Chemistry of β-functionalized α-nitroso ethylenes. Methyl β-nitroso acrylate as heterodienophile in [4 + 2]-cycloaddition to cyclic dienes

Article abstract of DOI:10.1021/ol0057885

(equation presented) β-Functionalized nitroso alkene 2, obtained from methyl β-nitropropionate 1 and W,O-bis(trimethylsilyl)acetamide, can function as a good heterodienophile in Diels-Alder reactions. Therefore, 2 was trapped by cyclic dienes to give adducts 4 with the corresponding stereoselectivity. Cycloadduct 4a undergoes refro-[4 + 2]-cycloaddition at 33 °C in solution; thus 4a can be used to generate nitroso alkene 2 in neutral medium. Cyclopentadiene reacts with adduct 4a according to an endo-[4 + 2]-cycloaddition scheme to give cycloadduct 5 in low yield.

Full text of DOI:10.1021/ol0057885

ORGANIC
LETTERS
2000
Vol. 2, No. 9
1323-1324
Chemistry of â-Functionalized r-Nitroso
Ethylenes. Methyl â-Nitroso Acrylate as
Heterodienophile in [4 + 2]-
Cycloaddition to Cyclic Dienes
Alexander A. Tishkov, Il’ya M. Lyapkalo, Sema L. Ioffe,* Yuri A. Strelenko, and
Vladimir A. Tartakovsky
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 117913 Moscow, Russian Federation
iof@cacr.ioc.ac.ru
Received March 10, 2000
ABSTRACT
â-Functionalized nitroso alkene 2, obtained from methyl â-nitropropionate 1 and N,O-bis(trimethylsilyl)acetamide, can function as a good
heterodienophile in Diels−Alder reactions. Therefore, 2 was trapped by cyclic dienes to give adducts 4 with the corresponding stereoselectivity.
Cycloadduct 4a undergoes retro-[4 + 2]-cycloaddition at 33 °C in solution; thus 4a can be used to generate nitroso alkene 2 in neutral
medium. Cyclopentadiene reacts with adduct 4a according to an endo-[4 + 2]-cycloaddition scheme to give cycloadduct 5 in low yield.
For nearly 20 years, conjugated nitroso alkenes have been
employed as potent intermediates in organic synthesis due
to their ability to react as 1,3-heterodienes in Diels-Alder
cycloadditions.1 Nitroso alkenes are normally generated in
situ because of their instability and high reactivity. Most
examples of their application are reactions of nitroso alkenes
which are smoothly generated from available R-halogen-
substituted keto-oximes and various bases2 (Scheme 1).
in a â-position was found which implies silylation of
â-functionalized aliphatic nitro compounds. For example, the
reaction of methyl â-nitropropionate 1 proceeds through the
initial formation of trimethylsilyl nitronate followed by Me3-
SiOH elimination (Schemes 1 and 2).3
Scheme 2
Scheme 1
â-Functionalized nitroso alkenes were shown to act as
N-electrophiles in reactions with silyl nitronates. They can
also act as 1,3-heterodienes in [4 + 2]-cycloadditions with
electron-enriched alkenes.3
Recently, an alternative approach to the novel type of
nitroso alkenes bearing an electron-withdrawing substituent
10.1021/ol0057885 CCC: $19.00 © 2000 American Chemical Society
Published on Web 04/14/2000

