Generation and in situ Diels-Alder reactions of activated nitroethylene derivatives

Article abstract of DOI:10.1016/S0040-4039(02)00348-9

Dienes readily undergo Diels-Alder reaction with CH₂=C(NO₂)SO₂Ph (2a), CH₂=C(NO₂)CO₂Et (2b), and CH₂=C(NO₂)COPh (2c), all observed in situ by ¹H NMR. The cycloadducts of 2a undergo S_RN1 reactions.

Full text of DOI:10.1016/S0040-4039(02)00348-9

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 2585–2588
Generation and in situ Diels–Alder reactions of activated
nitroethylene derivatives†
Peter A. Wade,a,* James K. Murray, Jr.,a Sharmila Shah-Patela and Patrick J. Carrollb
aDepartment of Chemistry, Drexel University, Philadelphia, PA 19104, USA
bDepartment of Chemistry, University of Pennsylvania, Philadelphia, PA 19104, USA
Received 4 January 2002; accepted 12 February 2002
Abstract—Dienes readily undergo Diels–Alder reaction with CH2ꢀC(NO2)SO2Ph (2a), CH2ꢀC(NO2)CO2Et (2b), and
CH2ꢀC(NO2)COPh (2c), all observed in situ by 1H NMR. The cycloadducts of 2a undergo SRN1 reactions. © 2002 Elsevier
Science Ltd. All rights reserved.
Although isolable,1 nitroethylene is of somewhat lim-
ited stability, readily undergoing polymerization and
conjugate addition with weak nucleophiles. Ethylene
derivatives in which one of two geminal W-groups is
nitro have never been isolated2 and only three of their
in situ Diels–Alder (D–A) reactions have ever been
reported.2,3 Here we describe a protocol for conducting
routine D–A reactions using the nitroethylene deriva-
tives 2a–c possessing a second electron attracting group
at the a-position.
able nitromethane derivatives 1a–c were condensed
with formalin in the presence of dienes and acetic acid
(Scheme 1). An excess of the nitromethane derivative
was routinely employed (three-fold excess of 1a, six-
fold excess of 1b–c) and yields are based on the starting
diene as the limiting reagent (Table 1). The presence of
acetic acid appears to serve two functions: facilitated
dehydration of the intermediate nitroaldol4 and control
of the reaction pH lowering potential side reactions of
the nitroethylene derivative. At no time were the
nitroethylene derivatives 2a–c observed under these
conditions. Uncharacterized polar compounds were
also present in the crude products.
In a simple, practical route to the D–A adducts of
nitroethylene derivatives 2a–c, the commercially avail-
Scheme 1.
* Corresponding author. Tel.: 215-895-2652; fax: 215-895-1265; e-mail: wadepa@drexel.edu
† Dedicated to Professor Henry Feuer on the occasion of his 90th birthday.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00348-9

2586
P. A. Wade et al. / Tetrahedron Letters 43 (2002) 2585–2588
Table 1. Diels–Alder adducts obtained from 2a–2c
MCPBA oxidation of the b-sulfide 4a–c gave the b-sulf-
oxide 5a–c (two diastereomers) and the nitroethylene
derivative 2a–c that could be detected in CD2Cl2 solu-
tion by 1H NMR.8 Warming the sample briefly
afforded the nitroethylene derivative at the expense of
the sulfoxide in each case. The NMR signals attributed
to the geminal olefinic protons are characteristic: in all
three cases, the proton cis to the nitro group gave a
sharp doublet while the proton trans to the nitro group
was broadened, presumably owing to greater
quadrapole coupling from the N-atom.9 Concentration
of solutions containing 2a at 0–5°C led to complete
decomposition of both the sulfoxide and the
nitroethylene derivative although solutions containing
When thiophenol was substituted for the diene in the
above reactions, the b-sulfides 4a–c and hydroxymethyl
b-sulfides 3a–b were obtained.5 During silica gel chro-
matography, 3a and 3b were converted to 4a and 4b. In
the case of 4c, little hydroxymethyl b-sulfide 3c was
obtained but acid-catalyzed elimination of benzoic acid
was a troublesome side reaction.5 Thus, b-sulfides 4a–c
were readily obtained in 67–88% yield.6 These b-sulfides
proved useful, stable precursors to the corresponding
nitroethylene derivatives.
Oxidation with either MCPBA or ozone provided the
b-sulfoxides 5a–c as unstable intermediates undergoing
b-sulfoxide elimination at 0–40°C. In each case,

