Simple and general synthesis of new 11H-11λ5-dibenzo[c,f][1,2,5]dithiaphosphepine derivatives

Article abstract of DOI:10.1016/S0040-4039(02)02376-6

Treatment at room temperature of benzothiadiphosphole 1 with bis-Grignard 2 gives intermediate A, which after 3 h gives intermediate A′. Subsequent addition of RMgX or sodium alcoholate and final treatment with S₈ and water affords the title compounds 5 in good yields. From the reaction mixture it is also possible to obtain the cyclic phosphine sulfide 6 or its dimeric form 7.

Full text of DOI:10.1016/S0040-4039(02)02376-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 9299–9302
Simple and general synthesis of new
11H-11l5-dibenzo[c,f ][1,2,5]dithiaphosphepine derivatives
Graziano Baccolini,* Carla Boga, Giulia Guizzardi and Stefano Ponzano
Dipartimento di Chimica Organica ‘A. Mangini’, Universita` di Bologna, Viale Risorgimento 4, I-40136 Bologna, Italy
Received 30 September 2002; revised 17 October 2002; accepted 22 October 2002
Abstract—Treatment at room temperature of benzothiadiphosphole 1 with bis-Grignard 2 gives intermediate A, which after 3 h
gives intermediate A%. Subsequent addition of RMgX or sodium alcoholate and final treatment with S8 and water affords the title
compounds 5 in good yields. From the reaction mixture it is also possible to obtain the cyclic phosphine sulfide 6 or its dimeric
form 7. © 2002 Elsevier Science Ltd. All rights reserved.
The facile synthesis of heterocyclic systems containing
phosphorus is of considerable current interest princi-
pally because they play a central role in coordination
chemistry and homogeneous catalysis.1 In the past we
It should be noted that the residue C of the reagent 1 is
inferred but never isolated in the final reaction mixture.
It is thus, presumably, unstable and lost by final
quenching with water.
reported2 that benzothiadiphosphole
1
is easily
obtained by an unexpected domino reaction treating
p-methylthioanisole with PCl3 and AlCl3. Compound 1
was separated by simple crystallization from reaction
mixture.2b,4b Compound 1 is an air-stable solid, it can
be stored for several years without particular precau-
tion and it is also easy to handle. We subsequently
found3 that 1 can be used as a phosphorus donating
reagent and we recently reported4 that the simultaneous
or the sequential addition of equimolar amounts of a
bis-Grignard 2 (n=1, 2) and a mono-Grignard RMgBr
(R=alkyl, phenyl, alkenyl) to 1 equiv. of 1 gave, after
addition of elemental sulfur, phosphines 3 or their
sulphides 4 in good yields at room temperature (Scheme
1).
In order to obtain further information about this reac-
tion we have now observed a new type of reactivity
which occurs when the intermediate A is allowed to
stand for about 3 h at room temperature before react-
ing with RMgBr. In particular, when we used RMgBr
with high steric hindrance of the R group (Scheme 3)
we have the prevalent formation6 of the new hetero-
cyclic compounds 5 (70%) with the concomitant forma-
tion of cyclic phosphine sulphide 6 (cases c, d). In
contrast, when R has a smaller steric effect (cases a, b)
the formation of both 5 and 4 occurs at a ratio of about
70:30.
These results were explained by the intervention of
hypervalent phosphorus intermediates (penta- and hex-
acoordinate)5 such as A and B (Scheme 2) in which the
‘dibenzo-butterfly’ moiety of reagent 1, as depicted in
Scheme 1, might favour their formation. In intermedi-
ate A the coordination of the Mg atom with sulfur
activates the P1 atom to undergo a further nucleophilic
attack.
Keywords: phosphorus heterocycles; phosphine sulfides; Grignard
reagents.
* Corresponding author. Tel.: +39-051-2093616; fax: +39-051-
2093654; e-mail: baccolin@ms.fci.unibo.it
Scheme 1.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)02376-6

9300
G. Baccolini et al. / Tetrahedron Letters 43 (2002) 9299–9302
and water, the P1 phosphoranide,8 an unstable hyper-
valent species, collapses to form compounds 5 and 6.
