Reactions of dibenzylphosphine oxide with α,β-unsaturated nitriles: synthesis of aminophospholene oxides

Article abstract of DOI:10.1023/A:1015876403665

The reactions of dibenzylphosphine oxide with α,β-unsaturated nitriles in the presence of two equivalents of NaH in Bu^tOMe afforded substituted aminophospholene oxides in 20-83 percent yields. In the presence of bulky substituents at the α and

Full text of DOI:10.1023/A:1015876403665

Russian Chemical Bulletin, International Edition, Vol. 51, No. 4, pp. 671—677, April, 2002
671
Reactions of dibenzylphosphine oxide with α,βꢀunsaturated nitriles:
synthesis of aminophospholene oxides
V. D. Kolesnika and A. V. Tkachevb
ꢀ
aDepartment of Natural Sciences, Novosibirsk State University,
2 ul. Pirogova, 630090 Novosibirsk, Russian Federation.
Fax: +7 (383 2) 34 4752
bN. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences,
9 prosp. Akad. Lavrent´eva, 630090 Novosibirsk, Russian Federation.
Fax: +7 (383 2) 34 4855. Eꢀmail: atkachev@nioch.nsc.ru
The reactions of dibenzylphosphine oxide with α,βꢀunsaturated nitriles in the presence of
two equivalents of NaH in ButOMe afforded substituted aminophospholene oxides in 20—83%
yields. In the presence of bulky substituents at the α and γ positions of unsaturated nitriles,
cyclization of the initially formed adducts proceeds with high stereoselectivity to give the
single stereoisomer of aminophospholene oxide.
Key words: aminophospholene oxides, dibenzylphosphine oxide, α,βꢀunsaturated nitriles,
heterocycles, terpenoids, nucleophilic addition, phosphorylation.
The use of readily available natural terpenoids in the
synthesis of new biologically active compounds and chiral
auxiliary agents calls for selective procedures for the inꢀ
troduction of heteroatomic functional groups, which can
substantially change the polarity, solubility, and coordiꢀ
nation ability of the starting terpene molecules. In this
respect, phosphorusꢀcontaining functional groups, which
often impart biological activity to the compounds, are
very attractive substituents. Particular attention has been
given to chiral organophosphorus compounds in which
both the phosphorus1,2 and the adjacent carbon atoms1—3
are chiral. The use of chiral organophosphorus comꢀ
pounds in the enantioselective synthesis is well known.
A few examples of phosphorusꢀcontaining terpenes reꢀ
ported in the literature provide evidence that phosphoꢀ
rylated terpenes show promise as auxiliary chiral agents.4,5
Among phosphorusꢀcontaining derivatives of terpenes,
phosphates of acyclic allylic alcohols (geraniol, nerol,
linalool, nerolidol, etc.) have received the most study
because they play an important role in the biosynthesis
of terpenes in plants. Due to high lability of terpenes and
severe conditions of phosphorylation of olefins, general
procedures for the selective introduction of phosphorus
substituents into terpene molecules are lacking.
phosphorusꢀcontaining heterocycles 3. Unsaturated keꢀ
tones (4) behave analogously to give heterocycles 5 10
(Scheme 1).
Scheme 1
The addition of phosphorus(III) halides to dienes has
commonly been used for the preparation of fiveꢀmemꢀ
bered phosphorusꢀcontaining heterocycles for years.6—8
In 1970s, it was found9 that the reactions of α,βꢀunꢀ
saturated esters (1) with secondary phosphine oxides (2)
containing the benzyl group afforded the corresponding
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 620—626, April, 2002.
1066ꢀ5285/02/5104ꢀ671 $27.00 © 2002 Plenum Publishing Corporation

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Russ.Chem.Bull., Int.Ed., Vol. 51, No. 4, April, 2002
Kolesnik and Tkachev
Scheme 2
Previously, using myrtenic acid nitrile as an example,
we have demonstrated that aminophospholene oxides
can be prepared by the reactions of dibenzylphosphine
oxide (7) with α,βꢀunsaturated nitriles.11 In the present
study, we examined the scope of this procedure for the
preparation of aminophospholene oxides and extended
the range of substrates by involving both terpenic
α,βꢀunsaturated nitriles (10, 12, and 15) (Scheme 2)
containing different carbon skeletons and simplest unꢀ
saturated nitriles (17, 18, and 19) (Scheme 3). Under
the action of dibenzylphosphine oxide 7, all nitriles, exꢀ
cept for acrylonitrile and cinnamonitrile, were transꢀ
formed into the corresponding aminophospholene oxꢀ
ides in good yields.
Scheme 3
* Two epimers (3 : 2).
Note. The atomic numbering scheme is given for the interꢀ
pretation of the NMR spectra.
The mechanism of the addition of dibenzylphosphine
oxide to unsaturated esters12 involves the initial addition

Preparation of aminophospholene oxides
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 4, April, 2002
673
of the phosphinite anion to the double carbonꢀcarbon
bond followed by cyclization of the resulting benzyl anꢀ
ion at the carboxy group (see Scheme 1). Most likely,
the reactions of α,βꢀunsaturated nitriles proceed by the
same mechanism. In the studies of the reactions of esꢀ
ters,12 it was demonstrated that the use of the second
equivalent of a base (for the purpose of generating
dianions) in the case of sterically hindered substrates
leads to an increase in the yields of phospholene oxides.
