Acetals potassium hexamethyldisilazide

Enol carbonates Di-f-butyl dicarbonate, 94 Potassium hexamethyldisilazide, 257 Enol esters Enol acetates Acetic anhydride, 93 Bis(7i5-cyclooctadienyl)ruthenium(II), 35... 

To a suspension of methyltriphenylphosphonium bromide (0.196 g, 0.55 mmol) in 1 mL of benzene under argon at room temperature was added a 0.5 M solution of potassium hexamethyldisilazide in toluene (1.2 mL, 0.6 mmol), and the yellow solution was stirred for 5 min. A solution of keto-ester (1) (0.1 g, 0.274 mmol) in 1.5 mL of benzene was added and the orange solution was stirred for 3 h at room temperature. The reaction mixture was filtered through a plug of silica gel with 40% ethyl acetate/hexane. The filtrate was concentrated to afford a solid. Flash chromatography (30% 40% dichloromethane/hexane) yielded the desired product (3) as a white solid (0.077 g, 78%) m.p. 167°-168°C Rf 0.4 (50% dichloromethane/hexane). The structure of the product was also confirmed using IR, iH NMR and mass spectroscopy. 

Hydrogenation of olefin 4, followed by 0-desilylation and 0-tosylation next procured tosylate 3, which cyclised readily when exposed to excess potassium hexamethyldisilazide. Elaboration of the ketophosphonate side chain of 20 was accomplished by condensing ester 2 with the lithiated anion of dimethyl methylphosphonate. After concurrent removal of the 1,3-dioxolane acetal and the MOM ether from 20, the resulting secondary alcohol was oxidised with pyridinium chlorochromate (PCC) to produce methyl ketone 1. 

During a synthesis of the immunosuppressant Discodermolide, Schreiber and co-workers,S9 used a procedure of Evans and Gauche-Prunet160-161 to create a benzylidene acetal with high 1,3-asymmetric induction via addition of an alkox-ide to benzaldehyde followed by intramolecular conjugate addition of the resultant hemiacetal derivative. Thus, treatment of 86.1 [Scheme 3.86] with benzaldehyde and catalytic potassium hexamethyldisilazide provided benzylidene acetal 86.2 as a single isomer in 73% yield. 

The most general protocol (eq 10) has therefore been based on potassium hexamethyldisilazide (KHMDS) as the base addition of trisyl azide at —78 °C and then acetic acid at the same temperature. Excellent levels of diastereoselectivity are ohsCTved with most substrates and the method has been used widely in the enantioselective synthesis of a-amino acids from chiral iniides. Chemoselective azidation of an imide enolate in the presence of an ester function has been demonstrated (eq 11). The product distribution is nevertheless finely balanced, as discovered with the respective dimethyl and dihenzyl ethers of the 3,5-substituted phenylacetyl imide (3) (eq 12). ... 

The chemical operations described in the literature to introduce or into citric acid molecule are based essentially on the Grimaux and Adam synthesis. Labeled citric acid was prepared by Wilcox et al. [35] in the reaction of Na CN with 3-chloro-2-carboxy-2-hydroxybutyric acid and the formed nitrile was hydrolyzed directly with hydrochloric acid. From this solution, citric acid was isolated in the form of calcium citrate and finally converted to the acid. An alternative procedme was proposed by Rothchild and Fields [36] to obtain trimethyl citrate from labeled sodium cyanide and di-chloromethyl glycolate. A more complex synthesis of C labeled citric acid is described by Winkel et al. [39]. They used labeled methyl acetate and acetyl chloride (in the presence of hthium 1,1,1,3,3,3,-hexamethyldisilazide, [(CH3)2Si]2NLi which was dissolved in tetrahydiofuran) to obtain methyl acetoac-etate. It reacts in the presence of lithium diisopropylamide, [(CH3)2CH]2NLi, also dissolved in tetrahydrofuran, with dimethyl carbonate to give dimethyl 1,3-ace-tonedicaiboxylate. It is dicarboxylated by the action of bisulfite and potassium cyanide is converted to 3-cyano-3-hydroxy-l,5 pentanedioate and finally hydrolyzed by hydrochloric acid to citric acid. 

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