A novel synthesis of α-azidocinnamates, α-azido-α,β-unsaturated ketones and β-azidostyrenes mediated by cerium(IV) ammonium nitrate

Article abstract of DOI:10.1016/S0040-4039(00)00350-6

Cerium(IV) ammonium nitrate mediated addition of azide to cinnamic esters, acids and α,β-unsaturated ketones, followed by reaction with sodium acetate afforded the α-azidocinnamates, β-azidostyrenes and α-azido-α,β- unsaturated ketones, respectively, in good yields. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)00350-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 3199–3201
A novel synthesis of α-azidocinnamates,
α-azido-α,β-unsaturated ketones and β-azidostyrenes mediated
by cerium(IV) ammonium nitrate
Vijay Nair ∗ and Tesmol G. George
Organic Chemistry Division, Regional Research Laboratory (CSIR), Trivandrum 695 019, India
Received 3 November 1999; revised 5 February 2000; accepted 28 February 2000
Abstract
Cerium(IV) ammonium nitrate mediated addition of azide to cinnamic esters, acids and α,β-unsaturated ketones,
followed by reaction with sodium acetate afforded the α-azidocinnamates, β-azidostyrenes and α-azido-α,β-
unsaturated ketones, respectively, in good yields. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: cerium(IV) ammonium nitrate; azides; radicals.
Cerium(IV) ammonium nitrate (CAN) has been widely used in carbon–carbon bond-forming
reactions.1–3 In addition, it has found important applications in carbon–hetero atom bond formation
also.4,5 As early as 1971, Trahanovsky and Robbins have reported the CAN-mediated addition of azide
to styrenes.6 Subsequent reports have involved the addition of azide radical to glycals7 and other enol
ethers8 and also to α-methoxy acrylonitrile.9 However, the oxidative addition of azide to α,β-unsaturated
carbonyl compounds like cinnamic esters and acids is hitherto unknown; inexplicably, previous attempts
have failed.6,8 With the premise that the reaction can give rise to α-azido-β-nitrato compounds that can
serve as precursors to biologically important α-amino-β-hydroxy acids or α-azidocinnamates that are
useful in the synthesis of indoles, azirines10 and isoquinolines,11 we have undertaken an investigation
of the reaction of azide with cinnamic acids and esters in the presence of CAN. Our preliminary results
indicating the usefulness of the process are presented here. The reported procedure for the synthesis of
α-azidocinnamates involves the condensation of aromatic aldehydes with ethyl azidoacetate in ethanolic
sodium ethoxide.12
Our initial experiment involved the reaction of ethylcinnamate and sodium azide with CAN resulting
in a 73% yield of the α-azido-β-nitrato ester 2 as a 1:1 mixture of syn- and anti-isomers (Scheme 1).
The crude product, on treatment with sodium acetate in dry acetone, afforded the α-azidocinnamate
1
3 in 68% yield (Scheme 2). The stereochemistry was assigned to be Z on the basis of the H NMR
spectrum.12
∗
Corresponding author. Fax: 91-471-491712; e-mail: gvn@csrrltrd.ren.nic.in (V. Nair)
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00350-6
tetl 16630

3200
Scheme 1.
Scheme 2.
The reaction was found to be of general application to other substituted cinnamic esters and also α,β-
unsaturated ketones (Table 1). Interestingly, when the experiment was conducted with cinnamic acid in-
stead of the ester, the resulting product underwent concomitant elimination of nitrate and CO2 to afford
the β-azidostyrene as a 1:1 mixture of E- and Z-isomers. This reaction also appears to be general (Table
2).
Table 1
Synthesis of α-azidocinnamates and α-azido-α,β-unsaturated ketones
The present work constitutes a novel and expeditious process for the synthesis of α-azidocinnamates,
α-azido-α,β-unsaturated ketones and β-azidostyrenes. In view of the experimental simplicity, the
process described is likely to emerge as the method of choice for the synthesis of these compounds
of proven versatility in heterocyclic synthesis.10,11 Further work is in progress.
Typical experimental procedure: To a deoxygenated solution of cinnamic ester 1 (176 mg, 1 mmol) and

3201
Table 2
Synthesis of β-azidostyrenes
NaN3 (98 mg, 1.5 mmol) in dry acetonitrile, a deoxygenated solution of CAN (1.370 g, 2.5 mmol) in the
same solvent (10 mL) was added dropwise at 0°C and stirred well. On completion of the reaction it was
worked up using CH2Cl2–water, dried and concentrated. The crude residue, on treatment with anhydrous
sodium acetate (123 mg, 1.5 mmol) in dry acetone (5 mL) followed by usual work up and purification by
silica gel column chromatography using hexane:ethyl acetate mixture (98:2) as eluent, afforded 3 (161
mg, 68%) as a pale yellow viscous liquid.
Compound 3:12 IR (film): 3069, 2119, 1707 cm−1; 1H NMR (300 MHz, CDCl3): δ 7.79 (m, 2H, ArH),
7.33 (m, 3H, ArH), 6.88 (s, 1H, olefinic), 4.35 (q, J=7.1 Hz, 2H, CH2), 1.39 (t, J=7.1 Hz, 3H, CH3).
Acknowledgements
T.G.G. thanks CSIR, New Delhi, for the award of research fellowship and Ms. Soumini Mathew for
NMR spectra.
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