Taking into account that the substrates under study are
sterically crowded molecules as well, we used two equivaꢀ
lents of the base.
The reaction of geranyl nitrile 10 with dibenzylꢀ
phosphine oxide (7) afforded a mixture of epimers 11a,b
in a ratio of 3 : 2. The major isomer was isolated by
crystallization. However, we failed to establish its threeꢀ
dimensional structure. Generally, the configurations of
substituents in the phospholene ring are determined from
the spinꢀspin coupling constants of the protons geminal
with respect to the phosphorus atom.13 However, comꢀ
pound 11 contains no these hydrogen atoms and, conseꢀ
quently, it is impossible to establish the mutual arrangeꢀ
ment of the C(12) atom and the phosphoryl oxygen atom
by spectroscopic methods.
The reaction of quinoxalineꢀcontaining nitrile 12 also
afforded two products, which are structural isomers 13
and 14. The nitrile, which was initially formed upon the
addition of the phosphorusꢀcontaining reagent, contains
two types of benzylic methylene groups (at the α posiꢀ
tion of the benzene rings and at the α position of the
quinoxaline fragment). Hence, two types of carbanions
can be produced. The latter can undergo subsequent
cyclization to give the final products (Scheme 4). Due to
a substantial difference in properties, compounds 13 and
14 were easily separated and obtained in the individual
form. Aminophospholene oxide 14 was isolated as the
only epimer. NMR spectroscopy did not reveal another
epimer in noticeable amounts even in the crude product.
The geminal spinꢀspin coupling constant 2JP—C(4)—H(4)
=
8.9 Hz is indicative of the mutual cis arrangement of the
alkyl substituent and the phosphoryl oxygen atom in the
phospholene ring.13 The fact that the yield of aminoꢀ
phospholene oxide 14 is lower than that of enamine 13
bearing the exocyclic phosphorus atom is attributable to
lower stability of anion 26 (compared to 25) due to stronꢀ
ger electronꢀwithdrawing properties of the quinoxaline
fragment compared to the unsubstituted benzene ring.
The reaction of nitrile 15 also gave rise to the single
stereoisomer of aminophospholene oxide 16. The signal
for the H(4) proton in the 1H NMR spectrum is involved
in a complex strongly coupled spin system. Analysis
of this system gave the spinꢀspin coupling constant
2JP—C(4)—H(4) = 8.8 Hz, which is indicative of the mutual
cis arrangement of the alkyl substituent and the phosꢀ
phoryl oxygen atom in the phospholene ring of comꢀ
pounds 16.
As in the case of the aboveꢀdescribed terpene derivaꢀ
tives, the addition of dibenzylphosphine oxide to the
simplest nitriles 17, 18, and 19 proceeded very readily,
but the resulting products are substantially different. In
the reaction with acrylonitrile 17, phosphine oxide 20
was isolated as the reaction product in good yield. Atꢀ
tempts to subject this product to subsequent cyclization
failed, whereas the reaction with nitrile 18 afforded
aminophospholene oxide 22. The reaction of cinnamoꢀ
nitrile (19) yielded diphosphine dioxide 24, which can
formally be considered as the product of the replaceꢀ
ment of the CN group by the dibenzylphosphinite anion
in intermediate 23. However, according to the published
data, the addition of the phosphorusꢀcontaining reagent
at the CN group is much more probable than the direct
replacement of the CN group by the phosphorusꢀconꢀ
taining reagent.14,15 Hence, we assumed the mechanism
of formation of compound 24 (Scheme 5), which inꢀ
volves (a) the rearrangement of the initially formed anꢀ
ion 27 into the benzylic anion 28, (b) elimination of the
cyanide anion to give the substituted αꢀstyrene 29, and
(c) the addition of the second equivalent of the phosꢀ
phorusꢀcontaining reagent at the activated double bond.
Nitrile 18 can produce four diastereomers (Scheme 6).
According to the results of calculations, the heats of
formation of these isomers differ only slightly (Table 1).
However, the only stereoisomer of aminophospholene
oxide 22 was isolated as the reaction product. The conꢀ
figuration of aminophospholene oxide 22 was unambiguꢀ
ously established based on analysis of the spinꢀspin couꢀ
Scheme 4
2
3
pling constants JH—C—P, ,
3JH—H 3JH—P, and JC—P in
the NMR spectra of compound 22 and the results of
calculations.
First, the geminal spinꢀspin coupling constant
2JH(4)—C(4)—P = 8.8 Hz (see Table 1) is indicative of the
cisoid arrangement of the ethyl group and the phosphoꢀ
ryl oxygen atom (this arrangement of the substituents is

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Russ.Chem.Bull., Int.Ed., Vol. 51, No. 4, April, 2002
Kolesnik and Tkachev
Scheme 5
Scheme 6
Ester/kcal mol–1 (MM2) = –0.4 (21a), 0.3 (21b), –3.0 (21c), –3.6 (21d).
typical of compounds 13 and 15). Hence, structures 22b
and 22c must be rejected. Second, it is known that the
spinꢀspin coupling constants 3JH—C—C—P and 3JC—C—C—P
depend on the corresponding dihedral angles and obey
the Karplus equation.13,16 In the spectrum of comꢀ
pound 22, the vicinal spinꢀspin coupling constant
3JH(3)—C(3)—C(4)—P is rather small (2.2 Hz), which is
indicative of the orthogonal arrangement (or nearly
orthogonal) of the H(3)—C(3) and C(4)—P bonds.
