Aza-Michael reaction as an efficient method for the synthesis of first representatives of β-azahetaryl-β-diphenylphosphorylalkanones

Article abstract of DOI:10.1007/s11172-016-1520-y

Aza-Michael reaction of (E)-4-(diphenylphosphoryl)but-3-en-2-one (1) with a number of mono-and bicyclic nitrogen heterocycles proceeds regioselectively in the absence of catalysts with the formation of corresponding β-azahetaryl β-diphenylphosphoryl keton

Full text of DOI:10.1007/s11172-016-1520-y

Russian Chemical Bulletin, International Edition, Vol. 65, No. 7, pp. 1855—1858, July, 2016
1855
AzaꢀMichael reaction as an efficient method for the synthesis of first
representatives of βꢀazahetarylꢀβꢀdiphenylphosphorylalkanones*
M. A. Galkina, G. V. Bodrin, E. I. Goryunov, I. B. Goryunova, A. A. Ambartsumyan, T. T. Vasil´eva,
P. S. Protopopova, A. E. Saifutiarova, A. B. Uryupin, V. K. Brel, and K. A. Kochetkov
A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
2
8 ul. Vavilova, 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 5085. Eꢀmail: const@ineos.ac.ru
AzaꢀMichael reaction of (E)ꢀ4ꢀ(diphenylphosphoryl)butꢀ3ꢀenꢀ2ꢀone (1) with a number of
monoꢀ and bicyclic nitrogen heterocycles proceeds regioselectively in the absence of catalysts
with the formation of corresponding βꢀazahetaryl βꢀdiphenylphosphoryl ketones; in the case of
imidazole, the presence of chiral organic catalysts allows one to increase the yields of the
adducts and to obtain them in enantiomerically enriched form.
Key words: βꢀdiphenylphosphorylꢀα,βꢀenones, nitrogen heterocycles, azaꢀMichael reacꢀ
tion, βꢀazahetarylꢀβꢀdiphenylphosphorylalkanones, synthesis, NMR spectra.
Addition process of Nꢀnucleophiles to electronꢀdefiꢀ
cient alkenes by the azaꢀMichael reaction is not only an
efficient method for the formation of carbon—nitrogen
bonds in organic compounds, but also meets all the reꢀ
quirements of "green" chemistry. This reaction uses
a wide range of Michael acceptors, such as enones, enals,
pounds would lead to the synthesis of a new series of corꢀ
responding phosphorusꢀ and nitrogenꢀcontaining strucꢀ
tures, among which it is promising to search for original
P,Nꢀligands and physiologically active compounds. In
fact, the nootropic properties of diarylphosphorylacetic
1
8
acid hydrazides are well known, whereas among nitroꢀ
nitro alkenes, etc.,1 and catalysts. As to the application
of unsaturated organophosphorus compounds as Michael
acceptors, the addition of NHꢀnucleophiles to vinylphosꢀ
,2
3
genꢀcontaining organophosphorus extractants (carbaꢀ
moylmethylphosphine oxides9 and Nꢀphosphorylureas )
derivatives containing diphenylphosphoryl group possessed
the highest efficiency.
,10
11
4
phonates was described for the first time for the reaction
of CH =CHP(O)(OEt) with ammonia, dimethylamine,
As to Michael acceptors, we used recently obtained12
(E)ꢀ4ꢀ(diphenylphosphoryl)butꢀ3ꢀenꢀ2ꢀone (1) and (E)ꢀ
1,5ꢀdiphenylꢀ5ꢀ(diphenylphosphoryl)pentꢀ1ꢀenꢀ3ꢀone
(2). The C=C bond in pentenone 2 is far from the diphenꢀ
ylphosphoryl fragment and is sterically more available for
the attack by a nucleophile, than in compound 1. However,
2
2
piperidine, aniline, and diphenylamine. In these examꢀ
ples, in the case of dimethylamine and piperidine no apꢀ
plication of any catalysts was required and the reactions
proceeded readily at room temperature, leading to the corꢀ
responding βꢀaminoethyl phosphonates R NCH CH ꢀ
2
2
2
31
1
P(O)(OEt) , while in all the other cases the use of a basic
according to the P{ H} NMR spectral and TLC data,
compound 2 does not react with imidazole (3), benzimidꢀ
azole (4), 3,5ꢀdimethylpyrazole (5), and 1Hꢀbenzotriazole
(6), despite a wide variation of the reaction conditions, that
indicates a decreased activity of the double bond in this
enone. Conversely, in the case of enone 1 the addition reacꢀ
tion of nitrogen heterocycles 3—6 proceeds readily enough
even in the absence of catalysts, while their presence is
usually necessary for the azaꢀMichael reaction of activated
2
catalyst such as sodium methoxide was a necessity. Afterꢀ
5
wards, the studies performed by both Russian and foreign
6
scientists resulted in the development of a general apꢀ
proach based on this reaction to the preparation of various
representatives of βꢀaminoethyl phosphonates, phosphiꢀ
nates, and phosphine oxides (additional information can
be found in the reviews1 ). However, there are no examꢀ
ples of using this methodology for the preparation of
nitrogen heterocycles containing ethyl substituents with
diarylphosphoryl fragments.
