On the [2,3] sigmatropic rearrangement of allylic nitro compounds

Article abstract of DOI:10.1021/ol051196g

(Chemical Equation Presented) Allylic nitro compounds undergo relatively clean [2,3] sigmatropic rearrangement upon heating in refluxing 1,2-dichlorobenzene in the presence of DABCO to give the corresponding allylic alcohols via the intermediate allylic n

Full text of DOI:10.1021/ol051196g

ORGANIC
LETTERS
2005
Vol. 7, No. 16
3489-3492
On the [2,3] Sigmatropic Rearrangement
of Allylic Nitro Compounds
Celia Alameda-Angulo, Be´atrice Quiclet-Sire, Elmar Schmidt, and Samir Z. Zard*
Laboratoire de Synthe`se Organique Associe´ au CNRS, Ecole Polytechnique,
91128 Palaiseau Cedex, France
zard@poly.polytechnique.fr
Received May 21, 2005
ABSTRACT
Allylic nitro compounds undergo relatively clean [2,3] sigmatropic rearrangement upon heating in refluxing 1,2-dichlorobenzene in the presence
of DABCO to give the corresponding allylic alcohols via the intermediate allylic nitrite.
Some years ago, we described the thermal conversion of
allylic nitro compounds 1 into the rearranged allylic alcohols
3.1 The reaction most probably proceeds through a [2,3]
sigmatropic rearrangement of the nitro group into the
corresponding nitrite 2, which then undergoes rapid hydroly-
sis to give allylic alcohol 3, as shown in Scheme 1. This
transformation would thus be related to the Mislow-Evans-
Braverman rearrangement of allylic sulfoxides and selenox-
ides,2 as well as the rearrangement allylic iodoxyl derivatives
and the Meisenheimer rearrangement of allylic tertiary amine
oxides.3
compounds, the yield hovers around 50-60%, rarely reach-
ing or exceeding 70%. It is even lower in the case of
secondary derivatives. Primary allylic nitro compounds are
not useful substrates since the temperature needed to induce
the transformation is much too high, and only extensive
decomposition is observed.
Initially, we thought that the problem was due to the
formation of nitrous acid by the three possible pathways
indicated in Scheme 2: (a) by hydrolysis of the intermediate
nitrite 2; (b) by the known syn elimination of the nitro group
from starting material 1 leading to dienes;5 and (c) by syn
elimination of the nitrite from 2 also leading to a diene.
Indeed, we had found variable quantities of dienes as side
products in some of the reactions. A further complication,
arising from partial homolytic decomposition of the nitrite
intermediate to give alkoxy radical 5 at the high temperatures
Scheme 1. Thermal Rearrangement of an Allylic Nitro Group
(2) For a review, see: Bru¨ckner, R. In ComprehensiVe Organic Synthesis;
Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 6, p 873.
(3) (a) Johnstone, R. A. W. In Mechanisms of Molecular Migrations;
Thyagarajan, B. S., Ed.; John Wiley & Sons: New York, 1969; Vol. 2, pp
249-266. (b) von Schickh, O.; Apel, G.; Padeken, H. G.; Scharz, H. H.;
Segnitz, A. In Houben-Weyl-Mu¨ller: Methoden der Organischen Chemie;
Thieme: Stuttgart, 1971, Vol. X/1. (c) Davies, S. G.; Fox, J. F.; Jones, S.;
Price, A. J.; Sanz, M. A.; Sellers, T. G. R.; Smith, A. D.; Teixeira, F. C. J.
Chem. Soc., Perkin Trans. 2002, 1, 1757 and references cited therein.
(4) For applications, see: (a) Barlaam, B.; Boivin, J.; El Kaim, L.; Zard,
S. Z. Tetrahedron Lett. 1991, 32, 623. (b) Boivin, J.; Barlaam, B.; El Kaim,
L.; Elton-Farr, S.; Zard, S. Z. Tetrahedron 1995, 51, 1675. (c) Dumez, E.;
Rodriguez, J.; Dulce`re, J.-P. Chem. Commun. 1999, 2009.
Despite its apparent simplicity and synthetic potential, this
new transformation of allylic nitro derivatives has not
attracted much attention from the synthetic community.4 One
of the reasons is the generally modest yield of allylic
alcohols. In the most favorable case of tertiary allylic nitro
(5) Chow, Y. L. In The Chemistry of Amino, Nitro, and Nitroso
Compounds and their DeriVatiVes; Patai, S., Ed.; Wiley-Interscience:
Hoboken, NJ, 1982; Suppl. F, Vol. 1, p 181.
(1) Boivin, J.; El Kaim, L.; Kervagoret, J.; Zard, S. Z J. Chem. Soc.,
Chem. Commun. 1989, 1006.
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(>150 °C) required for the rearrangement, was also a
Significant improvement was also observed in the case of
the open-chain derivative 1d, a substrate readily prepared
from hydrocinnamaldehyde by the sequence shown in
Scheme 3. The yield was 67%7 in the absence of DABCO
but increased to 87% in its presence. The most spectacular
improvement was observed with nitro-olefin 1e. This sub-
strate can be prepared in one step from 1-methyl-1-
nitrostyrene8 and was reported to rearrange into allylic
alcohol 3e in only 13% yield.4c In the presence of DABCO,
the yield of 3e was 47%, representing a nearly 4-fold
increase.
possibility (Scheme 2).6
Scheme 2. Side Reactions
Scheme 3. Examples of the Thermal Rearrangement
Attempts at improving the yield by addition of scavengers
for nitrous acid or additives that could react cleanly with
the nitrite were unfortunately not successful.1 The formation
of dienes could also arise by acid-catalyzed elimination of
water from the allylic alcohol or by acid-catalyzed elimina-
tion of nitrous acid from the intermediate nitrite. The silica
surface of the glass flask could become sufficiently acidic
at the high reaction temperature to cause these undesired
eliminations. Indeed, addition of glass wool to the reaction
medium increased significantly the amount of dienes in the
crude reaction mixtures.
To counteract the deleterious acidity of the silica on the
reaction outcome, we explored the effect of added base.
Various bases were screened, but no significant increase in
the yield of the allylic alcohol was observed in most cases.
In particular, we had high hopes for N,N-dimethylaniline,
which could act both as a weak base and as a scavenger for
nitrous acid and nitrogen oxides in general. Unfortunately,
our hopes did not materialize in practice. Some improvement
was found using proton sponge, but by far the best results
were obtained with DABCO. Indeed, as the following
examples will demonstrate, thermolysis in the presence of
DABCO of secondary and tertiary allylic nitro compounds
becomes a synthetically very useful process.
We had found that derivative 1a, obtained by a double
Henry reaction of 1-nitromethylcycloxenene with formalde-
hyde followed by protection as the isopropylidene ketal,
rearranged into alcohol 3a in 53% yield in the absence of
DABCO.1 When we repeated the experiment in the presence
of 1.5 equiv of DABCO, the yield jumped to 72%. The yield
was even higher with substrates 1b and 1c, which gave the
allylic alcohols 3b and 3c in 91 and 75% yields, respectively.
The beneficial effect of DABCO was also observed in the
case of secondary nitro derivative 1f. This compound was
prepared as essentially one diastereoisomer by Michael
addition of 1-nitromethylcyclohexene to chalcone and could
be rearranged into 3f in 68% yield. In the absence of
DABCO, the yield dropped to 42%. Interestingly, alcohol
3f was obtained as a single diastereoisomer (vide infra), the
relative stereochemistry of which was not determined.
The examples outlined in Scheme 4 further illustrate the
scope. These transformations start from commercially avail-
able 1-nitrocyclohexene, a compound exhibiting a remarkably
versatile chemistry.9 Thus, Henry addition to formaldehyde10
(7) Barlaam, B. The`se de Doctorat en Sciences, Universite´ Paris-Sud,
Orsay, France, 1992.
(8) Dumez, E.; Rodriguez, J.; Dulce`re, J.-P. J. Chem. Commun. 1997,
1831.
(9) (a) Corey, E. J.; Estreicher, H. J. Am. Chem. Soc. 1978, 100, 6294.
(b) Barrett, A. G. M.; Graboski, G. G. Chem. ReV. 1986, 86, 751.
(10) Ono, N.; Namamoto, I.; Kamimura, A.; Kaji, A.; Tamura, R.
Synthesis 1987, 258.
(6) Pyrolyses of simple nitrites are reported to proceed by way of alkoxyl
radicals: Batt, L. In The Chemistry of Amino, Nitroso and Nitro Compounds;
Pata¨ı, S., Ed.; Wiley: New York, 1982; Suppl. F, Chapter 12, p 417.
3490
Org. Lett., Vol. 7, No. 16, 2005

