8
A. Das et al. / Tetrahedron xxx (2015) 1e9
model (PCM).23 The single point calculations in methanol using the
gas phase optimized geometries with the M06-2X level of theory
show that the Si face attack for the Catalyst-1 is more favourable by
1.2 kcal/mol compared to the Re face attack. Further, the Re face
attack is favourable by 4.9 kcal/mol for Catalyst-3 is in good
agreement with the gas phase results.
(200 MHz, CDCl3) 171.6, 140.1, 128.1, 127.9, 127.8, 127.0, 68.3, 53.1;
HRMS (ESI, m/z) [MþꢁH] found 328.1422 C18H20N2O4 requires
328.1425.
5.2.2. General procedure for synthesis of ligand 2. In a flame dried
single necked round bottom flask, (1R,2R)-(þ)-1,2-diphenyl-1,2-
diaminoethane (424 mg,
2
mmol), freshly dried K2CO3
4. Conclusions
(w100 mg) in dry acetonitrile (30 mL) were taken under nitrogen
atmosphere, to which ethylbromoacetate (0.74 mL, 4.5 mmol) was
added at RT with stirring. The mixture was stirred for 24 h at 70 ꢀC.
The reaction was monitored by TLC and afterward the reaction
mixture was cooled to RT, filtered and the solvent was removed
from the filtrate under reduced pressure. The pure ligand 2 was
obtained by column chromatography (15:85, EtOAc/Hexane);
(360.4 mg, Yield 85%); Yellow colour oil; [Found: C, 68.17; H, 7.22;
This paper has disclosed the synthesis of new chiral ligands 1e4
and used them in copper catalysed asymmetric nitroaldol (Henry)
reaction of trifluoromethyl aryl ketones and aldehydes with nitro-
methane. The DFT calculations revealed the role of non-covalent
interactions and the steric effect towards the origin of enantiose-
lectivity with the variation in the size of the catalysts used in this
study. Optimization of the reaction parameters were carried out
and ligand 3 with highest bulkiness along with diphenyldiamine
collar proved to be the best one in combination with Cu(OTf)2 in
case of trifluoromethyl aryl ketones while Cu(OAc)2 as metal source
gave moderate to good yield along with excellent ee of the corre-
sponding nitroaldol products of aldehydes.
N, 7.20. C22H28N2O4 requires C, 68.73; H, 7.34; N, 7.29]; [
a]
25 þ18.25
D
(c 0.5 in CHCl3); nmax (KBr): 3372, 2925, 2362, 1729, 1458, 1378,
1125, 914, 845, 699 cmꢁ1
; dH (200 MHz, CDCl3, TMS) 7.23e6.97 (m,
10H), 4.69e4.65 (d, J¼8 Hz, 2H), 3.77e3.73 (q, 4H), 3.30e3.26 (m,
2H), 1.16e1.12 (m, 6H); dC (200 MHz, CDCl3) 171.0, 135.5, 129.1,
125.3, 114.9, 83.0, 69.3, 28.3; HRMS (ESI, m/z) [MþꢁH] found
385.1242 C22H28N2O4 requires 385.1246.
5. Experimental section
5.2.3. General procedure for synthesis of ligand 3. In a flame dried
single necked round bottom flask, (1R,2R)-(þ)-1,2-diphenyl-1,2-
5.1. Typical experimental procedure for the asymmetric
Henry reaction of trifluoromethyl aryl ketones
diaminoethane (424 mg,
2
mmol), freshly dried K2CO3
(w100 mg) in dry acetonitrile (30 mL) were taken under nitrogen
atmosphere, to which tert-butylbromoacetate (0.88 mL, 4.5 mmol)
was added at RT with stirring. The mixture was stirred for 24 h at
70 ꢀC. The reaction was monitored by TLC and afterward the re-
action mixture was cooled to RT, filtered and the solvent was re-
moved from the filtrate under reduced pressure. The pure ligand 3
was obtained by column chromatography (15:85, EtOAc/Hexane);
(373.2 mg, Yield 88%); Yellow colour oil; [Found: C, 70.86; H, 8.22;
Chiral ligand 3 (5 mol %) and Cu(OTf)2 (5 mol %) were added to
a screw-capped vial containing a stirring magnetic bar. A clear green
solution formed after adding MeOH (1 mL) as solvent, which was
stirred for 24 h at 0 ꢀC. To the resulting solution of desired substrates
trifluoromethyl aryl ketones (0.5 mmol, 1 equiv) were added and
nitromethane (5.0 mmol, 10 equiv) also added into the solution
using N,N-DIPEA (5 mol %) as additive. After running the reaction for
the specified time as given in Table 5 the volatile components were
removed under reduced pressure and the crude product was puri-
fied by flash column chromatography (EtOAc: Hexane 1:9).
