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1
crystal; mp = 73 °C; H NMR (300 MHz, CDCl , 30 °C) δ = 7.94 (d,
2.17 (td, J = 2.1, 14.1 Hz, 1H), 1.99 (dt, J = 3.9, 14.1 Hz, 1H), 1.47−
1.24 (m, 4H), 0.92 (t, J = 6.9 Hz, 3H); 13C{ H} NMR (75 MHz,
3
1
J = 7.2 Hz, 2H), 7.59 (t, J = 7.5 Hz, 1H), 7.46 (t, J = 7.8 Hz, 2H), 7.02
(
1
d, J = 8.7 Hz, 2H), 6,67 (d, J = 8.7 Hz, 2H) 5.07 (dd, J = 2.1, 12.3 Hz,
H), 4.96 (t, J = 4.2 Hz, 1H), 4.40 (br s, 1H), 3.97 (dd, J = 4.2, 12.3
CDCl , 30 °C) δ = 201.0, 140.5, 137.3, 134.5, 129.7, 129.2, 128.9,
3
127.9, 127.4, 92.4, 66.3, 45.6, 41.5, 34.2, 33.0, 32.2, 19.8, 14.0; IR
−1
Hz, 1H), 3.67 (s, 3H), 2.71 (br s, 1H), 2.60−2.53 (m, 1H), 2.17 (br t,
J = 14.1 Hz, 1H), 1.98 (dt, J = 3.6, 14.4 Hz, 1H), 1.47−1.23 (m, 4H),
(KBr) 3555, 2961, 2923, 1685, 1589, 1544, 1272, 1093, 702 cm ;
−
HR-MS ESI exact mass calcd for C H NO Cl [M − H] 400.1316,
22
23
4
.92 (t, J = 6.9 Hz, 3H); 13C{ H} NMR (75 MHz, CDCl , 30 °C) δ =
1
found 400.1320; [α]
25
= −102 (c = 0.01 in chloroform, 98% ee).
0
2
5
2
7
3
3
D
02.6, 158.9 136.3, 133.9, 129.4, 128.9, 128.5, 128.3, 114.2, 92.7, 66.4,
5.0, 45.6, 40.8, 34.3, 33.0, 32.1, 19.8, 14.0; IR (KBr) 3483, 2957,
929, 1672, 1613, 1544, 1514, 1447, 1375, 1343, 1251, 1180, 1034,
Enantioselectivity was determined by HPLC analysis with a Chiralpak
OD column, 20% ethyl alcohol in hexane, 1.0 mL/min, λ = 211 nm,
retention times minor 9.5 min, major 11.5 min.
−
1
−
00 cm ; HR-MS ESI exact mass calcd for C H NO [M − H]
((1R,2S,3S,4S,6S)-6-Hydroxy-3-nitro-2-phenyl-4-propylcyclohex-
23
26
5
96.1811, found 396.1820; [α]25 = −76 (c = 0.01 in chloroform,
99% ee). Enantioselectivity was determined by HPLC analysis with a
yl)-p-tolylmethanone (13g): yield 51% (109 mg); white crystal; mp =
D
1
>
192 °C; H NMR (300 MHz, CDCl
3
, 30 °C) δ = 7.85 (d, J = 8.1 Hz,
Chiralpak OD column, 10% ethyl alcohol in hexane, 1.0 mL/min, λ =
11 nm, retention times major 10.2 min, minor 14.7 min.