,7
1
α,βꢀenones with these substrates to proceed (Scheme 1).
The reaction was carried out under argon upon reflux
in anhydrous acetonitrile or toluene (Table 1). As it folꢀ
lows from the analysis of the structure of obtained comꢀ
We suggested that the reaction of unsaturated oxoalkylꢀ
diphenylphosphine oxides with aminoꢀcontaining comꢀ
1
1
31
31
1
pounds by H, H{ P}, and P{ H}) NMR spectroscopy
see Experimental section), the addition proceeds regiꢀ
(
*
Based on the materials of the International Congress on the
Heterocyclic Chemistry "KOSTꢀ2015" (October 18—23, 2015,
Moscow, Russia).
oselectively at the carbon atom closest to the dipheꢀ
nylphosphoryl group, that is not characteristic of the reacꢀ
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1855—1858, July, 2016.
066ꢀ5285/16/6507ꢀ1855 © 2016 Springer Science+Business Media, Inc.
1

1
856
Russ.Chem.Bull., Int.Ed., Vol. 65, No. 7, July, 2016
Galkina et al.
Table 1. Reaction of enone 1 with nitrogen heterocycles 3—6
The use of known chiral organocatalysts of Michael
reaction such as amino alcohols, diols, and binaphꢀ
3
,13—15
Heteroꢀ T/°C
cycle
τ/h
Solvent
Reaction
product
Yield
(%)
thols
sharply accelerates the reaction of enone 1
and imidazole 3, as well as increases the yield of the addiꢀ
tion product 7, though, the stereoselectivity of the process
is low: the best results (9% ee) were obtained with (S)ꢀ
BINOL. The results of the addition of imidazole to enone
1 in the presence of 5 mol.% of chiral catalysts at 110 °C in
toluene are given in Table 2. The acceleration of the proꢀ
cess by these compounds is probably related to the known
possibility of bifunctional catalysis through both the actiꢀ
vation of Michael acceptor 1 due to the formation of hyꢀ
drogen bonds at the carbonyl group and enhancement of
nucleophilicity of heterocycle 3 as a result of coordinaꢀ
3
4
5
6
80
15
16
65
48
МеCN
PhMe
PhMe
PhMe
7a
7b
7c
7d
78
37
80
41
110
110
110
Note. τ is the reaction time.
Scheme 1
1
,3,13—15
tion.
The yield was determined based on the reꢀ
sults of isolation and analysis of the final Michael product.
1
6
The calculations carried out using the PASS program
indicate a high (>90%) probability of the presence of nooꢀ
tropic physiological activity for compounds 7a—d.
In summary, the involvement of unsaturated organoꢀ
phosphorus functional compounds in azaꢀMichael reacꢀ
tion gave earlier unknown representatives of a series of
βꢀhetarylꢀβꢀdiphenylphosphorylalkanones, which are of inꢀ
terest as compounds with potential biological activity,
phosphorusnitrogen ligands capable of extracting fꢀeleꢀ
ments, and intermediate compounds for the synthesis of
various derivatives at the carbonyl group, for example,
hydrazones containing pharmacophoric fragments, includꢀ
ing alkaloid groups.
