Generation and reactions of ammonium ylides in basic two-phase systems: Convenient synthesis of cyclopropanes, oxiranes and alkenes substituted with electron-withdrawing groups

Article abstract of DOI:10.1055/s-1999-2757

Quaternary ammonium salts 1 react with electrophilic alkenes 2, aromatic aldehydes 3 and alkylating agents 4, in the presence of 50% aq sodium hydroxide or powdered potassium carbonate, in dichloromethane, to form cyclopropanes 5, oxiranes 6 and alkenes 7

Full text of DOI:10.1055/s-1999-2757

LETTER
1085
Generation and Reactions of Ammonium Ylides in Basic Two-Phase Systems:
Convenient Synthesis of Cyclopropanes, Oxiranes and Alkenes Substituted
with Electron-Withdrawing Groups
Andrzej JoÒczyk*, Anna Konarska
Warsaw University of Technology, Faculty of Chemistry, Koszykowa 75, 00-662 Warsaw, Poland
Fax +48 (22) 628 2741; E-mail: anjon@pw.edu.pl
Received 29 April 1999
Abstract: Quaternary ammonium salts 1 react with electrophilic
alkenes 2, aromatic aldehydes 3 and alkylating agents 4, in the pres-
ence of 50% aq sodium hydroxide or powdered potassium carbon-
ate, in dichloromethane, to form cyclopropanes 5, oxiranes 6 and
alkenes 7, respectively, usually in high yields. A key-step of these
transformations is the deprotonation of salts 1 which generates am-
+–
monium ylides 1 , undergoing further reactions.
Key words: quaternary ammonium salts, ammonium ylides, cyclo-
propanes, oxiranes, alkenes
1
2
Ammonium, unlike phosphorus ylides have attracted
chemist’s attention mainly because they undergo interest-
3
ing sigmatropic rearrangements. Searching of the litera-
ture reveals that reactions of ammonium ylides with
electrophiles like Michael acceptors, carbonyl com-
pounds or alkylating agents etc., have not been sufficient-
ly explored. Thus, an ylide generated from
cyanomethyl(trimethyl)-ammonium iodide by means of
sodium hydride in THF was allowed to react with chal-
cones, ethyl acrylate and cinnamate, to give the corre-
4
sponding cyclopropanes in 21–86% yield. Pyridinium
5
ylides formed from the corresponding salts, also resin-
6
5
6
bound ones, with triethylamine in ethanol or DMF, en-
tered the reaction with methylidene malonate derivatives
to afford functionalized cyclopropanes in good yields.
However, these reactions are restricted to alkenes substi-
tuted with two electron-withdrawing groups (EWG). Fur-
thermore, pyridinium ylides can also react as 1,3-dipoles
Scheme 1
1
,5,7
with electrophilic alkenes.
Reactions of alkyl halides
and carbonyl compounds engage nucleophilic center of
ammonium ylides affording functionalized ammonium
1
salts.
Now, we have found that reactions of ammonium ylides
with electrophilic alkenes, aldehydes or alkyl halides open
up a synthetically attractive approach to functionalized
cyclopropanes, oxiranes and alkenes, respectively. Thus,
ylides 1+ generated from phenyl- 1a, 2-thienyl- 1b or 2-
–
8
methyl-1-propenyl- 1c substituted salts, by means of
5
0% aq. sodium hydroxide (conditions A) or powdered
potassium carbonate (conditions B), in dichloromethane,
react with electrophilic alkenes 2 to form cyclopropanes
9
,10
5
(Scheme 1, Table 1).
Cyclopropanes 5 were obtained in good to excellent yields
as mixtures of Z and E isomers. In the case of perchlorate
1
b which is poorly soluble in dichloromethane, beneficial
Synlett 1999, No. 07, 1085–1087 ISSN 0936-5214 © Thieme Stuttgart · New York

1
086
A. JoÒczyk, A. Konarska
LETTER
effect of DMSO under conditions B, was noticed. Condi-
tions B are recommended for reactions with methyl acry-
late (2b) and a,b-unsaturated carbonyl compounds 2d-f,
which under conditions A undergo undesired processes.
Preliminary experiments indicated that the use of a- or b-
alkyl substituted electrophilic alkenes, significantly de-
1
3
crease the yields of the products.