Tentatively this decomposition may be a reductive
elimination reaction interpreted as a concerted ligand
coupling process.9
In addition, the best yields for these dithiaphosphep-
ines 5 are obtained when a bis-Grignard 2 with n=2
is used. In these cases 6 (n=2) is also obtained but it
undergoes a rapid dimerization to the bis-phosphine
sulfide 7,10 which has been separated and character-
ized. A similar conversion to a dimer of an unstable
secondary phospholane was reported.11
We have recently reported12 that treatment at room
temperature of benzothiadiphosphole 1 with bis-Grig-
nard 2, sodium alcoholates and finally with S8 affords
1-alkoxy cyclic phosphine sulfides in good yields. In a
similar manner we obtained the 11-alkoxy derivatives
5e,f using alcoholates as nucleophilic reagents.
Scheme 2.
It should be noted that compounds containing both
phosphorus and sulphur atoms should be particularly
useful to generate polydentate ligands. In addition,
compounds 5 represent the first examples of a new
heterocyclic system, namely 11H-dibenzo[c,f ][1,2,5]-
dithiaphosphepine 11-thione derivatives. The only
related compound reported in literature13 is the 11-
phenyl-11-oxo-derivative, obtained by a two-step pro-
cedure from lithium 2-lithiobenzenethiolate at −78°C
with phenylphosphonic dichloride. The 2-mercap-
tophenyl phosphine oxide obtained is then oxidized to
cyclic disulfide by DMSO at 90°C. It is clear that
with this procedure it is necessary to use various
RPOCl reagents for each cyclic disulfide; these
reagents are very difficult to prepare when R is not
phenyl or a simple alkyl group. On the other hand,
in our case it is possible to obtain compounds 5 bear-
ing several R or OR% groups using only different
mono-Grignard reagents or sodium alcoholates in a
one-pot two-step procedure carried out at room tem-
perature. In addition, the collateral product 7 is
another interesting phosphorus compound, which can
be separated in 30–40% yield. It should be noted that
compound 7 is reported7 to be obtained by an
anomalous and unexplained reaction in very low (6%)
yield.
Scheme 3.
We noticed that the ratio obtained in cases a, b
depends on the time of the first step of the reaction
with the formation of pentacoordinate5 intermediate
A. In fact, when PhMgBr is immediately added to A
we have only 4b, while when we added PhMgBr to A
after leaving it to stand alone for about 3 h we found
the prevalence of 5b. This fact indicates that the
pathway for the formation of 5 is more complex than
the one which explains the formation of 4.
Finally, obtaining and being able to isolate both com-
pounds 5 and 7 make it possible to consider our
reaction as a new high atom economy process.
Acknowledgements
Investigation supported by the University of Bologna
(funds for selected research topics AA 2000–2002).
Thanks are also due to Consiglio Nazionale delle
Ricerche (CNR, Roma) and Ministero della Ricerca
Presumably the new intermediate might be the iso-
meric ionic form A% which can explain the inversion
of reactivity of the two P atoms. In this manner, the
nucleophilic attack of the second reagent can occur
on the P2 atom which is now a very reactive pho-
sphenium ion.7 After this attack and addition of S8
Scientifica
e Tecnologica (MURST) for financial
support.

G. Baccolini et al. / Tetrahedron Letters 43 (2002) 9299–9302
9301
2,9 - Dimethyl - 11 - (phenyl) - 11H - 11l5 - dibenzo[c,f][1,2,5]-
dithiaphosphepine-11-thione (5b): Greasy solid, 50% yield,
Rf=0.45 (petroleum light:dichloromethane, 2:1); lH (300
References
1. (a) Noyori, R. Asymmetric Catalysis in Organic Synthe-
sis; Wiley: New York, 1994; (b) Burk, M. J.; Gross, M.
F.; Martinez, J. P. J. Am. Chem. Soc. 1995, 117, 9375; (c)
Jiang, Q.; Xiao, D.; Zhang, Z.; Cao, P.; Zang, X. Angew.
Chem., Int. Ed. Engl. 1999, 38, 516.
2. (a) Baccolini, G.; Mezzina, E.; Todesco, P. E.; Foresti, E.
J. Chem. Soc., Chem. Commun. 1988, 304; (b) Baccolini,
G.; Beghelli, M.; Boga, C. Heteroatom Chem. 1997, 8,
551; (c) Gang Wu, R.; Wasylishen, E.; Power, W. P.;
Baccolini, G. Can. J. Chem. 1992, 72, 1229.
3. Baccolini, G.; Orsolan, G.; Mezzina, E. Tetrahedron Lett.
1995, 36, 447.
