Reduction ketosulfone

Ketones containing sulfur or nitrogen atoms bound to a-carbons suffer carbon-sulfur or carbon-nitrogen bond cleavage under the conditions of the Clemmensen reduction [159, 864 (p. 118). A ketosulfone was reduced to a sulfone-alcohol with zinc in refluxing 80% acetic acid in 70% yield [920]. 

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. 

Reductive cleavage of 6-ketosulfones [166], RC0CHR S02R", in DMF at mercury is a practical way of preparing alkyl ketones the primarily formed radical anion cleaved to a radical RCOCHR and a sulfinate ion R"S02. Since the anodic reaction was the oxidation of R"S02" to R"S03, an undivided cell could be used. 

Desulfonylation. p-Ketosulfones undergo reductive desulfonylation at room temperamre with TiCl -Zn. 

Other Reducing Agents. 1,4-Dihydropyridines have been successfully employed for the reductive desulfonylation of functionalized sulfones. Of special interest is the desulfonylation of a-nitro sulfones with BNAH under sunlight irradiation to give the corresponding nitro compounds in good yields.90,91 The reaction takes place under mild conditions and tolerates ketones, nitriles, and isolated double bonds (Eq. 120).91 A photo-induced electron-transfer employing ascorbic acid as electron donor is also an efficient approach for the reductive desulfonylation of (3-ketosulfones.197... 

Synthesis of (—)-Laulimalide. Different approaches to the (3-hydroxy sulfone moiety needed for the olefination reaction are frequently used in the synthesis of natural products. For instance, a very common strategy consists of carbonyl reduction of the corresponding a-ketosulfone followed by reductive elimination. This sequence is employed in the synthesis of polyhydroxylated indolizidine alkaloids (Eq. 121),207 (+)-dihydromevinolin,268 pleraplysillin-1,269 amphidino-lide B,270 and the novel antitumor agent (—)-laulimalide (Eq. 158).271... 

Asymmetric reduction of the ketosulfone (490) has been tried under three different protocols (i) (—)-B-chlorodiisopinocamphenylborane, (ii) yeast reduction, and (iii) borane reduction catalyzed by chiral 1,3,2-oxazaborolidine. Of these, the third method gave the best results for large-scale process development <92JHC627>. The product (491) could be converted to (492) by tosylation and subsequent displacement of the —OTs group by isobutylamine (Scheme 100). This was then sulfonated (oleum) to yield a 90 10 mixture of the 2- and 3-sulfonic acids. 

With the same polymer-supported chiral sulphonamide 70 (200-400 mesh, 2% DVB, 2.29 mmol/g functionalization) the reduction of several P- ketonitriles [61] and P-ketosulfones [62] were tested... 

Ethyl stearate added with stirring at 0° under Ng to 2 equivalents of a ca. 1 M soln. of methylsulfingl carbanion (prepn. s. Synth. Meth. 17, 895) in dimethyl sulfoxide-tetrahydrofuran, allowed to warm to room temp, over 30 min., then water added j6-ketosulfoxide (Y > 98%) stirred and refluxed 60-90 min. with Al-amalgam in tetrahydrofuran containing 10% water n-heptadecyl methyl ketone (Y > 98%). F. e. also ketones from -ketosulfones and )6-ketosulfonic acid amides by the same reduction method, s. E. J. Gorey and M. Chaykovsky, Am. Soc. 86, 1639 (1964). 

Figure 5 Asymmetrical reduction of a ketosulfone to the desired (45,65)-hydroxysulfone, a key intermediate in the synthesis of a drug against glaucoma [40].

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