Phenylsulfonyl methane

The thermal decomposition of diazo(phenylsulfonyl)methane 223 under a nitrogen atmosphere generates phenylsulfonylcarbene which is trapped by olefin such as cyclohexene to give norcaranes 224 and 225 (equation 138)132. No cycloheptatriene derivative is isolated from the thermolysis of223 in benzene133. In contrast, intramolecular insertion of sulfonylcarbenes into a benzene ring is observed in the thermolysis of 226 (equation 139)134. 

Bis(alkylsuIfonyI)methanes or bis(phenylsulfonyl)methane readily reacted with aldehydes in the presence of bases to afford ) -hydroxysulfones or bis-adducts. For example, bis(ethylsulfonyl)methane was found to react with salicylaldehyde in the presence of piperidine, affording 2-ethylsulfonylbenzofuran in a good yield . ... 

However, it is interesting that the same reaction with bis(phenylsulfonyl)methane in the presence of NaH afforded 3-nucleophile-substituted-2-(phenylsulfonyl)-l-pro-pene 197 and the expected 2-[bis(phenylsulfonyl)methyl]-2-propenyl sulfone 198 in 94 and 4% yields, respectively. A similar reaction with methyl phenylsulfonylacetate afforded 199 and 200 in a ratio of 2 1. 

These two products must be formed via an S -type substitution of intermediate 201, which may be formed by the nucleophilic attack of benzenesulfmate with 1,2-pro-padienyl phenyl sulfone. This was further supported by the reaction of 1-methyl-1,2-propadienyl sulfone with bis(phenylsulfonyl)methane in the presence of sodium benzenesulfmate, in which allylic sulfone 202 and vinylic sulfone 203 were formed [103],... 

Electron-deficient alkenes, either these with conjugating substituents or of enones, undergo Michael-like additions with regiospecific introductions of the nucleophiles, and this approach has been successful for the formation of cyclopropyl derivatives—notably from some nucleosides. An example involves the addition of the anion of bis(phenylsulfonyl)methane to the phenylselenone 173 which gives the adduct 174 in 35% yield. This reaction presumably occurs by Michael addition to C-2 followed by Sn2 ring-closure reaction at C-3 with displacement of phenylselenic acid. Reductive desulfonylation affords the 2,3,-dideoxy-2,3 -cyclopropayuridine 175.199... 

Nitronsaure Phenylsulfonyl-methan- -methylester E14b, 894 (R2CH-N02 + CH2N2) Sulfinsaure 4-Nitro-benzoI- -ethylester Ell, 643 (Ar —S02H + R30 )... 

Methoxy(phenylthio)methane and methoxy(phenylsulfonyl)methane are useful formyl anion equivalents for one-carbon homologation. For instance, addition of methoxy(phenylthio)methyllithium to ketones, followed by rearrangement of the adduct, provides a new method for the preparation of a-(phe-nylthio) aldehydes (equation 39). The reanangement is stereospecilic. This method has been used for the total synthesis of annelated furans such as (-)-)-euryfiiran, butenolides such as isodenninin and con-fertifolin and spirocyclic tetrahydiofurans and butenolides. ... 

The first total synthesis of cristatic acid, a compound of considerable cytotoxic activity, was reported by A. Furstner et al." The disubstituted furan moiety was constructed by the Tsuji-Trost allylation of a vinyl epoxide intermediate by b/s(phenylsulfonyl)methane. The resulting 1,4-diol was obtained in an almost quantitative yield. 

The reaction of alkenes with bis(phenylsulfonyl)carbene generated from the iodonium ylide photolytically (400-W low-pressure mercury lamp), or thermally [in the presence of bis(acetylacetonato)copper(ll), in chloroform or benzene], apart from the expected cyclopropanes 4, always affords bis(phenylsulfonyl)methane and phenyl benzenethiosulfonate. °... 

A one-pot sequential palladium(0)-catalyzed allylic alkylation of bis(phenylsulfonyl)methane gives a 49% yield of the m-cvclohexene derivative, which can be cycloisomerized after acetylation l03. 

