instead of a tetramethylcyclopentadienyl group.6
Livinghouse and co-workers described in 2001 the activity of
lanthanide tris-silylamides, Ln[N(TMS)2]3, for the cyclization
of aminopentenes into racemic pyrrolidines.7 This work opened
the way to the synthesis of nonmetallocene lanthanide complexes
as catalysts for the intramolecular hydroamination of olefins.
Scott et al. thus prepared chiral bisaryloxide lanthanide com-
plexes from salicylaldimine-type ligands that catalyzed the test
reaction at 70 °C with enantiomeric excesses as high as 60%.8
A new chiral zirconium alkyl cation coordinated by a similar
aminobiphenoxide ligand proved to be an enantioselective
catalyst for the hydroamination/cyclization of secondary amines
(up to 82% ee).9 By the reaction of lanthanide amides with C2-
symmetric bisoxazolines, Marks et al. prepared enantioselective
catalysts active at room temperature for the test cyclization (67%
ee).10 Hultzsch et al. synthesized various sterically hindered
lanthanum and yttrium biphenolate and binaphtholate com-
plexes.11 3,3′-Trisalkylsilylbinaphtholate complexes with a
jacollin@icmo.u-psud.fr; emmaschulz@icmo.u-psud.fr
ReceiVed NoVember 9, 2005
Ytterbium and lutetium ionic complexes derived from
enantiopure substituted (R)-binaphthylamine ligands, of the
general formula [Li(THF)n][Ln[(R)-C20H12(NR)2]2], have
been investigated for the hydroamination/cyclization of
several aminopentenes and an aminohexene. Complexes with
isopropyl or cyclohexyl substituents on nitrogen atoms were
found to be efficient catalysts under mild conditions for the
formation of N-containing heterocycles with enantiomeric
excesses up to 78%.
(3) (a) Hong, S.; Marks, T. J. Acc. Chem. Res. 2004, 37, 673-686. (b)
Hultzsch, K. C. AdV. Synth. Catal. 2005, 347, 367-391. (c) Hultzsch, K.
C.; Gribkov, D. V.; Hampel, F. J. Organomet. Chem. 2005, 690, 4441-
4452.
(4) Molander, G. A.; Pack, S. K. J. Org. Chem. 2003, 68, 9214-9220
and references therein.
(5) (a) Gagne´, M. R.; Brard, L.; Conticello, V. P.; Giardello, M. A.;
Stern, C. L.; Marks, T. J. Organometallics 1992, 11, 2003-2005. (b)
Giardello, M. A.; Conticello, V. P.; Brard, L.; Sabat, M.; Rheingold, A. L.;
Stern, A. L.; Marks, T. J. J. Am. Chem. Soc. 1994, 116, 10212-10240. (c)
Giardello, M. A.; Conticello, V. P.; Brard, L.; Gagne´, M. R.; Marks, T. J.
J. Am. Chem. Soc. 1994, 116, 10241-10254.
Intramolecular hydroamination of alkenes is an atom eco-
nomic process leading to the formation of nitrogen heterocycles
that are found in numerous biologically active compounds.1
Since the pioneering work of Marks and co-workers on the
activity of lanthanocene for intramolecular hydroaminations,2
the interest for these reactions has increased, and some recent
(6) (a) Douglass, M. R.; Ogasawara, M.; Hong, S.; Metz, M. V.; Marks,
T. J. Organometallics 2002, 21, 283-292. (b) Ryu, J. S.; Marks, T. J.;
McDonald, F. E. J. Org. Chem. 2004, 69, 1038-1052.
(7) (a) Kim, Y. K.; Livinghouse, T.; Bercaw, J. E. Tetrahedron Lett.
2001, 42, 2933-2935. (b) Kim, Y. K.; Livinghouse, T. Angew. Chem., Int.
Ed. 2002, 41, 3645-3647.
