A practical access to acyl radicals from acyl hydrazides

Article abstract of DOI:10.1039/b210764c

Various acyl radicals can be generated from the corresponding acyl triphenylmethyldiazo derivatives, produced by in situ oxidation of hydrazide precursors with phenylseleninic acid.

Full text of DOI:10.1039/b210764c

A practical access to acyl radicals from acyl hydrazides
Sophie Bath, Nieves M. Laso, Heraclio Lopez-Ruiz, Béatrice Quiclet-Sire and Samir Z. Zard*
Laboratoire de Synthèse Organique associé au CNRS, Ecole Polytechnique, 91128 Palaiseau, France.
E-mail: zard@poly.polytechnique.fr; Fax: +33 1 6933 4872; Tel: +33 1 6933 4872
Received (in Cambridge, UK) 5th November 2002, Accepted 27th November 2002
First published as an Advance Article on the web 10th December 2002
Various acyl radicals can be generated from the correspond-
ing acyl triphenylmethyldiazo derivatives, produced by in
situ oxidation of hydrazide precursors with phenylseleninic
acid.
Portion-wise addition of phenylseleninic acid (0.5 mol equiv.)
to a refluxing solution of 1a and diphenyl diselenide (0.2 mol
equiv.) in toluene (concentration in hydrazide: 0.027 M)
provided the expected cyclic ketone 5a in 66% yield (Table 1).
The phenylseleninic acid oxidant must be added slowly, over
4–6 hours, to avoid a build up in the concentration of diphenyl
diselenide and therefore increasing the chances of untoward
capture of the acyl radical to give the corresponding acyl
selenide.†
Under similar experimental conditions, a number of other
cyclic ketones were prepared by this route, as shown by the
examples compiled in Table 1. The internal olefinic trap may be
varied and nitrogen or sulfur atoms may be included in the
substrate. Furthermore, the process is successful starting from
both aromatic and aliphatic carboxylic acids. The triphenyl
radical generated upon thermolysis of the diazo intermediate is
captured by the diphenyl diselenide to give non-polar, easily
separated co-products.
In the case where the loss of carbon monoxide from the
intermediate acyl radical is especially favoured, then an overall
decarboxylative phenylselenylation is observed. This is illus-
trated by the conversion of phenylacetyl derivative 1g into
benzyl phenyl selenide 7 in 78% yield (Scheme 2).
We also found that this approach could be used to make
alkoxycarbonyl radicals from alcohols by starting with the
corresponding chloroformate or oxalyl ester chloride (Scheme
2). In the latter case, the alkoxycarbonyl radical is formed upon
extrusion of a molecule of carbon monoxide. Depending on the
structure of the substrate, the alkoxycarbonyl radical may be
captured to give a lactone, as shown by the transformation of
hydrazide 1i into lactone 8 in 45% yield. Alternatively, loss of
carbon dioxide may be fast when it leads to a stabilised radical,7
A few years before his landmark work on the triphenylmethyl
radical, Gomberg, working under the supervision of Victor
Meyer,1 prepared tetraphenylmethane by thermally decompos-
ing phenylazotriphenylmethane (PAT). Unbeknown to him at
the time, this reaction also involved triphenylmethyl radicals.
Since the pioneering studies of Victor Meyer and his school, azo
derivatives have found extensive application as initiators for
many of the classical radical processes.2 Surprisingly, however,
the use of azo derivatives as stoichiometric precursors of
radicals has not been often exploited for preparative purposes.
Some scattered examples can be found in the literature, the most
synthetically interesting arising from the group of Baldwin.3 In
the present communication, we describe a practical approach to
acyl radicals,4 hinging on the thermal decomposition of acyl
azotriphenylmethane derivatives.5
The reasoning underlying our work is outlined in Scheme 1.
Oxidation of the hydrazide precursor 1 using phenylseleninic
acid leads to the desired azo derivative 2 and to the
corresponding amount of diphenyl diselenide.6 If this oxidation
is carried out at or above the decomposition temperature of the
azo compound, an acyl radical 3 is generated that can undergo
ring closure to a suitably located internal olefin. The resulting
carbon centred radical 4 is then rapidly captured by the highly
radicophilic diphenyl diselenide giving finally derivative 5.
Only a small amount of diphenyl diselenide needs to be added
at the beginning of the reaction to ensure a sufficient initial
concentration of the trap. One obvious pitfall is the premature
capture of the acyl radical by the diselenide leading to the
undesired acyl selenide 6.
Table 1 Generation and capture of acyl radicals
Triphenylmethylhydrazide 1a was easily prepared from O-
allyl salicylic acid chloride and triphenylmethylhydrazine.
Hydrazide 1
Cyclic ketone 5 (yield %)
Scheme 1
204
CHEM. COMMUN., 2003, 204–205
This journal is © The Royal Society of Chemistry 2003

