General metal-free baeyer-villiger-type synthesis of vinyl acetates

Article abstract of DOI:10.1021/ol401143q

Oxone, a cheap, stable, and nonhazardous oxidizing reagent, transforms α,β-unsaturated ketones of defined stereochemistry into their corresponding vinyl acetates through a Baeyer-Villiger reaction. This process is general and straightforward, tolerating a

Full text of DOI:10.1021/ol401143q

ORGANIC
LETTERS
XXXX
Vol. XX, No. XX
000–000
General Metal-Free BaeyerÀVilliger-Type
Synthesis of Vinyl Acetates
ꢀ
Belen Poladura, Angel Martınez-Castaneda, Humberto Rodrıguez-Solla,
ꢀ
Ricardo Llavona, Carmen Concellon,* and Vicente del Amo*
~
´
´
ꢀ
´
ꢀ
ꢀ
Departamento de Quımica Organica e Inorganica, Universidad de Oviedo,
ꢀ
´
C/Julian Claverıa 8, 33006, Oviedo, Spain
ccf@uniovi.es; vdelamo@uniovi.es
Received April 24, 2013
ABSTRACT
Oxone, a cheap, stable, and nonhazardous oxidizing reagent, transforms R,β-unsaturated ketones of defined stereochemistry into their corresponding
vinyl acetates through a BaeyerÀVilliger reaction. This process is general and straightforward, tolerating a wide range of functional groups.
Vinyl acetates are significant compounds forindustry, as
they are building blocks in the manufacturing of polymers
(polyvinyls). Although vinyl acetate itself is commercially
available, the preparation of other more elaborated deri-
vatives is a challenging synthetic task. Traditionally, this
family of compounds is accessed employing either of the
transition-metal-based methodologies available: the addi-
tion of carboxylic acids to terminal alkynes, catalyzed by
different ruthenium1 or rhenium complexes;2 the palladium-
catalyzed vinylation of organic halides;3 or the usage of
chromium carbene complexes.4 Such preparations imply
working with expensive and elaborated catalysts and lack
generality, with substituted vinyl acetate products being
rendered as undesired mixtures of (E)- and (Z)-isomers.
In this communication, we disclose a general transition-
metal-free synthesis of diastereopure vinyl acetates, prepared
by the BaeyerÀVilliger oxidation reaction5 of R,β-unsaturated
methylketones with Oxone (potassium monopersulfate triple
salt, KHSO5 1/2 KHSO4 1/2 K2SO4, Dupont registered
3
3
name).6
This work was not originally intended and resulted from
our long-term research program, where we explored the
chances of carrying out a facile multigram oxidation of
R,β-unsaturarted methylketones 1, to the corresponding
epoxides 2,7 with the latter to be tested as substrates for
our proline/guanidinium salt organocatalytic systems.8
Commercially available (E)-4-phenyl-3-buten-2-one, 1a,
was adopted as a model substrate and was reacted with a
range of standard oxidizing agents, at room temperature,
(1) (a) Ruppin, C.; Dixneuf, P. H. Tetrahedron Lett. 1986, 27, 6323.
(b) Opstal, T.; Verpoort, F. Synlett 2002, 935. (c) de Clercq, B.; Verpoort,
F. Tetrahedron Lett. 2001, 42, 8959. (d) Melis, K.; Samulkiewicz, P.;
Rynkowski, J.; Verpoort, F. Tetrahedron Lett. 2002, 43, 2713. (e) Opstal,
T.; Verpoort, F. Tetrahedron Lett. 2002, 43, 9259. (f) Melis, K.; Opstal,
T.; Verpoort, F. Eur. J. Org. Chem. 2002, 3779. (g) de Clercq, B.;
Verpoort, F. J. Organomet. Chem. 2003, 672, 11. (h) Opstal, T.; Verpoort,
F. Synlett 2003, 314. (i) Ye, S.; Leong, W. K. J. Organomet. Chem. 2006,
691, 1117. (j) Tan, S. T.; Fan, W. Y. Eur. J. Inorg. Chem. 2010, 4631.
(2) Hua, R.; Tian, X. J. Org. Chem. 2004, 69, 5782.
(6) For an up to date review on the applications of Oxone in organic
synthesis, see: (a) Hussain, H.; Green, I. R.; Ahmed, I. Chem. Rev. 2013,
113, 3329. For recent references regarding the use of Oxone in
BaeyerÀVilliger oxidation reactions of ketones, see: (b) Chrobok, A.
Tetrahedron 2010, 66, 6212. (c) Chrobok, A. Synlett 2011, 391. (d) Baj,
S.; Chrobok, A.; Siewniak, A. Appl. Catal. A: Gen. 2001, 395, 49.
(e) Wang, B.; Shen, Y. M.; Shi, Y. J. Org. Chem. 2006, 71, 9515.
(f) Narender, N.; Srinivasu, P.; Kulkarni, S. J.; Raghavan, K. V. Synth.
Commun. 2002, 32, 279.
(3) Ye, C.; Xiao, J.-C.; Twamley, B.; LaLonde, A. D.; Norton, M. G.;
Shreeve, J. M. Eur. J. Org. Chem. 2007, 5095.
(4) Soderberg, B. C.; Turbeville, M. J. Organometallics 1991, 10,
3951.
(7) Pouraldi, A. R. Mendeleev Commun. 2010, 20, 113.
~
(5) For recent, comprehensive reviews covering the traditional
BaeyerÀVilliger reaction of ketones, see: (a) Uyanik, M.; Ishihara, K.
ACS Catal. 2013, 3, 513. (b) Michelin, R. A.; Sgarbossa, P.; Scarso, A.;
Strukul, G. Coord. Chem. Rev. 2010, 254, 646. (c) Jimenez-Sanchidrian,
C.; Ruiz, J. R. Tetrahedron 2008, 64, 2011. (d) ten Brink, G.-J.; Arends, I.
W. C. E.; Sheldon, R. A. Chem. Rev. 2004, 104, 4105.
(8) (a) Martınez-Castaneda, A.; Poladura, B.; Rodrıguez-Solla, H.;
ꢀ
Concellon, C.; del Amo, V. Org. Lett. 2011, 13, 3032. (b) Martınez-
~
ꢀ
Castaneda, A.; Poladura, B.; Rodrıguez-Solla, H.; Concellon, C.; del
~
ꢀ
ꢀ
Amo, V. Chem.;Eur. J. 2012, 18, 5188. (c) Martınez-Castaneda, A.;
ꢀ
Rodrıguez-Solla, H.; Concellon, C.; del Amo, V. J. Org. Chem. 2012, 77,
10375.
r
10.1021/ol401143q
XXXX American Chemical Society

