Selective C - S bond formation via Fe-catalyzed allylic substitution

Article abstract of DOI:10.1021/ol901297s

In contrast to the formation of C - O and C - N bonds it was only recently that the selective C - S bond formation by means of transition metal complexes moved more into the center of research. This is somewhat surprising given the fact that the sulfur at

Full text of DOI:10.1021/ol901297s

ORGANIC
LETTERS
2009
Vol. 11, No. 15
3462-3465
Selective C-S Bond Formation via
Fe-Catalyzed Allylic Substitution
Markus Jegelka and Bernd Plietker*
Institut fu¨r Organische Chemie, FB Chemie, UniVersita¨t Stuttgart, Pfaffenwaldring 55,
D-70569 Stuttgart, Germany
bernd.plietker@oc.uni-stuttgart.de
Received June 10, 2009
ABSTRACT
In contrast to the formation of C-O and C-N bonds it was only recently that the selective C-S bond formation by means of transition metal
complexes moved more into the center of research. This is somewhat surprising given the fact that the sulfur atom in a functional group can
possess different oxygenation levels which correspond to different chemical properties and reaction portfolios. Herein we wish to communicate
a regioselective Fe-catalyzed allylic sulfonation that allows for the preparation of various chiral aryl allyl sulfones in good to excellent yields.
The selective formation of carbon heteroatom bonds remains
one of the most important challenges within organic syn-
thesis. Transition metal-catalyzed allylic substitutions serve
as a textbook example and have found frequent use for these
synthetic purposes.1 However, whereas a variety of C-O
and C-N bond forming processes have been developed
within the past years, similar reactions in which a sulfur atom
is introduced in a selective manner have found comparably
less attention.2,3 Among the various sulfur-containing organic
compounds sulfones occupy an important space. These
compounds allow for various follow-up reactions (e.g.,
Ramberg-Ba¨cklund reaction, Julia olefinations, etc.) and are
hence of significant synthetic interest.4,5 Palladium complexes
have proven to be suitable catalysts for the formation of
allylic sulfones starting from allylic acetates.2 Whereas in
most cases the dynamic character of the intermediate π-allyl
(1) Lu, Z.; Ma, S. Angew. Chem., Int. Ed. 2008, 47, 258.
(2) Pd-catalyzed allylic sulfonation: (a) review: Gais, H.-J. In Asymmetric
Synthesis with Chemical and Biological Methods; Enders, D., Ja¨ger, K.-E.,
Eds.; Wiley-VCH: Weinheim, Germany, 2007; p 215. (b) Boldrini, G. P.;
Savoia, D.; Tagliavini, E.; Trombini, C.; Umani-Ronchi, A. J. Organomet.
Chem. 1984, 268, 97. (c) Uozumi, Y.; Danjo, H.; Hayashi, T. Tetrahedron
Lett. 1997, 38, 3557. (d) Liao, M.; Duan, X.; Liang, Y. Tetrahedron Lett.
2005, 46, 3469. (e) Gais, H.-J.; Eichelmann, H.; Spalthoff, N.; Gerhards,
F.; Frank, M.; Raabe, G. Tetrahedron: Asymmetry 1998, 9, 235. (f) Seebach,
D.; Devaquet, E.; Ernst, A.; Hayakawa, M.; Ku¨hnle, F. N. M.; Schweizer,
W. B.; Weber, B. HelV. Chim. Acta 1995, 78, 1636. (g) Inomata, K.;
Yamamoto, T.; Kotake, H. Chem. Lett. 1981, 1357. (h) Julia, M.; Lave,
D.; Mulhauser, M.; Ramirez-Munoz, M.; Uguen, D. Tetrahedron Lett. 1983,
24, 1783. (i) Trost, B. M.; Schmuff, N. R. J. Am. Chem. Soc. 1985, 107,
396. (j) Trost, B. M.; Organ, M. G.; O’Doherty, G. A. J. Am. Chem. Soc.
1995, 117, 9662, and references cited therein. (k) Kang, S.-K.; Park, D.-
C.; Jeon, J.-H.; Rho, H.-S.; Yu, C.-M. Tetrahedron Lett. 1994, 35, 2357.
(l) Trost, B. M.; Crawley, M. L.; Lee, C. B. Chem.sEur. J. 2006, 12, 2171.
(m) Tsarev, V. N.; Konkin, S. I.; Shyryaev, A. A.; Davankov, V. A.;
Gavrilov, K. N. Tetrahedron: Asymmetry 2005, 16, 1737. (n) Vasen, D.;
Salzer, A.; Gerhards, F.; Gais, H.-J.; Bieler, N. H.; Togni, A. Organome-
tallics 2000, 19, 539. (o) Hiroi, K.; Makino, K. Chem. Pharm. Bull. 1988,
36, 1744.
(3) Allylic sulfenylations: Pd-catalyzed: (a) Goux, C.; Lhoste, P.; Sinou,
D. Tetrahedron Lett. 1992, 33, 8099. (b) Goux, C.; Lhoste, P.; Sinou, D.
Tetrahedron Lett. 1994, 50, 10321. (c) Moreno-Manas, M.; Pleixats, R.;
Villarroya, M. Tetrahedron 1993, 49, 1457. (d) Frank, M.; Gais, H-.J.
Tetrahedron: Asymmetry 1998, 9, 3353. (e) Goux, C.; Sigismondi, S.; Sinou,
D.; Pe´rez, M.; Moreno-Manas, M.; Pleixats, R.; Villarroya, M. Tetrahedron
1996, 52, 9521. (f) Trost, B. M.; Scanlan, T. S. Tetrahedron Lett. 1986,
27, 4141. Ru-catalyzed: (g) Kondo, T.; Morisaki, Y.; Uenoyama, S.; Wada,
K.; Mitsudo, T. J. Am. Chem. Soc. 1999, 121, 8657. Rh-catalyzed: (h) Leong,
P.; Lautens, M. J. Org. Chem. 2004, 69, 2194.
(4) For the use of sulfones possessing an acidic R-C-H bond see :(a)
Fuchs, P. L.; Braish, T. F. Chem. ReV. 1986, 86, 903. (b) Grossert, J. S. In
The Chemistry of Sulphones and Sulphoxides; Patai, S., Rapoport, Z.,
Stirling, C. J. M., Eds.; John Wiley and Sons Ltd.: Chichester, UK, 1988.
(c) Simpkins, N. S. Sulphones in Organic Synthesis; Pergamon Press:
Oxford, UK, 1993. (d) For an excellent review on Julia-olefinations see:
Blakemore, P. R. J. Chem. Soc., Perkin Trans. 1 2002, 2563. (e) For a
recent review on the Ramberg-Backlund reaction see: Taylor, R. J. K.;
Casy, G. Org. React. 2003, 62, 357.
10.1021/ol901297s CCC: $40.75
Published on Web 07/09/2009
 2009 American Chemical Society

