Nitration of silyl allenes to form functionalized nitroalkenes

Article abstract of DOI:10.1021/ol401735v

An efficient nitration of silyl allenes with nitrogen dioxide radical, generated from NaNO₂ and AcOH, to form α-nitro-α,β- unsaturated silyl oximes has been developed. A similar nitration could be achieved by using Fe(NO₃)₃·9H₂O and FeCl₃·6H₂O, but different from the regioselective oxime formation, two regioisomeric chloride-trapped products were isolated with varying ratios depending on the steric bulk of the silyl group. A novel ring-closure reaction of α-nitro-α,β-unsaturated silyl oximes upon treating with TBAF to form isooxazolidinone derivatives was also developed.

Full text of DOI:10.1021/ol401735v

ORGANIC
LETTERS
2013
Vol. 15, No. 15
3954–3957
Nitration of Silyl Allenes To Form
Functionalized Nitroalkenes
Venkata R. Sabbasani and Daesung Lee*
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street,
Chicago, Illinois 60607, United States
dsunglee@uic.edu
Received June 19, 2013
ABSTRACT
An efficient nitration of silyl allenes with nitrogen dioxide radical, generated from NaNO2 and AcOH, to form R-nitro-R,β-unsaturated silyl oximes
has been developed. A similar nitration could be achieved by using Fe(NO3)3 9H2O and FeCl3 6H2O, but different from the regioselective oxime
formation, two regioisomeric chloride-trapped products were isolated with varying ratios depending on the steric bulk of the silyl group. A novel
3
3
ring-closure reaction of R-nitro-R,β-unsaturated silyl oximes upon treating with TBAF to form isooxazolidinone derivatives was also developed.
The strong electron-withdrawing nature of the nitro
group and its facile conversion to other functional groups
makes nitro compounds versatile building blocks in che-
Scheme 1. Nitration of Simple Alkene versus Silyl Allene
mical synthesis.1 Nitro compounds are also widely used as
medicine, fuel, solvent, and raw material in the chemical
industry. Therefore, developing methods that can efficiently
introduce a nitro group onto saturated and unsaturated
hydrocarbons is highly sought after.
One of the most representative nitration methods is
based on the addition of nitrogen dioxide with an alkene
starting material (Scheme 1, eq 1).2 To generate structurally
more elaborate nitro compounds, we envisioned the corre-
(1) (a) Feuer, H.; Nielsen, T. Nitro Compounds: Recent Advances in
sponding nitration of silyl allenes, which so far has not been
reported in the literature (eq 2).3 Compared to the addition
of a nitrogen dioxyl with alkene, we expected that the
addition of a radical species with silyl allenes should be
more favorable due to the formation of a relatively more
stable allylic radical intermediate. The resulting radical
intermediate will be directly captured by another radical
species or be oxidized to the corresponding allylic cation,
which then reacts with a nucleophile. Herein we report the
result of our investigation for the nitration of silyl allenes
under two different conditions, and facile 5-endo-dig
Synthesis and Chemistry; VCH: New York, 1990. (b) Ono, N. The Nitro
Group in Organic Synthesis; Wiley-VCH: New York, 2001. (c) Ballini, R.;
Petrini, M. ARKIVOC 2009, 195.
(2) (a) Shechter, H.; Conrad, F.; Daulton, A. L.; Kaplan, R. B. J. Am.
Chem. Soc. 1952, 74, 3052. (b) Terada, A.; Hassner, A. Bull. Chem. Soc.
Jpn. 1967, 40, 1937. (c) Bachman, G. B.; Whitehouse, M. L. J. Org.
Chem. 1967, 32, 2303. (d) Park, J. R.; Williams, D. L-H. J. Chem. Soc.,
Perkin Trans. 2 1976, 828. (e) Corey, E. J.; Estreicher, H. J. Am. Chem.
