Efficient one-pot synthesis of secondary cyclic phosphanes with easy regeneration of the phosphorus-donor reagent used

Article abstract of DOI:10.1002/anie.200453820

Phosphanes: No pain, all gain. A regenerable phosphorus donor is the key to an efficient and economic one-pot synthesis of five- and six-membered secondary cyclic phosphanes. The reaction, at room temperature, of 1 with 1 equivalent of bis(Grignard reagent) 2 followed by treatment with aqueous acid gives cyclic phosphanes 3 in 70-80% yield and the new compound 4. Simply treating 4 with PCl₃ quantitatively regenerates the starting reagent 1, which can be reused without further purification.

Full text of DOI:10.1002/anie.200453820

Communications
Cyclic Phosphanes
Efficient One-Pot Synthesis of Secondary Cyclic
Phosphanes with Easy Regeneration of the
Phosphorus-Donor Reagent Used**
Graziano Baccolini,* Carla Boga, and Matteo Galeotti
New syntheses of cyclic phosphanes are of considerable
current interest, principally because they play a central role in
[
*] Prof. Dr. G. Baccolini, Dr. C. Boga, Dr. M. Galeotti
Dipartimento di Chimica Organica
Universita' di Bologna
Viale Risorgimento, 4-40136 Bologna (Italy)
Fax: (+39)051-209-3654
E-mail: baccolin@ms.fci.unibo.it
[
**] Work supported by the University of Bologna (ex 60% MIUR and
funds for selected research topics A.A. 2001–2003) and the
Ministero dell'Università e della Ricerca Scientifica e Tecnologica.
3
058
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/anie.200453820
Angew. Chem. Int. Ed. 2004, 43, 3058 –3060

Angewandte
Chemie
[
1]
coordination chemistry and homogeneous catalysis, but to
date the most widely used procedures for obtaining secondary
[
2–5]
cyclic phosphanes give very low overall yields (3–5%).
Secondary phosphanes are prepared by multistep proce-
dures in which the final step is reduction of a phosphorus
compound containing PÀO, PÀS, or PÀCl bonds with a wide
variety of reagents and reaction conditions. However,
whereas secondary acyclic phosphanes can be synthesized
by several routes, only a few procedures for secondary five-
(
phospholanes)and six-membered cyclic phosphanes (phos-
[
2]
phinanes)have been reported.
5
For example, phospholane
[
3]
a (see Scheme 3)was prepared by reaction of tetramethy-
lenebis(magnesium bromide)BrMgC 4H MgBr with dime-
8
thylphosphoramidous dichloride (Me) NPCl2 at À788C to
2
give the aminocyclophosphane (Me) NPC H in 8% yield.
Scheme 1. Preparation of 1 and synthesis of cyclic tertiary phosphanes
3 and their sulfides 4.
2
4
8
This aminocyclophosphane was treated with B H and then
2
6
kept in a sealable tube at 2208C. The tube was then
sealed up and heated for 21 h at 2108C, and
subsequent distillation gave a fraction containing
the desired C H PH (30%)and aminoborane
4
8
impurities, which were separated by treatment with
HCl. The overall yield of this multistep procedure
was not higher than 3%. In another recent prepa-
[
4]
ration, phospholane was obtained in approxi-
mately 5% yield by flash vacuum pyrolysis of
butyldichlorophosphane at 6008C.
Phosphinane 5b is obtained by similar multistep Scheme 2. Proposed reaction pathway for the formation of cyclic phosphanes 3.
[
5]
[4]
procedures or by flash pyrolysis. Other recent
syntheses of these cyclic phosphanes use (trimethyl-
[
6]
1
silyl)phosphane or an organolanthanide-catalyzed hydro-
sulfur atom would activate P toward further nucleophilic
[
7]
phosphination/cyclization reaction, but the former reagent
is very difficult and dangerous to prepare, and the latter
attack to give unstable hexacoordinate intermediate B. Treat-
ment of B with water or sulfur gives phosphane 3 or its sulfide
4, respectively.
[
7]
procedure often gives a mixture of phospholane and
phosphinane.
To develop further applications of this reaction we then
studied what happens when intermediate A, formed by
reaction of 1 with one equivalent of 2, is treated with water.
Surprisingly, in this case we found that it is possible to obtain
secondary cyclic phosphanes 5 in 70–80% yields (based on 2).
In addition, from the aqueous solution it is also possible to
isolate, in very good yield (90% based on 1), the new
compound 4-methyl-2-[(5-methyl-2-sulfanylphenyl)phospha-
nyl]benzenethiol (6)which is the end product derived from 1
(Scheme 3).
Herein we report a highly efficient and economical new
method for one-pot preparation of 5a and 5b (70–80% yield)
using an unusual phosphorus-donor reagent, namely, the
benzothiadiphosphole 1 which, at the end of the process, can
be easily regenerated by simple reaction of its end product 6
with PCl3.
[
8]
We have reported that 1 is easily obtained by simple
treatment of p-methylthioanisole with PCl and AlCl , and
3
3
that it can be isolated by crystallization from the reaction
mixture. Compound 1 is an air-stable solid that can be stored
for several years without particular precautions, and it is also
As depicted in Scheme 3, we first prepared intermediate
A by reaction of equimolar amounts of 1 and a bis(Grignard
reagent) 2 in THF. Partial evaporation of the solvent,
treatment of the reaction mixture with aqueous acid followed
by extraction with organic solvent (CH Cl , diethyl ether)
[
9]
easy to handle. Subsequently, we found that 1 can be used as
[
10]
a phosphorus donor, and we recently reported
that
simultaneous or sequential addition of an equimolar mixture
of a bis(Grignard reagent) 2 (n = 1, 2; Scheme 1)and a
Grignard reagent RMgBr (R = alkyl, phenyl, alkenyl)to an
equimolar amount of 1 gave phosphanes 3 or, after addition of
elemental sulfur, their sulfides 4 in good yield at room
temperature.
2
2
gave a mixture of secondary phosphanes 5 and residue 6.
These can be easily separated by treating the solution with
aqueous NaOH; in this way the sodium salt of 6 dissolves in
the aqueous solution, whereas the organic phase contains
almost pure phosphanes 5 (70–80%), which can be purified
by bulb-to-bulb distillation. Compounds 5a and 5b were
The above results were explained by the intervention of
hypervalent (penta- and hexacoordinate)phosphorus inter-
1
31
characterized principally by H, P NMR, and IR spectros-
copy and mass spectrometry, the data from which agree with
[
11]
mediates
such as A and B (scheme 2)in which the
[
4,6a,b]
“
dibenzo-butterfly” moiety of reagent 1, as depicted in
the reported values.
Compound 6 can be recovered from
Scheme 2, might favor their formation. In pentacoordinate
intermediate A coordination of the magnesium atom by a
the basic aqueous layer by acidification and extraction, and
purified by distillation. It was stored under argon and
Angew. Chem. Int. Ed. 2004, 43, 3058 –3060
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ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3059

