Yttrium(III)-catalyzed intramolecular alkyne hydroaminations

Article abstract of DOI:10.1002/adsc.200505448

The neutral Y(III) complex 4 has been shown to be an effective precatalyst for intramolecular alkyne hydroaminations that provide cyclic amines in good to excellent yields.

Full text of DOI:10.1002/adsc.200505448

COMMUNICATIONS
DOI: 10.1002/adsc.200505448
Yttrium(III)-Catalyzed Intramolecular Alkyne Hydroaminations
Hyunseok Kim,a Tom Livinghouse,b,* Jun Hwan Shim,a Seong Guk Lee,a
Phil Ho Leea,*
a
Department of Chemistry, Kangwon National University, Chunchon 200-701, Republic of Korea
Fax: (þ82)-33-253-7582, e-mail: phlee@kangwon.ac.kr
b
Department of Chemistry, Montana State University, Bozeman, MT 59717, U.S.A.
Fax: (þ1)-406-994-5407, e-mail: livinghouse@chemistry.montana.edu
Received: November 11, 2005; Accepted: February 9, 2006
This paper is dedicated to Professor Sunggak Kim on the occasion of his 60th birthday.
Abstract: The neutral Y(III) complex 4 has been
shown to be an effective precatalyst for intramolecu-
lar alkyne hydroaminations that provide cyclic
amines in good to excellent yields.
Scheme 1.
Keywords: alkynes; catalysis; cyclization; hydroami-
nation; yttrium
ity of group 3 metallocenes in alkyne hydroamination is
influenced by steric hindrance about the metal cen-
ter.[3o,7] Although we set out to determine the role that
sterically hindered chelating ligands might play in
À
À
Catalytic N H addition reactions to C Cmultiple
changing the reactivity of group 3 amido complexes,
bonds are among the most important methods for the we cannot draw a conclusion about the relationship of
synthesis of azacycles common to naturally occurring al- catalyst reactivity and structure of ligands because li-
kaloids.[1] Of the variety of early transition metal-based gand exchange of N,N’-bis(2,6-diethylphenyl)ethylene-
catalysts for this transformation, complexes of the lan- diamine with Y[N(TMS)2]3 was not completed even af-
thanides appear uniquely well suited for alkene and al- ter 10 days. However, attachment of the ligand 5 to Y
kyne hydroaminations under mild reaction conditions.[2] was quantitatively achieved by direct metalation with
The majority of the complexes that have found utility for 1 equivalent of Y[N(TMS)2]3 in C6D6 (1208C, 5 days)
this purpose are comparatively air- and moisture-sensi- to afford complex 4 via elimination of (TMS)2NH
tive metallocene derivatives.[3] In addition to the metal- (Scheme 2). Ligand exchange of N,N’-bis(P,P-diiso-
locene versions of these catalysts, very effective non- propylthiophosphinyl)-2,3-dimethyl-2,3-butanediamine
metallocene lanthanide and group 3 catalysts have with Y[N(TMS)2]3 proceeded to give precatalyst 2 in C6
been reported for alkene and alkyne hydroamination re- D6 (1208C, 10 days) via smooth elimination of bis(trime-
actions.[4] Recently, Livinghouse and co-workers dis- thylsilyl)amine.
closed that simple amido derivatives of the group 3 met-
At the outset, the catalytic activity of these complexes
als corresponding to the formula M[N(TMS)2]3 and (1, 2, and 4) was examined in the intramolecular hydro-
[L2YN(TMS)2 (L¼ligand)] are competent catalysts amination of 5-phenyl-4-pentyn-1-amine (6). The re-
for intramolecular alkene hydroamination.[4a,5] Herein sults are summarized in Table 1. Treatment of 6 with
we show that L2YN(TMS)2 obtained from coordination 5 mol % Y[N(TMS)2]3 or 4 in a J. Young NMR tube
of the active metal center to simple chelating diamide li- (C6D6, 0.46 M) produced the desired product 13 in
gands can be efficiently used for intramolecular alkyne 90% via 5-exo-dig intramolecular hydroamination
hydroamination (Scheme 1).
(258C, 480 h) and 67% (258C, 330 h) yields, respectively
As part of our previous study,[4a] we demonstrated that (entries 1 and 3). Heating the reaction mixture at 608C
the addition of a variety of aminoalkenes to catalytic with 5 mol % Y[N(TMS)2]3 accelerated the reaction to
amounts of Y[N(TMS)2]3 (1) in C6D6 at 248Cresulted
give 13 in 90% yield after 89 h (entry 2). Subjecting
in generation of the corresponding amine-ligated[6] ami- 5 mol % 4 to 6 afforded azacycles in 94% yield (entry 6).
do complexes with concomitant immediate liberation of Although reaction of 2 with 6 (608C, 1.5 h, C6D6, 1.0 M)
(TMS)2NH. It is well established that the catalytic activ- afforded 13 in 96% yield (entry 5), internal aminoal-
Adv. Synth. Catal. 2006, 348, 701 – 704
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
701

