Fragmentation-related phosphinylations using 2-aryl-2-phosphabicyclo[2.2.2]oct-5-ene- and -octa-5,7-diene 2-oxides

Article abstract of DOI:10.1002/hc.10176

The article discussed about fragmentation-related phosphinylations. A series of new P-methylphenyl P-heterocycles were introduced. The bridged P-heterocycles were useful in the photo- or thermoinduced fragmentation-related phosphinylation of hydroxy compo

Full text of DOI:10.1002/hc.10176

Heteroatom Chemistry
Volume 14, Number 5, 2003
Fragmentation-Related Phosphinylations
Using 2-Aryl-2-phosphabicyclo[2.2.2]oct-
5-ene- and -octa-5,7-diene 2-Oxides
2
1
1
1
´
Gyo¨rgy Keglevich, Helga Szelke, Agnes Ba´lint, T´ımea Imre,
Krisztina Luda´nyi,2 Zolta´n Nagy,3 Miklo´s Hanusz,4 Ka´lma´n Simon,4
Veronika Harmat,5 and La´szlo´ To˝ke6
1Department of Organic Chemical Technology, Budapest University of Technology and Economics,
1521 Budapest, Hungary
2Hungarian Academy of Sciences, Chemical Research Center, 1525 Budapest, Hungary
3Gedeon Richter Ltd., 1475 Budapest, Hungary
4Chinoin Co. Ltd. (Member of Sanofi-Synthelabo Group), 1045 Budapest, Hungary
5Department of Theoretical Chemistry, Eo¨tvo¨s University, 1518 Budapest, Hungary
6Research Group of the Hungarian Academy of Sciences, Budapest University of Technology
and Economics, 1521 Budapest, Hungary
Received 27 February 2003
ꢀ
C
anistic investigations.
2003 Wiley Periodicals, Inc.
ABSTRACT: A series of new P-methylphenyl P-
heterocycles are introduced. The para and ortho sub-
stituted 2,5-dihydro-1H-phosphole oxides (1a and 1b)
were converted to the double-bond isomers (A and
B) of 1,2-dihydrophosphinine oxides (3a and 3b) via
the corresponding phosphabicyclo[3.1.0]hexane ox-
ides (2a or 2b). Isomeric mixture (A and B) of the
dihydrophosphinine oxides (3a and 3b) gave, in turn,
the isomers (A and B) of phosphabicyclo[2.2.2]oct-
5-enes (4a and 4b) or a phosphabicyclo[2.2.2]octa-
5,7-diene (5) in Diels-Alder reaction with dienophiles.
The bridged P-heterocycles (4 and 5) were useful in the
photo- or thermoinduced fragmentation-related phos-
phinylation of hydroxy compounds and amines. The
new precursors (4a and 4b) were applied in mech-
Heteroatom Chem 14:443–451, 2003; Published online
in Wiley InterScience (www.interscience.wiley.com). DOI
10.1002/hc.10176
INTRODUCTION
The phosphinylation of nucleophiles by low-
coordinated P-fragments, like methylenephosphine
oxides or sulfides, is a novel synthetic method [1]. An
attractive approach is one wherein the methylene-
phosphine oxide is generated by the fragmentation
of bridged P-heterocycles, such as 2-phosphabicyclo-
[2.2.2]octa-5,7-diene- or phosphabicyclo[2.2.2]oct-
5-ene derivatives [2–10]; the simplest way of achiev-
ing the fragmentation is thermolysis above 200◦C
[3–5]. Because of their more strained framework,
the fragmentation of bicyclooctadienes is easier than
that of bicyclooctenes [4,11].
Correspondence to: Gyo¨rgy Keglevich; e-mail: keglevich@
oct.bme.hu.
Contract grant sponsor: OTKA.
Contract grant number: T 042479.
2003 Wiley Periodicals, Inc.
c
ꢀ
443

444 Keglevich et al.
To achieve phosphinylation, the low-coordinated
P-fragment should be generated in the presence of
a nucleophile [3–5]. Another way of utilizing the
phosphabicyclooctene derivatives in phosphinyla-
tions is their UV light-mediated reaction with al-
cohols or amines [6–10]. Besides the elimination–
addition (EA) mechanism via a methylenephosphine
oxide, a novel addition–elimination (AE) route in-
volving an intermediate with a pentavalent pentaco-
ordinated phosphorus atom was also substantiated
by us [9,10,12,13].
as an 80–20% mixture of isomers 2-1 and 2-2
(Scheme 1).
The assumption that 2-1 is the diastereomer
containing the aryl group cis to the dichlorocy-
clopropane ring, while the other one (2-2) is the
species with anti geometry is in full agreement
with earlier cases, according to which during the
dichlorocarbene addition reaction of the 1-phenyl-
2,5-dihydro-1H-phosphole only the cis isomer was
formed [14], while during the cyclopropanation of
model compounds with sterically demanding sub-
stituents, such as the 2,4,6-trimethylphenyl- and the
2,4,6-triisopropylphenyl, the resulting phosphabicy-
clohexane consisted of two isomers with minor cis
component [15,16].
In this paper, new P-aryl phosphabicyclooctene
derivatives are described as precursors in O- and
N-phosphinylations, and as suitable model com-
pounds in mechanistic studies.
The starting aryl-dihydro-1H-phosphole oxides
(1a and 1b), the phosphabicyclohexanes (2a-1, 2b-
1, and 2b-2), and the double-bond isomers (A and
B) of the dihydrophosphinine oxides (3a and 3b)
were characterized by 31P, 13C, and 1H NMR, as well
as mass spectroscopical data. The spectral param-
eters showed close resemblance to those of earlier
described analogues [15–17].