Soc. 1978, 100, 6294. (f) Hayama, T.; Tomoda, S.; Takeuchi, Y.;
Nomura, Y. Tetrahedron Lett. 1982, 23, 4733. (g) Jew, S.-S.; Kim,
H.-D.; Cho, Y.-S.; Cook, C.-H. Chem. Lett. 1986, 1747. (h) Butts,
C. P.; Calvert, J. L.; Eberson, L.; Hartshorn, M. P.; Robinson, W. T.
J. Chem. Soc., Perkin Trans. 2 1994, 1485. (i) Hata, E.; Yanada, T.;
Mukaiyama, T. Bull. Chem. Soc. Jpn. 1995, 68, 3629. (j) Campos, P. J.;
Garcıa, B.; Rodrıguez, M. A. Tetrahedron Lett. 2000, 41, 979. (k)
Stepanov, A. V.; Veselovsky, V. V. Russ. Chem. Rev. 2003, 72, 327. (l)
Jovel, I.; Prateeptongkum, S.; Jackstell, R.; Vogl, N.; Weckbecker, C.;
Beller, M. Adv. Synth. Catal. 2008, 350, 2493. (m) Sprecher, H.;
(3) For an example of N2O4 addition with sterically hindered trialkyl
allene, see: Wieser, K.; Berndt, A. Angew. Chem., Int. Ed. 1975, 14, 69.
€
Pletscher, S.; Mori, M.; Marti, R. Helv. Chim. Acta 2010, 93, 90.
r
10.1021/ol401735v
Published on Web 07/22/2013
2013 American Chemical Society

cyclization of the products of nitroso-nitration of silyl
allenes, R-nitro-R,β-unsaturated silyl oximes, upon treat-
ment with TBAF to form isooxazolidinone derivatives.
While developing a method for the synthesis of differ-
ently substituted allenes and exploring their reactivities,4
weprepared aseriesoftrisubstitutedsilylallenes viaathree-
component coupling reaction involving ketone, lithium
trimethylsilyldiazomethane, and free trimethylsilyldiazo-
methane.4b Occasionally in this study, we observed the
instability of some of these silyl allenes under air.5 Unaware
of any reported instabilty of the corresponding alkyl-
substituted allenes, we inferred that the instability of silyl
allenes should be caused by the silyl substituent. This
property, we envisioned, can be exploited in developing
new chemical processes such as nitration, which has been
extensively studied with alkenes under conditions that gen-
erate nitrogen dioxyl, and most representative conditions
are: NaNO2/AcOH/cerium ammonium nitrate (CAN),6a
Table 1. Optimization of Reaction Conditions
temp time
yielda
(%)
entry allene
conditions
solvent
CHCl3
CHCl3
(°C) (h) product
1
2
1a NANO2/
25
25
2
2
dec
dec
AcOH/CAN
1a NANO2/
AcOH/CAN
1a AgNO2/TEMPO ClCH2CH2Cl 25
3
4
5
8
8
dec
dec
1a AgNO2/TEMPO CHCl3
25
25
1b NANO2/
AcOH/CAN
1b NANO2/
AcOH/CAN
CHCl3
24 2b
81 (1:1)b
89 (1:1)b
6
CHCl3
50
3
2b
AgNO2/TEMPO,6b,c Fe(NO3)3 9H2O/FeCl3,6d and
7
1b NANO2/CAN
1b AcOH/CAN
CHCl3
CHCl3
50
50
50
3
3
3
no rxnc
no rxnc
2b
3
tBuONO/TEMPO.6e
8
9
10d
1b NANO2/AcOH CHCl3
85 (1:1)b
45 (1:1)b
Not knowing which conditions are most suitable for silyl
allenes, we decided to screen these systems to find the
optimal conditions (Table 1). When trimethylsilyl allene1a
was used as the substrate under NaNO2/AcOH/CAN-
(cerium ammonium nitrate) in CHCl3 or CH3CN, only de-
composition of the substrate was observed (entry 1 and 2).
