1.2- Diketones, synthesis, 1,2-diol conversions

An example of the construction of a 1,2-diketone from a 1,2-diol comes from the total synthesis of ( )-cephalotaxine (54) where the Corey-Kim conditions were used to convert diol 52 to diketone 53 in 89% yield while other oxidation methods were reported to have failed to affect this conversion.15 The more accessible ketone was then converted to the enol ether and LAH reduction afforded the racemic natural product 54. 

Gotor and coworkers reported the bioreduction of different diketones (Scheme 4.4) to obtain the enantiopure reduced products employing isolated ADHs and 2-propanol to recycle the cofactor 34]. Depending on the ADH used, the reaction was conducted for the synthesis of the diols or the intermediate hydroxy ketones. For example, when ADH-T from Thermoanaerobacter sp. was used to reduce 2,3-hexanedione (4a), diol (2S,3R)-6a was obtained with 91% conversion and 99% ee and 96% of diastereomeric excess (de), while LbADH afforded preferentially the intermediate hydroxy ketone (2R)-5a with >99% ee as the main product. 

The power of Noyori s Ru -BINAP system in ketone reductions has been amply demonstrated in numerous complex molecule syntheses. Schreiber, for example, has disclosed a route to the macrolide antibiotic mycoticin A (221, Scheme 2.27) [139] that relies on a strategy involving two-directional chain synthesis [140]. Catalytic asymmetric reduction of diketone 216 affords the C2-symmetric diol 217. Conversion of 217 into bis(ketoester) 218 then allows double ketone reduction to furnish 219, which was subsequently elaborated into the skipped polyol chain 220 of mycoticin A (221). 

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