To the contrary, the spinꢀspin coupling constant
3JC(5)—C(3)—C(4)—P is rather large (8.7 Hz), which points
to the synclinal or anticlinal arrangement of the
C(5)—C(3) and C(4)—P bonds. According to the results
of semiempirical quantumꢀchemical calculations (PM3
method), in the case of the cis arrangement of the meꢀ
thyl group with respect to the phosphoryl oxygen atom
(as in isomer 22d), the dihedral angle between the
H(3)—C(3) and C(4)—P bonds is 92° (as opposed to
Table 1. Enthalpies of formation (∆Hf°) and the dihedral angles
(ϕ) of conformers 22a—d calculated by the PM3 method
Conformer
∆H°
ϕ
ϕ
f
1
2
/kcal mol–1
deg
22a
22b
22c
22d
−4.9
−2.8
−4.3
−3.6
−140
−147
100
92
100
93
−141
−149
Note.
ϕ
and
ϕ
are the H(3)—C(3)—C(4)—P and
1
2
140° for isomer 22a), which is in the excellent agreement
C(5)—C(3)—C(4)—P dihedral angles, respectively. The exꢀ
3
with the spinꢀspin coupling constant JH(3)—C(3)—C(4)—P
.
perimental spinꢀspin coupling constants for compound 22:
3
3JH(3)—C(3)—C(4)—P = 2.2 Hz and JC(5)—C(3)—C(4)—P = 8.7 Hz.
The C(5)—C(3)—C(4)—P dihedral angle (149°) in isoꢀ

Preparation of aminophospholene oxides
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 4, April, 2002
675
lowed by heating to 100—150 °C. Column chromatography
was carried out with the use of KSK silica gel (Russia,
0.140—0.315 mm, airꢀdried, activated at 140 °C for 5 h) and
aluminum oxide (Russia, TU 6ꢀ09ꢀ3916ꢀ75, activated at 250 °C
for 3 h). The IR spectra were measured on a Specord Mꢀ80
instrument. The UV spectra were recorded on a Specord Mꢀ40
instrument. The melting points were determined on a Kofler
stage. The highꢀresolution mass spectra were obtained on a
Finnigan MAT 8200 instrument (EI, 100—220 °C, 70 eV). The
1H and 13C NMR spectra were recorded on a Bruker AMꢀ400
mer 22d agrees well with the observed spinꢀspin coupling
constant JC(5)—C(3)—C(4)—P, which must be equal to
0—2 Hz for isomer 22a.
3
The formation of the single isomer of 22 can be exꢀ
plained in terms of steric hindrance of the transition
state giving rise to cyclization with the formation of the
phospholane ring. If this transition state is close to the
conformation of primary adduct 21 involved in the reacꢀ
tion, the relative energies of the transition states producꢀ
ing particular isomers can be estimated from the relative
energies of the reactive conformations. These conformaꢀ
tions and their steric energies (Ester), which were calcuꢀ
lated by molecular mechanics (the MM2 force field), are
shown in Scheme 6. Apparently, isomer 22d obtained in
the experiment was generated through conformation 21d
with the lowest steric energy.
1
instrument (400.13 MHz for H and 100.61 MHz for 13C) for
solutions in CDCl3 (40—100 mg mL–1) at ∼20 °C. The residual
signals of the solvent (δ 7.24 and δ 76.90) were used as the
H
C
internal standard. The 31P NMR spectra were measured on a
Bruker ACꢀ200 instrument (81.015 MHz, 80% H3PO4 as the
external standard, δ 0.0) under the same conditions. The signs
P
of the spinꢀspin coupling constants were not determined. The
assignment of the signals was made using the 13C NMR spectra
recorded with the J modulation (protonꢀnoiseꢀdecoupled specꢀ
tra, the opposite phases for the signals of the atoms with the
odd and even numbers of the attached protons, tuning to the
constant J = 135 Hz) and based on the data of the 2D spectra:
(1) homonuclear 1H—1H correlation, (2) heteronuclear
13C—1H correlation at the direct spinꢀspin coupling constants
(J = 135 Hz), and (3) heteronuclear 13C—1H correlation at the
longꢀrange spinꢀspin coupling constants (J = 10 Hz).