1
characterized as (E)-styryl acetate by H NMR spectro-
scopy, from comparison of the value of the 3JHÀH coupling
constants for the olefinic protons of this material with those
Table 1. Initial Screening of Reagents for the Oxidation
Reaction of R,β-Unsaturated Ketone 1aa
previously reported in the literature [(E)-isomer: 3Jtrans
12.8 Hz; (Z)-isomer: 3Jcis = 7.4 Hz].1h
=
Table 2. Screening of Reaction Conditions for the
Oxone-Promoted Oxidation of R,β-Unsaturated Ketone
1a to Vinyl Acetate 3aa
entry
oxidant
conversionb
conversionc
1
mCPBA
9
18
À
À
À
À
9
2
Ca(ClO)2
À
À
À
À
À
3
H2O2 urea
3
4d
5e
6
H2O2
t-BuOOH
Oxone
a General reaction conditions: R,β-unsaturated ketone 1a (1 equiv),
oxidant (1.3 equiv), in acetone (0.5 M), 24 h, at room temperature.
b Conversion percentage of ketone 1a to epoxide 2a, as determined
by 1H NMR spectroscopy on crude reaction mixtures. c Conversion
percentage of ketone 1a to acetate 3a, as determined by 1H NMR
spectroscopy on crude reaction mixtures. d H2O2 30% weight in water.
e t-BuOOH was used as a 5.0 M solution in decane.
equiv
entry
Oxone
solvent
acetone
conversionb
1
2
3
4
5
6
7
8
1.3
1.5
1.5
1.5
1.5
1.5
2
9
acetone
13
77
83
0
CH3CN/H2O (10:1)
DMF
CH2Cl2/H2O (10:1)
EtOH
c
À
employing acetone as solvent (Table 1). The reaction mix-
tures were worked up and analyzed by 1H NMR spectro-
scopy. m-Chloroperbenzoic acid (mCPBA) converted
ketone 1a to a mixture consisting of epoxide 2a (9%) and
the BaeyerÀVilliger oxidation product vinyl acetate 3a
(18%), amid a complex reaction mixture (Table 1, entry 1).
While Ca(ClO)2, H2O2, or t-BuOOH did not react with the
R,β-unsaturated ketone (Table 1, entries 2À5), Oxone
rendered the vinyl acetate 3a in low conversion, although
no side products were spotted in the reaction media
(Table 1, entry 6). In the interest of preparing configu-
rationally stable vinyl acetate products such as 3a, to our
knowledge, this BaeyerÀVilliger reaction of Oxone had no
precedents in the literature and was worth studying. It is
relevant to remark that Oxone is a crystalline solid oxidant,
easy to handle, nontoxic or hazardous, soluble in water,
and, above all, stable and cheap.9
To improve the Oxone-promoted oxidation of R,β-
unsaturated ketone 1a to its corresponding vinyl acetate
3a, outlined in Table 1, different reaction conditions were
explored (Table 2). Withacetone as the solvent, a rise in the
number of equivalents of the oxidant from 1.3 to 1.5 did
not improve the reaction significantly (Table 2, entries 1
and 2). Accordingly, the effect of using either of a collection
of organic solvents, all of them previously used in other
Oxone-promoted reactions, was investigated. The results
obtained for CH3CN/H2O and N,N-dimethylformamide
(DMF) were comparable in terms of crude conversion of
ketone 1a to acetate 3a (Table 2, entries 3 and 4). Alter-
natively, a mixture of CH2Cl2/H2O, or neat EtOH, was
observed to be inappropriate as solvents for this reaction
(Table 2, entries 5 and 6). Full conversion of ketone 1a
to styryl acetate 3a was obtained in 24 h, using DMF and
a 2-fold excess of Oxone, under heterogeneous reaction
conditions(Table 2, entry8). Product3a was unambiguosly
CH3CN/H2O (10:1)
DMF
92
96
2
a General reaction conditions: R,β-unsaturated ketone 1a (1 equiv),
Oxone, solvent (0.5 M), 24 h, at room temperature. b Conversion
percentage of ketone 1a to vinyl acetate 3a, as determined by 1H
NMR spectroscopy on crude reaction mixtures. c Product 3a was
detected by 1H NMR spectroscopy amid a complex reaction mixture.
To study the stereoelectronic factors involved in our
oxidation reaction a selection of R,β-unsaturated methyl-
ketones 1aÀr, bearing diverse functional groups and sub-
stitution patterns, were reacted with an excess of Oxone
under our finest reaction conditions (Table 3). Ketones
1bÀr were prepared in diastereopure form, (E), according
to modified literature procedures.10 Although 2 equiv of
Oxone sufficed to convert ketone 1a to vinyl acetate 3a
(Table 2, entry 8), it was not the case for any other ketone
1bÀr. For these substrates a larger excess of the oxidizing
reagent was necessary to achieve acceptable conversion
values for products 3bÀr in a reasonable reaction time.11
The course of the reactions was carefully followed by TLC,
and they were stopped and worked up as soon as the
corresponding methylketone1 wasconsumed. Allthe vinyl
acetate products 3bÀr proved to be fragile in the presence
of water, suffering from some hydrolysis of the ester
moiety. In order to attain optimum yields of isolated pure
products 3, the DMF was rigorously dried, the reactions
were carried out under an inert atmosphere, and aqueous
workups were avoided.12 As evidence of these difficulties,
it has to be noted that styryl acetate, 3a, was isolated in
analytically pure form in a maximum yield of 73%
€
(10) (a) Zumbansen, K.; Dohring, A.; List, B. Adv. Synth. Catal.
2010, 352, 1135. (b) McNulty, J.; McLeod, D. Chem.;Eur. J. 2011, 17,
8794.
(11) Vinyl acetate products 3 were experienced to degrade within the
reaction media after prolonged reaction times.
(12) See Supporting Information for details.
(9) Oxone was purchased from Aldrich (1 g = $0.06).
B
Org. Lett., Vol. XX, No. XX, XXXX

