A straightforward synthesis of 3-acylphospholes

Article abstract of DOI:10.1021/ol051816d

(Chemical Equation Presented) The reaction of 2,5-diphenylphospholide, first with acyl chlorides, then with ^tBuOK, provides a direct access to 3-acyl-2,5-diphenylphospholides via a 1H-, 2H-, 3H-phosphole equilibrium.

Full text of DOI:10.1021/ol051816d

ORGANIC
LETTERS
2
005
Vol. 7, No. 20
511-4513
A Straightforward Synthesis of
-Acylphospholes
4
3
Magali Clochard, Joanna Grundy, Bruno Donnadieu, and Fran c¸ ois Mathey*
UCR-CNRS Joint Research Chemistry Laboratory, Department of Chemistry,
UniVersity of California RiVerside, RiVerside, California 92521-0403
fmathey@citrus.ucr.edu
Received July 29, 2005
ABSTRACT
t
The reaction of 2,5-diphenylphospholide, first with acyl chlorides, then with BuOK, provides a direct access to 3-acyl-2,5-diphenylphospholides
via a 1H-, 2H-, 3H-phosphole equilibrium.
Functionalization is the central synthetic problem of phos-
phole chemistry. The nonplanar nonaromatic structure of
phospholes prevents the use of the classical methods that
allow the synthesis of a wide range of functional pyrroles
such as electrophilic substitution and R-metalation reactions.
Today the simplest functionalization method in use in
phosphole chemistry relies on the equilibrium between 1H-
and 2H-phospholes.1 Its principle is depicted in Scheme
involves not only the 1H- and the 2H- but also the
3H-phosphole. The three species lie very close in energy,
but the barrier between the 1H- and the 2H-phosphole is
substantially smaller than the barrier between the 2H- and
-
1
the 3H-phosphole (19.6 vs 30.7 kcal mol ).
We reasoned that, if we took a phosphole with substituents
on the two R-positions of the ring and chose a Z-functionality
whose migration was especially easy, it might be possible
to use the same principle to prepare 3-functional phospholes.
-7
1
. The role of the base is to displace the equilibrium by
(
4) Toullec, P.; Mathey, F. Synlett 2001, 1977.
(5) Carmichael, D.; Mathey, F.; Ricard, L.; Seeboth, N. Chem. Commun.
Scheme 1. Synthesis of 2-Functional Phospholides from the
Equilibrium Mixture between 1H- and 2H-Phospholes
2002, 2976.
(6) Melaimi, M.; Ricard, L.; Mathey, F.; Le Floch, P. Org. Lett. 2002,
4
, 1245.
(
7) Carmichael, D.; Klankermayer, J.; Ricard, L.; Seeboth, N. Chem.
Commun. 2004, 1144.
8) Dinadayalane, T. C.; Geetha, K.; Sastry, G. N. J. Phys. Chem. A
003, 107, 5479.
(
2
(
9) Bachrach, S. M. J. Org. Chem. 1993, 58, 5414.
(10) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb,
M. A.; Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.; Kudin, K.
N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.;
Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.;
Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.;
Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li,
X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Adamo, C.; Jaramillo, J.;
Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.;
Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.;
Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels,
A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.;
Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.;
Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz,
P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.;
Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson,
B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian 03,
Revision B.05; Gaussian, Inc.: Pittsburgh, PA, 2003.
abstracting the acidic proton from the 2H-phosphole.
These [1,5] shifts have been studied from a theoretical
standpoint on the parent phosphole.8,9 The equilibrium
(
1) Holand, S.; Jeanjean, M.; Mathey, F. Angew. Chem., Int. Ed. Engl.
997, 36, 98.
2) Holand, S.; Maigrot, N.; Charrier, C.; Mathey, F. Organometallics
998, 17, 2996.
3) Frison, G.; Ricard, L.; Mathey, F. Organometallics 2001, 20, 5513.
1
1
(
(
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0.1021/ol051816d CCC: $30.25
© 2005 American Chemical Society
Published on Web 09/08/2005

