A novel CAN-mediated oxidative rearrangement of monoterpenes

Article abstract of DOI:10.1016/S0040-4039(02)02103-2

A facile CAN-mediated oxidative rearrangement of monoterpenes of the pinene family to afford bisamides and ether derivatives is described.

Full text of DOI:10.1016/S0040-4039(02)02103-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 8971–8974
A novel CAN-mediated oxidative rearrangement of
monoterpenes†
Vijay Nair,a,* Roshini Rajan,a Lakshmi Balagopal,a Siji Thomasa and K. Narasimlub
aOrganic Chemistry Division, Regional Research Laboratory (CSIR), Trivandrum 695 019, India
bIndian Institute of Chemical Technology (CSIR), Hyderabad 500 007, India
Received 13 May 2002; revised 13 September 2002; accepted 25 September 2002
Abstract—A facile CAN-mediated oxidative rearrangement of monoterpenes of the pinene family to afford bisamides and ether
derivatives is described. © 2002 Elsevier Science Ltd. All rights reserved.
As a consequence of the ever increasing applications of
radical methodology in organic synthesis, one electron
oxidants such as cerium(IV) ammonium nitrate (CAN)
have attracted considerable attention.1 Our investiga-
tions have uncovered a number of novel carbonꢀcarbon
and carbonꢀheteroatom bond forming reactions medi-
ated by CAN.2 In this context, we were interested in
probing the reactivity of CAN towards monoterpenes
such as the pinenes. Although the chemistry of pinenes
is well studied,3 work still continues in this area because
of their propensity to undergo skeletal rearrangements
via multiple pathways.4 These rearrangements deliver
menthane, bornane or fenchane derivatives of value
depending on the conditions employed for the
reaction.5
The bisamide 2 was characterized on the basis of
1
spectroscopic data. In its H NMR spectrum, the five
methyl groups gave sharp singlets at l 1.16, 1.29, 1.68,
1.90 and 1.97, the latter two corresponding to the acetyl
groups. The olefinic proton was discernible as a broad
singlet at l 5.56. The -NH proton attached to the
quaternary carbon C-7 resonated as a broad singlet at l
5.35, while the -NH proton attached to C-5 resonated
as a doublet at l 5.77, supporting the strong IR absorp-
tion at 3285 cm−1. In the 13C NMR spectrum, the two
amide carbonyls were seen at l 169.29 and 169.71,
respectively. The relative disposition of the substituents
at C-1 and C-5 was confirmed to be trans from the
NOESY spectrum of 2. It is also noteworthy that the
bisamide 2, on base catalyzed hydrolysis, affords the
corresponding amine which is useful in the preparation
of linear polymers and whose derivatives as Schiff’s
bases are unusually stable.7 It may be mentioned that
the bisamide 2 has been prepared earlier by the Ritter
reaction of trans-sobrerol and a-pinene oxide in the
presence of conc. H2SO4.8
Our studies commenced by exposing (+)-a-pinene 1 to a
solution of CAN in acetonitrile; a remarkable transfor-
mation occurred culminating in the bisamide 2 in 72%
yield (Scheme 1).6
The facility with which 1 underwent the transformation
leading to 2 prompted us to examine its reactivity along
with that of related strained monoterpene derivatives
towards CAN in different solvents and our results are
summarized in Table 1.
A tentative mechanistic rationale for the formation of
the different products from (+)-a-pinene 1 is presented
in Scheme 2.
Scheme 1. Reagents and conditions: (i) CAN (2.3 equiv.),
CH3CN, rt, 3 h, 72%.
* Corresponding author. Tel.: 91-471-490406; fax: 91-471-491712;
e-mail: gvn@csrrltrd.ren.nic.in
It is conceivable that the initial event involves the single
electron oxidation of (+)-a-pinene 1 to furnish a radical
cation II which presumably transforms to its distonic
† This paper is dedicated with best wishes to Professor Dr Weldemar
Adam on the occasion of his 65th birthday.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)02103-2

