Oxone-acetone mediated Wacker-type oxidation of benzo-fused olefins

Article abstract of DOI:10.1016/j.tetlet.2015.04.102

Herein we disclose a novel application of the oxone-acetone combination for the Wacker-type oxidation of indenes and dihydronaphthalenes leading, respectively, to indan-2-ones and 2-tetralones. The amount of the base employed in the reaction seems to switch the reaction path from dioxygenation to Wacker-type oxidation. Control experiments suggest that the reaction is not proceeding via the epoxide route and also that there is no role of trace amounts of metals present in the reagents on the current oxidation.

Full text of DOI:10.1016/j.tetlet.2015.04.102

Tetrahedron Letters 56 (2015) 3868–3871
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Oxone–acetone mediated Wacker-type oxidation of benzo-fused
olefins
⇑
Ravindra S. Phatake, Chepuri V. Ramana
Division of Organic Chemistry, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411008, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Herein we disclose a novel application of the oxone–acetone combination for the Wacker-type oxidation
of indenes and dihydronaphthalenes leading, respectively, to indan-2-ones and 2-tetralones. The amount
of the base employed in the reaction seems to switch the reaction path from dioxygenation to Wacker-
type oxidation. Control experiments suggest that the reaction is not proceeding via the epoxide route and
also that there is no role of trace amounts of metals present in the reagents on the current oxidation.
Ó 2015 Elsevier Ltd. All rights reserved.
Received 2 March 2015
Revised 23 April 2015
Accepted 24 April 2015
Available online 28 April 2015
Keywords:
Wacker oxidation
Oxone
Indene
Dihydronaphthalene
Epoxidation, dihydroxylation, and oxidation to ketone are some
of the important oxidative transformations of olefins that have
been well studied since the beginning of organic synthesis.1,2
Among these, the oxidation of olefins directly to carbonyl com-
pounds such as aldehydes and ketones has its own industrial and
academic significance.3 The conversion of olefins to carbonyl com-
pounds has been mainly dealt with by employing the complexes of
metals such Hg, Pd, Pt, Au, Ru, and Cu.4,5 The Wacker oxidation that
uses palladium in combination with copper in the presence of an
oxidant is one of the most useful and fundamental reactions in
organic synthesis.5 Several modifications have been carried out in
recent years that emphasize mainly on the use of green solvents
and oxidant free reaction conditions to achieve an effective envi-
ronment benign method.6 However, methods that employ less haz-
ardous, cost-effective, and metal free oxidation techniques are still
warranted.7 Herein, we describe a simple metal-free Wacker-type
olefin oxidation employing oxone albeit limited mainly to the ben-
zofused olefins such as indenes and tetralenes.
Oxone is a cheap (comparable with hydrogen peroxide and
bleach) and easy to handle reagent. Oxone is endorsed with the
ability to oxidize a broad spectrum of functional groups.8 Very
recently, we have shown that the combination of oxone–acetone,
which is well established for the olefin epoxidation reactions, can
be used for the cis-dioxygenation of the benzofused olefins leading
to a cis-vicinol diol protected as its acetonide.9 We have come
across this unusual dioxygenation accidently, while carrying out
the preparation of the known indene oxide on multi-gram scales
employing the oxone–acetone combination for the epoxidation. A
set of two side products (2–3%), namely the indan-2-one 3a and
the acetonide 4a along with the required epoxide 2a were obtained
under the described conditions (Fig. 1).10 In our previous commu-
nication, we have documented a successful realization of the con-
ditions for the direct conversion of indene 1a–4a. With this, we
next looked at the possibility of the Wacker-type oxidation of 1a
leading directly to 3a.
During our previous investigations on the dioxygenation of 1a,
it has been found that the indan-2-one was isolated as a single pro-
duct in 35% yield when the oxidation was performed in 0.5 equiv of
oxone in the presence of 3 equiv of NaHCO3 (Table S1 in SI). In
order to have a suitable reaction condition for the exclusive forma-
tion of 2-indanone, some logical experimentation has been put for-
ward. Optimization experiments have been conducted by varying
the proportions of both oxidant and base. The progress and the nat-
ure of the intermediates involved in this process have been ana-
lyzed with the help of GC–MS. In general, a noticeable change in
the consumption of starting material with the product formation
was observed with the variation especially in the amounts of base
employed (Scheme 1).