Stirring of salts 1a,c with aromatic aldehydes under con-
ditions A led to formation of substituted oxiranes 6, in
moderate yields (Scheme 1, Table 2). In all reactions, for-
mation of significant amounts of decomposition products
(
dark material which remained on silica gel column) was
observed. Furthermore, the mixtures from salt 1c con-
tained products of the Canizzaro reaction (in the case of
1
3
a benzyl alcohol and benzoic acid). H NMR spectra of requires conditions A. Olefination of alkyl halides by
crude reaction mixtures from salt 1a exhibit that only one, means of ammonium ylides complements earlier method-
2
1
Z stereoisomer of 6 was produced. On the other hand, ox- ologies which rely on use dimethylsulfonium methylide
22
iranes 6ca and 6cc were formed as mixtures of Z and E or triphenylarsonium alkylides. Reaction of salt 1b with
isomers, the corresponding structures were ascribed as the benzyl bromide (4d) again led to formation of dinitrile 8,
1
4
result of NOE experiments. To the best of our know- instead of the expected cyanoalkene.
ledge, such an approach to the synthesis of oxiranes is un-
The reactions reported above consist in deprotonation of
salts 1, addition of ylides 1 to alkenes 2 or aldehydes 3,
9
a,10,15
precedented.
+–
and cyclization of the betaines thus formed to cyclo-
propanes 5 and oxiranes 6, respectively. On the other
+
–
hand, alkylation of ylides 1 with 4 produces alkylated
salts which form alkenes 7 via base-mediated elimination
of amine (Scheme 1). The reactions are very simple, con-
sist in stirring of the salt 1 with electrophiles 2-4, usually
used in excess, in a two-phase basic system, at ca 25 °C,
and are exemplified by the synthesis of 5ac, 5bf, 6ac and
2
3
7
cd. This approach to products 5-7 is fully competitive
with known methods, and is recommended for laboratory
praxis.
Acknowledgement
We thank the State Committee for Scientific Research, Warszawa
Hetaryl substituted salt 1b did not form the corresponding
oxirane when it was allowed to react with benzaldehyde
(Grant No. 3 T09A 082 11) for the financial support of this work.
(
3a), but fumaronitrile derivative 8 was produced, instead.
References and Notes
The same product was isolated when salt 1b was stirred
without aldehyde, under conditions A (Scheme 2).
1
7
(
1) Zugr„vescu, I.; Petrovanu, M. N-Ylid Chemistry; Editura
Academiei Republicii Socialiste Romãnia, Bucuresti and
Mc Graw-Hill, New York, 1976.
(
2) Organophosphorus Reagents in Organic Synthesis, Codogan,
J. I. G., Ed.; Academic Press, London-New York, 1979.
3) Pine, S. H. Org. React. 1970, 18, 403. Maeda, Y.; Shirai, N.;
Sato, Y. J. Chem. Soc., Perkin Trans. 1 1994, 393 and the
references cited therein. Zdrojewski, T.; JoÒczyk, A. J. Org.
Chem. 1998, 63, 452 and the references cited therein.
4) Bhattacharjee, S. S.; Ila, H.; Junjappa, H. Synthesis 1982, 301.
5) Shestopalov, A. M.; Litvinov, V. P.; Rodinovskaya, L. A.;
Sharanin, Yu. A. Zh. Org. Khim. 1991, 146.
(
(
(
Scheme 2
(
6) Vo, N. H.; Eyermann, Ch. J.; Hodge, C. N. Tetrahedron Lett.
Finally, alkylation of salts 1a and 1c afforded alkenes,
conjugated dienes or trienes, substituted with a cyano
group 7 (Scheme 1, Table 3).
1997, 38, 7951.
(
7) Cycloaddition of azomethine ylides: Lown, J. W. in 1,3-
Dipolar Cycloaddition Chemistry, Padwa, A., Ed.; John
Wiley & Sons; New York, 1984, Vol. 1, p. 653.
8) The crystalline salts 1a,c were prepared by reaction of the
corresponding aminonitrile with methylsulfate, carried out at
ca –10 °C. Oily methylsulfate of thienylaminonitrile was
Except for 7ad (Z isomer), all products were formed as
mixtures of Z and E isomers. This reaction is restricted to
active alkylating agents, like benzyl or allyl halides, and
(
Synlett 1999, No. 07, 1085–1087 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Generation and Reactions of Ammonium Ylides in Basic Two-phase Systems
1087
converted into crystalline perchlorate 1b with 60% aq HClO .