(8) (a) O’Shaughnessy, P. N.; Scott, P. Tetrahedron: Asymmetry 2003,
14, 1979-1983. (b) O’Shaughnessy, P. N.; Knight, P. D.; Morton, C.;
Gillepsie, K. M.; Scott, P. Chem. Commun. 2003, 1770-1771. (c)
O’Shaughnessy, P. N.; Gillepsie, K. M.; Knight, P. D.; Munslow, I.; Scott,
P. Dalton Trans. 2004, 2251-2256.
(9) Knight, P. D.; Munslow, I.; O’Shaughnessy, P. N.; Scott, P. Chem.
Commun. 2004, 894-895.
(10) Hong, S.; Tian, S.; Metz, M. V.; Marks, T. J. J. Am. Chem. Soc.
2003, 125, 14768-14783.
(11) (a) Gribkov, D. V.; Hultzsch, K. C.; Hampel, F. Chem.sEur. J.
2003, 9, 4796-4810. (b) Gribkov, D. V.; Hultzsch, K. C. Chem. Commun.
2004, 730-731. (c) Gribkov, D. V.; Hampel, F.; Hultzsch, K. C. Eur. J.
Inorg. Chem. 2004, 4091-4101.
* Corresponding author. Tel.: 33-169154740 (J.C.); 33-169157356 (E.S.).
Fax: 33-169154680 (J.C.); 33-169154680 (E.S.).
† Dedicated to Professor H. B. Kagan on the occasion of his 75th birthday.
‡ Laboratoire de Catalyse Mole´culaire.
§ Laboratoire de Chimie Structurale Organique.
| G. A. Razuvaev Institute of Organometallic Chemistry of Russian Academy
of Sciences.
(1) For general reviews on hydroamination reactions, see: (a) Mu¨ller, T.
E.; Beller, M. Chem. ReV. 1998, 98, 675-703. (b) Nobis, M.; Driessen-
Ho¨lscher, B. Angew. Chem., Int. Ed. 2001, 40, 3983-3985. (c) Brunet, J.
J.; Neibecker, D. In Catalytic Heterofunctionalization from Hydroamination
to Hydrozirconation; Togni, A., Gruˆtzmacher, H., Eds.; Wiley-VCH:
Weinheim, Germany, 2001; pp 91-141. (d) Roesky, P. W.; Muller, T. E.
Angew. Chem., Int. Ed. 2003, 42, 2708-2710. (e) Pohlki, F.; Doye, S. Chem.
Soc. ReV. 2003, 32, 104-114. (f) Beller, M.; Tillack, A.; Seayad, J. In
Transition Metals for Organic Synthesis, 2nd ed.; Beller, M., Bolm, C.,
Eds.; Wiley-VCH: Weinheim, Germany, 2004; Vol. 2, pp 403-414.
(2) Gagne´, M. R.; Stern, C. L.; Marks, T. J. J. Am. Chem. Soc. 1992,
118, 275-294 and references therein.
10.1021/jo052322x CCC: $33.50 © 2006 American Chemical Society
Published on Web 02/24/2006
2514
J. Org. Chem. 2006, 71, 2514-2517

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TABLE 1. Intramolecular Hydroamination Reaction with
[Li(THF)4] [Yb[(R)-C20H12N2(C6H14)]2], 1a
Ta
(°C) (mol %)
cat. ratio
conv eeb
(%) (%)
entry
substrate
t
product
1
2
25
25
5
5
48 h
6 d
67
100
70
66
FIGURE 1. Structure of catalyst 1a, [Li(THF)4][Yb[(R)-C20H12N2-
(C6H14)]2].
3
4
25
60
10
10
7 d
46 h
49
98
69
42
50c
coordinating alkyl ligand revealed indeed highly active catalysts
for intramolecular hydroamination11b and catalyzed the cycliza-
tion of the aminopentene depicted in Scheme 1 with up to 53%
ee. To the best of our knowledge, the highest asymmetric
induction for intramolecular hydroamination to date (87% ee
for the test reaction) was obtained by the group of Livinghouse
with yttrium bisthiophenolate catalysts prepared in situ.12 They
showed, however, moderate activities because reactions were
performed at 60 °C.
