Ring-closing metathesis of 2,2-diallyl derivatives of pyrrolidine and piperidine: a route to azaspiroheterocyclic structures

Article abstract of DOI:10.1023/A:1015864100939

Transformations of 1-benzyl-2,2-di(2-propenyl)pyrrolidine and 1-benzyl-2,2-di(2-propenyl)piperidine into the corresponding 1-azaspiro[4.n]alkenes via ring-closing metathesis using accessible homogeneous catalytic systems WCl6-H2SiPh2, WOCl4-H2SiPh2, and R

Full text of DOI:10.1023/A:1015864100939

Russian Chemical Bulletin, International Edition, Vol. 51, No. 4, pp. 645—648, April, 2002
645
Organic Chemistry
Ringꢀclosing metathesis of 2,2ꢀdiallyl derivatives of pyrrolidine and
piperidine: a route to azaspiroheterocyclic structures
a
a
a
†b
N. B. Bespalova,a O. V. Shuvalova, V. G. Zaikin, R. S. Borisov, F. V. Pastukhov, and Yu. N. Bubnovb
ꢀ
аA. V. Topchiev Institute of Petrochemical Synthesis, Russian Academy of Sciences,
29 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (095) 230 2224. Eꢀmail: bnb@ ips.ac.ru
bA. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
28 ul. Vavilova, 117991 Moscow, Russian Federation.
Fax: +7 (095) 135 6549. Eꢀmail: ineos@ ineos.ac
Transformations of 1ꢀbenzylꢀ2,2ꢀdi(2ꢀpropenyl)pyrrolidine and 1ꢀbenzylꢀ2,2ꢀdi(2ꢀproꢀ
penyl)piperidine into the corresponding 1ꢀazaspiro[4.n]alkenes via ringꢀclosing metathesis
using accessible homogeneous catalytic systems WCl6—H2SiPh2, WOCl4—H2SiPh2, and
Ru(=CHPh)(PCy3)2Cl2 (Cy is cyclohexyl) were performed for the first time.
Key words: ringꢀclosing metathesis of olefins, homogeneous tungsten catalysts, dihydroꢀ
diphenylsilane, 1ꢀbenzylꢀ2,2ꢀdi(2ꢀpropenyl)pyrrolidine, 1ꢀbenzylꢀ2,2ꢀdi(2ꢀpropenyl)piꢀ
peridine, azaspirocyclic compounds.
Olefins metathesis that is essentially the redistribuꢀ
tion of alkylidene fragments allows one to synthesize
unsaturated compounds with a smaller number of stages
and byꢀproducts compared to the traditional routes of
organic chemistry.1—2 The main types of catalytic metaꢀ
thesis reactions used in synthesis are the following
(Scheme 1): (a) crossꢀmetathesis of terminal olefins with
ethylene elimination and the formation of new higher
olefins or bifunctional compounds, (b) ringꢀclosing metaꢀ
thesis of nonconjugated dienes to form the correspondꢀ
ing cycloolefins, (c) ringꢀopening metathesis polymerꢀ
ization of cycloolefins, and (d) crossꢀmetathesis of cycloꢀ
olefins with linear substrates.
Metathesis was discovered more than 30 years ago
but its wide use for preparative purposes became possible
rather recently, which is due to a great extent to the
creation of highly efficient catalysts, viz., sufficiently stable
carbene complexes of molybdenum3 and ruthenium4,5
tolerant to functional groups of the substrate. In recent
years, the ruthenium carbene complexes have been preꢀ
pared, which make it possible to perform metathesis in
methanol or water6 and obtain diꢀ, triꢀ, and even
tetrasubstituted carboꢀ and heterocycloolefins from the
corresponding dienes.7—9 Ringꢀclosing metathesis was
used for the preparation of nitrogenꢀcontaining heteroꢀ
cyclic compounds10 and cyclic peptides,11 diastereoꢀ
selective synthesis of pyrrolidine derivatives12 and
N,Oꢀcontaining heterocyclic spirocompounds.13 In most
† Deceased.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 596—599, April, 2002.