1
2,17
)
Recently,
we have developed a new approach to
the synthesis of phosphorylbutenone 1, which is based on
the reaction of chlorodiphenylphosphine (8) with comꢀ
mercially available 4ꢀmethoxybutꢀ3ꢀenꢀ2ꢀone (9) in the
presence of glacial AcOH (the Conant reaction) in anꢀ
hydrous benzene* at room temperature. This method was
considerably more efficient than the known multiꢀstep
Reagents and conditions: heating, 15—65 h, MeCN (PhCH ).
3
1
tion with disubstituted Michael acceptors, and the presꢀ
1
9
ence of the second possible regioisomer was not found
even in the trace amounts.
synthesis of 1, however, a relatively low rate of Conant
reaction under these conditions and environmentally unꢀ
These results demonstrate that imidazole 3 turned out
to be the most active heterocycle for this process, whereas
After publication of the Mikoіajczyk´s work,18 in which anꢀ
*
3
,5ꢀdimethylpyrazole 5 and 1Hꢀbenzotriazole 6 are the
hydrous benzene was suggested for the first time as a solvent in
the Conant reaction, such a version became widely used in the
least active in this reaction, that agrees with the data on
1
7
12,17
the basicity (pK ) of these compounds.
synthesis of diorganylphosphorylalkanones and ꢀalkenones.
b
Table 2. Formation of imidazolylꢀsubstituted ketone 7a in the presence of chiral catalysts
Catalyst
τ/h
Yield 7a
%)
ee 7a
(%)
(
(
(
4R,5R)ꢀ2,2ꢀDimethylꢀα,α,α´,α´ꢀtetraphenyldioxolaneꢀ4,5ꢀdimethanol (TADDOL)
4Sꢀtrans)ꢀ2,2ꢀDimethylꢀα,α,α´,α´ꢀtetra(1ꢀnaphthyl)ꢀ1,3ꢀdioxolaneꢀ4,5ꢀdimethanol
16
16
16
16
21
53
60
68
71
98
4
4
3
2
9
Cinchonidine
NꢀBenzylꢀ(S)ꢀproline
(
S)ꢀ(–)ꢀ1,1´ꢀBi(2ꢀnaphthol) ((S)ꢀBINOL)
Note. τ is the reaction time.

βꢀAzahetarylꢀβꢀdiphenylphosphorylalkanones
Russ.Chem.Bull., Int.Ed., Vol. 65, No. 7, July, 2016
1857
friendly process which uses carcinogenic solvent benzene,
stimulated its further improvement.
diately before use. Glacial acetic acid of reagent grade was disꢀ
tilled before use in reaction. Column chromatography was
performed on Al O (Brockmann I, 50—200 μm, Acros), silica gel
We found that carrying out the Conant reaction beꢀ
tween compound 8 and enone 9 in acetonitrile, rather
than benzene, allowed one to simultaneously sharply deꢀ
crease the reaction time (from 48 h to 1 h) and considerꢀ
ably (by ~20%) increase the yield of phosphorylenone 1
up to 77% (Scheme 2).
2
3
(
(
130—270 mesh, 60 Å, Aldrich), and Florisil® (60—100 mesh)
Acros).
Acetonitrile was dried before use by double distillation over
P O . Other organic solvents used in the work were purified
2
5
20
according to the standard procedures.
(E)ꢀ4ꢀ(Diphenylphosphoryl)butꢀ3ꢀenꢀ2ꢀone (1). A solution of
glacial AcOH (2.8 g, 46.6 mmol) in anhydrous acetonitrile (5 mL)
and a solution of compound 8 (9.1 g, 41.2 mmol) were sequenꢀ
tially added dropwise to a solution of 4ꢀmethoxybutꢀ3ꢀenꢀ2ꢀone
Scheme 2
(
9) (5.0 g, 49.9 mmol) in anhydrous acetonitrile (15 mL) with
stirring on a magnetic stirrer, the stirring was continued for 1 h
at room temperature. The solvent and other volatile compounds
were removed in vacuo (~15 Torr), the residue was allowed to
stand in vacuo (~1 Torr) for 2.5 h at ~50 °C, a dark red residue
was dissolved in CH Cl2 (50 mL) and sequentially filtered
2
through basic Al O (9.0 g), silica gel (9.0 g), and Florisil® (9.0 g),
2
3
every time eluting the support with CH Cl (30 mL), the solvent
2
2
Reagents and conditions: MeCOOH, ~20 °C, 1 h, acetonitrile.
