Oxazaborolidine, 5-methylated synthesis

E.J. Corey and co-workers synthesized the cdc25A protein phosphatase inhibitor dysidiolide enantioselectively. In the last phase of the total synthesis, the secondary alcohol functionality of the side-chain was established with a highly diastereoselective oxazaborolidine-catalyzed reduction using borane-dimethylsulfide complex in the presence of the (S)-6-methyl CBS catalyst. Finally, a photochemical oxidation generated the y-hydroxybutenolide functionality. This total synthesis confirmed the absolute stereochemistry of dysidiolide. 

In 2003, Molander et al. reported the synthesis of (+ )-isoschizandrin, a natural product displaying anti-ulcer activity in rats. The key step of the synthesis was the atropo-enantioselective reduction of a seven-membered lactone by using a chiral oxazaborolidine, (i )-2-methyl-CBS-oxazaborolidine, which provided the corresponding chiral lactone after recycling (Scheme 5.45). Similar conditions were also applied to the corresponding six-membered lactone, which led to the formation of the corresponding chiral diol in excellent yield and enantioselectivity, as shown in Scheme 5.45. 

Nicolaou and coworkers completed the enantioselective synthesis of these two natural products molecules through a short and equally efficient route (12 steps from commercially available material with the 4% overall yield) involving a series of cascade reactions and novel skeletal rearrangements [107b]. This unique route commenced with a CBS asymmetric reduction of ketone 288 that is easily generated from the resveratrol monomer (Scheme 10.55). The chiral benzylic alcohol 289 was obtained in 85% yield and 95% ee in the presence of one equivalent of catecholborane and catalytic amount of (/ )-(+)-2-methyl-CBS-oxazaborolidine. This newly formed C8a center would be served as a chiral source by which other stereocenters within the architectnre... 

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