Reductive desulfonylation

Beau and Sinay described a method which laid the groundwork for cyanohydrin acetonide alkylations [1]. Their strategy involved alkylation and reductive desulfonylation of glucopyranosyl sulfones 4. In this one-pot procedure, low temperature alkylation and subsequent reductive desulfonylation with lithium naphthalenide generated -C-glycosides with good selectivity >10 1 j3 a) and in moderate to good yield (Eq. 1). 

One of the most prominent characteristics of Fe(+2) is its ability to undergo oxidation leading to Fe(+3). This was used by Uchiyama et al. when they reported on Fe(+2)-ate complexes as potent electron transfer catalysts [7, 8]. These ferrates are accessible from FeCl2 and 3 equiv. of MeLi. The Fe(+2/+3) oxidation potential of [Me3Fe(+2)]Li 19 in THF is —2.50 V, thus being in between those of Sml2 (—2.33 V) and Mg (—3.05 V). With these alkyliron-ate complexes it was possible to realize a reductive desulfonylation of various A -sulfonylated amines 20 with different basicity. By using Mg metal to restore the active Fe(+2) species 19 a catalytic reductive desulfonylation process was achieved (Scheme 4). 

Sulfonamides are very difficult to hydrolyze. However, a photoactivated reductive method for desulfonylation has been developed.240 Sodium borohydride is used in conjunction with 1,2- or 1,4-dimethoxybenzene or 1,5-dimethoxynaphthalene. The photoexcited aromatic serves as an electron donor toward the sulfonyl group, which then fragments to give the deprotected amine. The NaBH4 reduces the radical cation and the sulfonyl radical. 

Reductive amination of carbonyl compounds, 59, 1 71, 1 Reductive cyanation, 57, 3 Redutive desulfonylation, 72, 2 Reductive desulfurization of thiol esters,... 

The reductive lithiation of a-alkoxy phenylsulfides is a slow process (typically 0.5-1 h at -78°C) and lowering the LUMO of the electron acceptor by using, for example, an anomeric sulfone, leads to a much faster electron transfer [11]. Reductive lithiation of sulfone 22 is fast (less than 1 min) and leads to similar a-lithio reagents to those described above and Scheme 8 shows examples of simple a-C-2-deoxyglycosides 23 and 24 prepared by this protocol. The most interesting feature of anomeric sulfones is that alkylation prior to the reductive desulfonylation event is achievable. In this way, a one-pot four-step sequence... 

The observed stereospecificity of the reductive desulfonylation of (5) by LiAlH, in refluxing ether is also of particular interest. 

For the reductive desulfonylation step, necessary when the formation of a single bond is wanted, a number of electron transfer agents are available [397]. A mild and convenient method makes use of magnesium in ethanol... 

Some Compounds Reductively Desulfonylated with Sodium Amalgam... 

Under appropriate conditions, Raney nickel can also cause reductive desulfonylation (compare, p. 156). Two procedures284 have been worked out, both involving, for tosyl esters, the over-all reaction ... 

Desulfonylation of a-sulfonylacetates. Desulfonylation of these substrates is not satisfactory by the usual methods (Zn-HOAc, Raney Ni-C,H5OH, sodium amalgam), but can be conducted in 70-75% yield with sodium-ethanol in THF (modified Bouveault-Blanc reduction). The substrates (2) are obtained by Wolff rearrangement of a-acyl-a-benzyl-sulfonyldiazomethanes (1).1... 

Reductive desulfonylation.1 A stereocont rolled method for addition of the steroid side chain to a 17-keto steroid is outlined in scheme (I). The various steps proceed selectively to the sulfone 5. Reductive desulfonylation of 5 with Na/Hg, Na2HP04 in CH3OH gives the desired 6 (57% yield) and the undesired alkene in a 2 1 ratio. The desired stereoselectivity was obtained with lithium in ethylamine. The final step was hydrogenation of the 17(20)-double bond to give a protected cholesterol (7). 

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... 

Desulfonylation of fi-keto sulfones.13 Radical reduction of these sulfones with Bu3SnH and AIBN can be more efficient than the conventional method with Al/Hg. An excess of initiator is necessary for ready and complete reduction, but yields of 80-95% can be obtained by use of 4 equiv. of the stannane and 2 equiv. of AIBN in refluxing toluene. 

The Schollkopf nucleophile was also used in the enantioselective synthesis of -methyl-tryptophan. In this case the dihydropyrazine nucleophile undergoes conjugate addition to the sulfone 35a, which yields afl -methyltryptophan after reductive desulfonylation and hydrolysis <95JOC4978>... 

The anion derived from sulfone 4 coupled readily to aldehyde 3 (Scheme 17.7) to give a mixture of P hydroxysulfones that could be converted to a 2.5 1 mixture of the olefins 2 and 32, after acylation and reductive desulfonylation. Unfortunately, problems were subsequently encountered during the attempted removal of the acetal unit from 2 and 32 with pyridinium p-toluenesulfonate in propanol and acetonitrile. Apparently, silyl ether cleavage competed with the desired deacetalation process. Notwithstanding this, the C(24),C(26) diol was isolated pure in 33% yield, along with 28% yield of recovered starting material. This diol... 

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