1
46
P. Drabina et al. / Tetrahedron: Asymmetry 26 (2015) 141–147
4
.3.1. (2R,5S)-5-tert-Butyl-5-methyl-2-(pyridine-2-yl)imidazoli-
3J = 4.8 Hz, 1H, Py), 7.70 (m, 2H, Py), 7.20 (m, 1H, Py), 6.87 (br s,
1H, CONH), 3.56 (s, 1H, CH), 2.64 (br s, 1H, NH), 1.70 (s, 3H, CH ),
): d 175.6, 163.6,
148.7, 137.0, 122.6, 119.3, 74.9, 66.9, 34.4, 31.2, 26.3. Anal. Calcd
for C13 O (233.3): C, 66.92; H, 8.21; N, 18.01. Found: C,
67.17; H, 8.14; N, 18.26. HR-MALDI-MS (DHB): calcd for
dine-4-one 8a
3
1
3
Yield: 45%; mp: 125–128 °C; R
f
0.43 (SiO
2
; acetone/AcOEt (1:1;
): d 8.57
m, 1H, Py), 7.73 (m, 1H, Py), 7.43 (d, J = 7.6 Hz, 1H, Py), 7.27 (m,
0.96 (s, 9H, 3ꢁ CH
3 3
); C NMR (100 MHz, CDCl
20
1
v/v); ½
aꢂ
D
3 3
= +48.0 (c 1, CH OH); H NMR (400 MHz, CDCl
3
(
19 3
H N
1
H, Py), 6.81 (br s, 1H, CONH), 5.51 (s, 1H, CH), 2.79 (br s, 1H,
1
3
+
NH), 1.33 (s, 3H, CH
3
), 1.10 (s, 9H, 3ꢁ CH
3
); C NMR (100 MHz,
13 19 3
C H N O m/z 234.1601 ([M+H] ), found 234.1602.
CDCl
5.6, 21.7. Anal. Calcd for C13
N, 18.01. Found: C, 67.22; H, 8.40; N, 17.78. HR-MALDI-MS
3
): d 180.0, 159.5, 149.6, 137.4, 123.8, 121.4, 71.4, 66.5, 38.0,
2
19 3
H N
O (233.3): C, 66.92; H, 8.21;
4
.3.7. (S)-2-(N-Pyridylmethylimino)-3,3-dimethylbutanamide 11
A solution of 2-aminoamide 7 (260 mg; 2 mmol), pyridine-2-
+
(
13 19 3
DHB): calcd for C H N O m/z 234.1601 ([M+H] ), found
carbaldehyde (224 mg; 2.1 mmol) and two drops of acetic acid in
dry methanol (4 mL) was refluxed for 18 h. The solvent was then
distilled off under reduced pressure, and the residue was treated
with CH Cl (10 mL) and extracted with a saturated aqueous solu-
2 2
tion of sodium carbonate (10 mL). The organic layer was dried over
sodium sulfate and concentrated in vacuo. The residue was treated
2
34.1601.
4
.3.2. (2S,5S)-5-tert-Butyl-5-methyl-2-(pyridine-2-yl)imidazoli-
dine-4-one 8b
Yield: 49%; mp: 62–63 °C; R
f
0.33 (SiO
2
; acetone/AcOEt (1:1; v/
): d 8.56
m, 1H, Py), 7.74 (m, 1H, Py), 7.54 (d, J = 8.0 Hz, 1H, Py), 7.27 (m,
20
1
v); ½
aꢂ
3 3
= ꢀ51.0 (c 1.03, CH OH); H NMR (400 MHz, CDCl
D
with toluene (10 mL), filtered off, and dried to afford 0.35 g (80%) of
3
(
20
D
white crystalline solid 11; mp: 191–193 °C, ½
aꢂ
= +12.2 (c 1.03,
1
H, Py), 6.54 (br s, 1H, CONH), 5.57 (s, 1H, CH), 2.56 (br s, 1H,
1
3 3
CH OH); H NMR (400 MHz, CDCl ): d 8.68 (m, 1H, Py), 8.24 (s,
1
3
NH), 1.40 (s, 3H, CH
3
), 1.07 (s, 9H, 3ꢁ CH
3
); C NMR (100 MHz,
1
6
1
1
C
H, CHN), 8.02 (m, 1H, Py), 7.75 (m, 1H, Py), 7.35 (m, 1H, Py),
CDCl
5.4, 18.9. Anal. Calcd for C13
N, 18.01. Found: C, 66.72; H, 8.41; N, 17.89. HR-MALDI-MS
3
): d 180.0, 159.1, 149.4, 137.3, 123.8, 121.3, 69.2, 66.3, 36.2,
.50 (br s, 1H, CONH), 5.99 (br s, 1H, CONH), 3.56 (s, 1H, CH),
2
H
19
N
3
O (233.3): C, 66.92; H, 8.21;
13
.03 (s, 9H, 3ꢁ CH
3 3
); C NMR (100 MHz, CDCl ): d 173.9, 163.1,
54.0, 149.8, 136.8, 125.4, 121.4, 83.7, 35.3, 27.3. Anal. Calcd for
O (219.3): C, 65.73; H, 7.81; N, 19.16. Found: C, 65.69;
O m/z
+
(
13 19 3
DHB): calcd for C H N O m/z 234.1601 ([M+H] ), found
H N
12 17 3
2
34.1601.
