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B.-H. Zheng et al.
LETTER
2004, 6, 4113. (d) Behenna, D. C.; Stoltz, B. M. J. Am.
Chem. Soc. 2004, 126, 15044. (e) Braun, M.; Meier, T.
Angew. Chem. Int. Ed. 2006, 45, 6952. (f) Bélanger, ;
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Chem. Soc. 2007, 129, 1034.
ural products such as agelastatin A.10 Removal of OMe
group was realized by using SmI2, generating N-Boc allyl
amine 6a in 92% yield, which was easily converted into
the chiral 1,3-amino alcohol 7a in 77% yield by routine
operations of hydroboration and oxidation (Scheme 1).
The analogues of the chiral allyl amine 6a and 1,3-amino
alcohol 7a have been reported to serve as key building
blocks in the synthesis of bioactive natural products and
pharmaceutically important compounds such as (+)-CP-
99,994, (+)-CP-122,721, (–)-cytoxazone, (S)-dapoxetin,
and (–)-lasubine.9,11
(3) (a) Yan, X.-X.; Liang, C.-G.; Zhang, Y.; Hong, W.; Cao,
B.-X.; Dai, L.-X.; Hou, X.-L. Angew. Chem. Int. Ed. 2005,
44, 6544. (b) Zheng, W.-H.; Zheng, B.-H.; Zhang, Y.; Hou,
X.-L. J. Am. Chem. Soc. 2007, 129, 7718. (c) Zhang, K.;
Peng, Q.; Hou, X.-L.; Wu, Y.-D. Angew. Chem. Int. Ed.
2008, 47, 1741. (d) Liu, W.; Chen, D.; Zhu, X.-Z.; Wan,
X.-L.; Hou, X.-L. J. Am. Chem. Soc. 2009, 131, 8734.
(e) Lei, B.-L.; Ding, C.-H.; Yang, X.-F.; Wan, X.-L.; Hou,
X.-L. J. Am. Chem. Soc. 2009, 131, 18250. (f) Chen, J.-P.;
Ding, C.-H.; Liu, W.; Hou, X.-L.; Dai, L.-X. J. Am. Chem.
Soc. 2010, 132, 15493.
(4) (a) Akermark, B.; Akermark, G.; Hegedus, L. S.; Zetterberg,
K. J. Am. Chem. Soc. 1981, 103, 3037. (b) Watson, I. D. G.;
Yudin, A. K. J. Am. Chem. Soc. 2005, 127, 17516.
(5) (a) You, S.-L.; Zhu, X.-Z.; Luo, Y.-M.; Hou, X.-L.; Dai,
L.-X. J. Am. Chem. Soc. 2001, 123, 7471. (b) Zheng, W. H.;
Sun, N.; Hou, X. L. Org. Lett. 2005, 7, 5151. (c) Watson, I.
D. G.; Styler, S. A.; Yudin, A. K. J. Am. Chem. Soc. 2004,
126, 5086. (d) Dubovyk, I.; Watson, I. D. G.; Yudin, A. K.
J. Am. Chem. Soc. 2007, 129, 14172. (e) Johns, A. M.; Liu,
Z.; Hartwig, J. F. Angew. Chem. Int. Ed. 2007, 46, 7259.
(6) For enantioselective Ir-catalyzed allylic aminations using
hydroxamic acid derivatives as nucleophiles, see:
MeO
Ph
Boc
MeO
N
NH
3 M HCl, EtOAc
99%
Ph
5a
98% ee
3a
98% ee
SmI2 (10 equiv)
THF, 92%
Boc
Boc
HN
HN
1. BH3, THF
2. H2O2
77%
Ph
Ph
OH
6a
98% ee
7a
96% ee
(a) Miyabe, H.; Matsumura, A.; Moriyama, K.; Takemoto,
Y. Org. Lett. 2004, 6, 4631. During the preparation of this
manuscript, Takamoto and Helmchen reported their results:
(b) Miyabe, H.; Moriyama, K.; Takemoto, Y. Chem. Pharm.
Bull. 2011, 59, 714. (c) Gärtner, M.; Jäkel, M.; Achatz, M.;
Sonnenschein, C.; Tverskoy, O.; Helmchen, G. Org. Lett.
2011, 13, 2810.
Scheme 1 Selective deprotection of the allyl amine 3a
In conclusion, a new type of N-nucleophile has been de-
veloped in Pd-catalyzed asymmetric allylic amination
with monosubstituted allyl substrates, affording corre-
sponding branched allyl amines in high regio- and enantio-
selectivities. Either OMe or Boc group in products can be
removed easily to provide primary amine derivatives with
the optical purity unchanged. Both Boc-protected allyl
amines and their hydroboration–oxidation products are
useful in organic synthesis. Further investigations on their
uses as well as the applications of the protocol in organic
synthesis are in progress.
(7) (a) Fleming, I. Molecular Orbitals and Organic Chemical
Reactions: Reference Edition; John Wiley and Sons: UK,
2010. (b) Heaton, M. M. J. Am. Chem. Soc. 1978, 100, 2004.
(8) (a) Fiaud, J. C.; Malleron, J. L. Tetrahedron Lett. 1981, 22,
1399. (b) Lloyd-Jones, G. C.; Stephen, S. C. Chem. Eur. J.
1998, 4, 2539. (c) Lloyd-Jones, G. C.; Stephen, S. C.;
Murray, M.; Butts, C. P.; Vyskočil, ; Kočovský, P. Chem.
Eur. J. 2000, 6, 4348. (d) Fairlamb, I. J. S.; Lloyd-Jones, G.
C.; Vyskočil, ; Kočovský, P. Chem. Eur. J. 2002, 8, 4443.
(9) Atobe, M.; Yamazaki, N.; Kibayashi, C. J. Org. Chem. 2004,
69, 5595.
(10) Trost, B. M.; Dong, G. J. Am. Chem. Soc. 2006, 128, 6054.
(11) (a) Torre, O.; Gotor-Fernández, V.; Gotor, V. Tetrahedron:
Asymmetry 2006, 17, 860. (b) Singh, O. V.; Han, H.
Tetrahedron Lett. 2007, 48, 7094. (c) Chandrasekhar, S.;
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50, 5686.
(12) General Procedure for the Allylic Amination
To a flame-dried Schlenk tube were added [Pd(C3H5)Cl]2
(1.8 mg, 0.005 mmol), ligand (R,R)-L1 (6.4 mg, 0.010
mmol), and CH2Cl2 (2.0 mL) under Ar at r.t. The solution
was allowed to stir for 5 min before ester 1 (0.2 mmol),
MeONHBoc (44 mg, 0.3 mmol), and K3PO4 (63 mg, 0.3
mmol) were added. The reaction was allowed to stir at r.t.
and monitored by TLC until the disappearance of the ester 1.
The reaction mixture was passed through a short plug of
kieselgur eluted with CH2Cl2. The solvent was removed
under reduced pressure. The crude residue [after 1H NMR
analysis to check the regioisomeric ratio (3/4)] was purified
by flash chromatography (FC) with EtOAc–PE as the eluent
(generally, the two regioisomers could be separated by FC)
to afford the compound 3.
Supporting Information for this article is available online at
Acknowledgment
Financial supported by the Major Basic Research Development
Program (2010CB833300), National Natural Science Foundation of
China (20872161, 20821002, 21032007), the External Cooperation
Program of Chinese Academy of Sciences (GJHZ200816), and the
Technology Commission of Shanghai Municipality.
References
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Synlett 2011, No. 15, 2262–2264 © Thieme Stuttgart · New York