A new P-heterocyclic family: A variety of six-membered and bridged P-heterocycles with 1-benzyl substituent

Article abstract of DOI:10.1002/hc.20363

The ring enlargement of 1-benzyl-2,5-dihydro-1H-phosphole oxide (1) via the corresponding 2-phosphabicyclo[3.1.0]hexane 2-oxide (2) afforded, depending on the conditions, the double bond isomers (A and B) of 1,2-dihydrophosphinine oxide 4 or that of 3-sub

Full text of DOI:10.1002/hc.20363

Heteroatom Chemistry
Volume 19, Number 1, 2008
A New P-Heterocyclic Family: A Variety of
Six-Membered and Bridged P-Heterocycles
with 1-Benzyl Substituent
Tibor Nova´k,1 Ja´nos Deme,2 Krisztina Luda´nyi,3,4
and Gyo¨rgy Keglevich2
1Research Group of the Hungarian Academy of Sciences at the Department of Organic Chemistry
and Technology, Budapest University of Technology and Economics, 1521 Budapest, Hungary.
2Department of Organic Chemistry and Technology, Budapest University of Technology and
Economics, 1521 Budapest, Hungary.
3Department of Pharmaceutics, Faculty of Pharmacy, Semmelweis University,
1092 Budapest, Hungary
4Chemical Research Center, Hungarian Academy of Sciences, 1525 Budapest, Hungary
Received 16 February 2007; revised 6 April 2007
ꢀ
C
2008 Wiley Periodicals, Inc. Heteroatom Chem
ABSTRACT: The ring enlargement of 1-benzyl-2,5-
19:28–34, 2008; Published online in Wiley InterScience
dihydro-1H-phosphole oxide (1) via the corresponding
(www.interscience.wiley.com). DOI 10.1002/hc.20363
2-phosphabicyclo[3.1.0]hexane 2-oxide (2) afforded,
depending on the conditions, the double bond isomers
(A and B) of 1,2-dihydrophosphinine oxide 4 or
that of 3-substituted 1,2,3,6-tetrahydrophosphinine
oxides 5 and 6. Dihydrophosphinine oxides (4)
INTRODUCTION
P-Heterocycles have attracted much attention re-
cently and represent growing field mainly
were suitable starting materials for 1,2,3,4,5,6-
hexahydrophosphinine oxide and 1,2,3,6-
a
7
from the point of view of their use as P-
ligands [1]. In our laboratory, a ring enlarge-
ment method was developed making available a
variety of 2-phosphabicyclo[3.1.0]hexane oxides,
1,2- and 1,4-dihydrophosphinine oxides, different
1,2,3,6-tetrahydrophosphinine oxides, 1,2,3,4,5,6-
hexahydrophosphinine oxides, phosphepine oxides,
and bridged phosphabicyclo[2.2.2]octene deriva-
tives [2–6], the latter being precursors of low-
coordinate fragments useful in the phosphory-
lation of nucleophiles [6]. The intermediates of
the above P-heterocycles are the suitably substi-
tuted 2,5-dihydro-1H-phosphole 1-oxides available
easily. The 1-benzyl-P-heterocycles form a rela-
tively less studied group; only simple derivatives,
tetrahydrophosphinine oxide 8 obtained by reductive
approaches and for the double bond isomers (A and
B) of 2-phosphabicyclo[2.2.2]octadiene 2-oxide 9 and
phosphabicyclooctene oxide 10 prepared in Diels–
Alder cycloaddition. Precursor 9 was utilized in the
fragmentation-related phosphorylation of alcohols.
The paper is dedicated to Professor Dr. Csaba Sza´ntay on the
occasion of his 80th birthday.
Correspondence to: G. Keglevich; e-mail: keglevich@mail.
bme.hu.
Contract grant sponsor: Hungarian Scientific Research Fund
(OTKA).
Contract grant number: T067679.
Contract grant sponsor: Bolyai Fellowship (for TN).
2008 Wiley Periodicals, Inc.
c
ꢀ
28

A New P-Heterocyclic Family 29
SCHEME 1
such as the corresponding 1H-phosphole [7],
2,5-dihydro- and 2,3,4,5-tetrahydro-1H-phosphole
oxides [8,9], as well as some other species includ-
ing 7-phosphanorbornene 7-oxides [10] have been
described. In this paper, the 1-benzyl derivatives of
a variety of six-membered P-heterocycles, mainly
phosphinines, as well as bridged P-heterocycles,
such as phosphabicyclooctenes, are discussed.
RESULTS AND DISCUSSION
1-Benzyl-2,5-dihydro-1H-phosphole 1-oxide 1 was
subjected to dichlorocyclopropanation reaction us-
ing dichlorocarbene generated from chloroform by
aqueous sodium hydroxide under phase transfer cat-
alytic conditions, as described for other cases [2].