Phil Ho Lee et al.
COMMUNICATIONS
Table 2. Intramolecular alkyne hydroamination catalyzed by
yttrium.
Scheme 2. In situ generation of the yttrium precatalyst for hy-
droamination.
Table 1. Optimization of intramolecular alkyne hydroamina-
tion catalyzed by yttrium.[a]
[a]
NMR yields based on p-xylene as an internal standard.
Isolated yield.
[b]
nitrogen was smoothly cyclized to give 14 in 95% yield
(258C, 1.5 h, entry 2). These results imply that cycliza-
tion of these substrates is facilitated by the Thorpe–In-
gold effect.[4a] Reaction of 8 with 4 at 1208Cfor 13 h pro-
duced the desired product 15 in 81% yield (entry 3). Al-
though treatment of 10 with 4 (5 mol %) furnished the
cyclized product 17 in 93% yield in C6D6 at 1508Cfor
71 h (entry 5), hydroamination of 11, having a methyl
[a]
Reaction performed in the presence of 5 mol % catalyst in
C6D6.
NMR yields based on p-xylene as an internal standard.
Isolated yield.
[b]
[c]
kynes lacking an aryl substituent did not give rise to the group at the carbon adjacent to the triple bond, was ac-
desired product.[8] Therefore, we examined the precata- celerated to afford 18 in 92% yield C6D6 at 1508Cfor
lyst 4 for intramolecular alkyne hydroamination. More- 18 h (entry 6). Exposure of 12 to 4 (5 mol %) resulted
over, it could be readily scaled up (3.0 mmol of aminoal- in the production of 19 in 48% yield, albeit under harsh
kyne 6) with the same efficiency (5 mol % of 4, 85% iso- conditions (C6D6, 1208C, 158 h) (entry 7).
lated yield, 406.0 mg).
In conclusion, we have shown that the neutral Y-di-
To demonstrate the efficiencyand scope of the present amine complex 4 is a competent precatalyst for intramo-
method, we applied the optimum conditions to a variety lecular alkyne hydroaminations involving primary
of aminoalkynes. The results are summarized in Table 2. amines. Complex 4 was quantitatively generated in situ
Addition of 9 to 4 (5 mol %) provided 16 in 98% yield by direct metalation reaction of the ligand 5 with 1
(by NMR) after 0.2 h at 258C(entry 4). [9] Also, aminoal- equivalent of Y[N(TMS)2]3 (1) in C6D6 (1208C, 5 days)
kyne 7 having a methyl group at the carbon adjacent to via elimination of (TMS)2NH. 5-exo-, 6-exo-, and 7-
702
asc.wiley-vch.de
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2006, 348, 701 – 704

