Mn(OAc)3 - An efficient oxidant for regeneration of DDQ: Deprotection of p-methoxy benzyl ethers

Article abstract of DOI:10.1016/S0040-4039(00)01855-4

Mn(OAc)₃ has been successfully developed as a new oxidant for the regeneration of DDQ from HDDQ. This DDQ regeneration technique, making use of 3 equiv. of Mn(OAc)₃-DDQ (10 mol%), was applied to the deprotection of p-methoxy benzyl (PMB) ethers. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01855-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 10323–10326
Mn(OAc)3—an efficient oxidant for regeneration of DDQ:
deprotection of p-methoxy benzyl ethers†
G. V. M. Sharma,* B. Lavanya, A. K. Mahalingam and Palakodety Radha Krishna
Discovery Laboratory, Organic Chemistry Division III, Indian Institute of Chemical Technology,
Hyderabad 500 007, India
Received 29 August 2000; revised 9 October 2000; accepted 19 October 2000
Abstract
Mn(OAc)3 has been successfully developed as a new oxidant for the regeneration of DDQ from
HDDQ. This DDQ regeneration technique, making use of 3 equiv. of Mn(OAc)3–DDQ (10 mol%), was
applied to the deprotection of p-methoxy benzyl (PMB) ethers. © 2000 Elsevier Science Ltd. All rights
reserved.
Keywords: oxidative regeneration; deprotection; manganese triacetate; catalytic; 2,3-dichloro-5,6-dicyanoquinone.
Quinones1 of high oxidation potential are versatile reagents; DDQ, particularly with its
oxidation ability and relative stability, is one of the most used reagents to perform several organic
transformations such as dehydrogenation,2 oxidation of allylic and benzylic alcohols3 and ethers,
oxidative removal of Cr,4 Fe,5 Mn6 arene complexes, etc. DDQ7 also has been used for the
deprotection8 of several protecting groups from alcohols such as allyl, p-methoxy benzyl (PMB)
and di-methoxy benzyl (DMB) groups. Of the several reagents available for removal of the PMB
group, DDQ has a prominent place, since the reaction conditions are nearly neutral. However,
the two main problems associated with DDQ are the cost and difficulty of removing HDDQ, the
by-product. To circumvent both these problems ‘regeneration’ of DDQ is an interesting
10
alternative, which resulted in the development of reagents such as HClO4, HIO4,9 HNO3 and
FeCl3,11 most of which are acidic, and are hence incompatible with acid sensitive functional groups.
Since DDQ is an expensive reagent, used in stoichiometric quantities and removal of the resulting
HDDQ is cumbersome, it is essential to develop mild and efficient methods for regeneration of
DDQ. Herein, we report Mn(OAc)3 (3 equiv.) as a mild oxidant for the regeneration of DDQ
and demonstrate the usefulness of reagent system for the deprotection of PMB ethers (Eq. (1)).
3 equiv. Mn(OAc)
3
ROPMB ꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢁ ROH
(1)
(10 mol%) DDQ, CH Cl , rt
2
2
* Corresponding author. E-mail: esmvee@iict.ap.nic.in
†
IICT Communication No. 4530.
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01855-4

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Mild and selective protocols for unmasking protecting groups play a prominent role in the
synthesis of complex natural products. PMB ethers are one of the protecting groups which are
usually removed oxidatively by DDQ.8 Mn(OAc)3,12 is a powerful and neutral one electron
oxidant which was chosen as an oxidant in the present study for the regeneration of DDQ from
HDDQ, thereby avoiding the use of DDQ in stoichiometric quantity.
Accordingly, PMB ether 1 (entry 1; Table 1) was treated with 10 mol% of DDQ–3 equiv.
Mn(OAc)3 in CH2Cl2 at room temperature to afford 1a in 75% yield, whose optical integrity was
intact. The study was then extended to PMB ethers 2, 3 and 4 having TBS, THP and benzoyl
Table 1
Mn(OAc)3–DDQ mediated deprotection of PMB ethers

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protective groups (entries 2, 3 and 4) to give the alcohols 2a (83%), 3a (90%) and 4a (79%),
respectively. These examples demonstrated that acid sensitive groups TBS and THP, as well as
base sensitive benzoyl groups are completely compatible with the present conditions. Homoal-
lylic ether 5 (entry 5) and steroidal ether 6 (entry 6) gave the expected alcohols 5a (86%) and 6a
(71%) in 10.5 and 6 h, respectively. Further, treatment of sugar ether 7 (entry 7) and propargylic
ether 8 (entry 8) afforded the respective alcohols 7a (81%) and 8a (61%). All the products
formed were characterised from the spectroscopic data.
The plausible mechanism12 for the regeneration of DDQ from HDDQ is shown in the Fig. 1.
Accordingly, electrons transfer from the Mn(III) complex B by the loss of Mn(II) results in the
formation of quinone.
Figure 1.
Thus, the present study demonstrated an efficient use of Mn(OAc)3 as an oxidant for the
‘regeneration’ of DDQ which is used in 10 mol% for the removal of PMB ethers. The reaction
conditions are: (a) compatible with both acid and base sensitive groups, (b) optical integrity is
retained and (c) homoallylic and propargylic systems were unaffected. Thus, the present
protocol demonstrating the use of Mn(OAc)3–DDQ for the removal of PMB ethers of aliphatic,
terpenoidal, steroidal and sugar substrates, should find use in organic synthesis. The use of the
Mn(OAc)3–DDQ reagent system for other synthetic transformations is in progress.
Typical experimental procedure: A mixture of 1 (0.276 g, 1 mmol), Mn(OAc)3·2H2O (0.804 g,
3 mmol) and DDQ (0.022 g, 0.1 mmol) in CH2Cl2 (5 mL) was stirred at room temperature for
8.5 h. The reaction mixture was treated with aq. NaHCO3 solution (10 mL) and the organic
layer was separated. It was washed with water (2×10 mL), brine (10 mL), dried (Na2SO4),
evaporated and the residue purified by column chromatography (Silica gel, 1:10 ethyl ace-
tate:petroleum ether) to afford 1a (0.117 g) in 75% yield as a solid, whose spectroscopic data was
comparable with a known compound.
Spectral data for selected compounds: (1H NMR, 200 MHz, CDCl3, TMS):
1: [h]D −20.86 (c 1.5, CHCl3); l 0.8 (d, 3H, J 3.48 Hz), 0.85–1.10 (m, 11H), 1.57–1.70 (m, 2H),
1.90–2.01 (m, 1H), 2.10–2.25 (m, 1H), 3.4 (dt, 1H, J 5.18, 2.07 Hz), 3.80 (s, 3H), 4.45 (s, 2H),
6.85 (d, 2H, J 4.41 Hz), 7.25 (d, 2H, J 4.41 Hz); EIMS: m/z 276 (M+); HRMS: calc. for
C18H28O2: 276.208930, observed: 276.207990; 8a: [h]D −94.86 (c 1.5, CHCl3); l 1.28 (s, 3H, CH3),
1.48 (s, 3H, CH3), 1.94 (m, 1H, H-8), 2.45–2.60 (m, 1H, H-6), 2.67–2.80 (m, 1H, H-6), 3.90–4.10
(m, 3H, H-3, H-4 and H-5), 4.50–4.75 (m, 3H, H-2 and CH2Ar), 5.89 (d, 1H, J 5.1 Hz, H-1),
7.35 (s, 5H, ArH); EIMS: m/z 317 (M+−1).

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Acknowledgements
The authors, B. Lavanya and A. K. Mahalingam are thankful to CSIR, New Delhi, for
financial support.
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