Functional transformation of aldehydes and ketones via homolytic induced decomposition of unsaturated peroxy acetals and peroxy ketals

Article abstract of DOI:10.1039/a808418a

Induced decomposition of unsaturated peroxy acetals prepared from trimethyl orthoformate, dodecanal or 2-methyl-undecanal and 2,3-dimethyl-2-hydroperoxybut-3-ene, in the presence of ethyl iodoacetate, CC1₄ or dodecanethiol, allowed respectively their iodo-, chloro- and hydro-decarbonylation with yields of over 70%; the same reaction applied to the monoperoxy ketal or diperoxy ketal of cyclohexanone in the presence of ethyl iodoacetate resulted in its functional transformation in methyl 6-iodohexanoate or 1,5-diiodopentane with respective yields of 65 and 40%.

Full text of DOI:10.1039/a808418a

Functional transformation of aldehydes and ketones via homolytic induced
decomposition of unsaturated peroxy acetals and peroxy ketals
L. Moutet, D. Bonafoux, M. Degueil-Castaing and B. Maillard*
Laboratoire de Chimie Organique et Organométallique, associé au CNRS UMR 5802, Université Bordeaux 1,
F-33405 Talence-Cedex, France. E-mail: b.maillard@lcoo.u-bordeaux.fr
Received (in Cambridge, UK) 30th October 1998, Accepted 23rd November 1998
Induced decomposition of unsaturated peroxy acetals pre-
pared from trimethyl orthoformate, dodecanal or 2-methyl-
undecanal and 2,3-dimethyl-2-hydroperoxybut-3-ene, in the
presence of ethyl iodoacetate, CCl4 or dodecanethiol,
allowed respectively their iodo-, chloro- and hydro-
decarbonylation with yields of over 70%; the same reaction
applied to the monoperoxy ketal or diperoxy ketal of
cyclohexanone in the presence of ethyl iodoacetate resulted
in its functional transformation in methyl 6-iodohexanoate
or 1,5-diiodopentane with respective yields of 65 and 40%.
scribed,7 we decided to approach these transformations using
the induced decomposition of unsaturated peroxy acetals.
Indeed, applying the type of methodology that we have just
described (Scheme 1, path B, RA = H), it appeared possible to
generate an alkyl iodide from the aldehyde, as it could be
obtained from the hemiacetal via Suarez’s method.8
The decomposition of benzoyl peroxide in a cyclohexane
solution of peroxy acetal, obtained from dodecanal, in the
presence of a stoichiometric amount of ethyl iodoacetate
(relative ratios 0.1:5:1:1.1) afforded the desired 1-iodoundecane
(Scheme 1, path B, R = C11H23, RA = H) in a 60% yield. In
order to check the general character of this reaction, ethyl
iodoacetate was replaced by CCl4: 1-chloroundecane was
obtained but with a much lower yield than the corresponding
iodide, even when operating in neat perhalogeno solvent (25%).
Moreover, in addition to the expected epoxide 2 (Z = CCl3), the
formation of epoxide 1 (R = C11H23) with a 46% yield was
observed, showing that competition occurred for the alkyl
radical between chlorine atom abstraction and addition to the
activated double bond of the peroxy acetal. Thus, in order to
achieve an effective decarbonylative functionalization of the
aldehyde, it appears that the double bond of the peroxy acetal
should not be too reactive towards the produced alkyl radical,
but very reactive towards the radical Z·, formed in the atom
transfer with ZX.
Allylic hydroperoxides, possessing a terminal double bond
with no electron-withdrawing substituent on it, appeared to be
attractive candidates as starting materials for the synthesis of the
desired unsaturated peroxy acetals. The easy preparation of