Yttrium(III)-Catalyzed Intramolecular Alkyne Hydroaminations
COMMUNICATIONS
120, or 1508C) in an oil bath until hydroamination was judged
complete by disappearance of the starting material in the 1H-
NMR relative to the aromatic resonance of the internal stand-
ard p-xylene.
exo-dig intramolecular hydroaminations were found to
proceed smoothly in all cases. These results should im-
mediately provide more opportunities for the elucida-
À
tion of efficient and selective new catalytic C N bond
forming reactions by way of neutral catalyst develop-
ment. Further studies to expand the utility of this reac-
tion are underway.
Acknowledgements
This work was supported by the Korea Research Foundation
Grant (KRF-2003-005-C00021). NMR and mass spectral data
were obtained from the central instrumental facility in Kangwon
National University.
Experimental Section
Preparation of N,N’-Bis(2-isopropylphenyl)ethane-
1,2-diamine (5)
References and Notes
To a solution of 2-isopropylaniline (2.35 g, 17.4 mmol) and trie-
thylamine (2.64 mL, 19.0 mmol) in THF(60 mL) at 08Cwas
added dropwise oxalyl chloride (1.0 g, 7.9 mmol). The reaction
mixture was stirred overnight, then refluxed for 1 h. After cool-
ing to room temperature, the reaction mixture was diluted with
ethyl acetate (50 mL), and then washed with H2O (20 mL), 1 N
HCl (10 mL), and saturated aqueous NaHCO3 (10 mL). The
organic layer was dried with anhydrous MgSO4, filtered, and
evaporated under vacuum to provide N,N’-bis(2-isopropylphe-
nyl)oxalamide as a white solid; yield: 2.5 g (97%); mp 179–
1818C.
N,N’-Bis(2-isopropylphenyl)oxalamide (2.0 g, 6.16 mmol)
was reduced by addition to LiAlH4 (0.47 g, 12.3 mmol) in
THF (30 mL) at room temperature and then heating the result-
ing mixture at reflux overnight. The reaction mixture was
cooled to 08Cand carefully quenched via sequential addition
of H2O (0.5 mL), 15% aqueous NaOH (0.5 mL) and H2O
(1 mL). The mixture was stirred at room temperature for 2 h,
and anhydrous MgSO4 (1.0 g) was added. After filtration, the
solvent was evaporated under vacuum. The residue was puri-
fied by bulb-to-bulb distillation (160–1658Cat 0.5 mmHg) to
afford N,N’-bis(2-isopropylphenyl)ethane-1,2-diamine (5) as
a white solid; yield: 1.0 g (55%); mp 47–488C. 1H NMR
(300 MHz, CDCl3): d¼7.15 (m, 4H, ArH), 6.76 (m, 4H,
ArH), 4.03 (bs, 2H, NH), 3.50 (s, 4H, CH2), 2.85 (septet, J¼
6.9 Hz, 2H, CH), 1.22 (d, J¼6.9 Hz, 12H, CH3); 13CNMR
(75 MHz, CDCl3): d¼144.6, 132.8, 126.8, 125.1, 118.0, 110.8,
43.5, 27.2, 22.3; IR (KBr): n¼3421.3, 2959.5, 2867.5, 1602.3,
1582.1, 1504.7, 1449.1, 1305.6, 1256.8, 744.7 cmÀ1; HR-MS
(CI, NH3): m/z¼297.2368, calcd. for C20H28N2H [Mþ]:
297.2331,
[1] a) F. Alonso, I. P. Beletskaya, M. Yus, Chem. Rev. 2004,
104, 3079; b) I. Bytschkov, S. Doye, Eur. J. Org. Chem.
2003, 935; c) F. Pohlki, S. Doye, Chem. Soc. Rev. 2003,
32, 104; d) J. S. Johnson, R. G. Bergman, J. Am. Chem.
Soc. 2001, 123, 2923; e) M. Kawatsura, J. F. Hartwig, J.
Am. Chem. Soc. 2000, 122, 9546; f) E. Haak, H. Siebe-
neicher, S. Doye, Org. Lett. 2000, 2, 1935; g) D. Vasen,
A. Salzer, F. Gerhards, H.-J. Gais, R. Stürmer, N. H. Biel-
er, A. Togni, Organometallics 2000, 19, 539; h) T. E. Mül-
ler, M. Grosche, E. Herdtweck, A.-K. Pleier, E. Walter,
Y.-K. Yan, Organometallics 2000, 19, 170; i) S. Burling,
L. D. Field, B. A. Messerle, Organometallics 2000, 19, 87;
j) T. E. Müller, M. Beller, Chem. Rev. 1998, 98, 675.
[2] a) J.-S. Ruy, T. J. Marks, F. E. McDonald, Org. Lett. 2001,
3, 3091; b) S. Tian, V. M. Arredondo, C. L. Stern, T. J.
Marks, Organometallics 1999, 18, 2568; c) G. A. Molander,
E. D. Dowdy, J. Org. Chem. 1998, 63, 8983 and references
´
cited therein; d) M. R. Gagne, C. L. Stern, T. J. Marks, J.
Am. Chem. Soc. 1992, 114, 275.
[3] a) S. Hong, T. J. Marks, Acc. Chem. Res. 2004, 37, 673;
b) J.-S. Ryu, T. J. Marks, F. E. McDonald, J. Org. Chem.
2004, 69, 1038; c) D. V. Gribkov, K. C. Hultzsch, F. Ham-
pel, T. Wagner, Organometallics 2004, 23, 2601; d) D. V.
Gribkov, K. C. Hultzsch, Angew. Chem. Int. Ed. 2004,
43, 5542; e) D. V. Gribkov, K. C. Hulzsch, F. Hampel,
Chem. Eur. J. 2003, 9, 4796; f) S. Hong, A. M. Kawaoka,
T. J. Marks, J. Am. Chem. Soc. 2003, 125, 15878; g) S.
Hong, S. Tian, M. V. Metz, T. J. Marks, J. Am. Chem.
Soc. 2003, 125, 14768; h) J.-S. Ryu, G. Y. Li, T. J. Marks,
J. Am. Chem. Soc. 2003, 125, 12584; i) S. Hong, T. J.
Marks, J. Am. Chem. Soc. 2002, 124, 7886; j) Y. Li, T. J.
Marks, J. Am. Chem. Soc. 1996, 118, 707; k) Y. Li, T. J.
Marks, Organometallics 1996, 15, 3770; l) Y. Li, T. J.
Marks, J. Am. Chem. Soc. 1996, 118, 9295; m) M. A. Giar-
Typical Experimental Procedure
In an argon-filled glove box, Y[N(TMS)2]3 (11.4 mg,
0.02 mmol) and N,N’-bis(2-isopropylphenyl)ethane-1,2-di-
amine (5) (5.93 mg, 0.02 mmol) in C6D6 (0.4 mL) were intro-
duced sequentially into a J. Young NMR tube with Teflon
screw cap (purchased from Aldrich or J. Young Ltd.). The reac-
tion mixture was stirred at 1208Cfor 5 days until ligand attach-
ment was judged to be complete by the disappearance of the
Y[N(TMS)2]3 with concomitant generation of the free
(TMS)2NH. The appropriate aminoalkyne (0.4 mmol) and p-
xylene (4.9 mL, 0.04 mmol) were added to the resulting com-
plex via a microsyringe and the reaction mixture was subse-
quently heated at the corresponding temperature (25, 60,
´
dello, V. P. Conticello, L. Brard, M. R. Gagne, T. J. Marks,
J. Am. Chem. Soc. 1994, 116, 10241; n) Y. Li, P.-F. Fu, T. J.
Marks, Organometallics 1994, 13, 439; o) M. R. Gagne,
C. L. Stern, T. J. Marks, J. Am. Chem. Soc. 1992, 114,
´
´
275; p) M. R. Gagne, L. Brard, V. P. Conticello, M. A.
Giardello, C. L. Stern, T. J. Marks, Organometallics 1992,
´
11, 2003; q) M. R. Gagne, S. P. Nolan, T. J. Marks, Organo-
´
metallics 1990, 9, 1716; r) M. R. Gagne, T. J. Marks, J. Am.
Chem. Soc. 1989, 111, 4108.
Adv. Synth. Catal. 2006, 348, 701 – 704
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
703

