Enantioselective Michael reaction of nitroalkanes and chalcones by phase-transfer catalysis using chiral quaternary ammonium salts

Article abstract of DOI:10.1016/S0040-4020(01)00891-2

The catalytic enantioselective Michael reaction promoted by quaternary ammonium salt from cinchonidine as a phase transfer catalyst is described. Treatment of nitroalkanes with chalcone derivatives under mild reaction conditions afforded the corresponding Michael adducts in good yields with good to moderate enantiomeric excesses.

Full text of DOI:10.1016/S0040-4020(01)00891-2

TETRAHEDRON
Pergamon
Tetrahedron 57 72001) 8933±8938
Enantioselective Michael reaction of nitroalkanes and chalcones
by phase-transfer catalysis using chiral quaternary
ammonium salts
Dae Young Kimp and Sun Chul Huh
Department of Chemistry, Soonchunhyang University, Asan P.O. Box 97, Chungnam 336-600, South Korea
Received 16 July 2001; accepted 4 September2001
AbstractÐThe catalytic enantioselective Michael reaction promoted by quaternary ammonium salt from cinchonidine as a phase transfer
catalyst is described. Treatment of nitroalkanes with chalcone derivatives under mild reaction conditions afforded the corresponding Michael
adducts in good yields with good to moderate enantiomeric excesses. q 2001 Elsevier Science Ltd. All rights reserved.
The Michael reaction of carbanionic reagents to a,b-
unsaturated carbonyl compounds is one of the most funda-
mental C±C bond-forming reactions.1 The products of
conjugated addition of nitroalkanes to enones are useful as
precursors to aminoalkanes2 through reduction and to other
functionality that can be derived from the nitro group.3
Catalytic asymmetric conjugate additions of nitroalkenes
to enones in the presence of chiral catalysts have been
studied. The reactions of nitroalkenes with chalcone cata-
lyzed by chiral ammonium salts,4 quinine,5 azacrown
ethers,6 proline±Rb complex,7 Ni7II) complexes,8 and Al
complex of aminoalcohol10 have been reported. Especially,
Shibasaki9 and Hanessian7d reported excellent Michael reac-
tion of nitroalkanes with up to 95 and 93% ee using La±BI-
NOL complex and l-proline, respectively. Recently, Corey
and co-workers reported enantioselective Michael reaction
of nitromethane to 4-chlorobenzylidineacetophenone
catalyzed by chiral cinchoninium salt as the phase-transfer
catalyst.11 This report prompts us to disclose our results with
new chiral cinchonidinium salts for the enantioselective
Michael addition of nitroalkanes to chalcones.
alkaloids leads to enhancement of the stereoselectivity in
catalytic phase-transfer reactions. As part of our research
program toward the development of a more effective cin-
chona-alkaloid-derived phase-transfer catalyst, we intro-
duced bulky environment at the bridgehead nitrogen by
73,5-di-tert-butyl-4-methoxy)benzyl group.15 In this paper,
we wish to report the catalytic asymmetric conjugate
addition of nitroalkanes to chalcones 1 using the new cin-
chona alkaloid-derived quaternary ammonium salts 4 and 5
containing
group.
the
9-73,5-di-tert-butyl-4-methoxy)benzyl
The new catalysts 4 and 5 are derived in two steps from the
cinchona alkaloids and 73,5-di-tert-butyl-4-methoxy)benzyl
Table 1. Catalytic asymmetric Michael reaction of nitromethane to chal-
cone 1a with phase-transfer catalysts
Entry
Catalyts Temperature 78C) Yields 7%) eea 7%) 7con®g)b
1
2
3
4
5
6
7
8
4a
4b
4c
5a
5b
5c
4b
4b
4b
4b
6
20
20
20
20
20
20
0
215
100
20
20
20
85
90
0
71
73
68
0
157S)
357S)
±
67R)
77R)
137R)
±
Phase-transfer catalysis is clean and ef®cient processes in
organic synthesis.12 Recently, there have been successful
applications to catalytic asymmetric synthesis using cin-
chona alkaloid-derived quaternary ammonium salts.13 The
attachment of the bulky group to a bridgehead nitrogen
leads to a quaternary ammonium structure of well-de®ned
geometry in which the tetrahedral face about ammonium
nitrogen is blocked by the bulky subunit.14 The introduction
of the bulky subunit at the bridgehead nitrogen of cinchona
0
±
9c
10d
11
12
70
87
59
74
117S)
97S)
37S)
67S)
7
a
Enantiopurity of 2a was determined by HPLC analysis with a Chiralcel
AS column, 2-propanol/hexane 71:9), 1.2 mL min21, lmaxˆ254 nm,
retention times: major 12.7 min, minor 16.3 min. It was established by
analysis of racemic 2a that the enantiomers were fully resolved.
