Weiss reaction

Ring Enlargement in Organic Chemistry, VCH, Welnhelm, 1991, p. 8-9. 

The formation of bicyclo[3.3.0]octane-3,7-diones 3 by reaction of an a-diketone 

1 with a 3-oxoglutaric diester 2 is called the Weiss reaction.  

Four carbon-carbon bonds are formed in a one-pot reaction that involves two aldol reactions and two Michael addition reactions. 

The initial step is an intermolecular aldol addition of 3-oxoglutaric diester 

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The reasonable mechanism outlined above has not yet been rigorously proven in every detail, but is supported by the fact that a 1 1-intermediate 5 has been isolated." The ester groups are essential for the Weiss reaction because of the /3-keto ester functionalities however, the ester groups can be easily removed from the final product by ester hydrolysis and subsequent decarboxylation. 

An illustrative example for the usefulness of the Weiss reaction for the construction of complex cyclopentanoid carbon skeletons is the synthesis of the all -cis [5.5.5.5]fenestrane 7 after Cook et al., starting from the a-diketone ... 

In order to obtain good yields from a Weiss reaction sequence, the H+-concentration has to be adjusted properly in the reaction mixture. The reaction is usually carried out in a buffered, weakly acidic or weakly basic solution. By the Weiss reaction simple starting materials are converted into a complex product of defined stereochemistry. There is no simpler procedure for the synthesis of the l,5-c -disubstituted bicyclo[3.3.0]octane skeleton it has for example found application in the synthesis of polyquinanes. ... 

Immunohistochemical studies carried out in our laboratories have demonstrated the presence of xanthine oxidase in synovial endothelial cells (Stevens etal., 1991). As expected, the activity of this enzyme per unit weight of tissue is generally higher in synovia taken from RA patients due to their increased vascularity (Allen et al., 1987). In addition, it has also been shown that rheumatoid synoviocytes contain increased levels of iron-saturated ferritin (Morris et d., 1986). Xanthine oxidase (but not dehydrogenase) is able to mobilize iron from ferritin, supplying the necessary transition metal catalyst for the Haber-Weiss reaction and promoting OH formation (Biemond eta/., 1986). 

Starke, P.E., and Farber, J.L. (1985). Ferric iron and superoxide ions are required for the killing of cultured hepatocytes by hydrogen peroxide. Evidence for the participation of hydroxyl radicals formed by an iron catalyzed Haber-Weiss reaction. J. Biol. Chem. 260, 10099-10104. 

Indeed, when present in concentrations sufficient to overwhelm normal antioxidant defences, ROS may be the principal mediators of lung injury (Said and Foda, 1989). These species, arising from the sequential one-electron reductions of oxygen, include the superoxide anion radical, hydrogen peroxide, hypochlorous ions and the hydroxyl radical. The latter species is thought to be formed either from superoxide in the ptesence of iron ions (Haber-Weiss reaction Junod, 1986) or from hydrogen peroxide, also catalysed by ferric ions (Fenton catalysis Kennedy et al., 1989). 

In the presence of trace amounts of iron, superoxide can then reduce Fe3+ to molecular oxygen and Fe2+. The sum of this reaction (equation 2) plus the Fenton reaction (equation 1) produces molecular oxygen plus hydroxyl radical, plus hydroxyl anion from superoxide and hydrogen peroxide, in the presence of catalytic amounts of iron - the so-called Haber-Weiss reaction (equation 3) (Haber and Weiss, 1934). 

In addition, superoxide, hydrogen peroxide and hydroxyl radicals can be interconverted via the so-called Haber-Weiss reaction ... 

Cuprous and cupric ions may substitute for ferrous and ferric ions in the Haber-Weiss reaction [22]. Peroxynitrite can be formed from the reaction of NO with 02 ... 

However, more recently Halliwell and Gutteridge (1984,1985) have supported the idea that mixtures of 02" and H2O2, together with transition-metal salts (e.g. iron and copper salts) will also result in the formation of -OH by the so-called metal catalysed Haber-Weiss reaction ... 

However, the formation of either 02 or OH by the myeloperoxidase system is debatable, and it has even been proposed that myeloperoxidase can actually lower OH formation by decreasing the concentration of H202 available for the Haber-Weiss reaction ( 5.4.2.5). 

In Scheme A-1.1 [7] a comparison of a typical Diels-Alder reaction (butadiene + /7-benzoquinone) with a typical Weiss reaction (dimethyl 3-glutarate + glyoxal), in terms of AC, is shown. The stereochemistry of the products is implicit in the... 

Proceeding in a similar way, the reader may substantiate, as an exercise, that the change in complexity for the Weiss reaction is substantially larger AC =... 

COMPUTER ALGORITHMS SOFTWARE HABER-WEISS REACTION HALDANE RELATION... 

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