was removed from the filtrate, to the residue was diluted with
hexane (35 mL) and refluxed for 2.5 h with stirring on a magnetꢀ
ic stirrer. A precipitate formed was separated, washed with
a mixture of hexane—diethyl ether 1 : 1 (3×20 mL), and dried in
air until the weight was constant. The yield was 8.816 g (77.4%),
m.p. 128—130 °C (cf. Ref. 19: m.p. 128—129 °C). Found (%):
C, 71.09; H, 5.58; P, 11.35. C H O P. Calculated (%): C, 71.11;
The monitoring of this Conant reaction by 31P{ H}
1
NMR spectroscopy showed that a compound with δ ≈ 30
P
is initially formed in the course of this process, which is
further transformed to phosphorylenone 1. Since chemiꢀ
cal shifts of various 4ꢀdiphenylphosphorylated 4ꢀsubstiꢀ
16
15
2
H, 5.59; P, 11.46. 3 P{ H} NMR, δ: 22.87 (s).
ꢀ(Diphenylphosphoryl)ꢀ4ꢀ(1Hꢀimidazolꢀ1ꢀyl)butanꢀ2ꢀone
7a). Imidazole 3 (0.076 g, 1.11 mmol) was added to a solution of
E)ꢀ4ꢀ(diphenylphosphoryl)butꢀ3ꢀenꢀ2ꢀone (1) (0.30 g, 1.11 mmol)
1
1
1
7
tuted butanꢀ2ꢀones lie in the range of δ 32—34, it can
P
4
be suggested that the intermediate product of the Conant
reaction between compound 8 and enone 9 is a low stable
adduct Ph P(O)CH(OMe)CH C(O)Me, which eliminates
(
(
2
2
in acetonitrile (10 mL). The reaction mixture was allowed to
the methanol molecule to be stereoselectively converted
to compound 1.
stand at 80 °C with continuous stirring on a magnetic stirrer for
31
1
15 h. The reaction progress was monitored by P{ H} NMR
spectroscopy. Upon completion, the mixture was concentrated
to dryness, the product was extracted with diethyl ether. Crystals
of the product were formed upon standing of the extract at 0 °C,
which were separated and dried at 50 °C in a drying oven until
the weight was constant. The yield of 7a was 0.23 g (53%), m.p.
In conclusion, based on the Conant reaction we sugꢀ
gested a new considerably more efficient and environmenꢀ
tally friendly approach to the synthesis of transꢀ4ꢀ(diꢀ
phenylphosphoryl)butꢀ3ꢀenꢀ2ꢀone (1), which makes this
original organophosphorus compound available for wide
synthetic practice.
1
39—141 °C. An additional amount of the product (0.11 g, 25%)
was isolated from the solution. Found (%): C, 67.61; H, 5.74;
N, 8.34; P, 9.16. C H N O P. Calculated (%): C, 67.45; H, 5.66;
1
9
19
2 2
–
1
31
1
N, 8.28; P, 9.15. IR, ν/cm : 1203 (P=O), 1719 (C=O). P{ H}
NMR, δ: 30.43 (s). H{ P} NMR, δ: 2.02 (s, 3 H, Me); 2.93 (dd,
Experimental
1
31
3
2
1
H, CH H , J
= 2.0 Hz, J
= 18.4 Hz); 3.34 (dd, 1 H,
H ,H
B
= 18.2 Hz); 5.49 (dd, 1 H,
H ,H
A
A
3
B
H ,H
A
A
1H, 1H{ P} and P{ H} NMR spectra were recorded on
31
31
1
2
CH H , J
PCH, J
= 10.1 Hz, J
= 2.1 Hz, 3J
7.15 (s, 1 H, H (5)); 7.34 (t, 2 H, mꢀPh, J
A
B
3
H ,H
B
B
1
1
31
a Bruker AVꢀ400 spectrometer (400,13 MHz ( H and H{ P})
and 161.98 MHz ( P{ H})) at 30 °C, the solvent was CDCl .