Forabsolute con®gulation see: Ref. 9.
Keywords: phase-transfer; Michael reactions; ammonium salt; asymmetric
reactions.
b
c
d
p
KOH was employed as base.
CH2Cl2 was employed as solvent.
Corresponding author. Tel.: 182-41-530-1244; fax: 182-41-530-1247;
e-mail: dyoung@sch.ac.kr
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020701)00891-2

8934
D. Y. Kim, S. C. Huh / Tetrahedron 57 ,2001) 8933±8938
Scheme 1.
bromide which is easily obtained from cheap 2,6-di-tert-
butyl-4-methylphenol 7BHT). In order to determine suitable
reaction conditions for the catalytic asymmetric conjugate
addition of nitroalkanes to chalcones 1, we initially investi-
gated the reaction system using 7 mol% of catalyst, with
nitromethane as the Michael donor and chalcone 1a as the
Michael acceptor7Table 1, Scheme 1).
enantiomerof 2a was determined to be S from the optical
rotation and chiral HPLC analysis.8,9 Catalyst 4b was more
effective than the othercatalysts 7Table 1, entries 1±6). The
absolute con®guration of the major Michael adduct 2a
differed between the cinchonidinium salts 74) and the cin-
choninium salts 75). The reaction did not proceed at 08C
below 7entries 7 and 8). In the presence of KOH as the
base, 2a was obtained in 70% yield and low enantio-
selectivity 7entry 9). The enantioselectivity was low, when
methylene chloride was used as the solvent 7entry 10).
Known cinchona-type phase-transfer catalysts 6 and 714
were less effective than catalyst 4b in this reaction 7entries
11 and 12). The stirring rate does not appear to in¯uence the
enantioselectivity of this reaction, however, it does affect
the rate of reaction and substantially decreased reaction
times can be achieved with high stirring rate.
Nitromethane reacted with chalcone in the presence of
t-BuOK and catalyst 4b 77 mol%), at room temperature, to
afford the Michael adduct 2a in 90% yield and 35% ee
7Table 1, entry 2). The absolute con®guration of the major
Table 2. Catalytic asymmetric Michael reaction of nitromethane to
chalcones 1 with phase-transfer catalyst 4b
Ar1
Ar2
Time 7h)
Yields 7%)
eea 7%) 7con®g)b
Under the optimized reaction conditions described above
77 mol% of catalyst 4b, t-BuOK, toluene, rt), we investi-
gated the catalytic asymmetric Michael reaction of nitro-
alkanes to chalcone derivatives 1. The reaction proceeded
smoothly to afford the corresponding adducts 2 with good
enantioselectivities. Reaction of 2.3 equiv. of nitromethane
with chalcone derivatives 1, cinchonidinium salt 4b 77
mol%), and t-BuOK 70.34 equiv.) in toluene at room
Ph
p-Cl, Ph
2-Naphthyl
Ph
Ph
Ph
16
20
24
2a, 90
2b, 85
2c, 57
357S)
427S)
31
a
Enantiopurity of 2 was determined by HPLC analysis with chiral column
7Chiralcel AS for 2a, AD for 2b and 2c), 2-propanol/hexane 71:9),
1.2 mL min21, lmaxˆ254 nm. In each case, it was established by analysis
of racemic 2 that the enantiomers were fully resolved.
b
Forabsolute con®guration see: Ref. 9.
Scheme 2.

D. Y. Kim, S. C. Huh / Tetrahedron 57 ,2001) 8933±8938
8935
Scheme 3.
Table 3. Catalytic asymmetric Michael reaction of 2-nitropropane to chal-
cones 1 with phase-transfer catalyst 4b
Daicel Chiralcel AS, AD, OJ, OD-H, and Regis Whelk-O1
columns 7250, 4.6 mm, eluent: hexane/2-propanol).
Ar1
Ar2
Time 7h)
Yields 7%)
ee%a
1.1.1.
