Asymmetric Sulfide Oxidation and Sulfoxide Resolution
the mixture was stirred at room temperature overnight (with a
change of the solution color from yellow to colorless, except in the
cases of ligands 2 and 8) and poured into H2O (30 mL). The re-
sulting mixture was extracted with CH2Cl2 (2ϫ30 mL), and the
extract was dried with CaSO4, diluted with hexane, and allowed to
evaporate slowly to yield solid 1–8.
Ti-salan complexes show poorly informative 1H NMR spectra
(broad signals).
General Oxidation Procedure
A: Catalysts Prepared in Situ: The appropriate salan ligand (1.68–
3.0 µmol) and the metal source [Ti(OiPr)4 or VO(acac)2 or
MoO2(acac)2, 2.0 µmol] were combined in CH2Cl2 (2 mL) and
stirred for 30 min. Sulfide (0.1 mmol) was added to the resulting
solution, followed by an appropriate amount of aqueous hydrogen
peroxide (25%), added in one portion. Stirring was continued at
room temperature for 1 h–48 h, the reaction progress being moni-
tored by TLC (eluent: EtOAc/hexane).
(R,R)-N,NЈ-Bis(3,5-di-tert-butylsalicyl)cyclohexane-1,2-diamine (1):
1H NMR (250 MHz, CCl4, 20 °C): δ = 10.17 (s, 2 H, OH), 7.24 (s,
2 H, Ar-H), 6.71 (s, 2 H, Ar-H), 3.98 (d, 2 H, N-CHH-), 3.90 (d,
2 H, N-CHH), 2.44 (2 H, C*H), 2.18, 1.72, 1.62, (6 H, cHex), 1.33,
(s, 18 H, tBu), 1.26 (s, 18 H, tBu) ppm; two cyclohexane protons
are masked by tBu peaks.
B: Preliminarily Prepared Ti Catalysts: The sulfide (0.1 mmol) was
added at the desired temperature to the appropriate Ti-salan cata-
lyst (1 µmol) dissolved in CH2Cl2 (2 mL). The appropriate amount
of aqueous hydrogen peroxide (25%) was then added to the re-
sulting solution in one portion. Stirring was continued at the de-
sired temperature for 1 h–48 h, the reaction progress being moni-
tored by TLC (eluent: EtOAc/hexane). For 0 °C experiments, the
reaction flask was cooled with an ice bath.
(R,R)-N,NЈ-Bis(5-tert-butyl-3-nitrosalicyl)cyclohexane-1,2-diamine
(2): 1H NMR (250 MHz, CCl4, 20 °C): δ = 11.7 (2 H, OH), 8.02
(d, 2 H, Ar-H), 7.72 (d, 2 H, Ar-H), 4.10 (d, 2 H, N-CHH-), 4.04
(d, 2 H, N-CHH-), 2.53 (2 H, C*H), 2.26 (2 H, cHex), 1.39 (s, 18
H, tBu) ppm; some peaks are masked by tBu signals and traces of
THF.
(S,S)-N,NЈ-Bis(3-adamantyl-5-methylsalicyl)cyclohexane-1,2-di-
1
amine (3): H NMR (250 MHz, CCl4, 20 °C): δ = 6.78 (2 H, Ar-
To stop the reaction, the mixture was diluted with water (1 mL).
The organic phase was separated, and volatiles were removed
quickly (in 1–2 min) in a flow of air. The residue was extracted with
CCl4 (8 mL), and the extract was dried with CaSO4 and analyzed
by 1H NMR. The enantiomeric excess values were measured by 1H
NMR with Eu(hfc)3 chiral shift reagent in CCl4 or CCl4/CDCl3.
The absolute configurations were determined by comparison of
Eu(hfc)3-shifted NMR patterns of sulfoxides with those of the sulf-
oxides of known absolute configuration (for details see ref.[7], Sup-
porting Information). The ee measurement uncertainty was Յ1%
(in the range of 10–80% ee) and not higher than 0.5% for Ͼ80% ee.
Conversion and selectivity were calculated from 1H NMR measure-
ments of the sulfide, sulfoxide, and sulfone relative concentrations.
Selected 1H NMR spectroscopic data for the compounds involved,
(250 MHz, CCl4, 20 °C): δ = p-BrPhSCH3 2.45, p-BrPhSOCH3
2.62, p-BrPhSO2CH3 2.94, PhSCH2Ph 4.05, PhSOCH2Ph 3.90 (m),
PhSO2CH2Ph 4.15, p-CH3PhSCH3 2.42, p-CH3PhSCH3 2.31, p-
CH3PhSOCH3 2.57, p-CH3PhSOCH3 2.42, p-CH3PhSO2CH3 2.90,
p-CH3PhSO2CH3 2.46, PhSCH3 2.35, PhSOCH3 2.61, PhSO2CH3
2.92; PhSCH(CH3)2 3.32, PhSOCH(CH3)2 2.64, PhSO2CH(CH3)2
2.92, 2-Naph-SCH3 2.55, 2-Naph-SOCH3 2.68, 2-Naph-SO2CH3
2.99 .