To this end, the use of 12 equiv of NaHCO3 along with 2 equiv of
oxone was found to be the best combination for the complete con-
version. Under these optimized conditions, 2-indanone 3a was
obtained in 78% yield at room temperature over the period of
15–20 h. However, no further improvement was observed by
increasing the quantity of either oxidant and/or base. Also, pro-
longing the reaction for longer durations had no effect. Control
⇑
Corresponding author. Tel.: +91 20 2590 2577; fax: +91 20 2590 2629.
E-mail address: vr.chepuri@ncl.res.in (C.V. Ramana).
http://dx.doi.org/10.1016/j.tetlet.2015.04.102
0040-4039/Ó 2015 Elsevier Ltd. All rights reserved.

R. S. Phatake, C. V. Ramana / Tetrahedron Letters 56 (2015) 3868–3871
3869
Table 1
Oxone (2 eq.)
NaHCO3 (5 eq.)
Scope of oxone–acetone mediated Wacker-type oxidation of indene derivativesa
O
Entry
Substrate
Product
Yieldb (%)
acetone (10 eq.)
2a
H2O:EtOAc (1:1)
previous work
O
O
O
reported
1
70
74
NaHCO3 (3 eq.)
O
by others
1b
3b
4-10 h
Oxone (2 eq.)
4a
3a
acetone:EtOAC:H 2O
present work
2
3
(5:1:1), rt
NaHCO3 (12 eq.)
1a
O
1c
3c
reports from
our group
15-20 h
O
O
74
72
61
75
Cl
Cl
Figure 1. Solvent and/or base dependent complementary oxidation of indene with
oxone.
1d
3d
4
5
6
N3
N3
O
3e
1e
1a
3a
O
Ph
Ph
1f
3f
O
Ph
Ph
Ph
1g
3g
O
7
78
Ph
1h
3g
3i
8
9
71
65
O
O
1i
Scheme 1. Selected conditions explored for the Wacker-type oxidation. Reagents
and conditions: All the reactions were carried out at rt with 0.5 mmol of indene in
2.5 ml acetone and 0.5 ml of (1:1 of H2O + EtOAc); (A) oxone (0.5 equiv), NaHCO3
(3 equiv); (B) oxone (1.0 equiv), NaHCO3 (6 equiv); (C) oxone (1.5 equiv), NaHCO3
(9 equiv); (D) oxone (2.0 equiv), NaHCO3 (12 equiv).
1j
MeO
3j
MeO
experiments revealed that the acetone/H2O/EtOAc (5:1:1)
employed for syn-dioxygenation was also found to be the best sol-
vent combination system for the current Wacker-type oxidation.
The optimized reaction conditions involve the addition of 2 equiv
of powdered oxone to a stirred slurry of 12 equiv of NaHCO3 and
1 equiv indene in a mixture of solvents (5:1:1 acetone/water/ethyl
acetate) stirred at room temperature over the prescribed time. The
oxidation of simple indene 1a under this condition provided the
required 3a in 78% yield as the sole product in 18 h.
10
11
61
76
O
1k
3k
O
Ph
Ph
3l
1l
MeO
MeO
The scope of this reaction has been generalized by employing
various substituted indene derivatives 1b–1h. In general, the reac-
tions proceeded smoothly and provided exclusively corresponding
2-indanones in good yields. As shown in Table 1, the substitution
at the C3 (1b–1g) and at C1 position (1h) of indene has little effect
on the outcome of the reaction (in terms of yields and the
regioselectivity) and proceeded smoothly. This suggested that the
reaction is highly regioselective in nature. As expected, the C-1
substituted indene 1h (1-benzyl-1H-indene) and the C-3
substituted 1g (3-benzyl-1H-indene) led to the formation of 1-ben-
zyl-1H-inden-2(3H)-one (3g). Gratifyingly, the reaction conditions
O
12
13
70
72
Ph
Ph
1m
3m
O
p-tolyl
1n
p-tolyl
3n
(continued on next page)

3870
R. S. Phatake, C. V. Ramana / Tetrahedron Letters 56 (2015) 3868–3871
Oxone (2eq.)