5
25
10
24 h
100
a Reactions were performed in C6D6. b Enantiomeric excesses were
determined by GC analysis of Mosher amides. c Enantiomeric excess
determined by NMR analysis in chiral liquid crystals.
carbon-13 NMR in a PBLG/DMF-d7 liquid crystal.16 The ee
measured on the aromatic carbons (Figure 2) was 50%.
It is obvious that the structure of the substituents placed on
the aminopentene chain has a significant influence on the
reaction rate. Thus, the presence of a gem-dimethyl group in
the backbone is known to facilitate the cyclization by both a
combination of Thorpe-Ingold effect (decrease of the angle at
the gem-dimethyl group) and a reactive rotamer effect (increase
in the population of the more reactive syn rotamer).17 The gem-
diphenyl and cyclohexyl groups contributions in hydroamination
reactions are more important compared to the gem-dimethyl
effect, because for substrates 2 and 6, a large increase in the
reaction rate is observed.
We then turned our efforts toward the preparation of a more
active catalyst. As ytterbium led in our previous attempts to
the most enantioselective complex,15b we decided to prepare
by the same route a new complex 1b bearing cyclohexyl
substituents on the nitrogen atoms (see Scheme 2). To gain
insight into the effect of the electronic factor on the catalysts
efficiency and enantioselectivity, we simultaneously prepared
the analogous lutetium complex 1c with an ionic radius nearly
identical to that of ytterbium [Yb(III) 1.008 Å, Lu(III) 1.001
Å] and possessing one additional electron.18
The cyclohexyl-substituted binaphthyldiamine ligand was
prepared in 73% yield according to a known procedure.19
Ytterbium and lutetium complexes 1b and 1c were synthesized
by the previously described method.15 After reacting 2 equiva-
lents of the dilithium salt of the ligand with YbCl3 or LuCl3 in
THF at room temperature (Scheme 2), solvent was removed.
The complexes were used either without further purification or
after removal of the LiCl salt by extraction with toluene.
Complexes 1b and 1c were isolated in 81 and 94% yield,
respectively.
In our ongoing research we focused on the preparation of
lanthanide catalysts coordinated by chiral amido ligands for
intramolecular hydroamination. We selected binaphthylamine,
which had never been used as a chiral ligand for lanthanides,
in contrast to binaphthol.13,14 We have previously reported the
preparation of a new family of lanthanide ate-complexes [Li-
(THF)4] [Ln[(R)-C20H12N2(C10H22)]2] (Ln ) Yb, Sm, Nd, Lu),
1, derived from chiral disubstituted (R)-binaphthylamido ligands.15a
In these compounds, coordination of two (R)-binaphthylamine
ligands to the lanthanide atom resulted in the formation of a
complex anion associated to a discrete counterion (Li(THF)4)+.
Their activity and enantioselectivity for intramolecular hy-
droamination were evaluated on the cyclization of C-(1-allyl-
cyclohexyl)-methylamine, 2. The ytterbium complex was found
to give the best results with the formation of the spiropyrrolidine,
3, with 41% ee. We further investigated the variation of the
nitrogen substituent and obtained spiropyrrolidine 3 with up to
70% enantiomeric excess with ytterbium complex 1a containing
(R)-1,1′-binaphthyl-2,2′-bis(iso-propylamido) ligands (see Figure
1).15b In view of a better comparison of the efficiency of
complex 1a with reported catalysts, we present here our results
concerning the enantioselective hydroamination starting from
various aminoolefins using new ytterbium or lutetium catalysts
bearing cyclohexyl groups on nitrogen atoms.