N-'4-Methoxy-3,5-di-tert-butylbenzyl)cinchoni-
Ph
Ph
Ph
Ph
Ph
Ph
Ph
16
15
15
14
14
15
15
15
20
20
20
20
3a, 94
3b, 61
3c, 92
3d, 62
3e, 63
3f, 62
3g, 63
3h, 87
3i, 75
3j, 82
3k, 64
3l, 68
31
39794)
59787)
57
61
71
dinium bromide '4a). To a suspension of cinchonidine
72.94 g, 10 mmol) in toluene 770 mL) was added 3,5-di-
tert-butyl-4-methoxybenzyl bromide 74.38 g, 14 mmol),
and the mixture was stirred at re¯ux for 4 h. The reaction
mixture was cooled at room temperature, evaporated, and
the residue was recrystallized from diethyl ether/CH2Cl2 to
give the product as a dark brown solid. Puri®cation of the
residue by ¯ash chromatography 793:7, dichloromethane/
methanol) afforded the desired product 4a 791%, 5.57 g)
p-CF3, Ph
p-Br, Ph
2-Thienyl
2-Furanyl
m-Br, Ph
Ph
p-CF3, Ph
3-Cl, 4-F, Ph
2-Naphthyl
2-Naphthyl
1-Naphthyl
1-Naphthyl
60
Ph
537.99)
697.99)
517.99)
57
m-Br, Ph
p-Br, Ph
m-Br, Ph
p-Br, Ph
as a brown solid: [a]25 ˆ277.8 7cˆ2, CHCl3); mp 210±
57
D
2128C; IR7®lm, cm21) 3504, 3040, 3000, 2950, 1700, 1585,
1500, 1460, 1450, 1410, 1389, 1352, 1262, 1225, 1210,
Parenthesis indicate ee% after recrystallization of each product from
ethanol.
Enantiopurity of 3 was determined by HPLC analysis with chiral column
1
1115, 1010; H NMR 7CDCl3, 300 MHz) d 1.38 7s, 18H),
a
1.69 7m, 1H), 2.05 7s, 1H), 2.14±2.20 7m, 2H), 2.66 7m, 1H),
3.30 7m, 1H), 3.45 7m, 1H), 3.64 7d, Jˆ11.4 Hz, 1H), 3.68
7s, 3H), 3.79 7t, Jˆ8.5 Hz, 1H), 4.86 7t, Jˆ11.0 Hz, 1H),
5.01 7d, Jˆ10.3 Hz, 1H), 5.08 7s, 1H), 5.13 7d, Jˆ5.9 Hz,
1H), 5.50±5.62 7m, 1H), 5.74 7d, Jˆ11.0 Hz, 1H), 6.56 7d,
Jˆ6.5 Hz, 1H), 6.74 7d, Jˆ6.2 Hz, 1H), 7.58±7.61 7m, 2H),
7.69 7s, 2H), 7.747d, Jˆ4.4 Hz, 1H), 8.01±8.07 7m, 2H),
8.85 7d, Jˆ4.4 Hz, 1H); 13C NMR 7CDCl3, 50 MHz) d
21.54, 24.85, 26.68, 32.01, 35.98, 37.88, 51.33, 60.37,
61.12, 63.59, 64.14, 64.33, 68.53, 117.87, 120.14, 121.06,
122.78, 124.70, 127.61, 129.15, 130.42, 132.37, 136.47,
144.84, 144.95, 148.02, 150.08, 161.19; MS 7EI) m/z 527,
7Chiralcel OJ for 3a, 3g, and 3h, OD-H for 3b, 3c, 3f, 3k, and 3l, AS for 3i
and 3j, Regis Whelk-O1 for 3d and 3e), 2-propanol/hexane 71:9),
1.2 mL min21, lmaxˆ254 nm. In each case, it was established by analysis
of racemic 3 that the enantiomers were fully resolved.
temperature with stirring for 16±24 h afforded the Michael
adducts 2 with good yields and moderate enantioselec-
tivities 731±42% ee) 7Table 2, Scheme 2).
As shown in Table 3, the addition of 2-nitropropane to
chalcone derivatives 1 produced the Michael adduct 3
with 61±94% of yields and 31±71% ee optical purity of
the products. Recrystallization of some of the Michael
adducts from ethanol furnished of 87±99% ee with good
recovery 7Table 3, entries 2±6). In all cases the enantio-
meric excesses were determined by HPLC analysis 7Scheme
3).
1
472, 456, 210, 165; HRMS: calcd forC 35H46N2O2
526.3559, found 526.3563.
1.1.2. O-Allyl-N-'4-methoxy-3,5-di-tert-butylbenzyl)cin-
chonidinium bromide '4b). To a suspension of N-73,5-di-
tert-butyl-4-methoxybenzyl)cinchonidinium bromide 4a
73.03 g, 5.0 mmol) in 40 mL of CH2Cl2 was added allyl
bromide 70.64 mL, 7.5 mmol) and 2.8 mL of 50% of aq.