allylic hydroperoxides by reaction of singlet oxygen with
alkenes9 prompted us to test the ones produced from the
photooxygenation of 2,3-dimethylbut-2-ene (2,3-dimethyl-
2-hydro-peroxybut-3-ene), 2-methylbut-2-ene (a mixture of
2-methyl-2-hydroperoxybut-3-ene and 3-methyl-2-hydro-
peroxybut-3-ene) and 6,7,7-trimethylbicyclo[3.1.1]hept-5-ene
(7,7-dimethyl-5-hydroperoxy-6-methylenebicyclo[3.1.1]hep-
tane). The thermolysis of benzoyl peroxide in mixtures of the
corresponding peroxy acetals of dodecanal and CCl4 (relative
molar ratios: 0.1:1:5) afforded the 1-chloroundecane in 72, 62
and 42% yield, respectively. These results led us to replace ethyl
2-(1-hydroperoxyethyl)propenoate with 2,3-dimethyl-2-hydro-
peroxybut-3-ene. The general method for achieving dec-
arbonylative functionalization of the aldehyde is summarized in
Scheme 2.
In the last decades, reactions involving free radicals have been
increasingly used1 in synthesis for the creation of carbon–
carbon and carbon–heteroatom bonds. Another important field
of interest for free radical reactions is the functional transforma-
tions one, pioneered by Barton and his group2 with the
development of the chemistry related to O-acyl thiohydrox-
amates. This allows the reductive decarboxylation of an acid or
its decarboxylative transformation into a halide, sulfone, nitrile,
alcohol etc. This methodology is based on a free radical chain
reaction, in which the decarboxylation step is the classical
generation of an alkyl radical from an acyloxy one.
In the last few years, our attention turned to the reactivity of
unsaturated peroxy acetals and peroxy ketals, via polymer
chemistry,3 since it was shown that their corresponding alkoxy
radicals undergo a very rapid b-scission reaction4 to generate an
alkyl radical. Thus, the homolytic induced decomposition of
unsaturated peroxy acetals and peroxy ketals, derived from the
ethyl 2-(1-hydroperoxyethyl)propenoate, was applied for the
preparation of glycidic esters5 (Scheme 1, path A). As this
method of producing glycidic esters requires the preparation of
a specific unsaturated peroxy derivative for each application,
we developed a more general method6 using ethyl 2-[1-(1-
methoxy-1-methylethylperoxy)ethyl]propenoate (Scheme 1,
path B, R = RA = Me). In the light of these results and taking
into account the fact that no general method for the de-
carbonylative functionalization of aldehydes has been de-
CO2Et
R′
OOCOMe
R
CO2Et
•
R′
OOCOMe
R
R•
+
R
–
EtO2C
O
R
Having determined the appropriate nature of the unsaturated
peroxide, it was necessary to optimize the temperature of the
reaction. Indeed, in addition to the expected 1-chloroundecane,
methyl dodecanoate was obtained (with a yield of about 5%
relative to the peroxy ketal). The formation of this compound
could be attributed to the disproportionation, in the solvent
cage, of the oxyl radicals formed by the spontaneous decom-
position of the unsaturated peroxy acetal.10 Performing the
same reaction at room temperature with initiation by BEt3–O2 (a
BEt3 solution in hexane was added slowly to the mixture of the
other reactants prepared under air, the needle of the syringe
being in the liquid) confirmed this origin since no methyl
dodecanoate was detected under these conditions and 1-chloro-
Path A
R′
1
R• + R′CO2Me
•OCOMe
R
EtO2C
Path B
O
–
R
+ZI
–RI
2
CO2Et
+
R′
CO2Et
•
R′
OOCOMe
R
Z•
OOCOMe
R
Z
Scheme 1
Chem. Commun., 1999, 139–140
139