Table 3. Oxone-Promoted Oxidation of R,β-Unsaturated Methylketones 1 to Vinyl Acetates 3a
a General reaction conditions: R,β-unsaturated ketone 1aÀz (0.5 mmol), Oxone (amount stated in the table), dry DMF (1 mL), dry nitrogen
atmosphere, room temperature (20 °C). b The course of these reactions was carefully followed by TLC. Reactions were stopped and worked up as soon as
the ketone was consumed. c Isolated yield of analytically pure products 3aÀz. d Product 3w was isolated as an inseparable mixture of diastereoisomers
(10.1:1 ratio) favoring the stereochemical configuration represented in the table. e trans-Cinnamaldehyde was used as the substrate affording styryl
formate 3x as the reaction product.
(Table 3, entry 1), featuring 96% conversion in the crude
reaction mixture (Table 2, entry 8).
(Table 3, entry 11), allow rendering styryl acetates 3j and
3k in 94% and 80% yield, respectively. Nitrile or nitro
groups, particularly sitting in position 2 or 4 of the phenyl
ring, hamper the reaction diminishing the isolated yield
of pure acetates 3lÀo (Table 3, entries 12À15). On the
other hand, strongly activating/electron-donating hydroxyl-
substituted ketone 1p was observed to be an excellent
substrate for the reaction (Table 3, entry 16). Polyaro-
matic derivatives, i.e. naphthyl-based ketones 1q and 1r,
also render the corresponding vinyl acetate products
smoothly and in good yield (Table 3, entries 17 and 18).
The coupling constants for the olefinic protons of pro-
ducts 3bÀr are in perfect agreement with typical transoid
values (3JHÀH = 12.6 to 12.9 Hz); hence they were
assigned an (E)-stereochemistry for the CÀC double
bond.
Our Oxone-promoted reaction is more efficient on
R,β-unsaturated methylketones that are conjugated with
aromatic structures (styrene derivatives). Early phenyl
halides (F, Cl, Br) are tolerated by the reaction conditions
(Table 3, entries 2À5), the same as the case for trifluor-
omethyl groups (Table 3, entry 6). Iodo substituents were
however oxidized by Oxone. R,β-Unsaturated methylke-
tones with phenyl rings equipped with alkyl chains, 1g
and 1h, are also suitable substrates, the corresponding
styryl acetates, 3g and 3h, being isolated with accept-
able yields (Table 3, entries 7 and 8). The presence
of strongly deactivating/electron-withdrawing groups is
equally permitted; ester (Table 3, entry 9) and amide
functions, either tertiary (Table 3, entry 10) or secondary
Org. Lett., Vol. XX, No. XX, XXXX
C

