Stereospecific synthesis of polysubstituted E-olefins by reaction of acyclic nitrones with free and platinum(II) coordinated organonitriles

Article abstract of DOI:10.1021/jo061659b

(Chemical Equation Presented) Free nitriles NCCH₂R (1a R = CO₂Me, 1b R = SO₂Ph, and 1c R = COPh) with an acidic α-methylene react with acyclic nitrones ^-O⁺N(Me)= C(H)R′ (2a R′ = 4-MeC₆H

Full text of DOI:10.1021/jo061659b

Stereospecific Synthesis of Polysubstituted E-Olefins by Reaction of
Acyclic Nitrones with Free and Platinum(II) Coordinated
Organonitriles
†
,†,‡
§
Jamal Lasri, M. Ad ´ı lia Janu a´ rio Charmier,* Matti Haukka, and
,
†
Armando J. L. Pombeiro*
Centro de Qu ´ı mica Estrutural, Complexo I, Instituto Superior T e´ cnico, AVenida RoVisco Pais, 1049-001,
Lisbon, Portugal, UniVersidade Lus o´ fona de Humanidades e Tecnologias, AVenida Campo
Grande no. 376, 1749-024, Lisbon, Portugal, and Department of Chemistry, UniVersity of Joensuu,
P.O. Box 111, FIN-80101, Joensuu, Finland
adilia.charmier@ist.utl.pt; pombeiro@ist.utl.pt
ReceiVed August 9, 2006
Free nitriles NCCH
react with acyclic nitrones O N(Me)dC(H)R′ (2a R′ ) 4-MeC
refluxing CH Cl , to afford stereoselectively the E-olefins (NC)(R)CdC(H)R′ (3a-3c and 3a′-3c′),
whereas, when coordinated at the platinum(II) trans-[PtCl (NCCH R) ] complexes (4a R ) CO Me
and 4b R ) Cl), they undergo cycloaddition to give the (oxadiazoline)-Pt complexes trans-
2
R (1a R ) CO
2
Me, 1b R ) SO
2
Ph, and 1c R ) COPh) with an acidic R-methylene
-
+
6
H
4
and 2b R′ ) 2,4,6-Me ), in
3 6 2
C H
2
2
2
2
2
2
II
[
PtCl {NdC(CH R)ON(Me)C(H)R′} ] (R ) CO Me, Cl and R′ ) 4-MeC , 2,4,6-Me ) (5a-5d).
2
2
2
2
6
H
4
3 6 2
C H
Upon heating in CH Cl , 5a affords the corresponding alkene 3a. The reactions are greatly accelerated
when carried out under focused microwave irradiation, particularly in the solid phase (SiO ), without
solvent, a substantial increase of the yields being also observed. The compounds were characterized
2
2
2
1
13
195
+
by IR and H, C, and Pt NMR spectroscopies, FAB -MS, elemental analyses and, in the cases
of the alkene (NC)(CO Me)CdC(H)(4-MeC ) 3a and of the oxadiazoline complex trans-
2
6 4
H
[
PtCl {NdC(CH Cl)ON(Me)C(H)(4-C Me)}
2
2
6
H
4
2
] 5c, also by X-ray diffraction analyses.
Introduction
selective synthesis are comprised of the Knoevenagel condensa-
2
3
4
tions, the McMurry and Wittig reactions from aldehydes or
ketones, which have been shown recently to be accelerated by
The stereoselective syntheses of substituted alkenes is an
important aim in organic chemistry. The most general approach
involves elimination reactions that, however, commonly give
rise to a mixture of double bond isomers with eventual
predominance of one of them (Zaytzev or Hofmann rules), but
5
microwave irradiation. Olefin metathesis provides powerful
synthetic tools within both functionalized and unfunctionalized
6
olefins.
Free nitriles are only rarely used for alkene synthesis due to
their usually low reactivity, namely, toward most dipolar
reagents. One of the first known feasible conversions into an
1
a high selectivity is rare. The first powerful methods for the
*
Corresponding author. Tel.: 351-21-841-9225. Fax: 351-21-846-4455.
Instituto Superior T e´ cnico.
Universidade Lus o´ fona de Humanidades e Tecnologias.
†
‡
§
(2) Knoevenagel, E. Ber. 1898, 31, 2596.
University of Joensuu.
(3) McMurry, J. E. Chem. ReV. 1989, 89, 1513-1524.
(4) Wittig, G.; Sch o¨ llkopf, U. Chem. Ber. 1954, 87, 1318.
(5) Spinella, A.; Fortunati, T.; Soriente, A. Synlett 1997, 93-94.
(
1) Nakatsu, S.; Gubaidullin, T.; Mamedov, V. A.; Tsuboi, S. Tetrahedron
2
004, 60, 2337-2349, and references cited therein.
10.1021/jo061659b CCC: $37.00 © 2007 American Chemical Society
7
50
J. Org. Chem. 2007, 72, 750-755
Published on Web 01/04/2007

Stereospecific Synthesis of Polysubstituted E-Olefins
SCHEME 1
olefin (i.e., a cyano-olefin or R,â-unsaturated nitrile) using acidic
These results stimulated our interest toward (i) the search
for another type of reaction centered at the acidic R-CH2 group
of NCCH2R, (ii) the extension of the studies to acyclic nitrones
that are less reactive than the cyclic ones, and (iii) the
investigation of the effects on the nitrile reactivity of the
electron-acceptor R group and of the nitrile coordination to a
methylene organonitriles with various types of catalysts, such
as AlPO4-Al2O47 or -Al2O3, was devised by using the
a
7b
7
Knoevenagel condensation with some carbonyl compounds.
