Optically active 6-membered p-heterocycles: 1-phenyl-1,2-dihydrophos- phinine oxide and 1-phenyl-3-diphenylphosphinoyl-1,2,3,6-tetrahydro- phosphinine oxide

Article abstract of DOI:10.2174/157017810790796345

The antipodes of racemic 1-phenyl-1,2-dihydrophosphinine oxides 1A and 1B were separated by resolution via formation of a diastereomeric complex using (-)-(2,R,3,R)-α,α,α',α'-tetraphenyl-1,4-dioxaspiro[4.5] decan-2,3-dimethanol (spiro-TADDOL) 2. The (+)-antipode of 1-phenyl-3- diphenylphosphinoyl-1,2,3,6-tetrahydrophosphinine oxide 3 was synthesized by the diastereoselective addition of diphenylphosphine oxide to the α β-double-bond of (-)-1,2- dihydrophosphinine oxide 1A. The new chiral tetrahydrophosphinine oxide (+)-3 served, after double deoxygenation, as a novel P-chiral bidentate ligand in the corresponding platinum complex.

Full text of DOI:10.2174/157017810790796345

110
Letters in Organic Chemistry, 2010, 7, 110-113
Optically Active 6-Membered P-Heterocycles: 1-Phenyl-1,2-Dihydrophos-
phinine Oxide and 1-Phenyl-3-Diphenylphosphinoyl-1,2,3,6-Tetrahydro-
phosphinine Oxide
Viktória Ujja,b, Andrea Kerényia, Andrea Lakia, Elemér Fogassya and György Keglevich*,a
aDepartment of Organic Chemistry and Technology, Budapest University of Technology and Economics, H-1521
Budapest, Hungary
bResearch Group of the Hungarian Academy of Sciences at the Department of Organic Chemistry and Technology,
Budapest University of Technology and Economics, H-1521 Budapest, Hungary
Received November 26, 2009: Revised January 07, 2010: Accepted January 12, 2010
Abstract: The antipodes of racemic 1-phenyl-1,2-dihydrophosphinine oxides 1A and 1B were separated by resolution via
formation of a diastereomeric complex using (–)-(2R,3R)-ꢀ,ꢀ,ꢀ’,ꢀ’-tetraphenyl-1,4-dioxaspiro[4.5]decan-2,3-dimethanol
(spiro-TADDOL) 2. The (+)-antipode of 1-phenyl-3-diphenylphosphinoyl-1,2,3,6-tetrahydrophosphinine oxide 3 was
synthesized by the diastereoselective addition of diphenylphosphine oxide to the ꢀ,ꢁ-double-bond of (–)-1,2-
dihydrophosphinine oxide 1A. The new chiral tetrahydrophosphinine oxide (+)-3 served, after double deoxygenation, as a
novel P-chiral bidentate ligand in the corresponding platinum complex.
Keywords: Resolution, dihydrophosphinine oxide, tetrahydrophosphinine oxide, Michael addition, platinum complex.
1. INTRODUCTION
oxides via molecular complex formation with the chiral host,
(–)-(4R,5R)-4,5-bis(diphenylhydroxymethyl)-2,2-dimethyl-
dioxolane (TADDOL) or (–)-(2R,3R)-ꢀ,ꢀ,ꢀ’,ꢀ’-tetraphenyl-
1,4-dioxaspiro[4.5]decan-2,3-dimethanol (spiro-TADDOL)
2 [16,17].
Among the six-membered P-heterocycles, dihydro- and
tetrahydrophosphinine oxides form a representative group
[1,2]. Perhaps the most convenient method for the
preparation of dihydrophosphinine oxides involves ring
enlargement of easily available 2,5-dihydro-1H-phosphole
oxides by the dichlorocarbene addition method [3,4].
Thermolysis of the 3-phosphabicyclo[3.1.0]hexane 3-oxides
obtained by dichlorocyclopropanation furnished dihydro-
phosphinine oxides [5,6]. 1,2,3,6-Tetrahydrophosphinine-
oxides with a P-function in position 3 have been introduced
recently [7,8]. The related diphosphine behaved as a suitable
P-ligand to form the corresponding cis chelate platinum
complex [9].
We could extend the method developed by us to the
resolution of methyl-4-chloro-1-phenyl-1,2-dihydrophos-
phinine 1-oxide 1. The resolution can be done via molecular
complex formation using spiro-TADDOL (–)-2. In the course
of the preparation of 1,2-dihydrophosphinine oxide 1, a 3:1
mixture of two double-bond isomers (A and B) were
obtained [5] that could not be separated by column
chromatography. Therefore, the mixture of dihydrophos-
phinine oxides 1A and 1B was resolved using spiro-
TADDOL (–)-2 in a mixture of acetone and hexane.
