A-Ketol rearrangement

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). 

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>. 

The a-ketol rearrangement can also be brought about by base catalysis, but only if the alcohol is tertiary, since if R1 or R2 = hydrogen, enolization of the substrate is more favored than rearrangement. 

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 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). 

Such a step, sp -sp C-C bond cleavage, is also presumed to be involved in the unique arylative fragmentation of l-hydroxy-l,l,3-triphenyl-2-propanone to give 1,2-diaryl-1,2-diphenylethanes and benzil (Eq. 32) [54]. The reaction seems to proceed via a-arylation [55] and subsequent a-ketol rearrangement to form an intermediary alcohol, 3-aryl-2-hydroxy-l,2,3-triphenyl-l-propanone [56]. Although the subsequent pathway leading to the final products is not well understood, one of the possible sequences is shown in Scheme 4. 

This constitutes the first catalytic enantioselective vinylogous a-ketol rearrangement reported in the literature. As depicted in Scheme 10.7, the reaction affords the corresponding spirocyclic rings in good yields and excellent stereoselectivities. The scope of the reaction is rather limited because of the nature of the vinylogous a-ketol rearrangement, which requires the presence of cyclobutanol moieties. 

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