An efficient method for the ether forming reaction between alkyl diphenylphosphinate and alkoxytrimethylsilane by the promotion of trimethylsilyl triflate

Article abstract of DOI:10.1246/cl.2004.1362

The trimethylsilyl triflate promoted reactions of alkyl diphenylphosphinates with alkoxytrimethylsilanes in chloroform, 1,2-dichloroethane or 1,2-dichloropropane, proceeded smoothly to give the corresponding ethers in good yields.

Full text of DOI:10.1246/cl.2004.1362

1362
Chemistry Letters Vol.33, No.10 (2004)
An Efficient Method for the Ether Forming Reaction between Alkyl Diphenylphosphinate
and Alkoxytrimethylsilane by the Promotion of Trimethylsilyl Triflate
Yohei Kobashi,y;yy Tomofumi Minowa,y;yy and Teruaki Mukaiyamaꢀy;yy
yCenter for Basic Research, The Kitasato Institute (TCI), 6-15-5 Toshima, Kita-ku, Tokyo 114-0003
yyKitasato Institute for Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641
(Received August 6, 2004; CL-040929)
The trimethylsilyl triflate promoted reactions of alkyl diphe-
nylphosphinates with alkoxytrimethylsilanes in chloroform, 1,2-
dichloroethane or 1,2-dichloropropane, proceeded smoothly to
give the corresponding ethers in good yields.
Table 1. Reactions of benzyl diphenylphosphinate (1) and tri-
methyl-(2-phenylethoxy)silane (2) in the presence of various
Lewis acids
Lewis Acid (1.0 equiv.)
TMSO(CH2)2Ph (2)
O
(1.0 equiv.)
Ph
BnO PPh2
BnO
A number of methods have been reported for etherification
of alcohols after the Williamson’s method of using alkyl halide
and metal alkoxide was reported.1 In these methods, strong bases
such as sodium hydride are used for generating alkoxy anions
from alcohols except for the case of reactive substrates like ben-
zyl alcohol.2 Therefore, development of a new and efficient
etherification reaction to be carried out under mild condition
is one of the most challenging and important topics in organic
synthesis.
Very recently, it was shown from our group that phosphine
oxide effectively promoted stereoselective glycosylation reac-
tions (Scheme 1).3 It is noteworthy that phosphine oxide attacks
glycosyl halide to form a reactive phosphonium salt intermediate
that immediately reacts with glycosyl acceptors to afford the cor-
responding ꢀ-glycosides effectively. In order to apply this
unique nucleophilic character of phosphine oxide to form the
highly reactive phosphonium salt, a new carbon–oxygen bond
forming reaction by using the phosphonium salt generated from
alkyl diphenylphosphinate and Lewis acid was planned.
CH2Cl2, rt, 3 h
1
3
Entry Lewis Acid Yield/% Entry Lewis Acid Yield/%
1
2
TMSI
BF3OEt2
AlCl3
N.D.a
N.R.
N.R.
N.R.
N.R.
N.R.
N.R.
N.R.
N.R.
N.R.
11
12
Sc(OTf)3
Hf(OTf)4
Yb(OTf)3
TMSOTf
TIPSOTf
TESOTf
TBSOTf
TMSOTf
TMSOTf
TMSOTf
N.R.
N.R.
N.R.
51
3
13
14
4
TiCl4
MgBr2OEt2
ZnCl2
5
15
16
49
52
6
7
Zn(OTf)2
Cu(OTf)2
SnCl4
17
53
58
8
18b
19b,c
20d
9
10
70
8
Sn(OTf)2