The stereostructure of phosphabicyclohexane
2b-1 was confirmed by single crystal X-ray analy-
sis. It can be seen in Fig. 1 that the relative po-
sition of the dichlorocyclopropane ring and the
aryl group is indeed cis. The C(1), C(2), P(3), C(4),
C(5) ring of 2b-1 has an envelope conformation
with P(3) atom below the plain of the other four
atoms. This type of conformation is due to the
C(1), C(5), C(6) cyclopropane ring attached to the
five-membered ring. The phenyl group attached to
P(3) atom is in the equatorial, while O(1) is in
the axial position. The tetrahedron around P(3) is
RESULTS AND DISCUSSION
First we prepared the starting materials of the
desired new precursors, the para- and ortho-
methylphenyl-1,2-dihydrophosphinine 1-oxides 3a
and 3b, respectively. The five-membered ring of
the corresponding aryl-2,5-dihydro-1H-phosphole
oxides (1a and 1b) was expanded by making use of
ring-enlargement method [14], according to which
dichlorocarbene was added to the double-bond of
the starting material (1a and 1b) in the first step, fol-
lowed by the thermal ring opening of the phosphabi-
cyclo[3.1.0]hexane 3-oxides (2a and 2b) so formed
to give the desired P-aryl 1,2-dihydrophosphinine ox-
ides (3a and 3b) as a ca. 3:1 mixture of double-bond
isomers (A and B).
The para-methylphenyl phosphabicyclohexane
(2a) was formed as a single isomer 2-1, while the
ortho-methylphenyl counterpart (2b) was formed
SCHEME 1

Fragmentation-Related Phosphinylations Using 2-Aryl-2-phosphabicyclo[2.2.2]oct-5-ene- and -octa-5,7-diene 2-Oxides 445
◦
◦
˚
FIGURE 1 Perspective view of 2b-1 with the bond distances (A), bond angles ( ), and torsion angles ( ) selected.
[P3 C2 1.817(10), C2 C1 1.515(11), C1 C6 1.477(13), C6 C5 1.483(15), C1 C5 1.515(11), C5 C4 1.509(13), C4 P3
1.841(9); P3 C2 C1 103.6(6), C2 C1 C6 116.1(8), C1 C6 C5 62.3(7), C6 C5 C4 120.7(9), C5 C4 P3 101.8(6),
C4 P3 C2 94.4(4), C4 P3 O1 112.2(4), O1 P3 C8 114.7(4), O1 P3 C2 113.3(5), C8 P3 C2 111.6(4), C8 P3 C4
108.8(4), C2 C1 C5 110.3(8), C1 C5 C4 114.4(7), C2 C1 C7 115.5(8); C14 C9 C8 P3 −0.8(14), C6 C1 C2 P3
92.3(9), C6 C5 C4 P3 −89.0(9), C7 C1 C5 C4 138.0(10), C7 C1 C2 P3 −116.6(9)].
somewhat distorted. The two most extreme values
are 94.4(4)◦ for C(4) P(3) C(2) and 114.7(4)◦ for
O(1) P(3) C(8) as expected
consisted of configurational isomers (5A-1, 5A-2,
5B-1, and 5B-2) (Scheme 2). The isomers were char-
acterized by 31P and 13C NMR, as well as mass spec-
troscopical data. NMR spectral features of the P-tolyl
cycloadducts (4a, 4b, and 5) were in agreement with
those reported for the P-phenyl analogues [7,9].
The P-aryl precursors (4a, 4b, and 5) were
then utilized in fragmentation-related phosphiny-
lations. The acetonitrile solutions of the tolyl-
phosphabicyclooctenes (4a and 4b) were irradiated
(254 nm) at 26◦C in the presence of simple alco-
hols or primary amines to give phosphinic esters
(7–11/a,b) or amides 12,13/a,b, respectively, in rea-
sonable yields after flash column chromatography
(Schemes 3 and 4) (Table 1).
In the next stage of our work, the aryl-1,2-
dihydrophosphinine oxides (3a and 3b) were uti-
lized in the synthesis of bridged P-heterocycles. The
Diels–Alder reaction of 1-tolyl-dihydrophosphinine
oxides 3a and 3b with N-phenylmaleimide in boil-
ing toluene furnished phosphabicyclooctenes 4a and
4b, respectively. Starting from the 3:1 isomeric mix-
ture of the dihydrophosphinine oxides (3), the cy-
cloadducts (4) were obtained as a ca. 3:2 isomeric
mixture after column chromatography (Scheme 2).
The isomers (A and B) of the products (4a and 4b)
were characterized by 31P, 13C, and 1H NMR, as well
as mass spectroscopical data.
Products 11a and 11b consisted of two diastere-
omers. The purity of the phosphinic derivatives
(7–13) characterized by 31P and, in some cases, by
13C NMR spectroscopical data was ca. 95% accord-
ing to GC–MS. The EI mass spectra were obtained
The para-methylphenyl-dihydrophosphinine ox-
ides (3Aa and 3Ba) were also converted to the cor-
responding phosphabicyclooctadienes (5A and 5B).
In this case, the double-bond isomers (5A and 5B)
SCHEME 2

446 Keglevich et al.
TABLE 1 Phosphinic Derivatives 7–12 Prepared by the Photolysis of Cycloadducts (4 or 5) in the Presence of Nucleophiles
HRFAB
Precursor Nucleophile Product Yield (%) δP (CDCl3)
MS, m/z (rel. int.)
