Hydrophosphination of propargylic ethers with diphenylphosphine in the presence of LiHMDS, N-Heterocyclic carbene, and Ti(NMe2)4

Article abstract of DOI:10.1246/cl.2010.276

Regio- and stereoselective hydrophosphination of propargylic ethers with diphenylphosphine has been achieved using three-component catalyst, LiN(SiMe₃)₂/1,3-dimethylimidazol-2-ylidene/Ti(NMe ₂)₄ (10 mol% of each

Full text of DOI:10.1246/cl.2010.276

doi:10.1246/cl.2010.276
276
Published on the web February 16, 2010
Hydrophosphination of Propargylic Ethers with Diphenylphosphine
in the Presence of LiHMDS, N-Heterocyclic Carbene, and Ti(NMe2)4
Ryosuke Sakae, Yuta Yamamoto, Kimihiro Komeyama, and Ken Takaki*
Department of Chemistry and Chemical Engineering, Graduate School of Engineering, Hiroshima University,
Kagamiyama, Higashi-Hiroshima 739-8527
(Received December 22, 2009; CL-091135; E-mail: ktakaki@hiroshima-u.ac.jp)
Table 1. Hydrophosphination of 1a by various catalysta
Regio- and stereoselective hydrophosphination of propar-
gylic ethers with diphenylphosphine has been achieved using
three-component catalyst, LiN(SiMe3)2/1,3-dimethylimidazol-
2-ylidene/Ti(NMe2)4 (10 mol % of each).
Yield of
2ab/%
Run Catalyst
Time/h
Z/E ratiob
Hydrophosphination, phosphinylation, and phosphonylation
of alkynes have been frequently used for the synthesis of ¡,¢-
unsaturated phosphorus compounds, which are valuable materi-
als as biologically active compounds, ligands, and synthetic
reagents.1 Promoters and catalysts for the reaction of trivalent
hydrophosphines have been limited, compared with pentavalent
phosphorus compounds.2 Beside radical initiators, a few metal
catalysts such as La,3 Co,4 Ni,5 and Pd5 have been reported for
the hydrophosphination of unactivated alkynes. Moreover
titanium phosphinidene complex, [Ti=PR], also catalyzes the
reaction of diphenylacetylene with PhPH2.6 However, these
catalysts are not always applicable to the reaction of a wide
range of alkynes and thus a search for new catalysts has been
continued. For example, hydrophosphination of propargylic
alcohols and that of 1-alkynylphosphines succeeded using Ru7
and Cu catalysts,8 respectively.
When we carried out the hydrophosphination of 3-methoxy-
1-phenyl-1-propyne (1a) with Ph2PH by Yb-imine catalyst,3b
the expected product 2a was formed in only 56% yields with a
low stereoselectivity (Scheme 1). The sophisticated Co(acac)2/
BuLi catalyst4 gave the three regioisomers, 2a, 3, and 4, though
with a perfect syn-selectivity. In order to overcome these
limitations, we tested various catalysts for this reaction, and
found that regio- and stereoselective hydrophosphination of
propargylic ethers can be conducted under mild conditions by
three-component catalyst, LiN(SiMe3)2/N-heterocyclic carbene/
Ti(NMe2)4.9 We report herein these results.
1
2
3
4
LiHMDS (A)
Ti(NMe2)4
IMes
Ti(NMe2)4/IMes
LiHMDS/Ti(NMe2)4
(B)
24
24
24
24
3
8
5
7
ndc
ndc
ndc
ndc
5
6
7
24
81
91
97
95/5
83/17
97/3
LiHMDS/IMe (C)
LiHMDS/IMe/
Ti(NMe2)4 (D)
30 min
5 min
aReaction conditions: 1a (1 mmol), Ph2PH (1 mmol), and
b
1
c
toluene (1 mL). Determined by H NMR. Not determined.
in 97% yield with a Z/E ratio of 97/3 after oxidative work-up
(Table 1, Run 7). Toluene solvent can be substituted by
cyclohexane, but THF and MeCN slightly decreased the yield
and stereoselectivity. Then, the reaction was repeated under
similar conditions using one or two components of D to
investigate which one really contribute to the good performance.
The reaction with LiHMDS alone (catalyst A) afforded 2a in
very low yields (Run 1). Similarly, isolated 1,3-dimesitylimi-
dazol-2-ylidene (IMes),10 Ti(NMe2)4, and their mixture (1/1)
showed nearly no catalyst activity (Runs 2-4). In contrast, the
reaction using a mixed catalyst of the LiHMDS and Ti(NMe2)4
(catalyst B) gave 2a in 81% yield (Z/E = 95/5), although longer
reaction time was necessary (Run 5). A complex of the LiHMDS
and IMe (catalyst C) reduced the reaction period and resulted in
good yield (91%), but the Z/E ratio decreased to 83/17 (Run 6).
Similar effects were confirmed in the reaction of 1-(4-chloro-
phenyl)-3-methoxy-1-propyne (1j) using the four catalysts A-D.
Based on these results, it is apparent that all individual
components of D take part in the reaction, and efficiency and
selectivity decrease drastically by lack of one or two catalytic
components, vide infra.
Surprisingly, treatment of propargylic ether 1a with equi-
molar amounts of Ph2PH in toluene at room temperature for
5 min in the presence of lithium hexamethyldisilazide
(LiHMDS), 1,3-dimethylimidazol-2-ylidene (IMe), and
Ti(NMe2)4 (10 mol % of each; catalyst D) gave the product 2a
Next, hydrophosphination of various propargylic ethers was
carried out with the three-components catalyst D (Table 2).
Substitution of the methyl ether moiety by other protecting
groups like t-butyldimethylsilyl, benzyl, and 2-tetrahydropyr-
anyl ethers did not affect the reaction efficiency to give the
products 2b-2d in high yields with nearly perfect Z-stereo-
selectivity (Runs 2-4). The alkyne 2e having methoxymethyl
substituent, which has been known as a good substrate for
carbolithiation of alkyne,11 showed inferior results (Run 5). Both
Scheme 1. Hydrophosphination of 1a by the conventional
catalysts.
Chem. Lett. 2010, 39, 276-277
© 2010 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