a45% of BnI was obtained. bThe reaction was performed in chloro-
form. c1.2 equiv. of 2 was used. d2-Phenylethylalcohol was used in
chloroform instead of 2.
were obtained in moderate yields when trialkylsilyl triflates were
used as Lewis acids (Table 1, Entries 14–17). Studies on solvent
effects and ratios of substrates and trimethylsilyl triflate showed
that the desired 3 was afforded in 70% yield when 1.2 equiv. of 2
and 1.0 equiv. of 1 were allowed to react in the presence of
1.0 equiv. of trimethylsilyl triflate in chloroform (Table 1, Entry
19) while the yield remained low when 2-phenylethyl alcohol
instead of 2 was used in the presence of trimethylsilyl triflate
(Table 1, Entry 20).
Next, etherifications of alkyl diphenylphosphinates and al-
koxytrimethylsilanes were tried (Table 2). When trimethylsilyl
triflate was treated with benzyl diphenylphosphinate and tri-
methyl(2-phenylethoxy)silane, benzyloxytrimethylsilane, or tri-
methyl(1-methyl-2-phenylethoxy)silane, the reactions proceed-
ed smoothly at room temperature to afford the corresponding
benzyl ether derivatives (Table 2, Entries 1–3). The etherifica-
tion of using 3-phenylpropyl diphenylphosphinate or 2-phen-
oxyethyl diphenylphosphinate proceeded in 1,2-dichloroethane
or 1,2-dichloropropane at refluxing temperature (Table 2,
Entries 5–7). When (S)-1-phenyethyl diphenylphosphinate was
used, the reaction proceeded more rapidly and completed at
0 ꢁC to afford racemic products within several hours, indicating
that this reaction proceeded by SN1 mechanism (Table 2, Entries
8–10). The use of less reactive D-menthyl diphenylphosphinate,
on the other hand, did not afford the desired ether product
(Table 2, Entry 11).
N
P=O
3
BnO
BnO
O
BnO
BnO
O
O
MS 5A
BnO
BnO
O
+
HO
BnO
X
O
X
BnO
CH2Cl2, rt
or
CHCl3, reflux
Br
α /β = 92/8 to 98/2
Scheme 1. Glycosylation of several acceptors with 2,3,4,6-tet-
ra-O-benzyl-D-glucopyranosyl bromide promoted by tri(1-pyr-
rolidino)phosphine oxide.
In this communication, we would like to report an efficient
method for carbon–oxygen bond forming reaction by using alkyl
diphenylphosphinate and alkoxytrimethylsilane in the presence
of trimethylsilyl triflate as a promoter.
In the first place, the reaction of benzyl diphenylphosphinate
(1) and trimethyl(2-phenylethoxy)silane (2) by using various
Lewis acids in dichloromethane at room temperature was tried
(Table 1). The use of iodotrimethylsilane that is known to react
readily with triphenylphosphine oxide4 resulted in the formation
of benzyl iodide in 45% yield (Table 1, Entry 1). On the other
hand, no reaction took place when powerful Lewis acids such
as AlCl3 and TiCl4, a mild one such as MgBr2OEt2 and transi-
tion metal triflates were used (Table 1, Entries 2–13). It was in-
teresting to note that the desired benzyl 2-phenylethyl ethers (3)
Copyright ꢀ 2004 The Chemical Society of Japan