4. (a) Baccolini, G.; Boga, C.; Negri, U. Synlett 2000, 1685;
(b) Baccolini, G.; Boga, C.; Buscaroli, R. A. Eur. J. Org.
Chem. 2001, 3421.
3
MHz, CDCl3): 8.58 (dm, 2H, JP–H=16.6 Hz), 7.42–7.20
(m, 9H), 2.43 (s, 6H, CH3); lC (75.56 MHz, CDCl3):
139.8* (d, J=70.1 Hz), 139.5 (d, J=12.8 Hz), 139.1 (d,
J=13.1 Hz), 139.0 (d, J=7.4 Hz), 133.7 (d, J=83.0 Hz),
132.8 (d, J=2.9 Hz), 131.3 (d, J=8.9 Hz), 130.7 (d,
J=3.3 Hz), 130.3 (d, J=11.3 Hz), 128.3 (d, J=13.3 Hz),
21.3 (s) (all the signals marked with * for compounds 5
are tentatively assigned); lP (121.47 MHz, CDCl3): 49.0
(m); MS (m/z, %): 384 (M+, 59), 352 (14), 320 (74), 275
(70), 243 (100), 211 (51), 185 (62); IR w, (cm−1): 488 (S–S),
690 and 745 (P=S), 1100 (PC), 1583; HRMS calcd for
C20H17PS3: 384.0230, found: 384.0221.
11-(2-Chlorophenyl)-2,9-dimethyl-11H-11l5-dibenzo[c,f]-
[1,2,5]dithiaphosphepine-11-thione (5c): greasy solid; 80%
yield, Rf=0.36 (petroleum light:dichloromethane, 2:1);
lH (300 MHz, CDCl3): 8.65–8.48 (m, 1H), 7.65–7.47 (m,
2H), 7.45–7.30 (m, 5H), 7.14 (d, 2H, J=7.8 Hz), 2.23 (s,
6H, CH3); lC (75.56 MHz, CDCl3): 139.2 (d, J=13.3
Hz), 136.2* (d, J=82.2 Hz), 138.7 (d, J=6.1 Hz), 136.5
(d, J=10.9 Hz), 136.3 (d, J=3.2 Hz), 135.3 (d, J=13.2
Hz), 133.1 (d, J=87.9 Hz), 133.2 (d, J=2.0 Hz), 132.0 (d,
J=3.4 Hz), 131.5 (d, J=9.5 Hz), 130.9 (d, J=6.1 Hz),
127.0 (d, J=12.0 Hz), 21.3 (s); lP (121.47 MHz, CDCl3):
47.0 (m); MS (m/z, %): 418 (M+, 2), 383 (100), 275 (6),
243 (10), 211 (8), 185 (10), 121 (5); IR, w (cm−1): 484
(S–S), 506, 633 and 739 (P=S), 1111 (PC), 1261, 1422,
1456, 1578; HRMS calcd for C20H16ClPS3: 417.9840,
found: 417.9832.
5. The formation of the intermediate A was observed by 31P
NMR spectroscopy as reported previously in Ref. 4b.
For reviews on pentacoordinated phosphorus and similar
hypervalent phosphorus compounds, see: Holmes, R. R.
Pentacoordinated Phosphorus Structure and Spectroscopy,
ACS Monograph 175, American Chemical Society:
Washington, DC, 1980, Vols. I and II; Holmes, R. R.
Acc. Chem. Res. 1998, 31, 535; Arduengo, A. J., III;
Stewart, C. A. Chem. Rev. 1994, 94, 1215.
6. Typical procedure for the synthesis of compounds 5a–f: A
solution of bis-Grignard reagent 2 (n=2, 1 mmol) in
THF was added dropwise, under a dry nitrogen atmo-
sphere, to a solution of 1 (1.0 mmol) in THF (15–25 mL)
at room temperature. The mixture was stirred for 30 min
and allowed to stand for an additional 150 min, always at
room temperature. A solution of mono-Grignard reagent
(1.1 mmol) (or alcoholate, 2.0 mmol) was then added.
The reaction mixture was allowed to stand for 25 h at
room temperature then treated with elemental sulfur (2.0
mmol) for 60 min, quenched with H2O and extracted
with CH2Cl2. The organic layer was dried over anhydrous
sodium sulfate and concentrated ‘in vacuo’. Compounds
5a–f (50–80%) and 7 (whose spectral data are in agree-
ment with Ref. 7) were purified by FC on a silica gel
column. According to spectral data the purity of products
5a–f and 7 is higher than 98%.