277
Table 2. Hydrophosphination of various propargylic alkynes
by the three-component catalyst Da
Yieldb Z/E
/% ratiob
Propargylic ether
Run
2
1
R1
R2 R3 R4
1
2
3
4
1a Ph
1b Ph
1c Ph
1d Ph
H
H
H
H
H
H
H
H
H
H
H
Et
H
H
H
H
H
H
H
H
H
H
H
H
OMe
OTBDMS 2b
OBn
2a
97 97/3
98 99/1
96 98/2
95 95/5
43 83/17
95 99/1
98 99/1
98 99/1
99 96/4
98 97/3
95 94/6
86 77/23
91 95/5
2c
2dc
2e
2f
2g
2h
2i
2j
2k
2l
Figure 1. 31P NMR spectra of the mixture of Ph2PH and the
catalysts A-D.
OTHP
MOM
OMe
OMe
OMe
OMe
OMe
OMe
OMe
5d 1e Ph
6
7
8
9
1f 2-MeC6H4
an activator of the Ph2PLi nucleophile, and Ti(NMe2)4 as a
controller of the stereochemistry.
1g 4-MeC6H4
1h 4-MeOC6H4
1i 2-ClC6H4
In summary, we have demonstrated regio- and stereo-
selective hydrophosphination of propargylic ethers with Ph2PH
by use of the three-component catalyst, LiHMDS/N-hetero-
cyclic carbene/Ti(NMe2)4.12 Further studies on mechanistic
aspects and scope and limitation are in progress.
10 1j 4-ClC6H4
11 1k 4-BrC6H4
12e 1l Ph
13f 1m Ph
Me Me OMe
2m
aReaction conditions: 1 (1 mmol), Ph2PH (1 mmol), and
toluene (1 mL). bDetermined by 1H NMR. cIsolated as 2-
diphenylphosphinyl-3-phenyl-2-propen-1-ol (2d¤). dReaction
was carried out at 100 °C for 24 h. Reaction period was 3 h.
fReaction period was 6 h.
References and Notes
1
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1992, 333. b) R. K. Haynes, S. C. Vonwiller, T. W. Hambley,
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e
2
3
a) F. Alonso, I. P. Beletskaya, M. Yus, Chem. Rev. 2004, 104,
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electron-donating and -withdrawing aromatic alkynes gave
exclusively the Z-alkenylphosphine oxides 2f-2k in quantitative
yields (Runs 6-11). Secondary and tertiary propargylic ethers
1l and 1m gave satisfactory product yields, though longer
reaction time was necessary to complete the reaction and
stereoselectivity was decreased in the former case (Runs 12 and
13). Unfortunately, merits of the three-component catalyst D
did not appear in the reaction of 1-phenyl-1-propyne, wherein
2-diphenylphosphinyl-1-phenyl-1-propene was obtained in sim-
ilar yields and selectivities (ca. 60%, Z/E = 70/30) with the
catalysts B-D.
In spite of the good performance of the catalyst D, the role
of the individual component is unclear. Thus, in order to get
some information on the active species generated in situ, NMR
tube reaction of Ph2PH with equimolar amounts of A-D was
carried out in THF and measured by 31P NMR (Figure 1).
Treatment with LiHMDS (A) changed a signal of Ph2PH at
¹40 ppm to the broad one of the aggregated Ph2PLi at ¹26 ppm.
With LiHMDS/Ti(NMe2)4 (B), a sharp signal appeared at
¹19 ppm in addition to the broad one. Because the sharp signal
was only observed in the presence of Ti(NMe2)4, it may be
assignable to the titanium phosphido species. With LiHMDS/
IMe (C), the broad signal of Ph2PLi shifted to lower field at
¹22 ppm probably because of the coordination of IMe to Li
cation. On the treatment with the three component catalyst D,
two signals were observed at ¹22 and ¹19 ppm. Combining the
results shown above and those given in Table 1, it is likely that
the two phosphido species appearing at ¹22 and ¹19 ppm are
responsible for the fast reaction rate and high stereoselectivity,
respectively, that is, the N-heterocyclic carbene seems to act as
4
5
6
H. Ohmiya, H. Yorimitsu, K. Oshima, Angew. Chem., Int.
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M. A. Kazankova, I. V. Efimova, A. N. Kochetkov, V. V.
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This three-component catalyst was previously used for
hydroamination of alkynes: K. Takaki, S. Koizumi, Y.
Yamamoto, K. Komeyama, Tetrahedron Lett. 2006, 47,
7335; Corrigendum: K. Takaki, S. Koizumi, Y. Yamamoto,
K. Komeyama, Tetrahedron Lett. 2007, 48, 4643.
7
8
9
10 IMes was used instead of IMe to evaluate the effect of NHC,
because the latter was somewhat difficult to isolate and
unstable when pure.
11 M. Hojo, Y. Murakami, H. Aihara, R. Sakuragi, Y. Baba, A.
Hosomi, Angew. Chem., Int. Ed. 2001, 40, 621.
12 Supporting Information is available electronically on the
CSJ-Journal Web site, http://www.csj.jp/journals/chem-lett/
index.html.
Chem. Lett. 2010, 39, 276-277
© 2010 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/