Table 1. Solvent Effects in Fe-Catalyzed Sulfonationsa
Scheme 1. Ligand Effect in Allylic Sulfonations
entry
solvent
2-A:2-Bb
yield (%)b
1
2
3
4
5
6
7
8
DMF
97:3
90:10
92:8
99:1
93:7
89:11
24:76
29:71
24:76
25:75
28:72
95:5
77
15
14
12
85
29
23d
DMSO
CH3CN
THF
2-methoxyethanol
t-BuOH
H2O
DMF/H2O
DMSO/H2O
CH3CN/H2O
t-BuOH/H2O
DMF/t-BuOH
DMF/2-methoxyethanol
DMSO/t-BuOH
CH3CN/t-BuOH
THF/t-BuOH
27c d
,
18c d
,
9
29c d
,
10
11
12
13
14
15
16
23c d
,
38e
92c
26c
40c
27c
97:3
92:8
89:11
87:13
a All reactions were performed on a 1.0-mmol scale in the presence of
sodium benzenesulfinate (2.0 mmol), TBAFe (0.05 mmol), and PPh3 (0.06
mmol) under a N2 atmosphere in the given solvent (1 mL). b Determined
by GC integration, using dodecane as external standard. c Both solvents
were used in equal amounts (0.5 mL). d Hydrolysis of the carbonate detected.
e Solvents were used in a mixture of DMF/2-methoxyethanol 3:1.
Pd complexes led to the formation of regioisomers, the
presence of enantiopure ligands allowed for a control of the
stereoselective course of this sulfonation. In light of these
important contributions and with regard to the importance
of sulfones in organic synthesis we envisioned an allylic ipso-
sulfonation to complement the set of existing sulfone
synthesis.
Recently we were able to show that low- valent iron(II)
complexes are useful catalysts for the regio- and stereose-
lective allylation of C- or N-nucleophiles.6 With regard to
the importance of sulfones as intermediates in organic
synthesis4,5 we set out to develop the corresponding allylation
of sulfinates by means of our Fe-catalyst. In particular the
regioselective formation of the new C-S bond in this type
of reaction seemed attractive from both a synthetic and a
methodological point of view.
Initially we employed the ferrate catalyst [Bu4N][Fe(CO)3-
(NO)] (TBAFe) under the reaction conditions that proved
successful in the corresponding alkylation and aminations.6a,b
However, although the yields were good the regioselectivity
was not as good as in the case of C- or N-nucleophiles.
Furthermore, the high nucleophile loading and low solubility
of the sulfinic acid salt appeared problematic. Hence, the
initial priority was set on an overall reduction of the amount
of nucleophile in order to obtain a more homogeneous
reaction mixture. Different solvents were tested (Table 1).
We were pleased to find our catalyst to be active in the
sulfonation under a variety of conditions. Even the presence
of water did not result in a decomposition of the complex
(entries 7-11, Table 1). At the outset of our solvent
screening a binary solvent mixture of DMF/2-methoxyetha-
nol (3:1) gave the most satisfying results (entry 13, Table
1). It has to be pointed out that the addition of a polar protic
solvent improved the solubility of the starting material as
well as that of the byproduct formed wihin the reaction, i.e.,
the carbonate leaving group. A further improvement of the
yield was observed upon reducing the amount of sulfinate
to 1.2 equiv.
(5) A variety of transformations using sulfones lacking an acidic R-C-H
bond have been reported, e.g., conjugate addition of Grignard reagents: (a)
Julia, M.; Righini, A.; Verpeaux, J.-N. Tetrahedron 1979, 26, 2393. (b)
Julia, M.; Righini-Tapie, A.; Verpeaux, J.-N. Tetrahedron 1983, 39, 3283.
(c) Julia, M.; Verpeaux, J.-N. Tetrahedron 1983, 39, 3289. (d) Masaki, Y.;
Sakuma, K.; Kaji, K. J. Chem. Soc., Chem. Commun. 1980, 434. (e) Masaki,
Y.; Sakuma, K.; Kaji, K. J. Chem. Soc., Perkin Trans. 1 1985, 1171. (f)
Trost, B. M.; Merlic, C. A. J. Am. Chem. Soc. 1988, 110, 5216.
ipso-substitution of allyl sulfones: (g) Trost, B. M.; Ghadiri, M. R. J. Am.
Chem. Soc. 1986, 108, 1098. Sulfones as leaving groups: (h) Trost, B. M.;
Merlic, C. A. J. Org. Chem. 1990, 55, 1127. (i) Trost, B. M.; Merlic, C. A.
J. Am. Chem. Soc. 1990, 112, 9590.
(6) (a) Plietker, B. Angew. Chem., Int. Ed. 2006, 45, 1469. (b) Plietker,
B. Angew. Chem., Int. Ed. 2006, 45, 6053. (c) Plietker, B.; Dieskau, A.;
Mo¨ws, K.; Jatsch, A. Angew. Chem., Int. Ed. 2008, 47, 198.
At this point the influence of the phosphane ligand was
reinvestigated (Scheme 1). As can be seen from Scheme 1
Org. Lett., Vol. 11, No. 15, 2009
3463