phenyl group also acted as a stereochemical marker in the
more complex structure 1l. This substrate was prepared from
nitroolefin 9, itself made from glutaraldehyde and ni-
tromethane by a short sequence devised by Seebach and co-
workers.11 The Michael addition to methyl vinyl ketone
proceeded in high yield and took place from the same side
as the phenyl group as determined by NMR (NOESY).
Thermolysis in the presence of DABCO in the usual manner
gave allylic alcohol 3l as the sole isomer in 84% yield,
confirming once again the suprafacial nature of the rear-
rangement. In the same fashion, allylic nitro derivative 1m
rearranged to give 3m, also as a single isomer. Interestingly,
in contrast to the case of 1l, the conjugate addition leading
to 1m occurred from the side opposite to the -OMOM
group. Because of the reversibility of the Michael addition,
both reactions are presumably under thermodynamic control
and result in the formation of the more stable diastereoisomer.
The synthetic utility of this rearrangement was further
confirmed by combining the rich chemistry of the nitro
group12 with an intermolecular radical addition mediated by
xanthates.13 As depicted in Scheme 6, lauroyl peroxide-
Scheme 4. Allylic Alcohols from 1-Nitrocyclohexene
and acetylation furnished allylic nitro derivative 1g, which
upon heating in o-dichlorobenzene gave rise to the expected
allylic alcohol 3g in 72% yield. Alternatively, Michael
addition to methyl vinyl ketone, methyl acrylate, and phenyl
vinyl sulfone provided precursors 1h, 1i, and 1j in generally
good yield. Thermolysis in o-dichlorobenzene furnished the
corresponding allylic alcohols 3h, 3i, and 3j in 73, 88, and
64% yields, respectively. Many of these compounds would
be tedious to make by traditional approaches. That the
Scheme 6. Stereoselective Synthesis of a Bicyclic Structure
Scheme 5. Stereochemical Aspects of the Rearrangement
induced addition of xanthate 11 to the diethyl acetal of
acrolein gave adduct 12 in 61% yield. The xanthate group
was reductively removed in 70% yield with tributylstannane
and the resulting ketone 13 subjected to condensation with
nitromethane. This Knoevenagel-type reaction, induced by
a catalytic amount of N,N-dimethylethylenediamine, provided
nitroolefin 14 in 65% yield. We had, many years ago,
demonstrated the efficiency of ethylenediamine and its
congeners as “organo-catalysts” for accomplishing difficult
rearrangement of the nitro group is indeed a suprafacial
process in the presence of DABCO was confirmed by the
transformation of 1k into 3k in 65% yield. Only the trans
isomer is formed, and this can be easily rationalized by the
transition structure 7, where the bulky phenyl group occupies
the expected equatorial position. In order for adequate orbital
overlap to take place, the incipient C-O bond has to form
from the axial position, leading to the observed isomer. A
(11) Seebach, D.; Calderari, G.; Knochel, P. Tetrahedron 1985, 41, 4861.
(12) (a) Ono, N. The Nitro Group in Organic Synthesis; Wiley-VCH:
New York, 2001. (b) Ballini, R.; Bosica, G.; Fiorini, D.; Palmieri, A.; Petrini,
M. Chem. ReV. 2005, 105, 933. (c) Rosini, G.; Ballini, R. Synthesis 1988,
833. (d) Seebach, D.; Colvin, E. W.; Lehr, F.; Weller, T. Chimia 1979, 33,
1.
(13) For a review, see: Zard, S. Z. Angew. Chem., Int. Ed. Engl. 1997,
36, 672; Angew. Chem. 1997, 109, 724.
Org. Lett., Vol. 7, No. 16, 2005
3491

