REDUCTIVE DESULFONYLATION OF PHENYL SULFONES BY SAMARIUM(II) IODIDE-HEXAMETHYLPHOSPHORIC TRIAMIDE

Article abstract of DOI:10.1016/0040-4039(91)85009-T

Samarium(II) iodide in tetrahydrofuran reductively desulfonylates phenyl sulfones in the presence of hexamethylphosphoric triamide.This transformation is illustrated here for ten substrates, which include secondary alicyclic, β-hydroxy, vicinal bis-, and α,β-unsaturated sulfones.

Full text of DOI:10.1016/0040-4039(91)85009-T

Tetr aheckon Letters, Vol.32, No.17, pp 1949-1952, 1991
printed in Great B~itain
0040 4039/91 $3.00 + .00
Pergamon Press pie
REDUCTIVE DESULFONYLATION OF PHENYL SULFONES BY
SAMARIUM(II) IODIDE-HEXAMETHYLPHOSPHORIC TRIAMIDE
H. Ktinzer,* M. Stahnke, G. Saner, and R. Wiechert
Research Laboratories, Schering AG Berlin,
Miillerstrasse 170-178, 1000 Berlin 65, Germany
Summary. Samarium(lI) iodide in teU'ahydrofumn reductively desulfonylates phenyl
sulfones in the presence of hexamethylphosphoric triamide. This transformation is
illustrated here for ten substrates, which include secondary aiicyclic, [5-hydroxy, vicinal
bis-, and ~,l]-unsaturated sulfones.
The most popular transformations for carbon-carbon bond formation, employing arylsulfonyl bearing
synthons, include alkylation of a-arylsulfonyl carbanions,1 Michael addition of organometallic reagents to
a,l~-unsaturated sulfones, occasionally followed by an additional alkylafion step on the intermediate
ct-sulfonyl carbanion,2 and Diels-Alder reactions with electron-deficient dienophiles, e. g., phenyl vinyl
sulfone,3 (Z)- and (E)-l,2-bis(phenylsulfonyl)ethylene, 4 or ethynyl p-tolyl sulfone.5 Since the ultimate
target molecules generally lack the sulfone moiety, the overall efficacy of such protocols is tightly related
to reliable methods for the removal of the sulfur substituent. Dissolving-metal reductive desulfonylations,
I--,II, have emerged as a particular important class of reactions in this context, with amalgams, preferably
those of Group IA-IIIA metals, in alcoholic solution ranking as the reagents of choice.6
RIR2R3C-SO2Ph
I
I.
RtR2R3C-H
II
Except for the solitary cases of a-phenylsulfonyl ketones7 and B-hydroxy imidazolyl sulfones,s where
samarium(ll) iodide (SmI2) in tetrahydrofuran (THF) has been reported to give rise to the parent ketones7
and to olefinic products,s respectively, the lanthanide reagent does not seem to have been successfully
applied in reductive desulfonylations of non-activated phenyl sulfones. In fact, Kende and Mendoza
noticed in their work on ~]-hydroxy imidazolyl sulfones that the corresponding [5-hydroxy phenyl sulfones
fail to be desulfonylated by SmI2.8 Interestingly, it has also been demonstrated that SmI2 promotes
deoxygenation of sulfoxides9 and certain sulfones1° to the corresponding sulfides.
These reports prompt us to disclose some of our own findings regarding Smlz-mediated reductive
desulfonylations of phenyl sulfones.
In our hands, neither deoxygenation nor desulfonylation occurred upon treatment of a series of sulfones
with Sm|2-THF at various temperatures, However, when bexamethylphosphoric triamide (HMPA)It was
added to a solution of commercially available or, preferably, freshly prepared SmI2 in THF containing a
phenyl sulfone substrate under an atmosphere of argon, a color change from blue-green to purple was
observed and thin-layer chromatography of samples withdrawn from the reaction mixture revealed
formation of a new, less-polar product, which was devoid of any sulfur functionality. Representative
examples for this transformation are compiled in the Table below. Reaction conditions have been
optimized to some degree, in or~r to secure satisfactory yields.
1949