= 9.8 Hz); 6.92 (s, 1 H, HHet(4));
H,HB
H,HA
31
1
3
= 7.6 Hz); 7.45
3
Het
H,H
3
Signals of residual protons of the deuterated solvent were used as
(t, 1 H, pꢀPh, J
= 7.6 Hz); 7.48 (s, 1 H, HHet(2)); 7.48 (d, 2 H,
H,H
1
1
31
3
3
an internal reference in the H/ H{ P} NMR spectra, 85% aqueous
oꢀPh, J
= 7.5 Hz); 7.57 (t, 2 H, mꢀPh, J
= 7.3 Hz); 7.63
H,H
H,H
31
1
3
3
H PO was used as an external standard for P{ H} NMR spectra.
(t, 1 H, pꢀPh, J
= 7.3 Hz); 7.88 (d, 2 H, oꢀPh, J
= 7.9 Hz).
3
4
H,H
H,H
IR spectra were recorded on a URꢀ20 spectrometer in CHCl3.
Mass spectra were recorded on a Finnigan SSQꢀ7000 mass
spectrometer. Elemental analysis was performed in the Laboraꢀ
tory of Microanalysis of the A. N. Nesmeyanov Institute of Orꢀ
ganoelement Compounds of the Russian Academy of Sciences.
Melting points were measured in a sealed capillary tube using an
Electrothermal IA 9000 indicator of melting points. Phosphorylꢀ
enone 2 was obtained according to the procedure described earꢀ
4ꢀ(1HꢀBenzimidazolꢀ1ꢀyl)ꢀ4ꢀ(diphenylphosphoryl)butanꢀ2ꢀ
one (7b) was obtained similarly to 7a from enone 1 (0.10 g,
0.37 mmol) and benzimidazole 4 (0.044 g, 0.37 mmol) in toluene
(15 mL) after heating at 110 °C for 16 h. The yield of 7b was
0.053 g (37 %), m.p. 162—164 °C (Et O). Found (%): C, 71.20;
2
H, 5.74; N, 6.51; P, 7.49. C H N O P. Calculated (%): C, 71.12;
2
3
21
2
2
–
1
H, 5.45; N, 7.21; P, 7.97. IR, ν/cm : 1194 (P=O), 1720 (C=O).
P{ H} NMR, δ: 30.93 (s). H NMR, δ: 1.97 (s, 3 H, Me); 3.16
3
1
1
1
1
2
3
3
2
lier. The starting azoles 3—6, as well as α,βꢀenone 9 (Acros)
were used without additional purification. Chlorodiphenylphosꢀ
phine (8) (from Acros) was purified by vacuum distillation immeꢀ
(ddd, 1 H, CH H , J
= 3.0 Hz, J
= 8.2 Hz, J
=
=
A
B
H ,H
H ,P
H ,H
B
A
A
A
3
3
= 18.5 Hz); 3.47 (ddd, 1 H, CH H , J
= 9.1 Hz, J
A
B
H ,H
H ,P
B
B
= 5.0 Hz, 2
J
= 18.5 Hz); 5.80—5.86 (m, 1 H, PCH);
H ,H
A
B

1
858
Russ.Chem.Bull., Int.Ed., Vol. 65, No. 7, July, 2016
Galkina et al.
7
.10—7.30 (m, 5 H, mꢀPh, pꢀPh + 2 HHet); 7.44 (dd, 2 H, oꢀPh,
Berdnikova, O. A. Mostovaya, S. M. Rybakov, R. A. Cherkaꢀ
sov, Zh. Org. Khim., 2007, 43, 1703 [Russ. J. Org. Chem.
(Engl. Transl.), 2007, 43]; (c) R. A. Cherkasov, A. R. Garifzyꢀ
anov, N. V. Kurnosova, E. V. Matveeva, I. L. Odinets, Russ.
Chem. Bull. (Int. Ed.), 2012, 61, 174 [Izv. Akad. Nauk, Ser.
Khim., 2012, 171]; (d) A. N. Yarkevich, L. N. Petrova, S. O.
Bachurin, Zh. Obshch. Khim., 2012, 82, 1633 [Russ. J. Gen.
Chem. (Engl. Transl.), 2012, 82]; (e) N. G. Khusainova, D. B.
Curvesolapov, A. V. Gerasimov, Zh. Org. Khim., 2014, 50,
492 [Russ. J. Org. Chem. (Engl. Transl.), 2014, 50].
6. (a) D.ꢀH. Suk, D. Rejman, C. C. Dykstra, R. Pohl, K. W.