Table 1 (continued)
NaHCO3 (12eq.)
O
O
Entry
14
Substrate
MeO
Product
Yieldb (%)
acetone:H2O:EtOAc (5:1:1)
rt, 20h
MeO
1p
1q
3p (69%)
3q (68%)
O
p-tolyl
69
p-tolyl
''
1o
3o
Reaction conditions.
a
Substrate 1 (1 equiv), oxone (2 equiv), NaHCO3 (12 equiv), acetone/H2O/EtOAc
(5:1:1), rt, 15–20 h.
PdCl2 (10 mol %)
Cu(OAc)2 (1.2 eq.)
b
Isolated yields.
O
O
2 balloon pressure
CH3CONMe2:H2O (4:1)
rt, 10 h
employed was found to be tolerable for a range of functional
groups like chloro and azide without affecting the yields of the
final products much (Table 1).
1q
5
(62%)
Scheme 3. Regioselectivity of Wacker-type oxidation of diene 1p and 1q.
To explore the scope of this reaction, we next examined the
oxidation of 1,2-dihydronaphthalene leading to 2-tetralones. 2-
Tetralones have been found to have a wide range of applications
as valuable intermediates in natural products synthesis and also
in the synthesis of pharmaceuticals.11 The 1,2-transposition of
scavenger for metals such as Pd, Cu(I), Cu(II), Ni, Pt, etc.) as an addi-
tive in the reaction medium.15 As shown in Scheme 2, there was no
interference from this added metal scavenger and there was no
change either in the time or the yield of the product. This control
experiment has precisely ruled out the possible involvement of
traces of metal impurities present in the reagents in the present
oxidation.
Next, examined was the olefin selectivity of the present process.
3-(but-3-en-1-yl)-1H-indene (1q) and 3-allyl-1H-indene (1p) have
been subjected for the present oxidation under established condi-
tions. Interestingly, the oxidation of both dienes 1p and 1q
occurred in a way such that the internal olefins only got oxidized
resulting in the corresponding indan-2-ones exclusively
(Scheme 3). Interestingly, when 1q was exposed to Pd-catalyzed
Wacker oxidation, the exclusive oxidation of the external olefin
without disturbing the internal olefin has been noticed. This com-
plementary selectivity clearly explains that the oxone–acetone
mediated oxidation is very selective for the benzo-fused olefins
despite the fact that this olefin is sterically hindered.
To conclude, we have documented the direct oxidation of inde-
nes and 1,2-dihydronapthalenes, respectively, to the correspond-
ing 2-indanones and 2-tetralones employing oxone–acetone and
sodium bicarbonate under relatively simple conditions. The control
experiments primarily reveal that the current reaction is similar to
the acetonide formation and did not occur due to the presence of
trace-metal impurities, nor is the epoxide an intermediate in the
path of the reaction. However, further investigation is underway
in our laboratory to rule out the other possibilities. In a nutshell,
it must be noted that a subtle variation in the reaction conditions
either in terms of the solvents employed and/or the amount
of base used seems to causes a complete change in the course of
the reaction. The current base-driven switching in reaction path
is very unusual and creates substantial opportunities for further
exploration.
the carbonyl group of a-tetralones is one of the generally adopted
direct methods for the preparation of b-tetralones.12 Also, the 1,2-
dihydronaphthalene derivatives have been converted into 2-te-
tralones by employing a sequence of hydroboration followed by
oxidation of the resulting alcohols.13
The 1,2-dihydronaphthalenes 1i–1o have been synthesized
following the established procedures and then subjected for the
oxone–acetone mediated olefin oxidation under the established
conditions. As shown in Table 1 (entries 8–14), in all the cases,
the reaction proceeded efficiently and provided the corresponding
2-tetralones with complete regioselectivity. It is worth mentioning
here that tetralones 3k and 3n have been prepared earlier in the
context of synthesis of an ABCD tetracyclic Bruceantin precursor
and a 2 step protocol has been employed.14
In order to have preliminary information on the course of this
oxidation reaction, some control experiments have been carried
out. At first, both epoxide 2a and acetonide 4a have been exposed
to the present conditions for a longer period. It has been found that
both 2a and 4a are intact which indicated that either epoxide or
the acetonide are not involved as intermediates in the current
transformation. Indeed, the GC–MS monitoring of this reaction
during the optimization studies has clearly indicated that none of
these intermediates are present. Next, the oxidation of 1a has been
conducted employing excess QuadraPure™ DMA (a known
Oxone (2 eq.)
