Synthesis of phosphane oxides and phosphonates by cerium-mediated addition of organolithium compounds to chloro-phosphorus compounds

Article abstract of DOI:10.1002/(sici)1099-0690(199909)1999:9<2299::aid-ejoc2299>3.0.co;2-y

The addition of organocerium reagents 2a-g to phosphinoyl chloride 1a or chlorophosphates 1b leads to the synthesis of phosphane oxides 3aa-ag and phosphonates 3bb, be in good to high yield. The reaction can be extended to cerium enolates 4 (of ketones) and 6 (of nitriles) except when a benzyl group bound to the carbonyl moiety should be metallated. The latter reaction is the first reported synthesis of β-oxophosphane oxides by a simple reaction between enolates and a phosphorus(V) halide.

Full text of DOI:10.1002/(sici)1099-0690(199909)1999:9<2299::aid-ejoc2299>3.0.co;2-y

FULL PAPER
Synthesis of Phosphane Oxides and Phosphonates by Cerium-Mediated
Addition of Organolithium Compounds to Chloro-Phosphorus Compounds
Renato Dalpozzo,*[a] Antonio De Nino,[a] Daniela Miele,[a] Antonio Tagarelli,[a]
and Giuseppe Bartoli[b]
Keywords: Organocerium reagents / Phosphane oxides / Phosphonates / Electrophiles / Synthetic methods / Electrophilic
Additions
The addition of organocerium reagents 2a–g to phosphinoyl
chloride 1a or chlorophosphates 1b leads to the synthesis of
phosphane oxides 3aa–ag and phosphonates 3bb, be in good
to high yield. The reaction can be extended to cerium
enolates 4 (of ketones) and 6 (of nitriles) except when a
benzyl group bound to the carbonyl moiety should be
metallated. The latter reaction is the first reported synthesis
of β-oxophosphane oxides by a simple reaction between
enolates and a phosphorus(V) halide.
The most common methods to prepare them[2c,6,7] are two-
step procedures, which require acylation of an alkyldiphen-
ylphosphane oxide or oxidation of the β-hydroxy intermedi-
ate of a WittigϪHorner reaction (Scheme 2). Moreover, the
introduction of an alkyl chain on the carbon atom between
the phosphorus atom and the carbonyl moiety is restricted
to short alkyl chains or benzyl groups.[8]
Introduction
New methods to prepare phosphane oxides are always
welcome. In fact, these compounds are useful intermediates
for the preparation of ligands for transition metal catalyzed
reactions. They are also precursors for the Wads-
worthϪEmmons and WittigϪHorner olefin syntheses,[1]
a
cornerstone of laboratory and industrial practice. Many
methods for the synthesis of phosphane oxides are known
(Scheme 1): a) the Arbusov reaction of alkyl halides with a
phosphinous ester,[2] b) the MichaelisϪBecker reaction of
alkyl halides with the sodium or lithium derivatives of a
secondary phosphane oxide,[3] c) the reaction of phos-
phorus halides with organometallic reagents (mainly Grig-
nard reagents),[4] d) the catalyzed coupling of secondary
phosphane oxides with alkyl halides[5] and e) the hydrolysis
of phosphonium salts.[6] Most of these reactions need high
temperatures to occur; others are two-step procedures.
Scheme 2. Synthesis of β-oxophosphane oxides
We were recently interested in the reactivity of organocer-
ium reagents with electrophiles.[9] These compounds are
nonexpensive, highly efficient reagents for nucleophilic
transfer of an alkyl group to electrophilic centres,[10] since
side-reactions are almost completely suppressed. As a part
of our research on the reactivity of organocerium com-
pounds, we tested the reaction of these reagents with phos-
phorus halides. Until now only one method, which employs
lanthanides in the synthesis of phosphane oxides, is known:
the SmI2-promoted coupling of alkyl halides and chloro-
phosphinites.[11] However, this procedure does not give high
yields; nevertheless, it is a very simple method to prepare
phosphane oxides.
Scheme 1. Synthesis of phosphane oxides
A direct synthesis of β-oxophosphane oxides from eno-
lates and phosphinoyl halides has not been reported so far.
[a]
`
Dipartimento di Chimica, Universita della Calabria,
I-87030 Arcavacata di Rende (Cosenza), Italy
Fax: (internat.) ϩ 39-0984/492044
E-mail: dalpozzo@pobox.unical.it
[b]
Dipartimento di Chimica Organica “A. Mangini”,
viale Risorgimento 4, I-40136 Bologna, Italy
Eur. J. Org. Chem. 1999, 2299Ϫ2301
WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
1434Ϫ193X/99/0909Ϫ2299 $ 17.50ϩ.50/0
2299