condensations of nitromethane with hindered ketones.14 In
the present case, the condensation leads to a 3:2 mixture of
isomeric nitro derivatives, the major being the kinetic,
deconjugated isomer with the least substituted olefin. How-
ever, both gave the same Michael addition product 15 in
59% yield (82% based on recovered starting material) as a
6:4 mixture of diastereomers. The addition to methyl acrylate
had to be performed using triethylamine, since the more basic
DBU caused extensive formation of the double Michael
adduct.
The stage was now set to construct the second ring.
Hydrolysis of the acetal group was accomplished with
p-toluenesulfonic acid in wet THF to give the intermediate
aldehyde 16 in 59% yield, still as a 6:4 mixture of
diastereoisomers. Exposure of the mixture to DBU in
methanol induced diastereoselective ring-closure into bicyclic
derivative 1n in 60% yield after acetylation. Clearly, the
reversibility of the intramolecular Henry reaction ensures the
formation of the most stable isomer, whose relative stereo-
chemistry was determined by NMR (NOESY). Finally,
thermolysis in refluxing o-dichlorobenzene in the presence
of DABCO provided the expected allylic alcohol 3n in 56%
yield as the sole isomer, as would be expected from a
suprafacial process.
In summary, we now have in hand a practical, flexible
route to even complex allylic alcohols. The precursors are
readily prepared by exploiting the remarkable ability of the
nitro group to mediate C-C bond formation under very mild
conditions, through the Henry and Michael reactions. Allylic
alcohols are direct precursors of enones, and the correspond-
ing acetates or carbonates serve as substrates in numerous
transition-metal-catalyzed transformations.
Acknowledgment. We wish to thank Ecole Polytechnique
for a Bourse Monge (to C.A.-A.).
Supporting Information Available: Experimental pro-
cedures and detailed analytical data. This material is available
free of charge via the Internet at http://pubs.acs.org.
(14) Barton, D. H. R.; Motherwell, W. B.; Zard, S. Z. J. Chem. Soc.,
Chem. Commun. 1982, 551; Bull. Chim. Soc. Fr. 1983, 61. For further
examples of this procedure, see: Tamura, R.; Sato, M.; Oda, D. J. Org.
Chem. 1986, 53, 4368.
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