P. A. Wade et al. / Tetrahedron Letters 43 (2002) 2585–2588
2587
2b could be concentrated at 20°C and reconstituted
without destruction of 2b and its sulfoxide precursor.
nitronic ester 17, was obtained in addition to the a-
nitrosulfone 6.
Nitroethylene derivatives 2a–c were then cleanly gener-
ated for in situ cycloaddition in the following manner.
A CH2Cl2 solution of the corresponding purified b-
sulfide was oxidized with ozone at −78°C and the
preformed cold solution was then added dropwise to a
warmed solution of diene. Under these conditions, D–A
cycloadducts were obtained in 57–97% yield based on
the b-sulfide as the limiting reagent.10,11 For example,
the Danishefsky diene worked well under these anhy-
drous conditions affording the sensitive cycloadducts 9
and 14 on work-up. Loss of methanol from 9 and 14
occurred readily.
SRN1 reactions. The secondary a-nitrosulfone D–A
adducts are highly functionalized and would be
expected to be useful synthetic intermediates. For
example, secondary nitrosulfones, formerly of limited
availability, have been reported to undergo SRN1 substi-
tution reactions in which the sulfone group can be
replaced by a nucleophile.14 We have accordingly sub-
jected nitrogen-degassed DMPU solutions containing
excess lithium 2-nitropropanate and a-nitrosulfones 6
and 10 to visible light (Scheme 2). The substitution
products 18 and 19 were formed in 87–90% yield.
Interestingly, 19 was formed as a single isomer (pre-
sumably with the nitro group endo) despite the radical
intermediate present in such reactions. Similarly, reac-
tion of a-nitrosulfone 7 with the sodium enolate of
ethyl 2-oxocyclopentanecarboxylate in DMSO solution
afforded substitution product 20 (mixture of
diastereomers) in 40% yield.
In the cases involving cyclopentadiene and its deriva-
tives, cycloaddition of CH2ꢀC(NO2)SO2Ph (2a)
occurred with a high preference for placing the nitro
group endo in the resulting adduct (cycloadducts 10–11
>97:3 isomer ratio). This high stereoselectivity was sur-
prising in view of the fact that E-PhSO2CHꢀCHNO2
has been reported to give
a 75:25 mixture of
Representative procedures. Synthesis of 6: procedure A.
A solution containing 1a (0.74 g, 3.7 mmol), 2,3-
dimethyl-1,3-butadiene (0.10 g, 1.2 mmol), 37% forma-
lin (0.99 g), and HOAc (0.73 g) in THF (5 mL) was
heated at 35–40°C for 1 day. Volatiles were removed in
vacuo and the residue partitioned between CH2Cl2 and
10% brine. The organic layer was separated, washed
with water, dried over Na2SO4, and concentrated. Flash
chromatography on silica gel (CH2Cl2 elution) followed
by recrystallization from 95% ethanol afforded 0.33 g
diastereomers on reaction with cyclopentadiene.12
MM2 calculations13 suggested a preferred conformation
of 2a where the phenyl group of the sulfone moiety is
perpendicular to the C,C double bond (Fig. 1) allowing
easier access to a transition state with endo-placement
of the nitro group. For reactions of the planar species
2b–c where this effect would be absent, substantially
less biased endo/exo mixtures were obtained (cycload-
ducts 15–16). In all cases, regioselectivity was high
(only one regioisomer for cycloadducts 7, 8, 9, and 14
was detected). In one case, reaction of 2a with 2,3-
dimethyl-1,3-butadiene, a 3% yield of a periisomer, the
1
(90% yield) of 6:7,15 mp 97–98°C; H NMR (250 MHz,
CDCl3) l 7.6–7.9 (m, 5H), 2.9–3.1 (m, 2H), 2.68 (dd,
1H, J=13.7, 5.7 Hz), 2.3–2.45 (m, 1H), 2.05–2.3 (m,
2H), 1.64 (s, 3H), 1.56 (s, 3H); 13C NMR (62.9 MHz,
CDCl3) l 135.1, 132.7, 130.5, 129.1, 125.1, 120.3, 106.3,
33.2, 27.9, 25.5, 18.7, 18.2.
Synthesis of 6: procedure B. Through a cold (−78°C)
solution of b-sulfide 4a (325 mg, 1.0 mmol) and HOAc
(63 mg) in CH2Cl2 (10 mL) over 30 min was passed a
stream of ozone in O2 (excess ozone). This solution
(kept cold) was stirred for an additional 30 min, purged
with N2, and transferred dropwise over 45 min to a
Figure 1. MM2 calculation: preferred conformation of 2a.
ONa
MeO2C
NO2
SO2Ph
NO2
O2N COOEt
R
Me
Me
NO2
Me
LiO2N=CMe2
DMSO
fluorescent
Me
Me
Me
DMPU
fluorescent
hν
O
20
18
6, R = Me
7, R = H
hν
NO2
Me
SO2Ph
NO2
LiO2N=CMe2
Me
NO2
DMPU
fluorescent
hν
10
19
Scheme 2.