(16) McDonald, K. N.; Hill, D. G. J. Org. Chem. 1970, 35, 2942.
(17) The formation of dinitrile 8 via carbanionic route (alkylation
4
1
1
a:80%; mp 115–116 °C (AcOEt/AcMe ~ 1:3); H NMR, δ
+
+–
(ppm, 200 MHz, CDCl ):3.35 (9H, s, N Me ), 3.65 (3H, s,
of ylide 1b with 1b, followed by elimination of
trimethylamine), as previously suggested for similar
3
3
–
MeSO ), 6.60 (1H, s, CH), 7.45–7.60 (3H, m, ArH), 7.65–
4
7
.75 (2H, m, ArH). Calcd for C H N O S: C, 50.33; H, 6.34;
transformation of α-chloro(phenyl)acetonitrile in PTC
system, seems feasible. Alternatively, cleavage of ylide 1b
may generate cyano-2-thienyl carbene which after
1
2
18
2
4
1
8
+–
N, 9.78. Found: C, 50.01; H, 6.39; N, 9.69.
1
1b:91%; mp 169–171 °C (MeOH); H NMR, δ (ppm, 200
+
MHz, DMSO-d ):3.23 (9H, s, N Me ), 6.82 (3H, s, CH), 7.31
dimerization produces 8. However, our attempts to intercept
this carbene with n-butylvinyl ether, failed.
(18) Mπkosza, M.; Serafinowa, B.; Gajos, I. Roczniki Chem. 1969,
43, 671; Chem. Abstr. 1969, 71, 101 498.
6
3
(1H, dd, J = 5.2 Hz, J = 3.7 Hz, ArH), 7.60 (1H, dd, J = 3.7
Hz, J = 1.2 Hz, ArH), 8.05 (1H, dd, J = 5.2 Hz, J = 1.2 Hz,
ArH). Calcd for C H N O ClS: C, 38.51; H, 4.67; N, 9.98.
9
13
2
4
Found: C, 38.52; H, 4.76; N, 9.90.
(19) Wawzonek, S.; Smolin, E. M. Org. Synth. 1955, Coll. Vol. III,
715.
1
1c:84%; mp 99–101 °C (AcMe); H NMR (ppm, 200 MHz,
DMSO-d ):1.84 (3H, d, J = 1.4 Hz, Me), 1.88 (3H, d, J = 1.2
(20) Janecki, T. Synthesis 1991, 167.
6
+
–
Hz, Me), 3.15 (9H, s, N Me ), 3.38 (3H, s, MeSO ), 5.50–
(21) Alcaraz, L.; Harnett, J. J.; Mioskowski, C.; Martel, J. P.; Le
Gall, T.; Shin, D.-S.; Falck, J. R. Tetrahedron Lett. 1994, 35,
5453.
3
4
5.65 (1H, m, C=CH), 5.70–5.80 (1H, m, CH). Calcd for
C H N O S: C, 45.44; H, 7.63; N, 10.60. Found: C, 45.49;
1
0
20
2
4
H, 7.63; N, 10.57.
9) Cyclopropanes via conjugate addition-nucleophilic
(22) Seyer, A.; Alcaraz, L.; Mioskowski, C. Tetrahedron Lett.
1997, 38, 7871.
(
substitution:
(23) 5ac: to a vigorously stirred solution of 1a (1.43 g, 5 mmol) in
CH Cl (20 mL), ester 2c (1.92 g, 15 mmol) then 50% aq.
(a) Arseniyadis, S.; Kyler, K. S.; Watt, D. S. Org. React. 1984,
2
2
3
1, 1. (b) Zwanenburg, B.; De Kimpe, N. in Methods of
NaOH (7 mL) were added, and the mixture was stirred at RT
for 7.5 h. The mixture was diluted with water, the phases were
separated, the water phase was extracted with CH Cl , the
Organic Chemistry (Houben-Weyl), de Meijere, A., Ed.;
Georg Thieme Verlag; Stuttgart, New York, 1997, Vol E17a,
p. 69.