KOH 725.0 mmol). The resulting mixture was stirred for
5 h. The mixture was diluted with 40 mL of water and
extracted with CH2Cl2 73£40 mL). The combined organic
extracts were dried over MgSO4, ®ltered and concentrated
in vacuo. The residue was puri®ed by chromatography on
silica gel 793:7, dichloromethane/methanol) to give product
In conclusion, we have developed a new class of asymmetric
phase-transfer catalysts, which show moderate enantio-
selectivity in the Michael reaction of nitroalkane to chalcones.
We are currently involved in the further development of
these catalyst systems and are investigating their applica-
bility to other asymmetric phase-transfer processes.
4b 792%, 2.98 g) as a yellow solid: [a]25 ˆ2142.5 7cˆ2,
1. Experimental
1.1. General
D
CHCl3); mp 220±2218C; IR7®lm, cm21) 3407, 3000, 2949,
1704, 1625, 1596, 1567, 1510, 1502, 1491, 1470, 1454,
1
1400, 1350, 1210. 1115, 1070, 1010; H NMR 7CDCl3,
1H NMR spectra were recorded on Bruker AC 300 and AC
200F spectrometers. 13C NMR spectra were recorded at
50 MHz on a Bruker AC 200F spectrometer. Optical
rotations were measured with a JASCO-DIP-1000 digital
polarimeter. Melting points were determined using an
electrothermal apparatus and are uncorrected. Mass spectra
were recorded on Shimadzu QP 5050A and Jeol HX 100/
110 instruments. Chiral HPLC analyses were carried out using
300 MHz) d 1.47±1.50 7s, 19H), 2.09±2.17 7m, 3H), 2.63
7s, 1H), 3.34±3.47 7m, 3H), 3.75 7s, 3H), 4.01 7m, 1H), 4.28
7m, 2H), 4.64 7d, Jˆ11.5 Hz, 2H), 5.01 7d, Jˆ8.4 Hz, 1H),
5.05 7d, Jˆ10.5 Hz, 1H), 5.32±5.43 7m, 3H), 5.77 7m, 1H),
6.18 7m, 1H), 6.23 7s, 1H), 6.31 7d, Jˆ11.5 Hz, 1H), 7.70 7s,
3H), 7.80 7t, Jˆ7.4 Hz, 1H), 7.93 7m, 1H), 8.14 7d, Jˆ
8.39 Hz, 1H), 8.71 7d, Jˆ8.48 Hz, 1H), 8.97 7d, Jˆ
4.39 Hz, 1H); 13C NMR 7CDCl3, 50 MHz) d 20.99, 22.54,

8936
D. Y. Kim, S. C. Huh / Tetrahedron 57 ,2001) 8933±8938
25.28, 27.02, 31.99, 35.92, 37.77, 42.30, 51.04, 59.39,
60.31, 62.72, 64.34, 65.73, 70.30, 115.55, 118.40, 119.17,
120.04, 121.14, 124.40, 125.10, 129.10, 129.85, 130.28,
132.37, 132.47, 136.29, 139.88, 144.82, 148.40, 149.40,
161.18; MS 7EI) m/z 567, 470, 394, 268, 167; HRMS:
NMR 7CDCl3, 200 MHz) d 1.54 7s, 3H), 1.63 7s, 3H),
3.27 7dd, Jˆ3.2 and 3.6 Hz, 1H), 3.67 7dd, Jˆ10.4 and
10.3 Hz, 1H), 4.15 7dd, Jˆ3.4 and 3.4 Hz, 1H), 7.25±7.85
7m, 10H); 13C NMR 7CDCl3, 50 MHz) d 195.8, 133.2,
129.2, 128.6, 128.4, 127.9, 127.7, 92.1, 48.9, 39.1, 26.1,
22.5; MS 7EI) m/z 250, 207, 105, 77; HRMS: calcd for
C18H19NO3 297.1365, found 297.1369; HPLC 790:10,
hexane/iso-PrOH, 254 nm, 1.2 mL min21) Chiralcel OJ
column, tRˆ25.8 min 7major), tRˆ35.4 min 7minor).
1
calcd forC 38H50N2O2 566.3872, found 566.3869.
1.2. General procedure for the Michael addition of
nitroalkanes to chalcones
1.2.5. 4-Methyl-4-nitro-3-phenyl-1-'4-tri¯uoromethyl-
phenyl)pentan-1-one '3b). Rf 0.46 7EtOAc/hexaneˆ1:8);
A mixture of nitroalkane 71.16 mmol), t-BuOK 719.6 mg,
0.17 mmol), chiral cinchonidinium salt 4b 722.6 mg,
0.035 mmol), and chalcone 70.5 mmol) in toluene 72 mL)
was stirred at room temperature for 14±20 h. The mixture
was diluted with water710 mL) and extarcted with ethyl
acetate 72£10 mL). The combined organic layers were
dried over MgSO4, ®ltered, concentrated, and puri®ed by
¯ash chromatography 7silica gel, ethyl acetate/hexaneˆ1:8)
to afford the Michael adduct.