2588
P. A. Wade et al. / Tetrahedron Letters 43 (2002) 2585–2588
warmed solution (50–55°C bath temp.) of 2,3-dimethyl-
1,3-butadiene (167 mg, 2.0 mmol) in benzene (10 mL).
Heating was continued an additional 30 min, volatiles
were removed, and the crude product was purified as in
procedure A: 270 mg (91% yield).
(d, 1H, J=3.2 Hz), 7.20 (broad d, 1H). 2b: l 6.47 (d, 1H,
J=2.6 Hz), 6.43 (broad s, 1H). 2c: l 6.88 (d, 1H, J=2.7
Hz), 6.21 (broad s, 1H). 1H NMR (250 MHz, CD2Cl2)
data. 5a (50:50 diastereomer mixture) l 7.35–8.1 (m,
10H), 6.08 (dd, 1H, J=9.2, 2.6 Hz, isomer i) 5.89 (dd,
1H, J=11.4, 1.9 Hz, isomer ii) 3.9–4.05 (m, 1H, both
isomers), 3.73 (dd, 1H, J=14.8, 9.2 Hz, isomer i), 3.50
(dd, 1H, J=14.8, 1.9 Hz, isomer ii).
References
9. The published spectrum of nitroethylene (Ref. 1) also
shows the same effect but without explanation.
1. Ranganathan, D.; Rao, C. B.; Ranganathan, S.; Mehro-
tra, A. K.; Iyengar, R. J. Org. Chem. 1980, 45, 1185 and
references cited therein.
2. Ethyl a-nitroacrylate: Babievskii, K. K.; Belikov, V. M.;
Tikhonova, N. A. Dokl. Akad. Nauk SSSR 1965, 160,
103 [Chem. Abstr. 1965, 62, 66174].
3. (a) There are no reports of in situ D–A reactions of
a-nitro-vinyl sulfones, but see: Zeilstra, J. J.; Engberts, J.
B. F. N. J. Org. Chem. 1974, 39, 3215; (b) 1,1-Dini-
troethene: Gold, M. H.; Hamel, E. E.; Klager, K. J. J.
Org. Chem. 1957, 22, 1665.
4. Wade, P. A.; Murray, J. K., Jr.; Shah-Patel, S.; Palfey, B.
A.; Carroll, P. J. J. Org. Chem. 2000, 65, 7723.
5. b-Sulfide 2a was prepared in DMSO at 35°C. b-Sulfides
2b and 2c were prepared in THF at 65°C. The THF
solution of crude 2c was diluted with CH2Cl2 and washed
(several portions of water) to remove the bulk of HOAc
before concentration: otherwise substantial elimination of
benzoic acid occurred.
10. Representative 1H NMR (250 MHz, CDCl3) data. 7: l
7.55–7.9 (m, 5H), 5.31 (m, 1H), 2.9–3.2 (m, 2H), 2.7–2.85
(m, 1H), 2.35–2.5 (m, 1H), 2.0–2.3 (m, 2H), 1.63 (s, 3H).
11: l 7.5–7.85 (m, 5H), 6.53 (dd, 1H, J=5.7, 3.0 Hz),
6.01 (dd, 1H, J=5.7, 3.0 Hz), 3.38 (m, 1H), 3.14 (dd, 1H,
J=13.8, 3.5 Hz), 2.55–2.60 (m, 2H), 1.15–1.25 (m, 1H),
