Benzilic-type rearrangement

The first step in the nonreversible degradation reactions is the formation of a reactive a-dicarbonyl species through the p-elimination of a hydroxide ion. The subsequent reaction pathways to all degradation products can be described by just five reaction types, namely, p-elimination, benzilic acid rearrangement, a-dicarbonyl cleavage, aldol condensation, and retro-aldol condensation (see Fig. 7).31 Retro-aldol condensation and a-dicarbonyl cleavage involve C-C bond... 

Aldoses generally undergo benzilic acid-type rearrangements to produce saccharinic acids, as well as reverse aldol (retro-aldol) reactions with j3-elimination, to afford a-dicarbonyl compounds. The products of these reactions are in considerable evidence at elevated temperatures. The conversions of ketoses and alduronic acids, however, are also of definite interest and will be emphasized as well. Furthermore, aldoses undergo anomerization and aldose-ketose isomerization (the Lobry de Bruyn-Alberda van Ekenstein transformation ) in aqueous base. However, both of these isomerizations are more appropriately studied at room temperature, and will be considered only in the context of other mechanisms. 

Saccharinic acids are (monocarboxylic) deoxyaldonic acids having the general formula CnH2 0 . Of interest here are only those that can be formed from 1,2- or 2,3-enediols by /3-elimination followed by benzilic acid rearrangement. They are of three types metasaccharinic, I, saccharinic, II, and isosaccharinic, III. The C-2 epimers are distinguished as a and /3. ... 

Fragmentation and recombination reactions predominate in nearneutral, alkaline solutions. Fragments from the cleavage of the carbohydrate, and from its dehydration products, undergo further dehydration, condensation, and intermolecular, Cannizarro-type reactions. The benzilic acid rearrangement, an intramolecular Cannizarro reaction, seems to be inoperative. 

The well documented oxidation of 1,10-phenanthroline (4) to 2,2 -bipyridyl-3,3 -dicarboxylic acid (53) by alkaline permanganate has been repeated. It is now found that 4,5-diazafluoren-9-one (54) is consistently a coproduct of the reaction in 20% yield.253 This provides a convenient route to this hitherto difficultly accessible compound. The formation of 4,5-diazafluoren-9-one almost certainly occurs by way of the intermediate, but not isolated, l,10-phenanthroline-5,6-dione, which is known to undergo a benzilic acid type rearrangement in the presence of hydroxide ions to give the diazafluorenone. This rearrangement of l,10-phenanthroline-5,6-dione has recently been studied further.115 Under some conditions 5,6-dihydro-5,6-dihydroxy- 1,10-phenanthroline can be isolated with the diazafluorenone. 

Exercise 17-43 Write a mechanism analogous to that for the Cannizzaro reaction for the benzilic acid transformation. What product would you expect to be formed from diphenylethanedione with potassium terf-butoxide in ferf-butyl alcohol Would you expect a benzilic acid-type rearrangement to occur with 2,3-butanedione Give your reasoning. 

Base-catalysed ring fission of 3,4-diphenylcyclobut-3-ene-l,2-diones (103) in 50% (v/v) aqueous DMSO proceeds by rapid reversible addition of hydroxide ion followed by rate-determining benzilic acid-type rearrangement to form an intermediate 1-hydroxycyclopropane-1-carboxylic acid which ring opens to the corresponding (Z)-2-oxo-3,4-diphenylbut-3-enoic acid (Scheme 8).173 This is supported by the value of Hammett p = 1.3 (for variation of substituents on one or both rings), the kinetic solvent effects, and the three-oxygen enrichment of (107) from reaction of (103) in 50% H2 180-DMSO. 

A similar investigation of the base-catalysed ring opening of 3,4-diphenylcyclobut-3-ene-l,2-diones (77) to give (Z)-2-oxo-3,4-diphcnylbut-3-cnoatcs (78) has been carried out in aqueous DMSO.108 The evidence points towards a rapid, reversible addition of hydroxide to one carbonyl, followed by a benzilic acid-type rearrangement to give a cyclopropene intermediate (79), which ring opens. 

The oxidation of the metal complexes of l,10-phenanthroline-5,6-quinone is thought to proceed in a similar manner, with the first step being a benzilic acid rearrangement. Rearrangements of this type may also be followed directly in nickel(u) and cobalt(m) complexes of 2,2 -pyridil. The first step of the reaction involves nucleophilic attack on an O-bonded carbonyl group to form a hydrate, followed by a benzilic acid rearrangement. In this case, the benzilic acid rearrangement products may be isolated as metal complexes (Fig. 8-43). 

The principal synthetic route to diazafluorenes involves the alkaline oxidation of phenanthrolines, presumed to give initially the rarely isolated 5,6-dione which (i) further oxidizes to a bipyridyl dicarboxylic acid (the main product) or (ii) undergoes a benzilic acid type rearrangement followed by oxidative decarboxylation to give diazafluorenones in moderate yields (Scheme 2) <77JPR959>. The process has been reviewed by Summers <78AHC(22)i>. The yields of 4,5-diazafluorenone have been optimized <73AJC2727>. 

P.A. Grieco et al. accomplished the total synthesis of (+)-shinjudilactone and (+)-13-ep/-shinjudilactone via a benzilic acid-type rearrangement. The substrate was exposed to basic conditions and the two desired products were obtained as a 1 1 mixture. Interestingly, when the Cl position was methoxy substituted, the rearrangement failed to take place under a variety of acidic and basic conditions. 

Novelli, A., Barrio, J. R. Carbon-14 tracer studies in the benzilic acid type rearrangement of 1-phenyl-and 1-(4-methoxyphenyl)-2-(3-pyridyl) glyoxal. Tetrahedron Lett. 1969, 3671-3672. 

Further examples and elimination types will undoubtedly be added to the hitherto known ones and it appears highly versatile that our classification system is not limited to complex eliminations, but also covers complex additions (e.g. the so called benzilic acid rearrangement 36a) in terms of a complex [l,2,3]-addition 170) of water to benzil) and complex substitutions. Thus, the well known technical camphor synthesis starting with a-pinene (Scheme 9) is the result of a sequence of a [l,2,3]-addition 170), [l,2,3]-elimination, (l,2,3]-addition, and finally saponification and oxidation. This appears to be a highly economic description of the underlying chemical processes. 

The released end-group forms an a-dicarbonyl structure which rearranges by an intramolecular, Cannizzaro type of reaction to yield saccharinates. Intramolecular reactions of the Cannizzaro type can occur not only with dialdehydes but also with a-ketoaldehydes and a-diketones ( benzilic acid rearrangement ) they can be exemplified by the base-catalyzed rearrangement of phenylglyoxal (VIII) [or of (2,4,6-trimethylphenyl)-glyoxal ] to the salt of mandelic acid (IX) (or of 2,4,6-trimethylmandelic acid). 

The only known taxoid with 11( 15—> 1), 11( 10— >9) bisabeotaxane skeleton is wallifoliol (232) from T. wallichiana (134). A benzil-benzilic acid type rearrangement of 10-dehydro-10-deacetyl-ll(15—>l)-abeobaccatin 111 (A) might be the biosynthetic pathway of this compound. 

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