Changing the conditions to AgNO2/TEMPO in CHCl3
or ClCH2CH2Cl resulted in the same negative outcome
(entry 3 and 4). Then, we changed the substrate from 1a
to 1b where the trimethyl silyl group is replaced with a tert-
butyldimethylsilyl group since we believed that substrate 1a
containing a trimethylsilyl group might not be compatible
with the acidic conditions that cause protodesilylation.7
Gratifyingly, tert-butyldimethylsilyl allene 1b smoothly
participated in the addition reaction under NaNO2/
AcOH/CAN in CHCl3 at room temperature to deliver
the product R-nitro-R,β-unsaturated silyl oxime 2b in 81%
yield with a 1:1 ratio of E/Z isomers (entry 5). Running the
reaction at higher temperature (50 °C) considerably short-
ened the reaction time and further improved the yield to
89% (entry 6). Reactions without AcOH or NaNO2 did
not proceed at all and returned the starting material intact
(entry 7 and 8). On the other hand, the same reaction
without CAN showed a similar reaction profile as that with
CAN, providing product 2b in 85% yield (entry 9). When
another reagent combination of AgNO2/TEMPO was tried,
product 2b was produced but only in 45% yield (entry 10).
With the optimized protocol for silyl allene nitration
in hand, we examined the substrate scope by using a variety
1b AgNO2/TEMPO ClCH2CH2Cl 60
10 2b
a Isolated yields after purification by flash chromatography. b E/Z
ratio were determined by 1H NMR. c Most starting material was
recovered. d Similar yield in CHCl3.
of silyl allenes (Table 2). Although CAN additive did not
play any major role for the reaction of 1b, we ran addi-
tional reactions with other substrates with and without
CAN in parallel (entries 1, 2, 4, 5, and 8). From these data,
we conclude that not only with 1b but also with most of
other silyl allenes examined in general the CAN additive
was unnecessary.
First, we probed the influence of the steric bulk of the
silyl group by comparing the reactivity between triethyl-
and triisopropylsilyl allenes 1c and 1d. Both substrates
reacted smoothly to provide silyl oxime products 2c and 2d
in 91 and 85% yield, respectively, both with 1:1 ratio of
E/Z isomers (entries 1 and 2). The slightly inferior yield of
the latter implies that the steric bulk of the silyl group plays
a certain role but only to a minor extent. On the other
hand, tert-butyl-substituted allene 1e decomposed when
treated under identical conditions (entry 3), which clearly
indicates the important role of the silyl group to promote
the current nitration reaction.
Next, we examined the effect of extra π-systems on
the allene containing benzyl/phenethyl (1f), phenyl (1g),
4-pentenyl (1g0), and 3-adamentylidene (1h) groups (entries
4ꢀ6). Other than a slight difference in yields, no byproducts
involving these extra π-systems were observed. While
benzyl-substituted substrate 1f provided product 2f in 83%
yield (entry 4), phenyl and 4-pentenyl group-substituted
substrate 1g and 1g0 afforded 2g and 2g0 in 88 and 86% yield,
respectively (entry 5). The differences in E/Z ratio for the
products should be the consequence of the steric bias of these
substituents. Allene 1h containing a 3-adamantylidene moi-
ety provided product 2h in 67% yield without complication
by the trisubstituted alkenyl functionality (entry 6). Based on
these results, we concluded that the silyl allene moiety is much
(4) (a) Zheng, J.-C.; Yun, S. Y.; Sun, C.; Lee, N.-K.; Lee, D. J. Org.
Chem. 2011, 76, 1086. (b) Venkata, R. S.; Phani, M.; Lu, H.; Xia, Y.; Lee,
D. Org. Lett. 2013, 15, 1552.
(5) Nakajima, R.; Ogino, T.; Yokoshima, S.; Fukuyama, T. J. Am.
Chem. Soc. 2010, 132, 1236.
