Methyl cyanoformate ketones

Another route to C-acylation is illustrated in Scheme 62. The benzofuranone (154) on reaction with methyl chloroformate in the presence of LDA gave the 0-acylated product (155) in 88% yield. With methyl cyanoformate, the C acylated product (156) was obtained in 94% yield. However, the larger scale use of this reagent was unsatisfactory, so an alternative strategy was devised. The ketone (154) was treated with carbon disulfide, dimethyl sulfate and base in DMSO to give the bis(methylthio) ketene acetal. Aqueous base yielded the C-acylated product (156) in 83% overall yield. 

A variety of reagents will effect the conversion C(XTH2 - C(XrHC02R the decarbonylation of glyoxalate esters was described above. The most recently described reagent, methyl cyanoformate, reported by Mander and Sethi in 1983, allows the conversion of a preformed lithium enolate to the 3-keto ester in high yield (Scheme 68). Diethyl dicarbonate with potassium hydride in benzene effects the same reaction wiA symmetrical ketones, and with lithium dicyclohexylamide in ether introduces the ethoxycarbonyl group into the a -position of a,3-unsaturated ketones (Scheme 69)."" Diethyl carbon-... 

As Mander and coworkers [101] have shown, methyl cyanoformate is the reagent of choice for C-alkylation in many cases. However, for ketone enolates with a hindered P-position increasing amounts of O-acylated product are observed. It has been demonstrated that the use of diethyl ether in place of TH F largely suppresses O-acylation. For instance, enolate 304 gave a 4 1-ratio of C- versus O-acylation in THF and 20 1 in ether [102]. Similarly, from enolate 307 enol carbonate 308 is predominantly formed in THF, whereas keto ester 309 is the main product in diethyl ether. The same phenomenon is observed if the enolate is generated from... 

A more efficient route to the pentacyclic ketone 367 not requiring indole protection has been developed by the Ninomiya group (Scheme 3.63) (66,67). Harmalane (336) was condensed with 3,4-dimethoxybenzoyl chloride (368) to provide enamide 369 which upon irradiation under reducing conditions afforded a mixture of desired bis-enol ether 370 and corresponding ketone 371. Lactam 370 was reduced, and the C(16), C(17) enol ether was hydrolyzed to afford predominantly 367 in addition to a small amount of the regio-isomeric hydrolysis product 372. Treatment of367 with methyl cyanoformate... 

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