17 3
H, 7.81; N, 19.07. HR-MALDI-MS (DHB): calcd for C12H N
+
2
20.1444 ([M+H] ), found 220.1445.
4
.3.3. (2R,5S)-5-tert-Butyl-2,5-dimethyl-2-(pyridine-2-yl)imidaz-
olidine-4-one 9a
4
.4. General procedure for the asymmetric Henry reaction
Yield: 42%; mp: 112–113 °C; R
f
0.65 (SiO
OH); H NMR (400 MHz, CDCl
3 3
2
; acetone/CH
2
Cl
2
(1:1;
): d
.52 (d, J = 4.4 Hz, 1H, Py), 7.63 (m, 2H, Py), 7.21 (br s, 1H, CONH),
.17 (m, 1H, Py), 2.70 (br s, 1H, NH), 1.63 (s, 3H, CH ), 1.10 (s, 9H,
); C NMR (100 MHz, CDCl ): d 179.7,
65.3, 148.9, 136.9, 122.5, 119.0, 73.7, 66.9, 36.5, 31.2, 25.5, 20.6.
O (247.3): C, 67.99; H, 8.56; N, 16.99.
Found: C, 68.10; H, 8.67; N, 16.81. HR-MALDI-MS (DHB): calcd
2
0
1
v/v); ½
a
ꢂ
= ꢀ51.7 (c 1.01, CH
D
3
A mixture of ligand 8–11 (30
2
lmol) and Cu(OAc) (4.9 mg;
8
7
3
1
2
7 lmol) in the appropriate solvent (1 mL) was stirred for 1 h at
3
13
room temperature. The resulting clear blue/green solution was
cooled at 6 °C, after which nitromethane (0.5 mL) and aldehyde
ꢁ CH
3
), 1.01 (s, 3H, CH
3
3
(
0.5 mmol) were added. The mixture was stirred for the time per-
21 3
Anal. Calcd for C14H N
iod indicated in Tables 1–3. The crude product was isolated by col-
umn chromatography. The enantiomeric excess was determined by
chiral HPLC (using Daicel columns Chiralcel OD-H or Chiralpak AD-
H). The characterization data for enantiomers of nitroalcohols were
+
for C14
21 3
H N O m/z 248.1757 ([M+H] ), found 248.1758.
4
.3.4. (2S,5S)-5-tert-Butyl-2,5-dimethyl-2-(pyridine-2-yl)imidaz-
6
,7
in accordance with the literature.
olidine-4-one 9b
Yield: 31%; mp: 108–110 °C; R
f
0.41 (SiO
2
; acetone/CH
2
Cl
2
(1:1;
): d
.51 (d, J = 4.8 Hz, 1H, Py), 7.67 (m, 2H, Py), 7.33 (br s, 1H, CONH),
.16 (m, 1H, Py), 2.31 (br s, 1H, NH), 1.69 (s, 3H, CH ), 1.48 (s, 3H,
); C NMR (100 MHz, CDCl ): d 178.0,
2
0
1
v/v); ½
aꢂ
= +18.0 (c 1.01, CH
3
OH); H NMR (400 MHz, CDCl
3
4.5. Crystallography
D
3
8
7
CH
The X-ray data for colorless crystals of 8a and 11 were obtained
at 150 K using Oxford Cryostream low-temperature device on a
Nonius Kappa CCD diffractometer with Mo
(k = 0.71073 Å), a graphite monochromator, and the / and
mode. Data reductions were performed with DENZO-SMN.
absorption was corrected by integration methods.
were solved by direct methods (Sir92) and refined by full matrix
least-square based on F (SHELXL97).