2-Phosphabicyclo[3.1.0]hexane 3-oxide 2 was ob-
tained as a 3:1 mixture of two (A and B) diastere-
omers (Scheme 1). The stereochemical assignment
was justified by earlier arguments [11]. The isomeric
mixture of phosphabicyclohexane oxide (2) was con-
verted to the corresponding sulfide 3 with phospho-
rus pentasulfide (Scheme 1).
The second step of the ring enlargement in-
volved opening of the dichlorocyclopropane ring,
which was carried out thermally to afford a 3:1 mix-
ture of the double bond isomers (A and B) of di-
hydrophosphinine oxide 4 (Scheme 2) or was done
under solvolytic conditions applying silver nitrate
and methanol or water to give a mixture of the
double bond isomers (A and B) of 3-methoxy- or 3-
hydroxy-1,2,3,6-tetrahydrophosphinine oxides 5 and
6, respectively (Scheme 3). The double bond iso-
mer (A and B) of compounds 5 and 6 consisted of
diastereomers.
SCHEME 2
as a mixture of two diastereomers (Scheme 4).
It was found earlier that the hydrogenation of
2-phosphabicyclo[3.1.0]hexane oxides at some-
what more forcing conditions may also lead to
the corresponding hexahydrophosphinine oxides
[12]. However, transformation of the isomeric
mixture of phospabicyclohexane 2 to 7 was not
too efficient. The reason for this experience may
stem the sensitivity of the P-benzyl moiety under
hydrogenation.
A selective reduction of the electron-poor double
bond of the isomers A and B of dihydrophosphinine
oxide 4 was achieved by dimethylsulfide borane. The
reduction of isomer 4A was found to be more effi-
cient than that of 4B. Hence, the 3:1 isomeric ratio
of starting isomers 4A and 4B was shifted to 9:1 in
regard to products 8A and 8B (Scheme 5).
Finally, 1,2-dihydrophosphinine oxides 4A and
4B were used as dienes in the Diels–Alder reac-
tion. In cycloaddition with dimethyl acetylenedicar-
boxylate (DMAD) and N-phenylmaleimide (NPMI),
the double bond isomers (A and B) of 2-
phosphabicyclo[2.2.2]octadiene 9 and phosphabicy-
clooctene 10 were formed, respectively (Scheme 6).
Isomers 9A and 9B consisted of two diasteromers.
In the next part of our project, 1,2-
dihydrophosphinine oxide (4) was utilized in
the synthesis of other P-heterocycles. Catalytic
hydrogenation of the isomeric mixture of 4 fur-
nished 1,2,3,4,5,6-hexahydrophosphinine oxide 7
Heteroatom Chemistry DOI 10.1002/hc

30 Nova´k et al.
SCHEME 3
39.2 and 40.5 ppm that could not be identified yet.
The expected phosphinate (11a) was formed only in
small proportion (less than 5%).
It is recalled that in the case of phenyl substi-
tution, the use of the corresponding dihydrophos-
phinine oxide–NPMI cycloadduct was more appro-
priate in photoinduced phosphorylation than that of
the DMAD cycloadduct [13].
P-Heterocycles 2–8, mostly as isomeric pairs,
were characterized by 31P, 13C, and 1H NMR, as well
as mass spectral data. At the same time, the spec-
tral parameters of precursors 9 and 10 were com-
pared with those of authentic samples prepared in
the meantime under microwave conditions and to
be published elsewhere [14].
In summary, new benzyl-substituted P-hetero-
cycles including 2-phosphabicyclo[3.1.0]hexane
oxide and sulfide, 1,2-dihydro-, 1,2,3,6.tetrahydro-
and 1,2,3,4,5,6-hexahydrophosphinine oxides, as
well as 2-phosphabicyclo[2.2.2]octadiene deriva-
tives were obtained and characterized. One of the
bridged P-heterocycles proved to be an efficient
reagent in the photoinduced phosphorylation of
alcohols.