Metal catalysts such as Ru have also been applied to give the
same type of olefins. Only activated nitriles RCN, with a strong
II
8
II
electron-withdrawing group (e.g., R ) CCl3, CO2R′) directly
ligated to the triple bond, react with some dipolar species such
as nitrones, unless rather harsh conditions and/or long reaction
Pt center.
In the first part of this work, we report an unprecedented
reaction of free acidic R-CH organonitriles with an electron-
2
9
times are employed. Nitrile coordination to a suitable metal
withdrawing substituent (R ) CO Me, SO Ph, COPh), with
2
2
center can also lead to its activation toward a variety of
nucleophiles and dipoles.10 A recent nitrile application in
heterocyclic synthesis, unreachable from a free nitrile, achieved
in our laboratory, involves the reaction of NCCH2R (R ) CO2-
acyclic nitrones, which constitutes a novel and simple alternative
method for the preparation of pure unsymmetrical cyano-
functionalized E-alkenes without the use of any catalyst. In the
II
second part, we examine the reactivity of the Pt -bound nitriles
II
11a
Me, Cl) at a Pt center with a cyclic nitrone. The dipolaro-
to form heterocyclic oxadiazoline complexes that can lead to
the cyano-alkenes. The reactions are markedly accelerated by
microwave (M.W.) irradiation, particularly in the solid phase
2
II
philicity of the triple bond is enhanced by the Pt site, and the
coupling reactions can also be promoted by microwave
irradiation.1 However, in those reactions, no role of the acidic
R-hydrogens in NCCH2R was recognized.
1c
(SiO ), which also results in a considerable yield improvement.
Results and Discussion
(6) (a) Grubbs, R. H., Ed. Handbook of Metathesis; Wiley-VCH:
-
+
Weinheim, 2003; (b) Grubbs, R. H.; Chang, S. Tetrahedron 1998, 54, 4413-
We have studied the reactions of acyclic nitrones O N(Me)d
C(H)R′ 2 (2a R′ ) 4-MeC6H4 and 2b R′ ) 2,4,6-Me3C6H2)
with various acidic methylene nitriles NCCH2R 1 bearing an
electron-acceptor group (1a R ) CO2Me, 1b R ) SO2Ph, 1c R
4
4
4
450. (c) Grubbs, R. H.; Miller, S. J.; Fu, G. C. Acc. Chem. Res. 1995, 28,
46-452. (d) Schrock, R. R.; Hoveyda, A. H. Angew. Chem., Int. Ed. 2003,
2, 4592-4633. (e) Schrock, R. R. Chem. ReV. 2002, 102, 145-179.
(
7) (a) Chalais, S.; Laszlo, P.; Mathy, A. Tetrahedron Lett. 1985, 26,
4
2
453-4454. (b) Texier-Boullet, F.; Foucaud, A. Tetrahedron Lett. 1982,
)
COPh, and 1d R ) Cl) by four different methods (conven-
3, 4927-4928. (c) Cabello, J. A.; Campelo, J. M.; Garcia, A.; Luna, D.;
tional solvent reflux, heating in a sealed tube, and microwave
irradiation in CH2Cl2 and in the solid phase) (see Experimental
Procedures). The corresponding E-cyano-alkene products
Marinas, J. M. J. Org. Chem. 1984, 49, 5195-5197. (d) Gedye, R. N.;
Wei, J. B. Can. J. Chem. 1998, 76, 525-532. (e) Kuster, G. J.; Scheeren,
H. W. Tetrahedron Lett. 2000, 41, 515-519.
(8) Murahashi, S. I.; Naota, T.; Taki, H.; Mizuno, M.; Takaya, H.;
(
NC)(R)CdC(H)R′ 3 were isolated by column chromatography
Komiya, S.; Mizuho, Y.; Oyasato, N.; Hiraoka, M.; Hirano, M.; Fukuoka,
and obtained as pale yellow or white solids (Scheme 1).
The reactions are greatly accelerated by focused M.W.
irradiation, taking then typically 2 h, whereas conventional
heating methods require much longer times (3 or 4 days in
refluxing CH2Cl2 or 12 h in CH2Cl2 heated in a sealed tube at
A. J. Am. Chem. Soc. 1995, 117, 12436-12451.
(9) (a) Yu, Y.; Ohno, M.; Eguchi, S. J. Chem. Soc., Chem. Commun.
1
994, 331-332. (b) Yu, Y.; Watanabe, N.; Ohno, M.; Eguchi, S. J. Chem.
Soc., Perkin Trans. 1 1995, 11, 1417-1421. (c) Yu, Y.; Fujita, H.; Ohno,
M.; Eguchi, S. Synthesis 1995, 498-500. (d) Van, den Broek, L. A. G. M.
Tetrahedron 1996, 52, 4467-4478. (e) Sang, H.; Janzen, E. G.; Poyer, L.
