P-Ketosulfone

All lation of Garbanions. Concentrated N a OH—hen syl triethyl amm onium chloride is the base/catalyst system normally used for this type of process (20). Classes of compounds alkylated in this way include phenylacetonitriles, ben2ylketones, simple aUphatic ketones, certain aldehydes, aryl sulfones, P-ketosulfones, P-ketoesters, malonic esters and nitriles, phenylacetic esters, indene, and fluorene (see Alkylation). 

NaBH4). " P-Ketosulfones are reduced with TiCU—Zn, " TiCl4—or... 

Application of this work to a domino process using 51 involves Michael addition of P-ketoesters [91], p-diketones or P-ketosulfones [92] to a,P-unsaturated ketones followed by an intramolecular aldol reaction provides highly functionalised cyclohexanone building blocks with up to four contiguous chiral centres. Gryko has also reported examples of this domino Michael/intramolecular aldol reaction in the coupling of 1,3-diketones and methyl vinyl ketone using L-proUne as catalyst [93],... 

Just as very few catalyst/modifier combinations give good optical yields, only certain types of substrate are suited (see Fig. 1). Reproducibly good ee values have been reported for a- and P-ketoesters (6, 1), a-ketolactone 7, p-diketone 2, p-ketosulfones (3) and methylketones (4, 5). C=N- and C=C-bonds are hydrogenated with poor to moderate optical yield. The hydrodehalo-genation of 22 is a unique case of substrate specificity [33]. 

Two equivalents18 of the anion derived from sulfone 47 were needed to obtain a satisfactory yield of the p-ketosulfone mixture 72 (Scheme 17.15)... 

Enhancement of the acceptor quality can be gained by switching from the ester group to a keto function. This has been realized by treating 258 with sodium or lithium salts of sulfones. In the resulting p-ketosulfones 259 the cyclopropane ring is... 

Not surprisingly, two trimethylsilylmethyl groups further increase reactivity of cyclopropanes. Therefore 262 opens to 263 even at —78 °C yielding a new functionalized allylsilane as the product. An attempt to transform 262 into the corresponding P-ketosulfone 264 leads to the unusual cleaved compound 265, which carries an allyl and vinylsilane unit as well as the P-ketosulfone moiety. It is evident that this mode of cyclopropane opening is initiated under the basic reaction conditions by deprotonating the intermediate 264 in the side chain a to one of the trimethylsilyl groups 113). 

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. 

Fig. 95. Reaction of phenolic Mannich bases with p-ketosulfones.

Lithium aluminum hydride reduces most sulfur compounds with cleavage of the C S bond, including thiols.Thioesters can be reduced with Ni2B (from NiBr2/ NaBH4). p-Ketosulfones are reduced with TiCLj—TiCLi or... 

Conjugate addition of sodium benzenesulfinate to a,(3-unsaturated carbonyl compounds produces P-ketosulfones, which may be elaborated into trans-a,ji-unsaturated aldehydes or ketones, respectively, by the sequence of reactions shown below. " ... 

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

The oxidative protocol simply involves grinding of the two solid substrates using a pestle and mortar a mildly exothermic reaction results in the formation of a yellowish eutectic melt and the reaction gets completed in a few minutes. The work has now been extended to the synthesis of p-ketosulfones from ketones employing another hypervalent iodine reagent. 

Other enolised compounds were also easily arylated. Such was the case of P-ketosulfones, which reacted easily with triphenylbismuth carbonate (5) to afford the corresponding a-phenyl-P-ketosul-fones. This reaction was put to good use in an efficient synthesis of isoflavanone and isoflavone... 

Applications of the chiral rhodium (II) carboxylates to the cycHzation of a-di-azo-p-ketosulfones, Eq. (35), have shown that while they are catalytically active at or below room temperature, they provide only low enantiomeric excesses [6]. 

Under these conditions, hydrogenation of P-ketosulfones is less selective (ee 70%) [578]. 

Aoai, Y. Aotani, A. Umehara, and T. Kokubo, Apphcation of silylether and silylester polymer for chemical amplification system, J. Photopolym. Sci. Technol 3, 389 (1990) M. Tsunooka, H. Yanai, M. Kitayama, and M. Shiraj, Photo initiated acid formation and its applications the acid formation mechanism in photolysis of p ketosulfones inpolymer matrices, J. Photopolym. Sci. Technol. 4, 239 (1991). 

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... 

It is noteworthy that aromatic P-ketonitriles and P-ketosulfones were reduced in good enantioselectivity (85-96% ee). Electron density (substituant in the para position) had little effect on enantioselectivity. For aliphatic P-ketonitriles or sulfones, both chemical yield and ee were lower compared to those obtained with aromatic analogs. 

New photochemical methods for the synthesis of esters and ketones have been also established. For instance, the visible-light mediated photoredox reaction of a-brominated carboxylates with enamines allowed to obtain y-ketoesters in good yields, under very mild conditions. Symmetrical and unsymmetrical 1,4-diketones could be synthesised from p-ketosulfones by visible light-induced C-S bond activation using... 

Chiral imidazolidine 106 is also a very effective organocatalyst for the enantio- and diastereoselective domino Michael-aldol reaction of P-diketones [215a], p-ketosulfones [215a], and p-ketoesters [214] with a,P-nnsaturated ketones at rt to afford optically active cyclohexanones having three or four contiguous stereogenic centers (Scheme 2.80). 

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