Chelating diamide based rate enhancement of intramolecular alkene hydroaminations catalyzed by a neutral Sc(III) complex

Article abstract of DOI:10.1021/ol051574h

(Chemical Equation Presented) Neutral scandium amido complexes are viable catalysts for intramolecular alkene hydroamination. Catalytic activity is strongly coupled to the electronic character of the Sc(III) ligand environment with chelating diamide coord

Full text of DOI:10.1021/ol051574h

ORGANIC
LETTERS
2
005
Vol. 7, No. 20
391-4393
Chelating Diamide Based Rate
Enhancement of Intramolecular Alkene
Hydroaminations Catalyzed by a Neutral
Sc(III) Complex
4
Joon Young Kim and Tom Livinghouse*
Department of Chemistry, Montana State UniVersity, Bozeman, Montana 59717
liVinghouse@chemistry.montana.edu
Received July 5, 2005
ABSTRACT
Neutral scandium amido complexes are viable catalysts for intramolecular alkene hydroamination. Catalytic activity is strongly coupled to the
electronic character of the Sc(III) ligand environment with chelating diamide coordination providing a precatalyst possessing substantially
improved activity and superb distereoselectivity in the synthesis of trans-2,5-disubstituted pyrrolidines.
The intramolecular hydroamination of unsaturated C-C
By virtue of the comparatively small covalent radius of Sc-
(III), complexes derived from this metal would be expected
to exhibit enhanced stereoselectivities in C-N bond forma-
tion, should active catalysts be identified. It is therefore of
interest that only one report has appeared describing Sc(III)
catalysts for alkene hydroamination and, additionally, that
linkages constitutes a powerful and atom-economic method
1
for the synthesis of nitrogenous heterocycles. The seminal
2
group 3 metallocenes developed by Marks and co-workers
have recently been joined by a variety of nonmetallocene
complexes of the group 3 metals as catalysts for the important
3
,4
6
variation of this reaction involving alkenes as addends.
these are cationic rather than neutral complexes. We have
Complexes derived from yttrium and the lanthanides have
been employed as catalysts in most cases involving the
internal hydroamination of alkenes involving early metals.
previously disclosed that chelating diamide and bis(thio-
(3) (a) Ryu, J.-S.; Li, G. Y.; Marks, T. J. J. Am. Chem. Soc. 2003, 125,
4,5
12584. (b) O’Shaughnessy, P. N.; Knight, P. D.; Morton, C.; Gillespie, K.
M.; Scott, P. Chem. Commun. 2003, 1770. (c) Gribkov, D. V.; Hultzsch,
K. C.; Hampel, F.; Wagner, T. Organometallics 2004, 23, 2601. (d) Kim,
Y. K.; Livinghouse, T.; Horino, Y. J. Am. Chem. Soc. 2003, 125, 9560. (e)
Kim, Y. K.; Livinghouse, T. Angew. Chem., Int. Ed. 2002, 41, 3645. (f)
Kim, Y. K.; Livinghouse, T.; Bercaw, J. E. Tetrahedron Lett. 2001, 42,
2933. (g) Gribkov, D. V.; Hulzsch, K. C.; Hampel, F. Chem. Eur. J. 2003,
9, 4796.
(4) Catalytic activity has also been observed for the following. (a) Simple
Ti(IV) amides: Bexrud, J. A.; Beard, J. D.; Leitch, D. C.; Shafer, L. L.
Org. Lett. 2005, 7, 1959. (b) A neutral Zr(IV)‚NPS complex: Kim, H.;
Lee, P. H.; Livinghouse, T. J. Chem. Soc. Chem. Commun. 2005, in press.
(c) And calcium complexes: Crimmin, M. R.; Casely, I. J.; Hill, M. S. J.
Am Chem. Soc. 2005, 127, 2042.
(1) (a) Pohlki, F.; Doye, S. Chem. Soc. ReV. 2003, 32, 104. (b) Muller,
T. E.; Beller, M. Chem. ReV. 1998, 98, 675. For hydroaminations catalyzed
by late transition metals, see: Vogels, C. M.; Hayes, P. G.; Shaver, M. P.;
Westcott, S. A. J. Chem. Soc., Chem. Commun. 2000, 51. Dorta, R.; Egli,
P.; Zurcher, F.; Togni, A. J. Am. Chem. Soc. 1997, 119, 10857. Casalnuovo,
A. L.; Calabrese, J. C.; Milstein, D. J. Am. Chem. Soc. 1988, 110, 6738.
Hegedus, L. S.; McKearin, J. M. J. Am. Chem. Soc. 1982, 104, 2444.
(2) (a) Hong, S.; Marks, T. J. Acc. Chem. Res. 2004, 39, 673 and
references therein. (b) Ryu, J.-S.; Marks, T. J.; McDonald, F. E. J. Org.
Chem. 2004, 69, 1038. (c) Gagn e´ , M. R.; Stern, C. L.; Marks, T. J. J. Am.
Chem. Soc. 1992, 114, 275. (d) Tian, S.; Arredondo, V. M.; Stern, C. L.;
Marks, T. J. Organometallics 1999, 18, 4421. (e) Ryu, J.-S.; Marks, T. J.;
McDonald, F. E. Org. Lett. 2001, 3, 3091. (f) Arredondo, V. M.; Tian, S.;
McDonald, F. E.; Marks, T. J. J. Am. Chem. Soc. 1999, 121, 3633 and
references therein.
(5) For the use of cationic Zr(IV) complexes, see: (a) Knight, P. D.;
Munslow, I.; O’Shaughnessy, P. N.; Scott, P. Chem. Commun. 2004, 894.
(b) Gribkov, D. V.; Hultzsch, K. C. Angew. Chem., Int. Ed. 2004, 43, 5542.
1
0.1021/ol051574h CCC: $30.25
© 2005 American Chemical Society
Published on Web 09/07/2005

