Chlorination reactions, hydroxyl group conversion

The sequence for preparing the hydroxyketone started by conversion of the acid 15-1 to its chloride with thionyl chloride. Reaction of that acid halide with diazomethane gives the diazoketone 15-2. The hydroxyl group at C3 is then oxidized to the corresponding ketone by means of an Oppenauer reaction. Treatment of the product 15-3 with gaseous hydrogen chloride replaces nitrogen in that intermediate by chlorine. Displacement of chlorine by acetate then leads to the 21-acetate 15-5. Saponification of the ester completes the sequence. 

We Studied the reaction of alkenes with chlorine or bromine in water to form halohydrins in Section 6.3E and saw that it is both regioselective and stereoselective (for an alkene that shows cis-trans isomerism, it is also stereospecific). Conversion of a halohydrin to an epoxide with base is stereoselective as well and can be viewed as an internal Sj. 2 reaction. Hydroxide ion or another base abstracts a proton from the halohydrin hydroxyl group to form an alkoxide ion, a good nucleophile, which then displaces halogen on the adjacent carbon. As with all S 2 reactions, attack of the nucleophile is from the backside of the C—X bond and causes inversion of configuration at the site of substitution. 

Extensive literature demonstrated that chlorosulfonic acid is an effective reagent for the conversion of phenols into phenolpolysulfonyl chlorides. The reagent caused four different types of reaction sulfonation, chlorosulfonation, chlorination and oxidation. In some instances, the phenolic hydroxyl group was esterified (sulfated) prior to sulfonation and in other cases condensation products, e.g. sulfonylides, were isolated. The predominance of any of the quoted reaction types depends on the experimental conditions, e.g. time, temperature, quantity of chlorosulfonic acid, solvent (if any) and the nature of the phenolic substrate. 

In another report, the traditional oxazolidinone auxiliary was attached to the acyl chloride for the [2+2] cycloaddition with an imine. Thus, both Holton s and Palomo s groups reported the reaction of 7.1.12 and 7.1.13 to yield lactam 7.1.14 in a virtually complete stereoselective fashion. The asymmetry at the C-3 position of the lactam was destroyed by hydroxylation or chlorination at this position. Hydrolysis of the auxiliary was achieved with silica gel (Si02) or silver nitrate (AgNOs). Diastereoselective reduction of the key intermediate ketolactam 7.1.15 to give 7.1.16 was then effected with NaBH4 in MeOH at 0°C (241, 242). An alternate approach to chiral /3-lactam uses baker s yeast to reduce racemic ketolactam 7.1.15 (243). The desired isomer 7.1.16 was obtained in up to 80% ee at 50% conversion. 

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