CL-140579
Received: June 10, 2014 | Accepted: June 26, 2014 | Web Released: July 3, 2014
Selective Deprotection of Me3Si-/Ph2P(O)-protected Arylalkynes: Methyl Grignard
Reagent-promoted Dephosphorylation of Ph2P(O)-protected Alkynes
Lifen Peng, Feng Xu, Kenta Shinohara, Akihiro Orita,* and Junzo Otera
Department of Applied Chemistry, Okayama University of Science, Kita-ku, Okayama 700-0005
(E-mail: orita@dac.ous.ac.jp)
A Ph2P(O)-protected alkyne underwent dephosphorylation by
treatment with MeMgBr in THF with Me3Si-protection untouched.
The dephosphorylation followed by a transition-metal-catalyzed
coupling of the resulting terminal alkyne with aryl halides was
carried out in a one-pot manner to afford the desired coupling
product. Selective deprotection of Me3Si-/Ph2P(O)-protected
alkynes enabled facile syntheses of expanded π-systems such
as cyclic phenyleneethynylenes and unsymmetrically substituted
ditriazol.
Table 1. Dephosphorylation of 1 using various basesa
base
H3O+
MeO
P(O)Ph2
MeO
THF,
conditions
1
2
Entry
Base
Conditions
Yield/%b
1
2
3
4
5
6
MeMgBr (1.0 equiv)
BuMgCl (1.0 equiv)
BuLi (1.0 equiv)
t-BuONa (1.5 equiv)
t-BuOLi (1.5 equiv)
LiHMDS (1.0 equiv)
0 °C, 0.5 h
0 °C, 0.5 h
¹78 °C, 0.5 h
r.t., 5 h
r.t., 5 h
r.t., 2 h
93
62
89
32
trace
11
Protection-deprotection is one of the commonly utilized
technologies in organic synthesis.1 A large number of protecting
groups have been developed so far, and new protecting groups are
still required for sophisticated organic syntheses.2 We have been
involved in syntheses of acetylene derivatives3 and their applica-
tion to organic materials such as organic field-effect transistors4
(OFETs), organic light-emitting diodes5 (OLEDs), organic photo-
voltaics6 (OPVs), and self-assembly material.7 In these studies,
we have developed a new protecting group for terminal alkynes,
Ph2P(O), which enabled easy isolation of products because of the
high polarity of the Ph2P(O) group,8 and successfully accom-
plished dephosphorylation/transition-metal-catalyzed couplings
such as Sonogashira, Migita-Kosugi-Stille, and Eglinton cou-
plings in the one-pot manner.9 Although the Me3Si group is the
most commonly used protecting group for terminal alkynes, it
suffers from desilylation when treated with t-BuOK,1 which is
required for dephosphorylation. To overcome this incompatibility
between Me3Si- and Ph2P(O)-protections, a new reagent was
investigated, which was commercially available and enabled the
phosphoryl-selective deprotection. Because it is well known that
Me3Si-protection can be removed selectively by treatment with
the fluoride anion,1 if a new technology for Ph2P(O)-selective
deprotection is developed, syntheses of more complicated acet-
ylene derivatives can be realized by taking advantage of Me3Si-/
Ph2P(O)-protected ethynes as key building blocks.
We report herein that the Grignard reagent (MeMgBr)
facilitates phosphoryl-selective deprotection in Me3Si-/Ph2P(O)-
protected alkynes and the resulting magnesium ethynide can be
used for nucleophilic addition to aldehydes and transition-metal-
catalyzed coupling with aryl halides. By invoking the selective
deprotection, Me3Si-/Ph2P(O)-protected alkynes serve well as
building blocks for syntheses of π-expanded acetylenes such
as cyclic phenyleneethynylenes and unsymmetrically substituted
ditriazol.
First, we evaluated the dephosphorylation ability of various
bases such as the Grignard reagent, alkyllithium, metal alkoxide,
and lithium amide (Table 1). Methylmagnesium bromide was most
efficient, and the treatment of 1 with 1.0 equiv of MeMgBr
followed by aqueous workup provided 2 in 93% yield (Entry 1).
When BuMgCl or BuLi was used, the formation of unidentified
by-products was observed (Entries 2 and 3). Dephosphorylation
aReaction conditions: 1 (1.0 mmol), THF (10 mL). bIsolated yields.
MeMgBr
(1.0 equiv)
H3O+
MeOOC
OHC
P(O)Ph2
P(O)Ph2
MeOOC
THF,
-78 - 0 °C,
15 min
91%
MeMgBr
(1.0 equiv)
Me
HO
H3O+
P(O)Ph2
THF,
-78 - 0 °C,
88%
15 min
Scheme 1. Dephosphorylation of Ph2P(O)-protected alkyne bearing
-COOMe and -CHO.
with other bases such as metal alkoxides and amide proceeded
sluggishly (Entries 4-6). Although the MeMgBr-promoted de-
phosphorylation was useful for the ester-substituted derivative, for
the formyl-substituted derivative, addition of the MeMgBr reagent
proceeded (Scheme 1).
Since the formation of 2 was not observed when 4-methoxy-
phenylethynyl(trimethyl)silane was treated with MeMgBr at 0 °C,
phosphoryl-selective deprotection of 3 was investigated. When
1.0 equiv of MeMgBr was added to THF solutions of 3a and 3b at
0 °C, the expected dephosphorylation proceeded smoothly to afford
4a and 4b in 92% and 93% yields, respectively, without a loss of
the silyl group (Scheme 2). In sharp contrast to this, when BuLi
was used for the dephosphorylation of 3b, unexpected desilylation
occurred, resulting in the formation of a mixture of 4b and 6b.
On the other hand, when tetrabutylammonium fluoride (TBAF)
was added to 3a and 3b, silyl-selective deprotection occurred to
furnish 5a and 5b in high yields, respectively.1 Although selective
deprotection of Me3Ge-/Me3Si-protected diynes has been reported
so far, this technology is not suitable for common use because
several rather expensive reagents are required: Me3GeBr for germyl
protection and 18-crown-6 for desilylation.10
The magnesium ethynide derived from the selective dephos-
phorylation of 3b could be used in the following nucleophilic
addition to aldehydes to provide trimethylsilylethynyl derivatives
bearing iodophenyl 7 and phosphorylethynylphenyl 8 (Scheme 3).
With these results in hand, we carried out dephosphoryl-
ation/transition-metal-catalyzed coupling in a one-pot manner
© 2014 The Chemical Society of Japan