Selective preparation of 1,3-butadienyl phosphines, 1-iodo- and 1,4-diiodo-butadienyl phosphine oxides via zirconocene-mediated cross-coupling of alkynylphosphines

Article abstract of DOI:10.1016/j.tetlet.2004.01.098

Stereodefined butadienyl phosphines and related derivatives were readily prepared in high yields with perfect regioselectivity via the zirconocene-mediated pair-selective coupling of alkynylphosphines with ethylene or alkynylphosphines with normal alkynes

Full text of DOI:10.1016/j.tetlet.2004.01.098

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 2427–2429
Selective preparation of 1,3-butadienyl phosphines, 1-iodo- and
1,4-diiodo-butadienyl phosphine oxides via zirconocene-mediated
cross-coupling of alkynylphosphines
Zhenfeng Xi,a,* Wenxiong Zhanga and Tamotsu Takahashib,*
aPeking University-Hokkaido University Joint Laboratory, College of Chemistry, Peking University, Beijing 100871, China
bCatalysis Research Center, Graduate School of Pharmaceutical Sciences, Hokkaido University, CREST,
Japan Science and Technology Corporation (JST), Kita-Ku, Sapporo 001-0021, Japan
Received 15 August 2003;revised 16 January 2004;accepted 16 January 2004
Abstract—Stereodefined butadienyl phosphines and related derivatives were readily prepared in high yields with perfect regio-
selectivity via the zirconocene-mediated pair-selective coupling of alkynylphosphines with ethylene or alkynylphosphines with
normal alkynes. Interesting and synthetically useful iodination reactions were found when the in situ generated a-phosphino-
zirconacyclopentenes or a-phosphinozirconacyclopentadienes were treated with I2.
Ó 2004 Published by Elsevier Ltd.
Tertiary phosphines and their oxides are the most pop-
ular ligands in organometallic chemistry and in coordi-
nation chemistry.1 The nature of these ligands has
critical influences on the reactivity of catalysis.1;2
Therefore, development of synthetically useful methods
for a variety of tertiary phosphines and their oxides with
a wide structural diversity continues to be a very
attractive area. Among a number of known methods,3;4
the zirconocene-mediated procedure has been demon-
strated to be useful.5 For example, preparation of
We found that stereodefined butadienyl phosphines
could be readily prepared in high yields with perfect
regioselectivity from an alkynylphosphine and a differ-
ent alkyne. Interesting and synthetically useful iodin-
ation reactions were found when the in situ generated
a-phosphinozirconacyclopentenes or a-phosphinozirc-
onacyclopentadienes were treated with I2. In this paper,
we report our preliminary results.
First, we investigated the pair-selective coupling of
alkynylphosphine 1a with zirconocene–ethylene com-
plexes, which were generated in situ from Cp2ZrEt2.12
The alkenyl(diphenyl)phosphine 3a was formed in 96%
GC yield (71% isolated yield) with perfect regio- and
stereoselectivity (Scheme 1).
phospholes
from
zirconacyclopentadienes
and
PhPCl2,6–8 and preparation of 1,4-diphosphino-1,3-buta-
dienes from CuCl-mediated reaction of zirconacyclo-
pentadienes with Ph2PCl have been achieved.9 As part
of our continuing interest in the development of syn-
thetic methodologies using the zirconocene-mediated
selective coupling of unsaturated substrates,10 we
examined coupling reaction of alkynylphosphines,7a;11
aiming at development of preparative methods for ter-
tiary phosphines with one alkenyl substituent, especially
butadienylphosphines and related compounds, which
are potentially very important ligands and are not
readily available via known methods.
In order to synthesize alkenylphosphines with more
functional groups, we treated the in situ generated
intermediate 2a with I2. Interestingly, we found that 2a
reacted with I2 in a different manner from the known
iodination reaction of zirconacyclopentenes.13 The
PPh2
ZrCp2
PPh2
PPh2
2) H+
1) Cp2ZrEt2 Bu
Bu
Keywords: Alkynylphosphine;Cross-coupling;1-Iodo-1-phosphino-
1,3-butadiene;1,3-Butadienyl phosphine;Zirconacyclopentene;Zir-
conacyclopentadiene.
Bu
2a
3a: 96% (71%)
1a
* Corresponding authors. Tel.: +81-11-706-9149;fax: +81-11-706-
9150;e-mail: tamotsu@cat.hokudai.ac.jp
Scheme 1.
0040-4039/$ - see front matter Ó 2004 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2004.01.098

