Ketones 9-Ketophosphonate esters

The term Honwr-Winlsnorth-Emmons reaction refers not only to the illustrated conversion of P-ketophosphonic esters 11 into rx,p ketones 12. but also to the reaction of P-alkoxvcmbonylphosphonic esters 40 to give a.p-unsaturated esters. 

Pyrimido[5,4-c]-l,2,5-oxadiazinones (417) are suitable starting materials to construct annulated pyrazines. Reaction with carbanions derived from CH-acidic compounds, activated by two different electron-withdrawing functions, proceed in a regioselective manner by initial attack at the N—O bond. Triethyl phosphonoacetate, /f-ketophosphonates, nitro ketones, nitro esters, sulfonylacetates, and JV-acetoacetylglycine have been applied to form 6,7-disubstituted lumazines (418) (Equation (18)) <91H(32)79>. 

Cyclopropanation. Sodium enolates of /3-ketophosphonate esters react with ethylene oxide in a sealed tube to form spiroannulated cyclopropyl ketones in moderate yields. Other epoxides give substituted cyclopropane derivatives. 

Whereas platinum-catalysed reduction of acid chlorides with triethyl-silane gives aldehydes, Eaborn has shown that rhodium catalysis can give predominantly ketones. a-Ketophosphonate esters, readily available from the action of carboxylic acid chlorides on trialkyl phosphites, are reduced by sodium borohyffiride to the ester (123), which fragments to the... 

Reduction of activated carbonyl groups of a-keto esters, benzils, cyclohexane-1,2-dione, and o -ketophosphonates by alkylphosphines afforded the corresponding cr-hydroxy esters or ketones in good to excellent yields. A mechanism has been suggested on the basis of deuterium and 180 labelling experiments.380... 

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. 

Commercially available dimethyl cyclopropylmalonate 30 was converted to mono ester 31 by careful saponification using sodium hydroxide. Coupling with l-amino-2-hexanol afforded the hydroxyamide 32 which was oxidized to ketone 33 under Swern conditions. Condensation to oxazole 34 was effectively achieved by utilizing a two-phase system consisting of dichloromethane and sulfuric acid. Reaction with deprotonated dimethyl methylphosphonate gave the 0-ketophosphonate 35 in an excellent overall yield. 

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