1950
Table. SmI2/HMPA-Promoted Reductive Desulfonylation Of Phenyl Sulfones, X=SO2Ph
......................................................................................................................................
Entry Substrate Product Reaction Conditions; Yield
........................................................................................................................................
OAc
OAc
1
2
~
1
~'x
~
2
-'~
-20°C, 70 min; 70%
-20°C, 90 rain; 87%
MeO
MeO
OAc
OAc
M e O ~ "3: ] ' - X
OR
M e O ~ 4"]
OR
MeO
H)
MeO
=H)
3b
4
7 (R=Ac)
~
8 (R=Ac)
~
-20°C, 90 min; 52%
-20°C, 30 min; 74%
9
10
OH
OH
5
6
+22°C, 60 min; 53%
-20°C, 30 min; 83%
-20°C, 30 min; 91%
-20°C, 90 min; 68%
-20°C, 30 min; 77%
MeO
Me/)
~
@
13
14
15
14
OAc
OAc
8
9
18
14

Thus, the cycloadduct 1, obtained by Diels-Alder reaction between phenyl vinyl sulfone and 17-
acetyloxy-3-methoxyestra-l,3,5(10),14,16-pentaene, a2 was submitted to desulfonylation at -20°C. After 70
minutes, the starting material was almost completely consumed and the product 21~ was isolated in 70%
yield following aqueous work-up and chromatography on silica gel, Remarkably, both the acetate
functionality and the norbornenyl double bond remained largely intact at -20°C, a situation which changed
to the worse, when the reaction was performed at 0°C. The superior stability of the hydrogenated steroid
312 versus 1 in the SmIffHMPA-promoted desulfonylation process is reflected by a high 87% yield of the
product 4.12 An additional secondary steroidal sulfone was prepared by Michael reaction between
thiophenol and 3-methoxyestra-l,3,5(10),15-tetraen-17-one, as NaBH4 reduction of the carbonyl group, and
oxidation14 of the sulfur atom. Acetylation of the T-hydroxy sulfone 5 led to the protected derivative 7.
From two desulfonylation runs, estradiol methyl ether (6) and the acetate g were isolated in 50% and 52%
yield, respectively. Approximately 30% of each starting material was recovered unchanged in these
instances. Reduction of the cycloadduct 9, readily synthesized from phenyl vinyl sulfone and anthracene,t5
furnished dibenzobicyclo[2.2.2]octadiene (10) in 74% yield,as As an example for the desulfonylation of
[3-hydroxy phenyl sulfones, we have listed the reduction of the steroid derivative 11, which was made
available by alkylation of the Li-anion of methyl phenyl sulfone with 3-methoxyestra-l,3,5(10)-tlien-17-
one. The tertiary alcohol 12 was isolated as the main product, together with 17-methylene-3-
methoxyestra-l,3,5(10)-triene (20%), and 20% of educt 11.
Not unexpectedly, the SmI2/HMPA reagent combination seems also excellently suited for the conversion
of vicinal bis(arylsulfonyl) derivatives into the corresponding olefins by reductive desulfonylation.16 This
useful reaction is realized here in the transformation of cycloadducts 13 and 15, derived from (Z)- and
(E)-l,2-bis(phenylsulfonyl)ethylene and anthracene, into dibenzobarrelene 14I6 in 83% and 91% yield,
respectively.
Acceptable results may also be achieved with certain ~,[~-unsaturated phenyl sulfones.17 The steroid
derivative 16 was obtained by thioketalization-eliminafion,18 followed by oxidation14 of the intermediate
vinyl sulfide. Again, mild reaction conditions guarantee a satisfactory 68% yield of the acetate 17. Still
another synthesis of dibenzobarrelene (14) was accomplished by reduction of the vinyl sulfone 18. The
starting material 18 was generated by elimination of benzenesulflnic acid from 13 in dimethylformamide
containing aqueous potassium carbonate.19
In conclusion, this novel reductive desulfonylation protocol2° expands the synthetic utility of the
SmI2-THF reagent to some extent, although the level of chemoselectivlty attainable in reactions with
highly functionalized molecules will be limited.TM21
Acknowledgment. We are grateful to Dr. G. Michi and Mr. J. Lorenz for their assistance in spectroscopic
structure determinations and to Mrs. H. Zahn for typing the manuscript.
References and Notes
For some recent examples, consult: (a) Hird, N. W.; Lee, T. V.; Leigh, A. J.; Maxwell, J. R.;
Peakman, T. M. Tetrahedron Lett. 1989, 30, 4867. (b) Ley, S.V.; Anthony, N. J.; Armstrong, A.;
Brasca, M. G.; Clarke, T.; Culshaw, D.; Greek, C.; Grice, P.; Jones, A. B,; Lygo, B.; Madin, A.;
1.

