Ketosulfonates

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). 

The 1,3-dianions formed across the sulfone330 of /J-ketosulfones may be selectively dialkylated331 with an a, w-dihalide and thus cy clize to give 2-ketothiane dioxides332. Due to its polarity, the 2-keto-substituent (or other polar group in the 2-position) adopts the axial orientation332 (equation 124). 

When methyltriflone 248 was treated with two equivalents of n-butyllithium at — 50 °C in THF, a, a-dianion 249 is formed. After methylation of this dianion, further treatment with two equivalents of n-butyllithium gives the a, a -dianion 250. This dianion can be alkylated at the terminal carbon atom, like the dianions from ketosulfones. On reaction with three equivalents of n-butyllithium, 248 gives a, a, a -trianion 251 which, upon methylation with methyl iodide, afforded methylated product 252. Hendrickson and Palumbo328 prepared cyclopentenone derivatives using 248 as the starting material. 

When the reaction between a-trifluoromethyl sulfone 286 and paraformaldehyde was carried out in the presence of potassium carbonate, the vinyl sulfone was obtained quantitatively upon elimination of triflate anion368. Such a deacylative methylenation was observed in the reaction between /J-ketosulfones 287 and 288 and paraformaldehyde3 69 3 71. 

Potassium salts of cyclic ketosulfones of various size 310 (n = 6, 8, 12) reacted with phenyl (Z)-l-propenyl selenone affording cyclic ketosulfones 311 of various ring sizes (n + 1) having a vinyl group at the 3-position391. 

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

In studies on l-diazo-2-ketosulfones, Shioiri et at. found that the thermal decomposition of benzoyl(sulfonyl)diazomethanes 6 with benzyl alcohol in acetonitrile also gave two products.<82CPB526> One is the 4-sulfonyloxazole 7 whereas the other product 8 results from rearrangement and reaction with the alcohol. The ratio of products varies with the nature of the sulfone substituent with the benzyl group giving highest yields of oxazole (Scheme 5). 

Carbanion 239 derived from vinyl sulfone 238 was shown to be alkylated regiospecifi-cally at the a-carbon atom The carbanions 240 and 241 derived from <5-ketosulfones were shown to be alkylated at both a- and y-carbons . Alkylation of 240 gave a-alkylated products predominantly, while the a/y ratio varied markedly by change of the alkylating agent in the reaction with 241. For example, methylation with methyl iodide gave the products in the a/y ratio of 72 28, while the a/y ratio was 27 73 in the ethylation with ethyl bromide ... 

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. ... 

Wenkert and co-workers were the first to disclose the use of Rh2(OAc)4 for C-H insertion leading to cyclopentanone formation. Then the versatility of this methodology was developed by Taber, Stork, and Nakatani. The first reported example of asymmetric induction was by McKervey and co-workers in 1990 and involved the Rh2(Y-BSP)4-catalyzed decomposition of cr-diazo-/3-ketosulfone 80 (Equation (69)).212 Cyclopentanone 81 was obtained in an excellent yield as a mixture of cis- and trans-isomers, although with poor enantioselectivity (12% ee). 

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]. 

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],... 

As CH-acids in the MCRs with aldehydes and aminoazoles, other classes of organic compounds were used as well. Cyanoacetic acid derivatives, acetoyl(aroyl) acetonitriles, ketosulfones, acetophenones, and other reagents were successfully introduced into these three-component heterocyclizations. For example, synthesis of pyrazolo[3,4-b]pyridine-5-carbonitriles 40 was carried out as the multicomponent treatment of 5-aminopyrazole, aldehyde, and benzoylacetonitriles solvent-free by fusion either in ammonium acetate at 120°C or in boiling ethanol with EtsN (Scheme 17) [69]. The second approach gave the worst results from the viewpoint of yields and purity of the target compounds. 

Three-component treatments of ketosulfones and aldehydes with 2-aminobenzi-midazole or 3-amino-l,2,3-triazole were carried out in microwave reactor as well... 

Three-component treatment of ketosulfones and related CH-acids with aldehydes and 5-aminopyrazoles was also patented by Han and Hu [74]. They used stirring of the starting materials in THF at 70°C and HPLC purification to synthesize biologically active pyrazolopyrimidines containing sulfonic group. 

For example, it was reported in several independent articles that multicomponent treatment of 5-amino-3-methylpyrazles with 1,3-cyclohexandiones and aldehydes under refluxing in EtOH [82, 83], in DMF with methanol [84], or with application of continuous-flow microwave-assisted procedure in DMSO [85] yielded exclusively pyrazoloquinolinones 50 (Scheme 23). On the other hand, the treatment of 3-unsub-stituted 5-aminopyrazoles with cyclic p-diketones or ketosulfones gave mixtures of Hantzsch dihydropyridines 51 and Biginelly dihydropyrimidines 52 in different ratios [86]. 

Sulfur-containing groups serve as acceptors successfully. /1-Ketosulfoxides and /1-ketosulfones 68 form aminopyrans 69 with UNs... 

Huoroacetates can also react as electrophiles they can acylate organometallic derivatives to afford monofluoroketones or fluoro-jS-ketosulfones. This type of reactivity is also found with di- and trifluoroacetates (vide infra). 

Esters of chlorodifluoroacetic acids, like the esters of monofluoroacetic acid, can acylate anions (e.g., organometallic derivatives, enolates, lithiated sulfones). They lead to chlorodifluoromethylketones and to S-ketosulfones and jS-ketoesters which have the —CFj motif (Figure 2.16). ... 

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