Table 2. Fe-Catalyzed Sulfonation: Nucleophile Scopea
Table 3. Fe-Catalyzed Sulfonation: Carbonate Scopea
a All reactions were performed on a 1.0-mmol scale in the presence of
sodium arylsulfinate (1.2 mmol), TBAFe (0.05 mmol), and ligand 5 (0.06
mmol) under a N2 atmosphere in DMF/2-methoxyethanol (2 mL).
b Determined by GC integration. c Isolated yields.
a All reactions were performed as indicated in Table 2. b Determined
by GC integration. c Isolated yields. d Performed in tert-butanol with Boc-
protected alcohol. e Performed on a 0.5-mmol scale. f Determined by HPLC.
most aryl-substituted phosphane ligands are suitable for the
allylic sulfonation. However, a methoxy substituent within
the ligand structure seems to accelerate the catalytic cycle
to a significant extent (e.g., ligand 5 and 15). Furthermore,
the regioselective course of the reaction remained unaffected
by the ligand structure and gave the products 2-A and 2-B
in a ratio of 97:3 in favor of the ipso-substitution product.
Having identified two potent ligands we finally set out to
decrease the catalyst concentration. However, the rate of
decrease in the catalyst loading corresponded well with the
decrease in the turnover rate. Hence, in order to obtain the
products in a reasonable time frame we subsequently
explored scope and limiations using the reaction conditions
shown in Scheme 1 and started with a screening of different
aryl sulfinates (Table 2). A variety of sulfinates can be
allylated in good to excellent yield with a high degree of
regioselective preference for the ipso-substitution product.
These results are in line with our previous reports on the
TBAFe/PPh3 system. Moreover, as for the allylic amination
a strong influence of the ortho-substituent in the nucleophile
was observed. Whereas both para- and meta-substitution led
to the desired products in good overall yield and selectivities,
an ortho-substituent inhibited the reaction or led to a
nonregioselective product formation in low yields. However,
apart from this limitation a variety of functional groups are
tolerated: halides, amides, or enolizable ketones are stable
under the reaction conditions.
With these encouraging results in hand we subsequently
set out to explore the scope of allylic carbonates (Table 3).
A variety of substituted allylic carbonates were transformed
into their corresponding allylic aryl sulfones in good to
excellent regioselectivities and isolated yields. The protocol
tolerates functional groups like thioethers, alkoxyl groups,
carboxylic acid esters, or oxazolines. Tertiary amines,
however, proved to inhibit the reaction. Although the scope
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Org. Lett., Vol. 11, No. 15, 2009

