Ketosulfones 1-hydroxy

In the reaction of a-sulfonyl carbanion with lactones, the corresponding hydroxy-co-ketosulfones were obtained " . Thus, various o-hydroxyketones were shown by Umani-Ronchi and coworkers to be formed from the corresponding lactones. For example, the reaction of a, a-dilithioalkyl phenyl sulfones with lactones in THF at low temperatures afforded co-hydroxy-jS-ketosulfones which, upon desulfonylation with aluminium amalgam, gave the corresponding hydroxyketones . This process was applied for the syntheses of cis-jasmone and dihydrojasmone by treating y-valerolactone with ds-3-hexen-l-yl phenyl sulfone and n-hexyl phenyl sulfone. ... 

Cyclization of the ketosulfone (ix) with 2-chloro-3-hydroxy-propenal (xv) in the absence of ammonium acetate... 

Cyclization of the lithium enolate of the ketosulfone (iv) with 2,3-dichloroacrolein (xviii), obtained by treatment of 2-chloro-3-hydroxy-propenal (xv) with oxalyl chloride and DMF in toluene, followed by reaction with ammonium acetate or anhydrous ammonia... 

An analog of the (6S)-methylketosulfone towards Trusopt , 5,6 dihydro-(6S)-pro-pyl-4H-thieno[2,3fc]thiopyran-4-one 7,7-dioxide ( ketosulfone , Figure 13.28), the precursor to the carbonic anhydrase inhibitor L-683393 (Merck), could be reduced to the trans-hydroxysulfone 5,6 dihydro-(4S)-hydroxy-(6S)-propyl-4H-thieno[2,3F] thiopyran 7,7-dioxide by whole cells of the yeast Rhodotorula rubra MY 2169 from the Merck collection (Lorraine, 1996). Low water-solubility limited the optimum substrate concentration to 2 g L, as organic solvents added to increase solubility resulted in lower rates, which at 0.04 g (g dew)-1 h 1 were not high to start with. Diastereomeric excess ranged from 89 to 94% d.e., and decreased with increasing conversion. 

Another yeast, Rhodotorula rubra MY 2169, has been shown to reduce a ketosulfone 8 to the corresponding Zrara-hydroxysulfone 9 (Scheme 7). This hydroxy sulfone is an intermediate in the drug candidate L-685,393 (10), a carbonic anhydrase inhibitor [58]. Results of this biotransfonnation yielded gram quantities of product with a de of > 96%. Studies by Zeneca discuss additional screening experiments aimed at finding microorganisms to reduce a similar ketosulfone [59]. 

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... 

The application range of modified Raney Ni has been extended to the enantio-selective hydrogenation of other -functionalized ketones such as y0-diketones (e. g. acetylacetone, 74% ee), 4-hydroxy-2-butanone and its methyl ether (68-70% ee), and ff-ketosulfones (67-71 % ee) [11]. 

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