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ChemComm
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DOI: 10.1039/C5CC05713B
COMMUNICATION
Journal Name
II, but also opened an opportunity to extend the present alcohol and benzhydrol.10 We futher examined with the
protocol on alcohol oxidation. substrate 5d containing mono & diactivated benzylic alcohols
A number of activated alcohols (Table 2) were subjected to and afforded siginificant yield of 6d with excellent selecitivity.
this oxidation protocol with Cs2CO3 as a base instead of KHCO3, These results have shown the importance and robustness of
as the reaction rate was very slow with KHCO3.6a Contrary to the present chemoselective oxidation strategy using DMSO as
our expectation benzyl alcohol (Table 2, entry 3) was intact an oxidant.
under the same reaction conditions even after 24 h. It is worth In summary, to best of our knowledge, this is the first report to
mentioning that the present reaction works equally well with utilize the electrophilic centre of DMSO without using any
K2CO3, but at a slower rate. In contrast to the other known activator for the oxidation of active methylene compounds
oxidation protocols,9 the developed protocol has the potential and benzhydrols. This procedure also shows unusual
to evolve as an efficient, transition metal free, green chemoselectivities in excellent yields. The role of DMSO in the
chemoselective oxidation method.
present oxidation strategy was successfully demonstrated with
To highlight the chemoselective application of the developed the help of analytical, experimental and 18O-isotopic labelling
protocol, we designed and synthesized model substrates with studies. The developed protocol neither utilizes the DMSO
competitive oxidizable functional groups. At first, we tested activators nor metal oxidant, which is highly desirable owing to
the developed protocol with a substrate 5a containing p- their practical applicability and environmentally benign nature.
benzyl alcohol and carbonyl activated benzylic methylene Further studies are in progress to explore and utilize the
groups.
electrophilic sulphur of sulfoxide for achieving various
selective oxidations.
a) p - benzylic alcohol vs active methylene
This work was supported by SERB, DST New Delhi (SR/FT/CS-
92/2011) and SEED Grant of IIT Mandi. RS, AB and VKM & RC
thank DST, CSIR and IIT Mandi respectively, for financial
assistance. AMRC sophisticated instrumental facilities are
gratefully acknowledged.
O
O
KHCO3 (25 mol%)
DMSO, 80 °C
HO
O
HO
5a
6a, 94%
b) s - benzylic alcohol vs active methylene
O
O
KHCO3 (25 mol%)
DMSO, 80 °C
Notes and references
O
OH
OH
1
2
3
(a) J. E. Bäckvall, Modern Oxidation Methods, Wiley-VCH,
Weinheim, 2004; (b) A. E. Wendlandt, A. M. Suess and S. S.
Stahl, Angew. Chem. Int Ed. 2011, 50, 11062-11087.
(a) Y. Ashikari, T. Nokami and J. – I. Yoshida, J. Am. Chem.
Soc. 2011, 133, 11840-11843; (b) Y. Ashikari, T. Nokami and
J. – I. Yoshida, Org. Lett. 2012, 14, 938-941.
6b, 89%
5b
c) s - dibenzylic alcohol vs active methylene
O
KHCO3 (25 mol%)
DMSO, 80 °C
O
O
OH
6c, 91%
(a) A. J. Mancuso and D. Swern, Synthesis, 1981, 165-185; (b)
V. Y. Kukushkin, Coord. Chem. Rev. 1995, 139, 375-407; (c) A.
O
OH
M. Khenkin and R. Neumann, J. Am. Chem. Soc. 2002, 124
4198-4199.
,
K2CO3 (1 equiv)
DMSO, 125 ° C
5c
O
4
(a) N. Kornblum, J. W. Powers, G. J. Anderson, W. J. Jones, H.
O. Larson, O. Levand and W. M. Weaver, J. Am. Chem. Soc.
1957, 79, 6562-6562; (b) W. Li, J. Li, M. Lin, S.
O
6c', 80%
d) p - benzylic alcohol vs s - dibenzylic alcohol
OH
O
Wacharasindhu, K. Tabei and T. S. Mansour, J. Org. Chem.
2007, 72, 6016-6021.
F. G. Bordwell and J. A. Harrelson Jr. Can. J. Chem. 1990, 68,
K2CO3 (1 equiv)
DMSO, 125 °C
HO
HO
5
6
5d
6d, 94%
1714-1718.
(a) See ESI† for more information. (b) All reactions were
performed with dry DMSO. The reaction works equally with
moist DMSO, but it needs stoichiometric amount of base
instead of catalytic amount.
Scheme 4. Evaluation of present DMSO oxidation protocol on chemoselective
substrates
To our delight the active methylene position got oxidized
selectively in high yields 6a with the primary benzylic alcohol
group intact (Scheme 4a). Next, the optimized conditions were
evaluated with the substrate 5b containing sec-benzylic
alcohol and carbonyl activated benzylic methylene groups, as
expected we got excellent chemoselective oxidation product
6b (Scheme 4b). Encouraged by these results, we further
designed a substrate 5c (Scheme 4c) with highly activated
benzhydrol unit and carbonyl activated benzylic methylene
unit. Even the highly activated benzhydrol remained intact and
selectively produced the diketone 6c in excellent yield. To the
best of our knowledge, this is the first report which specifically
oxidizes the active methylene group in presence of benzylic
7
D. H. B. Ripin, pKa in Practical Synthetic Organic chemistry:
Reaction, Principles, and Techniques, First Ed., John Wiley &
Sons, Hoboken, Chapter 18, 771-803.
A. H. Fenselau and J. G. Moffatt, J. Am. Chem. Soc. 1966, 88,
1762-1765.
(a) A. Rahimi, A. Azarpira, H. Kim, J. Ralph and S. S. Stahl, J.
Am. Chem. Soc. 2013, 135, 6415-6418; (b) L. D. Luca, G.
Giacomelli and A. Porcheddu, Org. Lett. 2001, 3, 3041-3043;
(c) S. Mannam, S. K. Alamsetti and S. Sekar, Adv. Synth. Catal.
2007, 349, 2253-2258.
8
9
10 Based on Scifinder substructure search and key words search
(chemoselective oxidation, diketones, benzylic alcohols) on
10th July, 2015.
4 | Chem. Commun., 2015, 00, 1-4
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