Synthesis of the starting α,βꢀunsaturated nitriles. Geranyl
nitrile (10),19 4,4ꢀdimethylꢀ5ꢀ(3ꢀmethylquinoxalinꢀ2ꢀyl)pentꢀ2ꢀ
enenitrile (12),20 and cinnamonitrile (19)21 were synthesized acꢀ
cording to known procedures. 2ꢀMethylpentꢀ2ꢀenenitrile (18)
was prepared from 2ꢀmethylpentꢀ2ꢀenal oxime.22
The formation of the single stereoisomer of aminoꢀ
phospholene oxides from nitriles 12 and 15 can also be
attributed to the fact that the reaction proceeds with the
participation of the most stable conformation of the iniꢀ
tially formed phosphine oxide 30, which must lead to
products with the cisoid arrangement of the alkyl subꢀ
stituent relative to the phosphoryl oxygen atom. The
result of the reaction of geranyl nitrile 11 yielding a
mixture of epimers also agrees with the results of conforꢀ
mational analysis of the primary adduct according to
which conformations 31a and 31b have close energies
(∆∆H° = 0.6 kcal mol–1). This is a reason for the formaꢀ
f
A sample of 5ꢀ[1,3]dioxolanꢀ2ꢀylꢀ4,4ꢀdimethylpentꢀ2ꢀ
enenitrile (15) was kindly provided by A. V. Rukavishnikov
(N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry,
Siberian Branch of the Russian Academy of Sciences).
tion of a mixture of isomers.
Standard procedure for the preparation of aminophospholenes.
Sodium hydride (0.27 g, 60% NaH, 6.80 mmol, Fluka) was
added to a solution of dibenzylphosphine oxide23 (1.56 g,
6.80 mmol) in ButOMe (25 mL). The reaction solution was
refluxed with stirring until gas evolution ceased and NaH was
dissolved. A solution of unsaturated nitrile (6.80 mmol) in
ButOMe (10 mL) was added dropwise with stirring and the
reaction mixture was refluxed with stirring for 1 h. Then NaH
(0.27 g, 60% NaH, 6.80 mmol) was added. The mixture was
refluxed for 1 h, cooled, diluted with ButOMe (10 mL), and
washed with a saturated solution of NaCl (30 mL). The organic
extract was dried over Na2SO4 and the solvent was evaporated
in vacuo using a waterꢀaspirator pump. The residue was dried in
vacuo using an oil pump. The product was purified by column
chromatography or recrystallization.
To summarize, the reactions of dibenzylphosphine
oxide with α,βꢀunsaturated nitriles in the presence of
sodium hydride afforded substituted aminophospholene
oxides, which are very difficult to synthesize by other
procedures.17,18 The presence of the bulky substituents
at the α and γ positions of unsaturated nitriles leads to
high stereoselectivity of cyclization of the initially formed
adducts and ensures the preparation of the only stereoꢀ
isomer of aminophospholene oxide.
1ꢀBenzylꢀ5ꢀmethylꢀ5ꢀ(4ꢀmethylpentꢀ3ꢀenyl)ꢀ1ꢀoxoꢀ2ꢀpheꢀ
nylꢀ4,5ꢀdihydroꢀ1Hꢀphospholꢀ3ꢀylamine (11). The yield was
68%, m.p. 182—185 °C (from a MeCN—CHCl3 mixture, 1 : 3
v/v); MS, m/z (Irel (%)): 379.20590 (M+, 24%, calculated for
C24H30NOP: 379.20649), 297 (19), 288 (100), 206 (12), 91
(15), 41 (9); IR (CHCl3), ν/cm–1: 3500, 3400, 3100—2900,
1625, 1600, 1490, 1380, 1150, 1120. Major isomer. 31P NMR
Experimental
All solvents were distilled immediately before use. Analytiꢀ
cal TLC was carried out on Silufol (Czech Republic) and
Armsorb (Armenia) plates. The spots were visualized by sprayꢀ
ing the plates with solutions of vanilline (1 g of vanilline +
5 mL of concentrated H2SO4 + 100 mL of 95% EtOH) or iron
chloride (10 g of FeCl3•6H2O in 100 mL of 95% EtOH) folꢀ
1
(CDCl3), δ: 65.30; H NMR (CDCl3), δ: 1.29 (d, 3 H, H(12),
J = 13.2 Hz); 1.58 (m, 1 H, H(6a)); 1.60 (s, 3 H, H(10)); 1.69
(s, 3 H, H(11)); 1.77 (m, 1 H, H(6b)); 2.02 (m, 1 H, H(7a));
2.16 (m, 3 H, H(7b) and H(4)); 3.14 (dd, 1 H, H(13a),

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Russ.Chem.Bull., Int.Ed., Vol. 51, No. 4, April, 2002
Kolesnik and Tkachev
J = 14.6 Hz, J = 12.5 Hz); 3.24 (dd, 1 H, H(13b), J = 16.6 Hz,
J = 14.6 Hz); 4.73 (s, 2 H, NH2); 5.07 (tm, 1 H, H(8), J =
7.2 Hz); 7.06 (m, 6 H, Ar); 7.19 (t, 2 H, H(c), J = 7.6 Hz);
7.29 (d, 2 H, H(b), J = 7.7 Hz). 13C NMR (CDCl3), δ: 17.53
(M+, 31% calculated for C30H32N3OP: 481.22829), 391 (10),
390 (35), 324 (24), 323 (18), 284 (21), 283 (88), 282 (100), 253
(15), 233 (10), 232 (57), 214 (10), 200 (57), 199 (16), 192 (48),
185 (10), 170 (12), 158 (23), 91 (64), 64 (15). IR (CHCl3),
ν/cm–1: 3500, 3400, 3100—2900, 1625, 1595, 1140, 1120.