SCHEME 4
The bridged P-heterocycles 9 and 10 were tested
in the UV light mediated fragmentation-related
phosphorylation of simple alcohols. Irradiation of
the acetonitrile solution of the isomeric mixture
of phosphabicyclooctadiene 9 in the presence of
methanol, ethanol, propanol, and butanol at 254 nm
led to phosphinates 11a–d (Scheme 7). Surprisingly,
precursor 10 was not found to be useful in similar
phosphorylations due to intensive decomposition in
UV light. In the presence of methanol, the photolysis
of 10 led to by products, revealing 31P NMR shifts at
EXPERIMENTAL
1
The 31P, 13C, and H NMR spectra were taken on a
Bruker DRX-500 spectrometer operating at 202.4,
125.7, and 500 MHz, respectively. Chemical shifts
are downfield relative to 85% H3PO4 and TMS. The
couplings are given in hertz. Mass spectrometry
was performed on a ZAB-2SEQ instrument. Iso-
meric ratios were determined on the basis of rela-
tive 31P NMR intensities. Photolyses were conducted
in a photochemical reactor equipped with a quartz,
water-cooled immersion well with a high-pressure
mercury lamp (125 W). The starting 1-benzyl-3-
SCHEME 5
Heteroatom Chemistry DOI 10.1002/hc

A New P-Heterocyclic Family 31
SCHEME 6
(J = 65.0, CPh), 35.3 (J = 7.5, C1), 36.1 (J = 6.0, C5),
36.9 (J = 55.1, C2), 71.7 (J = 8.7, C6), 126.6 (J = 3.0,
ꢁ
ꢁ
ꢁ
C4 ), 128.4 (J = 2.5, C3 ), 128.9 (J = 5.3, C2 ), 131.3
ꢁ
(J = 8.1, C1 ), Cipso, Cortho, Cmeta, and Cpara are marked
1
ꢁ
ꢁ
ꢁ
ꢁ
by C1 , C2 , C3 and C4 , respectively; H NMR (CDCl3)
δ: 1.63 (s, 3H, CH3), 2.03–2.22 (m, 1H, C5-H), 2.25–
2.45 (m, 2H, CH2), 2.52–2.80 (m, 2H, CH2), 3.31 (d,
2H, J = 12.8, CH2Ph), 7.15–7.45 (m, 5H, Ar).
SCHEME 7
2B. 31P NMR (CDCl3) δ: 82.4; 13C NMR (CDCl3) δ:
20.3 (J = 7.0, CH3), 27.0 (J = 63.6, C4), 33.1 (J = 63.8,
CPh), 35.4 (J = 7.3, C1), 36.0 (J = 6.5, C5), 37.0
methyl-2,5-dihydro-1H-phosphole oxide (1) was pre-
pared as described earlier [15].
ꢁ
(J = 54.2, C2), 71.8 (J = 11.6, C6), 126.8 (J = 2.9, C4 ),
ꢁ
ꢁ
128.5 (J = 2.4, C3 ), 129.0 (J = 5.1, C2 ), 130.7 (J = 7.2,
1
ꢁ
C1 ); H NMR (CDCl3) δ: 1.50 (s, 3H, CH3).
3-Benzyl-6,6-dichloro-1-methyl-3-phosphabicy-
clo[3.1.0]hexane 3-oxide 2
To 21.4 g (100 mmol) of dihydrophosphole oxide 1
and 5.0 g (22.0 mmol) of triethylbenzylammonium
chloride (TEBAC) in 200 mL of chloroform, 125 g
(3.13 mol) of sodium hydroxide in 125 mL of wa-
ter was added dropwise and the mixture was stirred
until it cooled down to room temperature. After fil-
tration and separation, the organic phase was made
up to its original volume and 1.7 g (7.5 mmol) of
TEBAC was added. The reaction mixture was treated
with three more times with aqueous sodium hydrox-
ide (125 g/125 mL, 150 g/150 mL, 150 g/150 mL
NaOH/H2O, respectively) as mentioned above. The
solution obtained after filtration and separation was
concentrated in vacuo, and the residue so obtained
was purified by chromatography (2% methanol in
chloroform, silica gel) to give 22 g (75%) of a 3:1 mix-
ture of 2A and 2B; HRMS, [M + H]+found = 289.0310,
C13H16Cl2OP requires 289.0316.
3-Benzyl-6,6-dichloro-1-methyl-3-phosphabicy-
clo[3.1.0]hexane 3-sulfide 3
To 0.30 g (1.0 mmol) of phosphabicyclohexane ox-
ide 2 consisting of isomers A (75%) and B (25%)
in 5 mL of degassed benzene, 0.16 g (0.7 mmol)
of P2S5 was added and the mixture was refluxed
for 20 h under nitrogen. The suspension was fil-
tered, the solvent of the filtrate evaporated, and the
residue purified by column chromatography (3%
methanol in chloroform, silica gel) to give 0.29 g
(91%) of 3 as a 4:1 mixture of diastereoisomers A
and B. HRMS, [M + H]+found = 305.0069, C13H15Cl2SP
requires 305.0087.