Phil Ho Lee et al.
COMMUNICATIONS
[4] a) Y. K. Kim, T. Livinghouse, J. E. Bercaw, Tetrahedron
Lett. 2001, 42, 2933; b) M. R. Bürgstein, H. Berberich,
P. W. Roesky, Organometallics 1998, 17, 1452.
[5] a) J. Y. Kim, T. Livinghouse, Org. Lett. 2005, 7, 4391;
b) J. Y. Kim, T. Livinghouse, Org. Lett. 2005, 7, 1737;
c) Y. K. Kim, T. Livinghouse, Y. Horino, J. Am. Chem.
Soc. 2003, 125, 9560; d) Y. K. Kim, T. Livinghouse, Angew.
Chem. Int. Ed. 2002, 41, 3645.
[7] a) J.-S. Ruy, T. J. Marks, F. E. McDonald, Org. Lett. 2001,
3, 3091; b) S. Tian, V. M. Arredondo, C. L. Stern, T. J.
Marks, Organometallics 1999, 18, 2568; c) G. A. Molander,
E. D. Dowdy, J. Org. Chem. 1998, 63, 8983 and references
cited therein.
[8] Treatment of 8 with catalyst 2 did not produce the desired
product 15.
[9] J. Young NMR tubes, purchased from Aldrich or J. Young
Ltd, were used under refluxing conditions (bath tempera-
ture, 1208Cor 150 8C) without any special precautions.
[6] M. F. Lappert, P. P. Power, A. R. Sanger, R. C. Srivastava,
Metal and Metalloid Amides, Wiley, New York, 1980.
704
asc.wiley-vch.de
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2006, 348, 701 – 704