Following this study, other substrates 1sÀz were pre-
pared in order to explore the scope and limitations of
our oxidation reaction in depth. In this sense, substrates
consisting of two R,β-unsaturated methylketones moieties
set on the same aromatic ring, 1s and 1t, underwent the
reaction giving access to diacetates 3s and 3t (Table 3,
entries 19 and 20). Interestingly, R,β,γ,δ-diunsaturated
methylketone 1u, prepared from trans-cinnamaldehyde,
can be oxidized to the vinyl substituted diene 3u in good
yield, with complete retention of the (E,E) configuration
of both CÀC double bonds, as determined by 2D NMR
experiments and from comparison with previously re-
ported literature data13 (Table 3, entry 21). Furthermore,
other diunsaturated ketones, decorated with a chlorine or
bromine halogen atom at position γ, 1v and 1w, also react
to the acetate products 3v and 3w (Table 3, entries 22
and 23). While chlorine derivative 3v preserves the (E,Z)-
stereochemical integrity of the starting material, pro-
duct 3w was isolated as a 10.1:1 mixture of (1E,3Z) and
(1Z,3Z)-isomers, favoring the first configuration. Surpris-
ingly, cinnamaldehyde, 1x, also underwent BaeyerÀ
Villiger-type oxidation with Oxone, affording vinylformate
3x in 71% isolated yield as the major reaction product14
(Table 3, entry 24). Finally, the ability of the reaction was
investigated on aliphatic R,β-unsaturated methylketones.
Accordingly, substrates 1y and 1z were prepared and
subjected to the reaction conditions. The two correspond-
ing vinyl acetate products 3y and 3z could be isolated
from their reaction mixtures in modest yield (Table 3,
entries 25 and 26). These last compounds proved to be
particularly sensitive to the presence of water and were
difficult to purify and isolate.
Based on the full set of results gathered in Table 3 we
can state that the configuration of the R,β-unsaturated
methylketones 1 used asstarting materials is retained in the
oxidized product.
In conclusion, we have developed and implemented a
novel, general, and straightforward metal-free synthesis
of vinyl acetates from R,β-unsaturated methyl ketones that
occurs through a BaeyerÀVilliger reaction employing
Oxone as the oxidant. This transformation tolerates a wide
variety of functional groups and substitution patterns,
and the vinyl acetate products retain the stereochemistry
of the R,β-unsaturated methyl ketones used as substrates.
Although the mechanism of this transformation is thought
to operate in agreement with other classical BaeyerÀ
Villiger-type reactions effected by Oxone, it is being in-
vestigated in our laboratory and will be reported in due
course.
Acknowledgment. We thank MICINN (CTQ2010-
14959) for financial support. B.P., C.C., and V.d.A. thank
MICINN for an FPI predoctoral fellowship, a Juan de la
Cierva contract, and a Ramon y Cajal contract, respectively.
Supporting Information Available. General procedures,
spectroscopic data, and copies of 1H and 13C NMR
spectra for compounds 1j, 1k, 1v, 1w, and 3aÀz. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(13) Dudnik, A. S.; Schwier, T.; Gevorgyan, V. Tetrahedron 2009, 65,
1859.
(14) Syper, L. Tetrahedron 1987, 43, 2853.
The authors declare no competing financial interest.
D
Org. Lett., Vol. XX, No. XX, XXXX