Regioselectivity pinacol rearrangement

A major disadvantage of this procedure is the lack of regioselectivity of the bishydroxylation which can take place on each of the four pyrrole rings of the macrotetracycle so that, in addition to the monoadduct, two bisadducts and one trisadduct are formed. The subsequent pinacol rearrangement of the diols can also occur in two directions, leading to a complex mixture of additional constitutional isomers. 

The acid-mediated intramolecular addition of the azide to the ketone proceeds by way of addition followed by a pinacol-type rearrangement, to give the amide 12. The regioselectivity of the bond migration is remarkable. Reduction of the amide then gave 3. 

Fig. 14.15. Regioselectivity of the pinacol rearrangement of an unsymmetrical glycol. The more stable carbenium ion is formed under product development control. Thus, the benz-hydryl cation B is formed here, while the tertiary alkyl cation D is not formed.

Fig. 14.16. Regioselective pinacol rearrangement of an asymmetric glycol. As in the case depicted in Figure 14.15, the reaction proceeds exclusively via the benzhydryl cation.

Therefore, it seems more than appropriate to begin with the longifolene example and the regioselective pinacol-pinacolone-type rearrangement, as shown in Scheme 45. 

The pinacol-pinacolone-type rearrangement with a sulfur atom instead of a second oxygen atom has been explored in a synthesis of scabronine, using Hg (II) catalysis in a now completely regioselective fashion, as shown in Scheme 49 [86]. 

Ring-expansions have been used in two syntheses of the monoterpene kara-hanaenone (12). In the first, the interest lies in the regioselectivity of the addition of thiophenol to the allene (13) and the rapid Cope rearrangement of the cis-product (Scheme 20), whilst in the second the availability of the pinacolic intermediate relies on the success of the titanium-mediated coupling of acetone with the requisite cyclohexanone [equation (17)]. ... 

Patra, D. and Ghosh, S., Regioselectivity and stereospecificity in a contrastereoelectronically controlled pinacol rearrangement of alkoxycyclobutane derivatives. A novel route to vicinally substituted cyclopentanones,/. Org. Chem., 60, 2526, 1995. 

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