Fluoromethylenation.11 Methods for fluoromethylcnation of ketones result in mixtures of (K)- and (Z)-vinyl fluorides, which are difficult to separate. A selective route involves reaction of the ketone with the carbanion of l-fluoro-l-(phenylsulfonyl)methane-phosphonate, prepared from fluoromethyl phenyl sulfones and diethyl chlorophosphate. The reaction provides mixtures of (E)- and (Z)-fluorovinyl sulfones, which can be separated by flash chromatography. Those products cannot be reduced by AI(Hg), but on treatment with tributyltin hydride (A1BN), they are converted into (fluorovinyl)stannancs with retention. Dcstannylation to vinyl fluorides can be effected with sodium methoxide in methanol or with CsF in methanolic ammonia.14... 

Kfirzlich wurde Vinylsulfonyl-phenylsulfonyl-methan in maBiger Ausbeute mit Dimethylsulfoxyd und Acetanhydrid zum Ylid (104) kondensiert (21). 

V. 1. ition of ketones result in mix-c--> o separate. A selective route I .. ro-l-(phenylsulfonyl)methane-f. r.v-. and diethyl chlorophosphate. j. . inyl sulfones, which can be ir.. o be reduced by Al(Hg), but on r. rted into (fluorovinyl)stannanes K Ltfected with sodium methoxide... 

Bis(phenylsulfonyl)methane has also been employed as an acidic carbon pronucleophile related to malonates and 1,3-diketones with success in the Michael reaction with ot,p-unsaturated aldehydes using 31c as catalyst (Scheme 3.6). The reaction showed a remarkable substrate scope when alkyl-substituted enals were employed but failed when cinnamaldehyde was tested as Michael acceptor. Alternatively, a more acidic cyclic gem-bissulfone has been used as Michael donor, keeping the high yields and enantioselectivities observed for the reaction and also allowing to expand the scope of the reaction to several aromatic enals.In all cases, the chemistry of the sulfonyl group was employed to generate a methyl group after metal-mediated desulfuration or, alternatively. 

Scheme 3.6 Enantioselective Michael reaction of bis(phenylsulfonyl)methanes to a, p-unsaturated aldehydes.

Cordova and coworkers showed that prolinol silyl ethers can also operate as iminium catalysts. The Michael addition of 1-fluorobis-(phenylsulfonyl)methane to a,p-unsaturated aldehydes proceeded with high enantioselectivity (Scheme 8.6). The primary Michael adducts were transformed to aldehydes, carbo>g7lic acids, or the sulfonyl groups could... 

Iminium activation has been recently used to achieve the enantioseleclive conjugate addition of geminal bis(sulfone)s and p-keto sulfones to a,P-unsaturated aldehydes. Almost simultaneously, different groups have reported the efficient use of catalyst 22a in the addition of bis(phenylsulfonyl)methane [200] and fluorobis(phenylsulfonyl) methane [201] to a wide variety of enals to yield the corresponding Michael adducts in excellent yields and enantioselectivities (Scheme 2.72). This reaction is particularly attractive since allows the preparation of interesting chiral building blocks by further synthetic transformations over the aldehyde moiety and reductive desulfonylation [91] of the bis(phenylsulfonyl) group. 

Scheme 2.72 Enantioselective Michael addition of bis(phenylsulfonyl)methanes to enals...

Scheme 2.90 PTC asymmetric conjugate addition of fluoro bis(phenylsulfonyl)methane to enones...

Shibata and Tom used this strategy for a highly enantioselective mono-fluoromethylation by an asymmetric Mannich reaction using 1-fluorobi-s(phenylsulfonyl)methane (FBSM) with quinidine-derived catalyst 49c and subsequent removal of the sulfonyl group by treatment with magnesium powder (99% enantiomeric excess). Palomo and coworkers used sulfonyl acetonitrile as a synthetic equivalent of acetonitrile and obtained the optically active p-aminonitriles 97 (76% enantiomeric excess). Bernard , Ricci, and coworkers also introduced the same strategy to synthesise N-protected p -amino acid esters 98 (R = Ph, 92% enantiomeric excess) and a-alkylidene-p-aminoesters 99 (R = Ph, 91% enantiomeric excess) by an asymmetric Mannich reaction of sulfonylacetate followed by the subsequent reductive removal of the sulfonyl moiety and olefination with formaldehyde, respectively (Scheme 16.32). ... 

---