phosphinic amidate) complexes of the group 3 metals
(
particularly Y and Nd) are potent catalysts for intramolecular
Table 1. Internal Alkene Hydroaminations Catalyzed by 7
3d-f
alkene hydroamination.
In this communication we show
that neutral complexes of Sc(III) are competent catalysts for
this transformation and that the activity of these species is
strongly coupled to the electronic characteristics of the ligand
environment surrounding Sc.
The internal hydroamination of 2,2-dimethylpent-4-ene-
1-amine (2a) was selected for initial examination as it was
expected that cyclization of this substrate would be facilitated
3
f
3d-f
by the Thorpe-Ingold effect. As in our previous studies,
7
the simple amide Sc[N(TMS)
catalytic activity. In contrast to Y[N(TMS)
N(TMS) , which led to the conversion of 2a to the
pyrrolidine 3a in 6 and 4 h, respectively, at 24 °C
M[N(TMS) (5 mol %), C ], the use of 1 (5 mol %)
required 3 h at 120 °C. We have previously shown that bis-
thiophosphinic amidate) “NPS” complexes of metals be-
2
]
3
(1) was first probed for
2 3
]
and Nd-
[
2 3
]
[
2
]
3
6 6
D
a
1
(
Yield ( H NMR) based on p-xylene as the internal standard.
3d
4b
longing to groups 3 and 4 possess dramatically enhanced
catalytic activities for intramolecular alkene hydroamination.
Successful generation of the desired NPS precatalyst 5
proved experimentally straightforward via amine elimination
Closely related reaction conditions were subsequently
utilized for the cyclization of a series of representative
primary amines 2b-e. Reaction times and yields obtained
employing the Sc(III)-chelated diamide 7 are compiled in
3d
involving 1 and bis(thiophosphinic amide) 4 [1 equiv, C
5 °C, 1 h]. To our initial disappointment, 5 proved inferior
in catalytic activity to 1 in that cyclization of 2a to 3a
>95%, 5 mol % 5) required fully 36 h at 120 °C. In light
6 6
D ,
7
8
Table 1. It is of preparative interest that cyclization of 2b
on a 3 mmol scale followed by separation of the products
from the catalyst by vacuum transfer and protonation (6 M
HCl in Et O) furnished 3b as its hydrochloride salt in 98%
2
(
of the pronounced activity decrease observed from 1 to 5
and the increase in ionization enthalpies known for metals
in the series Sc < Y < La, we predicted that rate acceleration
could be achieved by coordination of the electron-deficient
Sc(III) center within a strongly electron-donating ligand
environment. To this end, the chelated diamide 7 was
generated by amine elimination involving 1 and diamine 6
isolated yield.
Several of the trends that emerge from the foregoing
examples are worthy of comment. The presence of Thorpe-
Ingold buttressing is helpful but not a prerequisite for
successful cyclization. This stands in contrast to the results
of Piers, Shafer, and co-workers who have reported that 2c
is only incompletely converted (50%) to 3c in the presence
3e
[1 equiv, C
6 6
D , 120 °C, 1 h]. Significantly, cyclization of
6
2a to 3a (>95%) in the presence of 7 (5 mol %) required
of a cationic Sc(III) catalyst. It is also of significance that
only 2.5 h at 60 °C (Scheme 1). It should be strongly
emphasized that we have not observed rate differences of
this magnitude between complexes of the chelating diamide
and bis(thiophosphinic amidate) varieties for the metals Y,
2b, which is inert toward the Piers’ Sc catalyst, undergoes
efficient conversion with superb diastereoselectivity [49:1
(GC)] in the presence of 7. The unsymmetrical aminodiene
2e undergoes chemoselective cyclization involving the
monosubstituted alkene to afford the piperidines 3e albeit
with moderate (cis/trans ) 6:1) selectivity. In addition, the
aminodiene 2f undergoes selective monocyclization (22 °C,
3
d-f
Nd, and La.
1
6 h) [dr ) 49:1 (GC of the tosylamides)] to give 3f and
Scheme 1
ultimately stereospecific bicyclization of the trans-isomer to
the pyrrolizidine 8 [>95%, 90 °C, 5 h, (Scheme 2)].
Scheme 2
A probable mechanistic pathway for the intramolecular
hydroamination of 2b involving the putative amido complex
4392
Org. Lett., Vol. 7, No. 20, 2005