(C(11)); 21.03 (C(12), JC—P = 1.0 Hz); 23.49 (C(4), JC—P
7.6 Hz); 25.49 (C(10)); 35.34 (C(6)); 36.01 (C(13), JC—P
60.0 Hz); 39.48 (C(5), JC—P = 63.2 Hz); 43.81 (C(7), JC—P
=
=
=
1
31P NMR (CDCl3), δ: 62.52. H NMR (CDCl3), δ: 1.16 and
1.22 (both s, 3 H each, H(7) and H(8)); 2.31 (ddd, 1 H, H(4),
J = 8.9 Hz, J = 8.9 Hz, J = 6.4 Hz); 2.51 (ddd, 1 H, H(3a), J =
19.7 Hz, J = 16.5 Hz, J = 8.7 Hz); 2.70 (m, 1 H, H(3b)); 2.75
(s, 3 H, H(11)); 2.93 (dd, 1 H, H(6a), J = 13.6 Hz, J = 5.9 Hz);
3.07 (dd, 1 H, H(12a), J = 15.0 Hz, J = 15.0 Hz); 3.18 (dd,
1 H, H(12b), J = 15.0 Hz, J = 15.0 Hz); 3.28 (d, 1 H, H(6b),
J = 13.6 Hz); 5.02 (s, 2 H, NH2); 6.29 (dt, J = 7.5 Hz, J =
1.9 Hz); 6.83 (d, J = 7.4 Hz); 7.15 (m); 7.30 (t, J = 7.6 Hz);
7.51 (d, 10 H, Ph, J = 7.5 Hz); 7.60 (m, 2 H, H(15) and
H(16)); 7.80 and 7.93 (both dd, 1 H each, H(14) and H(17),
J = 8.1 Hz, J = 1.8 Hz). 13C NMR (CDCl3), δ: 23.75 (C(11));
25.34 (C(7) or C(8), JC—P = 4.4 Hz); 25.72 (C(7) or C(8),
JC—P = 5.1 Hz); 32.54 (C(3), JC—P = 6.5 Hz); 38.10 (C(4),
JC—P = 64.7 Hz); 38.30 (C(5), JC—P = 1.5 Hz); 39.46 (C(12),
JC—P = 62.5 Hz); 43.52 (C(6), JC—P = 5.1 Hz); 98.57 (C(1),
JC—P = 112.6 Hz); 125.76 (C(d´)); 125.78 (JC—P = 3.0 Hz);
128.49 and 128.57 (JC—P = 3.6 Hz); 129.22 and 129.62 (C(b);
C(c), C(d), C(b´), C(c´), JC—P = 5.8 Hz), 127.70, 128.17,
128.80, and 129.19 (C(14), C(15), C(16), C(17)); 133.61 (C(a´),
JC—P = 5.8 Hz); 134.60 (C(a), JC—P = 9.5 Hz); 140.36 and
140.39 (C(13) and C(18)); 154.04 and 154.47 (C(9) and C(10));
155.70 (C(2), JC—P = 40.0 Hz).
1ꢀBenzylꢀ5ꢀ(2ꢀ[1,3]dioxolanꢀ2ꢀylꢀ1,1ꢀdimethylethyl)ꢀ1ꢀoxoꢀ
2ꢀphenylꢀ4,5ꢀdihydroꢀ1Hꢀphospholꢀ3ꢀylamine (16) was isolated
from the crude product by column chromatography (Al2O3,
CHCl3). The yield was 57%. MS, m/z (Irel (%)): 411.19565
(M+, 6%, calculated for C24H30NO3P: 411.19632), 321 (22),
320 (100), 282 (10), 276 (48), 248 (11), 232 (15), 192 (11), 170
(24), 91 (61). IR (CHCl3), ν/cm–1: 3500, 3400, 3100—2900,
1625, 1595, 1145, 1120. 31P NMR (CDCl3), δ: 61.34. 1H NMR
(CDCl3), δ: 1.14 and 1.22 (both s, 3 H each, H(8) and H(9));
1.60 (dd, 1 H, H(6a), J = 5.5 Hz, J = 14.3 Hz); 1.85 (dd, 1 H,
H(6b), J = 14.3 Hz, J = 4.5 Hz); 2.15 (m, 2 H, H(3a) and
H(4)); 2.47 (m, 1 H, H(3b)); 3.12 (dd, 1 H, H(10a), J =
15.0 Hz, J = 15.0 Hz); 3.21 (dd, 1 H, H(10b), J = 15.0 Hz, J =
15.0 Hz); 3.69 and 3.83 (both m, 2 H each, H(11) and H(12));
4.73 (s, 2 H, NH2); 4.78 (t, 1 H, H(7), J = 5.0 Hz); 6.88 (d,
2 H, H(b´), J = 7.4 Hz); 7.14 (m, 4 H, Ar); 7.30 (t, 2 H, H(c),
J = 7.6 Hz); 7.46 (d, 2 H, H(b), J = 7.7 Hz). 13C NMR
11.1 Hz); 96.29 (C(2), JC—P = 110.4 Hz); 123.63 (C(8)); 125.50
and 125.92 (JC—P = 2.5 Hz); 127.75 (JC—P = 2.0 Hz); 127.88
(JC—P = 4.7 Hz); 128.46 and 129.84 (C(b), C(c), C(d), C(b´),
C(c´), C(d´), JC—P = 5.1 Hz); 131.88 (C(9)); 132.98 (C(a´),
JC—P = 6.7 Hz); 134.51 (C(a), JC—P = 7.6 Hz); 153.11 (C(3),
JC—P = 40.3 Hz). Minor isomer. 31P NMR (CDCl3), δ: 64.56.