3A. 31P NMR (CDCl3) δ: 88.4; 13C NMR (CDCl3) δ:
21.0 (J = 6.5, CH3), 33.3 (J = 51.7, C4), 37.0 (J = 7.3,
C1), 38.0 (J = 6.2, C5), 38.5 (J = 51.2, CPh), 41.0
ꢁ
(J = 40.0, C2), 72.5 (J = 11.9, C6), 127.9 (J = 3.4, C4 ),
2A. 31P NMR (CDCl3) δ: 85.6; 13C NMR (CDCl3)
δ: 21.0 (J = 6.0, CH3), 28.5 (J = 64.6, C4), 34.3
129.0 (J = 2.9, C3 ), 129.9 (J = 5.1, C2 ), 131.4 (J = 7.9,
ꢁ
ꢁ
1
ꢁ
C1 ); H NMR (CDCl3) δ: 1.35 (s, 3H, CH3), 1.75 (ddd,
Heteroatom Chemistry DOI 10.1002/hc

32 Nova´k et al.
5-1A.∗ 31P NMR (CDCl3) δ: 37.8; 13C NMR (CDCl3)
δ: 22.5 (J = 8.5, CH3), 29.8 (J = 63.2, C6),a 33.1
1H, J1 = 18.1, J2 = 8.3, J3 = 2.2, CH2), 1.23 (ddd, 1H,
J1 = 16.0, J2 = 7.6, J3 = 2.0, CH2), 2.29–2.43 (m, 2H,
CH2 and CH), 2.65–2.75 (m, 1H, CH2), 3.36 (dt, 2H,
J = 28.8, 13.5, CH2Ph), 7.22–7.40 (m, 5H, Ar).
3B. 31P NMR (CDCl3) δ: 88.6.
(J = 59.5, C2),a 36.4 (J = 63.0, CPh),b 55.8 (CH3O),
c
ꢁ
78.5 (J = 4.2, C3), 126.7 (C4 ), 128.6 (J = 5.3, C5),
d
e
ꢁ
ꢁ
128.4 (C3 ), 129.0 (J = 5.1, C2 ), 130.6 (J = 11.1,
f
1
ꢁ
C1 ), 137.3 (J = 11.4, C4); H NMR (CDCl3) δ: 1.88
(s, 3H, CH3), 2.00–2.72 (m, 4H, P(CH2)2), 3.21 (d,
2H, J = 15.0, CH2Ph), 3.43 (s, 3H, OCH3),g 4.00–4.30
(m, 1H, CH), 7.10–7.42 (m, 5H, Ar).
1-Benzyl-4-chloro-3-methyl-1,2-dihydrophosphi-
nine 1-oxide 4
5-2A. 31P NMR (CDCl3) δ: 35.0; 13C NMR (CDCl3)
δ: 22.9 (J = 8.5, CH3), 28.9 (J = 62.5, C6),h 31.3
(J = 62.0, C2),h 37.5 (J = 62.8, CPh),b 57.3 (CH3O),
A 0.50 g (1.73 mmol) sample of phosphabicyclo-
hexane oxide 2 consisting of isomers A (75%) and
B (25%) was heated at 135◦C in a vial for 4 min
(the evolution of hydrochloride acid started after
1 min). The crude product was purified by column
chromatography (2% methanol in chloroform, sil-
ica gel) to give 0.38 g (87%) of dihydrophosphi-
nine 1-oxide 4 as a 3:1 mixture of 4A and 4B. MS,
253 (100, [M + H]+), 154 (68), 136 (67), 91 (93), 69
(82); HRMS, [M + H]+found = 253.0555, C13H15ClOP re-
quires 253.0549.
c
d
ꢁ
ꢁ
79.1 (J = 5.3, C3), 126.7 (C4 ), 128.4 (C3 ), 129.4
e
f
ꢁ
ꢁ
(J = 5.1, C2 ), 131.0 (J = 8.5, C1 ), 137.5 (J = 9.6, C4);
1H NMR (CDCl3) δ: 1.94 (s, 3H, CH3), 2.00–2.72 (m,
4H, P(CH2)2), 3.21 (d, 2H, J = 15.0, CH2Ph), 3.37 (s,
3H, OCH3),g 4.00–4.30 (m, 1H, CH), 7.10–7.42 (m,
5H, Ar).
5-3B. 31P NMR (CDCl3) δ: 35.8; 13C NMR (CDCl3)
δ: 25.8 (J = 63.5, C6), 26.9 (J = 5.6, CH3), 35.7
4A. 31P NMR (CDCl3) δ: 23.9; 13C NMR (CDCl3) δ:
22.2 (J = 8.4, CH3), 31.6 (J = 69.3,C2), 37.0 (J = 68.1,
C7), 118.0 (J = 89.9, C6), 122.7 (J = 18.8, C3), 126.0
(J = 60.7, C2), 36.4 (J = 63.5, CPh),b 50.4 (CH3O),
c
ꢁ
77.0 (J = 3.1, C3), 122.4 (J = 6.2, C5), 126.7 (C4 ),
d
e
ꢁ
ꢁ
127.9 (J = 10.9, C4), 128.4 (C3 ), 129.1 (J = 4.9, C2 ),
130.7 (J = 8.1, C1 ) ; 1H NMR (CDCl3) δ: 1.52 (s,
3H, CH3), 2.00–2.72 (m, 4H, P(CH2)2), 3.21 (d, 2H,
J = 15.0, CH2Ph), 3.22 (s, 3H, OCH3),g 6.06 (bdt, 1H,
J1 = 23.0, J2 = 10.0, CH ), 7.10–7.42 (m, 5H, Ar).