We aimed at the synthesis of optically active 1-phenyl-3-
diphenylphosphinoyl-1,2,3,6-tetrahydrophosphinine
oxide
Racemic 1-phenyl-1,2-dihydrophosphinine oxide 1 was
resolved by adding first half equivalent of spiro-TADDOL
(–)-2 to the hot acetone solution of 1. The 1:1 crystalline
complex (–)-1•(–)-2 was precipitated on the addition of
hexane. The ratio of (–)-1 and resolving agent (–)-2 was
from one of the enantiomers of the 1-phenyl-1,2-
dihydrophosphinine oxide to make eventually available the
corresponding bidentate P-ligand in an optically active form.
Optically active P-ligands may be components of transition
metal complexes used as enantioselective catalysts in
homogeneous catalytic reactions [10]. Especially the homo-
and heterobidentate chiral P-ligands, such as BINAP, DIOP,
DIPAMP, BINAPHOS are of practical importance [11].
1
determined by H NMR spectoscopy. Complex (–)-1•(–)-2
was analyzed on a chiral HPLC column showing that the
enantiomeric excess (ee) of major isomer (–)-1A was 40%.
After two recrystallizations of the (–)-1•(–)-2 complex from
a 1:2 mixture of acetone and hexane, complex (–)-1A•(–)-2
was obtained with a 89% ee in 33 % yield. The complex
could be further purified by a third recrystallization giving
the complex with 96.5% ee, but the yield became rather low.
After flash column chromatography on a silica gel, (–)-1A
was recovered with an ee of 96.5%. Double-bond isomer 1B
did not separate from major isomer 1A during the process.
The enantiomeric excess of minor isomer 1B was >99.9%
after the three recrystallizations and the ratio of the double-
bond isomers in the crystalline phase did not change
2. RESULTS AND DISCUSSION
Recently, we have elaborated a simple method [12-15]
for the resolution of a variety of 3-methyl-3-phospholene 1-
*Address correspondence to this author at the Department of Organic
Chemistry and Technology, Budapest University of Technology and
Economics, H-1521 Budapest, Hungary; Tel: +36 1 4631111/5883;
Fax: +36 1 4633648; E-mail: keglevich@mail.bme.hu
1570-1786/10 $55.00+.00
© 2010 Bentham Science Publishers Ltd.

Optically Active Dihydro- and Tetrahydrophosphinine Oxides
Letters in Organic Chemistry, 2010, Vol. 7, No. 2
111
Cl
Cl
Cl
R1
R2
R1
R2
R1
R2
O
O
O
O
acetone
hexane
2
+
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
+
*
P
*
P
P
O
Ph
O
Ph
O
Ph
OH HO
OH HO
(-)-1 (-)-2
Precipitate
rac-1
(+)-1
(-)-2
Solution
R1 R2
Me (A) 75%
Me H (B) 25%
H
Scheme 1.
significantly (Scheme 1). Dihydrophosphinine oxide (+)-(1A
and 1B) remained in solution. This is the first case that a 1,2-
dihydrophosphinine oxide was obtained in an optically
active form.
1B in the Michael addition is a consequence of steric
hindrance due to the methyl group in position 5. Due to a
selectivity observed earlier [7,8], only one of the two
possible diastereomers was obtained. Column chromato-
graphy afforded tetrahydrophosphinine oxide (+)-3 in 50%
yield. The ee value of product (+)-3 was determined by
chiral HPLC. The structure of (+)-3 was confirmed by 31P
and 1H NMR spectral data (Scheme 2).
The resolution of 1-phenyl-1,2-dihydrophosphinine oxide
1 with half equivalent of (–)-2 was also accomplished from a
2:5 mixture of ethyl acetate and hexane, but in this case, the
resolution sequence was less efficient than using a mixture
of acetone and hexane. Crystallization of the corresponding
supramolecular formation involving 1,2-dihydrophosphinine
oxide 1 and TADDOL could not be accomplished.
A twist-boat conformer was established earlier for 1-
phenyl-3-diphenylphosphinoyl-1,2,3,6-tetrahydrophosphinine
oxide by DFT calculations [8]. Single crystal X-ray analysis
suggested a twist-boat/cis conformer containing the Ph2P(O)
moiety and the oxygen atom of the ring P=O moiety in the
cis disposition [18].