J. Chem. Soc., Perkin Trans. 2 1996, 6, 1183-1189. (f) Plate, R.; Hermkens,
P. H. H.; Smits, J. M. M.; Nivard, R. J. F.; Ottenheijm, H. C. J. J. Org.
Chem. 1987, 52, 1047-1051. (g) Smits, J. M. M.; Beurskens, P. T.; Smits,
J. R. M.; Plate, R.; Ottenheijm, H. J. Crystallogr. Spectrosc. Res. 1988,
8
0 °C).
The highest yields (80-55%, depending on the nitrile
substituent) are obtained under M.W. irradiation in the solid
phase (SiO2), without solvent, at 80 °C, while the other methods
typically lead only to 56-15% yields. The reactivity of the
nitriles follows the electron-withdrawing ability of the R
substituent (i.e., SO2Ph > CO2Me > COPh > Cl), with NCCH2-
SO2Ph as the more reactive nitrile, whereas no trace of olefin
was detected in the case of NCCH2Cl. Hence, the reactions are
quite sensitive to the nature of the nitrile substituent.
1
8, 15-24. (h) Eberson, L.; Hartshorn, C. M.; Hartshorn, M. P.; Mc-
Cullough, J. J. Synth. Commun. 1997, 27, 3779-3787. (i) Eberson, L.;
McCullough, J. J.; Hartshorn, C. M.; Hartshorn, M. P. J. Chem. Soc., Perkin
Trans. 2 1998, 1, 41-48. (j) Hermkens, P. H. H.; van Maarseveen, J. H.;
Kruse, C. G.; Scheeren, H. W. Tetrahedron 1988, 44, 6491-6504.
(
10) Kukushkin, V. Y.; Pombeiro, A. J. L. Chem. ReV. 2002, 102, 1771-
802.
11) (a) Charmier Janu a´ rio, M. A.; Haukka, M.; Pombeiro, A. J. L. Dalton
1
(
Trans. 2004, 2741-2745. (b) Charmier Janu a´ rio, M. A.; Kukushkin,
V. Y.; Pombeiro, A. J. L. Dalton Trans. 2003, 2540-2543. (c) de la Hoz,
A., D ´ı az-Ortiz, A., Langa, F., Loupy, A., Eds. MicrowaVes in Organic
Synthesis, Wiley/VCH: Weinheim, 2002; pp 295-343.
The formation of the E-alkene products 3 involves the overall
and formal removal of the two acidic methylene protons of the
J. Org. Chem, Vol. 72, No. 3, 2007 751

Lasri et al.
SCHEME 2
2
-
nitrile NCCH2R by the {NOMe} fragment of the nitrone
intermediate. Abstraction of the second proton from the cyano-
alkyl fragment by the amine nitrogen with concomitant CdC
bond formation and C-N bond cleavage leads (step c) to the
elimination of hydroxylmethylamine Me(H)NOH and the cor-
responding cyano-alkene (NC)(R)CdC(H)R′ 3.
-
+
O N(Me)dC(H)R′, which thus undergoes NdC bond cleav-
age, with coupling of the remaining nitrile- and oxime-derived
fragments to afford (NC)(R)CdC(H)R′. This unprecedented type
of reaction is determined by the acidic character of the R-protons
of the nitrile, which exhibit a higher reactivity than the cyano
group that remains unreactive. A conceivable mechanism is
proposed in Scheme 2. The reaction is initiated by single
deprotonation of the nitrile NCCH2R by the nitrone (step a) to
give the anionic basic form of the former (i.e., NCCHR ), which
upon nucleophilic attack at the CdN carbon of the cationic
protonated nitrone (step b) forms a cyano-alkylhydroxylamine
1
The cyano-alkene products 3 were characterized by IR, H
and 1 C NMR spectroscopies, FAB -MS, elemental analyses,
and (for 3a) single-crystal X-ray diffraction. In the IR spectra
of 3, υ(NtC) appears in the same range of wavenumbers as
3
+
-
-1
that observed for the starting nitriles (2214-2225 cm ), while
+
-1
the detection of new bands at 1595-1611 cm assigned to
1
υ(CdC) confirms the formation of the alkenes. In H NMR
SCHEME 3
752 J. Org. Chem., Vol. 72, No. 3, 2007

Stereospecific Synthesis of Polysubstituted E-Olefins
SCHEME 4
SCHEME 5
spectra, the CdCH resonance is detected at δ 8.06-8.51, and
the protons of the methyl groups at the aromatic rings appear
in the 2.22-2.46 ppm range. In the 13C{ H} NMR spectra, the
signals of the CdC carbons emerge in intervals from 101.5 to
1
1
16.4 and 152.2 to 158.9 ppm, while the carbons of the NtC
groups are observed in the 114.0-122.3 ppm range.
The single-crystal X-ray diffraction analysis of (NC)(CO2-
Me)CdC(H)(4-MeC6H4) 3a (see the Supporting Information)
confirms the E configuration. The cyano-C(4)tN(1) triple bond
length, 1.149 Å, and the alkene double bond C(3)dC(5)
1
2
distance, 1.349 Å, are in accord with the reported average
values of 1.144 and 1.340 Å, respectively.