Now we report that nitroso alkene 2 behaves as a
heterodienophile toward cyclic dienes. Intermediate 2 can
be efficiently trapped by cyclopentadiene 3a or cyclohexa-
diene 3b during the silylation of compound 1 with N,O-bis-
(trimethylsilyl)acetamide (BSA) (Scheme 2).4
For example, exposure of the solution of 4a in a 1:1 v/v
mixture of CHCl3 and ethyl vinyl ether for 3 days at 33 °C
gave a moderate yield of oxazine 6 (Scheme 3).8
Crystalline cycloadduct 4a can thus be considered to be a
“source” of intermediate 2 in neutral medium. This can
obviously be significant for synthetic applications of â-fuc-
tionalized nitroso alkenes.9
It is noteworthy that most nitroso alkenes react with either
dienes or alkenes as 1,3-heterodienes to give the correspond-
ing oxazines in moderate yields.1,5
Acknowledgment. This work was carried out at the
Scientific Educational Center for Young Chemists and was
supported partly by the Russian Basic Research Foundation
(Grants 96-03-32472 and 96-15-97332) and Federal Program
‘‘Integration” (Project A0082).
Both reactions presented in Scheme 2 are chemo- and
stereoselective; cycloadducts 4a and 4b were isolated as
individual endo-(E)-isomers (according to NMR data).
The reaction of methyl â-nitropropionate 1 with BSA in
a solution in pure diene 3a resulted (after 7 days) in partial
transformation of cycloadduct 4a into bisadduct 5; a 4:1
mixture of 4a and 5 was obtained.6 Individual cycloadduct
5 can be isolated in lower yield after exposure of the 4:1
mixture of 4a and 5 in cyclopentadiene (Scheme 3).7 The
Supporting Information Available: Characterization
data for compounds 4a,b, 5, and 6. This material is available
free of charge via the Internet at http://pubs.acs.org.
OL0057885
(1) Boger, D. L. Hetero Diels-Alder Methodology in Organic Synthesis;
Academic Press: New York, 1987. Boger, D. L. Chem. ReV. 1986, 781.
Lyapkalo, I. M.; Ioffe, S. L. Russ. Chem. ReV. 1998, 67, 467.
(2) Faragher, R.; Gilchrist, T. L. J. Chem. Soc., Perkin Trans. 1 1979,
249. Zimmer, R.; Reissig, H.-U. J. Org. Chem. 1992, 57, 339. Ciattoni, P.;
Rivolta, L. Chim. Ind. (Milan) 1967, 49, 1186.
Scheme 3
(3) Ioffe, S. L.; Lyapkalo, I. M.; Tishkov, A. A.; Danilenko, V. M.;
Strelenko, Yu. A.; Tartakovsky, V. A. Tetrahedron 1997, 53, 13085.
(4) Typical procedure: To a stirred solution of 1 (1 g, 7.5 mmol) in
CH2Cl2 (30 mL) and diene 3a (6.16 mL, 75.0 mmol) or 3b (4.65 mL, 75.0
mmol) was added distilled BSA (9.3 mL, 37.6 mmol) at 0 °C in an inert
atmosphere, and the mixture was kept at 20 °C for 48 h. Then it was
concentrated at 0.1 Torr. For 4a: the residue was diluted with hexane and
the white precipitate was filtered off to give 0.78 g of 4a (57%). For 4b:
the residue was diluted with MeOH (3 mL), stirred for 10 min, poured into
water (20 mL), and extracted with hexane (3 × 20 mL). The extract was
dried (Na2SO4) and evaporated to give 0.31 g of white crystalline 4b (21%).
(5) Clorinated nitroso alkenes are the exception; they react with
conjugated cyclic dienes as heterodienophiles. The adducts formed, however,
are unstable and rearrange to give epoxyaziridines (see Francotte, E.;
Merenyi, R.; Vandenbulcke-Coyette, B.; Viehe, H. G. HelV. Chim. Acta
1981, 64, 1208. Francotte, E.; Merenyi, R.; Viehe, H. G. Angew. Chem.,
Int. Ed. Engl. 1978, 17, 936. Viehe, H. G.; Merenyi, R.; Francotte, E.; Van
Merssche, M.; Germain, G.; Declarcq, J. P.; Bodart-Gilmont, J. J. Am. Chem.
Soc. 1977, 99, 2340).
(6) To a stirred solution of 1 (1 g, 7.5 mmol) in cyclopentadiene 3a
(12.4 mL, 151.5 mmol) was added distilled BSA (9.3 mL, 37.6 mmol) at
0 °C in an inert atmosphere, and the mixture was kept at 20 °C for 7 days.
For the workup, see typical procedure4 for 4a. The yield is 0.58 g (4:1 of
4a and 5, respectively).
(7) The 4:1 mixture of 4a and 5 (0.2 g) was dissolved in freshly distilled
cyclopentadiene 3a (1.5 mL) and kept for 7 days at 20 °C. Then it was
evaporated at 0.1 Torr; the residue was dissolved in MeCN (5 mL) and
extracted with hexane (4 × 7 mL). The combined hexane layers were
evaporated to ca. 2 mL, and the precipitate was filtered off to give 30 mg
(10%) of white crystalline 5.
configuration of bisadduct 5 is presented in Scheme 3 and
confirmed by NMR data.
(8) Cycloadduct 4a (90 mg, 0.5 mmol) was dissolved in CHCl3 (3 mL)
and ethyl vinyl ether (3 mL), and the solution was kept at 33 °C for 3 days.
Then the mixture was evaporated, the residue was extracted with hexane
(5 × 5 mL), and the combined hexane layers were filtered through Cellite
Cycloadduct 4a proved to be unstable in contrast to 4b.
4a can undergo facile retro-[4 + 2]-cycloaddition in solution
to give nitroso intermediate 2 which can be trapped by an
external dienophile.
1
and evaporated to give 50 mg (52%) of 6 as yellowish oil. The H NMR
for 6 was in good agreement with literature data.3
(9) White crystalline cycloadduct 4a is easy to handle and it could be
stored at -5 °C for several months.
1324
Org. Lett., Vol. 2, No. 9, 2000