Pankiewicz, S. E. Patterson, Bioorg. Med. Chem. Lett., 2007,
17, 2811; (b) V. Peruzzo, C. Pretzsch, F. Tisato, M. Porchia,
F. Refosco, C. Marzano, V. Gandin, E. Schiller, M. Walther,
H.ꢀJ. Pietzsch, Inorg. Chim. Acta, 2012, 387, 163; (c) N. Bou
Orm, Y. Dkhissi, S. Daniele, L. Djakovitch, Tetrahedron,
2013, 69, 115; (d) D. Hocková, Š. Rosenbergová, P. Mnová,
O. Páv, R. Pohl, P. Novák, I. Rosenberg, Org. Biomolec.
Chem., 2015, 13, 4449.
7. (a) E. S. Gubnitskaya, L. P. Peresypkina, L. I. Samarai, Usp.
Khim., 1990, 59, 1386 [Russ. Chem. Rev., 1990, 59]; (b) F. Palaꢀ
cios, C. Alonco, J. M. de los Santos, Chem. Rev., 2005, 105, 899.
8. (a) R. I. Tarasova, V. V. Moscow, Butlerov Communs., 1999,
1, No. 1, 77; (b). R. I. Tarasova, I. I. Semina, Butlerov Comꢀ
mun., 1999, 1, No. 2, 33.
9. B. F. Myasoedov, M. K. Chmutova, N. E. Kochetkova,
O. E. Koiro, G. A. Pribylova, N. P. Nesterova, T. Y. Medved´,
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10. E. V. Sharova, O. I. Artyushchin I. L. Odinets, Russ. Chem.
Rev., 2014, 83, 95.
3
JH,H = 7.4 Hz, 3JH,P = 11.4 Hz); 7.55—7.68 (m, 5 H, mꢀ,
3
3
pꢀC H + 2 H ); 7.95 (dd, 2 H, oꢀPh, J
= 7.7 Hz, J
=
6
5
Het
H,H
H,P
=
10.2 Hz); 8.20 (br.s, 1 H, HHet(2)).
ꢀ(3,5ꢀDimethylpyrazolꢀ1ꢀyl)ꢀ4ꢀ(diphenylphosphoryl)butanꢀ
ꢀone (7c). Compound 7c (0.107 g, 80%) was isolated from the
reaction mixture obtained similarly to 7a from enone 1 (0.10 g,
.37 mmol) and 3,5ꢀdimethylpyrazole 4c (0.035 g, 0.37 mmol)
4
2
0
in toluene (5 mL) upon heating at 110 °C for 65 h. The product
was separated by preparative TLC on silica gel (60 PF254 with
3
a CHCl : ethyl acetate (1 : 3) solvent mixture, m.p. 170—172 °C.
Found (%): C, 68.54; H, 6.04; N, 7.14. C H N O P. Calcuꢀ
lated (%): C, 68.84; H, 6.33; N, 7.65. IR, ν/cm : 1188 (P=O),
1
0% gypsum) deposited on 180×240ꢀmm glass plate, eluting with
3
21
23
–
2
2
1
721 (C=O). 3 P{ H} NMR, δ: 30.82 (s). H NMR, δ: 1.82 (s, 3 H,
1
1
1
C(3)MeHet); 2.05 (s, 3 H, COMe); 2.18 (s, 3 H, C(5)MeHet);
3
3
3
.14 (ddd, 1 H, CH H ,
J
= 1.8 Hz,
J
H ,P
A
= 5.8 Hz,
= 10.8 Hz,
A
B
H ,H
A
2
3
J
J
= 18.2 Hz); 3.75 (ddd, 1 H, CH H , J
A B H ,H
B
H ,H
A
B
3
2
= 4.2 Hz,
= 1.6 Hz, J
J
= 18.1 Hz); 5.28 (ddd, 1 H, PCH,
H ,H
B
H ,P
B
A
3J
3
= 10.8 Hz, J = 11.1 Hz); 5.56 (s, 1 H,
H,P
2
H,HA
H,HB
H(4) ); 7.34—7.58 (m, 8 H, oꢀ, mꢀPh, pꢀPh); 7.99 (dd, 2 H,
oꢀPh, J
Het
3
3
= 7.8 Hz, J
= 11.3 Hz).