H), 6.53 (2 H, Ar-H), 3.97 (d, 2 H, N-CHH-), 3.83 (d, 2 H, N-
CHH-), 2.39 (2 H, C*H), 2.19 (6 H, Ar-CH3), 2.04 (12 H, Ada-
CH2), 2.00 (6 H, Ada-CH), 1.74 (12 H, Ada-CH2) ppm. Some
peaks masked by intense signals in the range 2.2–2.0 ppm.
(R,R)-N,NЈ-Bis(salicyl)cyclohexane-1,2-diamine (4): 1H NMR
(250 MHz, CCl4, 20 °C): δ = 7.17 (t, 2 H, Ar-H), 6.94 (d, 2 H, Ar-
H), 6.77 (m, 4 H, Ar-H), 4.06 (d, 2 H, N-CHH-), 3.93 (d, 2 H, N-
CHH-), 2.44 (2 H, C*H), 2.20 (2 H, cHex), 1.73 (2 H, cHex), 1.3–
1.1 (4 H, cHex) ppm.
1
(R,R)-N,NЈ-Bis(5-bromosalicyl)cyclohexane-1,2-diamine (5): H
NMR (250 MHz, CDCl3, 20 °C): δ = 7.24 (dd, 2 H, Ar-H), 7.06
(d, 2 H, Ar-H), 6.68 (d, 2 H, Ar-H), 4.03 (d, 2 H, N-CHH-), 3.90
(d, 2 H, N-CHH-), 2.41 (2 H, C*H), 2.17 (2 H, cHex), 1.45 (2 H,
cHex), 1.3–1.1 (4 H, cHex) ppm.
(R,R)-N,NЈ-Bis(3-phenylsalicyl)-1,2-diphenylethylenediamine (6): 1H
NMR (250 MHz, CDCl3, 20 °C): δ = 7.47–6.93 (26 H, Ar-H), 3.91
(d, 2 H, N-CHH-), 3.90 (s, 2 H, C*H), 3.60 (d, 2 H, N-CHH-)
ppm.
(S,S)-N,NЈ-Bis(3-phenylsalicyl)cyclohexane-1,2-diamine (7): 1H
NMR (250 MHz, CDCl3, 20 °C): δ = 7.54, 7.39, 7.25, 6.95, 6.83
(16 H, Ar-H), 4.10 (d, 2 H, N-CHH-), 3.96 (d, 2 H, N-CHH-),
2.50 (2 H, C*H), 2.20 (2 H, cHex), 1.72 (2 H, cHex), 1.25 (4 H,
cHex) ppm.
Kinetic Resolution Procedure: PhSOCH2Ph (0.1 mmol) was added
at room temperature to the Ti-7 catalyst (1 µmol) dissolved in
CH2Cl2 (2 mL). Aqueous hydrogen peroxide (25%, 64 µmol) was
added in one portion to the resulting solution. Stirring was contin-
ued at the desired temperature for 16 h. The reaction products were
separated as described for the general oxidation procedure and
(R,R)-N,NЈ-Bis(5-nitro-3-phenylsalicyl)cyclohexane-1,2-diamine (8):
1H NMR (250 MHz, CDCl3, 20 °C): δ = 8.15 (d, 2 H, Ar-H), 7.88
(d, 2 H, Ar-H), 7.48, 7.36 (10 H, Ar-H), 4.20 (d, 2 H, N-CHH-),
4.04 (d, 2 H, N-CHH-), 2.45 (2 H, C*H), 2.23 (2 H, cHex), 1.78
(2 H, cHex), 1.26 (4 H, cHex) ppm.
1
were analyzed by H NMR spectroscopy.
Supporting Information (see also the footnote on the first page of
this article) includes the mathematical treatment of the model ki-
netic scheme for the tandem sulfoxidation/kinetic resolution pro-
cess.
(R,R)-N,NЈ-Bis(3-phenylsalicylmethyl)cyclohexane-1,2-diamine (7Ј):
This compound was prepared by Mannich condensation of (R,R)-
N,NЈ-dimethylcyclohexane-1,2-diamine with biphenyl-2-ol
(2 equiv.) and purified by column chromatography on SiO2 (eluent:
hexane/ethyl acetate).[12e] 1H NMR (250 MHz, CDCl3, 20 °C): δ =
7.5–6.8 (16 H, Ar-H), 3.90 (d, 2 H, N-CHH-), 3.64 (d, 2 H, N- Acknowledgments
CHH-), 2.72 (2 H, C*H), 2.27 (6 H, N-CH3), 1.8 (2 H, cHex) ppm.
Some signals not found (masked by admixtures of ethyl acetate and
butyl acetate).
The authors thank the Russian Foundation for Basic Research for
financial support, grant 06-03-32214.
Preparation of Bis(µ-oxo) Binuclear Ti-Salan Complexes: Ti-salan
complexes Ti-4 to Ti-8 were prepared by a procedure described in
ref.[6d] and were recrystallized from CH2Cl2/hexane at +4 °C. The
[1] a) G. Solladie, Synthesis 1981, 185–196; b) M. R. Barbachyn,
C. R. Johnson, in: Asymmetric Synthesis (Ed.: J. D. Morrison),
Eur. J. Org. Chem. 2008, 3369–3376
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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