Oxalylation ketones

Generally the most practical procedure for monoalkylation of steroidal ketones bearing geminal a-hydrogens is via formyl or oxalyl ketones. Some examples of the former method are described in this section. The alkylation of oxalyl ketones is described in the following section. 

The most widely used method for the preparation of 2a-methyl-3-keto steroids proceeds via a-oxalyl ketone intermediates. 

The preparation of 17j -hydroxy-4a-methyl-5a-androstan-3-one (3) which cannot be obtained by direct alkylation or via formyl or oxalyl ketones was achieved by Schaub in 40% yield by the Stork " alkylation procedure. As discussed in the introduction this method proceeds by trapping the A -enolate (2), obtained from (1) and lithium in liquid ammonia, with methyl iodide. 

Methylandrost-5-ene-3/8,17a-diol, 63 Methylation of a-oxalyl ketones, 95 5 -Methyl-17a,20 20,21-bismethylenedioxy-3,3-ethylenedioxy-5/8-pregnane-6,l 1-dione, 93... 

The reaction of diethyl oxalate with ketones in the presence of sodium ethoxide, or other bases, has been used extensively examples are given in Scheme 66. Reaction may occur with esterketone ratios of 1 1, 2 1, or 1 2, but only the 1 1 case finds substantial use in modem synthetic practice. Frequently the a-oxalyl ketone is thermally decarbonylated to give the 3-heto ester.An early example of this was provided by Bachmann s synthesis of equilenin. The mechanism of this reaction has teen examined labeling studies showed that it was the ester carbonyl that was eliminated. The intact oxalyl group has teen used as a directing group in steroid methylation while, more recently, 2-oxalylcyclohexanone has provided a route to (R)-(-)-hexahydromandelic acid (Scheme 67). The products of acylation of suitable acyclic ketones can cyclize to form (enolic) cyclopentane-1,2,4-triones (equation 39). ... 

Vinyl ketones. Enolates of methyl ketones react with diethyl oxalate to form oxalyl ketones (1) in satisfactory yield. The anion of (1) reacts with aldehydes to give diketo lactones (2) in yields of 60-907o> based on the methyl ketone. When the lactones are heated at 620°, CO and CO2 are eliminated with formation of vinyl ketones (3). 

Oxacyclanones, 281 1,2,4-Oxadiazoles, 337, 338 Oxaiyl chloride, 257-258 Oxalyl ketones, 106... 

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