Carbocupration of 1-alkynylphosphines followed by trapping with electrophiles

Article abstract of DOI:10.1021/ol0706657

Treatment of 1-alkynylphosphine with magnesium dlalkylcuprate in ether results in regio- and stereosetective syn-csrbocupration. The alkenyicopper Intermediate reacts with electrophile, which leads to allylation, acylation, and phosphination. The phosphin

Full text of DOI:10.1021/ol0706657

ORGANIC
LETTERS
2007
Vol. 9, No. 10
2031-2033
Carbocupration of 1-Alkynylphosphines
Followed by Trapping with Electrophiles
Shigenari Kanemura, Azusa Kondoh, Hideki Yorimitsu,* and Koichiro Oshima*
Department of Material Chemistry, Graduate School of Engineering, Kyoto UniVersity,
Kyoto-daigaku Katsura, Nishikyo-ku, Kyoto 615-8510, Japan
yori@orgrxn.mbox.media.kyoto-u.ac.jp; oshima@orgrxn.mbox.media.kyoto-u.ac.jp
Received March 19, 2007
ABSTRACT
Treatment of 1-alkynylphosphine with magnesium dialkylcuprate in ether results in regio- and stereoselective syn-carbocupration. The
alkenylcopper intermediate reacts with electrophile, which leads to allylation, acylation, and phosphination. The phosphination offers a new
route to gem-diphosphinoalkene, an interesting phosphorus-based organic structure.
Alkenylphosphines are important not only as ligands in
organometallic chemistry1 but also as reagents in organic
synthesis.2 Carbometalation3 of 1-alkynylphosphines is likely
to be an efficient method for the synthesis of alkenylphos-
phines.4 In 1976, Meijer et al. reported the addition of alkyl-
copper reagents to ethynyldiphenylphosphine and diphenyl-
(1-propynyl)phosphine.5 However, the scope of the addition
reaction was not fully investigated. In addition, no attempts
to trap the 1-diphenylphosphino-1-alkenylcopper species,
generated by the carbocupration, with electrophiles are
reported, except for hydrolysis. In the course of our study
on the use of 1-alkynylphosphines,6 we report herein our
detailed examination of the carbocupration of 1-alkynylphos-
phine. Trapping with electrophiles after the carbocupration
was also investigated.
Butylmagnesium bromide (1.6 mmol) was added to
copper(I) bromide dimethyl sulfide complex (0.75 mmol)
in ether at -78 °C to prepare magnesium dibutylcuprate
(Bu2CuMgBr) (Scheme 1).7 Diphenyl(phenylethynyl)phos-
Scheme 1
(1) Baya, M.; Buil, M. L.; Esteruelas, M. A.; On˜ate, E. Organometallics
2005, 24, 2030-2038 and references cited therein.
(2) (a) Organophosphorus Reagents; Murphy, P. J., Ed.; Oxford Uni-
versity Press: Oxford, UK, 2004. (b) Ohmiya, H.; Yorimitsu, H.; Oshima,
K. Angew. Chem., Int. Ed. 2005, 44, 2368-2370 and references cited therein.
(3) (a) Normant, J. F.; Alexakis, A. Synthesis 1981, 841-870. (b)
Lipshutz, L. H.; Sengupta, S. Org. React. 1992, 41, 135-631.
(4) Cross-coupling reaction of alkenyl triflates with secondary phosphines
provides an alternative route. (a) Gilbertson, S. R.; Fu, Z.; Starkey, G. W.
Tetrahedron Lett. 1999, 40, 8509-8512. (b) Kazankova, M. A.; Trosty-
anskaya, I. G.; Lutsenko, S. V.; Beletskaya, I. P. Tetrahedron Lett. 1999,
40, 569-572.
phine (1a, 0.50 mmol) was then added to the mixture, and
the resulting mixture was stirred for 2.5 h at 25 °C. The
reaction was quenched with water under argon. Crystalline
(5) (a) Meijer, J.; Westmijze, H.; Vermeer, P. Recl. TraV. Chim. Pays-
Bas 1976, 95, 102-104. (b) Alexakis, A.; Cahiez, G.; Normant, J. F.;
Villieras, J. Bull. Soc. Chim. Fr. 1977, 693-698.
(6) (a) Kondoh, A.; Yorimitsu, H.; Oshima, K. J. Am. Chem. Soc. 2007,
129, 4099-4104. (b) Kondoh, A.; Yorimitsu, H.; Oshima, K. Org. Lett.
2007, 9, 1383-1385.
(7) Lipshutz, B. H. In Organometallics in Synthesis, A Manual, 2nd ed.;
Schlosser, M., Ed.; John Wiley & Sons: Chichester, UK, 2002, Chapter
VI/3.2.3.
10.1021/ol0706657 CCC: $37.00
© 2007 American Chemical Society
Published on Web 04/17/2007

