Highly efficient methyl ketone synthesis by water-assisted C-C coupling between olefins and photoactivated acetone

Article abstract of DOI:10.1021/ol800999s

(Chemical Equation Presented) Photoirradiation of an acetone/water mixture containing olefins affords the corresponding methyl ketones highly efficiently via a water-assisted CsC coupling between acetonyl radical and olefins.

Full text of DOI:10.1021/ol800999s

ORGANIC
LETTERS
2008
Vol. 10, No. 14
3117-3120
Highly Efficient Methyl Ketone Synthesis
by Water-Assisted C-C Coupling
between Olefins and Photoactivated
Acetone
Yasuhiro Shiraishi,* Daijiro Tsukamoto, and Takayuki Hirai
Research Center for Solar Energy Chemistry, and DiVision of Chemical Engineering,
Graduate School of Engineering Science, Osaka UniVersity, Toyonaka 560-8531,
Japan
shiraish@cheng.es.osaka-u.ac.jp
Received May 23, 2008
ABSTRACT
Photoirradiation of an acetone/water mixture containing olefins affords the corresponding methyl ketones highly efficiently via a water-
assisted CsC coupling between acetonyl radical and olefins.
Ketones occupy pivotal positions as intermediates as well
as final products in the synthesis of natural products and
pharmaceutical materials. Traditional alcohol oxidation
requires stoichiometric amounts of inorganic oxidants,
notably chromium reagents, with concomitant formation of
copious heavy-metal waste.1 Recent advances in oxidation
catalysts allow clean alcohol oxidation with molecular
coupling reaction between organoborons and haloarenes or
acyl halides (Suzuki-Miyaura reaction); however, both
methods require Pd-based catalysts.
4
It is well-known that photoexcited acetone undergoes
Norrish type I,5 sensitization,6 and hydrogen abstraction
reactions.7 With olefins, the photoexcited acetone undergoes
[2 + 2]cycloaddition to produce oxetane.8 A few reports
reveal that addition of acetone to olefin proceeds via acetonyl
2
oxygen; however, these processes require noble metal
9
radical formation; photoirradiation of acetone containing
catalysts. Another powerful method for ketone synthesis is
the olefin oxidation (Wacker reaction)3 and the cross-
(4) Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 95, 2457–2483.
(5) (a) Norrish, R. G.; Bond, C. H. Nature 1936, 138, 1016–1016. (b)
Wessig, P.; Mu¨hling, O. Angew. Chem., Int. Ed. 2001, 40, 1064–1065. (c)
Turro, N. J. Modern Molecular Photochemistry; University Science Books:
Sausalito, 1978.
(1) (a) Cainelli, G.; Cardillo, G. Chromium Oxidants in Organic
Chemistry; Springer: Berlin, 1984. (b) Ley, S. V.; Madin, A. In Compre-
hensiVe Organic Synthesis; Trost, B. M., Fleming, I., Ley, S. V., Eds.;
Pergamon: Oxford, 1991; Vol. 7, p 251.
(6) (a) Borkman, R. F.; Kearns, D. R. J. Am. Chem. Soc. 1966, 88, 3467–
3475. (b) Krauch, C. H.; Kra¨mer, D. M.; Chandra, P.; Mildner, P.; Feller,
H.; Wacker, A. Angew. Chem., Int. Ed. Engl. 1967, 6, 956–956.
(7) (a) Porter, G. J. Chem. Soc., Faraday Trans. 1 1973, 69, 1462–
1474. (b) Scaiano, J. C. J. Photochem. 1973/74, 2, 81–118. (c) Nau, W. M.;
Cozens, F. L.; Scaiano, J. C. J. Am. Chem. Soc. 1996, 118, 2275–2282.
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76, 4327–4331. (b) Turro, N. J.; Dalton, J. C.; Dawes, K.; Farrington, G.;
Hautala, R.; Morton, D.; Niemczyk, M.; Shore, N. Acc. Chem. Res. 1972,
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Chem. Soc. 2006, 128, 12596–12597. (c) Schultz, M. J.; Park, C. C.; Sigman,
M. S. Chem. Commun. 2002, 3034–3035.
(3) (a) Cornell, C. N.; Sigman, M. S Inorg. Chem. 2007, 46, 1903–
1909. (b) Cornell, C. N.; Sigman, M. S. J. Am. Chem. Soc. 2005, 127,
2796–2797. (c) Mitsudome, T.; Umetani, T.; Nosaka, N.; Mori, K.;
Mizugaki, T.; Ebitani, K.; Kaneda, K. Angew. Chem., Int. Ed. 2006, 45,
481–485. (d) ten Brink, G.-J.; Arends, I. W. C. E.; Papadogianakis, G.;
Sheldon, R. A. Chem. Commun. 1998, 2359–2360.