(6) (a) Hwu, R. H.; Chen, K.-L.; Ananthan, S.; Patel, H. V. Organo-
metallics 1995, 15, 499. (b) Maity, S.; Manna, S.; Rana, S.; Naveen, T.;
Mallick, A.; Maiti, D. J. Am. Chem. Soc. 2013, 135, 3355. (c) Naveen, T.;
Maity, S.; Sharma, U.; Maiti, D. J. Org. Chem. 2013, 78, 5949. (d)
Taniguchi, T.; Fujii, T.; Ishibashi, H. J. Org. Chem. 2010, 75, 8126. (e)
Maity, S.; Naveen, T.; Sharma, U.; Maiti, D. Org. Lett. 2013, 15, 3384.
(7) Kim, S.; Kim, B.; In, J. Synthesis 2009, 12, 1963.
Org. Lett., Vol. 15, No. 15, 2013
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Table 2. Scope of the Reaction with NaNO2/AcOH with and
without CAN
Table 3. Nitration Reaction with Iron(III) Nitrate
a Combined yields after purification. b The ratios of 3 and 4 were
determined by 1H NMR analysis. c The double-bond geometry of 4 was
determined by NOE experiments.
group smoothly afforded nitration products 2m and 2n
in 88% and 81% yield, respectively (entries 11 and 12).
Unexpectedly, disubstituted silyl allene 1o was recovered
intact under identical reaction conditions (entry 12), which
is probably due to the difficulty in forming a relatively
unstable secondary carbon-centered radical intermediate
form 1n as opposed to the tertiary from trisubstituted silyl
allenes.
Having silyl allenes successfully engaged in nitration
with metal nitrites, we next examined their nitration using
Fe(NO3)3 9H2O as the source of nitrite under oxidative
3
conditions (Table 3). Even though silyl allene 1b decom-
posed when exposed to Fe(NO3)3 9H2O alone, by adding
an oxidant such FeCl3 6H2O to the reaction, chlorinated
a Isolated yields. b E/Z ratios were determined by 1H NMR. c The
yields in the parentheses are for the reactions with CAN. d Starting
material was recovered even after heating to 70 °C.
3
3
nitroalkenes 3b and 4b were obtained in 83% yield with a
1:1 ratio (entry 1). Gratifyingly, silyl allene 1p containing a
sterically lessencumberedtrimethylsilyl group, nota viable
substituent in the previous reaction, is not only compatible
with the conditions but also controlled the regioselectivity,
affording products 3p and 4p in 82% yield with a 10:1 ratio
(entry 2). The reaction of tert-butyl allene 1q afforded 3q
and 4q in 70% combined yield without regioselectivity
(entry 3). A related pair of cyclooctanylidene allenes 1l and
1r showed similar behaviors where both trimethylsilyl and
tert-butyl groups efficiently controlled the regioselectivity,
providing 3l/4l and 3r/4r in 78 and 80% yield with 25:1 and
more reactive than simple alkene functionality toward nitro-
gen dioxyl. Other silyl allenes 1iꢀk containing oxygen-based
functional groups such as ketal or silyl ether moiety afforded
expected products 2iꢀk in 93, 96, and 83% yield (entries
7ꢀ9). Only when two alkyl substituents on the allene are
substantially different in size did the E/Z ratio increase to
around 1.7ꢀ2:1 (entries 5 and 7) compared to 1:1, otherwise.
Even though cyclooctanylidene allene 1l containing
trimethylsilyl substituent decomposed (entry 10), cyclo-
hexanylidene allene 1m and 1n substituted with triethysilyl
3956
Org. Lett., Vol. 15, No. 15, 2013

Table 4. Conversion of R-Nitro R,β-Unsaturated Silyl Oximes
to Isooxazolidinones
Scheme 2. Plausible Mechanism for the Formation of R-Nitro
R,β-Unsaturated Silyl Oximes
not hydrolyzed, preserving the nitro group. The desily-
lation of 2j was chemoselective such that even a primary
silyl ether moiety in 2j was untouched while the silyl
ether of oxime moiety was desilylated and participated
in subsequent Michael reaction (entry 5).
