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.