A Journey from Discovery of New Pummerer Chemistry toCatalytic C-S Bond Cleavage

As represented by carbonyl umpolung, Swern oxidation, and sulfur ylide, organosulfur
compounds have played important roles in organic synthesis through their intriguing
reactivities that oxygen or halogen counterparts cannot show. Despite their stench, frequentcatalyst poisoning, and poor atom economy, the unique reactivities of organosulfurs havebeen fascinating us enough to explore new transformations of organosulfurs from a modern
viewpoint of organic chemistry. We are interested in how to tame organosulfur compounds(except for bad smells) to create new organic transformations.
Ketene dithioacetal monoxides (KDMs) are found to be interesting building blocks thatenable direct transformation of phenols into benzofurans.[1] Specifically, Pummerer-type
reactions of phenols with KDMs with the aid of trifluoroacetic anhydride provide thecorresponding 2-methylsulfanylbenzofurans. Subsequent rather difficult cross-coupling
arylation at the methylthio group culminates in modular synthesis of multisubstituted
benzofurans.
This two-step approach to multisubstituted benzofurans is powerful enoughto synthesize highly fluorescent benzofuran derivatives as well as naturally occurring
Eupomatenoid family.

OHO+Ni/NHC cat.
(CF 3CO)2OSMeSMeRO

Pummerer-typeannulation

OR MgXSMeRcross-coupling
RROOO

MeO
Me
eupomatenoid-3O
fluorescent molecules

Scheme 1. Modular Synthesis of Benzofurans through Pummerer Annulation/Cross-Coupling
The difficulty we experienced in converting the 2-MeS substituent into an aryl groupsolicited us to explore reliable, general, and efficient catalytic transformations of sulfides.
Accordingly, amination of aryl sulfides with amines[2] and cross-coupling of aryl sulfides witharylzinc reagents[3] have been invented. The former represents the first example ofamination of sulfides and the latter is widest in generality in cross-coupling of sulfides.
ArCl
BocO
TsOetc.

Pd/NHC cat.
ArZnX•LiCl
MeCN
rt or below

SMeR

Pd/NHC cat.
ArNH2, KHMDS
Dioxane100 ˚C, 12 hNHArR

Scheme 2. Palladium-Catalyzed Cross-Coupling of Aryl Sulfides

Aromatic skeletons are usually considered to be stable and to resist organictransformations. During the course of our research on organosulfur chemistry, we haveinvented a novel route to triphenylenes from readily available dibenzothiophenes through“aromatic metamorphosis”, which represents a transformation of an aromatic system toanother through partial disassembly of the starting aromatic ring.[4]The aromatic metamorphosis begins with AgBF4-mediated SN2 reaction ofdibenzothiophene with 1-bromo-4-chlorobutane to form the corresponding sulfonium salt.
The sulfonium salt is reactive enough to undergo palladium-catalyzed arylative ring-opening
with an arylboron compound for introducing the last benzene ring. The resulting chlorobutylteraryl sulfide is then converted to the corresponding tetramethylene sulfonium salt byAgSbF6-mediated intramolecular SN2 reaction. The final step, i.e., ring-closure into
triphenylenes, is achieved through unprecedented intramolecular direct C-H arylation with thesulfonium salt. Symmetrical as well as unsymmetrical triphenylenes of interest aresynthesized in a tailor-made fashion in satisfactory overall yields.
"
Ar1

Ar3"

Ar2
S

Ar1

Ar2
Ar3– "S"activation
Ar1

Ar2
S+ClC–H arylation

Mtl
Ar3
arylative ring-opening,then activation

Ar1
S+Ar2
Ar3

Scheme 3. Palladium-Assisted Aromatic Metamorphosis of Dibenzothiophenes toTriphenylenes
References
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Murakami, H. Yorimitsu, A. Osuka, Bull. Chem. Soc. Jpn. 2014, 87, 1349. (c) A. Baralle,
S. Otsuka, V. Guérin, K. Murakami, H. Yorimitsu, A. Osuka, Synlett 2015, 26, 327.
2. (a) T. Sugahara, K. Murakami, H. Yorimitsu, A. Osuka, Angew. Chem. Int. Ed. 2014, 53,9329. (b) K. Gao, H. Yorimitsu, A. Osuka, Eur. J. Org. Chem. 2015, 2678.
3. (a) S. Otsuka, D. Fujino, K. Murakami, H. Yorimitsu, A. Osuka, Chem. Eur. J. 2014, 20,13146. (b) S. Otsuka, D. Fujino, K. Murakami, H. Yorimitsu, A. Osuka, Chem. Eur. J.
2015, 21, 14703.
4. (a) D. Vasu, H. Yorimitsu, A. Osuka, Angew. Chem. Int. Ed. 2015, 54, 7162. (b) M.
Bhanuchandra, K. Murakami, D. Vasu, H. Yorimitsu, A. Osuka, Angew. Chem. Int. Ed.
2015, 54, 7162.