One-Pot Formation of Three Different C-P Bonds
steric hindrance. This can be explained by considering
the structure of 1, which possesses a folded geometry that
is very suitable for this kind of attack. This behavior,
which might be named the “butterfly effect”, was recently
observed in the facile formation of transition metal
complexes containing a “dibenzo butterfly” moiety.25
Experimental Section
One-Step Procedure: Synthesis of Phosphine Sulfides
with Simultaneous Addition of Grignard Reagents. The
three Grignard reagents (R1MgBr, R2MgBr, R3MgBr, 1.2 mmol
of each) were simultaneously added to a solution of benzothia-
diphosphole (1) (1.0 mmol) in anhydrous THF under a dry
nitrogen atmosphere. After 30-40 min, the solvent was
partially evaporated and the reaction mixture was treated with
aqueous acid solution (HCl). Extraction with CH2Cl2 gave a
mixture of phosphines and the residue 6. The phosphines were
easily separated from 6 by treating the organic solution with
aqueous NaOH; after this treatment, the sodium salt of 6 was
dissolved in the aqueous solution, whereas the phosphines
were in the organic phase. Treatment of this layer with a slight
excess of elemental sulfur gave the corresponding sulfides,
which were purified by flash chromatography and fully
characterized. Compound 620 was recovered (90%) from the
basic aqueous layer by acidification and extraction with
dichloromethane, and was then purified by distillation and
stored under argon. Simple treatment of a dry solution of
compound 6 with an equimolar amount of PCl3 led to the
regeneration of the starting reagent 1 in almost pure form,
allowing it to be reused without further purification.
To increase the yield of the desired product beyond the
statistical limit, we tried a second procedure in which
the different RMgBr reagents were added in two steps
with very short reaction times (4-5 min, to avoid the
decomposition of A′, which is more unstable26 than A)
between the first and second steps. In this manner, it
could be predicted, on a statistical basis, that the addition
in the first step of equimolar amounts of two different
Grignard reagents (R1MgBr and R2MgBr), followed by the
addition in the second step of the third Grignard reagent
(R3MgBr) would give a final mixture containing PR1R2R3
(50%), P(R1)2R3 (25%), and P(R2)2R3 (25%). In fact, when
we used this two-step procedure we obtained asymmetric
phosphines (10a,b) or their sulfides 13a,b in 45% yield
together with about 20-25% of the other symmetric
phosphine sulfides, which were separated by column
chromatography. In this procedure, the end product 6 can
be recovered and recycled as described above. Using this
one-pot two-step procedure, symmetric disubstituted
phosphines 9a-g (and their sulfides 12a-g) were ob-
tained in 75-80% yield. It should be noted that phos-
phines 8, 9, and 10 were analyzed only by GC-MS
analysis, and were not isolated. Rather, they were
immediately treated with sulfur to obtain the corre-
sponding sulfides 11, 12, and 13 (Scheme 3), which are
stable and thus were isolated and fully characterized.
The yields of the phosphines obtained by the one-step
procedure are as follows:
When R1 ) R2 ) R3, phosphine sulfides (11a-f) were
obtained in 85-90% yields. Triphenylphosphine (8a) and
triethylphosphine (8b) and their sulfides 11a and 11b were
characterized by comparison with physicochemical data of
commercially available authentic samples. When R1 ) R2 *
R3, the reaction mixture contains a mixture of phosphines
P(R1)2R3, P(R1)3, PR1(R3)2, and P(R3)3 in relative proportions
(calculated by GC-MS analysis) of about 45%, 29%, 23%, and
3%, respectively. When R1 * R2 * R3, the reaction mixture
contains a mixture of phosphines, in which PR1R2R3 is the most
prevalent (23% yield; calculated by GC-MS analysis). The
other nine possible symmetric tertiary phosphines such as
P(R1)3 or P(R1)2R2 were present in smaller proportions (about
3% and 11%, respectively).
It is worth noting that the synthesis reported herein
makes it possible to obtain, in a simple one-pot procedure,
sulfide derivatives of symmetric and asymmetric acyclic
tertiary phosphines, also containing alkenyl groups
(11d-f and 12c-g); the synthesis of such compounds,
which are of great interest in organic chemistry, has been
previously studied only to a very limited extent.
In these last two cases, phosphines 9 and 10 and the
corresponding sulfides 12 and 13 were obtained in higher
yields using the two-step procedure described below.
Two-Step procedure: Preparation of Phosphine Sul-
fides 12a-g and 13a,b. The first Grignard reagent (R1MgBr,
2.4 mmol) was added to a solution of benzothiadiphosphole
(1) (1.0 mmol) in anhydrous THF under a dry nitrogen
atmosphere. After 4-5 min, the second Grignard reagent (R2-
MgBr, 1.2 mmol) was added. After about 30-40 min, the
reaction mixture was treated as described above for the one-
step procedure. Phosphine sulfides 12a-g were purified by
FC and isolated in 75-80% yield. Phosphine sulfides 13a and
13b were obtained in 45% yield (they were easily separated
from the other phosphine sulfides by FC) as described above
for the preparation of compounds 12; in this case, two different
Grignard reagents, R1MgBr (1.2 mmol) and R2MgBr (1.2
mmol), instead of 2.4 mmol of the same organometallic, were
added to 1 in the first step and the Grignard reagent R3MgBr
(1.2 mmol) was added in the second step.
Conclusion
In conclusion, the one-pot synthesis of symmetric and
asymmetric tertiary acyclic phosphines reported herein
can be achieved through a very simple, efficient, low-cost
method and gives higher yields than previously reported
methods. In these procedures, the byproduct 6 was
recovered and transformed into the starting reagent 1,
making the process very atom-economic and environ-
mentally friendly. It should be noted that this method
can also be used to easily obtain trivinyl- or triallyl
phosphines or alkenyl-containing phosphines, making
this procedure a new general protocol and a very conve-
nient, quite unique, method for the simultaneous con-
struction of three different C-P bonds.
Acknowledgment. This work was supported by the
University of Bologna (ex 60% Ministero dell’Istruzione,
dell’Universita` e della Ricerca, funds for selected re-
search topics A. A. 2003-2004), and the Ministero
dell’Universita` e della Ricerca Scientifica e Tecnologica.
(25) (a) Lee, C.-M.; Chen, C.-H.; Ke, S.-C.; Lee, G.-H.; Liaw, W.-F.
J. Am. Chem. Soc. 2004, 126, 8406-8412. (b) Cerrada, E.; Falvello, L.
R.; Hursthouse, M. B.; Laguna, M.; Luqu´ın, A.; Pozo-Gonzalo, C. Eur.
J. Inorg. Chem. 2002, 826-833.
(26) This hypervalent intermediate A′ is presumably more unstable
than A because it not contains the additional ring derived by bis-
(Grignard reagent) as in A. For a review on the stability of hypervalent
phosphorus species, see ref 24.
Supporting Information Available: General experimen-
tal details, full characterization data for compounds 11, 12,
and 13, and copies of the 1H, 13C, and 31P NMR spectra of
compounds 11b-f, 12a-g, and 13a,b. This material is avail-
JO0502145
J. Org. Chem, Vol. 70, No. 12, 2005 4777