Notes and references
† Typical experimental procedure: a solution of tritylhydrazide (1c, 135 mg,
0.3 mmol) and diphenyl diselenide (19 mg, 0.06 mmol) in 10 ml of dry
toluene was refluxed for 10 minutes under an inert atmosphere. Solid
phenylseleninic anhydride (54 mg, 0.15 mmol) was added in small portions
every 15 min over a period of 4 h. The reaction mixture was allowed to cool
and the solvent removed under reduced pressure. Chromatography of the
residue on silica gel using a pentane–dichloromethane gradient afforded
pure thiochromanone 5c in 74%; dH (250 MHz; CDCl3) 7.55 (m, 2H),
7.4–7.1 (m, 7H), 3.50 (dd, 1H, J = 12 Hz; JA = 3.6 Hz), 3.46–3.26 (m, 2H),
3.16–2.94 (m, 2H); dC (62.5 MHz; CDCl3) 194.9, 141.9, 133.4, 133.1,
129.8, 129.4, 127.5, 125.1, 47.5, 30.9, 27.0; umax (film)/cm21 1672;
MS(EI): 334 [M]+, 256 [M 2 Ph]+, 177 [M 2 SePh]+; HRMS: found
333.9891 ([M]+); C16H14OSSe requires 333.9930.
1 J. M. McBride, Tetrahedron, 1974, 30, 2009 and references there
cited.
2 P. S. Engel, Chem. Rev., 1980, 80, 99.
3 (a) J. E. Baldwin, J. C. Bottaro, J. N. Kolhe and R. M. Adlington, J.
Chem. Soc., Chem. Commun., 1984, 22; (b) J. E. Baldwin, R. M.
Adlington, J. C. Bottaro, A. U. Jain, J. N. Kolhe, M. W. D. Perry and I.
M. Newington, J. Chem. Soc., Chem. Commun., 1984, 1095; (c) J. E.
Baldwin, R. M. Adlington and I. M. Newington, J. Chem. Soc., Chem.
Commun., 1986, 176; (d) J. E. Baldwin, R. M. Adlington, J. C. Bottaro,
J. N. Kolhe, I. M. Newington and M. W. D. Perry, Tetrahedron, 1986, 42,
4235; (e) G. Bouhadir, N. Legrand, B. Quiclet-Sire and S. Z. Zard,
Tetrahedron Lett., 1999, 40, 277; (f) S. H. Thang, Y. K. Chong, R. T. A
Mayadunne, G. Moad and E. Rizzardo, Tetrahedron Lett., 1999, 40,
2435.
Scheme 2
and this is then captured by the diselenide. This variant is
illustrated by the formation of benzyl phenyl selenide 7 in 73%
yield from 1h.
4 C. Chatgilialoglu, D. Crich, M. Komatsu and I. Ryu, Chem. Rev. , 1999,
99, 1991 and references there cited.
This approach to acyl radicals allies simplicity with the use of
readily available substrates and reagents. None of the yields has
been optimised and room for improvement certainly exists. One
interesting feature of this approach to cyclic ketones and
lactones is that the phenylselenide group ends up b- to the
carbonyl group; it is therefore easily eliminated with base or via
the selenoxide to provide the corresponding unsaturated
derivatives. This is a distinct advantage in comparison to
stannane based methods for generating acyl radicals (starting
usually from acyl selenides), where the last propagation step is
a hydrogen atom transfer.
5 (a) D. H. R. Barton, D. Crich, A. Lobberding and S. Z. Zard, Tetrahedron,
1986, 42, 2329; (b) D. H. R. Barton and S W. McCombie, J. Chem. Soc.,
Perkin Trans. 1, 1975, 1574; (c) D. E. Zabel and W. S. Trahanovsky, J.
Org. Chem., 1972, 37, 2413.
6 (a) D. H. R. Barton, D. J. Lester and S. V. Ley, J. Chem. Soc., Perkin
Trans. 1, 1980, 1212; (b) D. H. R. Barton, X. Lusinchi and J. Sandoval
Ramirez, Tetrahedron Lett., 1983, 24, 2995 (Bull. Soc. Chim. Fr., 1985,
849); (c) T. G. Back, S. Collins and R. G. Kerr, J. Org. Chem., 1981, 46,
1564; (d) T. G. Back, S. Collins and M. V. Krishna, Can. J. Chem., 1987,
65, 38.
7 P. A. Simakov, F. N. Martinez, J. H. Horner and M. Newcomb, J. Org.
Chem., 1998, 63, 1226.
CHEM. COMMUN., 2003, 204–205
205