2428
Z. Xi et al. / Tetrahedron Letters 45 (2004) 2427–2429
results are given in Scheme 2. When 1 equiv of I2 was
used, hydrolysis of the reaction mixture with aqueous
3 N HCl afforded a mixture of two products 4a and 3a.
When 2 equiv of I2 were used, the iodinated product 4a
was formed exclusively in 54% isolated yield. No for-
mation of other iodinated products was observed. The P
atom in the product was completely oxidized to be
pentavalent alkenylphosphine oxides. If the amount of
I2 was increased to 4 equiv, the diiodination product 5a
appeared. When 6 equiv of I2 were used, the mono-
iodination product 4a disappeared. In addition to 5a,
mixed halogenated product 6a was also formed. The Br
atom in 6a came from magnesium salt, which was in situ
formed by the reaction of EtMgBr with Cp2ZrCl2 for
the formation of Cp2ZrEt2.12 The desired diiodo com-
pound 5a was formed as the only product in good iso-
lated yield when 2a was first treated with 2 equiv of I2
and followed by further treatment with 1 equiv of CuCl,
and 1 equiv of I2.14 These results indicate that (1) the Zr–
yields (Scheme 3). It is noteworthy that only the cross-
coupling product 8 was formed in most cases. When
diphenylacetylene was used as the second alkyne, in
addition to the desired cross-coupling product 8e,
homocoupling product of diphenylacetylene was also
obtained in 19% isolated yield. To ascertain the stereo-
and regiochemistry of the product, the structure of 8e
was determined by single-crystal X-ray analysis (Fig. 1).
Like the case for iodination of the in situ generated
a-phosphinozirconacyclopentene 2a, treatment of
a-phosphinozirconacyclopentadienes 7 with I2 revealed
an interesting result.14 As demonstrated in Scheme 4, a
mixture of two products, the hydrolyzed product 8a,
and the monoiodinated product 9a, was formed when 7a
was treated with 1 equiv of I2. When 2 equiv of I2 were
used, the 1-iodo-1,3-butadienyl phosphine oxide 9a was
formed as the only product in 65% isolated yield. If 7a
was first treated with 2 equiv of I2, followed by addition
of CuCl and I2,14 1,4-diiodo-1,3-dienyl phosphine oxide
11a was formed exclusively in 56% isolated yield. These
results again demonstrated that (1) the Zr–C bond
attached with the Ph2P moiety reacted with I2 more
readily;(2) the P atom was oxidized more easily due to
the existence of the gem-I;15 (3) both monoiodo- and
diiodo-1,3-dienyl phosphine oxides 9, and 11 could be
readily prepared in high yields with perfect selectivity.
C
sp2 bond of zirconacyclopentene 2a is much more easily
iodinated than the Zr–Csp3 bond;(2) iodine oxidizes the
P atom more easily.
Zirconocene-mediated cross-coupling of two different
alkynes has been developed and applied to the synthesis
of various useful compounds. In order to develop pre-
parative methods for butadienylphosphines and related
compounds, we treated the in situ generated a-phosph-
inozirconacyclopentenes 2 with a different alkyne. After
the reaction mixture was stirred at 50 °C for 3 h,
a-phosphinozirconacyclopentadienes 7 were formed in
quantitative NMR yield. Hydrolysis of the reaction
mixtures with aqueous 3 N HCl afforded all-trans 1,3-
butadienyl diphenylphosphines 8 in good to excellent
1)
PPh2
ZrCp2
PPh2
ZrCp2
R
R
R
'
R'
50 oC, 3h
R'
2
R'
2a: R = Bu
2b: R = Ph
7
PPh2
H
2) H+
R
H
O
PPh2
H
PPh2
I
1) 1 I2, r.t., 1h
2) H+
Bu
R'
Bu
+
R'
8
4a: 25%
3a: 30%
8a: R = Bu, R' = Et, 98% (85%)
8b: R = Bu, R' = Bu, 95% (83%)
8c: R = Ph, R' = Et, 70% (56%)
8d: R = Ph, R' = Pr, 65% (43%)
8e: R = Ph, R' = Ph, (25%)
O
PPh2
1) 2 I2, r.t., 1h
2) H+
Bu
I
4a: 54%
O
PPh2
Scheme 3.
PPh2
ZrCp2
O
Bu
Bu
PPh2
1) 4 I2, r.t., 1h
2) H+
Bu
I
I
+
+
I
4a: 35%
O
2a
5a: 35%
O
PPh2
PPh2
1) 6 I2, r.t., 1h
2) H+
Bu
Bu
I
Br
I
I
6a: 8%
5a: 50%
O
PPh2
1) 2 I2, r.t., 1h
Bu
I
2) CuCl/1I2
r.t., 1h
3) H+
I
5a: 60%
Scheme 2.
Figure 1. Single-crystal structure of 8e.

Z. Xi et al. / Tetrahedron Letters 45 (2004) 2427–2429
2429
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PPh2
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ꢀ
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Scheme 4.
In summary, we have demonstrated that Ph2P-substi-
tuted zirconacycles have interesting reactivities toward
iodination. Significantly, these reactions reported in this
paper provide valuable synthetic methods for butadienyl
phosphines and related compounds, including 1-phos-
phino-1,3-dienes, 1-iodo-1,3-dienyl phosphine oxides,
and 1,4-diiodo-1,3-dienyl phosphine oxides. Further
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Acknowledgements
This work was partially supported by National Science
Fund for Distinguished Young Scholars (29825105), the
Major State Basic Research Development Program
(G2000077502-D), and the National Natural Science
Foundation of China.
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