1H NMR (CDCl3), δ: 1.27 (d, 3 H, H(12), J = 15.0 Hz); 1.51
(s, 3 H, H(10)); 1.60 (s, 3 H, H(11)); 1.65, 1.90, and 2.65
(all m, 2 H each, H(4), H(6), H(7)); 3.09 (m, 2 H, H(13));
4.49 (s, 2 H, NH2); 5.03 (tm, 1 H, H(8), J = 5.9 Hz); 7.01—7.28
(m, 10 H, Ph). 13C NMR (CDCl3), δ: 17.51 (C(11)); 21.40
(C(12), JC—P = 1.0 Hz); 23.28 (C(4), JC—P = 5.8 Hz); 25.45
(C(10)); 35.24 (C(6)); 36.12 (C(13), JC—P = 51.6 Hz); 38.41
(C(5), JC—P = 65.4 Hz); 44.55 (C(7), JC—P = 9.5 Hz); 124.06
(C(8)); 125.83, 125.95 (JC—P = 2.9 Hz); 127.88 (JC—P = 2.2 Hz);
128.02 (JC—P = 3.6 Hz); 128.69 and 129.97 (C(b), C(c), C(d),
C(b´), C(c´), C(d´), JC—P = 3.6 Hz); 131.53 (C(9)); 133.12
(C(a´), JC—P = 6.5 Hz); 134.53 (C(a), JC—P = 7.6 Hz); 153.67
(C(3), JC—P = 40.3 Hz).
[4ꢀAminoꢀ2,2ꢀdimethylꢀ3ꢀ(3ꢀmethylquinoxalinꢀ2ꢀyl)cycloꢀ
pentꢀ3ꢀenyl]dibenzylphosphine oxide (13) was isolated by reꢀ
crystallization of the crude product, which was prepared from
nitrile 12 according to a standard procedure. The yield was
60%, m.p. 194—198 °C (from CCl4). MS, m/z (Irel (%)):
481.22888 (M+, 13%, calculated for C30H32N3OP: 481.22829),
390 (9), 283 (19), 282 (20), 253 (35), 252 (100), 251 (14), 250
(11), 237 (12), 236 (37), 235 (10), 232 (14), 200 (14), 199 (13),
192 (10), 91 (45). IR (CHCl3), ν/cm–1: 3500, 3400, 3100—2900,
1640, 1600, 1500, 1380, 1170, 1120, 770, 700. UV (EtOH)
λ/nm (ε): 282 (5220), 320 (4250), 394 (1420). 31P NMR
(CDCl3), δ: 44.48. 1H NMR (CDCl3), δ: 1.06 and 1.58 (both s,
3 H each, H(15a) and H(15b)); 2.33 (ddd, 1 H, H(2), J =
11.0 Hz, J = 11.0 Hz, J = 8.8 Hz); 2.46 (ddd, 1 H, H(3a), J =
15.4 Hz, J = 8.8 Hz, J = 2.0 Hz); 2.63 (s, 3 H, H(14)); 2.79
(ddd, 1 H, H(3b), J = 15.4 Hz, J = 11.4 Hz, J = 11.4 Hz); 3.00
(dd, 1 H, H(16a), J = 14.5 Hz, J = 14.3 Hz); 3.20 (dd, 1 H
H(16a), J = 14.5 Hz, J = 10.9 Hz); 3.25 (dd, 1 H, H(16b), J =
14.6 Hz, J = 10.3 Hz); 3.38 (dd, 1 H, H(16b), J = 14.6 Hz, J =
14.6 Hz); 7.15—7.35 (m, 10 H, Ph); 7.66 (m, 2 H, H(8) and
H(11)); 7.91 (m, 2 H, H(9) and H(10)). 13C NMR (CDCl3), δ:
22.66 (C(14)); 25.20 (C(15b)); 28.83 (C(15a)); 33.79 (C(3));
(CDCl3), δ: 25.45 and 26.06 (both d, C(8) and C(9), JC—P
4.4 Hz); 32.50 (C(3), JC—P = 6.2 Hz); 34.60 (C(5), JC—P
2.2 Hz); 38.92 (C(4), JC—P = 65.4 Hz); 39.61 (C(10), JC—P
=
=
=
34.92 (C(16b), JC—P = 56.5 Hz); 36.10 (C(16a), JC—P
=
62.5 Hz); 44.71 (C(6), JC—P = 7.3 Hz); 64.14 and 64.43 (C(11)
and C(12)); 99.26 (C(1), JC—P = 111.5 Hz); 102.51 (C(7));
125.95 and 125.98 (JC—P = 3.0 Hz); 127.92 (JC—P = 5.1 Hz);
128.00 (JC—P = 2.5 Hz); 128.95 and 129.75 (C(b), C(c), C(d),
59.2 Hz); 46.86 (C(2), JC—P = 65.2); 50.87 (C(1)); 110.28
(C(5), JC—P = 10.4 Hz); 126.21 (Co, JC—P = 10.2 Hz); 127.76,
128.08, 128.16, and 128.42 (C(8), C(9), C(10), C(11)); 129.66
(Cm/p, JC—P = 4.7 Hz); 130.02 (Cm/p, JC—P = 4.7 Hz); 133.04
(Cipso, JC—P = 7.8 Hz); 133.13 (Cipso, JC—P = 8.2 Hz); 139.66
and 140.36 (C(7) and C(12)); 143.59 (C(4), JC—P = 14.4 Hz);
153.21 (C(13)); 154.79 (C(6)).
