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M.K. Choudhary et al. / Journal of Molecular Catalysis A: Chemical 409 (2015) 85–93
4-tert-butyl-2,6-diformylphenol from Aldrich Chemicals were used
as received without any further purification. All N-tosylaldimines
were prepared according to the methods reported in literature
[22]. Solvents used in the present study were dried by known
purification technique [23]. Chemical reactions were conducted
under anhydrous conditions using nitrogen atmosphere and
oven-dried glassware’s unless otherwise stated. FTIR spectra were
recorded on a PerkinElmer Spectrum GX spectrophotometer as
KBr pellet. Electronic spectra of the chiral Schiff base-Cu(II) com-
plexes were recorded in THF by UV–vis-NIR spectrophotometer.
Enantiomeric excess (ee) and diastereomeric excess of the prod-
ucts were determined by using programmable high performance
liquid chromatography (HPLC, Shimadzu SCL-10AVP). 200 MHz or
500 MHz spectrometers were used for the 1H and 13C NMR spectra.
Chemical shifts were reported in ppm from tetramethylsilane
with the solvent resonance as the internal standard (CDCl3 = 7.26).
Spectra are reported as follows: chemical shift (ppm), multiplicity
(s = singlet, d = doublet, t = triplet, br = broad singlet, q = quartet,
m = multiplet), coupling constants (Hz), integration and assign-
ment. High-resolution mass spectra were obtained with a LC–MS
(Q-TOFF) Model make Ultra flex TOF/TOF, Burker Daltonics,
Germany instruments. The product ˇ-nitro-N-tosylaldamines
were purified with flash chromatography using silica gel 60–200
mesh purchased from SD Fine-Chemicals Limited, Mumbai (India).
ring magnetic bar. A clear green solution formed after adding
anhydrous toluene (1 mL) as solvent was stirred for 4 h at RT
´
˚
under the N2-atmosphere using 4 A molecular sieve (50 mg).
added followed by addition of nitroalkanes like nitromethane,
nitroethane, 1-nitropropane and 1-nitropentane (5.0 mmol, 10
equiv). After running the reaction for the specified time as given in
Tables 1–4, the volatile components were removed under reduced
pressure and the crude product was purified by flash column chro-
matography.
2.4. Recycling of the catalyst Cu(II)–L2
At the end of the catalytic reaction (checked on TLC), the sol-
vent was completely removed from the reaction medium under
reduced pressure and the resulting mass was extracted with hex-
ane/ethylacetate (90:10) to remove the reactants and product. The
remaining solid was further washed with hexane for five times,
dried under reduced pressure for 3-4 h, and used as recovered cata-
lysts for recycling experiments of an asymmetric aza Henry reaction
of 1b as a representative substrate with nitromethane.
3. Results and discussions
In quest of developing highly active and enantioselective
catalysts for asymmetric aza-Henry reaction, we have synthe-
sized chiral Schiff base ligands L1-L6 by the condensation of
2-aminodiphenylethanol, (1R,2S)-(−)-2-aminodiphenylethanol (1
equi. for L1), (R or S)-valinol, (S)-2-amino-1,1-diphenylpropan-1-
ol and (1R,2S)-1-amino-2,3-dihydro-1H-inden-2-ol in quantitative
yields by reported method (Scheme 1) [25]. Chiral Schiff base lig-
ands were characterised by physicochemical techniques.
In our initial studies on asymmetric aza Henry reaction, we
have investigated the efficiency of in situ generated chiral Cu(II)
complex of L1–Cu(II) derived from Schiff base ligand L1 with
Cu(OAc)2·H2O (1:1) as metal source and used it as catalyst (loading
2.2. General method for preparation of Ligands (L1–L6)
Chiral ligands L1, L3–L6 were prepared and characterized
according to the methods reported in the literature [24].
2.2.1. Preparation of Ligands (L2)
To
a
solution
of
4-tert-butyl-2,6-diformylphenol
(250 mg, 1.21 mmol) in dry methanol, chiral (1R,2S)-(−)-2-
aminodiphenylethanol (516 mg, 2.42 mmol) was added and the
resulting solution was vigorously stirred for 2 days at RT. After two
days a yellow coloured solution of the desired ligand was obtained.
The solvent was evaporated under reduce pressure and residue
dried under vacuum, to get the desired ligand L2 in sufficient
amount.
with respect to 1b: 7.5 mol%) with imine 1b as a model sub-
strate and nitromethane as nucleophile in toluene at RT that gave
the desired product in 68% yield and 74% ee (Table 1, entry 1).
Switching over to bis-aminoalcohol ligand L2 resulted into sig-
nificant improvement in product yield (80%) and ee (99%) where
the molar ratio of L2 (7.5 mol%) and Cu(OAc)2·H2O (15 mol%)
was kept 1:2 by keeping other parameters constant. To assess
the role of variation in the steric property of aminoalcohol part
of the Schiff base, we have synthesized ligands L3–L6 by con-
densing 4-tert-butyl-2,6-diformylphenol with (R or S)-valinol,
(S)-2-amino-1,1-diphenylpropan-1-ol and (1R,2S)-1-amino-2,3-
dihydro-1H-inden-2-ol respectively. These modifications however,
resulted in a significant decrease in product yield (35–52%) and
enantioselectivity (25–65%) (entries 3–6). Therefore, the in situ
generated catalyst L2–Cu(II) was chosen for further optimization
of reaction conditions.
2.2.2. Characterization data of the Ligand (L2)
Yellow solid powder, Yield: 90%; 1H NMR (200 MHz, DMSO, ␦
ppm) ␦ 8.44 (s, 2H), 7.65 (s, 2H), 7.28–7.19 (m, 20H), 5.57 (m, 1H),
4.97 (m, 2H), 4.55 (m, 2H), 1.24 (s, 9H); 13C NMR (200 MHz, DMSO,
␦ ppm) ␦ 166.41, 160.61, 142.89, 142.15, 136.08, 134.59, 130.58,
129.49, 129.16, 128.54, 128.14, 127.82, 127.46, 127.26, 126.80,
126.70, 80.45, 77.05, 31.06, 30.88. TOF-MS (ES+) [M + H] calcd. for
(C40H40N2O3) 596.30, found: 597.49. Elemental analysis found: C
80.50, H 6.74, N 4.69; C40H40N2O3 calcd. C 80.51, H 6.76, N 4.69.
2.3. Typical experimental procedure for asymmetric aza-Henry
reaction
Chiral dimeric ligands L1–L6 (7.5 mol%) and Cu(OAc)2·H2O
(15 mol%) were added to a screw-capped vial containing a stir-