We first examined the reaction of 2,2-dimethyl-pent-4-
enylamine, 4, in the presence of catalyst 1a, which indeed
promoted the cyclization at room temperature. The correspond-
ing pyrrolidine, 5, was obtained with 69% ee, albeit with a low
conversion after a one week reaction time (see Table 1, entry
3). The activity of this catalyst could be increased by performing
the reaction at 60 °C, yielding the pyrrolidine in 2 days with a
full conversion however together with a loss in enantioselectivity
(42% ee, Table 1, entry 4). The cyclization of 2,2-diphenyl-
pent-4-enylamine, 6, at room temperature was achieved in only
24 h (Table 1, entry 5). The enantiomeric analysis of the
resulting pyrrolidine, 7, was performed using proton-decoupled
The hydroamination/cyclization of C-(1-allyl-cyclohexyl)-
methylamine 2 catalyzed by complex 1b and 1c was first
investigated, and the results are summarized in Table 2. With
1b, the pyrrolidine 3 was obtained with nearly quantitative
(16) (a) Lesot, P.; Merlet, D.; Meddour, A.; Courtieu, J.; Loewenstein,
A. J. Chem. Soc., Faraday Trans. 1995, 91, 1371-1375. (b) Meddour, A.;
Berdague´, P.; Hedli, A.; Courtieu, J.; Lesot, P. J. Am. Chem. Soc. 1997,
119, 4502-4508.
(17) (a) Sesenoglu, O.; Candela Lena, J. I.; Altinel, E.; Birlirakis, N.;
Arseniyadis, S. Tetrahedron: Asymmetry 2005, 16, 995-1015. (b) Curtin,
M. L.; Okamura, W. H. J. Org. Chem. 1990, 55, 5278-5287.
(18) Shannon, R. D. Acta Crystallogr. 1976, 32A, 751-767.
(19) Vyskocil, S.; Jaracz, S.; Smrcina, M.; Sticha, M.; Hanus, V.; Polasek,
M.; Kocovsky, P. J. Org. Chem. 1998, 63, 7727-7737.
(12) Kim, J. Y.; Livinghouse, T. Org. Lett. 2005, 1737-1739.
(13) (a) Shibasaki, M.; Yoshikawa, N. Chem. ReV. 2002, 102, 2187-
2209. (b) Kobayashi, S.; Sugiura, M.; Kitagawa, H.; Lam, W. L. Chem.
ReV. 2002, 102, 2227-2302. (c) Aspinall, H. C. Chem. ReV. 2002, 102,
1807-1850.
(14) Carre´e, F.; Gil, R.; Collin, J. Org. Lett. 2005, 7, 1023-1026.
(15) (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.sEur. J. 2005, 11, 3455-3462.
J. Org. Chem, Vol. 71, No. 6, 2006 2515

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those new catalysts, we tested the hydroamination of two other
aminopentenes, namely, the corresponding gem-diphenyl com-
pound 6 and the new C-(1-allyl-cyclopentyl)-methylamine
derivative, 8. As observed with catalyst 1a, cyclization of the
gem-diphenyl substrate was very fast in comparison with that
of other substrates: total conversion was observed within 21 h
with both catalyst 1b and catalyst 1c using low catalytic ratios
(3% for 1b, 2% for 1c; Table 2, entries 9 and 11). Similar
enantiomeric excesses (about 60%) were obtained. The reaction
performed at 0 °C allowed the isolation (77% yield) of
pyrrolidine 7 with an enantiomeric excess of 66% (Table 2,
entry 10). To the best of our knowledge, this value is the highest
reported to date for this substrate. The replacement of isopropyl
substituents by cyclohexyl radicals in the ligand structure thus
yielded significant improvements in both rate and asymmetric
induction.
