1.3- Dioxolanes carbonyl group protection

The oxidation of dihetarylethene 44 with m-chloroper-benzoic acid (m-CPBA) in CH2CI2 afforded 1,1-dioxide 67 (06T5855, 073173, 08CC4622, 09JMC97) in yields up to 90% in the case of the 6-acetyl derivative, the yield of bis-sulfone 68 was only 35% (06T5855) because of a Baeyer-ViUiger oxidation side reaction of the carbonyl group. Protection of the latter as the dioxolane derivative made it possible to increase the yield of 69 to 72% (Scheme 21). 

The carbonyl group can be deprotected by acid-catalyzed hydrolysis by the general mechanism for acetal hydrolysis (see Part A, Section 7.1). A number of Lewis acids have also been used to remove acetal protective groups. Hydrolysis is promoted by LiBF4 in acetonitrile.249 Bismuth triflate promotes hydrolysis of dimethoxy, diethoxy, and dioxolane acetals.250 The dimethyl and diethyl acetals are cleaved by 0.1-1.0 mol % of catalyst in aqueous THF at room temperature, whereas dioxolanes require reflux. Bismuth nitrate also catalyzes acetal hydrolysis.251... 

The carbonyl group in 24 could be temporarily protected as the dioxolane,16 or somewhat more efficiently as the dimethyl acetal 25.17 Subsequent conventional hydroboration led stereoselectively to the P alcohol 26. Although our earliest considerations called for ultimate base-promoted elimination of the OR substituent in intermediates more advanced than 16, we later came to recognize that a methoxy derivative was not going to fulfill this role to our satisfaction. Alternatively, the tactic of forming the benzyl ether at this point ultimately proved well suited to the eventual return to an unmasked hydroxyl at this site.17,18... 

This reaction provides a useful way of introducing a double bond next to a carbonyl group. Here it is in a synthesis by Barry Trost of the Queen Bee Substance (the compound fed by the workers to those bee larvae destined to become queens). The compound is also a pheromone of the termite and is used to trap these destructive pests. Trost started with the monoester of a dicarboxylic acid, which he converted to a methyl ketone by reacting the acyl chloride with a cuprate. The ketone was then protected as a dioxolane derivative to prevent it enolizing, and the sulfur was introduced by reacting the enolate of the ester with the sulfur electrophile MeSSMe. 

Reduction of (427) with lithium in liquid ammonia followed by trapping of the enolate with methyl iodide gave the pure 10/3-methyl compound, which was transformed into ( )-D-homotestosterone (428) by successive treatment with dilute aqueous acid at room temperature and with hot dilute aqueous methanolic sodium hydroxide. To synthesize ( )-progesterone, the carbonyl group of (428) was protected as its dioxolane, the alcohol oxidized, the derived 17a-ketone reacted with methylmagnesium bromide, the tertiary alcohol dehydrated, and the ketone deprotected to furnish the D-homo-17a-methyl-... 

Protected carbonyl groups such as a 4-phenyl-1,3-dioxolane may be deprotected by indirect oxidation in MeCN containing pyridine with 7V-hydroxyphthalimide as mediator [101]. 

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