Metallo-phosphorylation of alkynes: Reaction of alkynes with Cp 2Zr(1-butene)(PR3) and chlorophosphate

Article abstract of DOI:10.1039/b308595c

Reaction of alkynes with Cp₂ZrBu₂ and chlorophosphate in the presence PR₃ to form zircono- alkenylphosphonates, which can be converted into various β-functionalized alkenylphosphonates.

Full text of DOI:10.1039/b308595c

Metallo-phosphorylation of alkynes: reaction of alkynes with
Cp2Zr(1-butene)(PR3) and chlorophosphate†
Chunbo Lai, Chanjuan Xi,* Chao Chen, Mingming Ma and Xiaoyin Hong
Key Laboratory for Bioorganic Phosphorus Chemistry of Ministry of Education, Department of Chemistry,
Tsinghua University, Beijing 100084, China. E-mail: cjxi@tsinghua.edu.cn; Fax: 86-10-62618239;
Tel: 86-10-62782695
Received (in Cambridge, UK) 24th July 2003, Accepted 27th September 2003
First published as an Advance Article on the web 7th October 2003
Reaction of alkynes with Cp2ZrBu2 and chlorophosphate in
the presence PR3 to form zircono-alkenylphosphonates,
which can be converted into various b-functionalized
alkenylphosphonates.
Formation of zircono-alkenylphosphonate 1a (R1 = Ph, R2 =
H) was characterized by NMR spectroscopy before hydrolysis.
The 1H NMR (C6D6, Me4Si) spectrum showed a single signal at
6.09 ppm assigned to Cp protons, 6.04 ppm assigned to proton
of (PhC(Cp2Zr)NCHP), and 7.01–7.48 ppm assigned to protons
of benzene. In its 13C NMR (C6D6, Me4Si) spectrum, Cp
carbons appeared at 114.3 ppm and two sp2 carbons appeared at
187.2 and 120.6 ppm, assignable to Zr–C(Ph)N and
–C(Ph)NC(H)–P respectively. Its 31P NMR (THF, 85% H3PO4)
spectra showed a strong signal at 20.5 ppm assigned to NC(H)–
P(O)(OEt)2.
In Table 1, several representative examples of the phosphor-
ylation of alkynes are shown. It is noteworthy that in this
reaction alkynes could be terminal and internal alkynes as well
as bearing various substituents.
The zircono-phosphorylation product of alkynes could be
converted into various b-functionalized stereodefined alkenyl-
phosphonates by coupling with various electrophiles such as I2,
NBS, NCS, acyl chloride, and allyl bromide in the presence of
CuCl. A series of reactions were summarized in Scheme 3. The
reaction of zircono-alkenylphosphonate with I2 or NCS gave
Phosphorylation of alkynes is attractive reaction for the
synthesis of stereodefined alkenylphosphonates that are useful
intermediates in organic synthesis.1 Particularly interesting and
challenging in the reaction are those involving the region- and
stereoselective simultaneous introduction of phosphonate and
other functional groups to multiple carbon–carbon bonds.
Among them, metallo-phosphorylation of alkynes is the most
attractive since it is a versatile and elegant synthetic elaboration.
However, there is no procedure for the metallo-phosphorylation
of alkynes although hydro-phosphorylation of alkynes2 and
thio- or selenophosphorylation of alkynes3 and hydro-phosphi-
nylation of alkynes4 by transition metal catalyzed addition and
also metallo-esterification alkynes5 have been reported. In this
paper, we would like to report a novel reaction of alkynes with
Cp2ZrBu2 and chlorophosphate in the presence PR3 to form
zircono-alkenylphosphonates 1 (Scheme 1), which can be
converted into various b-functionalized alkenylphosphonates.
In a representative experiment, to a solution of Cp2Zr(1-
butene)(PMe3) (1 mmol),6 generated by the Cp2ZrBu2 (Negishi
reagent) with PMe3 in THF at room temperature, was added one
equivalent of phenylacetylene at room temperature and the
mixture was stirred for 3 h.6b,7 Diethyl chlorophosphate (1
mmol) was added to the mixture at the same temperature. The
mixture was warmed up to 50 °C and kept for 6 h and then
quenched with 3N HCl. Purification of crude product was
carried out by column chromatography on silica gel (ethyl
acetate/petroleum ether = 3/1). Diethyl-(E)-2-phenyl-ethenyl-
phosphonate 2a was exclusively obtained in 91% yield (isolated
yield 75%) with excellent region- and stereo-selectivity.
Deuteriolysis and iodinolysis of the reaction mixture afforded
mono-deuterated compound 3a in 92% yield with 95%
deuterium incorporation and mono-iodinated product 4a in 88%
yield, respectively (Scheme 2). The formation of 3a and 4a
indicated that zirconium-containing complex 1a (R1 = Ph, R2
= H) formed as a product. Moreover, the stereochemistry of the
reaction was determined by NMR analysis of coupling
constants. The relatively larger 3JPC coupling constant (ca. 23.0
Hz) and JHH coupling constant (ca. 17.4 Hz)8 of compound 2a
indicated that H or Cp2ClZr or another substituent at the b
position of ethenylphosphonate was in the cis position to
phosphorus and Ph was in the trans position.
Scheme 2
Table 1 Hydrophosphorylation of Alkyne via Zircono-alkenylphospho-
nate
Temp.
(°C)
Time
(h)
Yield
(%)a
Alkyne
Product
50
50
50
r.t
6
91 (75)
78 (69)
80 (55)
75 (46)
45 (33)
51 (40)
16
6
6
50
50
16
16
Scheme 1
† Electronic supplementary information (ESI) available: experimental
procedures and NMR data. See http://www.rsc.org/suppdata/cc/b3/
b308595c/
a GC yields. Isolated yields are given in parentheses.
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This journal is © The Royal Society of Chemistry 2003