In the case of substrate 8, 4 days were necessary to perform
the cyclization with high conversion (83%) and yield (57%
isolated product; Table 2, entry 12). To our delight, the reaction
performed at low temperature (0 °C, 6 days, 36% conversion)
led to the expected product, 9, with the highest enantiomeric
excess obtained to date with these new ate-complexes. The novel
spiropyrrolidine 9 was obtained with 78% ee under those
conditions (Table 2, entry 13). Furthermore, the ytterbium
catalyst 1b showed a very high stability, because for this
reaction, the conversion reached 74% after two weeks with a
similar high enantioselectivity (Table 2, entry 14). The use of
lutetium catalyst 1c led to analogous conversion than did 1b at
room temperature but to small amounts of pyrrolidine when
the reaction was performed at 0 °C.
FIGURE 2. Aromatic region of 13C-{1H} NMR spectrum of (a) a
racemic mixture of pyrrolidine 7 and (b) pyrrolidine 7 obtained using
catalyst 1a in PBLG/DMF-d7 liquid crystal at T ) 310 K. Peaks marked
with an asterisk (/) belong to the major enantiomer, and peaks marked
with (o) belong to the minor enantiomer.
SCHEME 2. Synthesis of Complexes 1b and 1c, [Li(THF)n]
[Ln[(R)-C20H12N2(C12H22)]2], Ln ) Yb and Lu
The hydroamination/cyclization reactions of aminohexenes
into piperidines are challenging transformations. They indeed
often require higher reaction temperatures, and they afford the
expected products with lower enantiomeric excesses than the
analogous five-membered rings.3 We selected the aminohexene,
10, as a test substrate for the synthesis of the corresponding
spiropiperidine, 11. By using the ytterbium ate complex 1b at
room temperature, no reaction was observed. Cyclization
occurred, however, with total conversion after a 66 h reaction
time at 60 °C (Scheme 3). The new spiropiperidine was isolated
in high yield with a promising enantiomeric excess of 45%.
conversion (57% isolated yield) and 65% ee after 18 h reaction
time (Table 2, entry 1). This catalyst thus seemed more active
than the analogous complex 1a with isopropyl substituents,
whereas no important variation in enantioselectivity was
observed. By using an isolated complex, similar enantioselec-
tivity was obtained (68% ee) but with a decrease in activity
(Table 2, entry 2).20 The in situ prepared catalyst was active
enough to allow the reaction to be run at 0 °C. Under those
conditions, the spiropyrrolidine 3 was isolated after 4 days in
65% yield (88% conversion) and with an enantiomeric excess
of 76% (Table 2, entry 3). The lutetium catalyst 1c afforded
similar results with this substrate at room temperature but did
not lead to a significant increase of enantioselectivity when the
reaction was carried out at 0 °C (Table 2, entries 4 and 5).
Complex 1b led interestingly to a higher conversion than 1a
for the transformation of 2,2-dimethyl-pent-4-enylamine 4 (77%
in one week at room temperature) and to a slight increase in
the enantiomeric excess (73%; Table 2, entries 6 and 7).
Complex 1c proved to be more active than 1b but less
enantioselective (Table 2, entry 8). To check the versatility of
Ytterbium and lutetium ate complexes 1b and 1c, coordinated
by N-substituted cyclohexyl binaphthylamine, displayed higher
activities and selectivities than ytterbium complexes coordinated
by N-substituted isopropyl ligands. The comparison of ytterbium
and lutetium catalysts 1b and 1c indicated that lutetium was a
more active catalyst, affording, however, slightly lower levels
of enantioselectivity. It should be emphasized that the lutetium
catalyst 1c was always used without purification, because it
proved to be poorly stable after crystallization. For all amino-
pentenes, the cyclization proceeded with high conversions at
room temperature, and enantiomeric excesses of the pyrrolidines
exceeded 60% in all cases. A temperature effect was observed
by obtaining an increased enantioselectivity when the reactions
were performed at 0 °C. We have successfully been able to
isolate new N-containing heterocycles, and we assume our
catalysts compete favorably with other previously described
systems, because they are readily prepared from commercially
available precursors. They proved to be active under mild
conditions, and up to 78% ee was furthermore obtained in the
preparation of spiropyrrolidines. We are currently directing our
efforts toward further optimization of our catalysts for intra-
(20) This catalyst was used again after several days storage and was
both less active and less enantioselective (49% conversion, 57% ee).