A plausible reaction mechanism for the formation of 2
and 3/4 are depicted in Scheme 2.9ꢀ11 The given reagents
combinations would generate nitrogen dioxyl, which then
react with silyl allene 1 to generate allylic radical 6.12 In the
case with NaNO2/AcOH, 6 reacts with nitroxyl, resulting
in the formation of 7,13 which then undergoes tautomer-
ization to provide observed product 2. On the other hand,
a Isolated yields. b A 1:1 mixture with 1-phenylheptan-1-one.
20:1 ratio, respectively (entries 4 and 5). Cycloheptanyli-
dene allene 1s also afforded a mixture of 3s and 4s in 79%
yield with 20:1 selectivity (entry 6). Carvone-derived cy-
clopropane-containing silyl allene 1t resulted in 64% yield
of only the cyclopropane ring-opened product 4t in a 2:1
ratio (entry 8).
Next, we examined the behavior of functionalized nitro-
alkenes 2 by treating them with desilylating agent (Table 4).
Upon treatment of 2 with TBAF, novel isooxazolidinone
derivatives 5 were obtained in moderate yields, which is the
consequence of a spontaneous Nef reaction initiated by
5-endo-dig Michael addition of the oxime oxygen onto the
electron-deficient nitroalkene moiety.8 In the case of 5i
(dr = 1.7:1), the nitronate intermediate, however, was
under the conditions with Fe(NO3)3 9H2O/FeCl3, inter-
3
mediate radical 6 would react with ferric chloride either
directly or indirectly via an electron-transfer process to
form ion pair 8 followed by chloride transfer to give 4 or 3
depending on the substituents on 8.
In summary, we have developed efficient nitration of
of trisubstituted silyl allenes: with NaNO2/AcOH, a new class
of nitroalkene, R-nitro-R,β-unsaturated silyl oximes were
synthesized, and with Fe(NO3)3 9H2O/FeCl3, allylic chloro-
3
substituted nitroalkene were generated. Another novel class
of compound isooxazolidinones were obtained upon treating
the initially formed R-nitro-R,β-unsaturated silyl oximes with
TBAF. This unprecedented nitration of silyl allenes clearly
demonstrated their unusual reactivity toward radicals, which
might be further exploited in other types of radical-based
transformations.
(8) A review on the Nef reaction: Ballini, R.; Petrini, M. Tetrahedron
2004, 60, 1017.
(9) (a) Burkhard, C. A.; Brown, J. F., Jr. J. Am. Chem. Soc. 1964, 86,
2235. (b) Hwu, J. R.; Chen, K.-L.; Ananthan, S.; Patel, H. V. Organo-
metallics 1996, 15, 499.
(10) Shuker, D. E. G. In Nitrasamines: Toxicology and Microbiology;
Hill, M. J., Ed.; Ellis Horwood: Chichester, 1988; pp 49ꢀ50.
(11) (a) Ashmore, P. G.; Tyler, B. J. J. Chem. Soc. 1961, 1017. (b)
Asquith, P. L.; Tyler, B. J. J. Chem. Soc. 1970, 744. (c) Ignarro, L. J.
Nitric Oxide: Biology and Pathobiology; Academic Press: New York, 2000;
Chapter 3, pp 41ꢀ55.
Acknowledgment. We are grateful for financial support
from the National Science Foundation (CHE 0955972).
We thank Mr. Furong Sun of the University of Illinois at
UrbanaꢀChampaign for high-resolution mass spectrome-
try data.
(12) (a) Pryor, W. A.; Lightsey, J. W.; Church, D. F. J. Am. Chem.
Soc. 1982, 104, 6685. (b) Giamalva, D. H.; Kenion, G. G.; Church, D. F.;
Pryor, W. A. J. Am. Chem. Soc. 1987, 109, 7059.
(13) The proposed sequence of events are assumed to be controlled by
electronic factors of the reacting counterparts; the electro-rich silyl allene
reacts faster with more electron-deficient nitrogen dioxyl over nitroxyl, which
is further supported by the lack of reactivity of electron-deficient allene 1e0.
Supporting Information Available. Experimental pro-
cedures and spectroscopic data for all new compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
The authors declare no competing financial interest.
Org. Lett., Vol. 15, No. 15, 2013
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