0.84–0.94 (m, 1H), 0.45–0.6 (m, 2H). 12: l 4.23 (q, 2H,
J=7.2 Hz), 2.85 (broad d, 1H, J=17.6 Hz), 2.68 (broad
d, 1H, J=17.6 Hz), 2.5–2.65 (m, 1H), 2.2–2.35 (m, 1H),
2.04 (app. broad s, 2H), 1.64 (s, 3H), 1.58 (s, 3H), 1.26 (t,
3H, J= 7.2 Hz). 16 (endo NO2): l 7.4–7.9 (m, 5H), 6.59
(dd, 1H, J=5.5, 2.9 Hz), 5.95 (dd, 1H, J=5.5, 2.9 Hz),
3.94 (broad s, 1H), 3.10 (broad s, 1H), 2.82 (dd, 1H,
J=13.5, 3.2 Hz), 2.26 (dd, 1H, J=13.5, 3.2 Hz), 1.67–
1.77 (m, 2H). 17: l 7.5–8.0 (m, 5H), 4.83 (m, 1H), 4.79 (s,
1H), 2.90–3.05 (m, 1H), 2.63–2.85 (m, 1H), 2.30–2.41 (m,
1H), 1.89–2.0 (m, 1H), 1.64 (d, 3H, J=0.5 Hz), 1.42 (s,
3H).
6. 1H NMR (250 MHz, CDCl3) data. 4a: l 7.55–7.9 (m,
5H), 7.25–7.45 (m, 5H), 5.44 (dd, 1H, J=11.7, 2.8 Hz),
3.72 (dd, 1H, J=14.9, 2.8 Hz), 3.50 (dd, 1H, J=14.9,
11.7 Hz). 4b: l 7.25–7.45 (m, 5H), 5.02 (dd, 1H, J=8.1,
6.8 Hz), 4.19 (q, 2H, J=7.2 Hz), 3.4–3.6 (m, 2H), 1.21 (t,
3H, J=7.2 Hz). 4c: l 7.30–7.75 (m, 10H), 6.09 (dd, 1H,
J=8.5, 5.5 Hz), 3.75 (dd, 1H, J=14.6, 8.5 Hz), 3.59 (dd,
1H, J=14.6, 5.5 Hz).
7. Crystallographic data (excluding structure factors) have
been deposited with the Cambridge Crystallographic data
Centre as supplementary publication numbers CCDC
178872 (10) and 178873 (16). Copies of the data can be
obtained, free of charge, on application to CCDC, 12
Union Road, Cambridge CB2 1EZ, UK [fax: +44 (0)
1223-336033 or e-mail: deposit@ccdc.cam.ac.uk].
8. 1H NMR (250 MHz, CD2Cl2) olefinic signals. 2a: l 7.25
11. Representative 13C NMR (62.9 MHz, CDCl3) data. 7: l
135.1, 133.9, 132.8, 130.6, 129.1, 114.9, 105.7, 28.3, 26.6,
25.3, 22.6. 11: l 142.3, 135.3, 134.8, 134.0, 130.1, 129.1,
116.9, 55.4, 48.6, 44.9, 35.2, 12.0, 5.6. 12: l 166.9, 124.8,
121.0, 92.0, 62.5, 37.1, 29.0, 28.0, 18.5, 18.3, 13.6. 16
(endo NO2): l 191.2, 142.0, 133.8, 131.6, 128.8, 101.2,
53.2, 50.3, 42.7, 37.5.
12. Ono, N.; Kamimura, A.; Aritsune, K. J. Org. Chem.
1986, 51, 2139.
13. MM2 calculation: CHEM-3D™ program.
14. (a) Kornblum, N. Angew. Chem., Int. Ed. Engl. 1975, 14,
734; (b) Kornblum, N.; Boyd, S. D.; Ono, N. J. Am.
Chem. Soc. 1974, 96, 2580.
15. Anal. calcd for C14H17NO4S: C, 56.93; H, 5.81; N, 4.75.
Found: C, 56.67; H, 5.61; N, 4.56%.