2516 J. Org. Chem., Vol. 71, No. 6, 2006

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TABLE 2. Intramolecular Hydroamination Reaction with [Li(THF)n][Ln[(R)-C20H12N2(C12H22)]2], Ln ) Yb, 1b, Ln ) Lu, 1c
Ta
cat.
% conv
eeb
entry
substrate
(°C)
(ratio, mol %)
t
product
(isolated yield, %)
(%)
1
2
3
4
5
25
25
0
25
0
1b (6)
18 h
20 h
4 d
44 h
88 h
94 (57)
58
88 (65)
100
65
68
76
66
68
1b (10)c
1b (10)
1c (8)
1c (10)
75
6
7
8
25
25
25
1b (10)
1b (10)
1c (10)
48 h
7 d
5 d
34
77
91
75
73
66
9
10
11
25
0
25
1b (3)
1b (10)
1c (2)
21 h
6 d
21 h
100
100 (77)
100 (34)
62d
66d
60d
12
13
14
15
16
25
0
0
25
0
1b (10)
1b (10)
1b (10)
1c (10)
1c (10)
4 d
6 d
16 d
2 d
4 d
83 (57)
36
74
80 (56)
10
69
78
77
68
75
a Reactions at 25 °C were performed in C6D6, and reactions at 0 °C were performed in toluene. b Enantiomeric excesses were determined by GC analysis
of Mosher amides unless otherwise indicated. c Isolated catalyst. d Enantiomeric excess determined by NMR analyses in chiral liquid crystals.
SCHEME 3. Synthesis of Piperidine 11 Catalyzed by the
Ytterbium Ate Complex 1b
hydrolysis and extraction with ether, the organic layers were
concentrated in vacuo. The crude product was used in the following
step without any purification. To a suspension of LiAlH4 (3.75 g,
98.8 mmol) in ether (100 mL) at 0 °C was added dropwise a
solution of C-(1-allyl-cyclohexyl)-nitrile in ether (20 mL) in 10
min. The reaction mixture was allowed to warm to room temper-
ature overnight and was then hydrolyzed with water until the
formation of white hydroxide aluminum salts occurred. The solid
was separated from the mixture by filtration. The organic layer was
dried and concentrated in vacuo, and the residue was distilled (bp
) 100 °C, 3 mBar) to afford compound 2 (11.3 g, 74 mmol, 75%)
molecular hydroamination reactions and broadening the scope
of the substrates.
Experimental Section
1
as a colorless oil. H NMR (250 MHz, CDCl3) δ 0.98 (br s, 2H),
Representative Procedure for Pyrrolidine Formation. Prepa-
ration of 3. Preparation of Complex 1b, [Li(THF)n] [Yb[(R)-
C20H12N2(C12H22)]2]. In an argon-filled glovebox, (R)-(+)-2,2′-
bis(cyclohexylamino)-1,1′-binaphthyl (0.20 g, 0.44 mmol) was
dissolved in hexane (10 mL) in a Schlenk flask equipped with a
magnetic stirring bar. n-BuLi (1.6 M in hexanes, 0.56 mL, 0.89
mmol) was introduced via microsyringe, and the reaction mixture
was stirred for 10 min. The solvent was removed in vacuo from
the subsequent yellow suspension to afford the corresponding
lithium amide salt as a yellow solid. YbCl3 (0.031 g, 0.111 mmol)
was added to a solution of the bislithium salt of (R)-(+)-2,2′-bis-
(cyclohexylamino)-1,1′-binaphthyl (0.102 g, 0.222 mmol) in THF
(10 mL) at room temperature. The reaction mixture was stirred until
the disappearance of YbCl3 (15 min), and the THF was evaporated
in vacuo. The resulting solid was extracted with toluene (10 mL).