1066ꢀ5285/02/5104ꢀ645 $27.00 © 2002 Plenum Publishing Corporation

646
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 4, April, 2002
Bespalova et al.
Scheme 1
7ꢀene (3) and 6ꢀbenzylꢀ6ꢀazaspiro[4,5]ꢀdecꢀ2ꢀene (4),
respectively.
Scheme 2
a. Cross metathesis of acyclic olefins.
b. Ringꢀclosing olefin metathesis.
c. Ringꢀopening metathesis polymerization.
d. Crossꢀmetathesis of cyclic olefins with acyclic olefins.
Cat is catalyst.
cases, Grabbs catalysts are used for these purposes, and
the catalyst concentration usually does not exceed
10 mol.% but very often, especially for the preparation
of fiveꢀ and sixꢀmembered nitrogenꢀcontaining heteroꢀ
cycles, one has to use from 25 to 50% catalyst.14 Thereꢀ
fore, the development of more accessible and cheaper
catalytic systems in which active metalꢀcarbene interꢀ
mediates are generated in situ during the interaction of
the components remains to be an urgent task.
The following catalytic systems were tested:
(1) WCl6—H2SiPh2,
(2) WOCl4—H2SiPh2,
(3) WCl6—
(1,1,3,3ꢀtetramethylꢀ1,3ꢀdisilaꢀ
cyclobutane),
(4) WOCl4—
,
(5) RuCl3•(H2O)n—H2SiPh2,
(6) RuCl2(PPh3)3—H2SiPh2,
The majority of the known catalytic systems are inacꢀ
tive for the metathesis of olefins containing functional
groups. With these aims in view, researchers used only
homogeneous and heterogeneous catalytic systems conꢀ
taining alkyl derivatives of tin or lead,1 whose applicaꢀ
tion is restricted by high toxicity of these compounds.
Another type of catalysts for metathesis of functional
olefin derivatives is represented by homogeneous sysꢀ
tems based on tungsten chlorides in combination with
organosilicon compounds (1,3ꢀdisilacyclobutane derivaꢀ
tives, dihydrodiarylsilanes). They have earlier been used
for the preparation of the functional olefin derivatives in
high yield and selectivity.15—17 In this work, we present
the results of application of the latter (catalytic systems)
for the transformation of 2,2ꢀdiallyl derivatives of
pyrrolidine and piperidine into the corresponding spiroꢀ
heterocyclic compounds, viz., synthetic analogs of natuꢀ
ral compounds.
(7) RuCl2(PPh3)3—
,
and (8) Ru(=CHPh)(PCy3)2Cl2 (Grabbs catalyst).
We established that only compounds bearing benzyl
substituents at the nitrogen atom entered into metathesis
reactions and only under the effect of catalytic systems
containing H2SiPh2 as a cocatalyst. The systems conꢀ
taining 1,1,3,3ꢀtetramethylꢀ1,3ꢀdisilacyclobutane did not
manifest catalytic activity. This was rather unexpected
because these systems exhibited a high activity in the
metathesis of nitrogenꢀcontaining linear compounds16
and ringꢀclosing metathesis of esters of unsaturated
aliphatic acids.17 The catalytic systems containing
H2SiPh2 make it possible to perform the metathesis in
moderate yields and with high selectivities, which is preꢀ
sented in Table 1. Under the chosen conditions at a low
diene concentration in a solution (0.05 mol L–1), interꢀ
molecular metathesis, which affords linear and cyclic
oligoꢀ and polymeric products, does not virtually occur
(Scheme 3). The selectivity of the reaction decreases at
higher concentrations of the substrate.
