An efficient and selective deprotecting method for methoxymethyl ethers

Article abstract of DOI:10.1081/SCC-200039382

Methoxymethyl ethers were selectively deprotected to the corresponding phenols in high yields by CBr₄ and PPh₃ in aprotic solvent (ClCH₂CH₂Cl) under slightly thermal reaction conditions.

Full text of DOI:10.1081/SCC-200039382

This article was downloaded by: [Karolinska Institutet, University Library]
On: 10 October 2014, At: 05:04
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954
Registered office: Mortimer House, 37-41 Mortimer Street, London W1T
3JH, UK
Synthetic Communications:
An International Journal
for Rapid Communication of
Synthetic Organic Chemistry
Publication details, including instructions for
authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
An Efficient and Selective
Deprotecting Method for
Methoxymethyl Ethers
Yungui Peng a , Changyun Ji a , Yingchun Chen b
Chengzhi Huang a & Yaozhong Jiang b
,
a The School of Chemistry and Chemical
Engineering , Southwest Normal University ,
Beibei, Chongqing, 400715, China
b Chengdu Institute of Organic Chemistry , Chinese
Academy of Sciences , Chengdu, China
Published online: 10 Jan 2011.
To cite this article: Yungui Peng , Changyun Ji , Yingchun Chen , Chengzhi Huang
& Yaozhong Jiang (2004) An Efficient and Selective Deprotecting Method for
Methoxymethyl Ethers, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 34:23, 4325-4330, DOI:
10.1081/SCC-200039382
To link to this article: http://dx.doi.org/10.1081/SCC-200039382
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all
the information (the “Content”) contained in the publications on our
platform. However, Taylor & Francis, our agents, and our licensors
make no representations or warranties whatsoever as to the accuracy,
completeness, or suitability for any purpose of the Content. Any opinions

and views expressed in this publication are the opinions and views of
the authors, and are not the views of or endorsed by Taylor & Francis.
The accuracy of the Content should not be relied upon and should be
independently verified with primary sources of information. Taylor and
Francis shall not be liable for any losses, actions, claims, proceedings,
demands, costs, expenses, damages, and other liabilities whatsoever
or howsoever caused arising directly or indirectly in connection with, in
relation to or arising out of the use of the Content.
This article may be used for research, teaching, and private study
purposes. Any substantial or systematic reproduction, redistribution,
reselling, loan, sub-licensing, systematic supply, or distribution in any form
to anyone is expressly forbidden. Terms & Conditions of access and use
can be found at http://www.tandfonline.com/page/terms-and-conditions

SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 23, pp. 4325–4330, 2004
An Efficient and Selective Deprotecting
Method for Methoxymethyl Ethers
1
2
Yungui Peng,1, Changyun Ji, Yingchun Chen,
*
Chengzhi Huang,1 and Yaozhong Jiang2
1The School of Chemistry and Chemical Engineering, Southwest
Normal University, Beibei, Chongqing, China
2Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences,
Chengdu, China
ABSTRACT
Methoxymethyl ethers were selectively deprotected to the corresponding
phenols in high yields by CBr4 and PPh3 in aprotic solvent (ClCH2CH2Cl)
under slightly thermal reaction conditions.
Key Words: Deprotecting; Methoxymethyl; Selectively.
*
Correspondence: Yungui Peng, The School of Chemistry and Chemical Engineering,
Southwest Normal University, Beibei, Chongqing 400715, China; Tel: (86)-(23)-
68252927; E-mail: pengyungui@hotmail.com.
4325
DOI: 10.1081/SCC-200039382
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