N, 6.13. C26H36N2O4 requires C, 70.88; H, 8.24; N, 6.36]; [
a
]
25 þ32.12
D
(c 0.5 in CHCl3); nmax (KBr): 3325, 2978, 2355, 1732, 1453, 1368,
1156, 941, 847, 701 cmꢁ1 dH (200 MHz, CDCl3, 25 ꢀC, TMS)
;
6.99e6.95 (m, 10H), 3.96e3.88 (d, J¼16 Hz, 2H), 3.13e3.06 (d,
J¼14 MHz, 4H), 1.45e1.30 (m, 18H); dC (200 MHz, CDCl3) 170.8,
137.9, 129.2, 127.8, 126.9, 80.0, 65.7, 52.6, 28.2; HRMS (ESI, m/z)
[MþꢁH] found 440.2729 C26H36N2O4 requires 440.2735.
5.1.1. Typical experimental procedure for the asymmetric Henry re-
action of aldehydes. Chiral ligand 3 (0.5 mol %) and Cu(OAc)2$H2O
(0.5 mol %) were added to a screw-capped vial containing a stirring
magnetic bar. A clear green solution formed after adding THF (1 mL)
as solvent, which was stirred at ꢁ5 ꢀC for 24 h. To the resulting
solution of desired substrates aldehydes (0.5 mmol, 1equiv) were
added and nitromethane (5.0 mmol, 10 equiv) also added into the
solution. After running the reaction for the specified time as given
in Table 8 the volatile components were removed under reduced
pressure and the crude product was purified by flash column
chromatography (EtOAc: Hexane 1:9).
5.2.4. General procedure for synthesis of ligand 4. In a flame dried
single necked round bottom flask, (R)-(þ)-1,10-binaphthyl-2,20-di-
amine (426 mg, 1.5 mmol), freshly dried K2CO3 (w100 mg) in dry
acetonitrile (30 mL) were taken under nitrogen atmosphere, to
which tert-butylbromoacetate (0.58 mL, 3 mmol) was added at RT
with stirring. The mixture was stirred for 24 h at 70 ꢀC. The reaction
was monitored by TLC and afterward the reaction mixture was
cooled to RT, filtered and the solvent was removed from the filtrate
under reduced pressure. The pure ligand 4 was obtained by column
chromatography (15:85, EtOAc/Hexane) (289.2 mg, Yield 68%);
Yellow solid; [Found: C, 74.92; H, 7.02; N, 5.24. C32H36N2O4 requires
5.2. Synthesis of ligands 1e4
5.2.1. General procedure for synthesis of ligand 1. In a flame dried
single necked round bottom flask, (1R,2R)-(þ)-1,2-diphenyl-1,2-
C, 74.97; H, 7.08; N, 5.46]; [
a
]
25 þ25.24 (c 0.5 in CHCl3); nmax (KBr)
D
diaminoethane (424 mg,
2
mmol), freshly dried K2CO3
3415, 3344, 2924, 2362, 1740, 16,199, 1431, 1365, 1248, 1156, 810,
(w100 mg) in dry acetonitrile (30 mL) were taken under nitrogen
atmosphere, to which bromoacetate (0.6 mL, 4.5 mmol) was added
at RT with stirring. The mixture was stirred for 24 h at 70 ꢀC. The
reaction was monitored by TLC and cooled to RT, filtered and the
solvent was removed from the filtrate under reduced pressure. The
pure ligand 1 was obtained by column chromatography (15:85,
EtOAc/Hexane); (313.7 mg, Yield 74%); Yellow colour oil; [Found: C,
619 cmꢁ1
; dH (200 MHz, CDCl3, TMS) 7.88e7.10 (m, 12H), 4.06 (s,
4H), 3.30 (s, 2H), 1.47 (s, 18H); dC (200 MHz, CDCl3) 171.0, 145.1,
135.5, 129.1, 125.3, 123.1, 114.9, 83.0, 69.3, 28.3; HRMS (ESI, m/z)
[MþꢁH] found 512.6409 C32H36N2O4 requires 512.6415.
5.3. Computational methods
65.82; H, 6.12; N, 8.15. C18H20N2O4 requires C, 65.84; H, 6.14; N,
We have performed the geometry optimization and frequency
calculations of Catalyst-1 and Catalyst-3 with 2,2,2-trifluoro-1-
phenylethanone and nitromethane with density functional theory
method using B3LYP,24,25 functional and 6-31G(d),26,27 basis set for
25
8.53]; [
a]
þ36.12 (c 0.5 in CHCl3); nmax (KBr) 3642, 3438, 2926,
D
2364, 1732, 1422, 1350, 1135, 700 cmꢁ1
7.13e6.98 (m, 10H), 3.71 (s, 2H), 3.15 (s, 4H), 2.11 (s, 2H); dC
; dH (200 MHz, CDCl3)