Alkanones with pyridines

Ethyl 3-oxoalkanoates when not commercially available can be prepared by the acylation of tert-butyl ethyl malonate with an appropriate acid chloride by way of the magnesium enolate derivative. Hydrolysis and decarboxylation in acid solution yields the desired 3-oxo esters [59]. 3-Keto esters can also be prepared in excellent yields either from 2-alkanone by condensation with ethyl chloroformate by means of lithium diisopropylamide (LDA) [60] or from ethyl hydrogen malonate and alkanoyl chloride usingbutyllithium [61]. Alternatively P-keto esters have also been prepared by the alcoholysis of 5-acylated Mel-drum s acid (2,2-dimethyl-l,3-dioxane-4,6-dione). The latter are prepared in almost quantitative yield by the condensation of Meldrum s acid either with an appropriate fatty acid in the presence of DCCI and DMAP [62] or with an acid chloride in the presence of pyridine [62] (Scheme 7). 

Reduction of the carbethoxy group to the hydroxymethyl group with lithium aluminum hydride at — 35° and Claisen condensation with ethyl acetate are known to take place with pyridazinecar-boxylic acids. 6-Oxo-l,6-dihydro-2-pyridazinyl aliphatic acids, having the pyridazinonyl residue attached at the a-position of the aliphatic radical, readily undergo decarboxylative acylation with acid anhydrides in the presence of pyridine to form the corresponding 2-alkanones (107). 

Ring expansion of cycloalkanones. 1-Trimethylsilyloxybicyclo[n.l.0]alkanes (1), prepared by Simmons-Smith reaction with silyl enol ethers of cycloalkanones, react with ferric chloride in DMF containing pyridine to form a 3-chlorocycIo-alkanone (2) in fair to high yield. Dehydrochlorination (sodium acetate) yields a 2-cycloalkenone (3) containing one more carbon atom than the starting cycloalkanone. 

A combination of PQQ derivatives with transition metals leads to form the efficient redox systems. Dropwise addition of terminal olefin to the solution of PdCl2 (0.1 molar equiv.), trimethyl ester of PQQ, (PQQTME, 0.1 molar equiv.) and H2O in DMF under molecular oxygen results in the formation of 2-alkanone (Scheme 3.2). It should be noted that PQQTME constitutes a catalytic redox cycle. The orthoqui-none function appears to reoxidize the reduced palladium species generated in situ. Use of 1,7- or 1,10-phenanthrolinequinone gives a poor result maybe due to the coordination of paUadium(II) species towards the pyridine moiety opposite to the quinone group [5]. Mediation ofp-benzoquinone in the palladium-catalyzed oxidation reactions has been reported to require electrochemical or cobalt porphyrin catalyzed oxidation of the quinol [6-8]. The above-mentioned results provide an example for efficient redox systems of coenzyme derivatives with transition metals, which is demonstrated to be synthetically useful. 

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