In the second part of this work, we investigated the
reactions of the nitriles with the nitrones after coordination of
the former to a Pt center, thus comparing the reactivities of
reaction of trans-[PtCl2(NCCH2CO2Me)2] 4a with 2a is under-
taken under more drastic conditions (1 day in refluxing CH2-
II
Cl2 or 2 h under M.W. irradiation at 80 °C) than those normally
the ligated and free nitriles and studying the metal acti-
used, we obtain a mixture of 5a and the cyano-alkene 3a.
Moreover, refluxing a CH Cl solution of 5a for 2 days or
vating effect. Treatment of trans-[PtCl2(NCCH2R)2] (4a R )
-
+
CO2Me and 4b R ) Cl) with O N(Me)dC(H)R′ (2a R′ )
2
2
heating it for 2 h under M.W. irradiation at 80 °C leads to the
cyano-alkene 3a. These results suggest that the formation of
an oxadiazoline complex via [2 + 3] cycloaddition of the nitrone
with a ligated nitrile can be kinetically driven and that such a
complex, upon prolonged reaction time and at a higher tem-
perature, can convert into the thermodynamically more stable
cyano-alkene product. A possible pathway for the conversion
of the oxadiazoline complex 5a into the corresponding alkene
4
-MeC6H4 and 2b R′ ) 2,4,6-Me3C6H2) upon heating (8 h,
refluxing CH2Cl2) gives 1:1 diastereomeric mixture
of the corresponding (∆ -1,2,4-oxadiazoline)-Pt complexes
a
4
II
trans-[PtCl2{NdC(CH2R)ON(Me)C(H)R′}2] 5a-d in moderate
yields (58-53%) (Scheme 3 a). The reaction time is drastically
reduced with M.W. irradiation (1 h, 60 °C) giving complexes 5
in comparable yields (60-55%).
These reactions allowed the direct synthesis of new oxadia-
3
a is proposed in Scheme 4, involving a retrocycloaddition
II
II
zoline-Pt complexes from nitrile Pt precursors upon nitrile/
nitrone coupling ([2 + 3] cycloaddition). The coordination of
process. Liberation (even only to a slight extent) of the
oxadiazoline ligand (step a) and dissociation of this species into
the starting nitrile and nitrone components (step b) would be
followed by proton abstraction from the methylene group of
the nitrile by the nitrone.
II
the nitrile NCCH2R to the Pt center activates the cyano group
to such an extent that it becomes more reactive toward the
nitrone than the acidic methylene moiety, in contrast to what
we have observed for the free nitrile. The oxadiazoline
1
13
complexes 5a-d have been characterized by IR, H, C, and
Conclusion
1
95
Pt NMR spectroscopies (data are in accord with those of other
11b,13-16
+
oxadiazoline complexes
), FAB -MS, elemental analyses,
Organonitriles bearing an acidic R-methylene group, NCCH2R
(R ) electron-withdrawing group), exhibit two reactive centers
(i.e., the CH2 and the cyano moieties). In the absence of a
coordinating metal site, the methylene group is more reactive
than the cyano center toward an acyclic nitrone, undergoing
deprotonation by the latter reagent to provide a simple and novel
stereoselective synthetic route for polysubstituted E-alkenes
(cyano-alkenes) (Scheme 5, route a). However, upon binding a
and (for 5c) single-crystal X-ray diffraction (see Supporting
Information). All bond lengths and angles are normal and agree
with those reported1
3,14
for other oxadiazoline-Pt complexes.
II
Interestingly, the oxadiazoline-Pt complex 5a leads to the
corresponding cyano-alkene 3a [Scheme 3b]. In fact, if the
(
12) Allen, F. H.; Kennard, O.; Watson, D. G.; Brammer, L.; Orpen,
A. G. J. Chem. Soc., Perkin Trans 2 1987, 1-19.
13) Wagner, G.; Pombeiro, A. J. L.; Kukushkin, V. Y. J. Am. Chem.
Soc. 2000, 122, 3106-3111.
14) Wagner, G.; Haukka, M.; Fra u´ sto da Silva, J. J. R.; Pombeiro,
A. J. L.; Kukushkin, V. Y. Inorg. Chem. 2001, 40, 264-271.
II
Pt Lewis acid site, the cyano group of the nitrile becomes more
(
reactive than the methylene group, being thus sufficiently
activated by coordination to undergo a [2 + 3] cycloaddition
with the acyclic nitrone to afford oxadiazoline complexes
(
(
15) Desai, B.; Danks, T. N.; Wagner, G. Dalton Trans. 2004, 166-
(Scheme 5, route b) that can be isolated without undergoing
1
2
71.
ring opening by N-O bond rupture, in contrast to what we have
(
16) Desai, B.; Danks, T. N.; Wagner, G. Dalton Trans. 2003, 2544-
1
1a
549.
previously observed for the case of the more reactive cyclic
J. Org. Chem, Vol. 72, No. 3, 2007 753

Lasri et al.
nitrones. Nevertheless, an oxadiazoline complex can react
further, corresponding to a kinetically favored product that, upon
ligand liberation and retrocycloaddition (Scheme 5, route c),
generates also the cyano-alkene (route a) and Me(H)NOH as
the final thermodynamically favored products.