2,9-Dimethyl-11-(1-methyl-2-propenyl)-11H-11l5-dibenzo-
[c,f][1,2,5]dithiaphosphepine-11-thione (5d): Greasy solid,
80% yield, Rf=0.58 (petroleum light:dichloromethane,
2:1); lH (300 MHz, CDCl3): 8.75 (dd, 1H, JP–H=15.9 Hz,
JH–H=1.4 Hz), 8.60 (dd, 1H, J=15.7 Hz, J=1.6 Hz),
7.45–7.30 (m, 2H), 7.25–7.12 (m, 2H), 5.75–5.50 (m, 1H,
HCꢀCH2), 5.00–4.90 (m, 1H, cis-HCꢀCH2), 4.85–4.70
(m, 1H, trans-HCꢀCH2), 4.40–4.20 (m, 1H, CHCH3),
2.45 (s, 3H, CH3), 2.41 (s, 3H, CH3), 1.07 (dd, JP–H=20.1
Hz, JH–H=6.9 Hz, CH3CH); lC (75.56 MHz, CDCl3):
141.0 (d, J=10.9 Hz), 140.8 (d, J=11.6 Hz), 140.4* (d,
J=83.2 Hz), 140.2* (d, J=83.0 Hz), 138.9 (d, J=12.2
Hz), 138.7 (d, J=12.5 Hz), 138.4 (d, J=5.9 Hz), 138.1 (d,
J=5.8 Hz), 134.7 (d, J=6.6 Hz), 132.5 (d, J=3.0 Hz),
132.4 (d, J=3.1 Hz), 131.2 (d, J=8.9 Hz), 131.0 (d,
J=9.2 Hz), 118.0 (d, J=13.1 Hz), 44.3 (d, J=51.3 Hz),
21.3 (s), 13.6 (d, J=2 Hz); lP (121.47 MHz, CDCl3): 62.1
(m); MS (m/z, %): 362 (M+, 22), 307 (100), 275 (12), 243
(78), 185 (37); IR w (cm−1): 495 (S–S), 645 and 737 (P=S),
820, 1117, 1449, 1582, 1631; HRMS calcd for C18H19PS3:
362.0386, found: 362.0380.
2,9-Dimethyl-11-(1-methylbutyl)-11H-11l5-dibenzo[c,f]-
[1,2,5]dithiaphosphepine-11-thione (5a): Greasy solid, 75%
yield, Rf=0.53 (petroleum light:dichloromethane, 2:1);
lH (300 MHz, CDCl3) 8.75–8.63 (m, 2H), 7.38–7.05 (m,
4H), 2.40–0.80 (m, 5H, CH2 and CH), 2.38 (s, 3H, CH3),
2.36 (s, 3H, CH3), 0.88 (dd, 3H, JPH=20.9 Hz, JHH=6.9
Hz, CH3CH), 0.66 (t, 3H, J=7.1 Hz, CH3CH2); lC (75.56
MHz, CDCl3): 140.8 (d, J=11.1 Hz), 140.4 (d, J=11.2
Hz), 139.0 (d, J=12.2 Hz), 138.7 (d, J=12.0 Hz), 138.4
(d, J=6.1 Hz), 138.1 (d, J=5.3 Hz), 132.6 (d, J=3.0 Hz),
132.4 (d, J=3.0 Hz), 131.4 (d, J=8.9 Hz), 130.9 (d,
J=8.6 Hz), 38.4 (d, J=53.3 Hz), 30.6 (d, J=135.8 Hz),
21.4 (s), 21.3 (s), 20.3 (d, J=14.6 Hz), 13.8 (d, J=8.9
Hz), 12.7 (s); lP (121.47 MHz, CDCl3): 65.0 (m); MS
(m/z, %): 378 (M+, 8), 308 (31), 275 (100), 243 (36), 211
(23), 185 (46), 121 (10); IR w (cm−1): 488 (S–S), 661 and
717 (P=S), 1116 (PC), 1455, 1584; HRMS calcd for
C19H23PS3: 378.0699, found: 378.0691.