R. Dalpozzo, A. De Nino, D. Miele, A. Tagarelli, G. Bartoli
Table 1. Reaction of chloro derivatives of phosphorus(V) with organocerium compounds at Ϫ20°C in THF for 14 h
FULL PAPER
Entry
R1
Substrate
R2
Reagent
Product
Yield (%)
1
2
3
4
5
6
7
8
9
Ph
1a
1a
1a
1a
1a
1a
1a
1b
1b
Me[a]
Bu[a]
2a
2b
2c
2d
2e
2f
2g
2b
2e
3aa
3ab
3ac
3ad
3ae
3af
3ag
3bb
3be
75
80
40
85
77
58
54
60
70
Ph
Ph
sBu[a]
n-C6H13
Ph[a]
[a]
Ph
Ph
[b]
Ph
CH2ϭCHCH2
[b]
Ph
Me3SiCH2
EtO
EtO
Bu[a]
Ph[a]
[a]
[b]
Organocerium reagent prepared from the corresponding organolithium compound. Ϫ
Organocerium reagent prepared from the
corresponding Grignard reagent.
Table 2b. Reaction of diphenylphosphinoyl chloride (1a) with ce-
rium enolates at Ϫ20°C in THF for 96 h; nitrile enolates
Results and Discussion
When organocerium compounds are allowed to react for
about 14 h with chlorophosphates and phosphinoyl chlo-
rides at Ϫ20°C, phosphonates and phosphane oxides,
respectively, are obtained in good to high yields (Table 1).
The reaction can be applied to primary, secondary, allylic
and silylated organocerium compounds both starting from
Grignard and organolithium reagents. Substitution of a
phenyl group can occur in the presence of a large excess
of methylcerium.
Reaction times are quite long but comparable with those
reported for the reaction with simple Grignard reagents,[12]
but nevertheless yields are higher and the procedures sim-
pler.
Entry
R
Reactant
Product
Yield (%)
5
6
7
H
Me
Ph
6a
6b
6c
7a
7b
7c
58
64
0
The reaction can be extended to dichlorophenylphos-
phane oxides and the reaction with butylcerium chloride led
to dibutylphenylphosphane oxide in 69% yield.
Table 2a. Reaction of diphenylphosphinoyl chloride (1a) with ce-
rium enolates at Ϫ20°C in THF for 96 h; ketone enolates
generated from ketones (Table 2a, entries 1Ϫ3), and nitriles
(Table 2b, entries 5, 6), but benzyl enolates did not react
under these reaction conditions (Table 2, entries 4 and 7).
We propose an addition-elimination reaction mechanism.
The cerium atom coordinates the oxygen atom, thus en-
hancing the electrophilic character of the phosphorus atom.
Then the carbanion moiety of organocerium compounds
can migrate and attack the phosphorus atom leading to a
pentacoordinated intermediate. Finally, ejection of a chlo-
ride ion gives the product.
Entry R2
R1
Reactant Product Yield (%)
An alternative 2 mechanism is discarded, since, at the
present time, displacements of halide ions by means of ce-
rium compounds are unknown.[10]
In conclusion, the reaction of organocerium compounds
with chloro derivatives of phosphorus(V) is feasible and is
competitive with respect to the known synthetic methods,
1
2
3
4
H
4-MeC6H4 4a
5a
5b
65
5d
77
56
Me
[CH2]5
Ph
Ph
4c
4b
5c
4d
[a]
Ph
0
[a] Cycloheptanone enolate.
The reaction was then extended to functionalized cerium which employ organometallic reagents, most of which re-
compounds such as cerium enolates (Table 2). The most quire a two-step procedure. Moreover, organocerium de-
remarkable difference with respect to the reaction with non- rivatives allow the first reported one-step synthesis of β-
functionalized cerium derivatives is the reaction time (96 h). oxophosphane oxides, bypassing the known three-step pro-
Yields are good and the reaction can be applied to enolates cedures.
2300
Eur. J. Org. Chem. 1999, 2299Ϫ2301

Synthesis of Phosphane Oxides and Phosphonates
FULL PAPER
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