1
[a]25 ˆ219.4 7cˆ1.0, CHCl3, 39% ee); mp 89±928C; H
D
NMR 7CDCl3, 200 MHz) d 1.54 7s, 3H), 1.63 7s, 3H), 3.28
7dd, Jˆ3.5 and 3.2 Hz, 1H), 3.68 7dd, Jˆ10.3 and 10.3 Hz,
1H), 4.13 7dd, Jˆ2.8 and 3.2 Hz, 1H), 7.26±7.97 7m, 9H);
13C NMR 7CDCl3, 50 MHz) d 199.4, 129.1, 128.5, 128.3,
127.9, 125.7, 91.0, 48.9, 39.4, 26.3, 22.6; MS 7EI) m/z 320,
173, 145, 131, 91, 77; HRMS: calcd forC 19H18F3NO3
365.1239, found 365.1247; HPLC 790:10, hexane/iso-
PrOH, 254 nm, 1.2 mL min21) Chiralcel OD-H column,
tRˆ6.6 min 7minor), tRˆ7.8 min 7major). One recrystalli-
1.2.1. 'S)-4-Nitro-1,3-diphenyl-butane-1-one '2a). Rf 0.41
7EtOAc/hexaneˆ1:8); [a]25 ˆ29.3 7cˆ1.0, CHCl3, 35%
D
zation from ethanol gave colorless crystals: [a]25 ˆ237.4
1
ee); mp 101±1038C; H NMR 7CDCl3, 200 MHz) d 3.46
D
7cˆ1.0, CHCl3), ee 94%.
7d, Jˆ5.2 Hz, 1H), 3.48 7s, 1H), 4.13±4.30 7m, 1H), 4.69
7dd, Jˆ8.0 and 7.8 Hz, 1H), 4.85 7dd, Jˆ6.6 and 6.6 Hz,
1H), 7.25±7.94 7m, 10H); 13C NMR 7CDCl3, 50 MHz) d
195.4, 133.5, 129.0, 128.7, 128.0, 127.8, 127.4, 124.8,
79.5, 41.5, 39.2; MS 7EI) m/z 228, 165, 105, 77; HRMS:
calcd forC 16H15NO3 269.1052, found 269.1048; HPLC
790:10, hexane/iso-PrOH, 254 nm, 1.2 mL min21) Chiralcel
AS column, tRˆ12.7 min 7major), tRˆ16.3 min 7minor).
1.2.6. 1-'4-Bromophenyl)-4-methyl-4-nitro-3-phenylpen-
tan-1-one '3c). Rf 0.47 7EtOAc/hexaneˆ1:8); [a]25
ˆ
D
1
235.2 7cˆ1.0, CHCl3, 59% ee); mp 124±1268C; H NMR
7CDCl3, 200 MHz) d 1.54 7s, 3H), 1.63 7s, 3H), 3.22 7dd,
Jˆ3.4 and 3.1 Hz, 1H), 3.65 7dd, Jˆ10.3 and 10.3 Hz, 1H),
4.13 7dd, Jˆ3.3 and 3.4 Hz, 1H), 7.20±7.97 7m, 9H); 13C
NMR 7CDCl3, 50 MHz) d 196.4, 137.6, 136.1, 131.0 130.2,
129.1, 128.5, 127.8, 126.4, 91.0, 48.8, 39.1, 26.2, 22.4; MS
7EI) m/z 330, 183, 131, 91, 76; HRMS: calcd for
C18H18BrNO3 375.0470, found 375.0477; HPLC 790:10,
hexane/iso-PrOH, 254 nm, 1.2 mL min21) Chiralcel OD-H
column, tRˆ7.4 min 7major), tRˆ8.4 min 7minor). One
recrystallization from ethanol gave colorless crystals:
1.2.2. 'S)-3-'4-Chlorophenyl)-4-nitro-1-phenylbutane-1-
one '2b). Rf 0.42 7EtOAc/hexaneˆ1:8); [a]25 ˆ210.8
D
7cˆ1.0, CHCl3, 42% ee), lit.11 [a]23 ˆ117.9 7cˆ1.0,
D
CH2Cl2, 70% ee, major7 R)); mp 108±1108C [lit.11 110±
1
1128C]; H NMR 7CDCl3, 200 MHz) d 3.43 7d, Jˆ7.0 Hz,
2H), 4.14±4.30 7m, 1H), 4.65 7dd, Jˆ8.0 and 8.0 Hz, 1H),
4.82 7dd, Jˆ6.4 and 6.0 Hz, 1H), 7.21±7.91 7m, 9H); 13C
NMR 7CDCl3, 50 MHz) d 196.4, 137.5, 136.1, 133.6, 129.2,
128.8, 128.7, 127.9, 79.3, 41.3, 38.6; MS 7EI) m/z 258, 207,
105, 77; HRMS: calcd forC 16H14ClNO3 303.0662, found
303.0669; HPLC 790:10, hexane/iso-PrOH, 254 nm,
[a]25 ˆ247.9 7cˆ1.0, CHCl3), ee 87%.