11 - Ethoxy - 2,9 - dimethyl - 11H - 11l5 - dibenzo[c,f][1,2,5]-
dithiaphosphepine-11-thione (5e): Greasy solid; 60% yield,
Rf=0.57 (petroleum light:dichloromethane, 2:1); lH (300
3
4
MHz, CDCl3): 8.55 (dd, 2H, JP–H=18.7 Hz, JH–H=1.4
Hz), 7.39 (dd, 2H, J=7.7 Hz, J=5.2 Hz), 7.25–7.19 (m,
2H), 4.05–3.85 (m, 2H, OCH2), 2.44 (s, 6H, CH3), 1.27 (t,
3H, J=7.1 Hz); lC (75.56 MHz, CDCl3): 16.2 (d, J=8.1
Hz), 21.3 (s), 61.4 (d, J=6.8 Hz), 131.2 (d, J=10.8 Hz),
132.9 (d, J=2.9 Hz), 135.1 (d, J=108.4 Hz), 138.3 (d,
J=12.6 Hz), 138.4 (d, J=6.8 Hz), 138.8 (d, J=13.4 Hz);
lP (121.47 MHz, CDCl3): 86.9 (m); MS (m/z, %): 352

9302
G. Baccolini et al. / Tetrahedron Letters 43 (2002) 9299–9302
(M+, 54), 320 (22), 275 (57), 259 (100), 243 (61), 211 (38),
500 (S–S), 650 and 717 (P=S), 994 (POC), 1117 (PC),
1256, 1378, 1456; HRMS calcd for C19H23OPS3:
394.0649, found: 394.0641.
185 (30), 121 (14); IR w (cm−1): 484 (S–S), 506, 635 and
717 (P=S), 1028 (POC), 1111 (PC), 1256, 1378, 1456;
HRMS calcd for C16H17OPS3: 352.0179, found: 352.0170.
2,9 - Dimethyl - 11 - (2 - methylbutoxy) - 11H - 11l5 - dibenzo-
[c,f][1,2,5]dithiaphosphepine-11-thione (5f): Greasy solid;
70% yield, Rf=0.63 (petroleum light:dichloromethane,
2:1); lH (300 MHz, CDCl3): 8.57 (dd, 2H, 3JP–H=16.8
7. For a review about phosphenium ions, see: Cowley, A.
H.; Kempt, R. A. Chem. Rev. 1985, 85, 367.
8. For a review about phosphoranide, see: Dillon, K. B.
Chem. Rev. 1994, 94, 1441.
9. For a review about ligand-coupling reactions of hyperva-
lent species, see: Oae, S.; Uchida, Y. Acc. Chem. Res.
1991, 24, 202.
4
Hz, 4JH–H=1.4 Hz), 7.39 (dd, 2H, 3JH–H=7.6 Hz, JP–
3
H=5.2 Hz), 7.22 (d, 2H, JH–H=7.6 Hz), 3.75–3.58 (m,
10. (a) Schmutzler, R. Inorg. Chem. 1964, 3, 421; (b) Lee, J.
D.; Goodacre, G. W. Acta Crystallogr., Sect. B 1970, 26,
507.
11. Douglass, M. R.; Marks, T. J. J. Am. Chem. Soc. 2000,
122, 1824.
12. Baccolini, G.; Boga, C.; Buscaroli, R. A. Synthesis 2001,
1938.
13. Block, E.; Ofori-Okai, G.; Zubieta, J. J. Am. Chem. Soc.
1989, 111, 2327.
2H, OCH2), 2.44 (s, 6H, CH3), 1.70–1.00 (m, 3H, CH2
and CH), 0.87 (d, 3H, JH–H=6.7 Hz, CH3CH), 0.81 (t,
3
3H, J=7.4 Hz, CH3CH2); lC (75.56 MHz, CDCl3): 138.7
(d, J=14.7 Hz), 138.6* (d, J=6.0 Hz), 138.5 (d, J=11.8
Hz), 135.0 (d, J=108.8 Hz), 132.8 (d, J=2.9 Hz), 131.2
(d, J=10.7 Hz), 69.7 (d, J=7.6 Hz), 35.3 (d, J=8.4 Hz),
25.7 (s), 21.3 (s), 16.3 (s), 11.1 (s); lP (121.47 MHz,
CDCl3): 87.3 (m); MS (m/z, %): 374 (M+, 5), 324 (20),
275 (8), 259 (100), 211 (14), 185 (10), 121 (5); IR w (cm−1):