1ꢀBenzylꢀ5ꢀ[1,1ꢀdimethylꢀ2ꢀ(3ꢀmethylquinoxalinꢀ2ꢀ
yl)ethyl]ꢀ1ꢀoxoꢀ2ꢀphenylꢀ4,5ꢀdihydroꢀ1Hꢀphospholꢀ3ꢀylamine
(14) was isolated by column chromatography (Al2O3, 1% MeOH
in CHCl3) from the mother liquor after recrystallization of
enamine 13. The yield was 20%. MS, m/z (Irel (%)): 481.22744
C(b´), C(c´)´, C(d´), JC—P = 5.1 Hz); 134.24 (C(a´), JC—P
6.2 Hz); 134.84 (C(a), JC—P = 9.5 Hz); 155.37 (C(2), JC—P
40.0 Hz).
=
=
Dibenzyl(2ꢀcyanoethyl)phosphine oxide (20) was isolated from
the crude product by column chromatography (Al2O3, CHCl3).
The yield was 58%. MS, m/z (Irel (%)): 283.11215 (M+, 20%,
calculated for C17H18NOP 283.11260), 192 (100), 91 (90).
IR (CHCl3), ν/cm–1: 3100—2900, 2250, 1490, 1450, 1150,
1120. 31P NMR (CDCl3), δ: 40.47. 1H NMR (CDCl3), δ:

Preparation of aminophospholene oxides
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 4, April, 2002
677
1.88 m, 2.24 m, 3.13 m, 7.25 m. 13C NMR (CDCl3), δ: 9.80
References
(JC—P = 2.2 Hz); 22.52 (JC—P = 64.7 Hz); 36.58 (JC—P
=
62.5 Hz); 118.71 (JC—P = 15.2 Hz); 127.29 (JC—P = 2.9 Hz);
128.93 (JC—P = 2.2 Hz); 129.42 (JC—P = 5.1 Hz); 130.64
(JC—P = 8.0 Hz).
1. L. P. A. de Jong and H. P. Benschop, in Stereoselectivity of
Pesticides; Eds. E. J. Ariëns, J. J. S. van Rensen, and
W. Welling, Elsevier, Amsterdam, 1988, 109.
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1ꢀBenzylꢀ5ꢀethylꢀ4ꢀmethylꢀ1ꢀoxoꢀ2ꢀphenylꢀ4,5ꢀdihydroꢀ1Hꢀ
phospholꢀ3ꢀylamine (22). The yield was 80%, m.p. 147—150 °C
(from hexane). MS, m/z (Irel (%)): 325.15946 (M+, 11%, calꢀ
culated for C20H24NOP: 325.15954), 235 (15), 234 (100),
91 (14). IR (CHCl3), ν/cm–1: 3100—2900, 1625, 1595, 1145,
1120. 31P NMR (CDCl3,), δ: 58.62. 1H NMR (CDCl3), δ: 0.77
(d, 3 H, H(5), J = 7.0 Hz); 1.01 (t, 3 H, H(7), J = 7.4 Hz);
1.35 (dddd, 1 H, H(4), J = 8.8 Hz, J = 5.5 Hz, J = 5.5 Hz, J =
5.3 Hz); 1.48 (m, 1 H, H(6a)); 1.80 (m, 1 H, H(6b)); 2.37
(qdd, 1 H, H(3), J = 7.0 Hz, J = 5.3 Hz, J = 2.2 Hz); 3.01 (m,
2 H, H(8)); 4.68 (s, 2 H, NH2); 6.88 (dt, 2H H(b´), J = 6.8 Hz,
J = 2.0 Hz); 7.17 (m, 4 H, H(d); H(c´), H(d´)); 7.35 (t, 2 H,
H(c), J = 8.0 Hz); 7.49 (d, 2 H, H(b), J = 8.0 Hz). 13C NMR
7. G. Markl, Angew. Chem., Int. Ed., 1965, 4, 1023.
8. L. D. Quin, The Heterocyclic Chemistry of Phosphorus: Sysꢀ
tems Based on the PhosphorusꢀCarbon Bond, WileyꢀInterꢀ
science: New York, 1981, 235.
(CDCl3), δ: 13.61 (C(7), JC—P = 5.8 Hz); 18.99 (C(5), JC—P
8.7 Hz); 22.23 (C(6), JC—P = 2.5 Hz); 38.42 (C(8), JC—P
62.1 Hz); 40.01 (C(4), JC—P = 66.9 Hz); 43.03 (C(3), JC—P
6.2 Hz); 98.18 (C(1), JC—P = 110.8 Hz); 126.02 and 126.13
(JC—P = 3.3 Hz); 128.01 (JC—P = 5.1 Hz); 128.06 (JC—P
=
=
=
9. R. Bodalski and K. M. Pietrusiewicz, Tetrahedron Lett.,
1972, 41, 4209.