2H), 7.26 (d, J = 7.8 Hz, 2H), 7.17−7.09 (m, 5H), 5.09 (dd, J = 1.8,
12.3 Hz, 1H), 4.99 (t, J = 4.2 Hz, 1H), 4.40 (d, J = 2.1 Hz, 1H), 4.02
(dd, J = 4.2, 12.3 Hz, 1H), 2.72 (br s, 1H), 2.62−2.56(m, 1H), 2.41 (s,
3H), 2.16 (td, J = 1.8, 15.9 Hz, 1H), 1.99 (dt, J = 3.9, 13.8 Hz, 1H),
2
(
(1R,2S,3S,4S,6S)-2-(4-Chlorophenyl)-6-hydroxy-3-nitro-4-
propylcyclohexyl)phenylmethanone (13c): yield 42% (95 mg); white
1
13
1
crystal; mp = 144 °C; H NMR (300 MHz, CDCl , 30 °C) δ = 7.94
1.47−1.24 (m, 4H), 0.93 (t, J = 6.6 Hz, 3H); C{ H} NMR (75 MHz,
3
(
d, J = 7.2 Hz, 2H), 7.62 (t, J = 7.2 Hz, 1H), 7.49 (t, J = 7.8 Hz, 2H),
CDCl , 30 °C) δ = 201.9 145.1, 137.5, 133.7, 129.6, 128.8, 128.5,
3
7
1
2
1
.18−7.03 (m, 4H), 5.06 (dd, J = 2.1, 12.3 Hz, 1H), 4.96 (t, J = 4.2 Hz,
H), 4.44 (br s, 1H), 4.02 (dd, J = 4.2, 12.3 Hz, 1H), 2.59−2.52 (m,
H), 2.17 (t, J = 13.5 Hz, 1H), 1.99 (dt, J = 3.9, 14.1 Hz, 1H), 1.47−
127.7, 127.4, 92.6, 66.4, 45.2, 41.5, 33.2, 33.1, 32.1, 21.7, 19.8, 14.0; IR
(KBr) 3491, 2960, 2926, 1682, 1668, 1606, 1548, 1280, 1181, 700
−
1
−
cm ; HR-MS ESI exact mass calcd for C H NO Cl [M + Cl]
2
3
27
4
13
1
25
.24 (m, 4H), 0.93 (t, J = 6.9 Hz, 3H); C{ H} NMR (75 MHz,
416.1629, found 416.1627; [α] = −116 (c = 0.01 in chloroform,
D
CDCl , 30 °C) δ = 201.8, 136.1, 136.0, 134.1, 133.7, 129.1, 129.0,
1
>99% ee). Enantioselectivity was determined by HPLC analysis with a
Chiralpak IA column, 30% ethyl alcohol in hexane, 1.0 mL/min, λ =
211 nm, retention times minor 9.0 min, major 13.3 min.
3
28.8, 128.3, 92.3, 66.3, 45.6, 40.9, 34.2, 33.0, 32.2, 19.8, 14.0 ppm; IR
−1
(
KBr) 3435, 2955, 2928, 1686, 1545, 1492, 1374, 1013, 698 cm ;
−
HR-MS ESI exact mass calcd for C H NO Cl [M − H] 400.1316,
((1R,2S,3S,4S,6S)-4-Ethyl-6-hydroxy-3-nitro-2-phenylcyclohexyl)-
22
23
4
found 400.1316; [α]25 = −76 (c = 0.01 in chloroform, >99% ee).
phenylmethanone (13k): yield 65% (128 mg); white crystal; mp =
D
1
Enantioselectivity was determined by HPLC analysis with a Chiralpak
OD column, 10% ethanol in hexane, 1.0 mL/min, λ = 211 nm,
retention times major 8.8 min, minor 11.4 min.