2-iodo-(Z)-alkenylphosphonate 4a or 2-chloro-(Z)-alkenyl-
phosphonate 6a in 88% and 85% yields, respectively. It was
notable that NBS reacted with zircono-alkenylphosphonate in
the presence of CuCl to give a mixture of two products –
2-bromo-(Z)-alkenylphosphonate 5a and 2-chloro-(Z)-alkenyl-
phosphonate 6a. Some halogen-exchange occurred during the
reaction. Moreover, treatment of zircono-alkenylphosphonate
with allyl bromide in the presence of CuCl obtained 7a in 78%
yield, in which one new carbon–carbon bond formed. The
reaction of zircono-alkenylphosphonate with acyl chloride gave
compound 8a.
To elucidate the mechanism, the reaction of
Cp2Zr(PhCCH)PMe3 with chlorophosphate was followed by
31P NMR spectroscopy. 31P NMR spectra showed two signals at
1.7 ppm and 4.7 ppm after ClP(O)(OEt)2 was added to the
solution of Cp2Zr(PhCCH)(PMe3) at 0 °C. It is confirmed that
the signals at 1.7 ppm and 4.7 ppm are assigned to
Cp2Zr(PhCCH)(PMe3) and ClP(O)(OEt)2. After the reaction
mixture was stirred at 50 °C for 1 h, two new signals had
appeared at 20.5 ppm and 41.7 ppm, The former became
stronger and the later weaker after the reaction mixture was
stirred at 50 °C for 6 h. These results indicated that two
intermediates formed and that the intermediate 14 (dP = 41.7
ppm) was unstable and gradually transformed into intermediate
1. After quenching with 3N HCl, only one new signal (chemical
shift 20.2 ppm) appeared in the 31P NMR spectrum of the
reaction mixture. The signals at 41.7 and 20.5 ppm both
completely disappeared. That means that the compounds
corresponding to 41.7 and 20.5 ppm in the 31P NMR afforded
exclusively diethyl-(E)-2-phenyl ethenylphosphonate 2a after
hydrolysis.
Based on the above results, a proposed reaction mechanism is
shown in Scheme 4. It is reported that treatment of Cp2Zr(1-
butene)PR3 with alkynes gives resonance hybrid zircono-alkyne
complex 9 and zirconacyclopropene 10.6 Compound 9 or 10
couples readily with other unsaturated compounds,6,7,9 as here
with chlorophosphate to give complex 1310 via compound 11 or
12. The intermediate 13 undergoes elimination of chloride to
give compounds 145,11 and 1. Both are in equilibrium but
compound 1 is favored, as confirmed by the 31P NMR spectrum.
After hydrolysis both compounds 14 and 1 give alkenylphos-
phonate 2.
Scheme 4
support. We also thank Professor T. Takahashi for his kind
suggestions.
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An alternative mechanism involving oxidative addition of
ClP(O)(OEt)2 to complex Cp2Zr(R1CCR2)(PR3 ) giving
3
Cp2ClZrP(O)(OEt)2(R1CCR2)(PR3) and subsequent insertion
of alkyne into the Zr–P(O)(OEt)2 moiety to afford 14 and 1 can
not be ruled out.
In conclusion, we have developed a novel reaction for the
direct preparation of stereodefined substituted metallo-alkene-
phosphonate, which could be converted into various b-
functionalized alkenephosphonates.
Further investigations are still in progress in this area.
We are grateful to the National Natural Sciences Foundation
of China (20172032) and Tsinghua University for financial
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Scheme 3
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