of the reaction is broad with regard to the functional group
tolerance the method is limited to tertiary allylic carbonates.
Secondary carbonates are reactive under the given condi-
tions; however, a fast base assisted isomerization of the
π-bond into the vinylic position was observed (Scheme 2).7
the stereochemical course of the sulfonation was examined
by using (R)-Linalool derived carbonate (R)-38. Subjecting
the stereoisomerically enriched starting material (R)-38 to
the standard sulfonation conditions led to the corresponding
sulfone (R)-27 in identical enantiomeric ratio with overall
retention of the configuration (Scheme 4).
Scheme 2. Double Bond Migration in Allylic Sulfonations
Scheme 4. Stereochemical Course
Future work will focus on the elaboration of an improved
protocol that allows for a similar effective transformation
of secondary carbonates.
With the results presented in this report we suggest the
mechanistic model shown in Figure 1 as the working hypothesis
for future development of this sulfonation reaction.
Although the regioselective course of most of the reaction
presented in this study is in strong favor of the ipso-substitution
product the decrease in some cases (e.g., entry 9, Table 3)
attracted our attention. Different mechanistic scenarios might
account for this observation. Apart from a metallotropic shift
of the metal via a σ-π-σ-equilibrium in the intermediate allyl
Fe-complex, a metal-by-metal displacement would result in a
similar decrease in the regioselecitvity.8 To shed light into the
isomerization mechanism the dependency of the regioselective
course of the catalyst concentration was investigated (Scheme
3). However, no significant influence was observed ruling out
Figure 1. Mechanistic proposal for Fe-catalyzed allylic sulfonation.
Scheme 3. Regioselectivity-Catalyst Concentration Interplay
In the present report we summarize our results in the Fe-
catalyzed regioselective allylic sulfonation of allylic carbon-
ates. Different aryl sulfinates can be converted into the
corresponding allylic sulfones in good to excellent yields
and regioselectivities with overall retention of the stereo-
chemistry in favor of the ipso-substitution product. A variety
of functionalized allylic carbonates can be employed in the
reaction; however, at the moment the reaction is clearly
limited to the use of tertiary carbonates. Future work will
focus on an expansion of the reaction’s scope and on the
use of this methodology in natural product synthesis.
the possibility of an isomerization via a metal-by-metal dis-
placement.
Acknowledgment. Financial support by the Fonds der
Chemischen Industrie (Ph.D. grant for M.J.), the Deutsche
Forschungsgemeinschaft, and the Deutsche Krebshilfe is
gratefully acknowledged.
With regard to the use of quarternary sulfones in organic
synthesis5 the stereochemical integrity of the final products
is another important issue that needs to be addressed. Hence,
(7) Although not in the focus of the present study vinyl sulfones are
imporant building blocks in medicinal chemistry, for a review see: Meadows,
D. C.; Gervay-Hague, J. Med. Res. ReV. 2006, 26, 793. Investigations on
the scope of the allylic sulfonation-isomerization are currently being carried
out in our laboratories.
(8) A metal-by-metal displacement was observed in the related Rh-
catalyzed allylic substitution: Wucher, B.; Moser, M.; Schumacher, S. A.;
Rominger, F.; Kunz, D. Angew. Chem., Int. Ed. 2009, 48, 4417.
Supporting Information Available: Characterization data
for all new compounds and experimental procedures. This
material is available free of charge via the Internet at
http://pubs.acs.org.
OL901297S
Org. Lett., Vol. 11, No. 15, 2009
3465