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V. Nair et al. / Tetrahedron Letters 43 (2002) 8971–8974
Table 1. Oxidative rearrangements of monoterpenes induced by CAN
acyclic version IV. The cationic center in IV is
quenched by the solvent while the radical center is
further oxidized by CAN to afford the cation V which
is then neutralized by the solvent to afford the final
product VII. Alternatively, the cationic intermediate V
loses a proton affording the product VI.
in which the cyclobutane ring was left intact (Scheme
3).
The preparation of 13 from a-pinene has been previ-
ously reported by its reaction with iodosobenzenedi-
acetate and trimethylsilylazide,9 and also by a multistep
process involving an oximation and Beckmann
rearrangement.10
The formation of products 11 and 12 from b-pinene
oxide was found to occur with equal ease in the pres-
ence of Lewis acids such as BF3·OEt2. Hence the possi-
bility of CAN acting as a Lewis acid in this case cannot
be ruled out.
In conclusion, we have uncovered some novel and
useful CAN-mediated reactions of monoterpenes of the
pinene family which are of interest both from the
mechanistic and synthetic standpoints. It is worthy of
note that in view of the experimental simplicity and
mild reaction conditions, the present method offers a
Interestingly, when (+)-a-pinene 1 was treated with
NaN3 and CAN in methanol, it afforded the product 13

V. Nair et al. / Tetrahedron Letters 43 (2002) 8971–8974
8973
Scheme 2.
S. Tetrahedron 2000, 56, 2461–2467; (f) Nair, V.; Rajan,
R.; Rath, N. P. Org. Lett. 2002, 4, 1575–1577.
3. (a) Ranganthan, S.; Ranganathan, D.; Mehrotra, A. K.
Tetrahedron Lett. 1973, 2265–2266; (b) Tingoli, M.;
Tiecco, M.; Chianelli, D.; Balduci, R.; Temperini, A. J.
Org. Chem. 1991, 56, 6809–6813; (c) Deleris, G.; Kowal-
ski, J.; Dunogues, J.; Calas, R. Tetrahedron Lett. 1977,
4211–4214; (d) Wang, D.; Chan, T. H. Can. J. Chem.
1987, 65, 2727–2731; (e) Arnold, D. R.; Du, X. J. Am.
Chem. Soc. 1989, 111, 7666–7667; (f) Delpech, B.;
Khuong-Huu, Q. J. Org. Chem. 1978, 43, 4898–4900; (g)
Stevens, R. V.; Kenney, P. M. J. Chem. Soc., Chem.
Commun. 1983, 384–386; (h) Burgess, K.; Li, S.; Rebe-
spies, J. Tetrahedron Lett. 1997, 38, 1681–1684; (i) Lopez,
L.; Mele, G.; Fiandanese, V.; Cardellicchio, C.; Nacci, A.
Tetrahedron 1994, 50, 9097–9106.
Scheme 3. Reagents and conditions: (i) NaN3, CAN (2.3
equiv.), CH3OH, 0°C, 61%.
convenient alternative to the existing methods for the
preparation of mono- and bisamides of monoterpenes.
Since the products are important intermediates for a
variety of compounds, it is conceivable that these reac-
tions will find practical applications.
4. Valkanas, G.; Ikonomou, N. Helv. Chim. Acta 1963, 46,
1089–1096.
5. Valkanas, G. J. Org. Chem. 1976, 41, 1179–1183.
6. Typical experimental procedure: A solution of CAN (1.37
g, 2.5 mmol) in acetonitrile (10 mL) was added dropwise
to a solution of 1R-(+)-a-pinene 1 (136 mg, 1 mmol) in
acetonitrile (5 mL) at room temperature. The reaction
mixture was stirred at room temperature for 3 h. On
complete consumption of the starting material, the reac-
tion mixture was diluted with water (10 mL) and
extracted with chloroform (5×20 mL). The combined
organic extracts were washed with water, brine and dried
over anhydrous sodium sulfate. After the removal of the
solvent on a rotary evaporator, the residue was subjected
to column chromatography on silica gel. Elution using a
chloroform–methanol mixture (98:2) afforded 2 as a
white crystalline solid (181 mg, 72%). Mp: 214°C (lit.8a
mp: 212–213°C). IR (KBr) wmax: 3285, 3076, 2975, 2935,
2840, 1640, 1546, 1438, 1371, 1297, 1196, 1094, 1040, 933,
Acknowledgements
R.R., L.B.G. and S.T. thank the Council of Scientific
and Industrial Research, New Delhi, for research fel-
lowships. The authors also thank Ms. Soumini Mathew
for NMR data.
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8974
V. Nair et al. / Tetrahedron Letters 43 (2002) 8971–8974
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