8
Tetrahedron
ACCEPTED MANUSCRIPT
(1.1 mmol) of oxalyl chloride at 0 °C according to the method
and energetics were calculated by scanning and the calculated TS
described by us.34 The chlorophospholenium salt 2a was
dissolved in 2.0 mL of dichloromethane, and the solution was
cooled to -78°C followed by the addition of 0.23 g (1.5 mmol) of
(‒)-menthol (3A) in 2.0 mL of dichloromethane over the period
of 10 min. The reaction mixture was stirred for 2 h at -78 °C, and
it was allowed to warm to 0°C. A small sample was taken from
the reaction mixture, the solvent was removed at 0°C. The
residue was dissolved in dry CDCl3 to determine diastereomeric
excess by 31P NMR. 2.0 mL of Toluene and 0.16 mL (2.0 mmol)
of pyridine were added to the reaction mixture. The flask was
placed into an oil bath, and the reaction mixture was heated for
2 h at 60 °C. The volatiles were evaporated, the residue was
dissolved in 2.0 mL of dichloromethane. The solution was
extracted with 1.0 mL of water, the organic phase was dried
(Na2SO4), and the solvent was removed in vacuo. The crude
product was purified by column chromatography (silica gel, 3%
methanol in dichloromethane) to give 0.17 g (91%) of (SP)-1-
phenyl-3-methyl-3-phospholene 1-oxide [(SP)-1a] in an ee of
21%. (Table 1, Entry 11).
indeed connected the two corresponding minima. The transition
states were optimized with the QST3 method. Transition states
were identified by having one imaginary frequency in the
Hessian matrix. All the geometries and transition states were
optimized and frequency calculations were made to assure that
the structures are in a local minimum. The reported ꢀH, ꢀG, ꢀS
values are the differences of the calculated sum of electronic and
thermal enthalpy, Gibbs free energy and total entropy,
respectively, between the corresponding structures.
Acknowledgements
This work was supported by the National Research,
Development and Innovation Office - NKFIH (Grant No. OTKA
PD 116096), and by the ÚNKP-17-4-I new national excellence
program of the ministry of human capacities (Grant No. ÚNKP-
17-4-I-BME-102).
Appendix A. Supplementary data
Supplementary data related to this article can be found at
References
In the optimization study, the amount of (‒)-menthol (3A), the
addition time, the reaction time and the temperature of each
reaction steps were changed. All reactions were accomplished
according to the general procedure described above by setting the
parameters as detailed in Table 1. The screening of the chiral
auxiliaries (3) was accomplished according to the general
procedure by using 1.15 equivalent of the auxiliary. The best
results are summarized in Table 2 (See Supporting Information
for the complete list of chiral auxiliaries, as well as for the
results).
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The 1-chloro-3-methyl-3-phospholenium chloride derivatives
(2) were freshly prepared in the reaction of 1.0 mmol of 3-
phospholene oxide (1) (1a: 0.19 g, 1b: 0.21 g, 1c: 0.21 g, 1d:
0.24 g, 1e: 0.14 g, 1f: 0.16 g, 1g: 0.17 g, 1h: 0.17 g, 1i: 0.19 g)
and 0.086 mL (1.1 mmol) of oxalyl chloride at 0 °C according to
our method.34 The chlorophospholenium salt 2 was dissolved in
2.0 mL of dichloromethane, and the solution was cooled to -78°C
followed by the addition of 0.18 g (1.15 eq.) of (‒)-menthol (3A)
or 0.13 g (1.15 eq.) of (+)-1-phenylethanol (3F) in 2.0 mL of
dichloromethane over the period of 10 min. The reaction mixture
was stirred for 2 h at -78 °C, and it was allowed to warm up to
0°C. 2.0 mL of Toluene and 0.16 mL (2.0 mmol) of pyridine
were added to the reaction mixture. The flask was placed into an
oil bath, and the reaction mixture was heated for 2 h at 60 °C.
The volatiles were evaporated, the residue was dissolved in 2.0
mL of dichloromethane. The solution was extracted with 1.0 mL
of water, the organic phase was dried (Na2SO4), and the solvent
was removed in vacuo. The crude product was purified by
column chromatography (silica gel, 3% methanol in
dichloromethane) to give the corresponding enantiomerically
enriched 1-substituted-3-methyl-3-phospholene oxides (1). The
results are summarized in Table 3.
4.5. Computational methods
In all quantum chemical calculations, the B3LYP/6-31+g(d,p)
method and basis set was used under the Gaussian09 program
package.40–42 The calculations were performed at 298 K and 1
bar. Dichloromethane was considered as the implicit solvent
applying the IEFPCM method.43–45 The H, G and S values
obtained are given at standard conditions. The reaction pathways