C O M M U N I C A T I O N S
Table 2. Scope of the Regioselective Rhodium-Catalyzed Allylic
Amination Reaction with the 1-Aminopyridinium Ylide (eq 1; rac-1
X ) NC5H5, Y ) I)a
available ammonia equivalent, which serves to illustrate the synthetic
potential of this nucleophile for the preparation of primary allylic
amines. Overall, this work provides an opportunity to investigate the
utility of this new class of nucleophiles in related metal-catalyzed
reactions.
allylic carbonate
rac-1 R2
ratio of
rac-2/3b c
,
entry
)
yield (%)d
1
2
3
4
5
6
7
8
Ph(CH2)2
a
b
c
d
e
g19:1
g19:1
g19:1
g19:1
g19:1
g19:1
g19:1
g19:1
g19:1
g19:1
g19:1
g19:1
g19:1
g19:1
g19:1
89
76
87
87
73
79
75
86
78
88
84
84
86
81
89
Me
Acknowledgment. Dedicated to Prof. Philip D. Magnus, FRS on
the occasion of his 65th birthday. We sincerely thank the NIH
(GM58877) for generous financial support. We also thank Prof. Jeffrey
N. Johnston for helpful discussions pertaining to the isolation of
primary amines. Finally we would like to acknowledge the Royal
Society for a Wolfson Research Merit Award (P.A.E.) and the
University of Liverpool for a Postgraduate Research Studentship
(E.A.C.).
nPr
nBu
CH2dCH(CH2)2
iPr
f
cHex
g
h
i
j
k
l
m
n
o
iBu
9
PhCH2
BnOCH2
BnO(CH2)2
TBSOCH2
TBSO(CH2)2
Ph
10
11
12
13
14
15
Supporting Information Available: Experimental procedures and
spectral data for rac-2a-o, (S)-4, and rac-5 (PDF). X-ray crystal-
lographic file in CIF format for rac-2o. This material is available free
Npth
a All reactions were carried out on a 0.25 mmol reaction scale.
b Regioselectivities were determined by 500 MHz 1H NMR analysis of
the crude reaction mixtures. c The linear products 3 were prepared
independently Via Pd(0) catalysis. d Isolated yields.
References
(1) For a recent review on allylic amination, see: Jørgensen, K. A. in Modern
Amination Methods; Ricci, A., Ed.; Wiley-VCH: Weinheim, Germany,
2000; Chapter 1, pp 1-35.
Additional studies examined the mechanistic course of the allylic
amination in the context of the stereospecificity. Treatment of the allylic
carbonate (S)-1j (98% ee) with the aza-ylide under the optimized
reaction conditions furnished the chiral nonracemic secondary allylic
pyridinium salt (S)-2j in 88% yield, with retention of absolute
configuration in accord with our previous studies with soft nucleophiles
(b/l g 19:1, 98% cee).11 Reductive cleavage of the pyridinium salt
(S)-2j with samarium diiodide furnished the enantiomerically enriched
primary allylic amine (S)-4 in 88% yield.12
(2) For recent reviews on metal-catalyzed allylic substitution, see: (a) Trost,
B. M.; Crawley, M. L. Chem. ReV. 2003, 103, 2921. (b) Leahy, D. K.;
Evans, P. A. In Modern Rhodium-Catalyzed Organic Reactions; Evans,
P. A., Ed.; Wiley-VCH: Weinheim, Germany, 2005; Chapter 10, pp 191-
214. (c) Helmchen, G.; Dahnz, A.; Du¨bon, P.; Schelwies, M.; Weihofen,
R. Chem. Commun. 2007, 675 and pertinent references cited therein.
(3) For examples of the stereospecific intermolecular rhodium-catalyzed allylic
amination reactions, see: (a) Evans, P. A.; Robinson, J. E.; Nelson, J. D.
J. Am. Chem. Soc. 1999, 121, 6761; 12214. (b) Evans, P. A.; Robinson,
J. E. Org. Lett. 1999, 1, 1929. (c) Evans, P. A.; Robinson, J. E.; Moffett,
K. K. Org. Lett. 2001, 3, 3269. (d) Evans, P. A.; Lai, K. W.; Zhang, H.-
R.; Huffman, J. C. Chem. Commun. 2006, 844. (e) Evans, P. A.; Qin, J.;
Robinson, J. E.; Bazin, B. Angew. Chem., Int. Ed. 2007, 46, 7417.
(4) For related examples of stereospecific metal-catalyzed allylic amination
reactions, see: (a) Fe: Plietker, B. Angew. Chem., Int. Ed. 2006, 45, 6053.
(b) Ir: Singh, O. V.; Han, H. Org. Lett. 2007, 9, 4801.