5-4B. 31P NMR (CDCl3) δ: 36.1; 13C NMR (CDCl3)
δ: 25.5 (J = 2.8, CH3), 26.1 (J = 64.2, C6), 31.7
(J = 63.4, C2), 37.8 (J = 63.7, CPh),b 49.9 (CH3O),
76.7 (J = 3.1, C3), 121.5 (J = 7.0, C5), 126.5 (J = 2.0,
f
ꢁ
ꢁ
(J = 3.3, C4), 126.1 (J = 3.3, C4 ), 127.8 (J = 2.8, C3 ),
ꢁ
ꢁ
ꢁ
128.6 (J = 5.3, C2 ), 130.0 (J = 7.9, C1 ), 142.4 (J = 1.2,
1
C5); H NMR (CDCl3) δ: 1.96 (s, 3H, CH3), 2.58 (dd,
1H, J = 18.6, 11.3, CH2), 2.76 (t, 1H, J = 19.5, CH2),
3.26 (dd, 2H, J = 15.5, 4.2, CH2Ph), 6.08 (t, 1H,
J = 12.7, C6H), 6.67 (dd, 1H, J = 34.1, 12.9, C5H),
7.22–7.38 (m, 5H, Ar).
4B. 31P NMR (CDCl3) δ: 22.5; 13C NMR (CDCl3)
δ: 23.6 (J = 12.5, CH3), 30.2 (J = 68.0, C2), 36.6
(J = 68.4, CPh), 117.5 (J = 93.6, C6), 122.2 (J = 10.2,
c
d
ꢁ
ꢁ
C4 ), 127.4 (J = 11.4, C4), 128.2 (C3 ), 129.1 (J = 5.0,
e
f 1
ꢁ
ꢁ
C2 ), 130.7 (J = 7.5, C1 ) ; H NMR (CDCl3) δ: 1.59 (s,
3H, CH3), 2.00–2.72 (m, 4H, P(CH2)2), 3.21 (d, 2H, J
= 15.0, CH2Ph), 3.16 (s, 3H, OCH3),g 6.06 (bdt, 1H,
J1 = 23.0, J2 = 10.0, CH), 7.10–7.42 (m, 5H, Ar).
ꢁ
C3), 125.8 (J = 3.1, C4), 126.1 (J = 3.3, C4 ), 127.8
ꢁ
ꢁ
ꢁ
(J = 2.8, C3 ), 128.7 (J = 5.3, C2 ), 130.2 (J = 8.0, C1 ),
1
143.7 (J = 1.6, C5); H NMR (CDCl3) δ: 2.12 (s, 3H,
CH3).
5- and 3-Methyl-1-benzyl-4-chloro-3-hydroxy-
1,2,3,6-tetrahydrophosphinine 1-Oxide 6
5- and 3-Methyl-1-benzyl-4-chloro-3-methoxy-
1,2,3,6-tetrahydrophosphinine 1-oxide 5
A solution of 0.40 g (1.38 mmol) of phosphabicyclo-
hexane oxide 2 consisting of isomers A (75%) and
B (25%) and 2.4 g (13.8 mmol) of silver nitrate in
10 mL of water was refluxed for 2 h. After filtration,
the mixture was extracted with chloroform and the
organic phase was dried over sodium sulfate and
concentrated. The crude product was purified by
column chromatography (3% methanol in chloro-
form, silica gel) to give 0.22 g (60%) of compound
6 as a 5.5:2.4:1.4:1 mixture of four isomers. MS,
271 (100, [M + H]+), 253 (82), 154 (91), 136 (90), 91
A solution of 0.40 g (1.38 mmol) of phosphabicyclo-
hexane oxide 2 consisting of isomers A (75%) and
B (25%) and 4.2 g (25.0 mmol) of silver nitrate in
15 mL of methanol was refluxed for 24 h. After filtra-
tion, the mixture was extracted with chloroform and
the organic phase was dried over sodium sulfate and
concentrated. The crude product was purified by col-
umn chromatography (3% methanol in chloroform,
silica gel) to give 0.29 g (70%) of compound 5 as a
40:28:21:10 mixture of four isomers with a purity of
95%. A further refinement by chromatography led
to a 1:1.1:1.2:1 mixture of the isomers. MS, 285 (88,
[M + H]+), 253 (64), 137 (100); HRMS, [M + H]+found
= 285.0799, C14H19ClO2P requires 285.0811.
∗ A,Bthe corresponding signals within the isomer pairs may be re-
versed. a−htentative assignment.