4326
Peng et al.
Selective introduction and removal of protective groups is an important
tool in organic synthesis.[1] Among various hydroxyl protecting groups, the
methoxymethyl (MOM) ether is one of the most commonly used.[2,3] Acidic
reaction is the typically used hydrolyzing method for protected hydroxyl func-
tionality. MOM ether is generally hydrolyzed in protic solvent by acids
such as HCl,[4–6] catechol boron bromide (CBB)/HOAc,[7] and pridinium
p-toluenesulfonate[8] or hydrolyzed by Lewis acid such as LiBF4,[9]
Me2BBr,[10] Ph2BBr,[11] (i-PrS)2BBr,[12] catechol boron bromide (CBB),[13]
Me3SiBr,[14] and TiCl4. In spite of their potential utility, some of the
methods suffer from drawbacks, like the use of strong acid, which has
somewhat restricted its utilization in molecules containing other acid-sensitive
functionality, lack of selectivity, and unsatisfactory yield. Although the use of
CBr4 in i-PrOH for deprotecting MOM ether was reported,[15] the success of
such deprotections relies on the in situ generation of HBr, which provides
an anhydrous acidic reaction condition. The combination of CBr4 and PPh3
in aprotic solvent can assist in avoiding the production of HBr, although use
its for the deprotection of MOM ethers has not been reported. Herewith, we
wish to report the efficient and selective deprotecting method for MOM ethers.
Our study started with 4-nitrophenolic MOM ether as a test substrate
(Scheme 1), in order to find the best reaction conditions, several reaction para-
meters had to be optimized (Table 1). A series of solvents including CH2Cl2,
CHCl3, CCl4, ClCH2CH2Cl (DCE), C6H6, C6H5CH3, THF, and Et2O were
screened. Although the CHCl3, C6H6, DCE showed just the same good
results when used 40% catalyst amount (Table 1, entries 6, 8, 11), but the
yields dropped sharply in CHCl3, C6H6 when the catalyst loads decreased
(Table 1, entries 7, 9). The yield still kept up with 92% in DCE (Table 1,
entry 12). And, the best solvent was found to be DCE. The optimum reaction
temperature was found to be 408C. We also found that a catalytic amount of
CBr4 (0.2 equiv.) and PPh3 (0.2 equiv.) were sufficiently enough for the
reaction.
The reaction of deprotection of MOM group did not proceed when used
40% of CBr4 or PPh3 independently as catalyst in CH2Cl2 under reflux. After
combination of CBr4 and PPh3 as catalyst, the reaction proceeded smoothly.
With use of only 20% (CBr4/PPh3) catalyst amount in anhydrous ClCH2CH2Cl,
a yield up to 92% was obtained. And so the possible mechanism and
catalytic cycle may be assumed as shown in Scheme 2. We have not obtained
more definite evidence to prove it.
Scheme 1.

Selective Removal of MOM Ether
Table 1. The influence of conditions on the reaction.
4327
Catalyst
(equiv.)
Temp.
(8C)
Yield
(%)a
Entry
Solvent
CH2Cl2
THF
1
2
0.4
0.4
0.4
0.4
0.4
0.4
0.1
0.4
0.2
0.1
0.4
0.2
0.15
0.1
0.2
408C
408C
408C
408C
408C
408C
408C
408C
408C
408C
408C
408C
408C
408C
258C
74
47
26
56
75
90
32
98
19
4
3
CCl4
Et2O
4
5
C6H5CH3
CHCl3
CHCl3
6
7
8
C6H6
C6H6
C6H6
9
10
11
12
13
14
15
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
93
92
74
58
65
aThe yields were determined after chromatographic purification.
Scheme 2.

4328
Peng et al.
Scheme 3.
To further explore the potential of this catalyst system, we examined the
selective removal of MOM group from other substrates in the presence of
various functional groups under the optimized condition (Scheme 3). MOM
ethers were cleaved selectively. The results are summarized in Table 2.
The deprotection proceeds smoothly by treatment of the ethers with 20%
catalyst loads in CH2ClCH2Cl at 408C. A series of MOM ethers were depro-
tected to their corresponding phenols with high yields (90–99%), Table 2
(entries 1–9). The functional groups, just as esters, methyl and benzyl
Table 2. Cleavage of MOM ethers by CBr4/PPh3.
Yield
(%)a
Entry
1
Substrate
Product
92
2
92
3
4
5
6
91
90
91
94
7
8
97
99
9
96
aThe yields were determined after chromatographic purification.

