MIKHEL’ et al.
1204
Results of Pd-catalyzed alkylation of cinnamyl acetate 4
with ethyl 2-oxocyclohexanecarboxylate 5 (20°C, toluene,
48 h, 2 mol % of [Pd(Аll)Cl]2)а
boiling, boiled for 20 min, cooled to 20°C, and filtered
through a short column packed with alumina. The
filtrate was concentrated in a vacuum (40 mmHg), the
reaction product was purified by flash-chromatography
on silica gel, eluent benzene. Yield 0.479 g (64%),
violet powder, mp 160–161°C. Mass spectrum, m/z
(Irel., %): 1497 (35) [M + H]+, 1292 (32), 1088 (20),
884 (11), 680 (17), 205 (86). Found, %: С 70.98; H
5.25; N 11.03. C88H82N12O4P4. Calculated, %: С 70.67;
H 5.53; N 11.24. М 1495.57.
Conversion
of compound 4, %
Enantiomeric excess of
L/Pd
compound 6, %
1 : 4
1 : 2
1 : 1
2 : 1
22
50
95
60
75 (S)
62 (S)
56 (S)
76 (S)
Asymmetric alkylation of cinnamyl acetate (4)
with ethyl 2-oxocyclohexanecarboxylate (5) [20, 21].
A solution of 0.0037 g (0.01 mmol) of [Pd(Аll)Cl]2
and 0.0075 g (0.005 mmol) [or 0.0015 g (0.01 mmol),
or 0.0299 g (0.02 mmol), or 0.0598 g (0.04 mmol)] of
ligand 3 in 5 mL of toluene was stirred for 40 min,
0.08 mL (0.5 mmol) of cinnamyl acetate was added,
and the mixture was stirred for another 15 min, then
0.12 mL (0.75 mmol) of ethyl 2-oxocyclohexanecar-
boxylate, 0.5 mL (2 mmol) of bis(trimethylsilyl)ace-
tamide (BSA), and 0.01 g of zinc acetate was added.
The reaction mixture was stirred for 48 h, diluted with
5 mL of hexane, and filtered through Celite. The
filtrate was concentrated in a vacuum (40 mmHg), the
obtained residue was dried in a vacuum (10 mmHg).
The conversion of substrate 4 and enantiomeric excess
in ethyl (1S)-2-oxo-1-[(2E)-3-phenylprop-2-en-1-yl]-
cyclohexanecarboxylate 6 was estimated by HPLC on
a chiral stationary phase Kromasil 5-CelluCoat.
31Р, 13С, and 1Н (242.9, 150.9, and 600.13 МHz res-
pectively) NMR spectra were registered on a spectro-
meter Bruker Avance III 600. Mass spectra (MALDI
TOF/TOF) were recorded on an instrument Bruker
Daltonics Ultraflex. Enantiomeric analysis of products
of the catalytic reaction was performed on a Sayer
system HPLC. Elemental analysis was carried out on a
CHN microanalyzer Carlo Erba EA1108 CHNS-O.
а
The conversion of cinnamyl acetate 4 and enantiomeric excess in
ethyl (1S)-2-oxo-1-[(2E)-3-phenylprop-2-en-1-yl]cyclohexane-
carboxylate 6 was estimated by HPLC [Kromasil 5-CelluCoat,
C6H14–i-PrOH, 95 : 5, 0.4 mL/min, 254 nm, tr(R) 14.3 min, tr(S)
16.4 min].
the signal at 130.9 ppm corresponding to the carbon
atoms of pyrrole ring was ~150 Hz. Both effects are obser-
ved in a wide range of concentrations (5–20 mg mL–1)
of compound 3 solution in C6D6 and CD2Cl2. Mass
spectra (MALDI TOF) confirmed the structure of
compound 3: the spectra contained both the molecular
ion and characteristic products of its fragmentation
resulting from the loss of one or several diazaphos-
pholidine rings.
Compound 3 was used in asymmetric alkylation of
cinnamyl acetate 4 with ethyl 2-oxocyclohexanecarbo-
xylate 5 (Scheme 3), in which process a quaternary
С*-stereocenter formed on a carbon atom belonging to
the nucleophile.
This reaction is an example of enantioselective
catalytic synthesis of compounds with a quaternary
asymmetric atom, which is a fairly complex problem
[16, 19–21]. The use in the reaction of compound 3 (L)
as a chiral inducer resulted in enantioselectivity up to
76% (see the table). The highest values of the asym-
metric induction were obtained at molar ratios L/Pd 1 : 4
and 2 : 1, the highest conversion, at the molar ratio L/Pd
1 : 1. In all cases (S)-enantiomer 6 prevailed.
The authors express their gratitude to the Russian
Science Foundation for the financial support of this
study (grant no. 14-13-01383).
The phosphorylating reagent 2 was prepared by
procedure [16].
REFERENCES
5,10,15,20-Tetrakis(4-{(2R,5S)-3-phenyl-1,3-
diaza-2-phosphabicyclo[3.3.0]octyloxy}phenyl)-
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phosphorylating reagent 2 and 0.834 mL (6 mmol) of
Et3N in 10 mL of THF under vigorous stirring at 20°C
was added in one portion 0.339 g (0.5 mmol) of
compound 1. The reaction mixture was heated to
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2. Alexakis, A. and Benhaim, C., Eur. J. Org. Chem.,
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 8 2015