sulfur was then added to convert the air-sensitive product to
stable phosphine sulfide.8 Extractive workup and silica gel
column purification provided the corresponding phosphine
sulfide 2a. The stereochemistry of 2a was unambiguously
determined by analyzing the characteristic coupling con-
stants.2b,6a Instead of the addition of water, trapping with allyl
bromide and benzoyl chloride was successful to yield 3a9
and 4a, respectively. In each case, the reaction was perfectly
regio- and stereoselective. Unfortunately, attempted trapping
with benzaldehyde or methyl iodide resulted in failure.
The scope of organocopper reagents was investigated
(Scheme 2). The steric factor of the organocopper reagents
Scheme 2
A variety of 1-alkynylphosphines were subjected to the
carbocupration reaction followed by allylation (Table 1).
Table 1. Carbocupration of Alkynyldiphenylphosphine 1 with
Dibutylcuprate Followed by Trapping with Allyl Bromide
has little influence on the carbocupration. For instance, the
magnesium dialkylcuprates derived from isopropyl- and tert-
butylmagnesium reagents participated in the carbocupration/
allylation reaction. Interestingly, addition of N,N,N′,N′-
tetramethylethylenediamine (TMEDA) was essential to attain
a high yield of 5a.11 Dibenzylcuprate was also reactive.
However, phenylation12 and vinylation did not proceed.
Although allylation of 1a with diallylcuprate provided a
complex mixture, allylcopper, derived from equimolar
amounts of allylmagnesium bromide and CuBr‚SMe2, was
effective for allylcupration of 1a.13,14
entry
R
1
3
yield (%)a
1
2
3
4
5
6
7
C6H13
1b
1c
1d
1e
1f
3b
3c
3d
3e
3f
80 (88)
71 (89)
0
56 (68)
70 (74)
53 (63)
59 (85)
iPr
tBu
H
p-MeO-C6H4
o-MeO-C6H4
2-pyridyl
1g
1h
3g
3h
Next we examined trapping the 1-phosphinoalkenylcopper
intermediate with chlorodiphenylphosphine (Scheme 3). The
a Isolated yields. Yields based on 31P NMR analysis are in parentheses.
Although a bulky tert-butyl group of 1d completely sup-
pressed the reaction (entry 3), isopropyl- and hexyl-sub-
stituted alkynylphosphine 1b and 1c underwent the carbocu-
pration (entries 1 and 2). The reaction of ethynyldiphe-
nylphosphine (1e) proceeded smoothly to afford 3e in good
yield after allylation with allyl bromide (entry 4). It is worth
noting that 2-methoxyphenyl-substituted 1g as well as
2-pyridyl-substituted 1h reacted with magnesium dibutyl-
cuprate, without suffering from conceivable adverse effects
of the proximal coordinating groups (entries 6 and 7).
Scheme 3
Treatment of dicyclohexyl(phenylethynyl)phosphine (1i)
with magnesium dibutylcuprate followed by addition of allyl
bromide provided the corresponding product albeit in modest
yield (eq 1). The carbocupration of phenyldi(phenylethynyl)-
phosphine (1j) took place at both of the alkynyl moieties to
yield 2j (eq 2).10
trapping would yield gem-diphosphinoalkene derivatives,
which are difficult to synthesize despite the interesting
structure.15 Intriguingly, TMEDA or 1,2-bis(diphenylphos-
(8) Without adding sulfur, the results obtained in this paper were not
reproducible. The lack of reproducibility originated mainly from formation
of the corresponding phosphine oxide during tedious workup and the
difficulty in decomplexation of copper-phosphine complexes generated in
situ.
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Org. Lett., Vol. 9, No. 10, 2007