(M + H)found (M + H)calc
4a
4a
4a
4a
MeOH
7aa
8ab
9a
91
89
85
88
45.3
43.5
43.3
41.8
184 (M+, 30), 183 (37), 169
(100), 154 (18), 139 (23),
91 (52)
185.0709
185.0731
EtOH
198 (M+, 13), 197 (5), 170
(59), 155 (100), 153 (20)
139 (24), 91 (54)
199.0859
199.0888
n-PrOH
i-PrOH
212 (M+, 2), 171 (100), 170
(35), 155 (99), 153 (58) 139
(16), 91 (53)
10a
212 (M+, 4), 171 (90), 170
(29), 155 (100), 153 (56)
139 (14), 91 (50)
4a
4b
sec-BuOH
11a
7b
42.3 (53%)
42.5 (47%)
45.0
227.1139
185.0705
227.1201
185.0731
MeOH
87
92
89
184 (M+, 64), 183 (56), 169
(47), 154 (35), 139 (96),
91(100)
4b
4b
EtOH
8b
43.0
41.3
198 (M+, 15), 197 (8), 170
(50), 155 (100), 153 (19)
139 (31), 91 (95)
199.0855
199.0888
i-PrOH
10b
212 (M+, 14), 171 (14), 170
(100), 155 (36), 153 (18),
139 (3), 91 (40)
4b
4a
4a
4b
4b
sec-BuOH
i-PrNH2
n-BuNH2
i-PrNH2
n-BuNH2
MeOH
11b
12a
13a
12b
13b
7a
41.3 (53%)
41.5 (47%)
30.1
227.1142
212.1164
226.1309
212.1167
226.1303
227.1201
212.1204
226.1361
212.1204
226.1361
69
78
65
82
86
211 (M+, 2), 196 (61), 153
(100), 91 (46)
32.1
29.3
31.5
45.2
225 (M+, 8), 153 (100), 91
(35)
211 (M+, 3), 196 (20), 153
(57), 91 (100)
225 (M+, 7), 153 (68), 91
(100)
5
(M + H)+ = 185
a
δC (CDCl3) 15.5 (J = 103.2, P-Me), 21.6 (Ar-Me), 51.0 (J = 6.2, MeO).
b
δC (CDCl3) 16.4 (J = 106.7, P-Me), 16.8 (CH2CH3), 22.0 (Ar-Me), 60.8 (J = 6.2, CH2O).
by GC–MS. Elemental compositions of the products
(7–13) were confirmed by HRFAB measurements.
The NMR and mass spectral parameters are listed
in Table 1. The isomeric composition of the precur-
sors (4) did not cause any problem, as the bridg-
ing unit of both isomers (A and B) was utilized
in the fragmentation-related phosphinylation. Aryl-
phosphabicyclooctadiene 5, as the mixture of four
isomers (A-1, A-2, B-1, and B-2), was used in both
SCHEME 3
SCHEME 4

Fragmentation-Related Phosphinylations Using 2-Aryl-2-phosphabicyclo[2.2.2]oct-5-ene- and -octa-5,7-diene 2-Oxides 447
reactivity during the phosphinylation. Some infor-
mation was anticipated to be able to substantiate
the involvement of the EA or the AE mechanism. Be-
cause of these reasons, the equimolar mixture of 4a
and 4b was irradiated in the presence of methanol,
isopropanol, and sec-butanol and the reaction was
monitored by 31P NMR spectroscopy. With methanol
and isopropanol, no discrimination between the two
aryl derivatives (4a and 4b) could be observed; the
precursors (4a and 4b) were consumed and the
SCHEME 5
products (7a/7b or 10a/10b) appeared in the same
rate. At the same time, by using sec-butanol, the
ortho-methylphenyl cycloadduct (4b) was consumed
somewhat slower than the para-methylphenyl coun-
terpart (4a) and the appearance of phosphinate 11b
was delayed as compared to that of 11a. Esters 11a
and 11b were formed as the mixture of diastere-
omers (Scheme 7 showing the molar percentages ob-
tained on the basis of relative 31P NMR intensities).
In an another kind of competitive experiment,
the aryl-phosphabicyclooctenes (4a and 4b) were ir-
radiated in the presence of an equimolar mixture of
methanol and sec-butanol. It was found that as a con-
sequence of the more relevant steric hindrance due
to the ortho-methyl substituent, significantly less of
the butylphosphonate (11) was formed in the reac-
tion of precursor 4b, than in that of 4a (12 and 19%,
respectively) (Schemes 8 and 9). This also refers to
the involvement of intermediate 17, whose forma-
tion is probably more sensitive toward steric effects.
Indicating the role of steric hindrance, the above
experiments seem to support the involvement of the
AE mechanism with the intermediate of type 17
present. At the same time, the EA route may be
a concurrent possibility in the UV light-mediated
fragmentation-related posphinylation of alcohols.
In summary, new aryl-phosphabicyclo[2.2.2]oct-
5-enes and an aryl-phosphabicyclo[2.2.2]octa-5,7-
diene were synthesized and utilized in photo- and
thermoinduced phosphinylation of alcohols, hydro-
quinone, and primary amines. Mechanistic stud-
ies with the aryl-substituted model compounds sug-
gested the involvement of the novel AE mechanism
for the photochemically induced fragmentation-
related phosphinylations.
UV light-mediated and in thermo-induced phos-
phinylations (see Schemes 5 and 6, respectively).
The phosphinylation of hydroquinone was not so ef-
ficient (the yield of phosphinate 15 was 35% after
flash column chromatography), since a temperature
of 240◦C had to be applied. Product 15 was identified
by 31P NMR and MS. It is recalled that only the phos-
phabicyclooctadienes exhibiting a considerable ring
strain are useful in thermally achieved phosphoryla-
tions [4,5].