We wished to synthesize optically active 1-phenyl-3-
diphenylphosphinoyl-1,2,3,6-tetrahydrophosphinine oxide 3
by the Michael addition of diphenylphosphine oxide on the
electron-poor ꢀ,ꢀ-double-bond of the (–)-1-phenyl-1,2-
dihydrophosphinine oxide 1A to obtain the precursor of an
optically active bidentate P-ligand. The ee value of the
starting (–)-1-phenyl-1,2-dihydrophosphinine oxide 1A was
89%. To activate the diphenylphosphine oxide, it was first
reacted with trimethylaluminium at 0°C in chloroform. Then,
the corresponding ([Ph2P(O)])– anion so formed reacted
easily with the ꢀ,ꢀ-double-bond of the (–)-dihydro-
phosphinine oxide 1A added to the reaction mixture at 0°C
furnishing the (+)-1-phenyl-3-diphenylphosphinoyl-1,2,3,6-
tetrahydrophosphinine oxide 3. The unreactivity of isomer
The new chiral tetrahydrophosphinine oxide (+)-3 may
serve, after deoxygenation, as a novel P-chiral bidentate
ligand in transition metal complexes. The bis(phosphine
oxide) (+)-3 was deoxygenated applying phenylsilane at
80 ˚C to give diphosphine 4. The silane reductions are
known to proceed with retention of configuration [19].
Diphosphine 4 was then reacted with one equivalent of
dichlorodiben-zonitrile platinum(II) in benzene to afford cis
chelate complex (+)-5 (Scheme 3). The structure of (+)-5
was confirmed by 31P NMR spectral data [9].
Cl
O
P
Cl
Ph
Ph
R1
R2
Me
1. Ph2P(O)H / Me3Al
0 °C, 20 h
*
P
P
2. H2O
O
Ph
O
Ph
( )-1
(+)-3
Scheme 2.
Cl
P
Ph
Ph
O
P
Cl
P
Cl
26 °C, 24 h
PtCl2(PhCN)2
benzene
P
Me
Ph
Ph
Ph
80 °C, 3 days
PhSiH3
Me
P
Me
Ph
Pt
Cl
Cl
P
Ph
O
Ph
Ph
(+)-3
4
(+)-5
Scheme 3.

112 Letters in Organic Chemistry, 2010, Vol. 7, No. 2
Ujj et al.
3. CONCLUSION
4.3. Preparation of (+)-4-chloro-5-methyl-1-phenyl-3-
diphenylphosphinoyl-1,2,3,6-tetrahydrophosphinine
oxide 3
1-
In summary, the (–)-antipode of 1-phenyl-1,2-
dihydrophosphinine oxide 1 was made available by a novel
resolution method applying a TADDOL derivative (–)-2.
Diastereoselective hydrophosphinoxidation led to the corres-
ponding (+)-Ph2P(O)-1,2,3,6-tetrahydrophosphinine oxide 3
that, after double deoxygenation, was a suitable optically
active bidentate P-ligand in a cis chelate platinum complex
(+)-5.
Tetrahydrophosphinine 1-oxide (+)-3 was prepared from
(–)-1 as described earlier for the racemic case [7]. Ee of
(+)-3: 89%; yield: 50%. 31P NMR (CDCl3), ꢀ 33.0 (d, 3JP-P
=
13.8, P1), 34.0 (d, 3JP-P = 13.8, P2), [ꢀPlit 34.0 (d, 3JP-P = 13.8,
3
P1), 34.8 (d, JP-P = 13.8, P2)] [7], [ꢀ]2D5 = +257.6 (c 0.5,
CHCl3). Retention times: 26.2 min for (–)-3 and 36.5 min for
(+)-3.
4. EXPERIMENTAL
4.1. General
4.4. Deoxygenation of the bis(phosphine oxide) precursor
(+)-3 and complexation of the bisphosphine 4 by
PtCl2(PhCN)2
1
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 downfield relative to TMS
and 85% H3PO4. The coupling constants are given in Hertz.
Optical rotations were determined on a Perkin-Elmer 241
polarimeter.