intramolecular alkene hydroaminations involving primary and
secondary amines. Although the catalytic activity of 7 is
lower than that exhibited by the corresponding Y(III) or Nd-
Scheme 3
3
e
(III) diamide chelates, the enhanced diastereoselectivities
obtained for the cyclizations of 1-substituted-4-penteny-
lamines are considerably higher.
Acknowledgment. Generous financial support for this
research was provided by the National Institutes of Health.
Supporting Information Available: Experimental pro-
cedures and characterization data for all new compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
OL051574H
(
6) Lauterwasser, F.; Hayes, P. G.; Brase, S.; Piers, W.; Schafer, L. L.
Organometallics 2004, 23, 2234.
7) Bradley, D. C.; Ghotra, J. S.; Hart, F. A. J. Chem. Soc. Dalton. Trans.
973, 1021.
8) For all reactions conducted on <3-mmol scale, yields were determined
(
1
A and Sc(III) alkyl B based on these observations is depicted
in Scheme 3.
In conclusion, we have shown that the neutral Sc(III)-
chelated diamide complex 7 is an effective precatalyst for
(
9
1
by H NMR using p-xylene as the internal standard.-
9) A similar mechanism has been proposed in connection with intramo-
(
lecular alkene hydroaminations catalyzed by metallocene complexes of the
lanthanides.2c
Org. Lett., Vol. 7, No. 20, 2005
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