10.1021/ol800999s CCC: $40.75
Published on Web 06/24/2008
2008 American Chemical Society

cyclic or exocyclic olefins, such as norbornene and meth-
ylenecycloalkanes, affords the corresponding acetone-olefin
adducts (methyl ketones). This photochemical CsC coupling
reaction proceeds at ambient temperature with acetone, which
is cheap, clean, and safe and, hence, has a potential as a
new methyl ketone production process; however, the reaction
suffers from low selectivity and low yield.
Scheme 1
.
Reaction of Photoactivated Acetone in the Presence
of Cyclohexene (1)
Here, we present highly efficient and selective methyl
ketone production, achieved by photoirradiation of an
acetone/water mixture containing olefins (see the Table of
Contents graphic). This extremely simple photoprocess,
efficiently promoted just by water addition, is driven by
hydration of acetone-derived radicals, which leads to an
enhancement of methyl ketone formation and a suppression
of byproduct formation.
The efficacy of adding water to acetone is evident from
the reaction with cyclohexene (1) as a substrate. Table 1
Table 1. Results of Photoreaction of Cyclohexene (1) in
Acetone Solutions Containing Various Cosolvents (40 vol %)a
(Scheme 1): the excited-state acetone undergoes [2 +
2]cycloaddition to 1 to form 6 (oxetane).8 The excited-state
acetone also undergoes hydrogen abstraction from ground-
state acetone to produce acetonyl (I) and 2-hydroxy-2-propyl
(II) radical pairs.11 These radical pairs undergo fast recom-
bination (deactivation to ground-state acetones) or dimer-
ization (formation of 7-9).11,12 The methyl ketone (2) is
formed by a radical addition of I to alkene 1 followed by
hydrogen abstraction from ground-state acetone.9 In contrast,
radical II abstracts an allylic hydrogen of 1 to produce
2-propanol (3) and cyclohexenyl radical (III). The radical
III reacts with radical II or itself and produces cyclohexene-
derived byproducts (4 and 5).13
The water-induced enhancement of the methyl ketone (2)
formation is probably due to the suppression of the radical
pair recombination (I and II) by hydration of each radical.
Figure 1 (black bar) shows the effect of water amount on
the product distribution of 1. Formation of 2, 3, and 6 is
enhanced with an increase in the water amount up to 40%.
The increased 6 formation is due to the stabilization of
intermediate by high polarity of water.8c Compounds 2 and
3 form via the reaction of 1 with respective radicals I and
II. These radical pairs are rapidly deactivated by recombina-
tion.12 The enhanced formation of 2 and 3 indicates that
water addition suppresses the radical pair recombination. It
is well-known that, in aqueous solution, carbonyl14 and
hydroxyl15 compounds are hydrated via a hydrogen-bonding
interaction. The suppression of the radical pair recombination
is probably due to the hydration of each radical. As shown
in Figure 1, the amount of acetone dimers (7-9) decreases
a Reaction conditions: acetone solution (10 mL), 1 (0.2 mmol), λ >300
nm (Xe lamp), photoirradiation time (6 h), temperature (40 °C).10
b Determined by GC.
shows the yield of 1-cyclohexylpropan-2-one (2) obtained
by photoirradiation at >300 nm.10 In pure acetone (entry
1), the yield of 2 is only 15%. In contrast, addition of 40
vol % water (entry 2) leads to drastic yield enhancement for
2 (43%). A similar enhancement (38%) is observed with D2O
(entry 3), but other solvents are ineffective (entries 4-7).
As described,8,9,11–13 reaction of photoexcited acetone in
the presence of 1 proceeds via the following mechanism
(9) (a) Reusch, W J. Org. Chem. 1962, 27, 1882–1883. (b) Majerski,
ˇ
K. M.; Pavlovic´, D.; Kulyk, M. S J. Org. Chem. 1993, 58, 252–254. (c)
Chung, W.-S.; Ho, C.-C. Chem. Commun. 1997, 317–318.