It is also recalled that while the thermoinduced
phosphinylation obviously take place through an
EA mechanism involving methylenephosphine oxide
(e.g. 16) as the intermediate [3–5], the photochem-
ically initiated phosphinylations may also involve a
novel AE route via an intermediate with a pentava-
lent pentacoordinated phosphorus atom (e.g. 17)
[9,10,12,13].
We utilized the newly synthesized precursors
4a and 4b to obtain new data on the mecha-
nism of the photoinduced phosphinylations. We
wondered if both para-methylphenyl- and ortho-
metylphenyl-substituted phosphabicyclooctenes (4a
and 4b) show a similar or a somewhat different
EXPERIMENTAL
The 31P{ H}-, 13C{ H}-, and 1H-NMR spectra were
recorded on a Bruker DRX-500 spectrometer operat-
ing at 202.4, 125.7, and 500 MHz, respectively. Chem-
ical shifts are downfield relative to 85% H3PO4 or
TMS. The couplings are given in Hz. The atoms of
the aryl rings are numbered by 1 , 2 , 3 , etc. Mass
spectrometry was performed on a PE SCIEX API
1
1
SCHEME 6

448 Keglevich et al.
SCHEME 7
2000 type triple quadrupol and on a ZAB-2SEQ in-
strument.
1-(2-Methylphenyl-)3-methyl-2,5-dihydro-1H-
phosphole 1-Oxide (1b)
Compound 1b was prepared similarly using 2-me-
thylbromobenzene instead of 4-methylbromoben-
zene. Yield: 22.3 g (57%) oil; 31P NMR (CDCl3)
1-(4-Methylphenyl-)3-methyl-2,5-dihydro-1H-
phosphole 1-Oxide (1a)
δ
59.2; 13C NMR (CDCl3)
δ
19.1 (3 J = 10.9,
C3–Me), 19.9 (3 J = 3.4, C2 –Me), 33.6 (1 J = 65.7,
C5), 36.7 (1 J = 68.8, C2), 120.0 (2 J = 7.4, C4),
124.7 (3 J = 11.4, C5 ),∗ 130.1 (1 J = 89.66, C1 ) 130.6
(3 J = 10.0, C3 ),* 130.6 (2 J = 10.3, C6 ),∗ 130.9 (C4 ),
To 28.9 g (0.19 mol) of 1-chloro-3-methyl-2,5-
dihydro-1H-phosphole oxide (obtained from the
reaction of 24.8 g (0.19 mol) of 1-hydroxy-3-
methyl-2,5-dihydro-1H-phosphole oxide and 17.0 ml
(0.22 mol) of thionyl chloride in 80 ml of dry chloro-
form at 26◦C for 20 h after concentration in vacuo)
in 70 ml of tetrahydrofuran was added dropwise 0.21
mol of 4-methylphenylmagnesium bromide in 70 ml
of tetrahydrofuran (prepared from 35.5 g (0.21 mol)
of 4-methylbromobenzene and 5.0 g (0.21 mol) mag-
nesium in 70 ml of tetrahydrofuran) at 0◦C with stir-
ring. After addition was complete, contents of the
flask were stirred at 26◦C for 4 h. Solvent was evap-
orated and the residue taken up in the mixture of
100 ml of chloroform, 5 ml of conc. hydrochloric
acid, and 50 ml of water. The organic phase was
dried (Na2SO4) and concentrated. The crude mix-
ture was purified by repeated column chromatog-
raphy (silica gel, 3% methanol in chloroform) to
afford 30.2 g (78%) of the aryl-dihydrophosphole
oxide (1a) as an oil. 31P NMR (CDCl3) δ 61.7;
13C NMR (CDCl3) δ 20.4 (3 J = 11.0, C3–Me), 21.8
(C4 –Me), 35.1 (1 J = 64.9, C5), 38.0 (1 J = 68.4, C2),
121.1 (2 J = 7.3, C4), 129.4 (3 J = 12.1, C3 ),∗ 129.6
(2 J = 10.2, C2 ),∗ 137.1 (2 J = 12.7, C3), 142.6 (C4’),∗
may be reversed; 1H NMR (CDCl3) δ 1.89 (s, C3–Me),
∗
135.8 (2 J = 12.4, C3), 139.7 (2 J = 9.3, C2 ), tentative
assignment; 1H NMR (CDCl3) δ 1.81 (s, C3–Me),
3
2.45 (s, Ar–Me), 5.57 (d, JPH = 31.0, C4–H); ES–MS,
207 (M + H); (M + H)+found = 207.0908, C12H15OP re-
quires 207.0939.
6,6-Dichloro-1-methyl-3-(4-methylphenyl-)3-
phosphabicyclo[3.1.0]hexane 3-Oxide 2a
To the solution of 15 g (37.2 mmol) of dihydrophosp-
hole 1a and 3.5 g (15.4 mmol) of trietylbenzylammo-
nium chloride (TEBAC) in 180 ml of chloroform was
added dropwise 90 g (2.25 mol) of sodium hydroxide,
whereupon the temperature gradually rose to reflux.
The contents of the flask were stirred for 4 h. Af-
ter filtration and separation, the organic phase was
made up to its original volume and 1.2 g (5.3 mmol)
of TEBAC was added. The reaction mixture was
treated with a second portion of aqueous sodium
hydroxide as above and the procedure was com-
pleted with a third such treatment—this time with-
out the addition of more catalyst. The solution ob-
tained after filtration and separation was concen-
trated. The crude product so obtained was purified
by column chromatography (silica gel, 3% methanol
3
2.42 (s, Ar–Me), 5.66 (d, JPH = 31.9, C4–H); ES–MS,
207 (M + H); (M + H)+found = 207.0907, C12H15OP re-
quires 207.0939.