H,H
H,P
4
ꢀ(1HꢀBenzotriazolꢀ1ꢀyl)ꢀ4ꢀ(diphenylphosphoryl)butanꢀ2ꢀ
one (7d) was obtained similarly to 7a from enone 1 (0.2 g,
.74 mmol) and 1Hꢀbenzotriazole 4d (0.088 g, 0.74 mmol) in
toluene (15 mL) after heating at 110 °C for 48 h. The yield of 7d
0
31
1
was 0.12 g (41%), m.p. 148—150 °C. P{ H} NMR, δ: 30.07 (s).
1
3
H NMR, δ: 2.07 (s, 3 H, Me); 3.44 (ddd, 1 H, CH H , J
=
A
B
H ,H
A
3
2
=
2.8 Hz, J
= 6.8 Hz, J
= 18.4 Hz); 3.90 (ddd, 1 H,
H ,H
B
H ,P
A
A
3
3
2
CH H , J
= 10.1 Hz, J
= 4.8 Hz, J
= 18.4 Hz);
H ,H
A
A
B
H ,H
H ,P
B
A
B
6
.25—6.32 (m, 1 H, PCH); 7.25—7.29 (m, 1 H, H(5)Het); 7.32—7.55
11. A. M. Safiulina, E. I. Goryunov, A. A. Letyushov, I. B.
Goryunova, S. A. Smirnova, A. G. Ginzburg, I. G. Tananaev,
E. E. Nifant´ev, B. F. Myasoedov, Mendeleev Commun.,
2009, 19, 263.
12. G. V. Bodrin, E. I. Goryunov, I. V. Goryunova, Yu. V. Nelyuꢀ
bina, P.V. Petrovskii, M. S. Grigor´ev, A. M. Safiulina, I. G.
Tananaev, E. E. Nifant´ev, Dokl. Chem., 2012, 447, 269
[Dokl. Akad. Nauk, 2012, 447, 401].
13. O. V. Maltsev, I. P. Beletskaya, S. G. Zlotin, Russ. Chem.
Rev., 2011, 80, 1067.
14. Yu. N. Belokon´, K. A. Kochetkov, T. D. Churkina, N. S.
Ikonnikov, S. A. Orlova, N. A. Kuz´mina, D. E. Bodrov,
Russ. Chem. Bull. (Engl. Transl.), 1993, 42, 1525 [Izv. Akad.
Nauk, Ser. Khim., 1993, 1591].
3
(
m, 7 H, mꢀPh, pꢀPh + HHet(6)); 7.61 (d, 1 H, HHet(7), J
=
H,H
=
8.4 Hz); 7.70—7.83 (m, 4 H, oꢀPh); 7.92 (d, 1 H, HHet(4),
3
+
JH,H = 8.3 Hz). MS [CH CN]: 390.1363 [M + H] ; 412.1188
3
+
[
M + Na] . Calculated for C H N O P 390.137140; calculatꢀ
2
2
21
3
2
ed for C H N NaO P 412.119085.
2
2
20
3
2
The azaꢀMichael reaction of imidazole 3 with (E)ꢀ4ꢀ(diꢀ
phenylphosphoryl)butꢀ3ꢀenꢀ2ꢀone (1) was carried out in the
presence of 5 mol.% of the chiral catalysts. The mixture was
concentrated and the product was analyzed by H and P{ H}
NMR spectroscopy and by HPLC on a chiral column (HPLC
analysis (Aligent) Daicel Chiracel ODꢀH column; eluent: hexꢀ
1
31
1
–
1
ane—isopropyl alcohol (95 : 15) + 0.2% Et NH; 0.75 mL min
UVꢀdetector 225 nm).
,
2
1
5. K. A. Kochetkov, S. R. Harutyunyan, N. A. Kuz´mina, T. F.
Savel´eva, V. I. Maleev, A. S. Peregudov, S. Vysko il, A. S.
Sagiyan, Russ. Chem. Bull. (Int. Ed.), 2001, 50, 1620 [Izv.
Akad. Nauk, Ser. Khim., 2001, 1543].
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 14ꢀ03ꢀ00525ꢀa).
1
1
6. O. Filz, A. Lagunin, D. Filimonov, V. V. Poroikov, SAR
QSAR Environ. Res., 2008, 19, 81.
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Received January 26, 2016;
in revised form April 29, 2016