Rearrangements anionic homo-fries rearrangement

The total synthesis of the potent protein kinase C inhibitor (-)-balanol was accomplished by J.W. Lampe and co-workers. They took advantage of the anionic homo-Fries rearrangement to prepare the sterically congested benzophenone subunit. To this end, 2-bromo-3-benzyloxy benzyl alcohol was first acylated with a 1,3,5-trisubstituted benzoyl chloride to obtain the ester precursor in 84% yield. Next, the ester was treated with n-BuLi at -78 °C to perform a metal-halogen exchange. The resulting aryllithium rapidly underwent the anionic homo-Fries rearrangement to afford the desired tetra ortho-substituted benzophenone in 51% yield. 

In an instructive application for the construction of hindered benzophenones, an initial metal-halogen exchange of a bromo-benzyloxy ester with BuLi sets the stage for anionic homo-Fries rearrangement of the intermediate aryllithium species (eq 39). The resulting tetra orf/zo-substituted benzophenone serves as an intermediate for the synthesis of the potent protein kinase C inhibitor (—)-balanol. 

Schmalz et al. [202] recently reported a tandem anionic homo-Fries rearrangement/ lactonization [203] for the synthesis of cyclo-mumbaistatin analogue 436 (Scheme 105). 

The requisite anthracene 431 was obtained by reduction and methylation of the anthraquinone 430. Halogen-metal exchange at low temperamre generated the arylmagnesium species 432, which underwent the anionic homo-Fries rearrangement and lactonization upon heating to 50 °C. The spirolactone 435 was thus obtained in good yield. Reoxidation of the anthracene with silver oxide and... 

Scheme 105 Anionic homo-Fries rearrangement in the synthesis of a spiroacetal [202]...

Aside from its summit position as a DMG (10, Scheme 3) the OCONEt2 provides versatile anionic aromatic chemistry anionic ortho-Fries rearrangement (9, Scheme 3) [11], a useful synthetic step by itself but also one that provides a path, after incipient phenol protection, to further DoM, resulting in a 1,2,3-sub-stituted aromatic derivative (9 —> 12, see also Scheme 13) [12] homo-ortho-Fries rearrangement to aryl acetamides (10 —> 11) providing a route to benzofura-nones which are difficult to prepare by Friedel-Crafts-based strategies [9] intra-... 

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