NaHCO3 (12 eq.)
O
No Reaction
acetone:EtOAC:H2O
(5:1:1), rt, 24 h
2a
O
Oxone (2 eq.)
NaHCO3 (12 eq.)
Acknowledgments
O
No Reaction
acetone:EtOAC:H2O
(5:1:1), rt, 24 h
The authors would like to acknowledge the CSIR (India) for pro-
viding the financial support for this project under the NICE
(CSC0109). Financial support from CSIR (New Delhi) in the form
of a research fellowship to R.S.P. is gratefully acknowledged.
4a
1a
Oxone (2 eq.)
NaHCO3 (12 eq.)
O
acetone:EtOAC:H2O
(5:1:1), rt, 20 h
QuadraPure DMA
Supplementary data
3a
(72%)
Supplementary data (the NMR spectra of all new compounds)
associated with this article can be found, in the online version, at
http://dx.doi.org/10.1016/j.tetlet.2015.04.102.
Scheme 2. Control experiments conducted to examine the involvement of epoxide
and trace metal impurities.

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3871
Krishna, A. D.; Prasad, A. R.; Hafeez Ur, R.; Rao, K. V.; Rao, A. B. Tetrahedron:
Asymmetry 2007, 18, 717–723; (e) Kulkarni, M. G.; Bagale, S. M.; Shinde, M. P.;
Gaikwad, D. D.; Borhade, A. S.; Dhondge, A. P.; Chavhan, S. W.; Shaikh, Y. B.;
Ningdale, V. B.; Desai, M. P.; Birhade, D. R. Tetrahedron Lett. 2009, 50, 2893–
2894; (f) Escola, J. M.; Botas, J. A.; Vargas, C.; Bravo, M. J. Catal. 2010, 270, 34–
39; (g) Michel, B. W.; Steffens, L. D.; Sigman, M. S. J. Am. Chem. Soc. 2011, 133,
8317–8325; (h) Bigi, M. A.; White, M. C. J. Am. Chem. Soc. 2013, 135, 7831–
7834; (i) DeLuca, R. J.; Edwards, J. L.; Steffens, L. D.; Michel, B. W.; Qiao, X.; Zhu,
C.; Cook, S. P.; Sigman, M. S. J. Org. Chem. 2013, 78, 1682–1686; (j) Zhang, G.;
Xie, X.; Wang, Y.; Wen, X.; Zhao, Y.; Ding, C. Org. Biomol. Chem. 2013, 11, 2947–
2950; (k) Fernandes, R. A.; Bethi, V. Tetrahedron 2014, 70, 4760–4767; (l)
Fernandes, R. A.; Chaudhari, D. A. J. Org. Chem. 2014, 79, 5787–5793.
7. (a) Hermans, I.; Janssen, K.; Moens, B.; Philippaerts, A.; Van Berlo, B.; Peeters, J.;
Jacobs, P. A.; Sels, B. F. Adv. Synth. Catal. 2007, 349, 1604–1608; (b) Michel, B.
W.; Sigman, M. S. Aldrichim. Acta 2011, 44, 55–62; (c) Nobuta, T.; Hirashima, S.-
I.; Tada, N.; Miura, T.; Itoh, A. Org. Lett. 2011, 13, 2576–2579; (d) Ahmad, A.;
Scarassati, P.; Jalalian, N.; Olofsson, B.; Silva, L. F., Jr. Tetrahedron Lett. 2013, 54,
5818–5820; (e) Harikrishna, K.; Mukkamala, R.; Hinkelmann, B.; Sasse, F.;
Aidhen, I. S. Eur. J. Org. Chem. 2014, 2014, 1066–1075; (f) Yang, Q.; Mao, L.-L.;
Yang, B.; Yang, S.-D. Org. Lett. 2014, 16, 3460–3463; (g) Rajbongshi, K. K.;
Hazarika, D.; Phukan, P. Tetrahedron Lett. 2015, 56, 356–358.