(10) Photoreaction procedures are as follows: each olefin was dissolved
in an acetone solution (10 mL) within a Pyrex glass tube (i.d. 10 mm;
capacity, 20 cm3), where the solvents were used without purification. The
tube was sealed using a rubber septum cap and purged with nitrogen. The
tube was photoirradiated with magnetic stirring by a Xe lamp (2 kW; Ushio
Inc; light intensity, 32.1 mW m-2 at 300-340 nm) or a high-pressure Hg
lamp (300 W; Eikohsha Co. Ltd.; light intensity, 38.2 mW m-2 at 300-340
nm). Substrate and product concentrations were determined by GC-FID
(Shimadzu GC-1700), where the product identifications were made by
GC-MS (Shimadzu GCMS-QP 5050A). The detailes are described in: (a)
Shiraishi, Y.; Saito, N.; Hirai, T. J. Am. Chem. Soc. 2005, 127, 8304–
8306. (b) Shiraishi, Y.; Saito, N.; Hirai, T. J. Am. Chem. Soc. 2005, 127,
12820–12822.
(11) Nakashima, M.; Hayon, E J. Phys. Chem. 1971, 75, 1910–1914
(12) (a) Shimizu, N.; Miyahara, T.; Mishima, M.; Tsuno, Y Bull. Chem.
Soc. Jpn. 1989, 62, 2032–2039. (b) Przybytek, J. T.; Singh, S. P.; Kagan,
.
(14) (a) Takebayashi, Y.; Yoda, S.; Sugeta, T.; Otake, K.; Nakahara,
M. J. Phys. Chem. B 2003, 107, 9847–9852. (b) Idrissi, A.; Longelin, S.;
Sokolic´, F. J. Phys. Chem. B 2001, 105, 6004–6009.
J. J. Chem. Soc., Chem. Commun. 1969, 1224–1225
.
(13) (a) de Mayo, P.; Stothers, J. B.; Templetone, W Can. J. Chem.
1961, 39, 488–497. (b) Borrell, P.; Sedler, J. Trans. Faraday Soc. 1970,
(15) (a) Filder, J.; Rodger, P. M. J. Phys. Chem. B 1999, 103, 7695–
7703. (b) Ruckenstein, E.; Shulgin, I. L.; Tilson, J. L. J. Phys. Chem. A
2005, 109, 807–815.
66, 1670–1679
.
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Org. Lett., Vol. 10, No. 14, 2008

Figure 1
. Product distribution of 1 during photoirradiation (λ >300 nm, Xe lamp) of (black) acetone/water and (white) acetone/D2O mixture
as a function of H2O or D2O amount. Reaction conditions are the same as those in Table 1.10
with an increase in the water amount. This indicates that
recombination of the radical pairs is in fact suppressed by
water addition. This enhances the addition of radical I to 1,
resulting in methyl ketone (2) formation enhancement.
The water addition selectively enhances the methyl ketone
formation (addition of radical I to 1) while maintaining the
activity of radical II low. As shown in Figure 1 (black bar),
without water, yields of 2 and 3 are similar. Upon addition
of 40 vol % water, 2 yield increases by 3-fold, while 3 yield
increases only by 1.5-fold. This suggests that water addition
selectively enhances the activity of radical I, although both
radicals are hydrated. The activity difference between radicals
I and II is probably due to the different hydration degree.
As reported,16 strong hydration takes place around the highly
polarized molecules. The radical II contains a highly
polarized hydroxyl group and, hence, is hydrated more
strongly than the radical I. The strong hydration probably
makes the radical II less reactive, resulting in low 3 yield
enhancement. This assumption is supported by experiments
with D2O in place of water (Figure 1, white bar). The 2 yield
increases with D2O addition, as is also the case with water,
whereas the 3 yield enhancement with D2O is much lower.
D2O solvates the solutes more strongly than water because
of stronger hydrogen-bonding interaction.14a The lower 3
yield enhancement with D2O is therefore probably because
the strong hydration of the radical II suppresses the reaction
with 1. In contrast, weakly hydrated radical I may react
efficiently with 1, thus resulting in high 2 yield enhancement.
The above findings suggest that the selective methyl ketone
formation, simply driven by water addition, is probably due
to the “selective” hydration toward the respective acetone-
derived radicals, I and II.
temperature. The hydrogen-bonding interaction is strength-
ened at higher temperature.14a This probably suppresses the
recombination of the radicals I and II more, resulting in 2
yield enhancement. At higher temperature, formation of 3,
4, 5, and 7-9 byproducts is much suppressed. This may be
because the strengthened hydration makes the radical II less
reactive. The above findings reveal that the present photo-
process shows the best performance at 40 °C; this allows
simple photoreaction control without severe conditions.