3
13
3
), 0.89 (s, 9H, 3ꢁ CH
3
3
1
64.3, 148.8, 136.8, 122.4, 119.1, 73.9, 67.0, 37.3, 33.9, 25.6, 23.4.
Anal. Calcd for C14 O (247.3): C, 67.99; H, 8.56; N, 16.99.
Found: C, 68.05; H, 8.64; N, 16.79. HR-MALDI-MS (DHB): calcd
K
a
radiation
H
21
N
3
v
scan
The
1
4a
+
14b
for C14
H
21
N
3
O m/z 248.1757 ([M+H] ), found 248.1758.
Structures
1
4c
2
14d
4
.3.5. (2R,5S)-5-tert-Butyl-2-methyl-2-(pyridine-2-yl)imidazoli-
Hydrogen atoms were
dine-4-one 10a
mostly localized on a difference Fourier map, however to ensure
uniformity of treatment of crystal, all hydrogen atoms were
recalculated into idealized positions (riding model) and assigned
temperature factors Hiso(H) = 1.2 Ueq (pivot atom) or of 1.5 Ueq
(methyl). H atoms in methyl, methine moieties and hydrogen
atoms in aromatic rings were placed with C–H distances of 0.96,
Yield: 17%; yellow oil; R
f
0.52 (SiO
OH); H NMR (400 MHz, CDCl
3 3
2
; acetone/CH
2
Cl
): d 8.53 (m,
H, Py), 7.68 (m, 1H, Py), 7.62 (m, 1H, Py), 7.19 (m, 1H, Py), 6.69 (br
s, 1H, CONH), 3.12 (s, 1H, CH), 2.61 (br s, 1H, NH), 1.68 (s, 3H, CH ),
): d 176.9, 163.7,
49.4, 137.1, 122.7, 118.7, 74.6, 66.8, 33.4, 30.1, 26.4. Anal. Calcd
O (233.3): C, 66.92; H, 8.21; N, 18.01. Found: C,
6.84; H, 8.44; N, 18.06. HR-MALDI-MS (DHB): calcd for
2
(1:1; v/v);
2
D
0
1
½
a
1
ꢂ
= ꢀ28.4 (c 0.5, CH
3
1
3
1
1
.09 (s, 9H, 3ꢁ CH
3 3
); C NMR (100 MHz, CDCl
0.98 and 0.93 Å. Hydrogen atoms of NH groups in 8a and NH
2
for C13
H
19
N
3
group in 11 were assigned from the Fourier difference map. Rint
=
P
P
P
2
2
2
2
2 2
½
6
C
|F
o
ꢀ Fo,mean|/
F
o
, GOF = [ (w(F
o
ꢀ F
c
) )/(Ndiffrs ꢀ Nparams)] for
P
P
P
+
2
H
19
N
3
O m/z 234.1601 ([M+H] ), found 234.1601.
all data, R(F) = ||F
o
| ꢀ |F
c o
||/ |F | for observed data, wR(F ) = [ (w
13
P
2
2 2
2 2 ½
(F
o
ꢀ F
c
) )/( w(F
o
) )] for all data. Crystallographic data for struc-
4
.3.6. (2S,5S)-5-tert-Butyl-2-methyl-2-(pyridine-2-yl)imidazoli-
tural analysis have been deposited with the Cambridge Crystallo-
graphic Data Centre, CCDC No. 1033971 and 1033970 for 11 and
8a. Copies of this information may be obtained free of charge from
the Director, CCDC, 12 Union Road, Cambridge CB2 1EY, UK
dine-4-one 10b
Yield: 29%; yellow oil; R
f
0.37 (SiO
2
; acetone/CH
2
Cl
2
(1:1; v/v);
2
D
0
1
½
aꢂ
= +5.6 (c 0.52, CH OH); H NMR (400 MHz, CDCl ): d 8.52 (d,
3
3