References and notes
1. (a) Backvall, J.-E. Modern Oxidation Methods; Wiley-VHC: Weinheim, Germany,
2004; (b) March, J. Advanced Organic Chemistry, 4th ed.; Wiley: New York, 1992.
pp 734–878; (c) Carey, F. A.; Sundberg, R. J. Advanced Organic Chemistry, 3rd ed.;
Plenum: New York, 1990. pp 624–642.
2. (a) Matsumoto, M. J. Synth. Org. Chem. JPN 1985, 43, 753–763; (b) Pedragosa-
Moreau, S.; Archelas, A.; Furstoss, R. Tetrahedron 1996, 52, 4593–4606; (c)
Bonini, C.; Righi, G. Tetrahedron 2002, 58, 4981–5021; (d) Kowalski, G.;
Pielichowski, J. Synlett 2002, 2107–2109; (e) Muzart, J. J. Mol. Catal. A: Chem.
2007, 276, 62–72; (f) Rao, T. S. S.; Awasthi, S. J. Indian Chem. Soc. 2007, 84, 902–
913; (g) Toda, H.; Imae, R.; Itoh, N. Tetrahedron: Asymmetry 2012, 23, 1542–
1549; (h) Wu, W.; Jiang, H. Acc. Chem. Res. 2012, 45, 1736–1748.
3. (a) Smidt, J. Chem. Ind. 1962, 54–61; (b) Sonoda, N. J. Synth. Org. Chem. JPN 1972,
30, 739; (c) Tsuji, J. Synthesis 1984, 369–384; (d) Ranu, B. C.; Chakraborty, R.
Synth. Commun. 1990, 20, 1751–1756; (e) Zhang, X. K.; Sullivan, D.; van Hal, J.
Arab. J. Sci. Eng. 1999, 24, 101–113; (f) Wang, S. B.; Murata, K.; Hayakawa, T.;
Hamakawa, S.; Suzuki, K. J. Chem. Technol. Biotechnol. 2001, 76, 265–272; (g)
Muzart, J. Tetrahedron 2007, 63, 7505–7521; (h) Kotali, A.; Lafazanis, I. S.;
Harris, P. A. Synthesis 2009, 836–840; (i) Wickens, Z. K.; Morandi, B.; Grubbs, R.
H. Angew. Chem., Int. Ed. 2013, 52, 11257–11260.
4. (a) Kano, S.; Yokomatsu, T.; Ono, T.; Hibino, S.; Shibuya, S. J. Chem. Soc., Chem.
Commun. 1978, 414–415; (b) Mihara, J.; Hamada, T.; Takeda, T.; Irie, R.; Katsuki,
T. Synlett 1999, 1160–1162; (c) Robinson, M. W. C.; Pillinger, K. S.; Mabbett, I.;
Timms, D. A.; Graham, A. E. Tetrahedron 2010, 66, 8377–8382; (d) Boisvert, L.;
Goldberg, K. I. Acc. Chem. Res. 2012, 45, 899–910; (e) Wang, Z.-M.; Sang, X.-L.;
Che, C.-M.; Chen, J. Tetrahedron Lett. 2014, 55, 1736–1739.
5. (a) Miller, D. G.; Wayner, D. D. M. J. Org. Chem. 1990, 55, 2924–2927; (b) Lai, J.