(i) By the conventional method: a solution of 1a (60.0 mg, 0.605
mmol), or 1b (60.0 mg, 0.331 mmol), or 1c (60.0 mg, 0.413 mmol)
in dry CH Cl (3.0 mL) was added at room temperature to the
2 2
appropriate nitrone 2 (1.2 equiv), and the mixture was heated to
reflux with stirring for 3 or 4 days. (ii) In a sealed tube: the
reagents, in amounts identical to those detailed previously, were
heated at 80 °C in a sealed tube for 12 h. (iii) By focused microwave
The reactions are greatly accelerated by microwave irradia-
tion, and in particular, the novel route a to the cyano-alkenes
thus proceeds in a considerably short reaction time (2 h) and,
when performed in the solid phase (SiO2), displays moderate
to good yields (up to 80%) thus providing a contribution toward
an environmentally friendly process with potential significance
in green chemistry. Other advantages of route a to polysubsti-
tuted E-alkenes include its simplicity, its stereoselectivity, the
possibility of extension to a variety of substituted alkenes (NC)-
2 2 2 2
irradiation in CH Cl : the CH Cl solution of the reagents in the
previous amounts was subject to microwave irradiation at 80 °C
for 2 h. (iv) By focused microwave irradiation onto silica gel
support: the previous amounts of reagents were mixed with SiO2
2 2
(1 g), and CH Cl (1 mL) was used for impregnation; after solvent
evaporation in vacuo, the dried solid mixture was heated at 80 °C
under microwave irradiation for 2 h. In all cases, the corresponding
cyano-alkenes 3 were isolated and purified as indicated previously,
as yellow or white hygroscopic solids.
Methyl (E)-2-Cyano-3-(4-methylphenyl)-2-propenoate (3a).
Method (i) (30% yield), method (ii) (51% yield), method (iii) (35%
(R)CdC(H)R′ simply by varying the electron-acceptor R group
and R′ of the starting nitrile and nitrone, respectively, the use
of easily available starting materials, and that it is not necessary
to apply any catalyst or promoter.
yield), and method (iv) (71% yield). TLC on SiO
2
: R
f
) 0.71
-1
(
eluent CH
2
Cl
2
). Mp: 92 °C. IR (cm ): 2222 (NtC), 1728 (CO -
2
As a final comment, the new oxadiazoline complexes with
ester or chloro substituents are expected to be potential
1
Me), 1599 (CdC). H NMR (CDCl
3
2
53.9 (CH O), 102.1 (C ) C), 116.5 (NtC), 129.5 and 130.8, 132.0
and 145.5 (Caromatic), 156.0 (CdC), 164.1 (CdO). FAB -MS, m/z:
3
), δ: 2.45 (s, 3H, CH
3
Ph),
.94 (s, 3H, CH
H), 8.24 (s, 1H, CH). C{ H} NMR (CDCl
3
O), 7.32 (d, JHH 8.1 Hz, 2H), 7.91 (d, JHH 8.1 Hz,
1
7
precursors for the synthesis of aminoacids and lactams and
eventually can also exhibit anticancer activity (as other platinum
complexes with N-heterocyclic ligands),18 aspects that are
currently under consideration in our group.
13
1
3
3
), δ: 22.5 (CH Ph),
3
+
+
201 [M] . Anal. Calcd for C12
2
H11NO : C, 71.6; H, 5.5; N, 6.9.
Found: C, 71.7; H, 5.7; N, 6.8.
Methyl (E)-2-Cyano-3-mesityl-2-propenoate (3a′). Method (i)
33% yield), method (ii) (52% yield), method (iii) (36% yield),
Experimental Procedures
(
and method (iv) (61% yield). TLC on SiO
2
: R
f
) 0.86 (eluent CH
Me), 1611
), δ: 2.29 and 2.31 (two s, 9H, CH Ph),
2
-
2 2 2
The organonitrile complexes trans-[PtCl (NCCH R) ] (4a R )
19
-
1
Me and 4b R ) Cl)1 and the nitrones 2a and 2b were
1a
19
Cl
2
). Mp: 102 °C. IR (cm ): 2225 (NtC), 1735 (CO
2
CO
2
1
(
3
CdC). H NMR (CDCl
.95 (s, 3H, CH O), 6.93 (s, 2H, Ph), 8.50 (s, 1H, CH). C{ H}
NMR (CDCl ), δ: 20.9 and 21.8 (CH
3
3
prepared according to published methods.
Syntheses. The heating methods used are as follows. (i)
Conventional method: the reaction was carried out in refluxing
1
3
1
3
3
3
Ph), 54.0 (CH
3
O), 111.0
(CdC), 115.0 (NtC), 129.7, 130.3, 136.8, and 140.9 (Caromatic),
CH
evaporation of the solvent in vacuo to dryness, the crude residue
was purified by column chromatography on silica (CH Cl as the
2 2
Cl with stirring, and its progress was monitored by TLC. After
+
+
158.9 (CdC), 162.7 (CdO). FAB -MS, m/z: 230 [M + 1] . Anal.
Calcd for C14
.7; N, 6.2.