SCHEME 8
SCHEME 9

Fragmentation-Related Phosphinylations Using 2-Aryl-2-phosphabicyclo[2.2.2]oct-5-ene- and -octa-5,7-diene 2-Oxides 449
(dd, 2 JPH
=
3 JHH = 12.8, C6–H), 6.89 (dd, 3 JPH = 34.6,
in chloroform) to give 14.3 g (68%) of dichlorocar-
bene adduct 2a-1 as an oil. 31P NMR (CDCl3) δ 76.3;
13C NMR (CDCl3) δ 21.1 (C4 –Me), 21.3 (3 J = 3.0, C1–
Me), 30.7 (1 J = 68.1, C4), 35.9 (2 J = 7.3, C1), 36.4
(2 J = 5.5, C5), 36.8 (1 J = 67.9, C2), 73.2 (3 J = 14.3, C6),
126.4 (1 J = 90.0, C1 ), 129.1 (2 J = 11.7, C2 ),∗ 130.0
(3 J = 9.7, C3 ),∗ 142.6 (C4 ), ∗may be reversed; 1H NMR
(CDCl3) δ 1.75 (s, C1–Me), 2.41 (s, Ar–Me); ES–MS,
289 (M + H); (M + H)+found = 289.0279, C13H15Cl2OP
requires 289.0316 for the 35Cl isotopomer.
3 JHH = 12.8, C5–H).
3Ba: 31P NMR (CDCl3) δ 15.3; 13C NMR (CDCl3)
δ
21.6 (C4 –Me), 25.0 (3 J = 12.7, C5–Me), 30.7
(1 J = 71.5, C2), 119.1 (1 J = 97.2, C6), 122.9 (2 J = 10.8,
C3), 129.4 (2 J = 13.1, C2 ),∗ 130.9 (3 J = 9.5, C3 ),∗ 142.7
(C4 ), 149.8 (C5), ∗may be reversed; 1H NMR (CDCl3)
δ 2.22 (s, C5–Me), 2.42 (Ar–Me), 6.29 (dt, C3–H).
3- and 5-Methyl-4-chloro-1-(2-methylphenyl-)-
1,2-dihydrophosphinine 1-Oxide 3Ab and 3Bb
6,6-Dichloro-1-methyl-3-(2-methylphenyl-)3-
phosphabicyclo[3.1.0]hexane 3-Oxide (2b)
Compounds 3Ab and 3Bb were prepared similarly
by heating 0.50 g (1.73 mmol) of the isomeric mix-
ture of dichlorocarbene adduct 2b at 135◦C for ca. 6
min. Yield: 0.31 g (70%) oil; ES–MS, 253 (M + H);
M+found = 253.0505, C13H14ClOP requires 253.0549
for the 35Cl isotopomer.
Compound 2b was prepared similarly using di-
hydrophosphole oxide 1b instead of 1a to fur-
nish a 8:2 mixture of isomers 2b-1 and 2b-
2. Yield: 13.1 g (66%); 2b-1 could be sepa-
rated as a crystalline compound by a simple
filtration, mp 125–127◦C (acetone); ES–MS, 289
(M + H); (M + H)+found = 289.0276, C13H15Cl2OP re-
quires 289.0316 for the 35Cl isotopomer.
3Ab: 31P NMR (CDCl3) δ 16.2; 13C NMR (CDCl3)
δ 20.5 (3 J = 3.3, C2 –Me), 22.3 (3 J = 8.7, C3–Me), 34.6
(1 J = 70.5, C2), 118.4 (1 J = 93.3, C6), 122.6 (2 J = 19.7,
C3), 124.8 (3 J = 12.0, C3 ),∗ 129.3 (1 J = 105.1, C1 ),
130.5 (3 J = 9.4, C4), 130.8 (3 J = 11.0, C5 ),∗ 131.1
(2 J = 10.6, C6 ),∗ 131.3 (C4 ), 139.8 (2 J = 10.0, C2 ),
2b-1: 31P NMR (CDCl3) δ 80.3; 13C NMR
(CDCl3) δ 21.2 (3 J = 3.5, C2 –Me), 21.4 (3 J = 5.2, C1–
Me), 30.1 (1 J = 68.3, C4), 35.6 (2 J = 7.5, C1), 36.1
(2 J = 6.0, C5), 36.2 (1 J = 68.3, C2), 72.1 (3 J = 11.5,
C6), 125.1 (3 J = 11.7, C5 ),∗ 129.8 (3 J = 11.7, C3 ),∗
130.2 (1 J = 93.3, C1 ) 131.0 (2 J = 9.9, C6 ),∗ 131.6 (C4 ),
140.5 (2 J = 7.4, C2 ), ∗tentative assignment; 1H NMR
(CDCl3) δ 1.76 (s, C1–Me), 2.67 (s, Ar–Me).
∗
1
142.4 (C5) tentative assignment; H NMR (CDCl3)
2
δ 2.10 (s, C3–Me), 2.50 (s, Ar–Me), 6.28 (dd, JPH
=
3 JHH = 12.3, C6–H), 6.91 (dd, 3 JPH = 34.9, 3 JHH = 12.8,
C5–H).