Results and Discussion
We studied the ringꢀclosing metathesis reactions of
1ꢀbenzylꢀ2,2ꢀdi(2ꢀpropenyl)pyrrolidine (1) and 1ꢀbenꢀ
zylꢀ2,2ꢀdi(2ꢀpropenyl)piperidine (2), which afford the
azaspirocyclic compounds: 1ꢀbenzylꢀ1ꢀazaspiro[4,4]nonꢀ
The replacement of the tungsten compounds by the
RuCl2(PPh3)3 ruthenium complex in the systems with
H2SiPh2 slightly increased the selectivity of the reaction
(see Table 1). The RuCl3•n H2O systems in combinaꢀ

Ring closing metathesis of Nꢀcyclic compounds
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 4, April, 2002
647
Table 1. Metathesis of 1ꢀbenzylꢀ2,2ꢀdi(2ꢀpropenyl)pyrrolidine
(1) and 1ꢀbenzylꢀ2,2ꢀdi(2ꢀpropenyl)piperidine (2)
ionizing electrons 70 eV, emission current 100 µA, temperature
of the ionization of chamber 200 °C). A capillary column
(SEꢀ30; 30 m × 0.25 mm) was used in the chromatograph. The
pressure of the carrier gas (helium) at the inlet of the column
was 30 kPa, the flow division being 1 : 30. The temperature in
the thermostat was risen from 30 to 120 °C with a velocity of
5 deg/min and from 120 to 270 °C with a velocity of 10 deg/min.
NMR spectra were recorded in СDCl3 on a Bruker WPꢀ200
spectrometer using Me4Si as the internal standard.
Catalytic
system
[1] [2]
[M] [W]
Yield
(%)
Selectivity
(%)
3
4
3
4
WCl6—H2SiPh2
10 10
20 20
40 40
17 18
15 14
67
87
85
69
89
89
All procedures were conducted in dry argon or in a vacuum
of 1•10–3 Torr.
9
8
WOCl4—H2SiPh2
10 10
20 20
19 19
16 15
72
89
76
89
Toluene was boiled for 12 h above the Na/K melt, distilled,
and stored in the Schlenk vessel. Chloroform was distilled,
passed through a column packed with silica gel, and stored in
the Schlenk vessel; WCl6 was purified by distillation off in
vacuo from hydroxychlorides (WOCl4 and WO2Cl2); WOCl4
was sublimed in vacuo. The tungsten compounds were used as
solutions in toluene. The H2SiPh2 cocatalyst was prepared acꢀ
cording to a known procedure,19 and a solution of the comꢀ
pound was stored above LiAlH4. 1,1,3,3ꢀTetramethylꢀ1,3ꢀ
disilacyclobutane was prepared by a previously described proꢀ
cedure,20 distilled above Na, and stored above molecular sieves
5 Å. 2,2ꢀDi(2ꢀpropenyl)pyrrolidine (5) and 2,2ꢀdi(2ꢀproꢀ
penyl)piperidine were synthesized according to a known proceꢀ
dure21 and stored in argon above sieves 5 Å.
40 40
10 10
90
90
RuCl2(PPh3)3—H2SiPh2 20
Ru(=CHPh)(PCy3)2(Cl)2 30
18
24
93
95
Note. Reagents and conditions: toluene, 60 °C, 40 h,
[W]/[H2SiPh2] = 1/2, [I] = 0.05 mol L–1
.
Scheme 3
1ꢀBenzylꢀ2,2ꢀdi(2ꢀpropenyl)pyrrolidine (1). Benzyl bromide
(5.34 mL, 44 mmol) and K2CO3 (12.5 g, 86 mmol) were added
to a solution of compound 5 (6.5 g, 43 mmol) in MeOH (50 mL).
The resulting mixture was boiled for 5 h, MeОН was evapoꢀ
rated, Н2О (40 mL) and benzene (20 mL) were added, the
organic layer was separated, the aqueous layer was extracted
with benzene, and the combined organic extract was dried
with Na2CO3. The yield of product 1 was 9.5 g (92%), b.p.
119—121 °C (0.5 Torr). Found (%): С, 84.33; H, 9.51; N, 5.69.
C17H23N. Calculated (%): С, 84.59; H, 9.60; N, 5.80. MS (EI,
70 eV), m/z (Irel (%)): 241 (30) [M+], 226 (72) [M – CH3]+,
212 (10) [М – С2Н5]+, 198 (45) [M – C3H7]+, 172 (68)
tion with H2SiPh2 and 1,1,3,3ꢀtetramethylꢀ1,3ꢀdisilaꢀ
cyclobutane did not exhibit catalytic activity. When
[Ru(=CHPh)(PCy3)2(Cl)2] (Grabbs catalyst) was used
in amounts close to those applied for the tungstenꢀconꢀ
taining systems, we observed an increase in the yield of
the target product by 5—7%. These reactions were carꢀ
ried out in open systems with ethylene removal. In addiꢀ
tion, Cy3P, (PhCH2)2O, and PhCH=CH2 were found in
the reaction mixture.