Scheme 1. Stereospecific Allylic Amination and N-N Bond
Cleavage
(5) For leading examples of intermolecular enantioselective metal-catalyzed
allylic amination reactions with various nitrogen pronucleophiles, see: (a)
Hayashi, T.; Kishi, K.; Yamamoto, A.; Ito, Y. Tetrahedron Lett. 1990, 31,
1743. (b) You, S.-L.; Zhu, X.-Z.; Luo, Y.-M.; Hou, X.-L.; Dai, L.-X. J. Am.
Chem. Soc. 2001, 123, 7471. (c) Ohmura, T.; Hartwig, J. F. J. Am. Chem.
Soc. 2002, 124, 15164. (d) Lipowsky, G.; Helmchen, G. Chem. Commun.
2004, 116. (e) Tissot-Croset, K.; Polet, D.; Alexakis, A. Angew. Chem.,
Int. Ed. 2004, 43, 2426. (f) Miyabe, H.; Matsumura, A.; Moriyama, K.;
Takemoto, Y. Org. Lett. 2004, 6, 4631. (g) Yamashita, Y.; Gopalarathnam,
A.; Hartwig, J. F. J. Am. Chem. Soc. 2007, 129, 7508. (h) Miyabe, K;
Yoshida, K.; Reddy, V. K.; Takemoto, Y. J. Org. Chem. 2009, 74, 305
and pertinent references cited therein.
(6) For examples of the regioselective allylic amination with hydrazine
derivatives, see: (a) Matunas, R.; Lai, A. J.; Lee, C. Tetrahedron 2005, 61,
6298. (b) Johns, A. M.; Liu, Z.; Hartwig, J. F. Angew. Chem., Int. Ed.
2007, 46, 7259.
(7) (a) Nitrogen, Oxygen and Sulfur Ylide Chemistry: A Practical Approach
to Chemistry; Clark, J. S., Ed.; Oxford University Press: Oxford, 2002. (b)
Phosphorus Ylides; Chemistry and Application in Organic Synthesis;
Kolodiazhnyi, O. I.; Wiley-VCH: Weinheim, 1999.
Finally, the synthetic utility of this process was further illustrated
with the development of a novel one-pot protocol using 1-aminopy-
ridinium iodide as a novel ammonia equivalent.13 Based on our
preliminary work with weak inorganic bases we envisioned that the
allylic amination could be promoted with catalytic base, which would
provide an opportunity to affect the in situ reductive cleavage to the
primary amine. Gratifyingly, treatment of the allylic carbonate rac-1a
under the analogous reaction conditions, albeit using catalytic potas-
sium carbonate at 30 °C, followed by the in situ reductive cleavage
using Zn/NH4Cl, furnished the allylic amine hydrochloride salt rac-5
in 74% overall yield (b/l g 19:1).14
(8) For the discussion of the stability of various ylides, see: (a) Naito, T.;
Nagase, S.; Yamataka, H. J. Am. Chem. Soc. 1994, 116, 10080. (b) Cheng,
J.-P.; Liu, B.; Zhao, Y.; Sun, Y.; Zhang, X.-M.; Lu, Y. J. Org. Chem.
1999, 64, 604. (c) Aggarwal, V. K.; Harvey, J. N.; Robiette, R. Angew.
Chem., Int. Ed. 2005, 44, 5468.
(9) Although potassium carbonate is a more convenient and cheaper base, the
reaction is not stereospecific (74% cee) and is less reliable with the
R-branched and hydroxymethyl substituents.
(10) Quenching the reaction with LiI/AcOH was more convenient than HI, which
afforded the pyridinium salt rac-2a in a reduced 74% yield.
(11) Rama Rao, A. V.; Bose, D. S.; Gurjar, M. K.; Ravindranathan, T.
Tetrahedron 1989, 45, 7031.
(12) Souppe, J.; Danon, L.; Namy, J. L.; Kagan, H. B. J. Organomet. Chem.
1983, 250, 227.
(13) For recent examples of the regio- and enantioselective metal-catalyzed allylic
amination with ammonia equivalents, see: (a) Weihofen, R.; Tverskoy, O.;
Helmchen, G. Angew. Chem., Int. Ed. 2006, 45, 5546. (b) Defieber, C.;
Ariger, M. A.; Moriel, P.; Carreira, E. M. Angew. Chem., Int. Ed. 2007,
46, 3139. (c) Pouy, M. J.; Leitner, A.; Weix, D. J.; Ueno, S.; Hartwig,
J. F. Org. Lett. 2007, 9, 3949.
In conclusion, we have developed a regio- and enantiospecific
rhodium-catalyzed allylic amination reaction using the aza-ylide derived
from 1-aminopyridinium iodide. This investigation demonstrates the
importance of the ylide-stabilizing group for obtaining the desired
nucleophilicity and the ability to utilize the aza-ylide as a commercially
(14) Shapiro, D.; Abramovitch, R. A. J. Am. Chem. Soc. 1955, 77, 6690.
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