1952
Sheppard, R. N.; Slawin, A. M. Z.; Williams, D. J. Tetrahedron 1989, 45, 7161. (c) Gopalan, A. S.;
Jacobs, H. K. Tetrahedron Lett. 1990, 31, 5575.
2. Hardinger, S. A.; Fuchs, P. L. J. Org. Chem. 1987, 52, 2739. Earlier developments have been
reviewed in: Fuchs, P. L.; Braish, T. F. Chem. Rev. 1986, 86, 903.
3. Paquette, L. A.; Can', R. V. C. Organic Syntheses 1986, 64, 157.
4. (a) De Lucchi, 04 Pasquato, L. Tetrahedron 1988, 44, 6755. (b) Paquette, L. A.; Ra, C. S.;
Edmonson, S. D. J. Org. Chem. 1990, 55, 2443.
5. Waykole, L.; Paquette, L. A. Organic Syntheses 1989, 67, 149.
6. For a review on this topic, see: Grossert, J. S. in The Chemistry of Sulphones and Sulphoxides;
Patai, S.; Rappoport, Z.; Stifling, C. J. M., Eds.; Wiley-Interscience: Chichester, 1988; Chapter 20.
7. Molander, G. A,; Hahn, G. J. Org. Chem. 1986, 51, 1135.
8. Kende, A. S.; Mendoza, J. S. Tetrahedron Lett. 1990, 3l, 7105.
9. Girard, P.; Namy, J. L.; Kagan, H. B. J. Am, Chem. Soc. 1980, 102, 2693.
10. Handa, Y.; Inanaga, J.; Yamaguchi, M. J. Chem. Soc., Chem. Commun. 1989, 298.
11. Inanaga, J.; lshikawa, M.; Yamaguchi, M. Chemistry Lett. 1987, 1485.
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13. Johnson, W. S.; Johns, W. F. J. Am. Chem. Soc. 1957, 79, 2005.
14. McKillop, A.; Tarbin, J. A. Tetrahedron Lett. 1983, 24, 1505.
15. Cart, R. V. C.; Williams, R..V.; Paquette, L. A. J. Org. Chem. 1983, 48, 4976.
16. (a) De Lucchi, O.; Lucchini, V.; Pasquato, L.; Modena, G. J. Org. Chem. 1984, 49, 596.
(b) Brown, A. C.; Carpino, L. A. J. Org. Chem. 1985, 50, 1749.
17. (a) Ochiai, M.; Ukita, T.; Fujita, E. J. Chem. Soc., Chem. Commun. 1983, 619. (b) Cuvigny, T.;
Herve Du Penhoat, C.; Julia, M. Tetrahedron 1987, 43, 859.
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Synthesis 1989, 143.
19. De Lucchi, 04 Lucchini, V.; Zamai, M.; Modena, G.; Valle, G. Can. J. Chem. 1984, 62, 2487.
20. A characteristic reductive desulfonylation procedure is as follows.
Under an atmosphere of argon, 0.494 g (1 mmol) of 3 was dissolved in 50 mL of a freshly prepared
solution of SmI2-THF (approximately 0.1 molar). This mixture was cooled to -20°C under stirring
and hexamethylphosphoric triamide (4 mL) was added dropwise by syringe, whereupon the color
of the solution changed from blue to purple. After 90 minutes, the reaction was terminated with
aqueous ammonium chloride (5 mL). Most of the tetrahydrofuran was removed in vacuo by rotary
evaporation. The product was precipitated by addition of cold hydrochloric acid (0.5 molar) and
isolated by suction-filtration. The solid residue was dissolved in ethyl acetate, the resulting organic
phase was washed with aqueous sodium thiosulfate solution, followed by brine, and then dried over
anhydrous sodium sulfate. Chromatography of the crude product on silica gel (hexane-ethyl
acetate, 9:1) provided 0.308 g (87%) of 4, mp 119-120 °C (acetone-hexane).
21. (a) Kagan, H, B.; Namy, J. L. Tetrahedron 1986, 42, 6573. (b) Kagan, H. B.; Sasaki, M.; Collin, J.
Pure & Appl. Chem. 1988, 60, 1725.
(Received in Germany 31 January 1991)