Heteroatom Chemistry DOI 10.1002/hc

A New P-Heterocyclic Family 33
(92); HRMS, [M + H]+found = 271.0641, C13H17ClO2P
requires 271.0655.
ꢁ
1
C1 ); H NMR (CDCl3) δ: 1.04 (dd, 3H, J = 6.3, 2.6,
CH3), 1.39–2.22 (m, 9H, 4 × CH2 + CH), 3.17 (d, 2H,
J = 12.6, CH2Ph), 7.19–7.41 (m, 5H, Ar).
6-1. 31P NMR (CDCl3) δ: 37.9; 13C NMR (CDCl3)
δ: 23.3 (J = 9.6, CH3), 31.3 (J = 64.3, C6),a 31.8
(J = 61.4, C2),a† 36.2 (J = 61.6, CPh), 69.5 (C3), 125.7
7B. 31P NMR (CDCl3) δ: 39.9; 13C NMR (CDCl3) δ:
20.5 (J = 5.7, C5), 24.6 (J = 14.3,CH3), 25.1 (J = 62.2,
C6), 28.1 (J = 4.8, C3), 34.2 (J = 62.4, CPh), 35.4
ꢁ
(J = 4.8, C5), 127.2 (J = 2.9, C4 ), 128.8 (J = 2.4,
ꢁ
ꢁ
ꢁ
C3 ), 129.2 (J = 5.1, C2 ), 130.4 (J = 8.0, C1 ), 131.1
(J = 10.3, C4); 1H NMR (CDCl3) δ: 1.92 (s, 3H, CH3),
2.00–2.65 (m, 4H, P(CH2)2), 3.25 (d, 2H, J = 15.0,
CH2Ph), 3.90 (bs, 1H, OH), 4.50 (bd, 1H, J = 19.0,
CH), 7.10–7.42 (m, 5H, Ar).
ꢁ
(J = 4.6, C4), 38.8 (J = 60.0, C2), 128.8 (J = 2.8, C4 ),
ꢁ
ꢁ
128.7 (J = 2.5, C3 ), 129.4 (J = 4.9, C2 ), 132.0 (J = 7.3,
1
ꢁ
C1 ); H NMR (CDCl3) δ: 0.98 (dd, 3H, J = 6.6, 2.1,
CH3), 1.39–2.22 (m, 9H, 4 × CH2 and CH), 3.14 (d,
2H, J = 15.5, CH2Ph), 7.19–7.41 (m, 5H, Ar).
6-2. 31P NMR (CDCl3) δ: 35.0; 13C NMR (CDCl3)
δ: 23.3 (J = 9.6, CH3), 31.3 (J = 64.3, C6),b 32.3
(J = 61.6, C2),b 37.0 (J = 61.9, CPh), 69.1 (J = 4.5,
1-Benzyl-3-methyl-1,2,3,4,5,6-hexahydrophosphi-
nine 1-oxide 7(from 3-Benzyl-6,6-dichloro-1-meth-
yl-3-phosphabicyclo[3.1.0]hexane 3-oxide 2)
ꢁ
C3), 126.4 (J = 4.9, C5), 126.9 (J = 3.0, C4 ), 128.5
ꢁ
ꢁ
(J = 2.6, C3 ), 129.7 (J = 5.3, C2 ), 130.5 (J = 11.0,
The hydrogenation of phosphabicyclohexane oxide 2
consisting of isomers A (75%) and B (25%) was per-
formed according to the procedure described above
except the mixture was kept under a 9-bar atmo-
sphere of hydrogen at 90◦C for 16 h. Workup and pu-
rification by column chromatography (2% methanol
in chloroform, silica gel) afforded 0.11 g (48%) of 7
as a 2:1 mixture of diastereoisomers A and B.
1
ꢁ
C1 ), 131.3 (J = 8.8, C4); H NMR (CDCl3) δ: 1.91 (s,
3H, CH3), 2.00–2.65 (m, 4H, P(CH2)2), 3.25 (d, 2H,
J = 15.0, CH2Ph), 3.90 (bs, 1H, OH), 4.69 (bd, 1H,
J = 20.4, CH), 7.10–7.42 (m, 5H, Ar).