23.0 mg (0.05 mmol, ee 89%) of 1-Phenyl-3-
diphenylphosphinoyl-1,2,3,6-tetrahydrophosphinine-1-oxide
(+)-3 and 32 ꢁL (0.26 mmol) of phenylsilane was kept at
80 ˚C under nitrogen for 3 days. Then, the mixture was taken
up in 4 mL of degassed benzene, the bisphosphine 4 so
obtained was immediately reacted with 25.0 mg (0.05 mmol)
of dichlorodibenzonitrile platinum(II) and the mixture was
stirred at room temperature for 24 h under nitrogen. After
crystallization from the benzene solution, 32.0 mg (+)-5
The enantiomeric excesses were determined by chiral
HPLC. The ee of 1 was determined by chiral HPLC (Daicel
Chem. Ind., having a 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, UV detector ꢀ=254 nm). The ee
of 3 was determined by chiral HPLC (Daicel Chem. Ind.,
having a Chiralcel OD column 250*4.6 mm ID, using
hexane/isopropanol 75/25 as the eluent with a flow rate of
0.8 ml/min, T=20 ˚C, UV detector ꢀ=254 nm).
(93%) was obtained, 31P NMR (CDCl3), ꢀP 14.4 (JPt-P = 3496,
lit
J
P-P = 7.4, P1), 47.6 (JPt-P = 3678, JP-P = 7.4, C3-P), [ꢀP 17.7
(JPt-P = 3496, JP-P = 6.7, P1), 50.3 (JPt-P = 3681, JP-P = 6.7, C3-
P] [9], [ꢀ]2D5 = +47.7 (c 0.5, CHCl3).
The starting 1-phenyl-1,2-dihydrophosphinine oxide [5]
1 and (–)-(2R,3R)-ꢁ,ꢁ,ꢁ’,ꢁ’-tetraphenyl-1,4-dioxaspiro [4.5]
decan-2,3-dimethanol [16] (–)-2 were synthesized as
described earlier. Trimethylaluminium, 2.0 M sol. in heptane
and cis-PtCl2(PhCN)2 were purchased from Aldrich
Chemical Co.
ACKNOWLEDGEMENTS
Authors are grateful for the financial support from the
Hungarian Scientific Research Fund (OTKA, Grants No.
T075236, T067679).
4.2. Resolution of methyl-4-chloro-1-phenyl-1,2-dihydro-
phosphinine 1-oxide 1 with spiro-TADDOL (–)-2
REFERENCES
[1]
Hewitt, D.G. Comprehensive Heterocyclic Chemistry II; Katritzky,
A.R.; Rees, C.W.; Scriven, E.F.V. Eds.; Pergamon: New York,
1996; Vol. 5, pp. 639-668.
To 0.43 g (1.80 mmol) of racemic 3- and 5-methyl-4-
chloro-1-phenyl-1,2-dihydrophosphinine 1-oxide 1A (75%)
and 1B (25%) and 0.46 g (0.90 mmol) of spiro-TADDOL
(–)-2 in 2.1 mL of hot acetone was added 4.3 mL of hexane.
After the addition, crystals of the complex started to appear
immediately. After 1 h, the crystals were separated by
filtration to give 0.54 g (80%) of complex consisting of
(–)-1A•(–)-2 (75%) with an ee of 40% and 1B•2 (25%) with
an ee of 55%. The complex was further purified by two
recrystallizations from acetone–hexane (2.1 mL/4.3 mL) to
afford 0.22 g (33%) of complex (–)-1A•(–)-2 with an ee of
[2]
[3]
Keglevich, G. Phosphorus Heterocycles I.; Bansal, R.K. Ed.;
Springer: Berlin 2009; Vol. 20, pp. 65-99.
Keglevich, G. 3-Phosphabicyclo[3.1.0]hexane 3-oxides: Useful
intermediates for dihydro-, tetrahydro- and hexahydrophosphinines
and phosphinines. Rev. Heteroatom Chem., 1996, 14, 119-136.
Keglevich, G. Synthesis of 6-membered and 7-membered P-
heterocycles by ring enlargement. Synthesis, 1993, 931-942.
Keglevich, G.; Androsits, B.; Tꢂke, L. Synthesis of
dihydrophosphorins by the thermal transformation of phosphole
dichlorocarbene adducts. J. Org. Chem., 1988, 53, 4106-4108.
Keglevich, G.; Brlik, J.; Janke, F.; Tꢂke, L. Convenient synthesis
of 1-alkoxy-1,2-dihydrophosphinine 1-oxides by ring enlargement.
Heteroatom Chem., 1990, 1, 419-424.
[4]
[5]
[6]
[7]
89% and 1B•2 with an ee of 95%, respectively, [ꢀ]2D5 = –
Keglevich, G.; Sipos, M.; Imre, T.; Ludányi, K.; Szieberth, D.;
Tꢂke, L. Diastereoselective synthesis of 1,2,3,6-tetrahydro-
phosphinine 1-oxides with an exocyclic P-function by a Michael
type addition. Tetrahedron Lett., 2002, 43, 8515-8518.
