Ketol rearrangements

LIEBIG BenzyBc Aad Rearrangement Benzylic a<5ds by rearrangement of diketones (also a-ketol rearrangement)... 

If the reaction is carried out with ketone labeled in the C=0 group with the first pathway predicts that the product will contain all the " C in the C=0 carbon, while in the second pathway the label will be in the a carbon (demonstrating migration of oxygen). The results of such experiments have shown that in some cases only the C=0 carbon was labeled, in other cases only the a carbon, while in still others both carbons bore the label, indicating that in these cases both pathways were in operation. With a-hydroxy aldehydes and ketones, the process may stop after only one migration (this is called the a-ketol rearrangement). 

The ot-ketol rearrangement can also be brought about by base catalysis, but only if the alcohol is tertiary, since if or = hydrogen, enolization of the substrate is more favored than rearrangement. 

Asymmetric synthesis of the rocaglamides was accomplished by employing [3+2] photo-cycloaddition mediated by functionalized TADDOL based chiral Brpnsted acids. The synthesis consisted of a [3+2] dipolar cycloaddition, a base-mediated a-ketol rearrangement and a hydroxyl-directed reaction <06JA7754>. Asymmetric synthesis of 1,2-dihydrobenzo /j]furans was achieved by adamantylglycine derived dirhodium tetracarboxylate catalyzed C-H insertion <06OL3437>. 

Like vinylogous ketol to ketol rearrangements (Section 3.2.4.5.), ketol to ketol rearrangements can be induced by treatment with acids, but are most often brought about by treatment with base. However, only a few examples exist where the rearrangement leads to enlargement of a three-membered ring.195 199 Of these cases, 5-hydroxybicyclo[3.2.0]heptan-6-ones were effectively produced by treatment of l-hydroxybicyclo[4.1.0]heplan-2-ones with base (Table 17).197-199... 

Table 17. Ring Enlargements via Ketol to Ketol Rearrangements...

Diaryl-2-hydroxypropiophenones (607) are obtained from 4-hydroxychalcone and a reactive phenol on treatment with alkaline hydrogen peroxide in an epoxide-mediated coupling reaction. The ketones undergo a base-catalyzed a-ketol rearrangement to the isomeric l-hydroxypropan-2-ones (608) and acid-catalyzed ring closure provides a route to 4-arylflavan-3-ones (Scheme 231) (80JCS(Pl)1025). 

Figure 4 Deoxyxylulose phosphate isomero-reductase (DXR) catalyzed conversion of DXP 11 into MEP 12 (a) a-ketol rearrangement, (b) retro-aldol/aldol reaction. Fosmidomycin 19, a DXR inhibitor.

The conclusion was reached that the biosynthetic route was by way of a two-carbon insertion into 2-oxo-3-hydroxy-3-methylbutyric acid (CLXXIV). Taken in conjunction with the established bios3uithesis of valine (CLXXV) from pyruvic acid by way of acetyllactic acid (CLXXVI) and the ketol rearrangement to CLXXIV the biosynthesis of echimidinic acid may be formulated as in Chart VI. 

The furyl carbonyl 26 was exposed to an aqueous solution of zinc chloride which presumably opens the furan to give the ketoaldehyde 27 that spontaneously cyclizes to 28. The cyclization is likely preceded by an acid promoted a-ketol rearrangement. Tanis and co-workers <98JOC6914> utilized a hydrolytic opening promoted by an initial electrophilic attack to synthesize the natural alkaloid epilupinine (Scheme 3). 

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