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make the current methodology particularly interesting in syn-
thetic chemistry. Efforts are currently underway to elucidate the
mechanistic details and the scope and limitations of this
reaction, and the results will be reported in due course.
This work is supported by 973 program (2011CB808600), the
National Natural Science Foundation of China (21172176),
NCET-10-0649, IRT1030, and the Fundamental Research Funds
for the Central Universities. We thank Prof. Hua Li at Wuhan
University for solving the crystal structure.
Fig. 1 X-ray structure of (2R,4R,5R)-3s.
Notes and references
‡ Crystal data for (2R,4R,5R)-3s: C23H21BrF2N2O3, Mr = 491.33, T = 293 K,
monoclinic, space group P2(1), a = 9.3652(17), b = 10.803(2), c =
11.038(2) Å, V = 1090.0(3) Å3, Z = 2, 6047 reflections measured, 4037
unique (Rint = 0.0441) which were used in all calculations. The final
wR2 = 0.1223 (all data), Flack w = 0.010(11). CCDC 894876 (3s).
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I. Ojima, Wiley-Blackwell, New York, 2009; (b) J.-P. Begue and
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5 For recent reviews on 1,3-dipolar cycloaddition reactions of azomethine
ylides, see: (a) J. Yu, F. Shi and L.-Z. Gong, Acc. Chem. Res., 2011, 44, 1156;
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this methodology. As shown in Table 3, the length of the linear alkyl
group in the imino moiety had little effect on the stereoselectivity of
this cycloaddition reaction, and substrates with primary n-alkyl
substituents such as n-propyl, n-butyl and n-pentyl groups all have
afforded excellent diastereoselectivity and high enantioselectivity
(entries 1–5). 3-Phenylpropanaldehyde derived imino ester 4f was
also well tolerated giving rise to the desired cycloadduct 5f exclu-
sively in high yield with excellent enantioselectivity (entry 6). To
further probe the steric effects of alkyl substituents on this catalytic
system, several substrates with branched and sterically bulky sub-
stituents such as iso-propyl, cyclohexyl and iso-butyl were employed,
and the cycloaddition proceeded smoothly providing the expected
cycloadducts with similarly high levels of diastereoselectivity and
enantioselectivity (entries 7–9).
The relative and absolute configuration of the cycloadduct
exo0-3s was determined unambiguously to be (2R,4R,5R) by single
X-ray crystallographic analysis,‡ and those of other adducts were
tentatively proposed on the basis of these results (Fig. 1).
The optically active cycloadduct 3a can serve as a precursor for
other stereochemically rich structures as exemplified in Scheme 2.
(2R,3R)-6, a trifluoromethylated analogue of synthetically useful
chiral 2,3-diaminobutanoic acid,11 was obtained by acidic hydrolysis
of the adduct 3a in good yield with complete retention of stereo-
chemistry. Treatment of compound 6 with triphosgen under basic
conditions gave rise to the cyclic urea 7. Then, oxidative cleavage of
the PMP group in the presence of Ce(NH4)2(NO3)6 afforded the
derived amide 8 without loss of the diastereo-/enantiomeric excess.
In summary, we have developed the first catalytic asymmetric
synthesis of fluorinated imidazolidines via Cu(I)/(S,Rp)-PPFOMe-
catalyzed 1,3-dipolar cycloaddition of azomethine ylides with
various fluorinated imines. The identified optimal catalytic
´
(e) C. Najera and J. M. Sansano, Angew. Chem., Int. Ed., 2005, 44, 6272.
6 For the only example of the catalytic asymmetric synthesis of
imidazolidines, see: W.-J. Liu, X.-H. Chen and L.-Z. Gong, Org. Lett.,
2008, 10, 5357.
7 A non-enantioselective example of 1,3-dipolar cycloaddition of
azomethine ylides with fluorinated imine has been reported, see:
H. Xie, J. Zhu, Z. Chen, S. Li and Y. Wu, J. Org. Chem., 2010, 75, 7468.
8 For catalytic asymmetric synthesis of exo0-pyrrolidines, see:
(a) T. Arai, N. Yokoyama, A. Mishiro and H. Sato, Angew. Chem.,
Int. Ed., 2010, 49, 7895; (b) A. Awata and T. Arai, Chem.–Eur. J., 2012,
18, 8278.
9 (a) C.-J. Wang, G. Liang, Z.-Y. Xue and F. Gao, J. Am. Chem. Soc.,
2008, 130, 17250; (b) T.-L. Liu, Z.-L. He, H.-Y. Tao, Y.-P. Cai and
C.-J. Wang, Chem. Commun., 2011, 47, 2616.
system exhibited extremely high reactivity, excellent diastereo- 10 T. Hayashi, T. Mise, M. Fukushima, M. Kagotani, N. Nagashima,
Y. Hamada, A. Matsumoto, S. Kawakami, M. Konishi, K. Yamamoto
and M. Kumada, Bull. Chem. Soc. Jpn., 1980, 53, 1138.
selectivity, good enantioselectivity and broad substrate scope.
The ready availability of the starting materials and the great
´
11 A. Viso, R. F. de la Pradilla, M. Tortosa, A. Garcıa and A. Flores,
importance of the enantioenriched fluorinated compounds
Chem. Rev., 2011, 111, PR1.
c
This journal is The Royal Society of Chemistry 2013
Chem. Commun., 2013, 49, 6277--6279 6279