2
2
combined organic extracts were washed with water, dried
(
(
10) Cyclopropanes and oxiranes substituted with EWG are
(MgSO ), the product was purified by column
4
1
1
conveniently synthesized via phase-transfer catalysed (PTC)
reactions of arylacetonitriles with carbon tetrachloride and
electrophilic alkenes or aromatic aldehydes, respectively:
Makosza, M.; Kwast, A.; Kwast, E.; JoÒczyk, A. J. Org.
Chem. 1985, 50, 3722. However, their scope is somewhat
restricted, side reactions often accompany the main pathway,
and the products are formed usually in 40–60% yields.
11) Dehmlow, E. V.; Dehmlow, S. S. Phase Transfer Catalysis;
chromatography on a short pad of silica gel (Merck Silica gel
60, finer than 230 mesh, eluent hexane-AcOEt, gradient) to
give 1.10 g (91%) of oily 5ac (Table 1, Entry 3).
5bf: the solution of 1b (1.40 g, 5 mmol) in CH Cl (60 mL)
and DMSO (15 mL) was vigorously stirred while ketone 2f
2
2
(0.66 g, 5 mmol) then powdered K CO (6.9 g) were added.
2
3
Stirring at RT was continued for 2 h, the reaction was worked
up as described for 5ac, and the product was purified by
Kugelrohr distillation [bp 130–140 °C (oven)/0.15 Torr] to
give 1.00 g (79%) of 5bf (Table 1, Entry 9).
3
rd Ed.; Verlag Chemie, Weinheim, 1993. Starks, C. M.;
Liotta, C. L.; Halpern, M. Phase-transfer Catalysis; Chapman
Hall; New York, London, 1994. Mπkosza, M.; FedoryÒski,
&
6ac: to vigorously stirred 1a (1.43 g, 5 mmol), aldehyde 3c
(0.70 g, 5 mmol) and CH Cl (30 mL), 50% aq NaOH (12 mL)
M. Polish J. Chem. 1996, 70, 1093. Mπkosza, M.; FedoryÒski,
M. in Handbook of Phase Transfer Catalysis; Sasson, Y.;
Neumann, R., Eds.; Blackie Academic & Professional;
London, 1997, p. 135.
2
2
was added, and stirring was continued at RT for 0.5 h and
refluxed for 8.5 h. The mixture was worked up as described
for 5ac, and the product was crystallized (MeOH) to give 0.60
g (47%) of 6ac, mp 111–113 °C (Table 2, Entry 3).
(
(
12) Saegusa, T.; Yonezawa, K.; Murase, I.; Konoike, T.; Tomita,
S.; Ito, Y. J. Org. Chem. 1973, 38, 2319.
7cd: the solution of 1c (1.32 g, 5 mmol) in CH Cl (20 mL)
2
2
13) For example, reaction of salt 1a with an excess of
methacrylonitrile under conditions A, gives 1,2-dicyano-1-
methyl-2-phenylcyclopropane, in 27% yield.
was vigorously stirred, bromide 4d (0.86 g, 5 mmol) then 50%
aq NaOH (7 mL) were added (exothermal effect), reaction was
continued for 4h, and worked up as described for 5ac. The
product was purified by Kugelrohr distillation [bp 125–
130 °C (oven)/0.03 Torr] to give 0.81 g (89%) of oily 7cd
(Table 3, Entry 6).
(
14) Irradiation of signals of oxirane protons at δ = 4.10 ppm or
δ = 4.51 ppm in Z and E isomers mixture of 6ca resulted in
increase of only one signal of olefinic protons at δ = 5.40 –
5.45 ppm (m), namely from Z-isomer.
(
15) Syntheses of oxirane substituted with EWG: Ballester, M.
Chem. Rev. 1955, 55, 283. Newman, M. S.; Magerlein, B.
J. Org. React. 1957, 5, 413. Shibata, I.; Yamasaki, H.;
Baba, A.; Matsuda, H. J. Org. Chem. 1992, 57, 6909 and the
references cited therein.
Article Identifier:
1437-2096,E;1999,0,07,1085,1087,ftx,en;G21599ST.pdf
Synlett 1999, No. 07, 1085–1087 ISSN 0936-5214 © Thieme Stuttgart · New York