As it was revealed, 2,2ꢀdi(2ꢀpropenyl)pyrrolidine (5)
without a protective group at the nitrogen atom did not
give the metathesis products. In this case, the Nꢀsilylation
of the pyrrolidine ring occurs (with H2 evolution), and
WCl6, WOCl4, and RuCl2(PPh3)3 are, most likely, the
catalysts of this reaction.18
1
[M – C3H5 – C2H5], 91 (100) [C6H5CH2]+. Н NMR, δ: 1.70
(m, 4 Н); 2.22 (m, 4 Н); 2.60 (t, 2 Н); 3.65 (s, 2 Н); 5.02
(s, 2 Н); 5.11 (s, 2 Н). 13С NMR, δ: 21.18 and 32.52
(С—СН2—СН2); 39.78 (2 CH2—CH=CH2); 50.71 and
52.09 (N—CH2 and N—CH2Ph); 64.59 (N—C); 116.87
(CH2—CH=CH2); 126.47, 128.08, 128.3 (CH phenylic); 135.75
(CH2—CH=CH2); 140.83 (Cquarter phenylic).
1ꢀBenzylꢀ2,2ꢀdi(2ꢀpropenyl)piperidine (2) was synthesized
using a similar procedure from 2,2ꢀdi(2ꢀpropenyl)piperidine.
The yield of compound 2 was 6.81 g (89%), b.p. 130—132 °C
(0.5 Torr). Found (%): С, 84.51; H, 9.83; N, 5.40. C18H25N.
Calculated (%): С, 84.65; H, 9.87; N, 5.48. MS (EI, 70 eV),
m/z (Irel (%)): 255 [M]+ (1), 240 [M – CH3]+ (2), 214
Thus, the nitrogenꢀcontaining spiroheterocycles were
obtained for the first time by the ringꢀclosing metathesis
of 2,2ꢀdiallylꢀ1ꢀazacycloalkanes, and rather simple hoꢀ
mogeneous systems based on tungsten chloride in comꢀ
bination with dihydrodiphenylsilane were used as the
catalysts.
1
[M – C3H5]+ (100), 91 [C6H5CH2]+ (60). Н NMR (CDCl3),
δ: 1.4 (m, 6 Н); 2.1 (dd, 2 Н, J = 14.7 Hz, J = 7.64 Hz); 2.38
(m, 2 Н); 2.6 (dd, 2 Н, J = 14.7 Hz, J = 6.92 Hz); 3.55
(s, 2 Н); 5.05 (m, 4 H); 5.90 (m, 2 Н); 7.25 (m, 5 Н).
Metathesis of 1ꢀbenzylꢀ2,2ꢀdi(2ꢀpropenyl)pyrrolidine (1). А.
Compound 1 (0.48 g, 2.0 mmol) was placed in a preꢀevacuated
and filled with argon 60ꢀcm3 ampule, and toluene solutions of
WCl6 or WOCl4 (0.1 mmol) and of H2SiPh2 (0.2 mmol) were
added in an Ar flow. The calculated amount of toluene
was added in such a way that the concentration of 1 was
0.05 mol L–1. The solution was frozen to the temperature of
Experimental
Reaction mixtures were analyzed using a Finnigan
MAT 95XL gas chromatograph/mass spectrometer (energy of

648
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 4, April, 2002
Bespalova et al.
liquid nitrogen and evacuated to 10–3 Torr, after which the
ampule was sealed. The reactions were conducted for 40 h at
60 °C. The violet (for WCl6) or darkꢀred (for WOCl4) solution
became darkꢀgreen, and a dark precipitate was formed. The
ampule was open, toluene was distilled off, and the residue was
distilled in vacuo and passed through a column packed with
SiO2 to separate the unreacted H2SiPh2 catalyst (eluent
nꢀhexane, Rf = 0.93). The mixtures were analyzed by the
GLC/MS method using toluene as the internal standard and
qualitatively by TLC on the Kieselgel 60F plates (Merсk).