E)-2-(4-Methylphenyl)-1-phenylsulfonyl-1-ethenyl Cyanide
3b). Method (i) (40% yield), method (ii) (56% yield), method (iii)
42% yield), and method (iv) (80% yield). TLC on SiO : R
). Mp: 146 °C. IR (cm ): 2218 (NtC), 1595
2
H15NO : C, 73.3; H, 6.6; N, 6.1. Found: C, 73.1; H,
2
2
6
eluent) followed by evaporation of the solvent in vacuo to give the
final yellow or white solids. (ii) In a sealed tube: the reagents were
heated in a sealed stainless steel tube (20 mL), and the progress of
the reaction was monitored by TLC. After evaporation of the solvent
in vacuo to dryness, the crude residue was purified as indicated in
(
(
(
2
f
)
-1
2 2
0.83 (eluent CH Cl
1
(CdC). H NMR (CDCl
3
3
), δ: 2.45 (s, 3H, CH
3
Ph), 7.28-8.02 (m,
(
i). (iii) By focused microwave irradiation in solution: the reagents
and solvent (CH Cl ) were added to a cylindrical Pyrex tube that
was then placed in a focused microwave CEM Discover reactor
10 mL, 13 mm diameter, 300 W), which was fitted with a rotational
1
1
9H), 8.21 (s, 1H, CH). C{ H} NMR (CDCl
3
), δ: 22.6 (CH Ph),
3
2
2
101.5 (CdC), 114.0 (NtC), 128.3, 129.3, 130.3, 130.9, 131.9,
+
(
135.2, 138.9, and 146.4 (Caromatic), 152.2 (C ) C). FAB -MS, m/z:
+
system and an IR detector of temperature. After the reaction, the
mixture was allowed to cool down, the solvent was removed in
vacuo, and the crude residue was purified as indicated in (i). (iv)
By focused microwave irradiation in the solid phase: the reagents
284 [M+1] . Anal. Calcd for C16
H13NO
2
S: C, 67.8; H, 4.6; N,
4.9. Found: C, 68.0; H, 4.7; N, 4.9.
E)-2-Mesityl-1-phenylsulfonyl-1-ethenyl Cyanide (3b′). Method
i) (38% yield), method (ii) (54% yield), method (iii) (41% yield),
and method (iv) (75% yield). TLC on SiO : R ) 0.84 (eluent CH
). Mp: 102 °C. IR (cm ): 2225 (NtC), 1602 (CdC). H NMR
(
(
and the silica (SiO
tube, and the mixture was impregnated with CH
2
) support were placed in a cylindrical Pyrex
Cl ; after subse-
2
f
2
-
-1
1
2
2
Cl
CDCl
Me
2
quent solvent removal, the system was placed in the microwave
reactor and irradiated at 80 °C for 2 h. The crude product was
(
3
), δ: 2.22 and 2.28 (two s, 9H, CH
3
Ph), 6.91 (s, 2H,
3
C
6
H
2
), 7.61-7.76 (m, 3H, Ph), 8.04 (d, JHH 7.8 Hz, 2H, Ph),
purified by column chromatography on silica with CH
eluent, as indicated previously.
2
Cl
2
as the
13
1
8.51 (s, 1H, CH). C{ H} NMR (CDCl
3 3
), δ: 20.7 and 21.8 (CH -
Ph), 112.7 (CdC), 122.3 (NtC), 129.1, 129.7, 129.8, 130.4, 135.4,
+
Reaction of Free Nitriles NCCH
SO Ph,and1cR)COPh)withAcyclicNitrones O N(Me)dC(H)R′
2a R′ ) 4-MeC and 2b R′ ) 2,4,6-Me ).
2
R (1a R ) CO
2
Me, 1b R )
136.9, 138.4, and 141.5 (C
312 [M + 1] . Anal. Calcd for C H NO S: C, 69.4; H, 5.5; N,
aromatic
), 155.2 (CdC). FAB -MS, m/z:
-
+
+
2
18
17
2
(
6
H
4
3 6
C H
4
4.5. Found: C, 69.3; H, 5.7; N, 4.3.
E)-1-Benzoyl-2-(4-methylphenyl)-1-ethenyl Cyanide (3c).
Method (i) (17% yield), method (ii) (48% yield), method (iii) (35%
yield), and method (iv) (56% yield). TLC on SiO : R ) 0.76
). Mp: 90 °C. IR (cm ): 2214 (NtC), 1668 (Cd
(
(
17) (a) Mukerjee, A. K.; Srivastava, R. C. Synthesis 1973, 327-346.
(
b) Morin, R. B., Gorman, M., Eds. Chemistry and Biology of â-Lactam
2
f
Antibiotics; Academic Press: New York, 1982; Vols. 1-3.; (c) Page, M.
I., Ed. The Chemistry of â-Lactams; Chapman and Hall: London, 1997.
-1
(
eluent CH
2 2
Cl
1
O), 1596 (CdC). H NMR (CDCl
7
2
3
), δ: 2.46 (s, 3H, CH
3
Ph), 7.32-
.97 (m, 9H, Ph), 8.06 (s, 1H, CH). 13C{ H} NMR (CDCl
), δ:
2.6 (CH Ph), 109.6 (C ) C), 118.1 (NtC), 129.3, 129.9, 130.8,
(
18) Orvig, C.; Abrams, M. J. Chem. ReV. 1999, 99, 2201-2204.
1
3
(19) D o¨ pp, D.; D o¨ pp, H. In Houben-Weyl Methoden der Organischen
Chemie; Klamann, D., Hagemann, H., Eds.; Thieme Verlag: Stuttgart, 1990;
Vol. E14b, part 2, p 1372.