phino)ethane (DPPE) proved to be essential as an additive
for the trapping. Without the additive, only trace amounts
of gem-diphosphinoalkenes were formed and the protonated
products were mainly obtained. The exact role of the additive
is not clear. Not only 7a16 but also symmetrical 7b and 7c
were obtained in high yields.
phines 10 and 11 would be difficult to synthesize by the
conventional approach.15
Acknowledgment. This work was supported by Grants-
in-Aid for Scientific Research and COE Research from
MEXT and JSPS.
Finally, desulfidation of the products was investigated. The
desulfidation with tris(dimethylamino)phosphine17 proved to
be the best method in our case, which is high-yielding and
easy to perform (Scheme 4). Treatment of the phosphine
Supporting Information Available: Experimental pro-
cedure and characterization data of compounds. This material
is available free of charge via the Internet at http://pubs.acs.org.
OL0706657
(11) Without TMEDA, 5a was obtained in 31% yield, along with the
protonated product in 37% yield. The exact role of TMEDA is not clear.
(12) Lithium diphenylcuprate, derived from PhLi and CuBr‚SMe2,
provided a mixture containing triphenylphosphine sulfide, phenylacetylene,
and 65% yield of the sulfide of 1a. In general, magnesium cuprates afforded
less complex mixtures in the present reaction than lithium cuprates.
(13) Attempts to trap the corresponding alkenylcopper intermediate with
allyl bromide resulted in failure.
Scheme 4
(14) Lipshutz, B. H.; Hackmann, C. J. Org. Chem. 1994, 59, 7437-
7444.
(15) (a) Cantat, T.; Ricard, L.; Me´zailles, N.; Le Floch, P. Organome-
tallics 2006, 25, 6030-6038. (b) Bookham, J. L.; Conti, D.; McFarlane,
H. C. E.; McFarlane, W.; Thornton-Pett, M. J. Chem. Soc., Dalton Trans.
1994, 1791-1797. (c) Goli, M. B.; Grim, S. O. Tetrahedron Lett. 1991,
32, 3631-3634.
(16) Experimental procedure: The alkenylcopper intermediate was
prepared by the same procedure described in ref 8. DPPE (1.0 g, 2.5 mmol)
and chlorodiphenylphosphine (0.39 g, 1.8 mmol) were added to the reaction
mixture at 25 °C. After the mixture was stirred for 2 h, crystalline sulfur
(0.33 g, 10.3 mmol) was added. The whole mixture was stirred for 1 h,
and the reaction was quenched with saturated ammonium chloride solution
(10 mL). Extraction followed by concentration gave a solid. Purification
by gel permeation chromatography provided 7a (0.25 g, 0.43 mmol, 85%)
as a white solid.
sulfides with 3 equiv (to a PdS bond) of tris(dimethylamino)-
phosphine in boiling toluene for 13 h provided the corre-
sponding trivalent phosphines in high yields.18 New diphos-
(9) Experimental procedure: CuBr‚SMe2 (0.15 g, 0.75 mmol) was
placed in a 30-mL reaction flask under argon. Ether (3.0 mL) was added
and the mixture was cooled to -78 °C. BuMgBr (1.0 M ether solution, 1.6
mL, 1.6 mmol) was then added. After the mixture was stirred for 1 h at
-78 °C, 1a (0.14 g, 0.50 mmol) was added. The mixture was stirred at 25
°C for 2.5 h. Allyl bromide (0.21 g, 1.8 mmol) was then added. After 1 h,
crystalline sulfur (24 mg, 0.75 mmol) was added. The whole mixture was
stirred for 30 min, and the reaction was quenched with saturated ammonium
chloride solution (10 mL). Extractive workup followed by purification on
silica gel provided 3a (0.17 g, 0.40 mmol, 80%) as a white solid.
(17) Matano, Y.; Miyajima, T.; Nakabuchi, T.; Imahori, H.; Ochi, N.;
Sakaki, S. J. Am. Chem. Soc. 2006, 128, 11760-11761.
(18) Experimental procedure: A mixture of 7a (0.059 g, 0.10 mmol)
and tris(dimethylamino)phosphine (0.098 g, 0.60 mmol) in toluene (2.0 mL)
was heated at reflux for 13 h under argon. The mixture was then allowed
to cool to room temperature. Water (10 mL) was added, and the product
was extracted with a mixture of hexane and ethyl acetate (3 × 10 mL).
The combined organic layer was dried over sodium sulfate and concentrated
in vacuo. Chromatographic purification on silica gel yielded 10 (0.041 g,
0.077 mmol, 77%) as a white solid.
(10) Attempts to allylate the corresponding dimetallic species resulted
in failure, obtaining mixtures of the non-, mono-, and diallylated compounds.
Org. Lett., Vol. 9, No. 10, 2007
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