D
1.2.7. 4-Methyl-4-nitro-3-phenyl-1-thiophen-2-ylpentan-
1-one '3d). Rf 0.48 7EtOAc/hexaneˆ1:8); [a]25 ˆ227.5
7cˆ1.0, CHCl3, 57% ee); mp 122±1258C; 1DH NMR
7CDCl3, 200 MHz) d 1.54 7s, 3H), 1.61 7s, 3H), 3.21 7dd,
Jˆ3.6 and 3.2 Hz, 1H), 3.59 7dd, Jˆ10.4 and 10.4 Hz, 1H),
4.12 7dd, Jˆ3.6 and 3.2 Hz, 1H), 7.11 7dd, Jˆ4.0 and
4.4 Hz, 1H), 7.22±7.30 7m, 5H), 7.60 7dd, Jˆ0.4 and
1.2 Hz, 1H), 7.72 7dd, Jˆ0.8 and 0.8 Hz, 1H); 13C NMR
7CDCl3, 50 MHz) d 189.5, 133.9, 131.9, 129.1, 128.4,
128.0, 127.8, 91.1, 49.1, 39.7, 26.0, 22.5; MS7EI) m/z 257,
165, 111, 77; HRMS: calcd forC 16H17NO3S 303.0929,
found 303.0933; HPLC 790:10, hexane/iso-PrOH, 254 nm,
1.2 mL min21) Regis Whelk-O1 column, tRˆ16.1 min
7major), tRˆ27.2 min 7minor).
1.2 mL min21
7major), tRˆ25.3 min 7minor).
)
Chiralcel AD column, tRˆ16.7 min
1.2.3. 3-Naphthalen-2-yl-4-nitro-1-phenylbutane-1-one
'2c). Rf 0.38 7EtOAc/hexaneˆ1:8); [a]25 ˆ27.4 7cˆ1.0,
D
CHCl3, 31% ee); mp 129±1338C; 1H NMR 7CDCl3,
200 MHz) d 3.56 7dd, Jˆ3.7 and 2.8 Hz, 1H), 3.67 7t, Jˆ
3.3 Hz, 1H), 4.30±4.45 7m, 1H), 4.79 7dd, Jˆ8.0 and
8.1 Hz, 1H), 4.91 7dd, Jˆ6.7 and 6.7 Hz, 1H), 7.39±7.96
7m, 12H); 13C NMR 7CDCl3, 50 MHz) d 196.7, 136.4,
133.5, 133.3, 132.7, 130.8, 128.9, 128.7, 128.0, 127.7,
127.6, 127.3, 126.5, 126.4, 126.1, 125.8, 125.0, 79.5, 62.7,
41.5, 39.3; MS 7EI) m/z 272, 244, 153, 105, 77; HRMS:
calcd forC 20H17NO3 319.1208, found 319.1212; HPLC
790:10, hexane/iso-PrOH, 254 nm, 1.2 mL min21) Chiralcel
AD column, tRˆ15.7 min 7major), tRˆ19.3 min 7minor).
1.2.8. 1-Furan-2-yl-4-methyl-4-nitro-3-phenylpentan-1-
one '3e). Rf 0.48 7EtOAc/hexaneˆ1:8); [a]25 ˆ232.1 7cˆ
D
1
1.0, CHCl3, 61% ee); mp 121±1238C; H NMR 7CDCl3,
200 MHz) d 1.53 7s, 3H), 1.62 7s, 3H), 3.08 7dd, Jˆ3.6
and 3.6 Hz, 1H), 3.59 7dd, Jˆ10.4 and 10.8 Hz, 1H), 4.12
7dd, Jˆ3.6 and 3.2 Hz, 1H), 6.50 7dd, Jˆ1.2 and 2.0 Hz,
1H), 7.13 7d, Jˆ3.6 Hz, 1H), 7.20±7.29 7m, 5H), 7.55 7d,
Jˆ1.2 Hz, 1H); 13C NMR 7CDCl3, 50 MHz) d 190.2, 146.3,
1.2.4. 4-Methyl-4-nitro-1,3-diphenylpentan-1-one '3a).