172 °C; H NMR (300 MHz, CDCl
3
, 30 °C) δ = 7.95 (d, J = 7.5 Hz,
2H), 7.60 (t, J = 7.8 Hz, 1H), 7.47 (t, J = 7.8 Hz, 2H), 7.15−7.10 (m,
5H), 5.13 (dd, J = 2.1, 12.3 Hz, 1H), 5.04 (t, J = 4.2 Hz, 1H), 4.43 (d,
J = 2.4 Hz, 1H), 4.03 (dd, J = 4.2, 12.3 Hz, 1H), 2.52−2.45 (m, 2H),
2.18 (dd, J = 2.1, 14.1 Hz, 1H), 2.01 (dt, J = 3.9, 14.1 Hz, 1H), 1.45−
(
(1R,2S,3S,4S,6S)-6-Hydroxy-3-nitro-4-propyl-2-p-
tolylcyclohexyl)phenylmethanone (l-13d): yield 48% (103 mg);
white crystal; mp = 154 °C; H NMR (300 MHz, CDCl , 30 °C) δ
=
1
13
1
3
1.29 (m, 2H), 1.03 (t, J = 6.9 Hz, 3H); C{ H} NMR (75 MHz,
7.95 (d, J = 7.2 Hz, 2H), 7.60 (t, J = 7.5 Hz, 1H), 7.47 (t, J = 7.8 Hz,
H), 7.01−6.93 (m, 4H), 5.10 (dd, J = 1.8, 12.3 Hz, 1H), 4.97 (t, J =
CDCl , 30 °C) δ = 202.3, 137.4, 136.1, 133.9, 128.88, 128.85, 128.3,
3
2
4
2
127.8, 127.5, 92.1, 66.3, 45.4, 41.5, 35.1, 32.0, 25.1, 11.4; IR (KBr)
−1
.2 Hz, 1H), 4.41 (br s, 1H), 3.99 (dd, J = 4.5, 12.3 Hz, 1H), 2.63−
3531, 2967, 1686, 1541, 1371, 1286, 1273, 698 cm ; HR-MS ESI
−
.55 (m, 2H), 2.19 (s, 3H), 1.98 (dt, J = 3.9, 14.1 Hz, 1H), 1.50−1.21
exact mass calcd for C H NO [M − H] 352.1549, found 352.1550;
21
22
4
m, 4H), 0.92 (t, J = 6.9 Hz, 3H); 13C{ H} NMR (75 MHz, CDCl ,
1
25
(
[α] = −72 (c = 0.01 in chloroform, >99% ee). Enantioselectivity
3
D
3
9
2
0 °C) δ = 202.4, 137.4, 136.2, 134.4, 133.9, 126.6, 128.9, 128.4, 127.3,
was determined by HPLC analysis with a Chiralpak IA column, 10%
ethyl alcohol in hexane, 1.0 mL/min, λ = 211 nm, retention times
minor 15.5 min, major 17.1 min.
2.7, 66.4, 45.5, 41.2, 34.3, 33.0, 32.2, 20.9, 19.8, 14.0; IR (KBr) 3449,
−1
957, 2929, 1681, 1546, 1449, 1375, 700 cm ; HR-MS ESI exact mass
−
25
calcd for C H NO Cl [M + Cl] 416.1629, found 416.1629; [α]
=
determined by HPLC analysis with a Chiralpak OD column, 10% ethyl
alcohol in hexane, 1.0 mL/min, λ = 211 nm, retention times major 8.9
min, minor 11.3 min.
((1R,2S,3S,4S,6S)-6-Hydroxy-3-nitro-2,4-diphenylcyclohexyl)-
23
27
4
D
−78 (c = 0.01 in chloroform, >99% ee). Enantioselectivity was
phenylmethanone (l-13l): yield 27% (61 mg); white crystal; mp =
1
234 °C; H NMR (300 MHz, CDCl
, 30 °C) δ = 7.99 (d, J = 7.5 Hz,
3
2H), 7.62 (t, J = 7.2 Hz, 1H), 7.49 (t, J = 7.5 Hz, 2H), 7.34−7.27 (m,
5H), 7.15 (br s, 5H), 5.22 (d, J = 12.0 Hz, 1H), 5.13 (br s, 1H), 4.62
(br s, 1H), 4.26 (dd, J = 3.6, 12.0 Hz, 1H), 3.98 (br d, J = 13.2 Hz,
1H), 3.00 (t, J = 13.5 Hz, 1H), 2.81 (br s, 1H), 2.20 (br d, J = 13.8 Hz,
(
( 1 R , 2 S , 3 S , 4 S , 6 S ) - 6 -H y d r o x y -3 - n i t r o - 2 - p h e n y l - 4 -
propylcyclohexyl)(4′-methoxyphenyl)methanone (13e): yield 41%
1
13
1
(
91 mg); white crystal; mp = 172 °C; H NMR (300 MHz, CDCl , 30
1H); C{ H} NMR (75 MHz, CDCl , 30 °C) δ = 202.1, 138.5, 137.1,
3
3
°
C) δ = 7.95 (d, J = 9.0 Hz, 2H), 7.16−7.09 (m, 5H), 6.93 (d, J = 8.7
136.1, 134.0, 128.94, 128.89, 128.3, 127.86, 127.84, 127.4, 127.3, 94.2,
66.4, 45.1, 41.9, 39.1, 30.6; IR (KBr) 3448, 1655, 1551, 1208, 1057,
Hz, 2H), 5.06 (dd, J = 1.8, 12.3 Hz, 1H), 4.98 (t, J = 4.2 Hz, 1H), 4.38
−
1
(
br s, 1H), 4.02 (dd, J = 4.2, 12.3 Hz, 1H), 3,87 (s, 3H), 2.86 (br s,
701, 688 cm ; HR-MS ESI exact mass calcd for C H NO [M −
2
5
22
4
−
2
5
1
3
H), 2.61−2.56(m, 1H), 2.16(td, J = 1.8, 13.8 Hz, 1H), 1.99 (dt, J =
H] 400.1549, found 400.1550; [α]
= −116 (c = 0.01 in
D
.9, 13.8 Hz, 1H), 1.47−1.24 (m, 4H), 0.92 (t, J = 6.9 Hz, 3H);
chloroform, >99% ee). Enantioselectivity was determined by HPLC
analysis with a Chiralpak IB column, 10% ethyl alcohol in hexane, 1.0
mL/min, λ = 211 nm, retention times major 12.7 min, minor 19.0 min.