The proposed photoprocess with 40% water is tolerant of
other olefins. As summarized in Table 2, several olefins are
successfully converted to the corresponding methyl ketones
with very high yields (>70%). The quantum yields of the
methyl ketone formation are determined to be >0.28,17
indicating that the photoprocess proceeds highly efficiently.
It must also be noted that the photoprocess is applicable for
production of long-chain methyl ketones, which are difficult
to achieve by other conventional processes;3c,d for example,
1-dodecene and 1-icosene are successfully converted to the
corresponding methyl ketones with 93 and 71% yields,
respectively (entries 12 and 15). In addition, the 0.1 mol L-1
scale reaction is also successful (entries 3, 6, 13, and 18),
even though in these cases the reaction proceeds heteroge-
neously due to low solubility of olefins and products.
Another notable feature of the present methyl ketone
production process is the high performance at ambient
temperature. Figure 2 shows the temperature-dependent
change in the product distribution of 1 during reaction with
40% water. The 6 formation is suppressed with a rise in
temperature due to rapid deactivation of the excited-state
acetone.8b In contrast, 2 yield increases with a rise in
Figure 2. Temperature-dependent change in product distribution
of 1 during photoirradiation (λ >300 nm, Hg lamp) of an acetone
solution containing 40 vol % water. Reaction conditions are the
same as those in Table 1.10
(16) (a) Kamlet, M. J.; Abboud, J.-L. M.; Abraham, M. H.; Taft, R. W.
J. Org. Chem. 1983, 48, 2877–2887. (b) Reichardt, C. SolVents and SolVents
Effects in Organic Chemistry, 3rd ed; Wiley-VCH: Weinheim, 2003; p 432.
Org. Lett., Vol. 10, No. 14, 2008
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a
Table 2. Methyl Ketone Formation from Various Olefins with Photoactivated Acetone
a Reactions were carried out with Xe lamp (λ > 300 nm).10 b Yields were determined by GC analysis; values in parentheses are the yields of the isolated
products. c Quantum yield of the methyl ketone formation determined by photoreaction experiments with a 313 nm emission line (Hg lamp; filtered through
a potassium chromate solution (K2CrO4, 0.27 g L-1; K2CO3, 1 g L-1); light intensity, 3.1 mW m-2). d Reaction proceeds heterogeneously because olefins
e
and products are not fully dissolved in solution. 1H NMR charts of the respective isolated products are shown in the Supporting Information (Figures
S1-S5) to show the purity of the products.
In conclusion, we found that simple photoreaction system
with an acetone/water mixture allows highly efficient and
selective methyl ketone production. Methyl ketone formation
via the acetonyl radical addition to olefins also proceeds
thermochemically;18 however, these methods require metal
oxidants for the radical formation. Our photoprocess exhibits
significant advantages: (i) metal-free, (ii) cheap reactant
(acetone), (iii) cheap additive (water), and (iv) mild reaction
conditions (40 °C). Although the detailed mechanism remains
to be clarified, applying the basic concept presented here
may help realize methyl ketone synthesis in an economically
and environmentally friendly way.
Acknowledgment. This work was partly supported by
Japan Science and Technology Agency (JST) (No. 11-066)
and the Grant-in-Aid for Scientific Research (No. 20360359)
from the Ministry of Education, Culture, Sports, Science and
Technology, Japan (MEXT). We thank the Division of
Chemical Engineering for the Lend-Lease Laboratory Sys-
tem.
Supporting Information Available: Materials, general
procedure, and H NMR charts for the isolated products in
Table 2 (Figures S1-S5). This material is available free of
charge via the Internet at http://pubs.acs.org.
(17) Quantum yields were determined with a trans-stilbene actinometer
(Φ ) 0.45, in benzene): Lewis, F. D.; Johnson, D. E. J. Photochem. 1977,
7, 421–423.
1
(18) (a) Heiba, E. I.; Dessau, R. M. J. Am. Chem. Soc. 1971, 93, 524–
527. (b) Citterio, A.; Gentile, A.; Minisci, F. Tetrahedron Lett. 1982, 23,
5587–5590. (c) Linker, U.; Kersten, B.; Linker, T. Tetrahedron Lett. 1995,
51, 9917–9926.
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