Rf 0.46 7EtOAc/hexaneˆ1:8); [a]25 ˆ230.5 7cˆ1.0,
D
1
CHCl3, 31% ee); mp 147±1498C [lit.6 146±1488C]; H

D. Y. Kim, S. C. Huh / Tetrahedron 57 ,2001) 8933±8938
8937
129.2, 128.4, 127.8, 117.1, 112.3, 91.3, 48.6, 38.7, 25.8,
22.6; MS7EI) m/z 240, 198, 131, 95, 77; HRMS: calcd for
C16H17NO4 287.1158, found 287.1158; HPLC 790:10,
hexane/iso-PrOH, 254 nm, 1.2 mL min21) Regis Whelk-
O1 column, tRˆ16.5 min 7major), tRˆ28.2 min 7minor).
1.2.13. 1-'4-Bromophenyl)-4-methyl-3-naphthalen-2-yl-
4-nitropentan-1-one '3j). Rf 0.40 7EtOAc/hexaneˆ1:8);
[a]25 ˆ247.2 7cˆ1.0, CHCl3, 51% ee); mp 120±1228C;
D
1H NMR 7CDCl3, 200 MHz) d 1.57 7s, 3H), 1.67 7s, 3H),
3.31 7dd, Jˆ3.1 and 3.2 Hz, 1H), 3.75 7dd, Jˆ10.4 and
10.4 Hz, 1H), 4.30 7dd, Jˆ3.3 and 3.3 Hz, 1H), 7.29±7.95
7m, 11H); 13C NMR 7CDCl3, 50 MHz) d 199.0, 131.9,
130.0, 129.5, 128.6, 128.3, 128.2, 127.9, 127.5, 127.0,
126.3, 126.2, 91.2, 49.1, 39.2, 26.5, 22.5; MS 7EI) m/z
378, 337, 257, 181, 152; HRMS: calcd forC 22H20BrNO3
425.0627, found 425.0631; HPLC 790:10, hexane/iso-
PrOH, 254 nm, 0.8 mL min21) Chiralcel AS column,
tRˆ7.9 min 7major), tRˆ8.8 min 7minor). One recrystalliza-
1.2.9. 1-'3-Bromophenyl)-4-methyl-4-nitro-3-phenylpen-
tan-1-one '3f). Rf 0.47 7EtOAc/hexaneˆ1:8); [a]25
ˆ
D
1
242.3 7cˆ1.0, CHCl3, 71% ee); mp 122±1258C; H NMR
7CDCl3, 200 MHz) d 1.53 7s, 3H), 1.62 7s, 3H), 3.22 7dd,
Jˆ3.6 and 1.4 Hz, 1H), 3.65 7dd, Jˆ10.4 and 10.3 Hz, 1H),
4.13 7dd, Jˆ3.0 and 3.4 Hz, 1H), 7.24±7.98 7m, 9H); 13C
NMR 7CDCl3, 50 MHz) d 195.3, 136.1, 130.9, 129.1, 128.7,
128.5, 127.8, 126.4, 91.0, 48.8, 39.1, 26.2, 22.4; MS 7EI)
m/z 330, 183, 131, 91, 76; HRMS: calcd forC 18H18BrNO3
375.0470, found 375.0478; HPLC 790:10, hexane/iso-
PrOH, 254 nm, 1.2 mL min21) Chiralcel OD-H column,
tRˆ7.4 min 7major), tRˆ8.4 min 7minor).
tion from ethanol gave colorless crystals: [a]25 ˆ290.3
D
7cˆ1.0, CHCl3), ee.99%.
1.2.14. 1-'3-Bromophenyl)-4-methyl-3-naphthalen-1-yl-
4-nitropentan-1-one '3k). Rf 0.40 7EtOAc/hexaneˆ1:8);
[a]25 ˆ252.5 7cˆ1.0, CHCl3, 57% ee); mp 120±1238C;
D
1.2.10. 4-Methyl-4-nitro-1-phenyl-3-'4-tri¯uoromethyl-
1H NMR 7CDCl3, 200 MHz) d 1.58 7s, 3H), 1.68 7s, 3H),
3.35 7dd, Jˆ3.2 and 3.2 Hz, 1H), 3.80 7dd, Jˆ10.4 and
10.5 Hz, 1H), 4.33 7dd, Jˆ3.1 and 3.2 Hz, 1H), 7.25±7.95
7m, 11H); 13C NMR 7CDCl3, 50 MHz) d 195.8, 131.8,
129.4, 128.9, 128.5, 126.6, 125.8, 124.8, 124.5, 123.6,
122.7, 120.3, 92.1, 48.9, 39.3, 27.0, 22.0; MS 7EI) m/z
378, 337, 257, 181, 152; HRMS: calcd forC 22H20BrNO3
425.0627, found 425.0631; HPLC 790:10, hexane/iso-
PrOH, 254 nm, 1.2 mL min21) Chiralcel OD-H column,
tRˆ8.5 min 7minor), tRˆ9.2 min 7major).