Selective Removal of MOM Ether
4329
ethers were found to be stable under the conditions (entries 4, 5, 6, 7, 8, 9).
Excellent chemoselectivity was also observed in the presence of aldehyde
and t-Bu ester groups (entries 7, 8). It is well known that the combination
of CBr4 and PPh3 is the olefinic reagent of aldehyde. In this system, no
olefin was observed. It is indicated that the reaction of CBr4 and PPh3 with
a1dehyde was suppressed. This method is also compatible with other function
groups, just as are the nitro and olefin groups (entries 1, 8, 9).
The procedure for deprotection of the MOM group is simple. A mixture of
MOM ether (0.5 mmol), CBr4 (0.1 mmol), and PPh3 (0.1 mmol) in anhydrous
CH2ClCH2Cl (2.5 mL) was heated at 408C for an appropriate time to complete
the reaction. After complete conversion as monitored by TLC, the solvent was
removed under reduced pressure. The product was purified by column chro-
matography on silica gel with ethyl acetate/petroleum ether.
In conclusion, we set up a mild and efficient method for the selective
removal of MOM ether group in the presence of other protective groups
using CBr4 and PPh3 in an aprotic solvent (CH2ClCH2Cl) at 408C. The
adopted procedure is simple, inexpensive, and high yield that makes it a
useful addition to the existing methods.
ACKNOWLEDGMENTS
We thank the Ministry of Education Foundation of China No. 2002 (27)
and the Southwest Normal University Doctoral Fund for financial support of
the study.
REFERENCES
1. Schelhaas, M.; Waldmann, H. Protecting group strategies in organic syn-
thesis. Angew. Chem., Int. Ed. Engl. 1996, 35, 2056.
2. Greene, T.W.; Wuts, P.G.M. Protective Groups in Organic Synthesis;
Wiley: New York, 1991; Chap. 2, 5.
3. Kocienki, P.J. Protective Groups; Georg Thieme: New York, 1994.
4. Auerbach, J.; Weinreb, S.M. Synthesis of Terrein, a metabolite of asper-
gillus terreus. J. Chem. Soc., Chem. Commun. 1974, 298.
5. Meyers, A.I.; Durandetta, J.L.; Munavu, R. 2-Thiazolines in organic syn-
thesis. Formation of beta-hydroxy aldehydes with protected hydroxy
groups. Synthesis of homoallylic alcohols. J. Org. Chem. 1975, 40, 2025.
6. Meyers, A.I.; Reider, P. Stereoselective synthesis of threo-3-hydroxy-2-
methylcarbocylic acids using alkoxyalkyl propionates. J. Chem. Soc.
1979, 101, 2501.

4330
Peng et al.
7. Cheng, Z.-Y.; Bin, L.; Long, Q.-H. A modified procedure for the depro-
tection of methoxymethyl ether. Tetrahedron Letter 2000, 41, 819–822.
8. Monti, H.; Leandri, G.; Klos-Rinquet, M.; Corriol, C. An efficient depro-
tective method for allylic alcohols protected as methoxyethoxymethyl
(MEM) and methoxymethyl ether. Synth. Commun. 1983, 13, 1021.
9. Ireland, R.E.; Vamey, M.D.J. Approach to the total synthesis of chloro-
thricolide: synthesis of (þ2)-19,20-dihydro-24-O-methylchlorothrico-
lide methyl ester ethyl carbonate. J. Org. Chem. 1986, 51, 635.
10. Quindon, Y.; Morton, H.E.; Yoalim, C. Dimethylboron bromide and
diphenylboron bromide. Acetal and ketal cleavage. Cleavage of MEM,
MOM and MTM ethers. Tetrahedron Lett. 1983, 24, 3969.
11. Shibasaki, M.; Ishida, Y.; Okabe, N. A novel synthesis of (2)-carpeti-
mycin. Tetrahedron Lett. 1985, 26, 2217.
12. Corey, E.J.; Hua, D.H.; Seitz, S.P. Methods for the interconversion of
protective groups. Ttransformation of MEM ethers into isopropylthio-
methyl ethers or cyanomethyl ethers. Tetrahedron Lett. 1984, 25, 3.
13. Boeckman, R.k., Jr.; Potenza, J.C. Catechol boron halides: mild and selec-
tive reagents for cleavage of common protecting groups. Tetrahedron
Lett. 1985, 26, 1411.
14. Stephen, H.; Daniel, D.; Yves, D. Mild cleavage of methoxymethyl
(MOM) ethers with trimethylsilyl bromide. Tetrahedron Lett. 1984, 25,
2515.
15. Lee, A.S.-Y.; Hu, Y.-J.; Chu, S.-F. A simple and highly efficient depro-
tecting method for methoxymethyl and methoxyethoxymethyl ethers.
Tetrahedron 2001, 57, 2121–2126.
Received in Japan May 24, 2004