3Bb: 31P NMR (CDCl3) δ 15.7; 13C NMR (CDCl3) δ
20.5 (3 J = 3.3, C2 –Me), 24.0 (3 J = 13.0, C5–Me), 28.8
(1 J = 70.7, C2), 117.8 (1 J = 96.8, C6), 122.6 (2 J = 11.1,
C3), 124.7 (3 J = 12.0, C3 ),∗ 129.3 (1 J = 105.1, C1 ),
2b-2: 31P NMR (CDCl3) δ 78.2; 13C NMR
(CDCl3) δ 21.0 (3 J = 6.2, C1–Me), 21.6 (3 J = 3.7, C2 –
Me), 27.8 (1 J = 68.5, C4), 32.7 (2 J = 11.7, C1), 34.1
(1 J = 67.0, C2), 34.3 (2 J = 9.7, C5), 72.4 (3 J = 14.3, C6),
125.5 (3 J = 11.4, C5 ),∗ 130.2 (1 J = 86.2, C1 ), 131.3
(3 J = 10.9, C3 ),∗ 131.9 (C4 ), 132.0 (3 J = 9.5, C6 ),∗
141.3 (2 J = 7.9, C2 ), ∗tentative assignment.
130.8 (3 J = 11.0, C5 ),∗ 131.1 (2 J = 10.6, C6 ), 131.2
∗
(C4 ), 139.9 (2 J = 11.2, C2 ), 148.0 (C5) tentative as-
∗
1
signment; H NMR (CDCl3) δ 2.24 (s, C5–Me), 2.52
(Ar–Me), 6.32 (dt, C3–H).
General Procedure for the Synthesis
of Cycloadducts 4a, 4b, and 5
3- and 5-Methyl-4-chloro-1-(4-methylphenyl-)-
1,2-dihydrophosphinine 1-Oxide 3Aa and 3Ba
A
solution of 1.0 g (3.96 mmol) of tolyl-
dihydrophosphinine oxide 3a or 3b consisting of
∼75% of the A isomer and ∼25% of the B isomer and
4.8 mmol of N-phenylmaleimide (0.84 g) or dimethy-
lacetylene dicarboxylate (0.59 ml) in 25 ml of toluene
was stirred at the boiling point for 5 days. Solvent
was evaporated and the residue so obtained purified
by column chromatography (silica gel, 3% methanol
in chloroform) to furnish cycloadducts 4a, 4b, and 5
as the mixture of isomers. The data are listed below.
A 2.0 g (6.92 mmol) sample of 2a was heated at
138◦C in a vial until the evolution of hydrochlo-
ric acid ceased (ca. 7 min). The crude prod-
uct was purified by column chromatography (as
above) to provide 1.2 g (67%) of oily 3a as a
3:1 mixture of isomers A and B; ES–MS, 253
(M + H); (M + H)+found = 253.0507, C13H14ClOP re-
quires 253.0549 for the 35Cl isotopomer.
3Aa: 31P NMR (CDCl3) δ 16.4; 13C NMR (CDCl3) δ
21.6 (C4 –Me), 23.4 (3 J = 8.5, C3–Me), 36.6 (1 J = 71.4,
C2), 119.5 (1 J = 93.8, C6), 123.8 (2 J = 19.8, C3),
129.5 (2 J = 12.4, C2 ),∗ 130.6 (3 J = 10.6, C3 ),∗ 142.8
(4 J = 2.8, C4 ), 144.1 (C5), ∗may be reversed; 1H NMR
(CDCl3) δ 2.07 (s, C3–Me), 2.42 (s, Ar–Me), 6.18
1- and 11-Methyl-10-chloro-4-phenyl-8-p-tolyl-4-
aza-8ꢀ5 -phosphatricyclo[5.2.2.02,6]undec-10-ene-3,5-
dione 8-Oxide (4Aa and 4Ba) [18]. Yield: 1.0 g
(61%) of 4a as a 6:4 mixture of isomers A
and B; mp 132–134◦C (acetone); ES–MS, 426

450 Keglevich et al.
(M + H); (M + H)+found = 426.0967, C23H22ClNO3P re-
quires 426.1026 for the 35Cl isotopomer.
26% mixture of three isomers; ES–MS, 395 (M + H);
(M + H)+found = 395.0741,
C19H21ClO5P
requires
4Aa: 31P NMR (CDCl3) δ 37.8; 13C NMR (CDCl3)
395.0815 for the 35Cl isotopomer.
δ
21.6 (C4 –Me), 23.7 (3 J = 10.8, C4–Me), 37.1
5A-1: 31P NMR (CDCl3) δ 44.5 (38%); 13C NMR
(CDCl3) δ 20.3 (J = 10.3, C4–Me), 21.7 (Ar–Me), 32.1
(J = 96.9, C3), 44.4 (J = 50.9, C1), 47.4 (J = 8.5, C4),
52.4, 52.5 (MeO), 116.8 (J = 8.4, C6), 162.6, 166.0
(C O).
(1 J = 75.7, C3), 39.4 (1 J = 62.9, C1), 40.5 (C7), 44.5
(2 J = 6.3, C4), 49.6 (2 J = 10.7, C8), 122.7 (2 J = 5.9, C6),
126.5 (C3 ),a 127.2 (1 J = 103.2, C1 ), 128.9 (C4 ), 129.2
(C2 ),a 129.7 (2 J = 12.4, C2 ),b 131.2 (3 J = 9.6, C3 ),b
131.6 (C1 ), 140.2 (3 J = 11.0, C5), 143.5 (C4 ), 174.2
5A-2: 31P NMR (CDCl3) δ 33.5 (36%); 13C NMR
(CDCl3) δ 20.2 (J = 11.2, C4–Me), 21.7 (Ar–Me), 32.3
(J = 96.8, C3), 45.1 (J = 50.1, C1), 48.0 (J = 8.7, C4),
52.4, 52.7 (MeO), 116.8 (J = 8.4, C6), 162.5, 166.1
(C O).