The reaction mixture was centrifuged, and the filtrate was concen-
trated in vacuo. The product was obtained as a brown powder with
81% yield. IR (KBr, Nujol) 1609, 1589, 1495, 1460, 1420, 1377,
1338, 1285, 1246, 1149, 1027, 810, 743, 728. The solid residue
was dissolved in THF (2 mL), and a slow diffusion of hexane in
THF solution at 25 °C resulted in the isolation of complex 1b as
brown crystals. The crystals were washed with cold hexane and
dried in vacuo at room temperature for 45 min. Anal. Calcd for
C72H84LiN4O2Yb: C, 71.07; H, 6.90. Found: C, 69.73; H, 6.59.
Preparation of C-(1-allyl-cyclohexyl)-methylamine, 2. A solu-
tion of cyclohexane carbonitrile (11 mL, 99 mmol) in THF (100
mL) was slowly added to a solution of freshly prepared lithium
diisopropylamine (118.6 mmol) in 150 mL of THF/hexane (50/
50) at 0 °C. The reaction mixture was subsequently stirred for an
additional hour, and a solution of allylbromide (9.9 mL, 113.6
mmol) in THF (20 mL) was added dropwise in 30 min. The mixture
was allowed to warm to room temperature overnight. After
1.15-1.47 (m, 10H), 2.07 (d, J ) 7.5, 2H), 2.54 (s, 2H), 4.94-
5.10 (m, 2H), 5.82 (m, 1H). 13C NMR (62.5 MHz, CDCl3) δ 21.4,
26.4, 33.2, 37.0, 39.8, 48.8, 116.7, 135.0. IR (CHCl3) 1156, 1272,
1422, 1552, 1637, 2306, 2411, 2686, 2855, 2929, 2987, 3055.
HRMS (EI) calcd for C10H19N, 153.1512; found, 153.1514.
Preparative-Scale Hydroamination Cyclization of 2. In an
argon-filled glovebox, 2 (0.616 mmol) was dissolved in C6D6 (0.5
mL) and dried on 4 Å molecular sieves for 2 h. The complex 1b
(6 mol %) was introduced into a vial and dissolved in C6D6 (1
mL), and the aminoalkene solution was then added at 25 °C. After
18 h, the reaction mixture was quenched with CH2Cl2. After the
evaporation of the solvents, the crude oil was distilled in vacuo
(bp ) 100 °C, 0.15 mBar) to afford 3 as a colorless oil (57% yield).
[R]D +26.9 (c 0.43, CHCl3) for 65% ee. The enantiomeric excess
was determined by a reaction with Mosher chloride. 1H NMR (250
MHz, CDCl3) δ 0.93 (dd, J ) 12.5, 9.2 Hz, 1H), 1.13 (d, J ) 6.5
Hz, 3H), 1.32-1.44 (m, 10H), 1.69 (dd, J ) 12.5, 6.5 Hz, 1H),
1.89 (br s, 1H), 2.56 (d, J ) 11.0 Hz, 1H), 2.75 (d, J ) 11.0 Hz,
1H), 3.13 (m, 1H). 13C NMR (62.5 MHz, CDCl3) δ 21.5, 23.7,
23.9, 26.1, 37.3, 38.6, 44.0, 47.6, 54.0, 59.2. IR (NaCl, CCl4) ν
1376, 1450, 2856, 2928 cm-1. MS (ESI): 154.2 (M - H+), 100%.
Acknowledgment. CNRS is acknowledged for giving
financial support and a postdoctoral grant for D.R.. A.T. thanks
the Russian Foundation of Basic Research for financial support
(Grant Nï. 05-03-32390).
Supporting Information Available: Complete experimental
procedures, full characterization, and enantiomeric excess deter-
minations. This material is available free of charge via the Internet
at http://pubs.acs.org.
JO052322X
J. Org. Chem, Vol. 71, No. 6, 2006 2517