phenyl)pentan-1-one '3g). Rf 0.46 7EtOAc/hexaneˆ1:8);
[a]25 ˆ220.5 7cˆ1.0, CHCl3, 60% ee); mp 105±1078C;
D
1H NMR 7CDCl3, 200 MHz) d 1.56 7s, 3H), 1.63 7s, 3H),
3.32 7dd, Jˆ3.2 and 3.4 Hz, 1H), 3.69 7dd, Jˆ10.2 and
10.2 Hz, 1H), 4.21 7dd, Jˆ3.2 and 3.2 Hz, 1H), 7.34±7.95
7m, 9H); 13C NMR 7CDCl3, 50 MHz) d 196.2, 136.2, 133.5,
129.5, 128.7, 127.9, 125.4, 125, 90.7, 48.6, 38.8, 25.9, 22.8;
MS7EI) m/z 320, 199, 105,77; HRMS: calcd forC 19H18NO3
365.1239, found 365.1244; HPLC 790:10, hexane/iso-
PrOH, 254 nm, 1.2 mL min21) Chiralcel OJ column, tRˆ
11.3 min 7major), tRˆ15.6 min 7minor).
1.2.15. 1-'4-Bromophenyl)-4-methyl-3-naphthalen-1-yl-
4-nitropentan-1-one '3l). Rf 0.40 7EtOAc/hexaneˆ1:8);
1.2.11. 3-'3-Chloro-4-¯uorophenyl)-4-methyl-4-nitro-1-
[a]25 ˆ244.8 7cˆ1.0, CHCl3, 57% ee); mp 119±1218C;
D
phenylpentan-1-one '3h). Rf 0.48 7EtOAc/hexaneˆ1:8);
1H NMR 7CDCl3, 200 MHz) d 1.58 7s, 3H), 1.68 7s, 3H),
3.30 7dd, Jˆ3.0 and 3.4 Hz, 1H), 3.79 7dd, Jˆ10.4 and
10.4 Hz, 1H), 4.31 7dd, Jˆ3.3 and 3.0 Hz, 1H), 7.26±7.98
7m, 11H); 13C NMR 7CDCl3, 50 MHz) d 195.2, 136.1,
133.0, 132.7, 131.0, 130.2, 128.2, 127.8, 127.5, 127.0,
126.5, 126.3, 126.2, 91.2, 48.8, 39.3, 26.4, 22.4; MS 7EI)
m/z 378, 337, 257, 181, 152; HRMS: calcd forC 22H20BrNO3
425.0627, found 425.0633; HPLC 790:10, hexane/iso-
PrOH, 254 nm, 1.2 mL min21) Chiralcel OD-H column,
tRˆ7.6 min 7minor), tRˆ9.3 min 7major).
[a]25 ˆ236.8 7cˆ1.0, CHCl3, 53% ee); mp 123±1268C;
D
1H NMR 7CDCl3, 200 MHz) d 1.57 7s, 3H), 1.63 7s, 3H),
3.29 7dd, Jˆ3.4 and 3.5 Hz, 1H), 3.60 7dd, Jˆ10.4 and
10.7 Hz, 1H), 4.11 7dd, Jˆ3.3 and 3.3 Hz, 1H), 7.09±7.90
7m, 8H); 13C NMR 7CDCl3, 50 MHz) d 196.1, 136.2, 135.1,
133.5, 131.0, 129.0, 128.8, 128.7, 127.9, 116.8, 116.3, 90.7,
47.9, 38.9, 25.8, 22.9; MS 7EI) m/z 302, 207, 105, 77;
HRMS: calcd forC 18H17ClFNO3 349.0881, found
349.0891; HPLC 790:10, hexane/iso-PrOH, 254 nm,
1.2 mL min21) Chiralcel OJ column, tRˆ26.1 min 7major),
tRˆ35.3 min 7minor). One recrystallization from ethanol
gave colorless crystals: [a]25 ˆ259.4 7cˆ1.0, CHCl3),
D
ee.99%.
References
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D
1H NMR 7CDCl3, 200 MHz) d 1.58 7s, 3H), 1.68 7s, 3H),
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D
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D. Y. Kim, S. C. Huh / Tetrahedron 57 ,2001) 8933±8938
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