RC(O)H
i,ii
Z•
TsOH, since the reaction of the hydroperoxide with the
corresponding acetal leads to a mixture of monoperoxy ketal
and diperoxy ketal. The addition of BEt3 to a non-degassed
solution of ethyl iodoacetate and 1-(1,1,2-trimethylprop-2-en-
ylperoxy)-1-methoxycyclohexane in cyclohexane, under the
conditions previously described, afforded the desired methyl
6-iodohexanoate (65%) (Scheme 3, Y = Me). The homolytic
induced decomposition of cyclohexanone diperoxy ketal,
obtained from the corresponding acetal, under the same
conditions, but using 2.2 equiv. of ethyl iodoacetate, produced
OOCHOMe
R
RX
+
Z
OOCHOMe
R
•
+ZX
O
Z
R•
+
HCO2Me
•OCHOMe
R
+
Scheme 2 Reagents and conditions: i, HC(OMe)3, TsOH; ii, 2,3-dimethyl-
2-hydroperoxybut-3-ene, TsOH.
1,5-diiodopentane in
a
40% yield (Scheme 3,
Y
=
CH2NCMeCMe2O).
In conclusion, homolytic induced decomposition of un-
saturated peroxy acetals and mono- and di-peroxyketals appears
to be a promising way of achieving decarbonylative functional-
ization of aldehydes and deacylative functionalization of
ketones. The search for new X–Z molecules able to generate
other useful transformations is in progress in our laboratory.
undecane was obtained with a yield of 86% relative to the
starting aldehyde. The iododecarbonylation of dodecanal re-
alized using the same conditions (ethyl iodoacetate–peroxy-
acetal–cyclohexane: 1.1:1:5; BEt3–O2; room temperature) led
to 1-iodoundecane with a yield of 75% relative to aldehyde.
The halodecarbonylation of 2-methylundecanal confirmed
the general character of this approach since 2-chloroundecane
and 2-iodoundecane were also isolated with yields of about
75%.11 Peroxy acetals formed from aldehydes bearing a tertiary
alkyl group have not been studied as a consequence of their
lower stability.12 Moreover, since the decarbonylation of the
corresponding acyl radical is a much faster process13 than that
for the one bearing primary and secondary alkyl groups, there is
less synthetic need for the setting of such a reaction.
Notes and references
1 B. Giese, Free Radicals in Organic Synthesis: Formation of Carbon-
Carbon Bonds, Pergamon Press, New York, 1986; M. Ramaiah,
Tetrahedron, 1987, 43, 3541; D. P. Curran, Synthesis, 1988, 417 and
489; C. P Jasperse, D. P. Curran and J. L. Feuig, Chem. Rev., 1991, 91,
1237; D. P. Curran, in Comprehensive Organic Synthesis, ed. B. M.
Trost and I. Fleming, Pergamon, Oxford, 1991, vol. 4.
2 D. Crich, Aldrichim. Acta, 1987, 20, 35; D. Crich and L. Quintero,
Chem. Rev., 1989, 89, 1413; D. H. R. Barton, Tetrahedron, 1992, 48,
2529; W. B. Motherwell and D. Crich, Free Radical Chain Reactions in
Organic Synthesis, Academic Press, London, 1992.
3 L. L. T. Vertommen, J. Meijer and B. Maillard, Int. Pat., 1992, WO
92/0953.
4 M. Degueil-Castaing and B. Maillard, unpublished results.
5 D. Colombani and B. Maillard, J. Chem. Soc., Chem. Commun., 1994,
1259; J. Org. Chem.,1994, 59, 4765.
6 F. Ramon, M. Degueil-Castaing and B. Maillard, J. Org. Chem., 1996,
61, 2071.
7 Comprehensive Organic Functional Groups Transformation, ed. A. R.
Katritsky, O. Meth-Cohn and C. W. Rees, Pergamon, 1995.
8 P. Armas, C. G. Francisco and E. Suarez, Angew. Chem., Int. Ed. Engl.,
1992, 31, 772; P. Armas, C. G. Francisco, E. Suarez, J. Am. Chem. Soc.,
1993, 115, 8865.
In order to identify possible extensions of this induced
decomposition of unsaturated peroxy acetals we decided, on the
first hand, to perform the same reaction with both aldehyde
derivatives, replacing ethyl iodoacetate by dodecanethiol to
achieve the reductive decarbonylations. In each case, undecane
was obtained with a yield of about 75%. Thus, this reaction
appears to be an attractive alternative, under less drastic
conditions, to the direct one designed from the aldehyde by
Berman et al.14
On the other hand, the efficiency of this reaction prompted us
to check a possible extension of this methodology to ketones.
We therefore tried to achieve the iododeacylation of cyclo-
hexanone. The peroxy ketal was prepared by addition of the
hydroperoxide to 1-methoxycyclohexene, with acid catalysis by
9 A. P. Schaap, Singlet Molecular Oxygen, Benchmark Papers in Organic
Chemistry Series, vol. 5, Dowden, Hutchinson and Ross, Stroudsburg,
1976; H. H. Wasserman, R. W. Murray, Singlet Oxygen, Academic
Press, New York, 1979; A. A. Frimer, Singlet Oxygen, CRC Press, Boca
Raton, 1985, vol. 2,.
O
O
O
Y
•O
O
Y
EtO2CCH2
+
10 C. Helgorsky, A. Saux, M. Degueil-Castaing and B. Maillard,
Tetrahedron, 1996, 52, 8263 and cited references.
•
EtO2CCH2
+
O
11 Reaction of the aldehyde with trimethyl orthoformate in presence of
TsOH yielded, after elimination of methyl formate and excess
orthoformate, the raw acetal. Addition of 2,3-dimethyl-2-hydro-
peroxybut-3-ene (ref. 6) to the acetal, with continuous distillation of
MeOH under vacuum (ref. 5), produced the peroxy acetal. After
elimination of TsOH by washing the ethereal solution with sodium
carbonate and water, followed by drying over magnesium sulfate, the
solvent was removed under vacuum. BEt3 in hexane was added to a
solution of the peroxy acetal and the required atom transfer agent in the
reaction solvent (cyclohexane, CHCl3 or CCl4) until total disappearance
of the peroxy acetal as determined by 1H NMR spectroscopy. After
elimination of the solvent and the low boiling reaction products, the
expected product was separated by column chromatography (SiO2).
12 C. Helgorsky, M. Bevilacqua, M. Degueil-Castaing and B. Maillard,
Thermochim. Acta, 1996, 289, 55.
O
O
Y
O
O
Y
EtO2CCH2I
I
•
+
•
EtO2CCH2
When
Y =
O
O
O•
EtO2CCH2
I
I
I
•
CO2
+
+
O
EtO2CCH2I
13 C. Chatgilialoglu, C. Ferreri, M. Lucarini, P. Pedrielli and G. F. Pedulli,
Organometallics, 1995, 14, 2672.
I
14 J. D. Berman, J. H. Stanley, W. V. Sherman and S. G. Cohen, J. Am.
Chem. Soc., 1963, 85, 4010.
Scheme 3
Communication 8/08418A
140
Chem. Commun., 1999, 139–140