6-3. 31P NMR (CDCl3) δ: 35.3; 13C NMR (CDCl3) δ:
26.0 (J = 64.4, C6), 29.5 (J = 5.6, CH3), 30.2 (J = 63.4,
C2), 36.4 (J = 63.2, CPh), 71.9 (J = 5.3, C3), 118.3
ꢁ
(J = 6.0, C5), 126.9 (J = 3.1, C4 ), 128.6 (J = 2.9,
1-Benzyl-4-chloro-5-methyl-1,2,3,6-tetrahydro-
phosphinine 1-oxide 8
ꢁ
ꢁ
ꢁ
C3 ), 129.5 (J = 5.2, C2 ), 131.0 (J = 8.5, C1 ), 140.4
(J = 12.4, C4); 1H NMR (CDCl3) δ: 1.63 (s, 3H, CH3),
2.00–2.65 (m, 4H, P(CH2)2), 3.25 (d, 2H, J = 15.0,
CH2Ph), 3.90 (bs, 1H, OH), 5.84 (bdt, 1H, J1 = 24.8,
J2 = 4.6, CH ), 7.10–7.42 (m, 5H, Ar).
To 0.50 g (2.0 mmol) of dihydrophosphinine ox-
ide 4 consisting of isomers A (75%) and B (25%)
in 10 mL of CH2Cl2, 1.5 mL of a 2 M solution of
borane–dimethyl sulfide in THF was added and the
mixture was stirred for 24 h. The reaction mixture
was treated with 0.5 mL of water, stirred for 10 min,
and the organic phase was dried over MgSO4. The
crude product was purified by column chromatogra-
phy (3% methanol in chloroform, silica gel) to give
0.36 g (70%) of compound 8 as a 9:1 mixture of two
double bond isomers A and B. HRMS, [M + H]f+ound
= 255.0689, C13H17ClOP requires 255.0706.
6-4: 31P NMR (CDCl3) δ: 38.4.
3-Benzyl-3-methyl-1,2,3,4,5,6-hexahydrophos-
phinine 1-oxide 7 (from 1-benzyl-4-chloro-3-
methyl-1,2-dihydrophosphinine 1-oxide 4)
To 0.30 g (1.19 mmol) of dihydrophosphinine ox-
ide 4 consisting of isomers A (75%) and B (25%) in
20 mL of ethanol 0.06 g of a 5% Pd C was added
and the mixture was stirred in an autoclave under
a 4.5-bar atmosphere of hydrogen at 23◦C for 24 h.
The suspension was filtered, the solvent of the fil-
trate was evaporated, and the residue purified by
column chromatography (2% methanol in chloro-
form, silica gel) to give 0.21 g (80%) of compound
7 as a 9:1 mixture of diastereoisomers A and B;
MS, 223 (100, [M + H]+), 191 (25), 136 (35), 91 (28);
HRMS, [M + H]+found = 223.1241, C13H19OP requires
223.1252.
8A. 31P NMR (CDCl3) δ: 34.7; 13C NMR (CDCl3)
δ: 23.2 (CH3), 23.6 (J = 74.1, C2), 31.2 (d, J = 64.1,
C6), 31.4 (J = 5,56, C3), 35.4 (J = 63.0, CPh), 124.4
ꢁ
(J = 5.3, C4), 126.6 (J = 12,6, C3), 127,1 (J = 3.1, C4 ),
ꢁ
ꢁ
128.9 (J = 2.6, C3 ), 129.4 (J = 5.2, C2 ), 131.2 (J = 7.9,
1
ꢁ
C1 ); H NMR (CDCl3) δ: 1.86 (s, 3H, CH3), 1.85–
2.20 (m, 2H, CH2), 2.28–2.55 (m, 2H, CH2), 2.58–2.80
(m, 1H, CH2), 2.80–3.02 (m, 1H, CH2), 3.19 (dd, 2H,
J = 14.3, 1.46, CH2Ph), 7.20–7.40 (m, 5H, Ar).
8B. 31P NMR (CDCl3) δ: 36.3.
7A. 31P NMR (CDCl3) δ: 39.8; 13C NMR (CDCl3) δ:
22.9 (J = 3.7, C5), 24.2 (J = 15.1, CH3), 26.0 (J = 62.1,
C6), 31.7 (J = 3.6, C3), 33.9 (J = 59.6, CPh), 34.5
4- and 6-Methyl-5-chloro-2-oxo-2-benzyl-2λ5-
phosphabicyclo[2.2.2]octa-5,7-diene-7,8-
dicarbonic Acid Dimethyl Ester 9
ꢁ
(J = 5.4, C4), 35.2 (J = 60.0, C2), 126.8 (J = 2.8, C4 ),
ꢁ
ꢁ
128.7 (J = 2.5, C3 ), 129.5 (J = 4.9, C2 ), 131.7 (J = 8.0,
To 60.0 mg (0.24 mmol) of dihydrophosphinine ox-
ide 4 consisting of isomers A (75%) and B (25%) in
† a,b
tentative assignment.