3
132.05, 133.9, 136.8, 137.0, and 145.5 (Caromatic), 156.3 (CdC),
754 J. Org. Chem., Vol. 72, No. 3, 2007

Stereospecific Synthesis of Polysubstituted E-Olefins
+
+
1
C
5
93.9 (CdO). FAB -MS, m/z: 248 [M + 1] . Anal. Calcd for
13NO: C, 82.6; H, 5.3; N, 5.7. Found: C, 82.6; H, 5.0; N,
NMR (CDCl
3 3 3
), δ: 20.9 and 21.7 (CH Ph), 34.1 (CH N), 47.8
17
H
(CH ), 53.5 (CH O), 90.7 (N-CH-N), 128.2, 128.5, 130.4, and 139.6
2 3
(Caromatic), 163.4 (CdN), 165.9 (CdO). 1 Pt NMR (CDCl
95
), δ:
.7.
E)-1-Benzoyl-2-mesityl-1-ethenyl Cyanide (3c′). Hygroscopic
compound becomes a viscous oil in air at room temperature but
remains a solid compound under a dinitrogen atmosphere. Method
3
+
+
(
-2221 (926 Hz) and -2254 (806 Hz). FAB -MS, m/z: 819 [M] .
Anal. Calcd for C30
C, 44.3; H, 4.5; N, 6.7.
40 4 6 2
H N O Cl Pt: C, 44.0; H, 4.9; N, 6.8. Found:
(
i) (15% yield), method (ii) (47% yield), method (iii) (38% yield),
and method (iv) (55% yield). TLC on SiO : R ) 0.87 (eluent CH
). IR (cm ): 2218 (NtC), 1668 (CdO), 1597 (CdC). H NMR
CDCl ), δ: 2.34 and 2.36 (two s, 9H, CH Ph), 6.98 (s, 2H,
Me ), 7.54-7.69 (m, 3H, Ph), 7.95 (d, JHH 7.5 Hz, 2H, Ph),
.29 (s, 1H, CH). C{ H} NMR (CDCl
Ph), 116.4 (CdC), 118.5 (NtC), 129.4, 129.6, 129.7, 130.0, 134.4,
36.2, 136.7, and 140.8 (Caromatic), 158.8 (CdC), 188.7 (CdO).
trans-[PtCl {NdC(CH
2
2
Cl)ON(Me)C(H)(4-MeC
: R ) 0.79 (eluent CH Cl
), δ: 2.39 (s, 6H,
N), 4.39 (two d, JHH 13.5,
Cl), 4.96 (two d, JHH 13.5, 13.2 Hz, 2H, CH Cl),
6
H
4
)}
2
] (5c).
2
f
2
-
-1
1
Yield: 58%. TLC on SiO
2
f
1
2
2
). Mp: 191
Cl
(
2
-
1
°
C. IR (cm ): 1664 (CdN). H NMR (CDCl
CH Ph), 2.92 and 2.93 (two s, 6H, CH
13.2 Hz, 2H, CH
.80 and 5.84 (two s, 2H, N-CH-N), 7.18-7.51 (m, 8H, Ph). C-
3
3
3
3
3
3
6 2
C H
13
1
2
2
8
3 3
), δ: 21.1 and 21.8 (CH -
1
3
5
{
1
3 3 3
H} NMR (CDCl ), δ: 22.1 (CH Ph), 34.2 (CH N), 46.7 and 46.8
1
+
+
2
(CH Cl), 92.9 (N-CH-N), 128.6, 130.0, 130.5, and 140.2 (Caromatic),
FAB -MS, m/z: 276 [M + 1] . Anal. Calcd for C19
O: C, 69.3; H, 7.0; N, 4.2. Found: C, 69.5; H, 6.9; N, 4.0.
Reactions of Organonitrile Platinum(II) Complexes trans-
PtCl (NCCH R) ] (4a R ) CO Me and 4b R ) Cl) with Acyclic
Nitrones O N(Me)dC(H)(R′) (2a R′ ) 4-MeC and 2b R′
2,4,6-Me ). A solution of 4a (50.0 mg, 0.107 mmol) or 4b
50.0 mg, 0.119 mmol) in dry CH Cl (3.0 mL) was added at room
H17NO•3/2
95
1
(
Cl
65.5 (CdN). 1 Pt NMR (CDCl
3
), δ: -2232 (701 Hz) and -2251
H
2
+
+
806 Hz). FAB -MS, m/z: 715 [M] . Anal. Calcd for C22
H
26
N
4
O
2
-
4
Pt: C, 36.9; H, 3.7; N, 7.8. Found: C, 37.1; H, 4.1; N, 7.7.
[
2
2
+
2
2
-
6
H
4
trans-[PtCl {NdC(CH Cl)ON(Me)C(H)(2,4,6-Me )} ] (5d).
2
2
3
C
6
H
2
2
)
(
3 6 2
C H
Yield: 53%. TLC on SiO : R ) 0.84 (eluent CH Cl ). Mp: 179
), δ: 2.30, 2.36,
Ph), 2.91 and 2.93 (two s, 6H, CH N),
.54 (d, JHH 13.2 Hz, 2H, CH Cl), 4.69 (d, JHH 13.2 Hz, 2H, CH
Cl), 5.94 and 6.05 (two s, 2H, N-CH-N), 6.83 (s, 4H, Ph). C-
2
f
2
2
2
2
-1
1
°
C. IR (cm ): 1662 (CdN). H NMR (CDCl
3
temperature to the nitrones 2a or 2b (2.2 equiv). The mixture was
heated to reflux with stirring for 8 h, and a bright yellow solution
was formed. The progress of the reaction was monitored by TLC.
