Secondary alcohols synthesis, sodium borohydride

Mitsunobu reaction as well as by mesylation and subsequent base treatment failed, the secondary alcohol was inverted by oxidation with pyridinium dichromate and successive reduction with sodium borohydride. The inverted alcohol 454 was protected as an acetate and the acetonide was removed by acid treatment to enable conformational flexibility. Persilylation of triol 455 was succeeded by acetate cleavage with guanidine. Alcohol 456 was deprotonated to assist lactonization. Mild and short treatment with aqueous hydrogen fluoride allowed selective cleavage of the secondary silyl ether. Dehydration of the alcohol 457 was achieved by Tshugaejf vesLCtion. The final steps toward corianin (21) were deprotection of the tertiary alcohols of 458 and epoxidation with peracid. This alternative corianin synthesis needed 34 steps in 0.13% overall yield. 

Numerous methods for the reduction of ketones and aldehydes to the corresponding secondary and primary alcohols, such as the use of several complex metal hydrides, have found wide application in organic synthesis. Lithium aluminum hydride (LiAlH4) and sodium borohydride (NaBH4) are the most popular of these achiral reagents. However, since a natural product synthesis has to fulfill demands in terms of both efficiency and stereoselectivity, these methods can seldom be used with prochiral substrates. 

A second synthesis for the preparation of 2H5V (29) starts by condensation of o-nitrobenzenediazonium chloride withT-hydroxyaceto-phenone. The azo compound was reduced with zinc and sodium hydroxide without reduction of the carbonyl group of the acetyl group. After acetylation, 2(2-acetoxy-5-acetylphenyl)2H-benzotriazole (2A5A) was reduced with sodium borohydride and the secondary alcohol was dehydrated with potassium hydrogen sulfate after hydrolysis, 2H5V was... 

In the pivotal reaction, a titanium-mediated aldol condensation of enol silyl ether 545 produces tetrahydropyran-4-ones 547 (11%) and 548 (38%), which are separable by chromatography. Unfortunately, the product with the desired stereochemistry is the minor isomer 547. The synthesis is completed by benzoylation of the primary alcohol, reduction of the ketone with sodium borohydride, and benzoylation of the newly formed secondary alcohol [132]. 

There is another choice for secondary alcohols the reduction of a ketone. The ketone reacts with sodium borohydride to give a secondary alcohol. An obvious case where this would be a good route is the synthesis of a cyclic alcohol. This bicycUc ketone gives the secondary alcohol in good yield, and in the second example a diketone has both its carbonyl groups reduced. 

---