Communications
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2] a)K. Dimroth, Heterocyclic Rings Containing Phosphorus in
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[
[
3] A. B. Burg, P. J. Slota, J. Am. Chem. Soc. 1960, 82, 2148 – 2151.
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38, 8417 – 8420.
[
[
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Scheme 3. Synthesis of secondary cyclic phosphanes 5a,b and
regeneration of the starting reagent 1 from end product 6.
[
[
1825.
8] a)G. Baccolini, E. Mezzina, P. E. Todesco, E. Foresti, J. Chem.
Soc. Chem. Commun. 1988, 304 – 305; b)G. Baccolini, M.
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1
31
characterized by H and P NMR spectroscopy and HR-
[
12]
MS.
Simply treating a dry solution of 6 with an equimolar
[
9] G. Baccolini, G. Orsolan, E. Mezzina, Tetrahedron Lett. 1995, 36,
amount of PCl regenerates 1 in sufficiently pure form that it
3
447 – 450.
can be reused without further purification (Scheme 3).
Finally, we carried out the reaction shown in Scheme 1 to
obtain tertiary phosphanes 3 using the same reaction con-
ditions and separation procedure used to obtain compounds
[
10] G. Baccolini, C. Boga, U. Negri, Synlett 2000, 1685 – 1687.
[11] For reviews on pentacoordinate and hexacoordinate phospho-
rus, see a)R. R. Holmes, Pentacordinate Phosphorus Structure
and Spectroscopy, Vols. I and II, ACS Monograph 175, American
Chemical Society, Washington, DC, 1980; b) C. Y. Wong, D. K.
Kennepohl, R. G. Cavell, Chem. Rev. 1996, 96, 1917 – 1951;
c)R. R. Holmes, Acc. Chem. Res. 1998, 31, 535 – 542.
5, and we found that also in this case it was possible to isolate
(Scheme 4).
6
[
12] 4-Methyl-2-[(5-methyl-2-sulfanylphenyl)phosphanyl]benzene-
thiol (6): 90%, colorless liquid, b.p. 110–1158C (0.5 mmHg);
1
H NMR (400 MHz, CDCl , TMS): d = 2.23 (s, 6H, CH ), 4.30
3
3
(
brs, 2H, exch. with D O, SH), 5.29 (d, 1H, J = 228 Hz, PH),
2
P
H
6
.99–7.07 (m, 2H), 7.07–7.12 (m, 2H), 7.63–7.72 ppm (m, 2H);
3
1
P NMR (161.89 MHz, CDCl3, ext. 85% H PO ): d =
3
4
Scheme 4. Regeneration of 1 from 6, obtained in the preparation of
tertiary phosphanes 3.
À52.0 ppm (brd, JPH = 228 Hz). HR-MS (EI) calcd for
C H PS : 278.0353, found: 278.0355.
1
4
15
2
[
13] a)B. M. Trost, Angew. Chem. 1995, 107, 285 – 307; Angew. Chem.
Int. Ed. Engl. 1995, 34, 259 – 281; b)B. M. Trost, Acc. Chem. Res.
2002, 35, 695 – 705.
In conclusion, the syntheses of secondary and tertiary
cyclic phosphanes reported herein can be carried out in a very
simple, efficient, and low-cost procedure that gives higher
yields than those previously reported. In addition, this
[
13]
synthesis is atom-economic and environmentally friendly,
because by-product 6 is easily transformed quantitatively into
starting reagent 1, which can be recycled.
Received: January 21, 2004 [Z53820]
Keywords: hypervalent compounds · phosphanes ·
.
phosphorus heterocycles · synthetic methods
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3
060
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
Angew. Chem. Int. Ed. 2004, 43, 3058 –3060