Heteroatom Chemistry DOI 10.1002/hc

34 Nova´k et al.
3 mL of toluene, 0.15 mL (1.20 mmol) of dimethyl
acetylenedicarboxylate was added and the mixture
was refluxed for 12 h. The volatiles were evaporated,
and the residue was purified by column chromatog-
raphy (3% methanol in chloroform, silica gel) to give
60.0 mg (66%) of compound 9 as a 37:27:18:18 mix-
ture of four isomers. The spectroscopic data of the
four isomers were similar to those published previ-
ously (δP: (CDCl3) δ: 55.2, 54.3, 51.0, and 50.0, δP lit
[13]: 55.3, 54.3, 51.1, and 50.1).
O-Ethyl-benzyl-methylphosphinate 11b [16].
Yield: 75%; 31P NMR (CDCl3) δ: 51.8; HRMS,
[M + H]+found
=
199.0871, C10H16O2P requires
199.0881.
O-Propyl-benzyl-methylphosphinate
11c.
Yield: 83%, 31P NMR (CDCl3) δ: 51.3; HRMS,
[M + H]+found = 213.1029,
C11H18O2P
requires
213.1044.
O-Butyl-benzyl-methylphosphinate
11d.
Yield: 85%; 31P NMR (CDCl3) δ: 51.4; HRMS,
4- and 6-Methyl-2-benzyl-5-chloro-10-phenyl-
10-aza-2 λ5-phosphatricyclo[5.2.2.07,8]undec-5-
ene-9,11-dion-2-oxide 10
[M + H]+found = 227.1191,
C12H20O2P
requires
227.1201.
To 60.0 mg (0.24 mmol) of dihydrophosphinine ox-
ide 4 consisting of isomers A (75%) and B (25%)
in 3 mL of toluene, 0.12 g (0.69 mmol) of N-
phenylmaleimide was added and the mixture was
refluxed for 8 h. The volatiles were evaporated, and
the residue was purified by column chromatogra-
phy (3% methanol in chloroform, silica gel) to give
50.0 mg (50%) of compound 10 as a 55:45 mixture
of diastereomers A and B. The spectroscopic data of
10A and 10B were similar to those published previ-
ously (δP (CDCl3) δ: 47.7 and 47.4, δP: lit [13] 47.5 and
47.0).
REFERENCES
[1] Phosphorus–Carbon Heterocyclic Chemistry: The
Rise of a New Domain; Mathey, F. (Ed.); Perga-
mon/Elsevier, Amsterdam, 2001.
[2] Keglevich, Gy. Synthesis 1993, 931.
[3] Keglevich, Gy. Rev Heteroatom Chem 1996, 14,
119.
[4] Keglevich, Gy.; To´´ke, L. Trends Org Chem 1993, 4,
245.
[5] Keglevich, Gy. Curr Org Chem 2006, 10, 93.
[6] Keglevich, Gy.; Szelke, H.; Kova´cs, J. Curr Org Synth
2004, 1, 377.
[7] Quin, L. D.; Borleske, S. G.; Engel, J. F. J Org Chem
1973, 38, 1858.
O-Alkyl-benzyl-methylphosphinates 11
[8] Buchanan, G. W.; Webb, V. L. Org Magn Reson 1983,
21, 436.
[9] Sander, M. Chem Ber 1962, 95, 473.
[10] Kova´cs, J.; Bala´zsdi Szabo´, N.; Nagy, Z.; Luda´nyi,
K.; Keglevich, Gy. Heteroatom Chem 2005, 16,
320.
[11] Keglevich, Gy.; Janke, F.; Fu¨lo¨p, V.; Ka´lma´n, A.; To´th,
G.; To´´ke, L. Phosphorus Sulfur 1990, 54, 73.
[12] Keglevich, Gy.; Tungler, A.; Nova´k, T.; To´´ke, L. J
Chem Res (S) 1996, 528.
[13] Keglevich, Gy.; Steinhauser, K.; Luda´nyi, K.; To´´ke,
L. J Organomet Chem 1998, 570, 49.
The solution of 40.0 mg (0.10 mmol) of benzyl-
phosphabicyclooctadiene 9 consisting of isomers
(37:27:18:18) and 4 mL of the corresponding alco-
hol in 45 mL of acetonitrile was irradiated in a pho-
tochemical reactor with a mercury lamp (125 W)
for 1 h. Volatile components were removed, and the
residue so obtained was purified by flash chromatog-
raphy (3% methanol in chloroform, silica gel) to give
the corresponding phosphinates 11.
[14] Keglevich, Gy.; Duda´s, E. Synth Commun (in press).
[15] Keglevich, Gy.; Kova´cs, J.; Szelke, H.; Ko¨rtve´lyesi, T.
J Heterocyclic Chem 2006, 43, 723.
O-Methyl-benzyl-methylphosphinate 11a. Yi+eld:
75%; 31P NMR (CDCl3) δ: 53.5; HRMS, [M + H]found
= 185.0741, C9H14O2P requires 185.0731.
[16] Steininger, E. Chem Ber 1963, 96, 3184.
Heteroatom Chemistry DOI 10.1002/hc