((1R,2S,6S)-2-Hydroxy-3-methyl-5-nitro-6-phenylcyclohexyl)-
phenylmethanone (13m−m″) isomer mixture. We were not able to
separate isomers from each other via chromatography. The structures
of the diastereomers were assigned by NMR techniques. The overall
yield of the mixture was 90% (171 mg). The ratio of diastereomers was
19:19:62. To exact mass and enantiomeric excess, the major isomer
could be determined from an enriched sample obtained by preparative
1
3
1
C{ H} NMR (75 MHz, CDCl , 30 °C) δ = 200.8, 164.3, 137.5,
3
1
3
1
30.8, 129.2, 128.8, 127.7, 127.5, 114.1, 92.6, 66.5, 55.5, 44.7, 41.6,
4.3, 33.1, 32.1, 19.8, 14.0; IR (KBr) 3483, 2959, 2927, 1676, 1600,
−1
547, 1257, 1169, 700 cm ; HR-MS ESI exact mass calcd for
−
25
C H NO Cl [M + Cl] 432.1578, found 432.1592; [α] = −140 (c
=
HPLC analysis with a Chiralpak IA column, 30% ethyl alcohol in
hexane, 1.0 mL/min, λ = 211 nm, retention times minor 10.6 min,
major 24.0 min.
23
27
5
D
0.01 in chloroform, 99% ee). Enantioselectivity was determined by
(
( 1 R , 2 S , 3 S , 4 S , 6 S ) - 6 -H y d r o x y -3 - n i t r o - 2 - p h e n y l - 4 -
thin-layer chromatography.
1
propylcyclohexyl)(4′-chlorophenyl)methanone (13f): yield 41% (93
mg); white crystal; mp = 186 °C; H NMR (300 MHz, CDCl , 30 °C)
δ = 7.87 (d, J = 8.7 Hz, 2H), 7.43 (d, J = 8.4 Hz, 2H), 7.17−7.07 (m,
5
Major component: H NMR (500 MHz, CDCl , 30 °C, major
3
1
isomer) δ = 7.94 (m, 2H), 7.57 (m, 1H), 7.45 (overlapping triplets,
2H),7.13−7.07 (m, 5H), 5.12 (dd J = 12.3, 1.9 Hz, 1H), 5.03 (td, J =
4.7, 1.8 Hz, 1H), 4.11 (br t, J = 1.9 Hz, 1H), 3.97 (dd, J = 12.3, 4.6 Hz,
1H), 2.49 (m, 1H), 2.27 (ddd, J = 15.0, 12.9, 5.0 Hz, 1H), 2.02 (ddd, J
3
H), 5.05 (dd, J = 1.8, 12.3 Hz, 1H), 4.98 (t, J = 4.5 Hz, 1H), 4.41 (d,
J = 2.1 Hz, 1H), 4.01 (dd, J = 4.2, 12.3 Hz, 1H), 2.62−2.56(m, 2H),
E
J. Org. Chem. XXXX, XXX, XXX−XXX