10. R. Bodalski, K. M. Pietrusiewicz, and J. Koszuk, Tetraꢀ
hedron, 1975, 31, 1907.
11. V. D. Kolesnik, T. V. Rybalova, Yu. V. Gatilov, and A. V.
Tkachev, Mendeleev Commun., 2001, 11, 98
12. W. R. Purdum and K. D. Berlin, J. Org. Chem., 1974, 39, 2904.
13. W. G. Bentrude and W. N. Setzer, in Phosphorusꢀ31 NMR
Spectroscopy in Stereochemical Analysis, Eds. J. G.Verkade
and L. D. Quin, VCH Publishers: Deerfield Beach, 1987, 365.
14. A. J. Kirby and S. G. Warren, The Organic Chemistry of
Phosphorus, Elsevier, Amsterdam, 1967, 39.
15. R. S. Edmudson, in The Chemisry of Organophosphorus Comꢀ
pounds, Ed. F. R. Hartley, John Wiley and Sons, Chichester,
1992, 2, 288—405.
=
2.9 Hz); 128.97 and 129.74 (C(b); C(c), C(d), C(b´), C(c´),
C(d´), JC—P = 5.1 Hz); 133.69 (C(a´), JC—P = 5.8 Hz); 134.68
(C(a), JC—P = 8.4 Hz); 159.72 (C(2), JC—P = 40.0 Hz).
Dibenzyl[2ꢀ(dibenzylphosphoryl)ꢀ1ꢀphenylethyl]phosphine
oxide (24). The yield was 50%, m.p. 250—251°C (from CHCl3);
MS, m/z (Irel (%)): 582.21568 (M+ 27%, calculated for
,
C36H36O2P2: 582.21904), 471 (18), 334 (22), 333 (72), 230 (15),
139 (15), 91 (100); IR (CHCl3), ν/cm–1: 3100—2900, 1600,
1490, 1450, 1150, 1120, 830. 31P NMR (CDCl3), δ: 43.75
1
(d, J = 40.5 Hz); 40.95 (d, J = 40.5 Hz). H NMR (CDCl3), δ:
2.50 (m, 2 H, H(2)); 2.80—3.80 (m, 9 H, H(1), CH2Ph);
7.00—7.40, 7.57 (m, 25 H, Ph). 13C NMR (CDCl3), δ: 27.18
(C(2), JC—P = 61.7 Hz, JC—P = 1.3 Hz); 33.79 (CH2Ph, JC—P
16. D. G. Gorenstein, Nonꢀbiological Aspects of Phosphorusꢀ31
NMR Spectroscopy, in Progress in Nuclear Magnetic Resoꢀ
nance Spectroscopy, 1983, 16, part 1.
=
60.6 Hz); 34.17 (CH2Ph, JC—P = 58.2 Hz); 35.70 (CH2Ph,
JC—P = 60.5 Hz); 36.33 (CH2Ph, JC—P = 58.3 Hz); 39.48
17. R. S. Jain, H. F. Lawson, and L. D. Quin J. Org. Chem.,
1978, 43, 108.
(C(1), JC—P = 57.9 Hz, JC—P = 3.6 Hz); 125.94 (Phm/p
JC—P = 2.3 Hz); 126.13 (Phm/p, JC—P = 2.4 Hz); 126.17 (Phm/p
JC—P = 2.8 Hz); 126.26 (Phm/p, JC—P = 2.6 Hz); 127.30 (Phm/p
,
,
,
18. L. D. Quin and R. C. Stocks, J. Org, Chem., 1974, 39, 687.
19. F. Tiemann and F. W. Semmler, Ber., 1893, 26, 2708.
20. A. V. Korovin, A. V. Rukavishnikov, and A. V. Tkachev,
Mendeleev Commun., 1997, 114.
JC—P = 2.2 Hz); 127.81 (Phm/p, JC—P = 2.2 Hz); 128.03—128.11
(Phm/p); 128.42 (Phm/p, JC—P = 2.0 Hz); 129.59 (Pho, JC—P
5.2 Hz); 129.69 (Pho, JC—P = 5.3 Hz); 129.77 (Pho, JC—P
5.1 Hz); 129.82 (Pho, JC—P = 4.7 Hz); 132.19 (Phipso, JC—P
7.4 Hz); 132.24 (Phipso, JC—P = 7.6 Hz); 132.27 (Phipso, JC—P
7.6 Hz); 132.40 (Phipso, JC—P = 7.5 Hz); 137.05 (Phipso, JC—P
5.3 Hz, JC—P = 1.9 Hz).
=
=
=
=
=
21. N. Campbell and A. E. S. Fairfull, J. Chem. Soc., 1949,
1239—1241.
22. G. Sosnovsky, J. A. Krogh, and S. G. Umhoefer, Synthesis,
1979, 722—724.
23. R. C. Miller, J. S. Bradley, and L. A. Hamilton, J. Am.
Chem. Soc., 1956, 78, 5299.
This study was financially supported by the INTAS
(Grant 97ꢀ0217).
Received June 9, 2001;
in revised form December 14, 2001