Preparation of Optically Active Six-Membered P-Heterocycles 183
with an ee of 87% led to (−)-4-chloro-5-methyl-
1-phenyl-1,2,3,6-tetrahydrophosphinine 1-oxide
tensity of the signals belonging to the characteristic
groups of the resolving agent and the enantiomers.
The ee of 1–4 was determined by chiral HPLC.
[(−)-4] with an ee of 87% and in a yield of 20%
(Scheme 1/(4); Table 1, entry 10). In our previous
studies, it was established that only the 4-chloro-
3-methyl-1-phenyl-1,2-dihydrophosphinine 1-oxide
(3A) isomer reacts in this reaction due to steric
factors [15]. Hence, the other double bond isomer
played no role in the reduction and was removed
during the purification.
Both the resolution of racemic 1,2,3,6-
tetrahydrophosphinine oxide 4 and the reduction
of optically active 1,2-dihydrophosphinine oxide 3A
are suitable for the preparation of optically active
tetrahydrophosphinine oxide 4. It is favorable to
accomplish the resolution in the starting material
phase, as half of the borane reagent can be saved
during the reduction.
ꢀR
The ee of 1 and 4 was determined using Kromasil
5-Amycoat 250 × 4.6 mm ID, hexane/ethanol 85/15
as an eluent with a flow rate of 0.8 mL/min, T =
20◦C, a UV detector α = 254 nm. Retention time:
11.4 min for (R)-1 and 13.1 min for (S)-1; 15.8 min
for (+)-4 and 23.2 min for (−)-4. The ee of 2 was
ꢀR
determined using Kromasil 5-Amycoat 250 × 4.6
mm ID, hexane/ethanol 90/10 as an eluent with a
flow rate of 1.0 mL/min, T = 20◦C, the UV detector
α = 254 nm. Retention time: 13.4 min for (−)-2 and
15.6 min for (+)-2. The ee of 3 was determined using
Daicel Chem. Ind. Chiralpack AD-H column 250 ×
4.6 mm ID, using hexane/isopropanol 85/15 as the
eluent with a flow rate of 0.8 mL/min, T = 20◦C, the
UV detector α = 254 nm. Retention time: 13.6 and
15.9 min for 3A, 15.1 and 18.1 min for 3B. Optical
rotations were determined on a Perkin–Elmer 241
polarimeter.
CONCLUSIONS
Our methods for the resolution of optical iso-
mers seem to be reproducible, and the deviation
of the ee and yields are mostly within 2.5% after
repetitions.
In conclusion, first in the literature, the resolution of
6,6-dichloro-1-methyl-3-phenyl-3-phosphabicyclo-
[3.1.0]hexane 3-oxide (2) and 4-chloro-5-methyl-1-
phenyl-1,2,3,6-tetrahydrophosphinine 1-oxide (4)
was accomplished by coordination and molecu-
lar complex formation using the easily available
and relatively inexpensive calcium hydrogen (−)-
The
(4R,5R)-(−)-4,5-bis(diphenylhydroxy-
methyl)-2,2-dimethyldioxolane (7) [17], the (2R,
3R)-(−)-α,α,αꢁ,αꢁ-tetraphenyl-1,4-dioxaspiro
[4.5]
decan-2,3-dimethanol (8) [18], calcium hydro-
O,Oꢁ-dibezoyl-(2R,3R)-tartarate
[Ca(H-DBTA)2]
gen (−)-O,Oꢁ-dibezoyl-(2R,3R)-tartarate (5) [9],
(5) and calcium hydrogen (−)-O,Oꢁ-di-p-tolyl-
(2R,3R)-tartarate [Ca(H-DPTTA)2] (6), or TAD-
DOL derivatives (7 and 8), respectively. It was
also proved that during the dichlorocarbene
addition on the double bond of 3-methyl-1-
phenyl-3-phospholene 1-oxide (1), racemization
occurs, but the ring opening of 6,6-dichloro-1-
methyl-3-phenyl-3-phosphabicyclo[3.1.0]hexane
3-oxide (2) and the selective reduction of the
α,β-double bond of the 4-chloro-3-methyl-1-
phenyl-1,2-dihydrophosphinine 1-oxide (3A) can be
accomplished by preserving the configuration of the
chiral P-centers. Overall, considering the principles
of green chemistry, whenever it is possible, it is
better to start the synthesis from the optically active
starting materials.
the
racemic
3-methyl-1-phenyl-3-phospholene
1-oxide (1) [19], 6,6-dichloro-1-methyl-3-phenyl-
3-phosphabicyclo[3.1.0]hexane 3-oxide (2) [20],
3-methyl-
1,2-dihydrophosphinine 1-oxide (3A and 3B)
[21], and 4-chloro-5-methyl-1-phenyl-1,2,3,6-
and
5-methyl-1-phenyl-4-chloro-
tetrahydrophosphinine 1-oxide (4) [16] were
prepared as described earlier.
Preparation of the Optically Active
3-Methyl-1-phenyl-3-phospholene 1-Oxide
((S)-1, (R)-1)
The (R)- and (S)-enantiomers of 3-methyl-1-phenyl-
3-phospholene 1-oxide (1) were prepared as de-
scribed earlier by resolution with (−)-Ca(H-DBTA)2
(5) and (−)-Ca(DPTTA)2 (6), respectively [9]. Yield
of (R)-1: 42%, ee: 94%; yield of (S)-1: 49%, ee: 93%.
EXPERIMENTAL
The H and 31P NMR spectra were recorded on a
Bruker DRX-500 spectrometer operating at 500 and
202.4 MHz, respectively. Chemical shifts are down-
field relative to TMS and 85% H3PO4.
1
Preparation of 6,6-Dichloro-1-methyl-3-phenyl-
3-phosphabicyclo[3.1.0]hexane 3-oxide (2) from
3-methyl-1-phenyl-3-phospholene-1-oxide (1)
The composition of the diastereomeric com-
Method A. The solution of 3.9 g (96.4 mmol) of
sodium hydroxide and 3.8 mL of water was added
plexes was determined by 1H NMR comparing the in-
Heteroatom Chemistry DOI 10.1002/hc