COMMUNICATION
Copper-catalyzed addition of H-phosphine oxides to alkynes forming
alkenylphosphine oxides{
Mingyu Niu,a Hua Fu,*a Yuyang Jiangab and Yufen Zhaoa
Received (in Cambridge, UK) 15th September 2006, Accepted 11th October 2006
First published as an Advance Article on the web 25th October 2006
DOI: 10.1039/b613416e
or in the presence of 2,29-dipyridyl (entries 2 and 3) using CuI as
the catalyst. However, when proline or pipecolinic acid was added
to the reaction system, the reaction yields were greatly improved
(entries 4–8). Solvents also influenced the progress of the reaction,
toluene or THF gave mild reaction yield (entries 4 and 5), and
ethanol is a bad solvent (entry 18). A good-yielded adduct was
obtained when DMSO was used as the solvent.
We have developed efficient copper-catalyzed additions of
P(O)H compounds to alkynes, and the reactions provided the
regio- and stereoselective E-alkenylphosphine oxides under
catalysis of the commercially available and inexpensive copper
catalyst system CuI/ethylenediamine. This finding is the first
example of copper-catalyzed hydrophosphinylation of alkynes
to synthesize alkenylphosphine oxides.
CuI/N,N9-dimethylethylenediamine showed mild catalytic effi-
ciency (entry 9). Various primary diamines were also attempted as
ligands of CuI, they all showed good catalytic activity, most
interestingly, CuI/ethylenediamine (EDA) almost gave a quantita-
tively transformed yield in DMSO at 60 uC in 3 h, (entry 14) and a
70%-yielded product was formed at room temperature in 18 h
(entry 15). The catalytic efficiency of the diamine ligands depends
on the electronic effect and steric hinderance. For example, 1,2-
diaminocyclohexane, with higher electronic density, gave a higher
yield than o-phenylenediamine (compare entries 11 and 13), and
ethylenediamine with smaller steric hinderance displayed higher
efficiency (compare entries 9 and 14). Several copper salts, CuI,
CuBr and CuSO4 (entries 14–17), were tested in the addition
reactions using DMSO as the solvent, ethylenediamine as the
ligand, and the results showed that CuI was the best catalyst. After
the optimization process of solvents, ligands and catalysts, we
decided that the following addition reactions were carried out in
our standard conditions, 10 mol% CuI as the catalyst, 15 mol%
ethylenediamine as the ligand relative to P(O)H compound,
DMSO as the solvent.
Transition metal-catalyzed addition of a heteroatom compound to
a carbon-carbon unsaturated bond is one of the most straightfor-
ward ways for the preparation of heteroatom compounds, which
have wide applications in organic synthesis and industrial
processes.1 Preparation of alkenylphosphine oxides has attracted
much attention for their important roles. For example, they are
used as biological active compounds2 and the key intermediates for
the preparation of the palladium ligand.3 Nucleophiles of amines,4
phosphines5 and carbanion species6 readily add to the olefinic
bond in alkenylphosphine oxides to give useful bifunctional
adducts, which allow further synthetic elaboration, so it is
necessary to develop convenient and efficient approaches to
alkenylphosphine oxides. Several efficient methods for metal-
catalyzed synthesis of alkenylphosphine oxides have recently been
developed including palladium,7 nickel,8 rhodium,9 ytterbium-
imine complex-catalyzed10 additions of P(O)H compounds to
alkynes. Here, we report a more convenient and inexpensive
copper-catalyzed method for the synthesis of alkenylphosphine
oxides.
(1)
We first chose phenylacetylene and diphenylphosphine oxide as
the model substrates to optimize the catalysis conditions (eqn (1)),
including optimization of the copper catalysts, ligands and solvents
in the hydrophosphinylations as shown in Table 1. Only traced
amount of product was obtained in the absence of ligand (entry 1)
ð2Þ
The scope of the copper-catalyzed addition reaction of P(O)H
compounds to alkynes was explored under our standard addition
conditions (eqn (2)). As shown in Table 2, the coupling reactions
were performed quite well for all the substrates examined, and the
desired alkenylphosphine oxides were obtained in good to excellent
yields. The data indicated that the yields depended primarily upon
the electronic and steric properties of the P(O)H compounds and
alkynes. Terminal aromatic alkynes showed better reactivity than
terminal aliphatic ones, for example, reaction of diphenylpho-
sphine oxide with phenylacetylene at 60 uC for 3 h provided a 99%
aKey Laboratory of Bioorganic Phosphorus Chemistry and Chemical
Biology, Ministry of Education, Department of Chemistry, Tsinghua
University, Beijing, 100084, P. R. China.
E-mail: fuhua@mail.tsinghua.edu.cn; Fax: 86 10 62781695;
Tel: 86 10 62797186
bKey Laboratory of Chemical Biology, Guangdong Province, Graduate
School of Shenzhen, Tsinghua University, Shenzhen, 518057, P. R.
China
{ Electronic supplementary information (ESI) available: Experimental,
procedure for copper-catalyzed additions of P(O)H compounds to
alkynes, characterization data for compounds 3–5, references, and 1H,
13C and 31P NMR spectra of compounds 3–5. See DOI: 10.1039/b613416e
272 | Chem. Commun., 2007, 272–274
This journal is ß The Royal Society of Chemistry 2007