The composition of the mixture after the reaction was 74%
compound 1, 11% isomers 1, and 15% 1ꢀbenzylꢀ10ꢀazaꢀ
spiro[4.4]nonꢀ7ꢀene (3). MS (EI, 70 eV), m/z (Irel (%)): comꢀ
pound 1, 241 [M]+ (30), 226 [M – CH3]+ (72), 212 [М –
С2Н5]+ (10), 198 [M – C3H7]+ (45), 172 [M – C3H5 – C2H5]+
(68), 91 [C6H5CH2]+ (100); compound 3, 213 [M]+ (52), 198
[M – CH3]+ (25), 184 [М – С2Н5]+ (50), 172 [M – C3H5]+
(86), 91 [C6H5CH2]+ (100), 77 (10).
The reactions of pyrrolidine 5 were carried out according
to procedures described for compounds 1 and 2, and no metꢀ
athesis products were observed. Gas evolution was observed at
the ratio [5] : [H2SiPPh2] : [W or Ru] = 2 : 2 : 1 and 20 °C.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 02ꢀ03ꢀ32024)
and the Program for State Support of Leading Scientific
Schools (Grant 00ꢀ15ꢀ97378).
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The metathesis reactions at other [substrate] : [catalyst]
ratios and under the effect of the Ru(Ph3)3Cl2 system were
carried out using analogous procedures. The results are preꢀ
sented in Table 1.
B. Compound 1 (0.48 g, 2.0 mmol) in CHCl3 (35 mL) was
placed in a preꢀevacuated and filled with argon reactor equipped
with a reflux condenser. Then Ru(=CHPh)(PCy3)2(Cl)2
(0.0543 g, 0.066 mmol) dissolved in CHCl3 (5 mL) was added
in an argon flow. The concentration of 1 was 0.05 mol L–1. The
reactions were conducted for 7 h at the temperature of chloroꢀ
form boiling. Samples were taken each hour and analyzed by
the GLC/MS method using toluene as the internal standard)
and qualitatively using TLC on the Kieselgel 60F plates (Merсk).
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compound 1, 24% compound 3, 13% PCy3, 10% (PhCH2)2O,
and 4% PhCH=CH2.
Metathesis of 1ꢀbenzylꢀ2,2ꢀdi(2ꢀpropenyl)piperidine (2) was
carried out using a procedure described above. Compound 2
(0.51 g, 2.0 mmol) was placed in a 60ꢀcm3 ampule. A toluene
solution of WCl6 or WOCl4 (0.1 mmol) and a solution of
H2SiPh2 (0.2 mmol) were added. The calculated amount of
toluene was added in such a way that the concentration of 2
was 0.05 mol L–1. The mixture was frozen to the temperature
of liquid nitrogen, and the ampule was evacuated to 10–3 Torr
and sealed. The reactions were carried out for 40 h and at
60 °C. The violet (for WCl6) or darkꢀred (for WOCl4) solution
became darkꢀgray, and then a dark precipitate was formed. The
ampule was open, toluene was distilled off, and the residue was
distilled in vacuo. The composition of the reaction mixture was
76% compound 2, 10% isomers 2, 14% 6ꢀbenzylꢀ6ꢀazaꢀ
spiro[4.5]decꢀ2ꢀene (4). MS (EI, 70 eV), m/z (Irel (%): comꢀ
pound 2, 255 [M]+ (2), 240 [M – CH3]+ (3), 214 [M –
C3H5]+(100), 91 [C6H5CH2]+ (60); compound 4, 227 [M]+
(20), 212 [M – CH3]+ (19), 198 [М – С2Н5]+ (38), 186 [M –
C3H5]+ (19), 172 [M – C4H7]+ (10), 136 [M – C6H5CH2]+
(16), 122 [M – C6H5CH2CH2]+ (37), 91 [C6H5CH2]+
(100), 82 (40).
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systems were carried out using the same procedure. The metꢀ
athesis products were not observed.
Received August 8, 2001;
in revised form February 11, 2002