(C9), 175.9 (3 J = 15.1, C11), a,bmay be reversed; H
1
NMR (CDCl3) δ 1.84 (s, C4–Me), 2.45 (s, Ar–Me), 6.09
(dd, 3 JPH
=
3 JHH 7.9, C6–H);
4Ba: 31P NMR (CDCl3) δ 37.5; 13C NMR (CDCl3)
δ 21.6 (C4 –Me), 19.0 (C6–Me), 28.1 (1 J = 77.2, C3),
39.6 (C7), 42.9 (2 J = 6.9, C4), 44.8 (1 J = 67.1, C1),
45.5 (2 J = 12.2, C8), 126.4 (C3 ),a 129.0 (C4 ), 129.3
(C2 ),a 129.8 (2 J = 12.2, C2 ),b 130.7 (2 J = 5.9, C6),
131.1 (3 J = 11.2, C3 ),b 143.5 (C4 ), 175.4 (C9), 176.2
(3 JPC = 14.7, C11), a,bmay be reversed; 1H NMR
(CDCl3) δ 1.55 (s, C6–Me), 2.45 (s, Ar–Me).
5B: 31P NMR (CDCl3) δ 44.9 (26%); 13C NMR
(CDCl3) δ 18.9 (C6–Me), 21.7 (Ar–Me), 46.9 (J = 9.2,
C4), 50.8 (J = 50.5, C1), 52.8, 52.9 (MeO), 161.8, 166.5
(C O).
General Procedure for the Photostimulated
Fragmentation-Related Phosphorylations
1- and 11-Methyl-10-chloro-4-phenyl-8-o-tolyl-4-
aza-8ꢀ5 -phosphatricyclo[5.2.2.02,6]undec-10-ene-3,5-
dione 8-Oxide (4Ab and 4Bb) [18]. Yield: 0.88 g
(52%) of 4b as a 58:42 mixture of isomers A
and B; mp 105–107◦C (acetone); ES–MS, 426
(M + H); (M + H)+found = 426.0952, C23H22ClNO3P re-
quires 426.1026 for the 35Cl isotopomer.
The solution of 0.10 g (0.24 mmol) of phosphabicy-
clooctene 4a or 4b consisting of ∼60% of the A and
∼40% of the B isomer in 45 ml of acetonitrile and
4 ml of the corresponding alcohol was irradiated in a
photochemical quartz reactor with a 125 W mercury
lamp for 1 h. The mixture was concentrated in vacuo
and the residue so obtained was purified by flash
column chromatography (silica gel, 3% methanol in
chloroform) to give the corresponding phosphinate
(7a, 8a, 9a, 10a, 11a, 7b, 8b, 9b, 10b, 11b) as an oil
(Table 1).
Using primary amines (4 ml of each) as the nuch-
leophile, the result of the photolysis was the cor-
responding phosphinic amide (12 or 13) (Table 1).
Phosphabicyclooctadiene 5 was used in the phos-
phorylation of methanol as described for the reac-
tion of precursor 4a (Table 1). The competitive pho-
tolysis was performed as above using a mixture of
0.05 g (0.12 mmol) of 4a and 0.05 g (0.12 mmol) of
4b and sec-butanol. The reaction was monitored by
31P NMR till completion.
4Ab: 31P NMR (CDCl3) δ 42.5; 13C NMR (CDCl3) δ
21.6 (3 J = 4.2, C2 –Me), 23.7 (3 J = 10.7, C4–Me), 37.7
(1 J = 62.8, C1), 37.9 (1 J = 74.9, C3), 40.4 (C7), 44.4
(2 J = 6.4, C4), 49.7 (3 J = 10.5, C8), 122.2 (2 J = 6.0, C6),
125.6 (3 J = 12.2, C3 ),a 126.3 (C3 ),b 128.7 (C4 ), 128.9
(1 J = 100.5, C1 ), 129.0 (C2 ),b 129.9 (3 J = 10.6, C5 ),a
131.4 (C1 ), 131.9 (2 J = 10.8, C6 ),a 132.3 (C4 ), 139.0
(3 J = 11.0, C5), 142.1 (2 J = 7.8, C2 ), 173.8 (C9), 175.8
a
b
(3 J = 14.8, C11), tentative assignment, may be re-
1
versed; H NMR (CDCl3) δ 1.81 (s, C4–Me), 2.74 (s,
Ar–Me), 6.12 (dd, 3 JPH = JHH 8.0, C6–H);
3
4Bb: 31P NMR (CDCl3) δ 42.4; 13C NMR
(CDCl3) δ 18.5 (3 J = 2.1, C6–Me), 21.9 (3 J = 3.8, C2 –
Me), 28.0 (1 J = 78.5, C3), 39.3 (2 J = 2.2, C7), 42.7
(2 J = 7.1, C4), 43.8 (1 J = 61.1, C1), 45.7 (3 J = 11.1, C8),
125.5 (3 J = 11.5, C3 ),a 126.2 (C3 ),b 128.1 (1 J = 99.3,
C1 ), 128.8 (C4 ), 129.1 (C2 ),b 130.1 (2 J = 5.8, C6),
130.9 (3 J = 10.7, C5 ),a 132.2 (2 J = 11.1, C6 ),a 142.8
(2 J = 8.4, C2 ), 175.0 (C9), 176.0 (3 J = 15.1, C11),
Thermoinduced Phosphorylation of
Hydroquinone, Using Phosphabicyclooctadiene
5
atentative assignment, may be reversed; H NMR
b
1
(CDCl3) δ 1.43 (s, C6–Me), 2.82 (s, Ar–Me).
