new CpRu-based catalytic system that efficiently brings about
the single-step deprotection of allyl ethers without the need
for any additional reagent other than an alcoholic solvent.
Table 1. Catalytic Deprotection of Allyl Ethers 1 by Use of a
[CpRu(CH3CN)3]PF6 (3)-Quinaldic Acid (4) Combined Systema
substrate
entry
(mM)
S/Cb
solvent
time, h % yieldc
1
2
3
1a (100)
1a (500)
1a (1000)
100 CH3OH
0.5
3
>99
99
98d
500 CH3OH
1000 CH3OH
3
4e, f 1a (1000) 10 000 CH3OH
17
41
99
98
82g
99
99
18
99
99
99
5
6
1a (100)
1a (100)
1a (100)
1a (100)
1a (100)
1a (100)
1a (100)
1a (100)
1b (500)
1c (500)
1d (100)
1e (500)
1f (500)
100 C2H5OH
2
3
100 i-C3H7OH
7
100 t-C4H9OH
13
6
8
100 1:1 CH3OH-H2O
100 1:1 CH3OH-DMF
100 1:1 CH3OH-CH3CN
100 1:1 CH3OH-THF
100 1:1 CH3OH-CH2Cl2
500 CH3OH
A 1:1 mixture of cyclopentadienyltris(acetonitrile)ruthenium-
(II) hexafluorophosphate ([CpRu(CH3CN)3]PF6) (3) and
triphenylphosphine (P(C6H5)3) catalytically deprotects allyl
esters in methanol via a π-allyl mechanism,7 but the system
is completely inert for the cleavage of allyl ethers.8 With
this result as the starting point, the ligand acceleration effect
for [CpRu(CH3CN)3]PF6 (3) was combinatorially examined
for the deprotection of allyl 2-phenylethyl ether (1a) in
methanol at 30 °C for 3 h with the standard fixed concentra-
tions of [1a] ) 100 mM, [ligand] ) 1 mM, and [3] ) 1
mM. Among the many ligands tested, including phosphines,
sulfides, amines, and pyridines and their derivatives pos-
sessing amino, hydroxyl, alkoxyl, carboxyl, or alkoxycar-
bonyl functionalities, 2-pyridinecarboxylic acid showed a
particularly high reactivity, affording 2-phenylethanol (2a)
in >99% yield. When the hexahydropyridine derivative,
2-piperidinecarboxylic acid, was used as a ligand, the
reactivity dramatically decreased. The use of pyridine,
benzoic acid, pyridinium benzoate, sodium 2-pyridinecar-
boxylate, 3-pyridinecarboxylic acid, 4-pyridinecarboxylic
acid, 8-quinolinecarboxylic acid, 2-(hydroxymethyl)pyridine,
and 2-(aminomethyl)pyridine as ligands resulted in virtually
no reactivity. These results clearly indicate the importance
of a synergetic effect between the ligand sp2-hybridized N
atom and the adjacent COOH group of the pyridinecarboxylic
acid producing a five-membered chelating ring with the
CpRuII catalyst precursor.
9
6
10
11
12
13
14
15
16
17
3
0.5
0.5
3
500 CH3OH
3
>99
>99
97
100 CH3OH
3
500 CH3OH
3
500 CH3OH
3
94
a Reactions were carried out in CH3OH at 30 °C with [3] ) [4] ) 1
mM unless otherwise specified. b S/C ) substrate/catalyst. c Determined by
GC analysis. For details, see Supporting Information. d Under 200 mmHg
Ar. e T ) 70 °C. f [Catalyst] ) 0.1 mM. g Catalyst was insoluble.
frequency (TOF) is 700 h-1. In addition to methanol, ethanol
and iso-propyl alcohol can also be used as solvents, while
tert-butyl alcohol gives a lower yield because of the low
solubility of the catalyst system (entries 5-7) in that solvent.
When water, DMF, THF, or dichloromethane is used as a
cosolvent with methanol (entries 8, 9, 11, and 12) the yield
remains high. However, a solvent mixture of 1:1 acetonitrile
significantly lowers the reactivity (entry 10).
The generality of this new catalytic deprotection process
is high. The allyl groups of the primary, secondary, and
tertiary alkanols such as 1a, 1b, and 1c are quantitatively
removed (entries 2, 13, and 14). Both aliphatic allyl ethers
and allyl phenyl ether (1d) are smoothly deprotected (entry
15). Allyl 4-pentenyl ether (1e) is converted to 4-pentenol
without any olefin isomerization (entry16). An acetylene-
containing alkyl allyl ether 1f can also be used (entry 17).
The high chemoselectivity is further demonstrated by the
reactions of a series of diprotected trans-1,2-cyclopen-
tanediols 5a-d, in which one hydroxyl functionality is
protected as the allyl ether and the other as the benzoate,
benzyl ether, methoxymethyl ether, or tert-butyldiphenylsilyl
ether. Even more highly multifunctionalized molecules such
as dipeptide 6a, possessing tert-butyl ester and Fmoc
protecting group, and nucleoside 7a are deprotected with high
chemoselectivity. In all these cases, only the allyl group is
removed in >99% yield ([5a-d] ) [6a] ) [7a] ) 100 mM,
[catalyst] ) 1 mM, 30 °C, 0.5-4 h).
As shown in Table 1, use of quinaldic acid (4), 2-quino-
linecarboxylic acid, even further increases the reactivity,
resulting in complete reaction within 30 min (entry 1).Depro-
tection is possible with a substrate/catalyst (S/C) ratio as high
as 1000 (entry 3) at 30 °C; this ratio can be further increased
10 000 at 70 °C (entry 4). Under the conditions of entry 4,
the turnover number (TON) is 4000 and the turnover
The allyl cleavage is assumed to proceed via a π-allyl-
ruthenium(IV) species, which reacts with the alcoholic
solvent to give the corresponding alcohols.7 Although the
reaction is reversible, excess solvent forces the equilibrium
to the product side. Consistent with this view, nearly
(6) Kitov, P. I.; Bundle, D. R. Org. Lett. 2001, 3, 2835-2838.
(7) Kitamura, M.; Tanaka, S.; Yoshimura, M. J. Org. Chem. 2002, 67,
4975-4977.
(8) The Ru-phosphine complex isomerizes allyl ethers to the corre-
sponding alkenyl ethers, although the reactivity is low.3a,b
1874
Org. Lett., Vol. 6, No. 11, 2004