Sulfonyl group, reduction

In contrast cyclic y-(rey/-butyldimethylsilyloxy)-a,/ -unsaturated sulfones undergo addition of organometallic reagents to give mainly trans-adducts after reductive removal of the sulfonyl group. 

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. 

Vinyl sulfones are reactive as dienophiles. The sulfonyl group can be removed reductively with sodium amalgam (see Section 5.6.2). In this two-step reaction sequence, the vinyl sulfone functions as an ethylene equivalent. The sulfonyl group also permits alkylation of the adduct, via the carbanion. This three-step sequence permits the vinyl sulfone to serve as the synthetic equivalent of a terminal alkene.68... 

Cis- and Pms-to-benzenesulfonylethene are also acetylene equivalents. The two sulfonyl groups undergo reductive elimination on reaction with sodium amalgam. 

In Entry 5, the carbanion-stabilizing ability of the sulfonyl group enables lithiation and is then reductively removed after alkylation. The reagent in Entry 6 is prepared by dilithiation of allyl hydrosulfide using n-bulyl lithium. After nucleophilic addition and S-alkylation, a masked aldehyde is present in the form of a vinyl thioether. Entry 7 uses the epoxidation of a vinyl silane to form a 7-hydroxy aldehyde masked as a cyclic acetal. Entries 8 and 9 use nucleophilic cuprate reagents to introduce alkyl groups containing aldehydes masked as acetals. 

The desired products were obtained in satisfactory to excellent yields by using only 1.2 equivalents of the allylsulfones with primary, secondary and tertiary alkyl radicals. Many different types of allylic sulfones bearing an ester group, a sulfonyl group, and a bromine atom react equally well (Scheme 46). The whole transformation represents formally a reductive allylation or hy-droallylation of alkenes. 

A more recent synthesis of 197 [365] is shown in Fig. 9. Enders introduced the stereogenic centre of (S)-lactic acid into the crucial position 10 in 197. The vinylsulfone B, readily available from lactic acid, was transformed into the planar chiral phenylsulfonyl-substituted (q3-allyl)tetracarbonyliron(+l) tetra-fluoroborate C showing (IR,2S,3 )-configuration. Addition of allyltrimethyl silane yielded the vinyl sulfone D which was hydrogenated to E. Alkylation with the dioxolane-derivative of l-bromoheptan-6-one (readily available from 6-bro-mohexanoic acid) afforded F. Finally, reductive removal of the sulfonyl group and deprotection of the carbonyl group furnished 197. A similar approach was used for the synthesis of 198 [366]. 

The allylic sulfonyl group is regioselectively cleaved in the presence of the alkyl-sulfonyl group by indirect reduction with anthracene as a mediator (Fig. 24) [125]. 

Tezacitabine is synthesized from the cytidine protected at 4 -OH, 5 -OH and 4-NH2. Swern oxidation provides a ketone, which is converted to a gem-fluoro-sulfonyl olefin with the anion of sulfonylfluorophosphonate. Reduction of the sulfonyl group is achieved with BusSnH (Fig. 33) [92]. 

Cyclobutyl phenyl sulfides are reduced with sodium in liquid ammonia,150 while cyclobutyl phenyl sulfones are reduced either by sodium amalgam,SI -152 or sodium in ethanol.153 In the latter case, an alkene results if the sulfonyl group has a neighboring acetyl group, i.e. reduction of li , 2/ , 3S )-l-(l-acetoxy-2-methylpropyl)-2,3-dimethyl-1-phenylsulfonylcyclobutane gave lram -l,2-dimethyl-3-(2-methylpropylidene)cyclobutane (16).153... 

Diels-Alder reactions.2 This ethylene derivative undergoes (4 + 2] cycloaddition even with relatively unreactive cyclic dienes. The adducts undergo reductive elimination of the sulfonyl groups on treatment with 2% sodium amalgam to provide bicyclodienes. The ethene therefore can function as an equivalent of acetylene in Diels-Alder reactions. 

In case (a), labelled secondary alkyl benzenesulfonates (alkyl = 2-adamantyl, 2-propyl, cyclopentyl, etc.) with 18-28% of lsO in the sulfonyl group were partially solvolysed in a range of solvents (SOH), and recovered unreacted alkyl benzenesulfonates were then subject to reductive cleavage of the O—S bond of the sulfonate ester [39]. For water as solvent, the... 

Compound 27 or one of the above-mentioned derivatives can also be reacted with a 2-hydroxyethylsulfonylaniline instead of with a diamine. After reduction of the 4-nitroaniline product 34 followed by condensation with chloranil, the cyclization takes place in oleum where, besides ring closure, the 2-hydroxyethyl-sulfonyl groups are also esterified to 3-sulfooxyethylsulfonyl groups [vinylsulfone (VS) groups]. Thus, the reactive anchor is formed concurrently during the cyclization reaction [64,65] (Scheme 3.2) ... 

Extensive studies by Corey have clearly revealed the wide range of applications of the CBS reduction [2]. However, recent observations of high enantioselectivity in the reduction of several a-hetero substituted aliphatic ketones catalyzed by 1 are worthy of mention (Scheme 2). A series of aliphatic a-hydroxyketones protected with tetrahydropyranyl [7], trialkylsilyl [12], and sulfonyl groups [8] as well as p-ketosulfones [9] were reduced to give the corresponding alcohols in up to >99% ee. 

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