Scheme 2. Equilibrium between 1H-, 2H-, and 3H-Phospholes
with a Formyl Migrating Group: Variation of the Electronic +
-
1
Zero Point Energies (data in kcal mol
)
Figure 1. Crystal structure of sulfide 4.
To check the feasibility of this approach, we performed DFT
10
calculations at the B3LYP/6-311+G(d,p) level on the 2,5-
dimethylphosphole ring with formyl as the migrating group.
The carbonyl groups are, indeed, known to migrate very
crystal structure analysis of 4 (Figure 1) shows that the
carbonyl group lies out of the plane of the phosphole ring
(C8-C9-C10-O1 torsion angle ) 36.8°) and is not
4
easily. The results are shown in Scheme 2. The transition
conjugated with the CdC double bond (C1-C8 ) 1.3526
Å; C9-C17 ) 1.3565 Å).
The yields of this synthesis of 3-acylphospholes are
states display one imaginary frequency and IRC calculations
have shown that they connect the 1H, 2H, and 3H minima.
As can be seen, the TS2-3 transition state is sufficiently low
to allow a practical use of the 3H-phosphole for synthetic
purposes. We thus allowed the 2,5-diphenylphospholide ion
sometimes quite modest due to the competing nucleophilic
t
attack of BuOK at the P-acyl bond. Nevertheless, this
synthesis is attractive by its simplicity, can probably be
(
made by cleavage of the P-Ph bond of 1,2,5-triphenylphos-
11
phole by lithium in THF) to react with several acyl
(11) Lukas, B.; Roberts, R. M. G.; Silver, J.; Wells, A. S. J. Organomet.
Chem. 1983, 256, 103.
chlorides and then studied the evolution of the resulting
-
3
(
12) Synthesis of 4: 1,2,5-Triphenylphosphole (0.5 g, 1.6 × 10 mol)
t
1
5
-acyl-2,5-diphenylphospholes in the presence of BuOK at
in dry THF (20 mL) was allowed to react with an excess of lithium wire
until the P-Ph bond cleavage was completed. After removing excess
lithium, the solution was treated with tert-butyl chloride (0.2 mL, 1.6 ×
0-60 °C. The reaction mixture is conveniently monitored
by P NMR spectroscopy. For R ) Ph, the starting 2,5-
diphenylphospholide (δ P ) 71 ppm) is first transformed
into the 1-benzoyl-2,5-diphenylphosphole (δ P ) 18 ppm).
31
-
3
10
mol) and heated at 60 °C for 1 h. Benzoyl chloride (0.2 mL, 1.6 ×
31
10-3 mol) was added dropwise at -50 °C. The mixture was warmed to
31
room temperature and monitored by 31P NMR. A yellow color is observed
t
upon completion of the reaction. After 10 min at 60 °C, BuOK (0.18 g,
t
Upon addition of BuOK, the 1-acylphosphole reacts to give
-3
1
.6 × 10 mol) was slowly added and the solution was stirred at the same
-3
a mixture of the starting phospholide resulting from the
temperature for a further 60 min. Iodomethane (0.1 mL, 1.6 × 10 mol)
was added through a syringe at -50 °C, and the solution was warmed to
room temperature. Sulfurization was performed by addition of sulfur powder
nucleophilic attack of the base at the P-acyl bond and the
31
-
3
expected 3-acylphospholide 1 (δ P ) 139 ppm) resulting
from the abstraction of the acidic proton from the 3H-
phosphole. Similar results were observed with the other acyl