0.30 g (0.76 mmol) of cycloadduct 5 as the mix-
ture of three isomers and 0.10 g (2.73 mmol)
of hydroquinone was heated at 240◦C in a vial
for 15 min. Flash column chromatography (sil-
ica gel, 3% methanol in chloroform) afforded
0.11 g (35%) of phosphinate 15 in a purity
of ca. 90%. 31P NMR (CDCl3) δ 44.5; ES–MS,
4-
and
7-Methyl-8-chloro-2-oxo-2-p-tolyl-2-
phosphabicyclo[2.2.2]octa-5,7-diene-5,6-dicarboxylic
Acid Dimethyl Ester (5) [18]. Yield: 0.67 g (43%)
oily product after an additional chromatography
(silica gel, benzene-acetone 2:3) as a 38, 36, and

Fragmentation-Related Phosphinylations Using 2-Aryl-2-phosphabicyclo[2.2.2]oct-5-ene- and -octa-5,7-diene 2-Oxides 451
263 (M + H); (M + H)+found = 263.0821, C14H16O3P re-
[6] Quin, L. D.; Tang, J.-S.; Keglevich, Gy. Heteroat Chem
quires 263.0837 for the 35Cl isotopomer. GC–MS, m/z
1991, 2, 283.
[7] Quin, L. D.; Tang, J.-S.; Quin, G. S.; Keglevich, Gy.
(rel. int.) 262 (M+, 27), 261 (27), 169 (2), 154 (9), 153
(100), 91 (37).
Heteroat Chem 1993, 4, 189.
´
[8] Keglevich, Gy.; Ujsza´szy, K.; Quin, G. S.; Quin, L. D.
Phosphorus Sulfur Silicon 1995, 106, 155.
[9] Keglevich, Gy.; Steinhauser, K.; Luda´nyi, K.; To˝ke, L.
J Organomet Chem 1998, 570, 49.
[10] Keglevich, Gy.; Szelke, H.; Nagy, Z.; Dobo´, A.; Nova´k,
T.; To˝ke, L. J Chem Res 1999, 580.
[11] Keglevich, Gy.; To˝ke, L.; Bo¨cskei, Zs.; Menyha´rd, D.;
Quin, L. D. Heteroat Chem 1995, 6, 593.
[12] Jankowski, S.; Rudzinski, J.; Szelke, H.; Keglevich,
Gy. J Organomet Chem 2000, 595, 109.
Crystal Data for Phosphabicyclohexane 2b-1
X-ray diffraction data of product 2b-1 were collected
at 293 K. Crystal data for 2b-1: C13H15Cl2OP, M =
298.12, transparent, needle shape crystal, approxi-
mate dimensions 0.32 × 0.12 × 0.1 mm, monoclinic,
˚
˚
space group P21/n, a = 8.947(4) A, b= 7.894(4) A,
[13] Keglevich, Gy.; Szelke, H.; Tama´s, A. M.; Harmat, V.;
◦
3
˚
˚
´
c= 19.347(3) A, ꢁ = 91.75(2) , V = 1366(1) A , Z = 4,
Dc = 1.406 gcm−1, ꢂ (Cu Kꢃ) = 5.226 mm−1. Struc-
ture solution with direct method was carried out
with the teXsan package [19]. Refinement was car-
ried out with SHELXL-97 [20]. Final R indices for
2b-1 are R= 0.2122, RW = 0.3305 (for all 5778 reflec-
tions) R= 0.1063, RW = 0.2716 (I > 2ꢄ(I)).
Luda´nyi, K.; Vasko´, A. Gy.; To˝ke, L. Heteroat Chem
2002, 13, 626.
[14] Keglevich, Gy.; Janke, F.; Fu¨lo¨p, V.; Kalman, A.; To´th,
G.; To˝ke, L. Phosphorus Sulphur Silicon 1990, 54,
73.
´
[15] Keglevich, Gy.; Vasko´, A. Gy.; Dobo´, A.; Luda´nyi, K.;
To˝ke, L. J Chem Soc, Perkin Trans 1 2001, 1062.
[16] Keglevich, Gy.; Keseru˝, Gy. M.; Forintos, H.; Szo¨llo˝sy,
´
A.; Luda´nyi, K.; To˝ke, L. J Chem Soc, Perkin Trans 1
CCDC 206074 contains the supplementary
crystallographic data for this paper. These data can
be obtained free of charge via www.ccdc.cam.ac.uk/
conts/retrieving.html (or from the Cambridge
Crystallographic Data Centre, 12, Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033 or
deposit@ccdc.cam.ac.uk).
1999, 1801.
[17] Keglevich, Gy.; Petneha´zy, I.; Miklo´s, P.; Alma´sy, A.;
To´th, G.; To˝ke, L.; Quin, L. D. J Org Chem 1987, 52,
3983.
[18] According to the IUPAC nomenclature, the following
numbering was used for naming the products:
REFERENCES
[1] Heydt, H. In Multiple Bonds and Low Coordination
in Phosphorus Chemistry; Regitz, M.; Scherer, O. J.
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[2] Keglevich, Gy. Curr Org Chem 2002, 6, 891.
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[3] Keglevich, Gy.; Ujsza´szy, K.; Quin, L. D.; Quin, G. S.
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[4] Keglevich, Gy.; Steinhauser, K.; Keseru˝, Gy. M.;
[19] teXsan for Windows version 1.06: Crystal Structure
Analysis Package; Molecular Structure Corporation,
1997–1999.
[20] Sheldrick, G. M. SHELXL-97; University of
Go¨ttingen, Germany, 1997.
´
Bo¨cskei, Zs.; Ujsza´szy, K.; Marosi, Gy.; Ravadits, I.;
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