Y.; Shi, X. X.; Dai, L. X. J. Org. Chem. 1992, 57, 3485–3487; (c) Higuchi, M.;
Yamaguchi, S.; Hirao, T. Synlett 1996, 1213; (d) Li, H. M.; Shu, H. M.; Ye, X. K.;
Wu, Y. Progr. Chem. 2001, 13, 461–471; (e) Mitsudome, T.; Umetani, T.; Nosaka,
N.; Mori, K.; Mizugaki, T.; Ebitani, K.; Kaneda, K. Angew. Chem., Int. Ed. 2006, 45,
481–485; (f) Cornell, C. N.; Sigman, M. S. Inorg. Chem. 2007, 46, 1903–1909; (g)
Keith, J. A.; Henry, P. M. Angew. Chem., Int. Ed. 2009, 48, 9038–9049; (h) Michel,
B. W.; Camelio, A. M.; Cornell, C. N.; Sigman, M. S. J. Am. Chem. Soc. 2009, 131,
6076; (i) Winston, M. S.; Oblad, P. F.; Labinger, J. A.; Bercaw, J. E. Angew. Chem.,
Int. Ed. 2012, 51, 9822–9824; (j) Wang, Y.-F.; Gao, Y.-R.; Mao, S.; Zhang, Y.-L.;
Guo, D.-D.; Yan, Z.-L.; Guo, S.-H.; Wang, Y.-Q. Org. Lett. 2014, 16, 1610–1613.
6. (a) Monflier, E.; Tilloy, S.; Blouet, E.; Barbaux, Y.; Mortreux, A. J. Mol. Catal. A:
Chem. 1996, 109, 27–35; (b) Ansari, I. A.; Joyasawal, S.; Gupta, M. K.; Yadav, J. S.;
Gree, R. Tetrahedron Lett. 2005, 46, 7507–7510; (c) Cornell, C. N.; Sigman, M. S.
Org. Lett. 2006, 8, 4117–4120; (d) Yadav, J. S.; Reddy, G. S. K. K.; Sabitha, G.;
8. (a) Hussain, H.; Green, I. R.; Ahmed, I. Chem. Rev. 2013, 113, 3329–3371; (b)
Parent, A. R.; Crabtree, R. H.; Brudvig, G. W. Chem. Soc. Rev. 2013, 42, 2247–
2252; (c) Murray, R. W. Chem. Rev. 1989, 89, 1187–1201; (d) Adam, W.; Curci,
R.; Edwards, J. O. Acc. Chem. Res. 1989, 22, 205–211.
9. Phatake, R. S.; Ramana, C. V. Tetrahedron Lett. 2015, 56, 2183–2186.
10. Hashimoto, N.; Kanda, A. Org. Process Res. Dev. 2002, 6, 405–406.
11. (a) Rice, L. M.; Scott, K. R.; Grogan, C. H. J. Med. Chem. 1966, 9, 765; (b) Reddy, J.;
Tschaen, D.; Shi, Y. J.; Pecore, V.; Katz, L.; Greasham, R.; Chartrain, M. J. Ferment.
Bioeng. 1996, 81, 304–309; (c) Anjanamurthy, C.; Basavaraju, Y. B. Indian J.
Chem., Sect B 1999, 38, 137–140; (d) Sadashivamurthy, B.; Basavaraju, Y. B.;
Sathisha, A. D.; Hemakumar, K. H. Bulg. Chem. Commun. 2007, 39, 264–268.
12. (a) Fristad, W. E.; Bailey, T. R.; Paquette, L. A. J. Org. Chem. 1978, 43, 1620–1623;
(b) Hauser, F. M.; Prasanna, S. Synthesis 1980, 621–623; (c) Braun, M.; Bernard,
C. Liebigs Ann. Chem. 1985, 435–437.
13. Kirkiacharian, B. S.; Koutsourakis, P. G. Synth. Commun. 1993, 23, 737–742.
14. (a) Packer, R. A.; Whitehurst, J. S. J. Chem. Soc., Chem. Commun. 1975, 757–758;
(b) Suryawanshi, S. N.; Fuchs, P. L. J. Org. Chem. 1986, 51, 902–921; (c)
Hedstrand, D. M.; Byrn, S. R.; McKenzie, A. T.; Fuchs, P. L. J. Org. Chem. 1987, 52,
592–598.
15. Hinchcliffe, A.; Hughes, C.; Pears, D. A.; Pitts, M. R. Org. Process Res. Dev. 2007,
11, 477–481.