After evaporation of the solvent in vacuo to dryness, the crude
residue was purified by column chromatography (SiO
Et O) followed by evaporation of the solvent in vacuo to dryness
and 2.39 (three s, 18H, CH
3
3
4
2
2
-
13
1
{
4
H} NMR (CDCl
7.7 (CH Cl), 91.4 (N-CH-N), 128.0, 128.4, 130.6 and 140.0
aromatic), 164.7 (CdN). Pt NMR (CDCl
3 3 3
), δ: 20.6, 20.9 and 21.8 (CH Ph), 34.2 (CH N),
2 2 2
/CH Cl ,
2
2
195
(C
3
), δ: -2191 (806 Hz).
FAB -MS, m/z: 771 [M] . Anal. Calcd for C26 Cl Pt•1/
CH Cl : C, 39.1; H, 4.3; N, 6.8. Found: C, 38.9; H, 4.3; N, 6.5.
to give a yellow powder of the corresponding final oxadiazoline
complex 5 (two diastereoisomers; distinct δ values are indicated
below when the resonances are resolved). The reaction is greatly
accelerated with microwave irradiation (1 h, 60 °C) to give the
products in yields (60-55%) that are comparable to those (58-
+
+
H
34
N O
4 2
4
2
2
2
The solvent of crystallization CH
spectra.
2 2
Cl has been detected in the NMR
5
3%) obtained in conventional refluxing CH
2
Cl
2
.
2 2 2
Conversion of trans-[PtCl {NdC(CH CO Me)ON(Me)C(H)-
(
4-MeC
conventional method: a solution of 5a (20.0 mg, 0.026 mmol) in
dry CH Cl (2.0 mL) was refluxed with stirring for 2 days to give
the alkene 3a (46% yield). (ii) By focused microwave irradiation
in CH Cl : after 2 h at 80 °C, the alkene 3a was isolated (51%
yield).
6 4 2
H )} ] 5a into the Corresponding Alkene 3a. (i) By the
trans-[PtCl {NdC(CH CO Me)ON(Me)C(H)(4-MeC H )} ]
2
2
2
6 4 2
(
(
5a). Yield: 57%. TLC on SiO : R ) 0.64 (eluent CH Cl
2
f
2
2
/Et
2
1
O
-
1
2
2
20:1)). Mp: 182 °C. IR (cm ): 1749 (CdO), 1657 (CdN). H
NMR (CDCl
CH N), 3.77 and 4.46 (m, 10H, CH
N), 7.19-7.52 (m, 8H, Ph). C{ H} NMR (CDCl
Ph), 34.3 (CH N), 47.4 (CH ), 53.7 (CH O), 92.6 (N-CH-N), 128.4,
30.2, 131.1, and 133.1 (Caromatic), 160.9 (CdN), 165.1 (CdO).
3
), δ: 2.39 (s, 6H, CH
3
Ph), 2.91 and 2.96 (two s, 6H,
CO Me), 5.83 (m, 2H, N-CH-
), δ: 22.0 (CH
2
2
3
2
2
13
1
3
3
-
3
2
3
195
Acknowledgment. This work has been partially supported
by the Funda c¸ a˜ o para a Ci eˆ ncia e a Tecnologia (FCT) and its
POCI 2010 program (FEDER funded) (Portugal). J.L. expresses
gratitude to FCT for a post-doctoral fellowship (Grant SFRH/
BPD/20927/2004).
1
-
+
+
Pt NMR (CDCl
Anal. Calcd for C26
3
), δ: -2290 (614 Hz). FAB -MS, m/z: 762 [M] .
Cl Pt•1/2CH Cl2•Et O: C, 41.6; H, 4.9;
N, 6.3. Found: C, 41.9; H, 4.7; N, 6.1. The solvents of crystal-
lization CH Cl and Et O have been detected in the NMR spectra.
H
32
N
O
4 6
2
2
2
2
2
2
trans-[PtCl {NdC(CH CO Me)ON(Me)C(H)(2,4,6-
2
2
2
Supporting Information Available: Information concerning the
material, instrumentation, and X-ray crystallographic data (and
ORTEP drawings) for compounds 3a and 5c. This material is
available free of charge via the Internet at http://pubs.acs.org.
Me
CH
3
C
6
H
2
)}
2
] (5b). Yield: 56%. TLC on SiO : R ) 0.66 (eluent
2
f
-
1
2
Cl
2
/Et
2
O (20:1)). Mp: 145 °C. IR (cm ): 1747 (CdO), 1666
1
(
CdN). H NMR (CDCl
3
), δ: 2.30, 2.37, and 2.40 (three s, 18H,
Ph), 2.88 and 2.90 (two s, 6H, CH N), 3.74 and 4.21 (m, 10H,
CO
Me), 6.02 (s, 2H, N-CH-N), 6.80 (s, 4H, Ph). 13C{ H}
CH
CH
3
3
1
2
2
JO061659B
J. Org. Chem, Vol. 72, No. 3, 2007 755