C O M M U N I C A T I O N S
Table 2. Enantioselective Allylation of N-Benzoylhydrazones with
lower ee values and yields (entries 12-13). Functional groups such
as chloro, bromo, nitro, ketone, amide, and methoxy were intact
under conditions. Interestingly, the labile phenolic functionality did
not require protection.
[1aH]+
Enantioselective allylation of N-benzoylhydrazones with the
chiral promoter [1bH]+, the pseudoenantiomer of [1aH]+, also
underwent the reactions efficiently and provided allylated products
with reversed chiralities (Table 3). The allylation of N-benzoylhy-
drazones with [1bH]+ was comparable to that of [1aH]+ in terms
of chemical yield and enantioselectivity. The two promoters [1aH]+
and [1bH]+, which are salts, were readily recovered after a simple
aqueous workup in more than 95% yield. The absolute configuration
of 3c was determined to be S by comparing the optical rotation
with that reported in the literature.8 The absolute configurations of
all other allylated products were determined in reference to 3c.
In conclusion, we developed an enantioselective allylation of
N-benzoylhydrazones in the presence of a protonated chiral amine
affording enantioenriched homoallylic amines in high yields, with
extremely high enantioselectivities. To the best of our knowledge,
this is the first example of employing a protonated chiral amine
with organometallic reagents. The method presented here has several
features including operational simplicity, generality of substrates,
low cost, and reuse of chiral promoters. Further work to expand
the scope of the reaction is underway.
Yield
(%)a
ee
(%)b
Entry
Substrate
R
Product
1
2
3
4
5
6
7
8
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
2m
2n
4-F-Ph-
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
94
92
92
90
90
88
90
86
90
90
92
95
80
99 (S)
98 (S)
99 (S)
99 (S)
99 (S)
99 (S)
99 (S)
99 (S)
99 (S)
99 (S)
99 (S)
86 (R)
80 (R)
4-Cl-Ph-
4-NO2-Ph-
4-MeC(O)-Ph-
4-MeC(O)NH-Ph-
4-Et-Ph-
4-OMe-Ph-
4-OH-Ph-
3-Cl-Ph-
2-Br-Ph-
2-OMe-Ph-
PhCH2CH2-
CH3(CH2)6-
9
10
11
12
13
a Isolated yield. b Enantiomeric excess was determined by HPLC
analysis using chiral column (Daicel Chiralpak IA) with
a
hexane-isopropanol as the solvent.
mixture in 83% yield (entry 7). A reaction performed in the presence
of Et3N+HPF6- and 1a afforded a racemic mixture (entry 8). These
results and NMR evidence indicate that the promoter [1aH]+ might
interact with N-benzoylhydrazone via hydrogen bonding and π-π
interaction, providing a chiral environment, while the allylindium
nucleophile generated in situ attacks at the Si-face of the CdN
bond, resulting in an allylated adduct with high enantioselectivity
(see Supporting Information). The addition of allylindium to the
N-benzoylhydrazone 2a in THF afforded the product 3a with a high
selectivity of 95% ee, but only in 38% yield (entry 9). Other organic
solvents such as toluene, acetonitrile, dichloromethane, and 1,2-
dichloroethane compared to methanol were less effective in terms
of chemical yield and enantioselectivity (entries 10-13).
We evaluated the scope of the reaction with a wide range of
N-benzoylhydrazones derived from aldehydes under optimal condi-
tions, and the results are summarized in Table 2. Reactions with
aryl aldehyde-derived N-benzoylhydrazones with either an ortho
substituent or a para/meta substituent proceeded smoothly at ambient
temperature in the presence of the protonated chiral amine [1aH]+,
affording allylated products in high yields with extremely high
enantioselectivities, demonstrating the generality of the reaction
(entries 1-11). N-Benzoylhydrazones derived from aliphatic alde-
hydes underwent allylation at room temperature with relatively
Acknowledgment. This research was funded by the National
Research Foundation of Korea (2009-0074839). CBMH is also
acknowledged.
Supporting Information Available: Experimental procedures,
compound characterization, NMR spectra, and HPLC traces. This
References
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Table 3. Enantioselective Allylation of N-Benzoylhydrazones with
[1bH]+
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Entry
Substrate
R
Product
Yield (%)a
ee (%)b
(7) Protonated chiral catalysts: (a) Singh, A.; Johnston, J. N. J. Am. Chem. Soc.
2008, 130, 5866. (b) Wilt, J. C.; Pink, R. M.; Johnston, J. N. Chem. Commun.
2008, 4177. (c) Jang, D. O.; Kim, S. Y. J. Am. Chem. Soc. 2008, 130, 16152.
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K. A.; Borths, C. J.; MacMillan, D. W. C. J. Am. Chem. Soc. 2000, 122,
4243.
1
2
3
4
5
6
7
2a
2b
2d
2e
2g
2h
2n
Ph
4-F-Ph-
ent-3a
ent-3b
ent-3d
ent-3e
ent-3g
ent-3h
ent-3n
92
90
89
90
90
88
81
99 (R)
99 (R)
99 (R)
99 (R)
96 (R)
99 (R)
78 (S)
4-NO2-Ph-
4-MeC(O)-Ph-
4-Et-Ph-
4-OMe-Ph-
CH3(CH2)6-
(8) Kobayashi, S.; Orgawa, C.; Konish, H.; Sugiura, M. J. Am. Chem. Soc. 2003,
125, 6610.
a Isolated yield. b Enantiomeric excess was determined by HPLC
analysis using chiral column (Daicel Chiralpak IA) with
hexane-isopropanol as the solvent.
a
JA1035336
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J. AM. CHEM. SOC. VOL. 132, NO. 35, 2010 12169