chlorides (Scheme 3). The formula of the 3-acylphospholides
(0.05 g, 12.8 × 10 mol). After vacuum distillation of the solvent, the
residue was chromatographed with dichloromethane-hexane 60:40 to yield
31
0
.3 g (49%) of a bright-yellow solid. P NMR (CDCl3) δ + 46.1 (dq,
2
3
1
2
J(P-H) ) 12 Hz, J(P-H) ) 40 Hz); H NMR (CDCl3) δ 1.84 (d, J(H-
1
3
P) ) 12 Hz, 3H, CH3), 7.09-7.88 (m, 16H, Ph + Hâ); C NMR (CDCl3)
1
δ 19.92 (d, J(C-P) ) 49.5 Hz, -CH3), 126.96-129.95 (m, C ortho, meta,
2
1
para), 132.28 (d, J(C-P) ) 21.9 Hz, CâH), 140.32 (d, J(C-P) ) 74.8
1
2
Hz, CR), 140.40 (d, J(C-P) ) 72.2 Hz, CR), 142.37 (d, J(C-P) ) 23.0
3
Hz, Câ), 195.36 (d, J(C-P)) 15 Hz, -C(O)Ph); mass spectrum (EI, 70
Scheme 3. Synthesis of 3-Acyl-2,5-diphenylphospholides
+
+
+
eV) m/z 386 (M , 100%), 371 (M - CH3, 16%), 354 (M - S, 20%),
+
+
2
81 (M - C(O)Ph, 9%), 233 (M - 2Ph, 8%). Synthesis of 5: As for 4
-3
with 2-thienoyl chloride (0.17 mL, 1.6 × 10 mol). Yield 0.2 g (33%).
3
1
1
2
3
P NMR (CDCl3) δ + 41.3 (dq, J(P-H) ) 11 Hz, J(P-H) ) 37 Hz);
2
H NMR (CDCl3) δ 1.84 (d, J(H-P) ) 13.5 Hz, 3H, CH3), 6.82-7.87
13
1
(
m, 14H, Ph + Th + Hâ); C NMR (CDCl3) δ 19.81 (d, J(C-P) ) 48.0
2
Hz, -CH3), 126.95-136.43 (m, Ph + Th), 131.97 (d, J(C-P) ) 20.7
1
1
Hz, CâH), 139.78 (d, J(C-P) ) 72.5 Hz, CR), 148.48 (d, J(C-P) ) 73.7
2
3
Hz, CR), 142.42 (d, J(C-P) ) 27.6 Hz, Câ), 187.24 (d, J(C-P)) 16.1
+
+
Hz, -C(O)Th); mass spectrum (EI, 70 eV) m/z 392 (M , 63%), 377 (M
+
+
-
CH3, 10%), 361 (M - S, 100%), 383 (M - C(O)Thiophene, 12%).
Synthesis of 6: Same conditions as for 4 and 5, except that a higher
concentration of 1,2,5-triphenylphosphole is used (0.5 g in 5 mL of THF).
3
1
1
Yield 0.05 g (10%). P NMR (CDCl3) δ +44.9; H NMR (CDCl3) δ 1.74
2
(
d, J(H-P) ) 12.9 Hz, 3H, P-CH3), 1.97 (s, 3H, COCH3), 7.20-7.85
13 1
(
m, 11H, Ph + Hâ); C NMR (CDCl3) δ 18.96 (d, J(C-P) ) 49.0 Hz,
2
P-CH3), 29.83 (s, CH3), 126.69-132.05 (m, Ph), 131.17 (d, J(C-P) )
1
2
2
1.0 Hz, CâH), 139.36 (d, J(C-P) ) 73.8 Hz, CR), 142.63 (d, J(C-P) )
1 3
was definitively established by transformation into the
2
2.1 Hz, Câ), 143.63 (d, J(C-P) ) 69.9 Hz, CR), 198.95 (d, J(C-P))
12
+
corresponding 1-methylphosphole sulfides 4-6. The X-ray
15 Hz, -C(O)Me); mass spectrum (EI, 70 eV) m/z 324 (M , 100%).
4512
Org. Lett., Vol. 7, No. 20, 2005

generalized to other good migrating groups, and represents
Acknowledgment. The authors thank the University of
California Riverside and the CNRS for financial support of
this work.
the first synthetic application of 3H-phosphole chemistry.
13
As far as we know, only one 3-acylphosphole and one 3H-
phosphole with tetracoordinate phosphorus14 have been
described so far.
Supporting Information Available: Theoretical calcula-
tions (structures and energies) and X-ray data for sulfide 4.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(
13) Keglevich, G.; Bocskei, Z.; Keseru, G. M.; Ujszaszy, K.; Quin, L.
D. J. Am. Chem. Soc. 1997, 119, 5095.
14) Barluenga, J.; Lopez, F.; Palacios, F. J. Chem. Soc., Chem. Commun.
986, 1574.
(
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