90.2 (c 1, CHCl3). Column chromatography (silica gel, 3%
methanol in chloroform) of the complex regenerated 0.07 g
(0.3 mmol, 31%) of (–)-3- and 5-methyl-4-chloro-1-phenyl-
1,2-dihydrophosphinine 1-oxides 1A and 1B, 1A (ꢀP 16.1
[ꢀPlit 15.3] [5]) with an ee of 89%, 1B (ꢀP 15.0 [ꢀPlit 14.2] [5])
[8]
[9]
Keglevich, G.; Sipos, M.; Szieberth, D.; Nyulászi, L.; Imre, T.;
Ludányi, K.; Tꢂke, L. Weak intramolecular interactions as
controlling factors in the diastereoselective formation of 3-
phosphinoxido- and 3-phosphono-1,2,3,6-tetrahydrophosphinine 1-
oxides. Tetrahedron, 2004, 60, 6619-6627.
Keglevich, G.; Sipos, M.; Szieberth, D.; Petꢂcz, G.; Kollár, L. 4-
Chloro-5-methyl-3-diphenylphosphino-1-phenyl-1,2,3,6-tetrahydro-
with an ee of 95%), [ꢀ]2D5 = –169.1 (c 0.5, CHCl3). Based on
31P NMR, the ratio of 1A and 1B remained ca. 3:1. Retention
times: 13.5 and 15.9 min for 1A, 15.0 and 18.1 min for 1B.

Optically Active Dihydro- and Tetrahydrophosphinine Oxides
Letters in Organic Chemistry, 2010, Vol. 7, No. 2
113
phosphinine as a bidentate P-ligand in a cis chelate Pt(II) complex.
J. Organomet. Chem., 2004, 689, 3158-3162.
[15]
[16]
Fogassy, E.; Keglevich, G.; Novák, T.; Schindler, J.; Ujj, V. In
Hung. Pat. HU0700278, 2007.
[10]
Brunner, H.; Zettlmeier, W. Handbook of Enantioselective
Catalysis with Transition Metal Compounds, VCH: Weinheim,
1993.
Noyori, R. Asymmetric Catalysis in Organic Synthesis; John Wiley
& Sons: New York, 1994.
Beck, A.K.; Bastani, B.; Plattner, D.A.; Petter, W.; Seebach, D.;
Braunschweiger, H.; Gysi, P.; Lavecchia, L. Large-scale
preparation of alpha,alpha,alpha,alpha-tetraaryl-1,3-dioxolane-4,5-
dimethanols (TADDOLE) - versatile auxiliaries for epc synthesis
and its solid-state structure. Chimia, 1991, 45, 238-244.
[11]
[12]
Novák, T.; Schindler, J.; Ujj, V.; Czugler, M.; Fogassy, E.;
Keglevich, G. Resolution of 3-methyl-3-phospholene 1-oxides by
molecular complex formation with TADDOL derivatives.
Tetrahedron: Asymmetry, 2006, 17, 2599-2602.
Novák, T.; Ujj, V.; Schindler, J.; Czugler, M.; Kubinyi, M.; Mayer,
Z.A.; Fogassy, E.; Keglevich, G. Resolution of 1-substituted-3-
methyl-3-phospholene 1-oxides by molecular complex formation
with TADDOL derivatives. Tetrahedron: Asymmetry, 2007, 18,
2965-2972.
Novák, T.; Schindler, J.; Ujj, V.; Czugler, M.; Fogassy, E.;
Keglevich, G. Chiral P-heterocycles: Efficient method for the
resolution of 3-methyl-3-phospholene 1-oxides. Phosphorus,
Sulfur, Silicon, 2008, 183, 543-546.
[17]
[18]
Seebach, D.; Beck, A.; Heckel, A. TADDOLs, their derivatives,
and TADDOL analogues: versatile chiral auxiliaries. Angew.
Chem. Int. Ed. Engl., 2001, 40, 92-138.
Czugler, M.; Körtvélyesi, T.; Fábián, L.; Sipos, M.; Keglevich, G.
Intra- and intermolecular interactions and water pincer in the
[13]
[14]
crystal structure of
a
3-P(O)Ph-2 substituted 1,2,3,6-
tetrahydrophosphinine oxide hydrate. Cryst. Eng. Commun., 2007,
9, 561-565.
Quin, L.D. A guide to Organophosphorus Chemistry; John Wiley
& Sons: New York, 2000.
[19]