Chemistry Letters Vol.33, No.10 (2004)
1363
Table 2. Reaction of alkyl diphenylphosphinate and alkoxyltri-
methylsilane in the presence of TMSOTf
form (1 mL) was added trimethylsilyl triflate (36.2 mL,
0.196 mmol) at 0 ꢁC. The mixture was stirred for 4 h at room
temperature and then quenched with sat. NaHCO3. After the re-
sulting mixture was extracted with dichloromethane, dried over
MgSO4, filtered and evaporated, it was purified by preparative
TLC (silica gel, THF/n-Hex = 25/1) to give the desired benzyl
2-phenylethyl ether (3) (0.0299 g, 70%) as a colorless oil.
Thus, etherification between alkyl diphenylphosphinate and
alkoxytrimethylsilane proceeded successfully to afford the cor-
responding ether in good yield by promoting with trimethylsilyl
triflate. This reaction is quite practical because alkyl diphenyl-
phosphinates are prepared easily from the corresponding alco-
hols and diphenylchlorophosphinate often as white crystals in
the presence of triethylamine. Moreover, diphenylphosphinic
acid trimethylsilyl ester, a co-product, is easily separated by
washing with saturated NaHCO3 solution.
TMSOTf
(1.0 equiv.)
Ph2P(=O)OR
R'OTMS
ROR'
CHCl3
(1.2 equiv.)
(1.0 equiv.)
Entry Ph2P(=O)OR R0OTMS
Temp.
Time Yield/%
1
1
1
1
1
4
4
5
6
6
6
7
2
8
rt
rt
4 h
4 h
70
74
2
3
9
rt
4 h
4 h
69
63
4
10
2
rt
5a
6b
7a
8
reflux
reflux
reflux
12 h
12 h
12 h
80
68
9
2
71
2
ꢂ60 ꢁC ! 0 ꢁC 2 h
ꢂ60 ꢁC ! 0 ꢁC 3 h
ꢂ60 ꢁC ! 0 ꢁC 3 h
82c
90c
59c
N.D.
9
8
10
111
10
2
This study was supported in part by the Grant of the 21st
Century COE Program, Ministry of Education, Culture, Sports,
Science and Technology (MEXT), Japan.
reflux
11 h
a1,2-Dichloropropane was used as a solvent. b1,2-Dichroloethane
c
was used as a solvent. Racemic product was obtained.
References and Notes
O
O
1
Recent reports on C–O bond formation: B. D. Sherry, A. T.
Radosevich, and F. D. Toste, J. Am. Chem. Soc., 125, 6076
(2003); H. Kim and C. Lee, Org. Lett., 4, 4369 (2002);
P. A. Evans and D. K. Leahy, J. Am. Chem. Soc., 124,
7882 (2002); T. Shintou and T. Mukaiyama, Chem. Lett.,
32, 984 (2003).
Ph
Ph POBn
2
Ph PO
Ph
OTMS
Ph
2
2
4
1
O
O
O
O
Ph PO
Ph
Ph PO
2
2
Ph PO
2
5
6
2
O. Mitsunobu, ‘‘Comprehensive Organic Synthesis,’’ ed. by
B. M. Trost and I. Fleming, Pergamon Press, Oxford (1991),
Vol. 6, pp 22–28; M. B. Smith and J. March, ‘‘March’s
Advanced Organic Chemistry, Reaction Mechanism and
Structure,’’ 5th ed., John Wiley & Sons, New York (2001),
pp 477–478.
T. Mukaiyama and Y. Kobashi, Chem. Lett., 33, 10
(2004); Y. Kobashi and T. Mukaiyama, Chem. Lett., 33,
874 (2004).
L. A. Paquette, ‘‘Encyclopedia of Reagents for Organic
Synthesis,’’ John Wiley and Sons, Chichester (1995), pp
2857–2858.
Alkyl diphenylphosphinate was prepared according to the re-
ported procedure and purified by silica gel chromatography.
K. Goda, R. Okazaki, K. Akiba, and N. Inamoto, Bull. Chem.
Soc. Jpn., 51, 260 (1978).
7
OTMS
BnOTMS
Ph
OTMS
8
9
10
The present reaction is assumed to proceed via the reactive
phosphonium triflate intermediate generated by the activation of
oxygen atom of alkyl diphenylphosphinate with TMSOTf. Then,
the SN1 attack of alkoxytrimethylsilane to the carbon atom of the
alkoxy phosphonium triflate afforded the corresponding ether
and a complex of diphenylphosphinic acid trimethylsilyl ester
and TMSOTf, that is easily separated by washing with sat.
NaHCO3 solution.
3
4
5
The typical experimental procedure is described for the re-
action of 15 and 2 (Table 2, Entry 1): to a stirred mixture of 1
(0.0621 g, 0.201 mmol) and 2 (0.0469 g, 0.241 mmol) in chloro-
Published on the web (Advance View) September 18, 2004; DOI 10.1246/cl.2004.1362